In the news

  • Newsletter Edition
The PHG Foundation monthly newsletter features news and views about genetics and genetics research, from a public health perspective. The newsletter is written by staff of the PHG Foundation.

In the news

News story   |   By Dr Sowmiya Moorthie   |   Published 29 June 2010

The Human Heredity and Health in Africa Project (H3 Africa) has been established by the Wellcome Trust and US National Institutes of Health (NIH) to support African researchers conduct population-based genetics studies of common, non-communicable and communicable disorders (see press release). The aim of the project is to gain insight into gene-environment interactions and their influence on disease risk. It is hoped that studying African populations which are thought to have a greater genetic diversity, rare variants that affect other populations can be identified.


The Wellcome Trust and NIH along with organisations such as the African Society of Human Genetics will provide both monetary resources and administrative support. It is hoped that this will aid building research capacity, including infrastructure and training in African countries thereby allowing the conduct research relevant to solving African problems. In addition, it is hoped that this will also foster collaborations with researchers in other parts of the world. Working groups have been established to help guide the initiative, and the project is due to begin in 2011.

News story   |   By Dr Philippa Brice   |   Published 28 June 2010

The International Society for Stem Cell Research (ISSCR) has a launched a new website for people considering stem cell treatments for different conditions.

The ISSCR, whilst promoting basic and clinical stem cell research, has expressed concern in the past about the potential exploitation of patients by clinics and practitioners offering unproven and potentially unsafe stem-cell based therapeutics, calling for improved regulation (see previous news). Their Task Force on Unproven Stem Cell Treatments released a report earlier this month setting out criteria for evaluation, to aid accountability and transparency and combat ‘rogue’ treatment providers (see Medical News report).


The new website, A Closer Look at Stem Cell Treatments, provides information for potential patients, family members and clinicians, and was created as a response to the increasing levels of ‘aggressive marketing campaigns’ for stem cell treatments. Users are offered tools to help them evaluate a clinic or treatment, including background information about scientific principles and questions to ask about the treatment, such as whether there is a medical ethics committee to protect patients’ rights or supervision by an official regulatory body. The intention is to eventually list stem cell clinics and whether or not they provide the ISSCR with evidence of suitable oversight.


ISSCR President Irving Weissman commented: “We feel it is an obligation of the ISSCR to both a) alert patients and caregivers about clinics and other entities that are selling unproven ‘stem cell’ therapies, and b) help shepherd real stem cell advances from discovery to successful patient treatments as rapidly as possible” (see press release).


Certainly, the move to provide consumers with accurate and sensible information to allow them to make their own choices about possible treatments seems an excellent approach to regulation, the more so since it comes from a body that promotes the potential medical benefits of stem cell treatments. A similar method for genetic tests, such as with the proposed Genetic Test Registry (see previous news), is also good idea, although the spectrum of costs and applications for genetic tests is broader and the risks arguably smaller than for stem cell therapeutics.

News story   |   By Dr Philippa Brice   |   Published 25 June 2010

This month marks the tenth anniversary of the completion of the first draft human genome sequence, with a range of events and commentaries marking the occasion. In an interview with the Times, Francis Collins, who led the US arm of the international Human Genome Project (HGP), has said that he expects most people to have their genomes fully sequenced within the next ten years.


In the UK, biomedical research charity the Wellcome Trust, which in partnership with the Medical Research Council (MRC) led the UK HGP sequencing efforts, has today launched a new project to sequence 10,000 human genomes. This is intended to advance understanding of the biological basis of difference diseases, and may also in some cases produce findings of more immediate clinical relevance.


The Wellcome Trust Sanger Institute is to work with other UK researchers on the UK10K project, which will involve genomic sequencing and analysis of two groups.  Full genome sequences will be produced for 4000 individuals already involved in long-term medical research projects, the TwinsUK (see previous news) and ALSPAC (see previous news) studies.


Exome (gene-coding region only) sequences will be completed for a further 6000 individuals with specific severe medical conditions thought to have a significant genetic cause including extreme obesity, autism, schizophrenia and congenital heart disease.

Lead investigator Dr Richard Durbin commented: "Although genetics over the past five years has yielded a rich harvest of hundreds of variants associated with disease, much more remains to be discovered…we are seizing the chance to use technological advances in DNA sequencing to find variants that have even greater consequence for health” (see press release). 

News story   |   By Dr Philippa Brice   |   Published 23 June 2010

The Royal Brompton Hospital in London has announced that it will be using a new Next Generation Genetic Sequencer machine, funded by the National Institute for Health Research (NIHR), to investigate the genetics of heart disease. Recent advances in both genetics and cardiology have made it possible to offer greatly improved care for patients with inherited forms of cardiac disease, an area now designated as a priority for UK Department of Health commissioners of specialised services following the 2009 PHG Foundation Report Heart to Heart: Inherited Cardiovascular Conditions Services.

