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 and Dr Caroline Wright   |   Published 30 April 2008

In recent weeks, the health department of New York State has issued letters warning companies which offer direct-to-consumer tests that they require a permit in order to carry out gene scans (see news source). Public health law in New York State prohibits clinical laboratories from providing direct-to-consumer tests without the intervention of a medical professional, unless the tests have been approved by the FDA for direct, over-the-counter sale to consumers (see guidance on Direct Access Testing). In California, health regulators are investigating companies that offer genetic tests without the presence of a physician (see news source). The need for an adequate framework to regulate genetic tests and companies that offer them direct-to-consumer is becoming an increasingly important issue.

A number of US organisations have called for policies to regulate genetic tests, especially those that are available direct-to-consumer. The American College of Medical Genetics has released a policy statement outlining five minimum requirements for genetic testing protocols. This follows a statement on direct-to-consumer genetic testing released by the American Society for Human Genetics containing similar recommendations, and a report from the UK Human Genetics Commission on the availability, marketing and regulation of genetic tests supplied directly to the public (see previous news story), both published in December 2007. The US Genetics and Public Policy Center has also recently called for tighter regulation of genetic tests in an article published in Science (see press release).

These organisations call for greater transparency in the evidence in support of genetic tests so that physicians and the public can make an informed choice. They also recommend health professionals to be involved in ordering and interpreting tests and a greater oversight of laboratories and companies that provide them.

News story   |   By Dr Philippa Brice   |   Published 29 April 2008

In the last month there have been several new moves form the US intended to accelerate the pace of change in pharmacogenomics, the study of genetic influences on drug responses. The National Institutes of Health (NIH) has sought input from scientists, the pharmaceutical sector and other on challenges and barriers to pharmacogenomics research, on behalf of the Trans-NIH Pharmacogenomics Working Group, with a view “to highlight opportunities, reveal gaps, and aid in identifying specific, achievable goals that will advance the field” (see Request for Information).

Scientists from the NIH Pharmacogenetics Research Network have joined with Japanese scientists from the Centre for Genomic Medicine (part of the RIKEN Yokohama Institute) to sign a letter of intent for the creation of a new Global Alliance for Pharmacogenomics. The aim is to co-ordinate ongoing research efforts to identify genetic factors that influence responses to drugs, with initial projects including investigation of warfarin and selected drugs for breast and pancreatic cancers, as well as exploring genetic factors that affect drug-induced long QT syndrome.Yusuke Nakamura, director of the Center for Genomic Medicine said: "By bringing together our resources, we will advance the understanding of how changes in DNA affect our responses to medicines. Thus we can begin to realize the promise of personalized medicine" (see press release).

Meanwhile, in a move intended to harmonize pharmacogenomic definitions and guidance with Japan and the EU, the US Food and Drug Agency (FDA) has issued a new industry guideline for comment. E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories defines a genomic biomarker as a measurable DNA or RNA characteristic that is an indicator of normal biologic or pathogenic processes or a response to therapeutic or other interventions, and also notes that certain principles in the document may also be applicable to proteomics and metabalomics (see FDA news).

News story   |   By Dr Alison Stewart   |   Published 28 April 2008

Our inheritance, our future, the 2003 White Paper on genetics, set out the UK Government’s first explicit policy commitments in the field of human genetics. Significant investment was announced in a range of areas including clinical genetic testing, pharmacogenetics research, service development, and education and training of health professionals. The Genetics Knowledge Parks programme aimed to look ahead to the scientific and policy developments that would be needed to bring genetics advances into mainstream health care and public health.

Five years on, the Department of Health has reviewed progress on the White Paper’s commitments. Some important achievements are highlighted, notably the development of a system for evidence-based evaluation of clinical DNA tests through the auspices of the UK Genetic Testing Network, the setting up of the National Genetics Education and Development Centre, and some improvement in the speed and capacity of clinical genetic testing services. The progress of White Paper-funded research projects in pharmacogenetics, service development and gene therapy is also described.

