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China’s mass collection of human DNA without informed consent is contrary to the right to privacy
China holds the largest searchable DNA database in the world; genetic information from over 40 million individuals that is ostensibly to be used in the fight against crime. However, the way in which these data are collected and the protection given to providers leave much to be desired, according to the European Society of Human Genetics (ESHG).
"There is growing evidence that DNA is being collected from ordinary individuals who have not been convicted nor even suspected of a crime, and that this collection is compulsory. Police have also taken samples from groups that are already under increased government surveillance, such as dissidents, migrant workers, and ethnic minorities," said Professor Martina Cornel, chair of the ESHG Public and Professional Policy Committee, today [date]. "Because police powers in China are so extensive and people have little right to privacy, they are unable to refuse to provide such personal data."
People who have been compelled to provide DNA have reported their experiences via social media. Collections are made by police at their workplaces, homes, and schools, with no prior notice and without the presentation of any official document justifying the taking of samples. Some people have also been asked to provide DNA samples when applying for documents such as residency permits from the police.
In Xinjiang, a province that is home to around 10 million Muslim Uyghurs, an ethnic group already suffering state repression, all passport applicants are now required to provide DNA samples, irrespective of whether or not they are suspects in a criminal case. "This is in total contradiction to all existing regulations and safeguards concerning the collection of DNA samples from individuals", says Prof Cornel.
"We know that such databases can be used for government surveillance, including identification of relatives. Collection of DNA without the subject’s full, informed consent can only be justified in extremely limited circumstances, for example in order to solve a very serious crime. A collection of samples from individuals where no such consent has been given has been ruled illegal by many international bodies, and the very existence of such a database is dangerous."
"ESHG calls on the Chinese government to follow in the footsteps of all responsible authorities and ensure that human DNA is collected only from individuals suspected of having committed serious crimes, and that informed consent is given whenever possible."
European Human Genetics Conference 2017, May 27-30, Copenhagen, Denmark
Increasing the age limit for Lynch syndrome genetic testing may save lives
Copenhagen, Denmark: Raising the age limit for routine genetic testing in colorectal cancer could identify more cases of families affected by Lynch syndrome, a condition that accounts for around 5% of all colon cancers, according to new research to be presented at the annual conference of the European Society of Human Genetics today (Monday). Professor Nicoline Hoogerbrugge, head of the Radboud university medical centre expert centre on hereditary cancers, Nijmegen, The Netherlands, will tell the conference that there is an urgent need to find families carrying a mutation for Lynch syndrome in order to decrease mortality from the disease.
“We know that, at present, only between 20% and 30% of people with Lynch syndrome have been identified. Most countries rely on detection through family history and early age at diagnosis, and this leads to significant underdiagnosis. We have shown that, by raising the age limit for testing we are able to detect new affected families who would not have been identified previously,” she says.
The researchers studied results of mismatch repair (MMR) testing in patients up to 70 years of age with colorectal cancer from 14 pathology laboratories. Previously, in The Netherlands, such testing was carried routinely in patients who were aged up to 50. Of 87 patients whose results suggested that they are at high risk of Lynch syndrome, 35 were referred for genetic counselling.
After further testing, Lynch syndrome mutations were definitely identified in 13 of 32 patients with complete genetic testing, and 11 of these patients came from families in which the disease had previously not been detected. Eight of them were aged between 50 and 70 and did not comply with previous referral criteria for genetic testing based on age and family history.
“If we had not studied these older patients, their family predisposition to Lynch syndrome would not have been detected until it was too late,” says Prof Hoogerbrugge. “In every affected family, we can find an average of three people with Lynch. This is clearly a massive advance in the identification of people at risk.”
By implementing appropriate prevention measures, deaths from Lynch syndrome in affected families can be reduced by more than 60% over 15 years, the researchers say. The disease, otherwise known as hereditary nonpolyposis colorectal cancer (HNPCC), also leads to an increased risk of cancers of the stomach, upper urinary tract, brain, skin and prostate, with women carriers at an additional of endometrial and ovarian cancers.
The study covered 20% of the Dutch population. “Part of our results surprised us; we had not expected to find so many mutations in Lynch syndrome associated genes with a relatively high risk of developing tumours in patients without a family history of the disease. This has only strengthened our desire to see an increase in the age limit for MMR testing applied across The Netherlands, and indeed across Europe, so that every new colorectal cancer patient aged below 70 can benefit from it,” says Prof Hoogerbrugge.
“The age limit in the UK has recently been increased; although it is too early to be able to see signs of value there, we have been able to provide clear evidence of its advantages in The Netherlands, both for patients and for health services,” she concludes.
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “It is very important to recognise whether a person suffers from sporadic or familiar cancer, as this identifies family members at risk who can take preventative measures. For this, genetic tests need to be done in cancer patients. This study shows that we should extend these genetic tests to older colorectal cancer patients of whom a significant number suffer from familiar cancer.”
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Abstract no: C17.6
The research was funded by the Dutch Maag-Lever-Darm society and the Vriendenloterij.
The data have been updated since submission of the abstract, which accounts for the difference in numbers.
New genomic analysis promises benefit in female urinary incontinence
Copenhagen, Denmark: Urinary incontinence in women is common, with almost 50% of adult women experiencing leakage at least occasionally. Genetic or heritable factors are known to contribute to half of all cases, but until now studies had failed to identify the genetic variants associated with the condition. Speaking at the annual conference of the European Society of Human Genetics today (Monday), Dr Rufus Cartwright, MD, a visiting researcher in the Department of Epidemiology and Biostatistics, Imperial College, London, UK, will say that his team’s investigations hold out the promise that drugs already used for the treatment of other conditions can help affected women combat this distressing problem.
Pelvic floor disorders, including urinary incontinence, but also faecal incontinence and pelvic organ prolapse, have a devastating effect on quality of life. Most commonly they occur after childbirth, or at menopause, though some women report incontinence dating from childhood. Of the 25% who are affected sufficiently for it to affect their daily lives, most suffer from stress incontinence – the loss of small amounts of urine associated with laughing, coughing, sneezing, exercising or other movements that increase pressure on the bladder. Isolated urgency incontinence – where a sudden pressing need to urinate causes the leakage of urine – affects only around 5% of women, and 5-10% have a combination of both forms.
“25% of adult women will experience incontinence severe enough to impact on their quality of life,” says Dr Cartwright. “Finding a genetic cause and a potential treatment route is therefore a priority.”
The researchers undertook a genome-wide association study (GWAS) in just under 9,000 women from three groups in Finland and the UK, confirming their findings in six further studies. Genome-wide association studies work by scanning markers across the complete sets of DNA of large numbers of people in order to find genetic variants associated with a particular disease.
Analysis of the study data yielded a risk locus for urinary incontinence close to the endothelin gene, known to be involved in the ability of the bladder to contract. Drugs that work on the endothelin pathway are already used in the treatment of pulmonary hypertension and Raynaud’s syndrome, a condition where spasm of the arteries causes reduced blood flow, most usually to the fingers.
“Previous studies had failed to confirm any genetic causes for incontinence. Although I was always hopeful that we would find something significant, there were major challenges involved in finding enough women to participate, and then collecting the information about incontinence. It has taken more than five years of work, and has only been possible thanks to the existence of high quality cohort studies with participants who were keen to help,” says Dr Cartwright.
Current treatment for urinary incontinence in women includes pelvic floor and bladder training, advice on lifestyle changes (for example, reducing fluid intake and losing weight), drugs to reduce bladder contraction, and surgery.
However, as the number of identified risk variants for urinary incontinence grows, there will be potential to introduce genetic screening for the condition, and improve advice to pregnant women about the likely risks of incontinence in order that they may make an informed choice about delivery method. “We know that a caesarean section offers substantial protection from incontinence. However, across Europe there are efforts to reduce caesarean section rates, and establishing such a screening programme during pregnancy may run against current political objectives in many maternity care systems.
“Clearly this will need further debate and an analysis, not just of the cost to healthcare systems, but also of the benefit to women who may be spared the distress of urinary incontinence,” Dr Cartwright will conclude.
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This work reveals the first links between urinary incontinence and genetic factors. It provides important insight into the biological mechanisms for incontinence and suggests the potential of identifying women at risk.”
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Abstract no: C18.4.
The research was mainly funded by the UK Medical Research Council, with additional grants from the International Continence Society and the International Urogynecological Association.
Genomics tracks migration from lost empires to modern cities
Copenhagen, Denmark: New genomic tools are enabling researchers to overturn long-held beliefs about the origins of populations, a researcher will tell the annual conference of the European Society of Human Genetics today (Monday). Dr Eran Elhaik, Assistant Professor of Animal and Plant Sciences at the University of Sheffield, Sheffield, UK, will say that new technologies are enabling scientists to track the origins and migrations of populations with increasing accuracy.
Until recently, assumptions about origins were based on where people were buried. “However, this does not take into account the migrations which we now know took place thousands of years ago,” says Dr Elhaik, who carried out the research with colleagues including Dr Umberto Esposito.
Using a recently-developed technology, the ancient Geographic Population Structure (aGPS) tool, the researchers were able to find the geographical origins of ancient DNA, with the only limitation being the availability of DNA data. This in turn enabled them to combine hundreds of snap shots from the past into a reconstruction of modern history from 12,000 BC to the modern era. “This is by far the most comprehensive reconstruction of our genetic history. Our work reveals the colonisation of Europe, step by step, and answers many questions concerning the origins and migrations of Europeans,” says Dr Elhaik.
Applied to a dataset of over 300 ancient Eurasians and Near-Easterners during the Ice Age to Late Iron Age period, aGPS localised around 50% of the samples at up to 200km from their burial site, about 32% at between 200 and 1000km, and the remainder at between 1000 and 3,175km. “The migration patterns revealed by our work were remarkably complex and dynamic, and the difficulties in interpreting them correctly are significant.
“The challenge for us now is to understand why these migrations took place. What caused a particular group of people to make a journey of over 3000km at a time when travel was complicated and dangerous? When we combine our results with archaeological and climate data, we can begin to see why,” says Dr Elhaik. “For example, we can identify areas where the land became exhausted from over-farming, and thus caused the movement of populations. We can also pinpoint the formation of city states and ‘biodiversity centres’, corresponding to ancient empires that drew immigrants from other countries.”
The results allow the researchers to confirm the theory of the massive migration of populations from the steppes of the Caucasus (the Yamnaya) to Central Europe during the Late Neolithic period (3500 to 2300 BC). “We discovered that Central Europeans were always on the move, continuously mixing with other populations and forming ancient cities in Germany, Denmark and Hungary, for example close to modern-day Hamburg and Berlin, and Budapest. In contrast, Near Eastern peoples tended to stay close to home,” says Dr Elhaik.
“Genetic data can answer many questions that archaeology alone cannot. For example, is a specific decoration indicative of an alien culture, or simply an import? These new insights are fascinating, not just in a historical context, but because they provide additional proof of the unlikelihood of a ‘day zero’ of ethnic homogeneity, except perhaps in a very few isolated places. Even if it had existed, there must be practically no-one alive on earth who could trace all their ancestors to one ethnically homogenous population”.
There are endless challenges in this research. “Imagine working with a very short DNA sequences with more holes than bases – not only can we not align this with other ancient sequences, but we also do not know where it is from. And this is before we get to the question of “when?” which is, again, linked to “where?” because different regions entered developmental periods, like the Iron Age, at different times.
“However, our findings to date have already brought about a far greater understanding of the identity of Old World residents, and our goal is now to reconstruct the full “Human Atlas” showing ancient migration patterns worldwide,” he will conclude.
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This fascinating work illustrates the power of modern genetic approaches to study human history and migration. The scientists demonstrate that information in ancient DNA samples, even of low quality, can be used to provide a very precise geographical localisation of the origin of a person.”
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Abstract no: C14.6
The research was partly funded by the DNA Diagnostics Centre, UK.
Obesity can cause cardiovascular ill-health, even in the young
Copenhagen, Denmark: Higher than normal body mass index (BMI) is known to lead to cardiovascular ill-health in mid-to-late life, but there has been limited investigation of its effect in young, apparently healthy, adults. Researchers have now shown that having a higher BMI can cause worse cardiovascular health in those aged as young as 17, according to a study to be presented to the annual conference of the European Society of Human Genetics today (Sunday).
Dr Kaitlin Wade, a Research Associate at the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) at the University of Bristol, Bristol, UK, and colleagues used data from The Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate the potential link between increased BMI and cardiovascular health. “ALSPAC is a world-leading birth cohort study, started in the early 1990s with the inclusion of more than 14,000 pregnant mothers and their partners and children, and provides an excellent opportunity to study environmental and genetic contributions to a person’s health and development. It was therefore ideal for this purpose,” Dr Wade will say.
The researchers hypothesised that cardiovascular risk due to increased BMI was likely to emerge in earlier life. The design of existing observational studies (those just looking for associations in the population) have meant that they are unable to make a distinction between correlation and causation. The MRC-IEU specialises in the use of genetics to help these difficult analytical situations and in this case researchers were able to use genomic data from ALSPAC to detect the likely causal relationship between higher BMI and higher blood pressure and left ventricular mass index (LVMI) in those aged 17 and 21. A thickening of the left ventricle in the heart (hypertrophy) means that it has to work harder to pump blood and is a common marker for heart disease.
Higher BMI did not appear to have an effect on heart rate in these young adults, although previous studies have shown an association - most likely due to bias caused by the mixing of effects of an additional factor resulting in a distortion of the true relationship (confounding). “Our results showed that the causal impact of higher BMI on cardiac output was solely driven by the volume of blood pumped by the left ventricle (stroke volume). This, at least in part, can explain the causal effect of higher BMI on cardiac hypertrophy and higher blood pressure that we observed in all our analyses,” says Dr Wade.
The results support efforts to tackle the obesity epidemic from an early age in order to prevent the development of cardiovascular changes known to be precursors of cardiovascular ill-health and disease. “It is the first time that the nature of this relationship has been shown in group of young adults where it has been possible to draw improved conclusions about its causation," says Dr Wade.
The researchers are now trying to untangle the relationship between higher BMI and disease mechanisms including metabolomics (the study of the chemical processes involved in the functioning of cells and the abundance and diversity of microbes living in the gut - the gut microbiome). “We have also begun an analysis of the causal role of higher BMI on detailed measures of cardiac structure and function within the ALSPAC data. We hope to further explore these associations within an older population - the UK 1946 birth cohort.
“Whilst randomised controlled trials are important for disentangling cause and effect in disease, they are expensive, time-consuming and labour-intensive. Modern genomics allows us to detect causality more quickly and cheaply, and the availability of large quantities of genetic data means that we can overcome the limitations of observational epidemiological studies. We believe that there are clear messages for cardiovascular health in our findings and we hope that they may lead to increased efforts to tackle obesity from early life,” Dr Wade will conclude.
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University¸ Newcastle, United Kingdom, said: “Distinguishing between correlation and causation is tremendously difficult in medical sciences, especially for complex interactions like those between obesity and cardiovascular disease. In this study, statistical genetics approaches were applied to longitudinal cohorts from the UK to improve this. The scientists could demonstrate that obesity also causes poorer cardiovascular health in young adults. In contrast, higher BMI did not seem affect heart rate in this group.’’
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Abstract no: C10.3
The research was funded by the British Heart Foundation, the UK Medical Research Council, The University of Bristol and The Wellcome Trust.
Open-access genetic screening for hereditary breast cancer is feasible and effective
Copenhagen, Denmark: Ashkenazi Jewish women are known to have a predisposition to the inherited breast cancers BRCA1 and BRCA2, but currently genetic testing in this group is limited to women affected by breast and ovarian cancers and those who are unaffected but have a family history of the disease.
Ms Sari Lieberman, a genetic counsellor at the Shaare Zedek Medical Centre, Jerusalem, Israel, will tell the annual conference of the European Society of Human Genetics tomorrow (Sunday) that offering open-access BRCA testing to Ashkenazi women unaffected by cancer, regardless of their family history, enables the identification of carriers who would otherwise have been missed. Carrying one of the mutations for the BRCA genes means that women affected have a 50-80% risk of developing breast cancer and a 20-50% risk for ovarian cancer.
“We knew that half of these carriers have no family history of cancer, and therefore would not have been identified had the test been offered on the current personal and family history criteria,” she says. “As a genetic counsellor, it is frustrating and saddening to see the results of this policy, where patients are often only identified as BRCA carriers once they have been diagnosed with cancer.”
The researchers streamlined the pre-test process so that traditional genetic counselling, which can be time-consuming and difficult, was excluded. Instead they provided written information about the BRCA genes, the genetic test, and about the implications of being a carrier.
“Current strategies for testing focus on women who are 50 and older, which is not the optimal age for effective prevention. In order to address this, we would like to continue this study and look for other approaches that could include younger women,” says Ms Lieberman.
participants in the study either referred themselves or were recruited by health professionals. Two-year follow up of the 1771 women tested included looking at psychosocial outcomes and health behaviours. Both groups reported a high level of satisfaction (94%) and low stress. Those who had referred themselves tended to be more knowledgeable about breast cancer issues than those who were recruited.
“Among the 25 women carriers we identified, 94% expressed satisfaction and 92% endorsed the idea of population screening. Their stress was understandably higher, but it declined over time, and their knowledge was greater than in non-carriers. All of them had breast surveillance, and three underwent risk-reducing bilateral mastectomy. Of those aged over 40, fifteen out of a total of 16 had their ovaries and Fallopian tubes removed in order to reduce risk,” Ms Lieberman reports.
The researchers say that their study provides convincing evidence that open access genetic testing overcomes major barriers; not just lack of family history, but also referral and bureaucratic barriers, and that it is acceptable to those likely to be affected and their families.
“We were concerned that ‘low risk’ participants, with no family history, might not be able to cope with being offered BRCA testing and particularly with positive test results. We also worried that being found not to be a carrier might provide false reassurance and cause women to think they had no cancer risk and therefore avoid standard surveillance. We were pleasantly surprised on both counts,” Ms Lieberman will say. In fact, mammography screening rates did not decline post-test in non-carriers, and even increased in some.
Falling prices for genetic sequencing and new techniques to avoid evaluating irrelevant gene variants will most likely make mutation screening available to wider populations in the near future. “We believe that our results are useful and highly relevant for other populations. On a personal note, I hope that this new approach means that one day I will not have to counsel someone with no family history and therefore no awareness of increased risk who says to me that she only wished she had known before,” Ms Lieberman will conclude.