Next-generation sequencing technologies allow increasingly rapid and affordable DNA sequencing. The Royal Brompton researchers plan to use genomic sequencing on a total of 10,000 adult patients over ten years to investigate the links between specific genetic variants and forms of cardiomyopathy, with a view to improving understanding of and personalised treatment for this group of cardiac conditions. Cardiomyopathies may be inherited; where these conditions do not appear to have been directly inherited, other genetic factors may nevertheless influence the risk of developing them.


The new project will focus on the ‘exome’ – the gene-coding regions of the genome – in combination with clinical investigations such as MRI scanning of hearts. Patients will receive genetic counselling before testing, since the analysis could also reveal genetic factors associated with other forms of disease (see BBC news).


Developments in technology for genomic sequencing are progressing rapidly; the Applied Biosystems sequencing machine to be used in this project is reportedly 200,000 times faster and 10,000 cheaper than those used for the sequencing of the first human genome ten years ago (see press release), and costs are expected to fall further in coming years whilst speeds continue to rise. The PHG Foundation is currently undertaking a major new programme of work to examine the implications of whole genome sequencing using next-generation technologies for health, since the potential impact on a wide range of medical fields is profound.


The journal Nature has celebrated the tenth anniversary of completion of the first draft human genome sequence with a poll of scientists about genome sequencing. Although the majority considered the Human Genome Project to have helped basic biological science, only around 20% thought that clinical medicine had benefited so far, due to the complexity of data and the enormous difficulties in interpretation. Over half expect that it will take more than 10-20 years before personalised medicine using genetic information will become common practice – and opinions about genetic sequencing and analysis of their own genomes varied: some had already tried it, many would if the cost were sufficiently low – and 17% reportedly said they would not do it even if paid to do so.

News story   |   By Dr Sowmiya Moorthie   |   Published 21 June 2010

The Biotechnology and Biological Sciences Research Council (BBSRC), together with the Engineering and Physical Sciences Research Council (EPSRC) initiated a project last year to develop a dialogue with the public regarding their concerns and aspirations in the emerging field of synthetic biology. They have now published a report on the findings from a series of public workshops and stakeholder interviews on the on the science and issues surrounding synthetic biology (see press release) and will use the findings to inform their strategic plans on funding and policy in this area.

The process initially involved interviews with various stakeholders such as consumers, scientists, religious groups, industry and regulators in order to provide some background and inform the workshops. They were asked about the field as well as potential applications and ethical consideration. Three workshops then explored different aspects of synthetic biology; the first explored views on science and technology, the second views on synthetic biology and how this is funded and regulated and the final workshop explored specific applications of synthetic biology. The discussions encompassed a number of applications of synthetic biology including medical, energy, environmental and food. Areas for future dialogues were also identified.

In general, the findings of these workshops showed that there was support for synthetic biology; especially if it can help address current concerns such as the energy crisis and treatment of diseases. However, the acceptability of research was dependant on how much progress could be made in each application area. There were concerns about control of biological organisms, who benefits, health or environmental impacts, misuse and governance. A number of conclusions were reached as to how to regulate innovation, the unique nature of this field and developing the capabilities of scientists to think through responsibilities. It was felt that continued dialogue was needed in order ensure that different stakeholder views are considered and incorporated into developing practices.

The recent report of the creation of a bacterial cell controlled by a synthetic genome (see previous news) has also stimulated a lot of debate in this field and lead to a hearing in the US Congress (see Reuters news). Although the hearing concluded that there are no immediate security, environmental or ethical concerns arising from developments in this field, there is some concern from researchers about the impact of regulations and patents in this field (see BBC news).

News story   |   By Dr Philippa Brice   |   Published 18 June 2010

A genetic research project is using a novel approach with respect to patient involvement and feedback. The Gene Partnership Project (GPP), based at the Children's Hospital Boston in the US, is a longitudinal study that aims to analyse links between genetics and disease by linking clinical and environmental data with genetic analysis. The intention is to collect 10,000 DNA samples a year, ultimately making sampling part of routine hospital care.

The difference from other projects of this type involving DNA databases is that a deliberate decision has been made to allow participants secure access to selected information about their own samples, as well as keeping them informed of discoveries arising from the research project. This could include identification of genetic factors associated with disease susceptibility.


Although it is not unknown for major research findings to be communicated directly to study participants, it is clearly less practical for large-scale, long-term studies such as this one. It is particularly unusual for participants to be informed about medical findings. This is due to concerns about protecting the privacy of patient data, and of providing information that may be unhelpful (for example, if it is misinterpreted by recipients). Incidental findings, where researchers inadvertently uncover evidence of serious medical conditions (see previous news), are actually quite rare in genetic research compared with other forms of clinical analysis – for example, involving medical imaging, which can identify undiagnosed tumours.


Reportedly, any decision to feedback genetic information from the GPP is taken by an oversight board (including ‘geneticists, ethicists and advocates’) on the basis of scientific validity and clinical utility (such as whether intervention to prevent or treat disease is possible); contact is made via a ‘secure electronic-messaging system’ (see Wall Street Journal article). Issues relating to consent are also relevant. In this instance, permission is sought from parents and also the participating children at ages 7, 13 and 18; withdrawl of consent means that DNA samples are destroyed.


Comment: The project website says that the innovative data-sharing approach will allow patient and families to ‘become full partners in this research, knowledgeable participants who can benefit from the discoveries made during the study’. This is a laudable aim, and indeed suitable benefit-sharing from research is an area of increasing importance. However, the fact that the study participants are all recruited as children does raise some issues around informed consent, despite the appropriate plan to re-obtain consent as children get older; for example, a potential conflict between the wishes of the parents and that of participating children. Also, how far can (or should) a child be a ‘full partner’ in such research, and how does the transition in involvement evolve from parent to child as the child's understanding and autonomy increases over time?


Making recruitment part of routine hospital practice, in combination with the feedback process, could also cause some confusion between scientific research and normal clinical investigation. It may be that increased patient involvement in long-term genetic research projects of this nature, whilst probably a good thing, would be better trialled in an adult population.

News story   |   By Dr Caroline Wright   |   Published 17 June 2010

Following the revelation last week that the  US Food and Drug Administration (FDA) now plans to start regulating consumer genomic services as ‘devices’ (see previous news), and the recent launch of the National Institutes of Health (NIH) Genetic Testing Registry (see previous news), various additional regulatory involvements in genomic medicine have now been announced.

Firstly, the FDA has expanded on its previous announcement relating to consumer genetic tests and has now indicated that it is intending to regulate all laboratory-developed tests (LDTs), i.e. those in vitro diagnostic tests that are manufactured and offered by the same laboratory (see press release). The FDA is planning a public meeting in July 2010 to discuss how it will regulate these tests, the scope of which will be much broader than just genetic or consumer tests and include myriad diagnostic tests developed and implemented by pathology labs throughout the US. Evaluation and regulation of LDTs has long been a bone of contention within the US, as they fall outside the existing medical device regulation, but this has become more pressing in recent years as the tests have become more complex and more widely offered (for more detail, see Genomics Law Report).


Secondly, writing the New England Journal of Medicine, the Directors of both the NIH and the FDA have laid out a roadmap for personalised medicine [Hamburg M & Collins F, NEJM (2010): doi: 10.1056/NEJMp1006304]. It is widely recognised that the financial and regulatory requirements for developing targeted treatments with companion diagnostics are very different from the standard models used currently in either the pharmaceutical or diagnostic industries. To address this issue, the NIH and the FDA will invest in “advancing translational and regulatory science” to "better define regulatory pathways for coordinated approval of co-developed diagnostics and therapeutics, develop risk-based approaches for appropriate review of diagnostics to more accurately assess their validity and clinical utility, and make information about tests readily available.”


Thirdly, in a separate move, the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS) has announced that it is assembling a task force to tackle the medical issues relating to affordable whole genome sequencing (WGS), focussing particularly on what it will mean for patients and doctors in the US (reported in GenomeWeb News). The staggering rate of development of ever cheaper WGS technologies has created a need to establish the clinical validity and utility of these tools, to assess their [potential impact on clinical practice and pathology services, and to consider their wider ethical and legal implications. The PHG Foundation has already recognised this need, and is working with partners to analyse the health implications of WGS within the UK NHS, focusing particularly on clinical utility for diagnosing inherited diseases and improving cancer care. 


News story   |   By Dr Caroline Wright   |   Published 14 June 2010

The US Food and Drug Administration (FDA) has dealt the controversial world of consumer genomics a major blow, by issuing five major companies with letters stating their intention to formally regulate the industry (see FDA archive). The letters – sent to 23andme, deCODEme, Navigenics, Knome, and the sequencing company Illumina – equate a personal genome service with a medical device, which falls under section 201(h) of the Federal Food, Drug, and Cosmetic Act. This action follows hot on the heels of the FDA’s recent intervention in relation to relative newcomer Pathway Genomics, which recently withdrew plans to sell its genome profile over-the-counter in the US (see previous news).


The Medical Device Amendments to the Act require premarket review and approval by the FDA of medical devices intended for human use, to ensure that they are analytically and clinically accurate “so that individuals are not misled by incorrect test results or unsupported clinical interpretations”. By allowing for independent and unbiased assessment, the Act aims to “protect the public from medical products that may pose an unreasonable risk of harm”.