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “This important study highlights the importance of population-wide genetic screening to identify women at risk of developing breast and ovarian cancer because of a genetic predisposition. The study also showed that most people cope very well with this genetic information; carriers of these mutations undertake breast cancer surveillance, whereas non-carriers are aware they can still develop breast cancer.’’
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Abstract no: C12.3
The research was funded by the Breast Cancer Research Foundation.
Balancing rights and responsibilities in insurers’ access to genetic test results
Copenhagen, Denmark: Genetic testing is widely used across the developed world in order to diagnose and predict disease. However, along with its usefulness comes concern about how others, such as employers and insurers, can have access to and use its results. This in turn leads to the risk that individuals may avoid medically recommended genetic testing, or participation in genetic research, if they fear that they may be discriminated against based on their results.
At the annual conference of the European Society of Human Genetics tomorrow (Saturday), Anya Prince, JD MPP, a postdoctoral research associate at the Centre for Genomics and Society, University of North Carolina, Chapel Hill, USA, will present results of her study comparing the regulation of life insurers’ use of genetic information in the UK, Canada, and Australia.
“Such a study is necessary in order to appreciate the effectiveness and potential downsides of different policy options,” says Ms Prince, who hopes to use her results to inform the development of regulations addressing life insurer use of genetic information in the United States. “Understanding which policy options most effectively assuage fear of discrimination has the potential to improve human health by encouraging individuals to undergo testing when medically recommended and to participate in genomics research.”
In Australia, private life insurers are permitted to use genetic test results when setting insurance rates and deciding whether or not to accept an application. Although they are only allowed to use test results based on actuarial or statistical data, they are free to use their own judgements as to which tests meet these requirements.
In Canada, while life insurers are currently allowed to use genetic test results, the Parliament recently passed legislation that would prohibit them from doing so when drawing up insurance contracts. But in Canada insurance regulation comes under the jurisdiction of the provinces, so there is some doubt as to whether this ban is constitutional. The legislation is currently under judicial review.
Of the three countries studied, the United Kingdom had the most comprehensive protection against insurer use of genetic information. Life insurers have agreed to a moratorium on the use of predictive genetic test results for life insurance policies below £500,000 (five hundred thousand pounds). Above this figure, insurers are allowed to use genetic tests sanctioned by a government advisory committee, but to date only Huntington’s Disease testing has been permitted.
“The two-tiered UK system is seen by many both within and outside of the country as being an effective way of balancing individual and insurer concerns—on the one hand about genetic discrimination and on the other about the economic viability of the industry. And the flexible nature of the moratorium, which is not permanent legislation, helps insurers feel comfortable that they will be able to react to advances in genomic research if necessary,” says Ms Prince.
However, discussions with insurers in Australia and Canada showed that they felt that to lose access to genetic test results would have a drastic effect on their industry, and could threaten financial collapse. Unsurprisingly, individuals in those countries were much more likely to fear discrimination as a result of genetic testing than those interviewed in the UK.
Ms Prince has now widened the scope of her study to include Sweden, where insurers are barred from taking genetic test results into consideration. “I hope this comparative research will help to foster international dialogue about the ethical and legal implications of genetic research and insurance. Personally, I think that a two-tier system, as implemented in the UK, creates an appropriate balance. If insurers are allowed to use test results, I believe their model of an independent committee controlling which test results they may use is necessary,” she says.
However, a major question remains. Are genetic test results relevant to insurance underwriting? “While genetic testing may promise to reduce risk, it is important to keep in mind that most genetic information can be affected by so many other factors. These include the environment, the likelihood of developing symptoms if someone has a genetic mutation (called the penetrance), the variation in signs and symptoms that can occur among people with the same condition, and how easy it is to minimise risks in individuals.”
“Where there are tests for highly penetrant conditions, it is relatively easy to predict outcomes, but these conditions affect only a very small percentage of the population. It is therefore unsurprising that there is active debate about how loss of access to genetic test results would really affect the economic viability of the insurance industry,” Ms Prince will conclude.
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “Genetic testing is becoming more mainstream and providing an increasing amount of information that can be used to predict disease risks. It is therefore important to evaluate who may or may not have access to these data and for what purpose, and make sure we develop common rules that can be internationally applied and upheld. This work provides an important analysis of the way different countries deal with this. It points to considerable differences that need to be addressed with all stakeholders involved.”
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Abstract no: P20.03C
The research was funded by the National Human Genome Research Institute of the National Institutes of Health (USA) under Award No. K99HG008819.
The European Society of Human Genetics condemns move to impose obligatory genetic testing for employees in the USA
For immediate release: Thursday 16 March 2017
A Bill that would allow companies to require employees to undergo genetic testing and disclose the results to their employers, or risk having to make health insurance payments of thousands of dollars extra, was recently approved by the US House of Representatives Committee on Education and the Workforce, with all 22 Republicans supporting it and all 17 Democrats opposing.
Genetic tests can predict health risks. In the US, where companies cover significant parts of the health insurance of their employees they may, understandably, want to minimise these risks. In the past, however, decisions on whether or not to undergo genetic testing have been the voluntary choices of individuals. Both the Council of Europe and the US law (Genetic Information and Non-Discrimination Act, GINA) uphold this standpoint.
The European Society of Human Genetics (ESHG) defends the principle that employees should be employed on the basis of their skills and expertise, and not on their future health risks. This Bill has apparently been integrated into the activities related to the revision of the Affordable Care Act, otherwise known as Obama Care. Transparency is needed on the potential decision to discontinue the GINA. The genetic and health information of individuals needs protection,” said Professor Martina Cornel, chair of the ESHG Public and Professional Policy Committee.
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Geneticists welcome Kuwaiti decision to amend law on compulsory DNA collection
For immediate release: Wednesday 19 October 2016
Responding to the decision of the Emir of Kuwait to request the Kuwaiti Prime Minister to reconsider the scope of the law that would have imposed compulsory DNA testing on all residents as well as visitors to the country, Professor Olaf Horst Rieß, President of the European Society of Human Genetics (ESHG), said:
“This is a wise and responsible decision. The law as originally proposed was disproportionate and likely to be ineffectual in tackling the problem of terrorism, and would have had negative consequences not just for Kuwaiti society, but also for medical science and research.”
Note to editors: Background to the law and the ESHG position can be found below.
ESHG Statement and Press release on the New Kuwaiti law on the collection of human DNA
New Kuwaiti law will severely affect international collaborations
Following a terrorist attack, the Kuwait Government introduced a law mandating compulsory collection of DNA samples from its entire population (citizens, legal, and illegal residents), as well as foreign visitors. The law will also apply to tourists and visiting scientists, and will impose a one year
prison term and a fine on those who refuse to provide samples. This makes Kuwait the first country in the world to legislate for the mandatory collection of human DNA samples. Several important organisations have opposed this law and called upon the Kuwait government to amend it[i].
The President of the European Society of Human Genetics and the chair of the Professional and Public Policy Committee have sent a letter dated 31 August 2016 to His Highness Sheikh Jaber Mubarak Al-Hamad Al-Sabah and to The Council of Ministers of the State of Kuwait asking them to reconsider this law and to amend it so that human DNA is collected for legal purposes only from individuals suspected of having committed serious crimes. This would be in line with The European Convention on Human Rights, which in ARTICLE 8 on the Right to respect for private and family life states that:
1. Everyone has the right to respect for his private and family life, his home and his correspondence.
2. There shall be no interference by a public authority with the exercise of this right except such as is in accordance with the law and is necessary in a democratic society in the interests of national security, public safety or the economic wellbeing of the country, for the prevention of disorder or crime, for the protection of health or morals, or for the protection of the rights and freedoms of others.
As the professional organisation bringing together human geneticists across Europe we are in agreement with the UN Human Rights Committee that such a law is disproportionate and violates the right to privacy. We understand that the current government is building the collection of human DNA samples for the protection of the Kuwaiti citizens. However, the simple existence of such a resource could be dangerous in the future, for example, if hacked or in the event of a régime change.
Fears voiced in the media and elsewhere include the possibility of discrimination based on the attribution of ancestry, whether correct or wrongful. While many countries consider that a child’s rights are determined by the country of birth, fears are that DNA testing might lead to exclusion of persons not considered belonging to the country.
An additional concern is the potential effect of the compulsory testing of all visitors, including scientists. We believe that this is likely to lead to the isolation of Kuwaiti research institutions, as visiting scientists may refuse to give samples and therefore will not attend valuable scientific conferences in Kuwait, for example. We consider that the global challenges in human health and demography can best be addressed by all industrialised countries in a collaborative way. We see this new law as a major threat to joint actions in the field of genomic health that involve national European genetic societies.
[i] U.N. rights panel urges Kuwait to amend broad DNA testing law http://www.reuters.com/article/us-kuwait-security-un-idUSKCN0ZV1VY
GeneWatch UK PR: Expansions of police DNA databases worldwide urgently need human rights safeguards
http://www.genewatch.org/article.shtml?als[cid]=566699&als[itemid]=576234
For immediate release: Thursday 8 September 2016
New Kuwaiti law on the collection of human DNA is contrary to human rights and threatens scientific collaboration, says ESHG
The law requiring compulsory DNA testing of all Kuwaiti residents, as well as of all those visiting the country for whatever purpose, is a serious assault on the right to privacy of individuals, and is also likely to lead to the isolation of Kuwaiti scientific research and researchers, the European Society of Human Genetics (ESHG) said today [Thursday 8 September]. In a letter addressed to the Prime Minister and the Council of Ministers of the State of Kuwait, the Society calls upon the government to amend the law.
According to the Kuwaiti government, the new measure has been introduced to try to tackle the problem of terrorism in the country. It provides for the imposition of a one-year prison term and a fine on those who refuse to provide samples. “Not only does this law constitute a disproportionate response to the problem, but the very existence of such a comprehensive database of human DNA could be dangerous in the future, in the event of hacking or a regime change, for example,” said Professor Olaf Horst Rieß, ESHG President.
Another concern for the Society is the potential effect of the compulsory testing of all visitors, including scientists. “We believe that this is likely to lead to the isolation of Kuwaiti research institutions, as visiting scientists may refuse to give samples and therefore will not attend valuable scientific conferences in the country”, said Professor Rieß. “The current global challenges in human health and demography must be addressed by all industrialised countries in a collaborative effort.”
“We see this new law as a major threat to joint actions in the field of genomic health that involve national European genetic societies, and therefore we request the Kuwait government to reconsider and to amend this law so that human DNA is collected for legal purposes only from individuals suspected of having committed serious crimes,” said Professor Martina Cornel, Chair of the ESHG Public and Professional Policy Committee.
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Reproduction of an article in the New Scientist.
Kuwait’s mass DNA database is a huge attack on genetic privacy
The Gulf State will soon be the first nation to force all residents and visitors to hand over DNA, risking its reputation and more, warns geneticist Olaf Rieß
Could collecting DNA have prevented the suicide attack at this Kuwaiti mosque in June 2015? It’s hard to see how
By Olaf Rieß
Compulsory DNA testing of all citizens and visitors sounds like an Orwellian nightmare, but this is the new reality in a wealthy Gulf State. Kuwait has become the first country to order blanket genetic sampling – a worry on so many fronts.
What happens if the DNA database is hacked? And even if the current government can keep the database secure, what might happen in the event of a regime change?
The Kuwaiti government says DNA testing, reportedly due to begin within weeks, is needed to combat terrorism, and introduced the measure in the wake of a bombing that killed 27 people there last year. While the need to have a swab taken may discourage attackers from entering the country, we should not forget that a lot of terrorism these days is home-grown. And who ever heard of a suicide bomber being dissuaded because they might be identified after blowing themselves up?
The government has also said the database could help identify victims. But if a bomb causes many fatalities, DNA will not help much in distinguishing the attacker from those killed. The terrorism argument is so spurious that even the least suspicious among us might begin to wonder whether there is an ulterior motive for this wholesale collection of DNA.
Let’s just try to imagine some of the other potential uses. Worrying examples spring easily to mind: checking paternity in a country with severe adultery laws or trying to uncover someone’s ethnic origin in order to discriminate. And we know from history that many initiatives that started out with the best of intentions have ended up used for nefarious purposes.
Matching names to genes: The end of genetic privacy?
It seems to me, too, that the Kuwaiti government could cause irreparable harm to the country’s economy and reputation. Tourists may not know that their DNA will be collected upon arrival; neither will they understand all that this implies. Some may accept the sampling, but others will choose to stay away.
There are implications for business and science. European industry and research has benefited hugely from the loosening of travel restrictions and the subsequent boosting of trade with Kuwait. Companies will now think twice about opening facilities there.
And will scientists from abroad still wish to attend conferences in Kuwait in the knowledge that their right to privacy will be invaded so dramatically? I think not. This could have a major impact on Kuwait’s standing as a conference host and hinder joint research projects.
As a scientist using genetics to seek medical advances, I also worry that compulsory collection of DNA might affect public willingness elsewhere to support research. If sampling becomes linked to coercion in the public eye, this is likely to reduce people’s readiness to include their genome in research databases, which are so important in the quest to better understand and treat disease.
Kuwait has invested heavily in genetic technology, so collecting DNA on this scale would probably be feasible, at least in the first instance. But the question is not whether it is feasible, but rather whether it is desirable.
The answer is clear; it is neither appropriate nor helpful in tackling the dangers it is designed to confront, and the threat posed in the event of its misuse is highly alarming.
Article amended on 12 September 2016
Since this article was first published, the context of some potential (mis)uses of DNA sampling in Kuwait has been made clearer.
Olaf Rieß is a medical geneticist and president of the European Society of Human Genetics, which has called on Kuwait to abandon blanket sampling
European Human Genetics Conference 2016, May 21-24, Barcelona, Spain
Loss of Y chromosome in blood cells is associated with developing Alzheimer’s disease: new research could lead to a simple test to identify those at risk
Embargo: 00.01 hrs CEST Tuesday 24 May 2016
Barcelona, Spain: Men with blood cells that do not carry the Y chromosome are at greater risk of being diagnosed with Alzheimer’s disease (AD), and this is in addition to an increased risk of death from other causes, including many cancers, the annual conference of the European Society of Human Genetics will hear today (Tuesday). The paper is published today in the American Journal of Human Genetics*. The loss of the Y chromosome, or LOY, is known to affect up to 20% of men who are aged over 80, and is the most common genetic mutation acquired during a man’s lifetime.
Professors Lars Forsberg and Jan Dumanski, from the Department of Immunology, Genetics and Pathology at Uppsala University, Uppsala, Sweden, and colleagues from Sweden, France, the UK, the US and Canada, investigated LOY in over 3200 men with an average age of 73, and an age range of 37-96. Around 17% of them showed LOY in blood cells, and this increased with age. The researchers found that those with an existing diagnosis of AD had a higher degree of LOY, and that LOY was also a marker for the likelihood of developing the disease during the follow-up period.
“The idea for this research project came to me when I was writing our first paper on the relationship between LOY and the development of non-blood cancers,” Prof Forsberg explains. “In thinking about the process known as immunosurveillance – the body’s ability to fight disease development throughout life – I found that it had been well studied in AD, and hence it occurred to me that LOY might be involved in this disease too.”
Using standard molecular techniques, the identification of LOY in blood is easy to determine when it occurs in 10% or more of blood cells with a nucleus containing DNA. As well as being relatively common in older men, it also occurs less frequently in those who are younger.
Since women do not carry a Y chromosome, and men have, on average, shorter lives, it is possible that LOY may be related to the earlier death of men. However, the researchers say, the mechanisms and causes for their findings are still not properly understood. They are currently investigating the functional effects of LOY, and looking at its role in different groups of men and in other diseases, in order to understand better which types of cancer are associated with LOY, as well as whether there is a link with early signs of dementia, for example mild cognitive impairment.
Another question to be answered relates to how LOY in blood cells can be related to disease in other organs. “The blood cells we studied are involved in the immune system, and the fact that LOY in them is associated with disease in other tissues is striking. We therefore hypothesise that the loss of LOY in blood cells leads them to lose part of their immune function,” says Prof Forsberg.
Previous research by the same group has shown that smoking greatly increases the risk of acquiring LOY, by as much as 400%. However, smoking appears to have a transient effect, and is also dose-dependent, so quitting could reverse the effect. This could be important to emphasise in smoking-cessation programmes, the researchers say.
More difficult to tackle is the question of diagnosis and treatment of serious conditions such as AD and cancer. This currently based on identifying clinical symptoms, and the development of diagnostic tools for their earlier detection could lead to strategies aimed at preventing their development before symptoms occur. For example, in the future it might be possible to use an LOY test to identify men at risk and then carry out oncological or neurological evaluations to try to detect early, mild, symptoms of disease. LOY might also become an important diagnostic tool in combination with other biomarkers that may be used to predict risks for various diseases.
“The addition of LOY testing in the general population could give medical practitioners the possibility of using preventive strategies in men at risk,” says Prof Forsberg. “For example, in cancer, primary tumours are usually not deadly; it is the metastatic process that it normally responsible for deaths. If we could predict which men have an increased risk of cancer, we could watch them closely for the development of disease and also use appropriate preventive treatments. In short, the widespread use of LOY testing could radically decrease male mortality rates, and even perhaps eliminate the difference in life expectancy between the sexes.”
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Abstract no: C23.1: Mosaic loss of chromosome Y (LOY) in peripheral blood is associated with age, smoking, shorter survival and increased risk of cancer and Alzheimer’s disease
The research was funded by the European Research Council (ERC), Stiftelsen Olle Engkvist Byggmästare Foundation, Swedish Research Council (VR), the Wellcome Trust, Swedish Cancer Society, Swedish Heart-Lung Foundation, Science for Life Laboratory at Uppsala University, Uppsala University Hospital, Uppsala University, Heart and Lung foundation, GenomEUtwin, NIH, Swedish Foundation for Strategic Research (SSF), French National Fondation on Alzheimer’s disease and related disorders, Fondation pour la récherche sur le cerveau (FRC), Lille Métropole Communauté urbaine, LABEX and DISTALZ.
Discovery of new disease gene will lead to better screening for severe paediatric heart disease
Embargo: 00.01 hrs Tuesday 24 May 2016
Barcelona, Spain: Cardiomyopathy, or a deterioration of the ability of the heart muscle to contract, generally leads to progressive heart failure. It is frequently inherited, and, because approximately 40% of children born with it are likely to die within five years of diagnosis, being able to identify its genetic basis is particularly important. Now, an international team of researchers has identified a new disease gene which is implicated in the development of severe paediatric cardiomyopathies. The gene is probably also involved in a milder, adult-onset form of the condition.
Presenting the results of the study to the annual conference of the European Society of Human Genetics today (Tuesday) Johanna Herkert, MD, a clinical geneticist at the University Medical Centre of Groningen, The Netherlands, will describe how analysis of the exomes (the parts of the genome that produce proteins) of children who were seriously ill with early-onset cardiomyopathies led to the finding that a mutation in the gene alpha-kinase 3 (ALPK3) had been inherited from both their fathers and mothers. In cases where both parents carry the mutation, the risk of having a child with a severe cardiomyopathy is 25%. Since the child does not carry a normal copy of gene the condition will develop at an early age.
“However, several family members who carried only one mutated gene copy also developed cardiac disease, albeit at a later stage in life,” says Dr Herkert. “The identification of these mutations enables us to provide genetic counselling, predictive testing of family members, and prenatal testing in future pregnancies. It also allows us to provide early treatment, and a potential target for drug development in the future.”
The researchers studied five children with cardiomyopathy from three unrelated families of different ethnic backgrounds. The families had previously been screened for mutations in other cardiomyopathy-related genes. Four patients were diagnosed during foetal life, or within hours of birth, and the fifth only developed symptoms at four years old. Three of the children died between 35 weeks of gestation and five days of birth; the other two were still alive at 11 years old, but showed signs of severe cardiomyopathy.
“We knew that mice without a functional ALPK3 gene displayed very similar cardiomyopathy related features to those observed in our paediatric patients,” says Dr Herkert, “but we did not quite know how dramatic its effect would be in humans. Our findings show that we now should include this gene in routine diagnostic screening in order to be able to identify affected children and their family members at risk. This will also give us an insight into the prevalence of ALPK3-related cardiomyopathy in the general population.”
Although the possibility of treating an affected foetus in the womb is still a long way off, the gene could provide a drug development target for a medicine to be administered immediately after birth before the disease has a chance to develop further. Affected family members with only one ALPK3 mutation could also be treated later in life.
“We are currently studying the effect of the ALPK3 mutations on the production of the protein in heart muscle, but also in skeletal muscle, as ALPK3 gene mutations may result in skeletal muscle problems too. Moreover, a large genome study has shown a possible link between ALPK3 and cardiac hypertrophy, or thickening of the heart muscle. We would like to explore this finding further as it may well mean that ALPK3 is implicated in other heart diseases in the general population, and once again this could suggest new treatment possibilities.
“Better knowledge of the precise role of the gene in disease development, as well as the elucidation of the molecular pathways involved, should lead us towards improved clinical care from the point of view of screening and surveillance, and to targeted drug development,” Dr Herkert will conclude.
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Abstract no: C22.2
How does obesity cause disease in organs distant from those where fat accumulates? New genetic evidence points the way
Embargo: 00.01 hrs CEST Sunday 22 May 2016
Barcelona, Spain: Obesity is on the rise throughout the world, and in some developed countries two-third of the adult population is either overweight or obese. This brings with it an increased risk of serious conditions such as heart disease, stroke, cancer and osteoarthritis. Many of these conditions do not appear to affect the parts of the body where the excess fat accumulates, but rather to involve body systems that are remote from the fat accumulation. Now an international group of scientists has taken an important step towards understanding the links between obesity and the related, yet physically distant, diseases it causes, the annual conference of the European Society of Human Genetics will hear today (Sunday).
Ms Taru Tukiainen, D.Sc., a postdoctoral researcher working at the Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland and colleagues from the UK and US, set out to study the relationship between body mass index (BMI), a common-used way of measuring obesity, and gene expression in 44 different tissue types, including some that are rarely accessible in large sample sizes, for example the brain and internal organs. “Most tissue sampling is invasive, but we were able to use the GTEx* dataset of tissues from autopsy donors, and therefore sample a far wider range than is usually possible,” Ms Tukiainen explains. “This is the first time that such changes in human tissue function in response to alterations in BMI have been explored among so many body systems simultaneously.”
The researchers found simultaneous changes in response to obesity in almost all the tissues studied. “These results show that obesity really is a systemic condition, and particularly a condition of systemic inflammation. Interestingly, though, the changes in tissue function appeared to be only partially shared between different types of tissues; some tissues clearly act in pairs with one half of the pair compensating for – or enhancing - the dysfunction of the other. For instance, adipose tissue and adrenal glands, which are both organs secreting hormones essential to metabolism, often react to changes in BMI in completely opposite ways, including a decrease in metabolic activity in the former and an increase in the latter,” Ms Tukiainen will say.
Although lifestyle changes are the most effective way to combat obesity, they can be hard work and difficult to maintain. Therefore the biological processes identified by the researchers may help the treatment of obesity by identifying potential drug targets, and particularly tissue-specific targets, they say. The results may also help to distinguish groups of individual who are at higher risk of developing complications, and lead toward personalised care.
“Our research highlights the burden of overweight and obesity on the digestive system. Although this is unsurprising, given the role of digestive system tissues in food processing, we found alarming links between BMI-related changes in different parts of the digestive tract and genes implicated in some diseases, for example Crohn’s disease.
“An association between two variables does not necessarily imply there is a causal link and, from the gene expression results alone, we cannot tell which is driving which. Do changes in BMI or changes in gene expression come first? We can, however, address the potential causes by using genetic variants known to be associated with BMI in combination with our data on gene expression,” says Ms Tukiainen.
Large-scale genome-wide association studies have already identified nearly 100 genetic variants that influence BMI. Analyses by the group that interpret this information further have shown that many of these gene expression changes, particularly in adipose tissue, appear to be caused by increased BMI.
“I believe that our work adds to the weight of evidence, and provides hypotheses for other researchers to follow up in the hope of being able to translate the results into ways of preventing and treating the very serious complications of obesity,” Ms Tukiainen will conclude.
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*GTEx is a dataset consisting of thousands of tissue samples in which the RNA from each sample has been sequenced to measure gene expression. Because it is not a dataset collected specifically for obesity research, the donors are representative of the population as a whole, and the obesity epidemic is clearly reflected in that only 31% of GTEx donors are or normal weight; the remainder are either overweight or obese.
Abstract no: C08.1 – Multi-tissue transcriptome analysis reveals disease-relevant and causal links between obesity and gene expression
GTEx is funded by the US National Institutes of Health. Ms Tukiainen is funded by the Academy of Finland.
Mouse studies hold promise for a simple, non-surgical treatment for an aggressive gastric neuroendocrine tumour
Embargo: 00.01 hrs Friday 20 May 2016
Barcelona, Spain: Patients with aggressive neuroendocrine tumours (NETs) have limited treatment options and there are few oncologists who are specialised in this relatively rare disease. Normally a total gastrectomy (removal of the stomach) is employed in these cases, with a subsequent dramatic reduction in the quality of life for patients. Now researchers have identified a mutation in the human ATP4a gene that is involved in the gastric acid secretion regulation and has been identified as responsible of an aggressive form of inherited, early-onset gastric NET.
Dr Oriol Calvete, from the Human Genetics Group at the Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain, will present his work to the annual conference of the European Society of Human Genetics tomorrow (Saturday). “Our research has enabled us to determine important clinical ‘red lights’ for the early diagnosis of patients who will develop these tumours at a younger age, and to identify characteristics that distinguish a good from a poor prognosis for these patients,” he says.
The researchers generated a genetically-engineered mouse carrying the mutation. This developed most of the changes seen in human patients, including not just achlorhydria (a lack of or total absence of gastric secretions in the stomach), but also iron-deficiency anaemia and other pathological changes that replicate the human clinical traits involved, through the presence of which the researchers were able to confirm the mutation as the primary one responsible for the development of gastric NETs.
The researchers were able to restore chlorhydria in affected mice by adding a 3% solution of hydrogen chloride to their drinking water. Mice that drank this water from birth did not develop gastric NETS, and in those where treatment was started later in the life cycle, the main causative biochemical alterations responsible for their development were blocked. “Gastric acid regulation is quite complicated,” Dr Calvete explains. “Because gastric secretions are activated by the intake of food via the stomach, there are no signs of being abnormal before birth, but by restoring normal gastric acid balance as soon as possible afterwards, we can eliminate the conditions that lead to the development of tumours.”
NETS develop in the neuroendocrine system that is responsible for producing the hormones that regulate the working of different organs in the body. They are rare, incurable, and treatments for them are limited, especially once they become advanced. Because all NETS are classified as rare diseases by regulatory authorities in the EU and the US, there are few drugs available to treat these patients.
“The younger age of onset – around 30 years - of this particularly aggressive form of gastric NET in humans means that it is particularly important to try to find a treatment that is relatively simple, cheap, and does not compromise quality of life,” says Dr Calvete. “Total gastrectomy at 30 years old can have a devastating effect, and because NETS are highly infiltrating tumours, does not always mean that it will avoid metastasis. We hope that our work has given a lead towards a way of avoiding patients having to undergo this kind of aggressive surgery.”
“Additionally, the genetically-engineered mouse model will allow us to test potential treatments aimed at correcting achlorhydria, not just for gastric NETS, but also for other diseases of the gastrointestinal system such as Barrett’s oesophagus (chronic inflammation of the lower part of the oesophagus), or hiatus hernia,” says Dr Calvete.
The researchers are now intending to carry out further investigations into the genetic causes of other gastric NETS. “For example, we have studied two more families with similar pathological characteristics, but with no mutation in the ATP4a gene. This implies that other genes may be responsible and we hope to discover them using a similar methodology,” Dr Calvete will conclude.
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Abstract no: P12.098B
The research was funded by the Spanish Center for Biomedical Network Research on Rare Diseases (CIBERER), by the European Commission’s Horizon 2020 (BRIDGES project) and by the Spanish Government’s Proyectos de investigación en Salud (PIS) PI012-00070.
For immediate release
The proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) negotiations, currently at the stage of tripartite negotiations between the Council (representing Member State governments), the European Parliament, and the European Commission, still risks restricting the rights of patients and doctors to carry out essential genetic testing, says the European Society of Human Genetics (ESHG) today (19 October 2015) in a statement issued by a range of organisations representing geneticists and patients.
ESHG 2015 Conference Press Release: People want access to their own genomic data, even when uninterpretable
Glasgow, United Kingdom: The largest study to date of attitudes towards the use of genomic information shows that the majority of people want access to results from genome sequencing, even if these are not directly related to the condition for which the analysis has been undertaken. This applies even when the data are not health-related or are simply ‘raw’, a researcher will tell the annual conference of the European Society of Human Genetics today (Monday).
Dr Anna Middleton, a Principal Staff Scientist at the Wellcome Trust Sanger Institute, Cambridge, UK, will describe the results of a survey into the attitudes of the various groups involved in sequencing research – patients, public, health professionals, and genomic researchers – towards the types of genomic information they would be interested in receiving. Just under 7000 people from 75 countries took part in an on-line survey, advertised on social and traditional media, and by an email list-serve.
“We asked participants to imagine that they were taking part in sequencing research with the option to receive personal results, and carefully explained the sorts of results that might come from a sequencing study in ten short films. We found that 98% of participants wanted to know about genes linked to treatable conditions that were serious or life-threatening; they were still interested even if the chance of such a condition occurring was as low as 1%. What was important to them was being ‘forewarned’ about their future risk of disease so that they could take steps to protect their health. This makes sense, but we also found that 59% of those surveyed were interested in having access to their own raw data, even though, on its own, it would tell them nothing useful about their future health. Participants perceived a value a value in raw data that may or may not exist: ‘if the scientists know it, I’d like to know it too.’ They felt the genomic information simply ‘belonged to them’ and thus they should be able to have access to it, even if the reality was that they would do nothing with it,” Dr Middleton will say.
Participants appeared to be excited and positive about genomics, and they also wanted to be connected to the research process; for example, they were keen that genomic researchers should keep re-analysing their data and report to them if there were new findings. But they also recognised that scientists had an important job to do in doing good quality research; the work of answering a particular research question should not be side-tracked by a necessity to supply personalised results. Participants said they were willing to forego the return of individual findings if the delivery of such data compromised the ability of scientists to focus on the answer to a research question.
“It would now be very helpful to explore the value that people put on genomic data. For example, would they pay for an interpretation and, if so, how much?” says Dr Middleton. “Creating clinical-grade health information in a research setting requires funding, resources, and strong clinical connections to the health professionals who will deliver it, explain it, and follow up the patient. This may be out of reach for many researchers. So if research participants expect personalised results, but they also don’t want researchers to compromise their research in order to deliver such results, then would they be willing to pay for these services?
“What we did in our research is explore what people say they might do in a hypothetical situation, and what we need to do next is explore the actual experience of research participants who are given personal results from sequencing research. We know already that some research participants ask for their raw sequence files and so it would be really useful to follow such participants over time to see what they do with these. We also want to know more about the psychosocial impact of receiving genomic data and whether it has an emotional resonance that people didn’t expect.
“Researchers have a responsibility not to harm their research participants, and if they are going to provide results, they need to do this in an ethical way. At the moment our genomics community agrees that if researchers choose to return results that could potentially be clinically actionable these need to be confirmed in a clinically accredited laboratory before they are returned, and there should be a clinician available to share the information with the patient and to provide screening services if necessary. For research participants who ask for their raw sequence data (that by their very nature, come with no interpretation), then they should be given a clear explanation of the limits of these data together with some signposts to services that they can access for interpretation and support. Without this there is a risk that research participants will turn up at the door of their GP and ask them what it all means.” Dr Middleton will say.
“Whilst I feel that autonomy is important, and research participants do have the right to their own data, should they want them, we also have a responsibility to explain the reality of the difficulties with interpretation – and to do this without misleading people. By allowing research participants access to raw sequence data, they have the choice as to how these are explored and what sorts of information they would like to glean from them. However, they can only really do this when there is easy access to interpretation services that can be endorsed by health professionals and genomic researchers alike. Such services are not easily accessible currently and there is an urgent need to address this if sharing raw sequence data becomes a reality. Some of our participants mistakenly thought they could put their data into Google and an interpretation would pop out. Researchers mustn’t leave their participants stranded, so they should only share raw sequence data together with an explanation of what can be done with this. We also have to think carefully about the potential impact of this on health services,” she will conclude.
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Abstract no: C14.5
Anna Middleton is a member of the Deciphering Developmental Disorders (DDD) project (www.ddduk.org). The DDD project is funded by the Health Challenge Fund, a partnership between the Wellcome Trust and the UK Department of Health.
ESHG 2015 Conference Press Release: Non-invasive prenatal testing: effective, safe, preferred by parents, and applicable in a range of disorders
Glasgow, United Kingdom: Non-invasive prenatal testing (NIPT) for Down’s syndrome is feasible, acceptable to parents, and could be introduced into the National Health Service (NHS), UK researchers say. The results of a National Institute for Health Research (NIHR) study carried out by the first NHS laboratory to provide NIPT testing will be reported to the annual conference of the European Society of Human Genetics today (Saturday).
Presenting her team’s findings, Professor Lyn Chitty, from the UCL Institute of Child Health and Great Ormond Street Hospital, London, UK, will announce the results of the study evaluating the possibility of introducing NIPT into the NHS screening programme for Trisomy 21 (Down’s syndrome). The researchers will present their study to the UK National Screening Committee later this month and hope that it will inform their decisions on if and how to implement NIPT in the NHS.
As part of the study, carried out by the NHS laboratory at Great Ormond Street Hospital, women at high and medium risk of having a child with Down’s syndrome were offered NIPT, and over 2,500 undertook the test.
Prof Chitty says: “There was a very high uptake of testing and we saw invasive test numbers fall sharply. NIPT performed well in identifying problems, and women were very positive about it.
“The cost of providing an NIPT service will depend on the cost of the test itself and how it is implemented. There will be significant savings resulting from a decrease in invasive testing whilst increasing the detection of affected babies. The reduction in invasive testing also means there will be a reduction in miscarriages and loss of unaffected babies which is much better for parents.”
Commenting on NIPT, a woman classified as ‘high risk’ who was involved in the study said: “You get told 1 in 30 and although that sounds relatively high…we probably wouldn’t have done [invasive testing] because there’s a risk of miscarriage. ..I think that we were very lucky. It’s enabled us to make an informed choice about what happens for the rest of our lives.”
Another woman involved in the study said: “I think it’s a real advancement. At the moment, if you are put in a high risk category you’re automatically offered the invasive test, whereas this will reduce the amount of invasive tests that need to take place.”
Reporting the results of a second study from the same group, Dr Suzanne Drury, a translational research and development scientist from Great Ormond Street Hospital, will describe the team’s experience in the use of NIPD (non-invasive prenatal diagnosis) to diagnose the disorder congenital adrenal hyperplasia (CAH). CAH exposes a female fetus to male hormones, which can result in the development of masculinised external genitalia. It is an autosomal recessive (AR) disorder, in which the defective gene must be passed on from both parents in order to cause disease.
Dr Drury will say: “We chose CAH because the gene that causes it is particularly challenging to study. It is the most common adrenal disorder in childhood and affects one in every 18,000 live births. In the UK, NIPD for fetal sex determination is carried out for an average of 13 pregnancies per year at risk of CAH because it is the female fetuses that are at risk.
“Fetal sex determination allows targeting of invasive testing to see if the female fetus is carrying two mutant copies of the CAH gene and is therefore affected. As we were already carrying out NIPD for sex determination, and there is a potential in utero treatment for CAH available, we felt that this was a good condition to select to allow treatment to be very specifically targeted to only those female fetuses that are affected.”
In 2014, the researchers say, 32% of prenatal diagnostic tests for monogenic disorders in their laboratory were non-invasive. NIPD for single gene disorders in a fetus is diagnostic, as it targets specific genetic changes present in a high risk family. For this reason it will remove the need for invasive testing completely, reducing the risk of miscarriage and making prenatal diagnosis for these conditions safer and more accessible to families who would not otherwise be prepared to take the risk.