Comment: The international implications of this move to regulate DTC genomics through statutory legislation, and how the test companies themselves will respond, remain unclear (see Genomics Law Report). The move will certainly be welcomed by some for providing long overdue protection for consumers from potentially harmful tests, and condemned by others as an unnecessarily paternalistic reaction to this fledgling industry.


Although there are many reasons why some kind of regulation in this area is advisable, regulators should proceed with caution and be clear about the harms they are trying to prevent (see our response to the UK Human Genetics Commission Consultation on their Common Framework of Principles for DTC Genetic testing services for a detailed analysis). One of the biggest issues is that, while classifying DTC genetics tests as devices is certainly appropriate for assessing their analytical validity and direct safety, it does not and cannot provide an assessment of the service. Unlike testing kits, for which the devices legislation is designed, genome scans include an additional element of interpretation provided by the companies. This aspect of the testing service is extremely difficult to regulate, not least because the interpretation and performance of the test vary substantially between different contexts. Hence standard medical testing has traditionally been overseen by professional medical bodies. Simply trying to classify the complete genomic testing service as “a device” is entirely inadequate and will not address the difficult issues at hand.


Such an argument might point towards requiring genetic tests to be ordered through registered health care professionals, as is now the case in various jurisdictions (for example, see previous news). However, this knee-jerk reaction points towards the nub of the problem: genomic risk profiling tests, in their current form, are simply not good enough to be used by health care services. They have scant evidence of clinical validity or utility, and are unlikely to yield clinically actionable results for individuals. Requiring the involvement of qualified medical doctors and genetic counsellors lends them greater legitimacy than is justified by the science. Even full genome sequencing is currently of limited use for most people (in the absence of a family history of an inherited disorder), and interpretation of the surfeit of data is far beyond the training and expertise of even the most well informed clinicians.


Nonetheless, this does not mean that a genome scan cannot provide interesting or useful information to individuals seeking to learn about their genomes, and to reduce access might considered to be unwarranted genetic exceptionalism. The best way to deal with this issue may be to ensure transparency and the provision of accurate information to consumers, to allow them to make informed decisions and to minimise the opportunities for harm.

News story   |   By Dr Philippa Brice   |   Published 11 June 2010

Following the news earlier this year that blood samples used for genetic research were to be returned to the indigenous Havasupai Indians in the US by Arizona State University (see previous news) comes a new report that a similar repatriation will take place to the Yanomamö Indians of Brazil. Originally collected for biomedical research by anthropologist Napoleon Chagnon from the 1960s, who studied the Yanomami tribe in their Amazonian rainforest homes between Brazil and southern Venezuela, the samples have been stored in various US laboratories ever since.


Five centres will now return these samples to the US Brazilian Embassy, which will return them to the Yanomami for disposal. This move was prompted by allegations that the original sample collection (in the days before informed consent procedures were standard for such activities) was unethical, leading to demands for the return by tribal representatives. The Yanomami cremate their dead and are unhappy with the concept of retained samples.


Spokesman Davi Kopenawa said: “I am very happy that the white people have now understood the importance of returning the blood… Science is not a god who knows what is best for everybody. It is we Yanomami who know whether or not research is good for our people” (see Survival news).

However, Chagnon has reportedly commented that they may, rather, be worse off, saying: "The Yanomamö, like all populations, depend on medicines…I think it's reasonable that they should participate in what it takes to develop medicines, instead of being just the recipients" [Couzin-Frankel J. Science. 2010 Jun 4;328(5983):1218].

News story   |   By Dr Philippa Brice   |   Published 7 June 2010

The UK charity the Genetic Interest Group has become the Genetic Alliance UK. First established in 1989, the Genetic Alliance UK works to improve the lives of people affected by genetic conditions, by promoting awareness and understanding of these disorders with a view to driving the provision of high quality health services. This role includes research, advocacy and patient support.


Members of the Genetic Alliance UK include individuals, families, and more than 130 organisations (patient groups and charities), many representing genetic conditions that are individually very rare.The rebranding has been prompted by a desire to provide ‘better insight into the voices we represent and the wide range of work we do’ (see announcement).

News story   |   By Dr Philippa Brice   |   Published 8 June 2010

The US National Institutes of Health (NIH) has issued a call for input and feedback on recently announced plans to create a Genetic Testing Registry from stakeholders including researchers, test developers and manufacturers. The Genetic Testing Registry (GTR) will provide information for consumers on the availability, validity and usefulness of genetic tests (see previous news).

The new consultation poses questions about the potential uses of the GTR for different groups and purposes: researchers, patients/consumers, health care providers, clinical laboratory professionals, funders, genetic test providers, policy makers, and electronic health records It also seeks responses to a range of questions, including:

  • The potential uses of the GTR for different groups and purposes
  • The potential risks and benefits of facilitating public access to information about genetic tests
  • Which data elements are required to describe each genetic test
  • Whether references to other sources of data would be beneficial
  • How to ensure ongoing stakeholder input to maintenance of the GTR
  • Barriers and drivers for submission of data about genetic tests
  • Whether any types of genetic test should not be included in the GTR

Responses are requested by 27th June 2010.