Dr Drury adds: “Our results have shown NIPD to be sufficiently precise to be diagnostic and therefore we do not recommend confirmatory invasive testing. Currently we are developing non-invasive tests for other conditions caused by mutations in a single gene, including cystic fibrosis, sickle cell anaemia, and beta-thalassaemia. At present invasive testing is required for definitive prenatal diagnosis of these disorders, but our experience with CAH leads us to believe that NIPD will have the same diagnostic efficacy in other AR disorders.”
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Abstract nos: C01.1 and C01.3
Prof Chitty’s work was funded by National Institute for Health Research (NIHR) Programme Grants for Applied Research (RP-PG-0707-10107), the NIHR Biomedical Research Centre at Great Ormond Street NHS Foundation Trust, and the Great Ormond Street Hospital Children’s Charity.
Dr Drury’s work was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research (RP-PG-0707-10107), the NIHR Biomedical Research Centre at Great Ormond Street NHS Foundation Trust, and the Great Ormond Street Hospital Children’s Charity.
ESHG 2015 Conference Press Release: Non-invasive prenatal foetal testing can detect early stage cancer in mothers
Glasgow, United Kingdom: Non-invasive prenatal testing (NIPT) for chromosomal foetal disorders is used increasingly to test for conditions such as Down’s syndrome. NIPT examines DNA from the foetus in the mother’s blood, and therefore does not carry the risk of miscarriage involved in invasive testing methods. Now, for the first time, researchers have found another advantage of NIPT; it can detect maternal cancers at an early stage, before symptoms appear. The study, to be presented to the annual conference of the European Society of Human Genetics today (Saturday), is published simultaneously in the journal JAMA Oncology.
Nathalie Brison, PhD, a senior scientist in the Clinical Cytogenetics laboratory at the Centre for Human Genetics, UZ Leuven, Leuven, Belgium, will tell the conference that the team had set out to increase the accuracy of the NIPT test in order to overcome some of the technical problems that can cause it to come up with false negative or false positive results when screening for chromosomal disorders in the foetus. Down’s, or trisomy 21, is the most frequent chromosomal abnormality, and occurs in about one in 700 live-born babies. The risk of giving birth to a baby with Down’s increases with the age of the mother, and rises sharply from the age of 36 years.
“We therefore felt it important that we improved the accuracy of the test,” Dr Brison says. ”Even though it is very reliable, we believed that we could make it even better, and in doing so we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes - Down’s, Edward’s (trisomy 18), and Patau (trisomy 13). Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified three different genomic abnormalities in three women that could not be linked to either the maternal or foetal genomic profile. We realised that the abnormalities bore a resemblance to those found in cancer, and referred the women to the oncology unit.”
Further examination, including whole body MRI scanning and pathological and genetic investigations, revealed the presence of three different early stage cancers in the women: an ovarian carcinoma, a follicular lymphoma, and Hodgkin’s lymphoma. Although this incidence is within the range to be expected in the normal population (one per 1000-2000 person years in women aged 20 – 40), without NIPT these cancers would have been unlikely to have been detected until they became symptomatic, and therefore at a much later stage.
“Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT,” comments principal investigator Professor Joris Vermeesch, Head of the Laboratory for Cytogenetics and Genome Research at Leuven. “During pregnancy, cancer-related symptoms may well be masked; fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women.”
Two out of the three diagnosed women were treated, one of them during her pregnancy. She subsequently gave birth to a healthy girl. The third had indolent disease that was not considered to be in need of treatment at that stage. Follow-up investigations in the treated women showed that NIPT had the additional advantage of allowing the effectiveness of treatment to be monitored, and the researchers were able to see that the chromosomal profiles became normal during and after chemotherapy.
Because the procedure involves looking at chromosomes other than 13, 18, and 21, women taking part were informed about the possibility of incidental findings. “However, our study feeds into the ethical debate about whether or not to report incidental findings to patients, and also has implications for the current political discussions concerning reimbursement and funding of NIPT by national health care systems,” says Prof Vermeesch.
The results suggest that NIPT might enable the detection of pre-symptomatic cancers not just in pregnant women, but more widely. “We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods,” says Dr Brison. “The normalisation of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy. Of course, larger scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage.”
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Abstract no: C01.5
The work was funded by the University of Leuven, the Belgian Cancer Plan (Ministry of Health), and the Belgian Science Policy Office.
ESHG 2015 Conference Press Release: First national study of non-invasive prenatal testing shows it works and is preferred by high-risk women
Glasgow, United Kingdom: Results from a national study of non-invasive prenatal testing (NIPT) in women at high risk of having a baby with Down’s syndrome will be presented at the annual conference of the European Society of Human Genetics today (Saturday). The Netherlands is the first country in the world to include NIPT in a government supported, healthcare-funded trisomy syndrome screening programme. In many other countries, such screening is offered by commercial companies and without governmental guidance, so studying the accuracy of the programme and its acceptability to prospective parents was important, the conference will hear.
Dr Erik Sistermans, head of the Genome Diagnostics department, VU Medical Centre Amsterdam, The Netherlands, will present results from the TRIDENT (Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing) study, of which he is the project leader. Together with colleagues from other academic centres in The Netherlands, he formed a consortium including all stakeholders – gynaecologists, clinical geneticists, midwives, and laboratory specialists – to apply for the ministerial licence which is needed to screen for untreatable disorders such as Down’s.
“The study was in two parts; first concerned with its implementation in eight university laboratories, and the second to examine the perspective of pregnant women. After receiving positive advice from the Health Council, a temporary licence for two years was granted allowing us to enrol women with an elevated risk of carrying a foetus with three syndromes caused by the presence of an abnormal number of chromosomes - Down’s (trisomy 21), Edward’s (trisomy 18), and Patau (trisomy 13),” Dr Sistermans will say. Entry to the study was based on the results of a combined test, taking account of maternal age and involving a blood test and a nuchal fold measurement – a measurement of a skin fold in the neck of the foetus.
After nine months, 3306 high-risk pregnant women had undergone NIPT and 3278 reports on the status of the foetus issued. The researchers found 89 cases of trisomy 21, 11 of trisomy 18, and ten of trisomy 13. Follow up of 103 cases revealed only nine false positives.
Although NIPT carried a much lower risk of miscarriage than do invasive tests, it is slightly less accurate, because it only analyses DNA from the outer layers of the placenta. In some cases a trisomy will be present in these outer layers, but not in the foetus. “For this reason a positive NPT result should always be followed by an invasive test,” says Dr Sistermans.
“Currently the costs for NIPT and invasive tests are about the same, but we believe that with a greater uptake of NIPT the cost will fall. Given that the vast majority of the women we surveyed preferred to undergo NIPT in order to be more certain of avoiding risks to the child, it seems likely that the demand for this test will increase over the years to come.”
The researchers now expect the Dutch Heath Ministry to continue the offer of NIPT as a second test to women at high risk of carrying a child with a trisomic disorder. “Whether NIPT will be offered as a first screening test to all pregnant women is currently under debate, and will depend partly on the reaction of the health ministry to our study. Based on our findings, the TRIDENT consortium believes this test can benefit all pregnant women, not just those who are identified as being at risk, and has applied for a licence to offer it to them,” Dr Sistermans will conclude.
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Abstracts no: C01 and PS01.49
The research was funded by the Ministry of Health, the Dutch health insurance companies, and the Netherlands Organisation for Health Research and Development (ZonMw).
ESHG 2015 Conference Press Release: Discovery of new genetic mutation in aortic disease allows better diagnosis and brings personalised medicine a step closer
Glasgow, United Kingdom: Thoracic aortic aneurysm and dissection (TAAD), an enlargement or tearing of the walls of the aorta in the chest, is, together with abdominal aortic aneurysms, responsible for about 2% of all deaths in Western countries. The aorta is the largest artery in the body, and carries blood from the heart. About one out of every five patients with TAAD has a family member with the same disorder, therefore indicating a genetic cause. However, the relevant genetic mutations discovered so far only explain about 30% of all cases. Through the study of a large family with TAAD features, an international team of genetic researchers have now discovered that a mutation in the TGFB3 gene is also responsible for the condition.
Elisabeth Gillis, MSc, a PhD student in the Centre for Medical Genetics at Antwerp University Hospital, Antwerp, Belgium, will tell the annual conference of the European Society of Human Genetics today (Saturday) that she and colleagues from seven other countries are the first to link this particular genetic mutation to serious aortic disorders. This is important, she says, because it means that the TGFB3 gene can be included in diagnostic screening. “Armed with this knowledge, we can screen patients with symptoms of TAAD, and also family members without symptoms. Early identification of a risk of aortic aneurysm formation will allow us to implement preventive treatment with medication aimed at slowing down the process of aneurysm and, ultimately, replacement of the aorta before a significant risk of dissection arises”, she will say.
An aortic aneurysm occurs where there is a weakness in the walls of the aorta, creating an outward bulge. Weakness in the aorta is dangerous, because it can lead to rupture (dissection) which is life-threatening.
The researchers studied 9 patients from a large Flemish-Dutch family with the cardiovascular, skeletal and facial features typical of a form of TAAD, called Loeys-Dietz syndrome. They screened DNA from each family member without finding any genetic mutations known at that stage to be connected with TAAD. However, further investigation revealed two candidate genomic regions that appeared to be involved, one of which contained the TGBF3 gene. “This gene was an obvious candidate because it has previously been shown that the TGFbeta-signalling pathway has a key role in the formation of aortic aneurysm,” says Ms Gillis.
After sequencing the gene, the researchers identified a mutation that was present in all affected family members. Finally, 470 TAAD patients were screened for TGFB3 mutations, and causal mutations were found in ten other families.
“This is an important finding because incidence of TAADs may be much higher than currently reported,” says Ms Gillis. “Acute aortic dissections may be disguised as heart attacks, and we know that the genetic component of TAAD is strong – in about 20% of patients, it is also found in family members. Therefore anything we can do to enable early identification of people at risk will help. However, aortic aneurysm formation is not yet fully understood, so reversing the risk of dissections remains a challenge, even though effective treatments are available.”
The choice of treatments for TAAD depends on a number of factors, such as size/location of the aneurysm and rate of growth. Current therapies include surgery, for example replacing the weakened part of the aorta, and medical treatments such as beta-blockers or angiotensin receptor blockers.
“Research on the TGFbeta-pathway in TAAD is far from finished. In addition to investigating further the role of these mutations in the condition, the discovery of new TGBF3 patients will help us improve follow-up guidelines for them. We hope that the identification of these new genetic factors will speed progress towards truly personalised medicine. The more we can link mutated genes to specific patients, the more we can identify the right symptoms and link specific therapies to them,” Ms Gillis will conclude.
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Abstract no: C05.2
The research was funded by the European Research Council, the Fondation Leducq, the University of Antwerp, and the Fund for Scientific Research, Flanders.
ESHG 2015 Conference Press Release: Novel genetic mutations may arise during early embryonic development rather than being acquired from the parents’ germline
Glasgow, United Kingdom: New, sophisticated gene sequencing techniques are leading to an increasing understanding of the causes of genetic disease, and can help parents with affected children make informed reproductive choices, the annual conference of the European Society of Human Genetics will hear today (Saturday). Until now, de novo genetic mutations, alterations in a gene found for the first time in one family member, were believed to be mainly the result of new mutations in the sperm or eggs (germline) of one of the parents and passed on to their child.
Using whole genome sequencing technology, researchers from The Netherlands have now succeeded in determining that at least 6.5% of de novo mutations occur during the development of the child (post-zygotic) rather than from the germline of a parent. The research is published today in the American Journal of Human Genetics.
Christian Gilissen, PhD, Assistant Professor in Bioinformatics at Radboud University Medical Centre, Nijmegen, The Netherlands, will tell the conference that, due to the technical difficulties of identifying and validating post-zygotic events, until now there have been very few estimates as to how common they are. “Determining exactly how many mutations occur during the development of the child has been challenging because conventional genetic sequencing is not sensitive enough to reliably identify post-zygotic mutations,” he will say.
Unlike germline mutations, the post-zygotic genetic changes are only present in a proportion of the cells of the individual. This is important because the proportion in which the de novo mutation is present in a patient, as well as the type of cells in which it occurs, may not only determine the clinical outcome of a disease for the patient, but also affect the risk of the parents having another child with the same disease in future pregnancies.
“Currently, patients with a child with a disease caused by a de novo mutation are counselled that the risk of recurrence due to the same mutation in another child is between 1 and 5 percent, but if the disease is the result of a post-zygotic change, the recurrence risk will be extremely low,” says Dr Gilissen. Better information on the origin of de novo mutations will enable better information on recurrence risk, and will enable parents to make more informed reproductive choices.
It is difficult at this stage to foresee the full impact of post-zygotic mutations in terms of treatment options for disease because the study was mainly focused on the technological aspects of these genetic changes, the researchers say. “The knowledge that our genomes may be much more dynamic and changeable than previously thought and the ability to detect such changes by using sophisticated sequencing techniques will certainly have clinical implications in the future. It may also be reasonable to assume that post-zygotic mutations restricted to specific types of cells, or organs, may also be involved in causing disease.
“We now also know that for us to be able to find post-zygotic mutations, our sequencing needs to be even more sensitive. We intend to follow up this work by trying to get yet more detail on the prevalence of such mutations as well as by testing for these events in other tissues; most genetic investigations are performed only in blood, so we may have missed some disease-causing mutations by not testing elsewhere,” Dr Gilissen will conclude.
(ends)
Abstract no: C02.6
The work was partially funded by the Netherlands Organisation for Scientific Research and the European Research Council.
ASHG and ESHG Issue Position Statement on Non-Invasive Prenatal Screening
For Immediate Release
Tuesday, March 25, 2015
16:00 hrs CET
BETHESDA, MD, USA and VIENNA, AUSTRIA – Two of the world’s largest professional societies of human geneticists have issued a joint position statement on the promise and challenges of non-invasive prenatal testing (NIPT), a new procedure to test blood drawn from pregnant mothers for Down syndrome and other chromosomal disorders in the fetus. The document addresses the current scope of and likely future improvements in NIPT technology, ways it may best fit with existing prenatal screening tools and protocols, options and priorities in its implementation, and associated social and ethical issues.
The statement, drafted by the Social Issues Committee of the American Society of Human Genetics (ASHG) and the Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), was published online March 18 in the European Journal of Human Genetics.
Current prenatal screening protocols for common structural abnormalities in the chromosomes vary among countries and medical practices. Generally, though, pregnant women are offered a combined first-trimester screening (cFTS), a risk assessment test based on blood and ultrasound markers. Women who receive abnormal cFTS results undergo a second step of testing to confirm or deny whether the fetus has a chromosomal abnormality such as Down syndrome. This second step involves invasive procedures, such as amniocentesis, that in 0.5-1% of cases may lead to a miscarriage.
One important drawback of cFTS is the high rate of false alarms that lead to invasive procedures that put pregnancies at risk when the fetus is actually chromosomally normal. The main benefit of NIPT, apart from a significantly higher detection rate, is that it dramatically lowers the false alarm rate from about 5% to about 0.2%, making prenatal screening more accurate and safe. This is achieved by analyzing fragments of DNA in maternal blood, some of which provides information about the fetus. The fact that this ‘fetal DNA’ actually derives from the placenta is one reason why NIPT is not fully reliable. An important implication of this is that women who receive an abnormal NIPT result should still be advised to confirm this result through a second step of testing if they are considering a termination of pregnancy, the statement authors write.
The authors explored the benefits and drawbacks of various ways to implement NIPT, such as adding it to the current two-step process or using it to replace cFTS. As NIPT is significantly more expensive, the cost per test would need to be reduced considerably for the latter option to be feasible in fully funded prenatal screening programs, they noted. They also considered implications of the technology, including pressures on women to undergo the test and act upon the results, and the loss of ultrasound data that would indicate fetal problems if that step is removed from the screening process.
“Throughout our discussion, we kept in mind that the goal of prenatal screening is to enable autonomous, informed reproductive choices by pregnant women and their partners, not to prevent the birth of children with specific abnormalities,” said Yvonne Bombard, PhD, 2014 chair of the ASHG Social Issues Committee.
The two committees also addressed emerging advances in NIPT technology that would allow testing for additional genetic conditions, such as rare microdeletion syndromes and syndromes that interfere with sexual development. They noted that as NIPT grows to include more conditions – producing results of varying certainty – pre-test genetic counseling will become significantly more complex.
“We are concerned about prematurely expanding NIPT beyond Down syndrome and a few other chromosomal abnormalities to include rare conditions for which it may not be sufficiently validated, or of which the clinical implications may not be fully understood. For example, parents-to-be will have to make difficult choices about how to act upon abnormal results for such conditions,” said Wybo Dondorp, PhD, first author of the statement.
“A related concern about prematurely expanding the scope of the test is that it will reverse the significant decrease in false alarms and subsequent need for follow-up diagnostic procedures, which has been regarded as the main gain of NIPT in prenatal screening,” said Diana Bianchi, MD, a member of the ASHG Social Issues Committee and co-author on the statement.
The statement authors also considered the longer-term question of how extensive prenatal genetic screening should be, and emphasized the role of infrastructure in enabling responsible use of NIPT. Priorities included educating health professionals and the public about its benefits and limitations, promoting equal access despite cost issues, controlling the quality of pre-test counseling and laboratory practices, and systematically evaluating the whole process. In all, the two committees published ten recommendations for the broader implementation of NIPT, including suggested next steps.
“We are excited about the potential of NIPT to produce more accurate results and reduce the need for invasive testing,” said Martina Cornel, MD, PhD, chair of the ESHG Public and Professional Policy Committee. “However, in view of its future potential, the responsible introduction and expansion of this technology remains an important challenge. In countries where prenatal screening is offered as a public health service, governments and public health authorities should take a more active role in this regard.”
Resource: W Dondorp et al. (epub 2015 Mar 18). Non-invasive prenatal testing for aneuploidy and beyond: Challenges of responsible innovation in prenatal screening. European Journal of Human Genetics. DOI: 10.1038/ejhg.2015.57
About the European Society of Human Genetics (ESHG)
The European Society of Human Genetics is a non-profit organization. Founded in 1967, its aims are to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. The Society encourages and seeks to integrate research and its translation into clinical benefits and professional and public education in all areas of human genetics. www.eshg.org
About the American Society of Human Genetics (ASHG)
Founded in 1948, the American Society of Human Genetics is the primary professional membership organization for human genetics specialists worldwide. Its nearly 8,000 members include researchers, academicians, clinicians, laboratory practice professionals, genetic counselors, nurses, and others with an interest in human genetics. The Society serves scientists, health professionals, and the public by providing forums to: (1) share research results through the ASHG Annual Meeting and in The American Journal of Human Genetics; (2) advance genetic research by advocating for research support; (3) educate current and future genetics professionals, health care providers, advocates, policymakers, educators, students, and the public about all aspects of human genetics; and (4) promote genetic services and support responsible social and scientific policies. For more information, visit: http://www.ashg.org.
ESHG 2014, Milan - Uncovering deletions and duplications in the exome can help pinpoint cause of unexplained genetic diseases
Embargo: 00.01 hrs CEST Monday 2 June 2014
Milan, Italy: Analysis of genetic variation in the exome, the DNA sequence of genes that are translated into protein, can aid in uncovering the cause of conditions for which no genetic cause could previously be found, and this can directly impact clinical management, the annual conference of the European Society of Human Genetics will hear today. Dr Jayne Hehir-Kwa, Assistant Professor of Bioinformatics in the Translational Research group, Department of Human Genetics, Radboud UMC, Nijmegen, The Netherlands, will describe results from her group’s study that set out to determine whether copy number variants (CNVs), large genomic deletions or duplications, can contribute to diseases other than intellectual disability.
The role of CNVs in intellectual disability is well known, but their implication in other conditions is less so. “There are, for example, case reports describing deletions in blindness, but no-one has determined the full extent of CNVs in other patient groups,” Dr Hehir-Kwa will say.
The team screened 600 patients for which no diagnosis or causal mutation could be found using current whole exome sequencing (WES) methodology, and looked genome-wide for a causal deletion or duplication. It is, they say, the first time anyone has screened systematically for a disease mechanism in such a large and diverse patient group, including five heterogeneous conditions – intellectual disability, deafness, blindness, metabolic disorders, and movement disorders.
“For these patient groups, targeted gene approaches have been traditionally used for mutation screening and hence the contribution of CNVs to these disease groups has never been established and genome-wide testing rarely applied,” says Dr Hehir-Kwa. “Our results show that CNVs are a relatively common, clinically-relevant event.”
CNVs were found in patients with many different kinds of disorders, for example retinitis pigmentosa (blindness), Usher syndrome (deafness), Bethlem/Ulrich myopathy (a congenital form of muscular dystrophy), hypotonia-cystinuria syndrome (a neonatal-onset metabolic disorder) and X-linked immunodeficiency (an inherited disorder of the immune system).
“Although WES is not perfect in terms of completely cataloguing genomic variation, our work has shown that it can play an important part in diagnosis. In addition to helping us devise better clinical management strategies for patients, it also affects their prognosis and provides information which can aid us with reproductive counselling for affected individuals,” says Dr Hehir-Kwa. “As a result, we are now offering the CNV screening performed in our study as a standard diagnostic procedure in exome analysis for patients where the genetic cause of their condition has not been found previously.”
The diagnostic yield differs between the different disease categories, the researchers say. Traditional screening for genetic mutations can explain 27% of intellectual disability, 52% of blindness, and up to 20% of individuals with mitochondrial and movement disorders. “This means that between 48-80% of patients screened with WES are not given a genetic diagnosis. By looking for CNVs in the exon regions of these undiagnosed patients we estimate that we can find such a diagnosis in about a further four percent. In particular, the blindness conditions seem to have the highest yield of CNVs – up to seven percent,” says Dr Hehir-Kwa. “I would like to see screening for more types of genomic variants become standard procedure in genetic diagnostics. The genome of an individual can contain all kinds of different variants, in all shapes and sizes, and it is important that we take all these variations into account.”
WES, when offered as a first tier diagnostic test, can give a high diagnostic yield, and the result is faster diagnostics at lower cost. “The more complete and thorough we can make such a diagnostic test, the more accessible we make genetic testing for the public. However clinical health care professionals need to be well informed about the different genetic disease mechanisms to provide the best possible counselling for patients,” Dr Hehir-Kwa will conclude.
(ends)
Abstract no: P14.80/M
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 2000 members from 72 countries. About 3000 delegates are expected to attend this year’s conference.
ESHG 2014, Milan - Discovery of new genes involved in food preferences will revolutionise diets and improve health
Embargo: 00.01 hrs CEST Monday 2 June 2014
Milan, Italy: New understanding of the genes involved in taste perception and food preferences could lead to personalised nutrition plans effective not just in weight loss but in avoiding diseases such as cancer, depression, and hypertension, Italian researchers will tell the annual conference of the European Society of Human Genetics (ESHG) today (Monday). Knowing why individuals prefer certain food tastes and being able to personalise health interventions based on them will help people age in a healthier way and greatly improve their quality of life, as well as engender considerable savings for health systems, they say.
Dr Nicola Pirastu and Dr Antonietta Robino, from the University of Trieste and the IRCCS Burlo Garofolo Institute for Maternal and Child Health, Trieste, Italy, set out to identify novel genes and pathways involved in taste perception and food preferences, and to investigate their implications in protecting against or predisposing to diet-related disorders such as overweight, obesity, and diabetes. “To date most studies have focused on specific taste receptors, especially bitter ones, and this has been partly successful in an attempt to understand the genetics behind the perception of specific compounds such as caffeine and quinine,” says Dr Robino. “Our work has expanded these studies to the whole genome, with the goal of clarifying which specific genes drive individual differences in taste perception and food preferences.”
The researchers undertook genome wide association studies (GWAS) to try to unravel the genetic basis for certain food preferences. 2311 Italian subjects participated in the discovery step, while 1755 from other European countries and from Central Asia were used in order to further verify the findings. They uncovered 17 independent genes related to liking for certain foods, including artichokes, bacon, coffee, chicory, dark chocolate, blue cheese, ice cream, liver, oil or butter on bread, orange juice, plain yoghurt, white wine and mushrooms. Surprisingly, none of the genes thus identified belonged to the category of taste or smell receptors.
“There is still much that needs to be done to understand what are the characteristics of certain foods affected by the genetic make-up of an individual,” says Dr Pirastu. “For example, we found a strong correlation between the HLA-DOA gene and white wine liking, but we have no idea which of the characteristics of white wine this gene influences. Our studies will be important for understanding the interaction between the environment, lifestyles, and the genome in determining health outcomes. Although there has been a lot of work on food-related diseases such as obesity, these have rarely taken food preferences into account. This is a major limitation which our work attempts to remedy, and as yet we have only really scratched the surface of this issue.”
In a second study, the researchers amassed the response of around 900 healthy adults from North Eastern Italy to salt, and related this to a DNA sequence variation found on the KCNA5 gene, known to be related to taste pathways in mammals. Salt perception and the related genetic variation in taste receptors are important determinants of individual differences in salt intake, which in turn represents an important risk factor for the development of hypertension and cardiovascular diseases. “Genetic variations for taste perception are well known for bitter, sweet, and umami taste, but until now we knew little about their role in salt perception and liking,” says Dr Robino. “Identifying the receptor associated with individual differences in the perception of salt could help us better understand how chemosensory differences can interact to influence and predict food choices and hence human nutritional behaviour. This could also play an important role in the development of salt substitutes, in which there is a growing commercial interest.”
Nutritional intervention could be greatly improved by tailoring it to the food preferences of each person, the researchers say. And food preferences are also much easier to collect and study; while it is almost impossible to remember much one has eaten in the past ten years, it is easy to remember food likes and dislikes.
“By uncovering the genetic bases of taste and food preferences, we will be able to increase not only the effectiveness of nutritional interventions, but also compliance with them. For example, we have recently carried out a study where we applied our knowledge of 19 different genes in order to personalise diets for 191 obese individuals for were trying to lose weight. They were divided into two groups, 87 in a test group and 104 controls,” says Dr Pirastu.
“We devised a standard weight-loss diet subtracting 600 calories from individual nutritional needs, and analysed DNA from the test group for 19 genes known to affect different metabolic areas and taste. We then modulated the diets according to individual genetic profiles – for example, people whose genetic profile showed that they had less efficient lipid metabolism were given fewer lipids in their diet – but kept the overall amount of calories the same for everyone.
“Although there were no significant differences in age, sex and BMI between the two groups at the beginning of the trial, we found that people in the group who had followed the gene-based diet lost 33% more weight than the controls over two years, and the percentage of lean body mass also increased more in this group,” he will say.
Food preferences are the first factor driving food choice, nutrition and ultimately diet-related diseases and as such are the key to understanding human nutrition and its relationship with health on a large scale, the researchers say. A recent study1 carried out on more than 40,000 people showed that people who prefer fat have a completely different eating pattern than people who dislike it. “So something as simple as measuring fat liking can provide us with a great deal of information. Understanding the genetics of these traits will open new possibilities for the development of personalised diets and of functional foods aimed at improving people’s health and therefore their quality of life,” Dr Pirastu will conclude.
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Abstract nos. C14.3, P17.26-M, and P15.19-S
1. Association between intake of nutrients and food groups and liking for fat, Caroline Mèjean et al. Appetite, 2014
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 2000 members from 72 countries. About 3000 delegates are expected to attend this year’s conference.
ESHG 2014, Milan - Poor coverage of specific gene sets in exome sequencing give cause for concern
Embargo: 00.01hrs CEST Sunday 1 June 2014
Milan, Italy: With services based on exome sequencing becoming affordable to patients at a reasonable price, the question of the quality of the results provided has become increasingly important. The exome is the DNA sequence of genes that are translated into protein. These protein-coding regions contain most of the currently-known disease-causing genetic mutations. The American College of Medical Genetics and Genomics (ACMG) has recommended the reporting to patients of clinically actionable incidental genetic findings in the course of clinical exome testing. Specifically, mutations of 56 specific genes with known clinical importance should be reported even when they are incidental to the patient’s current medical condition. However, a new study to be reported to the annual conference of the European Society of Human Genetics (ESHG) today (Sunday) shows that exome sequencing, as currently performed, does not always produce high quality results when examining subsets of genes such as the 56 ACMG genes.
Dr Eric Londin1, Assistant Professor in the Computational Medicine Centre, Department of Pathology, Anatomy and Cellular Biology, Thomas Jefferson University, Philadelphia, USA, will tell the conference that analysis of 44 exome datasets from four different testing kits showed that they missed a high proportion of clinically relevant regions in the 56 ACMG genes. “At least one gene in each exome method was missing more than 40 percent of disease-causing genetic variants, and we found that the worst-performing method missed more than 90 percent of such variants in four of the 56 genes,” he says.
A central question, the researchers say, is not how often a clinical diagnosis can be made using exome sequencing, but how often it is missed, and the study shows clearly that there is a high false-negative rate using existing sequencing kits. “Our concern is that when a clinical exome analysis does not report a disease-causing genetic variant, it may be rather that the location of that variant has not been analysed rather than the patient’s DNA being free of a disease-causing variant,” says Dr Londin. “Depending on the method and the laboratory, a significant fraction (more than ten percent) of the exome may be untested and this raises concerns as to how results are being communicated to patients and their families. “
A total of 17,774 disease-causing genetic variants are annotated in the Human Gene Mutation Database (HGMD) for the 56 genes mentioned in the ACMG recommendations. The researchers examined the coverage of the exome datasets for the locations where the 17,774 disease-causing variants can occur. Although the exome datasets are comparable in quality to other published clinical and research exome data sets, the coverage of the disease-causing locations was very heterogeneous and often poor. The researchers believe that clinical laboratories that implement the ACMG reporting guidelines should recognise the substantial possibility of reporting false negative results.
One potential improvement would be to have clinical exome sequencing use methods designed to provide a maximum yield of all clinically relevant genes. “Many of the currently used exome kits are designed to provide a very broad dataset including genomic features that do not yet have a well-established clinical association. There is a need to develop new kits and methods which provide adequate and reliable coverage of genes with known disease associations. If adequate performance cannot be obtained across the exome, then further use of targeted disease-specific panels of genes should be explored,” Dr. Londin says.
The study also found that exome datasets generated from low amounts of sequence data (fewer than six gigabases) performed much worse than datasets that were generated from higher amounts of sequence data (more than ten gigabases). This finding is consistent with previous studies showing that exome methods do not have a linear relationship between sequence-generated and nucleotide2 coverage. Instead, a minimum threshold of sequencing data needs to be met before optimum nucleotide coverage is obtained.
“Current consensus and regulatory guidelines do not prescribe a minimum data requirement for clinical exome tests. The result is that when a causative variant cannot be identified it does not necessarily imply that the variant is not present, rather that there may be a technical issue with the exome technology used. In other words, a clinical ‘whole exome’ study may not be ‘wholesome’ in coverage. Patients and their families should be made aware of this problem and of the implications of the genomic findings of clinical exome sequencing in its current state,” Dr. Londin will conclude. (ends)
1. In collaboration with Dr Jason Park at the University of Texas Southwestern Medical Center and Children’s Medical Center, Dallas, Drs. Larry Kricka at University of Pennsylvania, Dr Marialuisa Sponziello at the University Sapienza, Rome, Dr Peter Clark at the Children’s Hospital of Philadelphia and Dr Paolo Fortina at the Kimmel Cancer Center of Thomas Jefferson University.
2.Nucleotides are the subunit molecules of DNA
Funding: This work was supported in part by the Kimmel Cancer Center (PF), the Computational Medicine Center (ER), by a grant from Sapienza University of Rome (MS).
Abstract no. C07.6
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 2000 members from 72 countries. About 3000 delegates are expected to attend this year’s conference.
ESHG 2014, Milan - Genetic researchers take a major step towards better diagnosis and treatment of osteoporosis
Embargo: 00.01hrs Sunday 1 June 2014
Milan, Italy: A new target that may be critical for the treatment of osteoporosis, a disease which affects about 25% of post-menopausal women, has been discovered by a group of researchers in The Netherlands and in Germany. Professor Brunhilde Wirth, Head of the Institute of Human Genetics, University of Cologne, Germany, will tell the annual conference of the European Society of Human Genetics tomorrow (Sunday) that new studies in zebrafish and mice have shown that either injection of human plastin 3 (PLS3) or related proteins in zebrafish where PLS3 action has been suppressed can replace its loss and repair the bone development anomalies associated with this deficiency. Furthermore, overexpression of human (PLS3) in normal mice had a significant impact on bone development and maintenance making them more resistant to fractures.
The discovery that PLS3 mutations could cause osteoporosis was published last year in The New England Journal of Medicine. 1 The results came as a surprise to the researchers, since mutations in the PLS3 gene had not previously been known to be related to osteoporosis and fractures, or to play a role in bone formation. “In our most recent research, we started out by using zebrafish embryos in which PLS3 was knocked-out and studying their development at the three and five day-old stage,” says Professor Wirth, “and we found that they had massive impairment of craniofacial skeletal development. However, this was fully restored when we added human PLS3. The same thing happened when we added two other proteins, actinin 1 and actinin 4, F-actin proteins2 which are involved in ‘bundling’ or building the ‘scaffolding’ for cells, and it seems that these proteins can compensate for the loss of PLS3. Thus we have been able to verify the essential role of actin in bone development and maintenance.”
The subsequent mouse studies confirmed the findings in zebrafish, the researchers say, and open up possibilities for new treatments. They now intend to use PLS3 knock-out mice, where the PLS3 gene has been removed, in the search for the disease-causing mechanism involved. PLS3 is expressed in three different types of cells - osteocytes and osteoclasts, both involved in bone growth and remodelling, as well as in muscle cells. Using a transgenic mouse that overexpresses PLS3, they will also investigate whether this overexpression could be effective in other diseases involving in bone weakness.
“Since we know that about five percent of the human population expresses higher than normal levels of PLS3, we can hypothesise that these people may be protected against osteoporosis,” says Professor Wirth.
Once the researchers understand the exact disease-causing mechanism, it may be possible to translate the knowledge into therapy, they say. PLS3 overexpression is also protective against spinal muscular atrophy, the second most frequent autosomal recessive disorder in humans.3 This implies that understanding the protective role of PLS3 is crucial in both disorders. “We are currently trying to unravel the whole protein network and, once we have understood the signalling pathways influencing PLS3 expression, we should be able to identify drugs or molecules that influence PLS3 expression or actin proteins,” she says.
Osteoporosis affects not only post-menopausal women, but also older men, and the condition currently causes more than 8.9 million fractures per year or an osteoporitic fracture every three seconds. Worldwide one in three women over 50 will experience fractures due to osteoporosis, as will one in five men. Currently, emphasis for sufferers is on the prevention of falls that can cause broken bones. Although bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained an osteoporotic fracture, they are otherwise of little use.
“Osteoporosis poses an urgent health problem that is going to become more important as years go with the numbers of elderly people in the community continuing to increase,” says Professor Wirth. “Although in itself it is not a fatal illness, large numbers of people die prematurely as a result of health complications following falls. We believe that our work has led to a better understanding of the condition and has pointed the way towards improved diagnosis and prevention, and, we hope, an effective treatment in the future.”
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1.N Engl J Med 2013; 369:1529-1536 DOI: 10.1056
2.F-actin is a multi-functional filamentous protein essential for regulating the mobility and contraction of cells.
3.An autosomal recessive disorder is one where two copies of an abnormal gene must be present in order to the disease or condition to develop.
Abstract no. C10.2
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 2000 members from 72 countries. About 3000 delegates are expected to attend this year’s conference.
ESHG 2014, Milan - New genetic sequencing methods mean quicker, cheaper, and equally accurate embryo screening
Embargo: 00.01 hrs CEST Saturday 31 May 2014
Milan, Italy: Results from the first study of the clinical application of next generation DNA sequencing (NGS) in screening embryos for genetic disease prior to implantation in patients undergoing in-vitro fertilisation treatments show that it is an effective reliable method of selecting the best embryos to transfer, the annual conference of the European Society of Human Genetics will hear tomorrow (Sunday). Dr Francesco Fiorentino, from the GENOMA Molecular Genetics Laboratory, Rome, Italy, will say that his team’s research has shown that NGS, a high throughput sequencing method, has the potential to revolutionise pre-implantation genetic screening (PGS). The technique can result in reduced cost, faster results, and accurate identification of good embryos resulting in more ongoing pregnancies, he will say.
The researchers undertook a prospective, double blind trial using two methods of embryo screening, NGS, and the older method array-comparative genomic hybridisation (Array-CGH) of 192 blastocysts, or early embryos, obtained from 55 consecutive clinical pre-implantation genetic screening (PGS) cycles. Array-CGH was the first technology to be widely available for the accurate analysis of chromosomal abnormalities in the embryo and is used extensively across the world for this purpose.