News story   |   By Dr Philippa Brice   |   Published 6 June 2010

A new PHG Foundation report sets out evidence for using tandem mass spectrometry (MS/MS) to screen for an expanded range of inherited conditions in newborn babies. Newborn screening allows early diagnosis of rare but serious diseases, typically those where prompt medical intervention can prevent serious adverse outcomes.

The current UK newborn screening programme, first initiated in 1969, is relatively conservative in scope in comparison with that in some other countries, screening for phenylketonuria, congenital hypothyroidism, sickle-cell disorders (haemoglobinopathies), cystic fibrosis and Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD). This contrasts with the position in the US, where a core panel of 29 conditions is screening for across the country, with an additional 25 secondary conditions that may optionally be added (see previous news).


The addition of MCADD to the UK screening panel in 2007-8 (see previous news) involved the introduction of MS/MS technology, making it feasible to simultaneously test for additional conditions for little additional cost using the same technique and equipment. However, deciding whether new conditions should be screened for is not straightforward, since evaluating the clinical, economic and ethical issues is particularly difficult for very rare conditions for which little data is available (see previous news).


Recently, pressure to consider expansion of the current UK screening panel in the light of advances in not only diagnostic potential but also improved treatment options has been mounting from both clinicians and families of affected children.


The report Expanded newborn screening: A review of the evidence, funded by the National Institute of Health Research Collaboration for Leadership in Applied Health Research and Care - South Yorkshire (CLAHRC-SY), examines the evidence to support introduction of five additional rare inherited metabolic diseases (IMDs) considered to be strong candidates by experts in the field:

  • Maple Syrup Urine Disease (MSUD)
  • Homocystinuria
  • Glutaric Aciduria Type I (GA1)
  • Isovaleric Acidaemia (IVA)
  • Long-chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHADD)

It concludes that there is potential to reduce death and severe disability caused by these conditions in a cost-effective manner, and proposes that a pilot study is required to more fully assess cost-effectiveness, quality standards and patient outcomes, taking into account issues such as the availability of appropriate specialist care for babies diagnosed with these IMDs and the need for resources to support patients and families. These findings were presented to the UK National Screening Committee earlier this year.

News story   |   By Dr Sowmiya Moorthie   |   Published 7 June 2010

The US Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) has released a draft report reviewing the status of genetics education of health care professionals, public health providers and consumers. The findings were based on literature reviews and surveys of both professionals and the public. Along with reviewing the status of genetics education, the report outlines some gaps in the education and training needs of these groups and makes recommendations on how to address them. The draft report is open for comment until the end of June.

The report makes seven recommendations including calling upon the US Department of Health and Human Services (HHS) to convene a workshop in order to identify innovative education and training approaches. A particular recommendation to identify education models and programmes that will improve the training of those who serve underrepresented groups is also made. The education and training of health care professionals is believed to be a significant factor limiting the integration of genetics into clinical care. In relation to the public health workforce, the authors recommend “a systematic effort to evaluate the composition of the public health workforce with current job responsibilities related to genetics and genomics and to identify future priorities, such as the potential impact of affordable genomic analysis”.

They also recommend making funding available to endorse and maintain a web-based portal containing information for consumers. They stress the importance of providing information that is understandable at all levels and call on the HHS to support research that identifies methods of providing information which can be used by consumers to make informed health decisions. The report also calls for incentives such as reimbursement for time spent in direct patient care or members of teams providing genetic services in order to encourage investment and resources in developing education and training programmes.



Keywords : US

News story   |   By Dr Caroline Wright   |   Published 4 June 2010

Cancer is characterised by massive genomic changes, ranging from single point mutations to major chromosomal rearrangements and duplications (see previous news). As a result, the genome of a cancerous tumour is often very different from other tumours, and indeed from an individual’s inherited genome – a fact which has been exploited previously to develop personalised diagnostics (see previous news). Moreover, these changes can affect a tumour’s ability to grow, and how it responds to different drugs.

Cancer Research UK (CRUK) has this week announced a major programme of investment into providing stratified therapies to NHS patients based on genetic testing of their tumours (see press release). The scheme will include six new centres dedicated to systematic genetic testing of cancer tumours. By classifying cancers by the specific genetic changes that drive them, it is hoped that these tests will help physicians decide which of numerous different possible treatment options each patient should receive. Given the substantial proportion of drugs that are currently ineffective or cause intolerable side-effects, if this strategy works, it could not only improve patient care but also save the NHS money through better targeting of resources.