Fifty five patients with an average age of 40 years were enrolled; in 45 cases they were undertaking IVF because of advanced age and in ten because of repeated IVF failures. Two different teams of researchers carried out biopsies and analysed the genetic make-up of the embryos at between five and six/seven days, depending on the speed of growth, and then measured the consistency of the diagnosis by comparing results from the two sequencing methods.
This comparison showed concordant results for 191 of the 192 embryos analysed. One embryo showed a false positive for three copies of chromosome 22 (trisomy 22) using the NGS technique. But analysis of this embryo also showed concordance between the two methods in detecting several other chromosomal abnormalities, and it would therefore have been ruled for transfer in any event. There were no other false negative diagnoses for chromosome abnormalities, and no inaccurate predictions of gender. NGS also showed itself to be as capable of identifying small, difficult to detect abnormalities.
“We found that results from the NGS and array-CGH diagnostic tests were highly concordant,” Dr Fiorentino will say. “NGS allowed us to detect a number of different abnormalities in 4608 chromosomes with a very high degree of accuracy, and following the transfer of 50 healthy embryos in 46 women, 30 pregnancies continued.”
These pregnancies were confirmed by the presence of a foetal sac and a heartbeat, and all have now completed at last 20 weeks of gestation.
PGS has been the subject of controversy over recent years. Initially hailed as an opportunity to improve clinical outcome in sub-fertile patients undergoing IVF, a number of studies later appeared to show that it might not help to identify and select chromosomally normal embryos for transfer based on its lack of benefit with respect to improving life birth rates.
“However, these studies used an older screening technique, fluorescent in-situ hybridisation (FISH),” says Dr Fiorentino, “and we hypothesised that NGS might come up with more accurate results. The results of our study have proved this to be the case, and that NGS can improve clinical outcomes. We expect that the use of NGS technologies will increase as evidence of their utility becomes better-known.
“A further advantage of the technique is that it is quicker and cheaper, while remaining just as sensitive as other methods of screening. Our next step will be to participate in a large randomised controlled trial, the results of which will be critical for the acceptance of NGS-based pre-implantation embryo assessment into wider clinical practice.”
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Abstract no: P01.023/S
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 2000 members from 72 countries. About 3000 delegates are expected to attend this year’s conference.
Proposed amendments to EU Regulation on Medical Devices are counter to patients’ interests and unworkable, says ESHG
Recent amendments to the proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) currently before the European Parliament will restrict the rights of patients and doctors to carry out essential genetic testing, says the European Society of Human Genetics (ESHG) today (Monday 7 April 2014). Furthermore, an independent legal opinion now shows that the European Union (EU) has no competence to enact the Regulation as amended by the Parliament.
European Society of Human Genetics urges caution over use of new genetic sequencing techniques
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. However, it can also pose major ethical problems if used incorrectly, say new recommendations from the European Society of Human Genetics (ESHG) published on line today (16 May 2013) in the European Journal of Human Genetics (http://www.nature.com/ejhg/journal/v21/n1s/index.html).
Many services based on whole genome and on exome* sequencing and analysis are now available to patients at an affordable price, and this raises the question of how to ensure that they are provided appropriately. “Such sequencing generates huge amounts of information that needs to be processed, analysed, and stored in a responsible manner”, said Professor Martina Cornel, chair of the Professional and Public Policy Committee of ESHG. “It is preferable to use sequencing or analysis specifically targeted at a particular health problem to avoid unsolicited findings, or those that cannot yet be interpreted, which can cause considerable anxiety to patients and their families. Clear guidance on how to deal with such findings is needed.
”Targeted analysis will limit such unsolicited findings, says the ESHG, and this is particularly important at present when there are only a limited number of clinicians properly trained to inform patients on the significance of the results of GWAs and exome sequencing. While the Society believes that the duty to inform patients may outweigh their right not to know in some circumstances, the new recommendations propose that analysis should be limited to genome regions linked to the clinical problem for which the analysis is being undertaken.
“We are opposed to the type of opportunistic screening that throws up large numbers of incidental results. If such results reveal a treatable or preventable condition, then clearly it is advantageous to patients to be informed about them. But in the majority of cases it is very difficult to interpret exactly what such incidental results mean for patients and their families. The evidence currently available often comes from families with affected persons, but it is lacking on the interpretation of results in other situations. Furthermore, in genetics healthcare, autonomy is considered very important: patients should be allowed consent on what would be screened for and reported to them. We believe that it is premature today to look for such results other than the clinical problem in circumstances where there are no prior clinical indications or family history ”, said Professor Cornel.
“A sustained effort to educate clinicians in genetics is needed in order to be able to cope with advances in analysis. We also believe that the Society has an important role to play in raising awareness of genetics among the general public. Only with the benefit of a general increase in genetic literacy can society become properly involved in the debate over who has the right to know what and in which circumstances,” she said.
Professor GertJan van Ommen, Editor in Chief of the European Journal of Human Genetics, said: “The importance of this issue has been underlined by the US Government's Bioethics Advisory Panel's plans to report on how incidental findings encountered in genomics research should be handled. I believe that ESHG has made an important contribution to the debate, which will be further discussed at their conference in Paris in June.”
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*Exomes are the short sequences of DNA representing the regions in genes that are translated into protein
Privately owned genetic databases may hinder diagnosis and bar the way to the arrival of personalised medicine: ESHG reacts to today's report in the European Journal of Human Genetics
Wednesday, October 31, 2012
In response to the on-line publication by the European Journal of Human Genetics today (Wednesday) of an article by US researchers led by Dr. Robert Cook-Degan, a former member of the US Office of Technology Assessment, showing that Myriad Genetics, providers of the BRCA1/2 genetic test in the US, has amassed vast quantities of clinical data without sharing it, Professor Martina Cornel, chair of the European Society of Human Genetics' Professional and Public Policy committee, said:
“We are very concerned that such important data is being withheld from those who most need it. Interpreting the variants of unknown significance (VUS) that may be found on analysing the patient's genome plays an essential part in being able to provide proper counselling and if necessary, preventive or therapeutic guidance. By not sharing their data on the VUS obtained from individuals undergoing BRCA1/2 testing, where Myriad is the sole commercial provider of a test in the US, geneticists have been unable to develop the up-to-date algorithms that are necessary to best interpret the effects of genetic variants. While Myriad has access to public databases in order to help interpret their VUS results, this is currently not reciprocal.
“We know that, regrettably, medical geographic inequities are common, but what is particularly worrying about this situation is that it is the first time that such inequities have been based on a lack of access to clinical information, rather than lack of a product. Myriad's stated aim to enter the European market more vigorously may lead to unfair competition with academic institutions for predictive precision. It is vital that progress towards personalised medicine, which holds out so much promise, is not hindered by companies maintaining private genomic databases. Policymakers should take an urgent look at the regulatory and reimbursement issues involved in genomic testing in order for all the data that is essential to understanding the clinical significance of VUS to be made public, to the benefit of patients and healthcare providers alike.”
ESHG condemns use of testing to establish 'racial purity'
Wednesday, June 13, 2012
The use of genetic testing to establish racial origins for political purposes is not only scientifically foolish, but also unethical and should be condemned, the European Society of Human Genetics (ESHG) said today (Thursday June 14). The society, which promotes research in basic and applied human and medical genetics and ensures high standards in clinical genetic practice, said that the use by a member of parliament from the Hungarian far-right Jobbik party of a genetic test to attempt to prove his ”˜ethnic purity' was ethically unacceptable.
The company Nagy Gén scanned 18 positions in the MP's genome for variants that it said were characteristic of Roma and Jewish ethnic groups and concluded that Roma and Jewish ancestry could be ruled out.
Professor Joerg Schmidtke, President of ESHG, said on behalf of the Executive Board: “This is a gross distortion of the values of genetic testing, which is intended to be used to diagnose disease rather than to claim racial purity. In addition, the test proves nothing; it is impossible to deduce someone's origins from testing so few places in the genome. I am sure that clinical geneticists worldwide will join me in condemning this scandalous abuse of a technology that was developed to help the sick, rather than to promote hatred.”
Professor Béla Melegh, President of the Hungarian Society of Human Genetics added: “We were shocked to hear that a laboratory authorised to carry out genetic analysis for diagnostic purposes carried out such a test. Not only does it not serve a diagnostic purpose, but it has been used to create tension between people of different ethnic origins. We are asking the Hungarian government to prosecute the company concerned under the 2008 law on genetics, and to take action to ensure that similar abuse of genetic testing cannot take place in our country in future.”
The 2012 European Genetics Conferences in Nuremberg, Germany (June 23-26) will provide a further opportunity for the ESHG to denounce such an unethical perversion of genetic science, and insist, at the same time, on the importance of genetic testing in the medical or scientific context of good practice.
Annual Meeting 2011
May 28-31, 2011
Amsterdam the Netherlands
Direct-to-consumer genetic tests neither accurate in their predictions nor beneficial to individuals, European geneticists say
Embargo: 00.01 hrs CEST Tuesday 31 May 2011
Amsterdam, The Netherlands: Direct-to-consumer (DTC) genetic tests give inaccurate predictions of disease risks and many European geneticists believe that some of them should be banned, the annual conference of the European Society of Human Genetics will hear today (Tuesday). In the first of two studies to be presented, Rachel Kalf, from the department of epidemiology at Erasmus University Medical Centre, Rotterdam, The Netherlands, will say that her research is the first to look at the real predictive ability of such tests, the results of which are available directly to an individual without having to go through a healthcare professional.
Working under the supervision of Associate Professor Cecile Janssens, together with researchers from Leiden, The Netherlands, and Boston, USA, Ms Kalf examined the risk predictions supplied by two large DTC companies, deCODEme (Iceland) and 23andMe (USA). They simulated genotype data for 100,000 individuals based on established genotype frequencies and then used the formulas and risk data provided by the companies to obtain predicted risks for eight common multi-factorial diseases - age-related macular degeneration (AMD), atrial fibrillation, celiac disease, Crohn's disease, heart attack, prostate cancer, and Type 1 and Type 2 diabetes (T2D).
Although the predictive ability of the DTC tests in the study was moderate for all diseases, both companies assigned an increased risk to a substantial part of the group. Yet the risk of disease in this group was often not substantially higher than the risk in the rest of the population studied. For AMD, the disease with the highest predictive ability, both companies assumed that the risk in the population was around 8%. Of all subjects designated as having an increased risk, 16% using the 23andMe risk estimations and 19% using deCODEme's estimations would develop AMD, compared to the 4% found in the rest of the population studied.
“So individuals in the increased risk group may have a four-fold increased risk of disease, but they are still far more likely not to develop the disease at all. For T2D, where the companies calculated the average risk at around 25%, 32% of those assigned to the increased risk group would actually develop T2D compared to 22% in rest of the study population. This difference in disease risk is too small to be of relevance”, said Professor Janssens.
“deCODEme predicted risks higher than 100% for five out of the eight diseases”, Ms Kalf will say. “This in itself should be enough to raise considerable concern about the accuracy of these predictions - a risk can never be higher than 100%. In the case of AMD one in every 200 individuals in the group would have received a predicted risk of higher than 100%, suggesting that they would definitely develop the disease.”
The DTC companies have been criticised for giving an exaggerated and inaccurate message about the connection between genetic information and disease risk. “They only take genetic factors into account when predicting risks for consumers, whereas in most multi-factorial diseases other modifiable risk factors, such as diet, environment, exercise and smoking have a much stronger impact on disease risk”, said Professor Janssens. “We are all aware of the ethical problems surrounding DTC genetic testing, but this study also confirms that their predictions are inaccurate. At a time when some governments are considering regulating such tests, we believe that we have made an important contribution to the debate”, she concluded.
In the second study, Dr. Heidi Howard from the University of Leuven, Belgium, and her colleague Professor Pascal Borry reported the results of a survey of a representative sample of clinical geneticists from 28 countries across Europe on their experience of and attitudes to DTC genetic testing. “This is the first ever survey of European clinical geneticists on the subject”, Dr. Howard will say, “and the results were conclusive - 69% of respondents felt that prenatal gender tests should be legally banned, and 63% wanted to proscribe whole genome scans carried out by DTC companies.”
One of the problems with DTC tests is that the companies' tendency to overstate the potential of predictive information does not help to produce a public properly educated about the potential value and limitations of genetic information. This is particularly true when it comes to whole genome scans, where a lot of results are given for many different conditions, the researchers say.
“Clinical geneticists' concerns with DTC genetic tests are mostly related to the fact that these tests usually lack clinical validity and utility. Moreover, these tests are usually carried out without the provision of genetic counselling. According to the experiences of clinical geneticists, patients often do not know how to interpret the results they receive and are often confused by them. However, almost all clinical geneticists feel that they have a duty to provide counselling if patients contact them after having purchased a DTC genetic test,” says Dr. Howard.
“A person who undergoes a genetic test has to be accompanied - explanations, physical aid, the right to choose whether to know or not - and this is not true in the case of direct access to such a test”, said one survey respondent.
“Genome-wide scans by companies are totally unacceptable, as they can derive sensitive information about medically relevant conditions and will also provide lots of information which is difficult to interpret, even for medical professionals”, said another respondent. Presenting the results of such tests directly to individuals is unacceptable, the majority of those surveyed said.
90% of respondents felt that a pre-symptomatic test - predicting if an asymptomatic person had a very high probability of developing a condition - should not be allowed without face-to-face medical supervision; 93% felt the same for a predictive test for a condition that has a penetrance (the proportion of individuals with the mutation who exhibit clinical symptoms) of 50 - 60%; 79% for a carrier test for homozygous monogenic disorders, such as sickle-cell anaemia; and 72% for a predictive test for a condition that increased or decreased a person's risk of developing it by 4% when compared to the general population.
At the moment, DTC genetic tests reach the market without having undergone any form of regulation. “Better regulation is needed at the level of market introduction of these tests”, says Professor Borry. As in the case of drugs, a procedure should be developed for genetic tests.”
Currently only a few European countries, for example France and Switzerland, have legislation that states that genetic tests can only be accessed via individual medical supervision. “Although this model is sometimes criticised for being too paternalistic”, says Professor Borry, “in the absence of a good working pre-market control of genetic tests, it could be a useful way of responding to some of the concerns over DTC testing.”
The provision of genetic testing services outside the regular healthcare system can also lead to unnecessary visits to healthcare providers and hence an increased burden on healthcare resources, the researchers say.
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Abstract nos : C14.5 (Kalf) and C14.3 (Howard) Tuesday, May 31, 2011, 11:00 am
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes for editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are expected to attend this year's conference.
Pre-implantation genetic diagnosis can permit the birth of healthy children to women carrying mitochondrial DNA disease
Embargo: 13.00 hrs CEST Monday 30 May 2011
Amsterdam, The Netherlands: Pre-implantation genetic diagnosis (PGD) can give women at risk of passing on a mitochondrial DNA disorder to their offspring a good chance of being able to give birth to an unaffected child, a researcher told the annual conference of the European Society of Human Genetics today (Monday). Dr. Debby Hellebrekers, from Maastricht University Medical Centre, Maastricht, The Netherlands, said that the scientists' findings could have a considerable effect on preventing the transmission of mitochondrial diseases.
Mitochondria are cellular organelles involved in the conversion of the energy of food molecules into ATP, the molecule that powers most cellular functions. Disruptions of this energy-producing process, due to a defect in the mitochondrial DNA (mtDNA) or nuclear genes, can cause mitochondrial disorders which represent the most common group of inborn errors of metabolism. The manifestation of mtDNA disorders can be quite varied, but the diseases are almost always serious and, if they do not lead to death, they can result in life-long serious disability for children born with them. Symptoms of mtDNA disorders include loss of muscle co-ordination, visual and hearing problems, poor growth, mental retardation, heart, liver and kidney disease, neurological problems, respiratory disorders and dementia.
Prenatal diagnosis is in general not possible for mtDNA diseases, because the clinical signs cannot be reliably predicted from the mutation load (the relative amount of mutated mtDNA molecules) in chorionic villus sampling, so the team of scientists from The Netherlands, Australia, and the UK decided to look at whether PGD would be a better alternative. “If we could find a minimal level of mtDNA mutation load below which the chance for an embryo of being affected was acceptably low”, said Dr. Hellebrekers, “we could offer PGD to women who otherwise had little chance of giving birth to a healthy child.”
The researchers studied data on 159 different disease-causing mtDNA mutations derived from 327 unrelated patients or families. They combined data on muscle mutant levels - which correlate best with prenatal tissues - of affected individuals and relatives on their mothers' side who were not affected., and were able to predict that a 95% or greater chance of being unaffected was linked to a mtDNA mutant level of 18% or less.
Mitochondria have their own DNA, which is strictly inherited from the mother. Normal and mutant DNA co-exist in most disease-causing mtDNA mutations, and there is a threshold of mutant mtDNA which must be exceeded before clinical symptoms occur. The mtDNA mutation level inherited by the offspring of a female mutation carrier can vary greatly, and even in twin births, it is possible for one baby to receive considerably more of the mutant mtDNA molecules than the other.
“Being able to find the minimal level of mutant mtDNA below which the chances of passing on a disorder is low was therefore very important”, said Dr. Hellebrekers. Currently, there are no effective treatments for mtDNA disorders. Although we cannot guarantee that a mutant mtDNA level of 18% or lower will result in the birth of an unaffected child, we think that the chances of having a healthy child are high enough to make using PGD in this instance morally acceptable.
“Our research enables us to give genetic counselling to women at risk with respect to their reproductive choices and to provide them, for the first time, with the opportunity to give birth to a healthy baby. The prevalence of mtDNA disorders is 1 in 5,000, which means that the families of about 146,000 patients in Europe can now have the option of having a healthy child. This is a choice that they do not currently have”, she concluded.
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Abstract no: C07.2 Session Monday, May 30, 2011, 1:15 pm
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are expected to attend this year's conference.
New advances in lipid genetics lead to better detection and prevention of major diseases
Embargo: 00.01 hrs CEST Monday 30 May 2011
Amsterdam, The Netherlands: Studying the genetic make-up of different varieties of lipids (fatty molecules) in the blood plasma of an individual can lead to a better and earlier prediction of diseases such as diabetes, atherosclerosis, and heart disease, two researchers will tell the annual conference of the European Society of Human Genetics today (Monday 30 May). In the first study, Dr. Joanne Curran from the Texas Biomedical Research Institute, San Antonio, USA, will tell the conference that lipidomic profiling will become a more reliable early indicator of individuals likely to develop diabetes than the more commonly used predictors such as blood glucose and insulin levels.