In addition to building valuable partnerships between academic research, industry, health care providers, and patients, the work should provide important evidence about which types of genetic changes in cancer result in better or worse response to treatments. Ultimately, it is hoped that this will “revolutionise cancer care”, and if the initial pilots of a few thousand patients are successful, there are plans to “roll this out across the country starting in 2012”. However, before that can happen, robust evidence will be needed that the testing actually improves outcomes.

Research articles

Research article   |   By Dr Caroline Wright   |   Published 30 June 2010

Often cited as the archetypal ‘genetic’ disease, Huntington’s disease (HD) is a degenerative neurological disorder inherited in an autosomal dominant manner with almost 100% penetrance. The discovery of the faulty huntingtin gene in 1993 allowed a highly predictive molecular diagnostic genetic test to be developed, which offers benefits particularly to young people at risk of the disease (see previous news).

Although HD is officially classed as ‘rare’, with a prevalence of less than 50 people per 100,000 of the population (see Orphanet), it may not be as rare as was previously thought. A Comment published in the Lancet  puts the prevalence of the disease as at least 12.4 per 100,000 population in the UK, based on figures from the Huntington’s Disease Association, which is almost double previous estimates [Rawlins M. Lancet (2010) doi:10.1016/S0140-6736(10)60974-9]; the prevalence of presymptomatic people is believed to be roughly double again. An independent Perspective in the same issue highlights the stigma faced historically by families with the disease [Wexler A. Lancet (2010) doi:10.1016/S0140-6736(10)60957-9], which partly explains why HD has been under-diagnosed for so long. This stigma is still in evidence today – for example, HD is the only exception to the voluntary moratorium on the use of genetic tests by the insurance industry in the UK (see previous news) – and the majority of those at risk of inheriting the disease decline to take a diagnostic test (see previous news).

These papers coincide with the launch today of an All Party Parliamentary Group (APPG) on HD (see Hidden No More), which aims to raise the public profile of HD and give a voice in UK Parliament to those suffering from the disease, as well as their families and carers. The group will seek to highlight the need for better support services for those families affected by the disease and more funding for scientific research, as although treatments are being developed (see previous news), the disease remains incurable and fatal.

Keywords : huntingtonsjournal

Research article   |   By Dr Gurdeep Sagoo   |   Published 30 June 2010

Type 2 diabetes (T2D) is a common life-long condition where the level of blood glucose is too high, either because the body cannot produce enough insulin (which is needed for glucose to enter the body’s cells) or the insulin that is produced does not function properly. To date, several genes have been confirmed as being involved in T2D, along with many more common variants associated at the genome-wide significance level (see previous news). But despite all this research, less than 10 percent of the overall estimated genetic contribution to T2D predisposition is accounted for.

A new study published in the journal Nature Genetics has identified further novel loci, increasing the number of confirmed loci for T2D to 38. The study, performed by researchers from the across the world, combined data from over 40,000 T2D cases and almost 100,000 controls all of European descent [Voight et al. Nature Genetics (2010) doi:10.1038/ng.609]. The results from eight genome-wide association studies involving 8,130 cases and 38,987 controls were combined using a meta-analysis. After removing SNPs located near previously identified genes, the 23 most strongly associated autosomal SNPs were followed-up in a further 19 studies comprising of up to around 34,000 cases and 60,000 controls. An X chromosome signal was also followed up in 4 studies involving 8,500 cases and 12,000 controls. The researchers then combined both stages in a further meta-analysis, with 14 loci (13 autosomal and 1 X chromosome) reaching genome-wide significance. Two loci represent associations already reported in subsets of the data leaving twelve loci for further investigation, of which nine represent truly novel associations. The new loci include genes involved in beta-cell function, insulin action and cell cycle regulation.

Comment: It is becoming increasingly evident that common SNPs are not going to fully explain the heritability of common complex diseases; even including these new loci only, the genetic risk variants association with T2D only account for a small fraction of the disease. This suggests that elusive rare genetic variants may be playing a larger role. Interestingly, a number of loci associated with T2D susceptibility have also been implicated in other common traits, suggesting an overlapping and hitherto unsuspected shared genetic architecture.

Research article   |   By Dr Gurdeep Sagoo   |   Published 14 June 2010

In the UK, around 1 in every 100 people has autism (according to The National Autistic Society). The autism spectrum disorders (ASD) are a group of heterogeneous conditions that cause variable degrees of lifelong developmental disability by affecting the way a person communicates with and relates to others. Although ASD is known to be highly heritable (see previous news), uncovering the genetic basis for this group of conditions has been more tricky (see previous news). A new study published in the journal Nature has investigated rare copy number variants (CNVs) across the genome in individuals with ASD compared with controls.