Dr. Curran and colleagues from the US and Australia measured 356 different lipid varieties from about 1100 Mexican American members of large extended families who were part of the San Antonio Family Heart Study. The Mexican American population is at high risk of diabetes with about 25% of this population ultimately becoming diabetic. At the start of the research, 861 of the individuals studied did not have diabetes. However, over the 10 year follow-up examined in the study, 110 individuals did develop the disease.
The scientists were able to isolate 128 different varieties of lipids that predicted the progression to diabetes by measuring the the lipidomic profiles of each individual at multiple timepoints during the follow-up period. “The single best predictor we found was a novel component called dihydroceramide (dhCer). This was substantially increased in people with diabetes. It is also heritable, and appears to be an independent risk factor unconnected to blood sugar and insulin levels,” says Dr. Curran.
After uncovering the link between dhCer and diabetes, the team searched the genome to find locations that harboured genes that influence dhCer levels. They identified a region on chromosome 3 that appeared to contain a gene with substantial importance for the production of dhCer. “Through whole genome sequencing, we are now attempting to identify this causal gene in the hope that it will be informative in the understanding of the pathogenesis of diabetes, and also suggest new avenues for treatment,” Dr. Curran says.
In the future, the researchers say, measurement of dhCer levels could become routine in the prediction of individuals likely to become diabetic. One of the difficulties of the current predictive methods is that they do not function until a patient is near to developing the disease. Being able to identify those at risk at the earliest stage would mean that individuals have plenty of time to make the lifestyle changes that could help them avoid the disease - through a change in diet, or increasing physical activity, for example.
“Currently one in ten US adults suffers from diabetes and recently the Centers for Disease Control has predicted that this will increase to one in three by 2050”, says Dr. Curran. “We are optimistic that our discovery will lead to new treatments, but in the short-term the importance of finding out at an early stage whether any individual is likely to develop it cannot be overstated. A test based on dhCer levels will help to avoid the serious health effects that diabetes has in its own right, such as kidney failure, amputations, and blindness. It is, of course, also a risk for cardiovascular disease, so the health burden of this condition is enormous”, she concludes.
In the second study, Dr. Sara Willems, from the Erasmus Medical Centre, Rotterdam, The Netherlands, will describe to the conference research carried out on the influence of common genetic lipid variants on atherosclerosis and related heart disease. “A recent genome-wide meta-analysis of more than 100,000 individuals identified a large number of genetic variants associated with levels of LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. These molecules are, at increased levels of LDL and triglycerides and decreased levels of HDL, important risk factors for cardiovascular disease”, says Dr. Willems.
The researchers used risk scores from these genetic variants to test the hypothesis that their cumulative effects were associated with cardiovascular disease. For this purpose they used genetic data from more than 8000 individuals from the population-based Rotterdam Study and more than 2000 individuals participating in the Dutch family-based Erasmus Rucphen Family study.
They found an association between the LDL risk score and arterial wall thickness, and a strong association of this risk score with carotid plaque. These conditions can cause arterial blockage which leads to stroke. The same risk score was also associated with coronary heart disease.
“Our findings show that an accumulation of common genetic variants with small effects on lipid levels can have a significant effect on clinical and sub-clinical outcomes”, says Dr. Aaron Isaacs, who led the project. “In the future, as our knowledge of genetic variation increases, effective pre-clinical genetic screening tools may be able to enhance the prediction and prevention of diseases such as cardiovascular disease.
New genetic variants influencing lipid levels are being identified all the time, the researchers say. “As new variants are discovered, we would like to be able to continue to test them, both singly and combined, for association with cardiovascular disease. The cost of these diseases to individuals, families, society and healthcare systems is immense”, says Dr. Willems.
“Cardiovascular disease is the main cause of death in Europe, killing over 4 million people per year. It also represents 23% of the total disease burden (illness and death) across the continent. Managing cholesterol levels is important for prevention. This can be done early in life by effective treatment. We hope that our study, showing that common genetic variants play an important role in the occurrence of cardiovascular disease, marks a starting point for early prediction and prevention and may thus reduce the burden of disease,” she concludes.
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Abstract nos : C10.5 (Curran) and C10.4 (Willems) Monday, May 30, 2011, 1.15pm
Note: When obtaining outside comment, journalists are requested to ensure that their contacts are aware of the embargo on this release.
Notes to editors: The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are expected to attend this year's conference.
Annual Meeting 2010
June 12, 2010
New gene makes the difference in Usher syndrome
New gene makes the difference: genetic modifier in Usher Syndrome explains variability in symptoms and will lead to better diagnosis
Usher syndrome (USH), an inherited condition involving both hearing and vision loss, is not simply a recessively inherited disease, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Saturday). Dr. Hanno Bolz, Associate Medical Director of the Bioscientia Centre for Human Genetics, Ingelheim, Germany, and active in teaching and research at the University Hospital of Cologne, will say that his team's research challenges the traditional view that USH was inherited as a single gene disorder, and shows that it may result from at least two different genetic mutations. This could lead to more accurate diagnosis of this condition, which is responsible for up to 10% of all cases of childhood deafness and 50% of all deaf/blindness in adults.
Some USH patients have only one mutant copy of an Usher gene, which in itself is insufficient to explain a recessive disease, and there is often an unexplained variability of the visual characteristics of the condition, even between close family members. Dr. Bolz's team, including scientists from Cologne University, Germany and zebrafish researchers from the University of Oregon, USA, decided to look for additional USH genes and genetic modifiers that could be involved in disease causation.
“We became interested in researching sensory diseases such as Usher syndrome because they can be very debilitating and affect people at a young age”, said Dr. Bolz. “Despite extensive research into USH, there is currently no effective treatment for it.”
Apart from linkage studies of recessive disease, where a particular trait or disease characteristic is traced within a family, another way of identifying genes linked to disease is to analyse genes that encode proteins which are similar to the proteins involved in the disorder being studied. Using a genome-wide database search, the team identified a gene, PDZD7, which encoded a protein with striking similarity to the proteins whirlin and harmonin, both known to be involved in USH.
“We found that some patients with only a single mutation of the gene responsible for the condition, GRP98, also had a mutant copy of PDZD7, and that this gene interacts with proteins involved in USH”, said Dr. Bolz. “We were able to validate these findings in transgenic zebrafish, and to show that PDZD7 localises to cilia, thus providing further confirmation that USH is a retinal ciliopathy.”
Cilia are antenna-like protuberances that project from cells and are often involved in sensory activity such as vision, hearing or smell. Genetic mutations can affect their proper functioning, and these defects in turn affect critical signalling pathways essential to cell development. As a result, cilia defects are involved in many diseases which produce multiple symptoms.
Diagnosis of USH is complicated, the scientists say. At present it is normally related to clinical symptoms, such as childhood hearing impairment and the vision disease retinitis pigmentosa in the first or second decade of life. Retinitis pigmentosa affects the layer of light-sensitive tissue in the retina and vision loss occurs as the light-sensing cells gradually deteriorate, causing blind spots which eventually merge to produce tunnel vision and sometimes total blindness.
“When hearing and visual loss are both present, the most likely diagnosis is Usher syndrome”, said Dr. Bolz. “More precise genetic diagnosis is essential, but the genes are large and not easily accessible to genetic testing. However, by considering clinical data of the patient and the background of his/her family - ethnicity, for example - one can apply efficient testing strategies. For the parents of a deaf child, it would be advantageous to be aware of the retinal degeneration that will occur later on.
“Research on new Usher genes must therefore be translated quickly into genetic testing in order to aid parents to choose appropriate therapies to diminish the later consequences of the disease,” he said. The decision to opt for a cochlear implant, for example, could be influenced by the knowledge as to whether the causative mutation is in a gene for isolated deafness or in a USH gene.
“We believe that our work may serve as a paradigm for the future”, said Dr. Bolz. “In many recessive diseases, variability of disease characteristics is the rule rather than the exception, and in most cases this phenomenon is unexplained. With advances in new sequencing techniques that permit simultaneous analysis of several genes, we will need to interpret variants in all Usher genes in a patient, not only in one. Two hits in a single Usher gene may explain the disease in a patient, but not its variability. Our research is a step on the road to understanding that variability and to being able to provide an accurate prognosis of disease progression.”
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Understanding genetic mixing through migration
Understanding genetic mixing through migration: a tool for clinicians as well as genealogists
Gothenburg, Sweden: Understanding the genetic ancestry of mixed populations, such as those found in North America, can not only help to detect their origins but also to understand the genetic basis of complex diseases, a scientist will tell the annual conference of the European Society of Human Genetics today (Saturday June 11). It is the first time that the genomes of individuals of admixed ancestry have been sequenced in such detail, says Dr. Francisco De La Vega of Life Technologies, Foster City, California, USA.
Working with Professor Carlos Bustamante and his team in the Department of Genetics at Stanford University, the scientists analysed the genomes of two people - one of African-American and one of Hispanic-Latino origin. The majority of the personal genomes sequenced to date come from individuals of either European, African, or Asian descent, because it is in these groups that most genetic disease association studies are being carried out. However, populations where genetic mixing through migration has taken place relatively recently make up a sizable proportion of the world's population, and have been not been well studied to date because of the complexity of dealing with the contributions of genes from different ancestries in disease.
“We set out to provide a better understanding of the genome structure in admixed populations by sequencing one African-American and one Mexican sample”, said Dr. De La Vega. “By analysing genetic variants in mixed people whose frequency differs in the ancestral populations, we can work out the ancestry of different chromosomal segments in an individual. This has already been done in a number of different ways. The difference with our work is that, by using whole genome sequencing using the SOLiDâ„¢ System, we can greatly increase the resolution of our analyses and achieve a very much clearer picture of the ancestry of genome sequences for the individuals studied.
“We already know that present-day African-Americans trace their ancestry to a rich mosaic of migrants from the mainly West African and Northern European populations who settled in North America and the Caribbean. Mexicans, on the other hand, are descendants of Meso-American indigenous populations - themselves derived from population migrations from Asia (through the Bering straits) - and largely Southern European (mainly Spanish) settlers”, said Dr. De La Vega. “But the added value of our research is that we can show the approximate number of generations at which the genetic mixing occurred, estimate the rate at which admixture occurred, and understand better the genetic diversity in the ancestral populations.”
To date there are few comprehensive studies of genetic diversity in native populations in the Americas, and by analysing them scientists can begin to piece together the population history of both the admixed and indigenous populations. They can also begin to analyse the contribution of native American genetic variants to the disease burden in the Americas of today, something which at present is relatively unknown.
“We believe that our work will help move forward genetic disease association studies in these admixed populations”, said Dr. De La Vega. “This would not only provide valuable information on the genetic component of disease in these people, but would also help refine genetic association findings in other populations by replicating the findings in admixed samples. And the high resolution admixture maps we can generate can help in studies to map variants of disease whose prevalence is very different in the ancestral populations of admixed groups.”
The scientists intend to follow up their work by sequencing many more genomes of different populations in the Americas in order to understand further differentiation within the continent and the frequency of the genetic variants. “The decreasing costs of sequencing genomes through new sequencing instruments such as those developed by Life Technologies, is making possible for the first time to compare at large scale genetic variants among and within populations” said Dr. De La Vega.
The scientists are also participants in the 1000 Genomes Project, an international research effort to sequence the genomes of at least 1000 subjects from a number of different ethic groups, and thus establish the most detailed catalogue of human genetic variation to date.
“The Project will sequence the genomes of around 500 admixed individuals from diverse populations including African-Americans from the South West and South East US, Afro-Caribbeans from Barbados, Mexicans from Los Angeles, Peruvians from Lima, Colombians from Medellin, and Puerto Ricans from Puerto Rico. We are incredibly excited about the inclusion of these populations in the Project, since we hope that the genomic resources developed by it will encourage the development of genetic studies in under-represented communities in the US and Latin America”, said Professor. Bustamante, co-director of the study. “In the long run, the information obtained from such studies could become the basis of personalised genomic therapies for individuals of admixed origins.”
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mary(at)mrcommunication.org
Smell holds the key to early diagnosis of Parkinson's
Sense of smell holds the key to diagnosis and treatment in early-stage Parkinson's disease
Gothenburg, Sweden: A fast, simple and non invasive test of the ability to smell may be an important tool to screen people who are likely to develop Parkinson's disease (PD), in which motor symptoms only become evident at a later stage of the disease, a German scientist will tell the annual conference of the European Society of Human Genetics today (Saturday). Dr. Silke Nuber, from the Department of Medical Genetics, University of Tübingen, Germany, will say that her team's research could help in the development of treatments for the early stages of the disease.
Dr. Nuber and colleagues from Germany, Switzerland, and the UK, decided to study transgenic mice with high levels of human alpha-synuclein, a protein known to be crucial in the development of PD. Alpha-synuclein can be turned off in these animals by administration of an antibiotic, allowing scientists to look at the reversibility of neuropathological alterations. “The mice expressed alpha-synuclein primarily in neurons of the olfactory bulb”, said Dr. Nuber, “and we therefore expected to find alterations in smell-related behaviour in these animals. Since one of the earliest symptoms in PD patients is a reduction in the sense of smell, we felt that these mice could mimic the early stages of the disease.”
Parkinson's disease is a degenerative disorder of the central nervous system that affects the control of motor skills, speech, mood and behavioural problems, and cognitive functions. It is characterized by muscle rigidity, tremor, and slowing or loss of physical movement. It is a chronic, progressive condition and there is currently no cure.
The scientists tested the sense of smell of the transgenic mice by analysing their behaviour when exposed to a new scent, for example the male mice were exposed to the scent of female mice. They then looked at neurotransmitter activity in different areas of the brain and found a malfunction of dopamine regulation.
When expression was blocked in middle-aged mice, the dopamine level was comparable to those of wild-type (normal) animals, implying both direct influence of transgenic expression on dopamine levels, and the reversibility of symptoms. Dopamine receptors are involved in a number of neurological processes, and abnormal dopamine receptor signalling is known to be implicated in PD. “We believe that we have developed one of the first models to show this olfactorial dopamine deficit without additional abnormalities in the nigrostriatal pathway”, said Dr. Nuber.
The nigrostriatal pathway is one of the major dopamine pathways in the brain, and is particularly involved in the control of movements. Loss of dopaminergic neurons in the substantia nigra, a structure located in the midbrain, is one of the main features of PD, but the motor symptoms of the disease do not show themselves until more than half of the dopamine function has been lost. Being able to identify the early stages of dopaminergic dysfunction is therefore particular important both for diagnosis and treatment of PD.
The scientists also carried out a fear-related smell test, in which the animals would normally have been expected to remain motionless because they sensed the presence of a predator. However, the mice showed reduced anxiety in this test. “In animals with olfactory bulbectomy - a suppression of the sense of smell - hyperactivity and increased exploratory behaviour are strong markers of behavioural alterations”, said Dr. Nuber. “These animals model depression and anti-depressive drugs can ameliorate their depressive symptoms.”
Increased exploratory behaviour may diminish the anxiety and depressive signs in new surroundings that would be normal for mice lacking any sense of smell. The researchers therefore surmised that this behaviour might also exist in mice with a reduced dopamine transmission in the olfactory bulb. “It would be interesting to study whether early treatment with anti-depressive drugs might increase odour sensitivity in PD patients”, said Dr. Nuber. At present, diagnosis of PD is based entirely on the motor symptoms which appear at a later stage, and all drug treatments have been approved for use only at this stage.
The researchers say that it would be worthwhile to develop some standardised tests for testing smell function. “We don't know whether the existing drugs used at a later stage in PD would be effective in the earlier phases of the disease, but having an early biomarker would enable us to try to develop different treatment strategies”, said Dr. Nuber. “Based on what we know now, the clinical definition for the diagnosis of PD should not rely solely on the diagnosis of motor symptoms. It would be helpful to test the ability of olfactory detection and learning. Even if we cannot preserve olfactory structures and functioning, it will enable us to diagnose the disease earlier on and also help with the development of treatment strategies to halt or even reverse the underlying disease process in PD.
“We believe that detailed functional imaging analyses paralleled by behavioural studies in the mouse model could lead to the development of an efficient preclinical therapy that can be used to halt the massive dopaminergic neurodegeneration that takes place in human PD patients”, she concluded.
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Personalised therapy for Hepatitis C a step closer
Small genetic variant can predict response to hepatitis C treatment; may spare side effects to those in whom treatment would be ineffective
Gothenburg, Sweden: A small genetic change can predict how people infected with hepatitis C react to treatment, paving the way to personalised therapy for this difficult to treat disease, the annual conference of the European Society of Human Genetics will hear today (Sunday 13 June). Dr. Zoltan Kutalik, from the Department of Medical Genetics, University of Lausanne, Switzerland, will tell delegates that individuals with this change, in a gene encoding for the antiviral cytokine (cell-signalling molecule) interferon lamda, reacts less well to treatment. This knowledge could spare them the unpleasant side effects of a therapy which most likely would have little benefit for them, he says.
Hepatitis C is a serious liver disease, normally contracted through drug use, blood transfusion or sexual transmission. About 10% of all patients have no identifiable source of infection. The virus produces chronic infection in around 80% of infected individuals, and half of these do not respond to existing therapies. Current treatment involves a combination of an interferon and the antiviral medication ribavirin. Side effects are common and can be serious to the extent that some people are unable to continue to work.
The fact that people respond so differently to the same treatment is usually because a genetic variation in the non-responders is, via complex genetic pathways, inhibiting the effects of therapy. “The Lausanne University Hospital (CHUV) has a large cohort of Hepatitis C patients seen at the hospital over many years”, said Dr. Kutalik, “so this provided the opportunity for us to do a genome-wide association study on 1362 of them to see if we could track down any differences relating to patients' failure to respond to therapy.”
Genome-wide association studies look at variations across the entire genome of individuals to look for genetic associations with well-defined traits, including why some people get a particular disease and condition as well as why they might react or not to therapy for it. In this case, approximately half of the patients studied had responded successfully to therapy, giving the scientists the opportunity to compare their genomes with those from patients who had not responded.