The study by Pinto et al. report findings from the second phase of the Autism Genome Project (see previous news) [Pinto et al. Nature (2010) doi:10.1038/nature09146]. This involved initial genotyping of 1,275 ASD cases and their parents (from 1,256 families) and 1,981 unaffected controls at 1 million SNPs. Data from 996 ASD cases (from 876 families) and 1,287 controls of European ancestry were chosen for analysis. Rare CNVs were defined as those

1) present at less than 1% frequency in the total sample and;

2) greater than 30kb in size (to maximise the possibility of verification);

3) additional statistical and other quality control measures were also included.

Almost 5,500 CNVs were identified and chosen for analysis. When assessing the impact of rare CNVs between the cases and controls, no difference was observed with the number of CNVs per individual and the estimated size of these CNVs The number of genes affected by the CNVs was found to be higher in cases than controls.

Parent to child transmission of these rare CNVs was also assessed and confirmed 5.7% of cases (50 out of 876) had at least one de novo CNV that could be associated with ASD, not being present in either of the parents. A total of 226 validated de novo (7) and inherited (219) CNVs that affected genes were identified in cases but not controls. Novel candidate genes such as SHANK2 (related to known ASD susceptibility gene SHANK3), SYNGAP1, DLGAP2, and maternally-inherited X-linked deletions at DDX53-PTCHD1 were identified. Further validation of these genes was conducted in an additional 3,677 controls and again, CNVs were not identified.

Comment: Although this, the largest genetic study into ASD, provides additional clues to the underlying genetic basis of ASD, there remains much more research to be done. The candidate genes identified are biologically interesting, although any talk of targets for genetic testing and therapeutic intervention are highly premature. With the continuing use of microarrays for genetic analysis (see previous news) as well as whole-genome approaches (see previous news) identification of rare CNVs involved in disease aetiology is sure to continue.

Research article   |   By Dr Susmita Chowdhury   |   Published 4 June 2010

Most complex diseases including breast cancer are associated with both genetic and environmental risk factors. It is well established that several environmental and lifestyle factors such as childbearing, hormone replacement therapy (HRT), obesity, alcohol consumption are significantly associated with breast cancer. To date, 17 genetic variants or SNPs (single nucleotide polymorphisms) have been identified, which account for around 8% of breast cancer risk. However, there have been inconsistent findings related to the possible interactions between the effects of variants and environmental risk factors. Gene–environment interactions mean that some people carry genetic factors that confer susceptibility or resistance to a certain disorder only in particular environments.


In order to test for evidence of gene-environment interactions in relation to breast cancer, researchers  compared the genotypic relative risks for 12 SNPs across categories for ten established environmental risk factors in one of the largest prospective UK cohorts [Travis et al. 2 June 2010 doi:10.1016/S0140-6736(10)60636-8]. 7160 cases with breast cancer and 10196 controls from the Million Women Study cohort were included in the final analyses. Information for both cases and controls about the ten environmental risk factors (age at menarche, parity, age at first child birth, breastfeeding, menopausal status, age at menopause, use of HRT, body mass index, height and alcohol consumption) was recorded at the time the women joined the study. For this study cases and controls were mixed and genotyped by laboratory personnel unaware of the sample status.    


120 separate statistical tests for gene-environment interaction were carried out and no significant association was found between 11 of the 12 polymorphisms and the ten risk factors. For the 12th SNP, there was a significant association with height, with taller women at slightly increased risk of breast cancer. The results of this study suggest that the low-penetrance susceptibility loci investigated here do not generally affect breast cancer risk through mechanisms involving these environmental factors. The only major environmental risk factor not studied here is postmenopausal hormone concentrations in the blood.


Comment: Though this is one of the largest studies to investigate gene-environment interaction in relation to breast cancer, tens of thousands of cases will be needed to assess reliably a comprehensive range of biologically plausible gene-environment interactions. The design of this study is generally sound, with a few limitations such as lack of information about risk in young women, multiple testing and relatively few a-priori hypotheses. The findings of the study are generally reassuring because, as genetic and environmental factors independently increase breast cancer risk, women with inherited genetic variants can still reduce breast cancer risk by modifying their lifestyle such as maintaining a healthy weight, limiting alcohol and HRT. Indeed, since lifestyle factors are the main risk factors for breast cancer, all women should maintain healthy lifestyle habits to reduce their risk, irrespective of family history.


Research article   |   By Dr Gurdeep Sagoo   |   Published 2 June 2010

In the UK, around 1 in every 131 people has epilepsy (according to the Joint Epilepsy Council). Epilepsy is a common neurological condition which causes recurrent seizures due to the over-activity of the brain. There are over 50 distinct epilepsy syndromes and although various causes of epilepsy are known, such as brain damage or brain tumours, idiopathic epilepsy occurs in the absence of an identifiable cause, with genetic factors thought to contribute (see previous news). A new study published in the journal PLoS Genetics has identified copy number variants (CNVs) in regions of interest not only in epilepsy but also other neurological conditions such as intellectual disability, autism, and schizophrenia.