“Using a gene-chip technology, a team of clinicians, geneticists and statisticians looked at over one million polymorphic nucleotides, the letters A, C, G and T of the DNA sequence”, said Dr. Kutalik. “Our analysis revealed that a single nucleotide polymorphism, or SNP, was present in a gene called IL28B, which encodes for interferon lambda. This was significantly associated with both natural and drug-induced clearance of the hepatitis C virus from the body. This polymorphism may exert its influence by modulating the expression level of the interferon lambda gene.”
Individuals who carry the protective allele (letter) at this genetic locus are twice as likely to clear the virus and, even if they do not, they will respond to therapy in a sustained manner; the scientists say. “Individuals infected with the less malignant subtype of the virus and carrying no risk allele were five times more likely to respond than those who were infected with other subtypes and who carried at least one copy of the risk allele. Based on our results we can speculate that the interferon lamda gene is key to increasing the success of therapy, as such therapy could, in theory, compensate for the effect of the polymorphism. Phase 1B trials of interferon lamda therapy in patients with hepatitis C have already shown promising results”, Dr. Kutalik said.
The scientists intend to follow up their work by focusing on a better understanding of the more complex characteristics of hepatitis C, including finding the genetic variants that are responsible for hepatitis C liver fibrosis. “This disease affects up to 300 million people worldwide. It is insidious, and often individuals are not aware that they are infected until serious liver damage has taken place”, said Dr. Kutalik. “Finding better treatments is vital. As well as sparing those who would not react well to current treatment from side effects, we hope that our work may provide pointers to the development of effective therapies for the future.”
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Do study participants have the right to know?
Children born after assisted reproduction at greater risk of congenital malformations; doctors should be prepared to inform parents of these risks, scientists say
Gothenburg, Sweden: Couples considering undergoing assisted reproductive technology (ART) treatment should be informed about the increased risk of congenital malformation posed by the use of ART, the annual conference of the European Society of Human Genetics will hear today (Monday). Dr. Géraldine Viot, a clinical geneticist at the Maternité Port Royal hospital, Paris, France, will say that she believed that most doctors working in ART clinics in France only told couples about such risks if they were asked specific questions.
Dr. Viot and colleagues conducted a survey in 33 French centres registered for ART, around one third of the total number of clinics registered to perform ART procedures in France. All ART births from these clinics from 2003 to 2007 were included; 15 162 children in total. The study was the largest to date on this subject. Questionnaires were completed both by the parents and the paediatrician and the prevalence of malformations found compared with the data obtained from national registers and in published papers.
“We found a major congenital malformation in 4.24% of the children”, said Dr. Viot, “compared with the 2-3% that we had expected from previous published studies. This higher rate was due in part to an excess of heart diseases and malformations of the uro-genital system. This was much more common in boys. Among the minor malformations, we found a five times higher rate of angioma, benign tumours made up of small blood vessels on or near the surface of the skin. These occurred more than twice as frequently in girls than boys.”
However, the scientists say, their results are a long way from the 11% of major malformations that have been reported by some studies. “Given that our study is the largest to date, we think that our data are more likely to be statistically representative of the true picture”, said Dr. Viot.
The average age of the parents of children born with malformations was not statistically different from the other parents in the ART group. The origins of the malformations are probably multiple, says Dr. Viot. “We need more research in order to understand the relationship between embryo culture media, timing of embryo transfer, the effects of ovarian stimulation, the use of ICSI, where sperm is injected directly into the egg, freezing of gametes and embryos and these disorders.
“We estimate that in France some 200 000 children have been born after ART and therefore a malformation rate of this magnitude is a public health issue. It is important that all doctors and also politicians are informed about this. We also need to follow up all children born after ART and to put much more effort into trying to understand which of the procedures involved is implicated in this problem.”
Dr. Viot and colleagues intend to follow up their work analysing a further 4000 questionnaires, from children born in 2008, and to look at the motor development of children born in 2003, who are now aged 7. “By following all these children we hope to understand more about not only what can go wrong after ART, but why it goes wrong”, she said. “At a time when infertility is increasing and more and more couples need to use ART to conceive, it is vitally important that we find out as much as we can about what is causing malformations in these children, not only so that we can try to counteract the problem but also in order for health services to be able to plan for their future needs.”
The scientists are now trying to find out the origin of parental infertility for each child born after ART who has been affected by major malformation or epigenetic disorders. “With this knowledge, we can better establish the origin of the malformation and whether it is more likely to be related to parental infertility or the ART procedure itself”, said Dr. Viot. “We already know that imprinting disorders - where the mechanism in which gene expression depends on parental origin - are clearly more frequent in our cohort than in the general population.”
Imprinting disorders are all acquired because of either a maternal or paternal deletion on a chromosome, through inheritance of both chromosomes of a pair from only one parent, through mutations in some imprinted genes, or because of loss or gain of methylation (a process which is normally removed during zygote formation and re-established through successive cell divisions during development. “The prevalence of the imprinting disorder Beckwith Wiedemann syndrome in our cohort is six times higher than we would expect in the general population, and for retinoblastoma the prevalence among ART children is 4.5 higher than in the general population”, said Dr. Viot.
“These results could be due to the effect of a number of different mechanisms. They could be due to the infertility itself, the ovarian stimulation for supernumerary oocyte production, the in vitro maturation of oocytes, the use of ICSI (direct injection of sperm), the culture media, the cryopreservation of gametes and embryos - we just don't know at present. Finding this out will be a major step towards improving the health of children born after ART.”
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Doctors should tell couples about ART risks
Should the results of individual genetic studies be disclosed to participants? Study queries the right to information in every case
Gothenburg, Sweden: Individual results of genetic research studies should not be disclosed to participants without careful consideration, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday). Dr. Robin Hayeems, from the Department of Health Policy, Management and Evaluation at the University of Toronto, Canada, will say that she believes that the view held by many ethicists that individual genetic research findings should always be reported to participants involved in genetic research studies was perhaps misguided, and that to do so without careful consideration of evidentiary assumptions and clinical capacity could distort the responsibilities of researchers and lead to misunderstanding.
Dr. Hayeems leads the GE3LS (Genomics and its Ethical, Economic, Environmental, Legal and Social Aspects) component of a Genome Canada funded basic science project that is looking at identifying the genes that can modify the severity or clinical effects of cystic fibrosis (CF). Together with the study co-lead Professor Fiona Miller, in charge of the GE3LS component of the Genome Canada funded autism genome project, her team surveyed researchers from around the world who were involved in genetics research related to CF and autism. “We were interested in their perspectives about sharing genetic research results with individual study participants in order to be able to add their voices to the ongoing debate about whether and under what circumstances researchers are under an obligation to report these results to research participants”, she said.
The survey found that 80% of the researchers agreed that individuals in whom a genetic variation had been identified should be informed of this finding if it were judged to be clinically significant. Yet it also revealed considerable variation among researchers in deciding when a result was clinically significant. Researchers felt less confident about the clinical significance of a result when the finding was related to autism research, was less scientifically robust, and was incidental to the condition being studied. Further, researchers were 40% less likely to report it when they were unable to provide participants with the requisite medical advice related to the finding. There were also differences between scientific disciplines, with clinical researchers being 1.8 times more likely to class a particular finding as clinically significant and 1.5 times more likely to report it to study participants than were molecular and statistical researchers.
“Our understanding of how genetic factors contribute to the heterogeneous collection of conditions that comprise the autism spectrum disorders is in its infancy. By contrast, though much remains to be learned about the genetics of CF, the clinical consequences of classical CF and the basic genetic defect that causes it has been known for some time”, said Dr. Hayeems.
“I think our discovery that an autism-relevant finding engenders less confidence with respect to clinical significance compared to a CF-relevant finding reflects researchers' implicit sense of the fundamental uncertainty that still prevails with respect to the genetics of autism. What is interesting about the survey design is that we can say overall that confidence in an autism-related genetic finding was lacking compared to a CF-related finding, even when the autism-related finding they were asked to judge was, by design, quite robust.
“Most, but not all, ethicists endorse an obligation to report genetic research results about individuals because they consider it to be clinically relevant information that individuals have a right to receive. This argument presumes that these research results constitute such information, and that the judgment of clinical significance is relatively straightforward. Our work suggests that this presumption may be misplaced. The results of the survey identify a set of factors that appear to influence researchers as they consider whether a result is clinically significant and whether it should indeed be reported. These factors go beyond scientific standards of robustness to include underlying uncertainties about the role of genetics in certain conditions, as well as researcher training and research team capacity”, she said.
The GE3LS team now intends to encourage institutional research bodies and the wider research ethics community to revisit their thinking about the obligation to report research results to include a broader set of factors so that the complexity of the issue is fully reflected. “Our work highlights an important intersection between health research and health care”, said Professor Miller. “This intersection raises important questions. Are results being interpreted and reported in the context of a research relationship in which the norms of clinical care cannot be expected or, in the context of clinical care, in which case these norms are assumed? What context is assumed, and who is responsible - researchers, or health care systems - for ensuring appropriate disclosure and follow up?” she concluded.
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Annual Meeting 2009
May 25, 2009
Opposites attract - how genetics influences humans to choose their mates
Vienna, Austria: New light has been thrown on how humans choose their partners, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday May 25). Professor Maria da Graça Bicalho, head of the Immunogenetics and Histocompatibility Laboratory at the University of Parana, Brazil, says that her research had shown that people with diverse major histocompatibility complexes (MHCs) were more likely to choose each other as mates than those whose MHCs were similar, and that this was likely to be an evolutionary strategy to ensure healthy reproduction.
Scientists find shared genetic link between the dental disease periodontitis and heart attack
Vienna, Austria: The relationship between the dental disease periodontitis and coronary heart disease (CHD) has been known for several years. Although a genetic link seemed likely, until now its existence was uncertain. Now, for the first time, scientists have discovered a genetic relationship between the two conditions, a researcher told the annual conference of the European Society of Human Genetics today (Monday 25 May).
Identification of genetic variants affecting age at menopause could help improve fertility treatment
Vienna, Austria: For the first time, scientists have been able to identify genetic factors that influence the age at which natural menopause occurs in women. Ms Lisette Stolk, a researcher from Erasmus MC, Rotterdam, The Netherlands, told the annual conference of the European Society of Human Genetics today ( Monday 25 May) that a greater understanding of the factors influencing age at menopause might eventually help to improve the clinical treatment of infertile women.
Comprehensive cardiogenetic testing for families of sudden unexplained death victims can save lives, scientists say
Vienna, Austria: Relatives of a young person who dies suddenly should always be referred for cardiological and genetic examination in order to identify if they too are at risk of sudden death, a scientist told the annual conference of the European Society of Human Genetics today (Tuesday 26 May). Dr. Christian van der Werf, a research fellow at the Department of Cardiogenetics, Academic Medical Centre, Amsterdam, The Netherlands said that, although his team's research showed that inherited heart disease was present in over 30% of the families of sudden unexplained death (SUD) victims, the majority of such relatives were currently not being referred for examination.
Annual Meeting 2008
June 3, 2008
Greater awareness of genetic testing possibilities for impaired fetal movement can save babies' lives
Barcelona, Spain: New genetic mutations responsible for impaired fetal movement, which leads to a multitude or problems in later life as well as early spontaneous abortion, have been identified by a group of scientists, the annual conference of the European Society of Human Genetics will hear today (Saturday 31 May). Dr. Katrin Hoffmann, of the Charité University Hospital, Berlin, Germany, will say that her team's findings could lead to strategies to prevent multiple miscarriages, and for children born with fetal akinesia deformation sequence (FADS) due to impaired fetal movement in the womb.
Genetic mutation linked to walking on all fours: discovery could help answer basic questions of upright walking
Barcelona, Spain: What are the genes implicated in upright walking of humans? The discovery of four families in which some members only walk on all fours (quadrupedality) may help us understand how humans, unlike other primates, are able to walk for long periods on only two legs, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday 2 June).
Prenatal biochemical screening only detects half of chromosomal abnormalities; women should be better informed before deciding to undertake it
Barcelona, Spain: Prenatal biochemical screening tests are widely used to look for chromosomal abnormalities in the fetus which can lead to serious handicap, or even death during gestation or in the first few days after birth. But these tests are only able to detect fewer than half of the total chromosomal abnormalities in the fetus, a scientist will tell the annual conference of the European Society of Human Genetics today (Monday 2 June) Dr. Francesca R. Grati, of the TOMA Laboratory, Busto Arsizio, Italy, says that these findings mean that women should be better informed on the limitations of such diagnostic tests.
Gene therapy involving antibiotics may help patients with Usher syndrome
Barcelona, Spain: A new approach to treating vision loss caused by Type 1 Usher syndrome (USH1), the most common condition affecting both sight and hearing, will be unveiled by a scientist at the annual conference of the European Society of Human Genetics today (Tuesday 3 June). Ms Annie Rebibo Sabbah, from the Genetics Department of the Rappaport Faculty of Medicine, Technion, Haifa, Isreal, will tell the conference that preliminary results using a class of drugs called aminoglycosides, commonly used as antibiotics, had had promising effects in vitro and in cell culture.
Discovery of new family of genetic mutations brings hope of better treatment for patients with inflammatory intestinal disease
Barcelona, Spain: The discovery of new genetic mutations involved in inflammatory intestinal disorders could lead to a better understanding of these common conditions, two scientists told the annual conference of the European Society of Human Genetics today (Monday 2 June).
January 10, 2008
ESHG 2007 Abstract Press Release featured in EurekAlert!'s 10 Most Popular Stories in 2007:
"Noninvasive screening in early pregnancy reduces Down's births by 50 percent"
The EurekAlert! 10 Most Popular Stories in 2007 were identified by monitoring Web site traffic and isolating the news releases that received the highest total number of visits between January and December of 2007.
EurekAlert! is an online, global news service operated by the American Association for the Advancement of Science (AAAS). EurekAlert! provides a central place through which learned societies, universities, medical centres, journals, government agencies and other organisations engaged in research can bring their news to the media and the public.
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Annual Meeting 2007
June 17, 2007
Gene responsible for common hearing loss identified for first time
A gene responsible for the single most common cause of hearing loss among white adults, otosclerosis, has been identified for the first time, a scientist told the annual conference of the European Society of Human Genetics in Nice, France, today (Sunday 17 June). Ms Melissa Thys, from the Department of Medical Genetics, University of Antwerp, Belgium, said that this finding may be a step towards new treatments for otosclerosis, which affects approximately 1 in 250 people.
Non-invasive screening in early pregnancy reduces Down's births by 50%
Nice, France: Non-invasive screening of pregnant women with ultrasound early in pregnancy, combined with maternal blood analysis, has reduced the number of children born in Denmark with Down Syndrome by 50%, a scientist will tell the annual conference of the European Society of Human Genetics today (Sunday 17 June). Professor Karen Brøndum-Nielsen, of the Kennedy Institute, Glostrup, Denmark, will say that another benefit of the introduction of this procedure in her country was a drop in the number of invasive pre-natal diagnostic procedures from 11% to approx. 6% of pregnancies.
Changes in chromosomal constitution of preimplantation embryos suggest caution in genetic screening
Nice, France: Embryos that are selected out as abnormal can undergo chromosomal modifications, a scientist will tell the annual conference of the European Society of Human Genetics in Nice, France, today (Tuesday 19 June). Ms Tsvia Frumkin, from the Racine IVF unit, LIS Maternity Hospital, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel, will tell the conference that her team's findings meant that the results of preimplantation genetic screening (PGS) for chromosomal abnormalities were not always reliable and should be interpreted with caution.
Children born after PGD as healthy as those born after conventional IVF treatment
Nice, France: Children born after embryo biopsy for preimplantation genetic diagnosis (PGD) do not show any more major malformations than those born after artificial reproduction technologies (ART) without PGD, a scientist will tell the annual conference of the European Society of Human Genetics today (Sunday June 17). Professor Ingeborg Liebaers, from the Research Centre for Reproductive Genetics, Free University of Brussels, Brussels, Belgium, will say that the results of her study of 583 children born after PGD was reassuring.
Ancient Etruscans were immigrants from Anatolia (now Turkey) - geneticists find the final piece in the puzzle
Nice, France: The long-running controversy about the origins of the Etruscan people appears to be very close to being settled once and for all, a geneticist will tell the annual conference of the European Society of Human Genetics today (Sunday June 17). Professor Alberto Piazza, from the University of Turin, Italy, will say that there is overwhelming evidence that the Etruscans, whose brilliant civilisation flourished 3000 years ago in what is now Tuscany, were settlers from old Anatolia (now in southern Turkey).
Human genetic 'deserts' are teeming with significant life
Nice, France: Many of the areas of the human genome previously thought to be deserts are in fact teeming with life, a scientist will tell the annual conference of the European Society of Human Genetics today (Tuesday 19 June). Most known human genes in the genome map are still incompletely annotated, says Professor Alexandre Reymond, from the Centre for Integrative Genomics, University of Lausanne, Switzerland and the Department of Genetic Medicine, University of Geneva, Geneva, Switzerland. "We found that the vast majority of the protein coding genes we studied utilised often in a tissue-specific manner previously unknown set of exons [the regions of DNA within a gene that are transcribed to messenger RNA] outside the current boundaries of the annotated genes ", Professor Reymond will say.
July 1, 2005
EPO upholds limited patent on BRCA2 gene: singling out an ethnic group is a "dangerous precedent" says European Society of Human Genetics
Following the decision of the European Patent Office (EPO) to uphold the slimmed-down version of University of Utah Research Foundation's European patent on the BRCA2 breast cancer gene, Professor Gert Matthijs, from the Department of Human Genetics, Catholic University of Leuven, Belgium, and chair of the ESHG Patenting and Licensing Committee, said: "The patent owners have been able to rescue a small bit of their original patent on BRCA2 testing by putting Ashkenazi women into their claim. This apparently renders the test for the 6974delT mutation, which happens to be frequent in the Ashkenazi population, inventive, novel and industrially applicable. ..."
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June 15, 2005
Geneticists oppose singling out Jewish women in European breast cancer patent
Jewish women in Europe may face genetic discrimination in access to breast cancer diagnosis if the patent on the BRCA2 gene, which is currently being disputed, is not withheld by the European Patent Office (EPO) on June 29. The European Society for Human Genetics (ESHG) is strongly opposed to the selection of a particular racial group as a diagnostic target in a gene patent claim and is calling on the EPO to take action to prevent this situation.
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