The study by Mefford et al. reports a whole-genome oligonucleotide array comparative genomic hybridisation of 517 individuals of European descent with various idiopathic epilepsies [Mefford et al. PLoS Genet 6(5): e1000962. doi:10.1371/journal.pgen.1000962]. Patients were collected from five centres and included diagnoses such as idiopathic generalised epilepsy or IGE, idiopathic focal epilepsy, and other forms of epilepsy. In 46 individuals, one or more rare CNVs ranging in size from 13kb to 15.9Mb were identified. These variants were not identified in a previously reported cohort of nearly 2,500 controls, suggesting that they may be causal.

The identified CNVs also involved genes or regions that have been previously implicated in other neurological phenotypes such as autism. Deletions on chromosomes 15 (15q11.2 and 15q13.3) and 16 (16p13.1) were mostly observed in IGE individuals. On chromosome 15q11.2, the candidate gene is CHRNA7, a subunit of the nicotinic acetylcholine receptor, although the epidemiological evidence from the small studies conducted to date is mixed. Chromosome 16p13.1 is a novel susceptibility locus for epilepsy. Several other candidate genes were also reported including CNTNAP2, CNTNAP4, and AUT2. The authors suggest that these regions and genes should be investigated as candidate genes with possible roles both across subtypes of IGE as well as in specific subtypes. Overlapping regions with other neurological conditions suggests some common aetiological genetic factors across these conditions.

Comment: The use of microarrays for genetic analysis is becoming more commonly applied (see previous news) including databases cataloguing variation observed with clinical or healthy phenotypes to aid with clinical evaluation of identified CNVs (see previous news). This paper is the first whole-genome array-CGH analysis in epilepsy and has identified some previously known regions and candidate genes (see previous news) as well as some novel regions that warrant follow-up work. This work is based on the common disease, rare variant model of disease where common diseases are caused by multiple rare variants. Finding these rare variants requires large sample sizes and high resolution technology such as array-CGH and some difficulty still remains in determining whether a CNV is causal or benign.

Keywords : journal

New reviews and commentaries

Selected new reviews and commentaries, 1 June 2010

Reviews & commentaries : by Dr Philippa Brice

Is modern genetics a blind alley? Yes.

Le Fanu J. BMJ. 2010 Mar 30;340:c1156. doi: 10.1136/bmj.c1156.


Is modern genetics a blind alley? No.

Weatherall DJ. BMJ. 2010 Mar 30;340:c1088. doi: 10.1136/bmj.c1088


Genomic Medicine - An Updated Primer
Feero WG, Guttmacher AE, Collins FS. NEJM, 2010 May 27; 362:2001-2011.


Ten Years On — The Human Genome and Medicine

Varmus H. NEJM, 2010 May 27; 362:2028-2029.


Uncovering the roles of rare variants in common disease through whole-genome sequencing.

Cirulli ET, Goldstein DB. Nat Rev Genet. 2010 Jun;11(6):415-25.


Challenges in the clinical application of whole-genome sequencing.

Ormond KE et al. Lancet. 2010 May 15;375(9727):1749-51.


Missing heritability and strategies for finding the underlying causes of complex disease.

Eichler EE et al. Nat Rev Genet. 2010 Jun;11(6):446-50.


Genomics goes beyond DNA sequence.

Katsnelson A. Nature. 2010 May 13;465(7295):145. 


Gene regulation: Breaking the second genetic code.

Tejedor JR, Valcárcel J. Nature. 2010 May 6;465(7294):45-6.


Transcription: Enhancers make non-coding RNA.

Ren B. Nature. 2010 May 13;465(7295):173-4. 


Informed Consent in Genomics and Genetic Research.

McGuire AL, Beskow LM. Annu Rev Genomics Hum Genet. 2010 May 17. [Epub ahead of print]


Research ethics. Beyond access vs. protection in trials of innovative therapies.

London AJ, Kimmelman J, Emborg ME. Science. 2010 May 14;328(5980):829-30. 


Reaching the limits of genome-wide significance in Alzheimer disease: back to the environment.

Pedersen NL. JAMA. 2010 May 12;303(18):1864-5.


Chromosome 9p21 and coronary artery disease.

McPherson R. N Engl J Med. 2010 May 6;362(18):1736-7. 


Mendelian randomisation, triglycerides, and CHD.

Pare G, Anand SS. Lancet. 2010 May 8;375(9726):1584-6. 


Neuroscience. Epigenetics and cognitive aging.

Sweatt JD. Science. 2010 May 7;328(5979):701-2. 


Susceptibility pathways in Fanconi's anemia and breast cancer.

D'Andrea AD. N Engl J Med. 2010 May 20;362(20):1909-19.  

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