So far, so good, but the report, while acknowledging ‘future challenges and opportunities’ in a general way, fails to offer any real commitment or strategy, on the part of Government, to tackle these challenges. It is clear that five years is far too short a time for significant benefits from investment in genetics to have been realised. Genomics research is generating a flood of new information about associations between genetic variants and common diseases. What is needed is a rational approach, with realistic resources, for identifying and evaluating clinical applications of this information, and for steering health services through the process of change management that will be needed if validated new tests and interventions are to be successfully implemented.   

News story   |   By Carol George   |   Published 25 April 2008

Amendments proposed last year in a review of the 1990 Human Fertilisation and Embryology Act contain a new provision in relation to fertility treatment that has offended members of the deaf community and raises important questions about government policies on embryo selection and serious disability. The controversy is centered on a new licensing condition proposed in clause 14(4) of the Human Fertilisation and Embryology Bill that would prohibit the selection of a ‘disabled’ embryo when a normal one is available. Embryos known to have a genetic abnormality (including a gender-related abnormality) that places them at ‘significant risk’ of ‘serious disability or illness’ are not to be preferred over those that are not known to have the abnormality. The same prohibition extends to the preference of persons with a genetic condition who might act as donors of gametes or embryos. The express intention of the clause, indicated in both the explanatory notes and proceedings in the House of Lords, was to prevent situations similar to those reported elsewhere in which deliberate attempts had been made to produce a deaf child through positive selection of embryos or donors.

The ensuing legal and ethical debate is far from theoretical for the deaf couple who wish to share their experience with a deaf child rather than a hearing one. Tomato Lichy and his partner Paula Garfield view their deafness as membership in a linguistic minority, rather than a serious disability, and attempts to prevent them from choosing a deaf child as discrimination violating their rights to equality and privacy. This view is opposed by members of the medical community, who have serious concerns about permitting the deliberate selection of deaf babies. Professor Peter Braude, director of the Assisted Conception Unit at Guy’s and St Thomas’ Hospital in London is quoted as saying that “This is the same as taking a normal child and deliberately making it deaf so that it can fit in with a community. I don’t see how that can be acceptable” (see Telegraph article). Neither is it a view that is accepted by some of those who campaign on behalf of the unhearing. The Royal National Institute for Deaf People (RNID) does not support the choice of deaf embryos over those who would not be born with hearing problems. Chief executive Jackie Ballard says that “No one should be forced into having genetic testing if they don't want it. But if they do, we would want the embryos without the gene to be implanted” (see BBC news).

Nevertheless, the outcry and media coverage has elicited a response from the Department of Health, which has reportedly agreed to drop any reference to deafness as a serious medical condition. The concession does not extend to removal of the general prohibition against preference of embryos with genetic conditions, but it could pave the way for a challenge in the House of Commons later this year as to whether deafness should be classed as a serious medical condition for the purposes of the Bill. If successful, amendment of the Bill might permit parents undergoing IVF treatment to choose an embryo that will develop into a deaf child.

14 Conditions of licences for treatment

(1)        Section 13 of the 1990 Act (conditions of licences for treatment) is amended in accordance with subsections (2) to (4).

(4)        After subsection (7) insert:

(8)       Subsections (9) and (10) apply in determining any of the following:

(a)      the persons who are to provide gametes for use in pursuance of the licence in a case where consent is required under paragraph 5 of Schedule 3 for the use in question;

(b)     the woman from whom an embryo is to be taken for use in pursuance of the licence, in a case where her consent is required under paragraph 7 of Schedule 3 for the use of the embryo;

(c)      which of two or more embryos to place in a woman.

(9)            Persons or embryos that are known to have a gene, chromosome or mitochondrion abnormality involving a significant risk that a person with the abnormality will have or develop—

(a)      a serious physical or mental disability,

(b)      a serious illness, or

(c)      any other serious medical condition,

must not be preferred to those that are not known to have such an abnormality.”

Clause 14(4) of the Bill (above) effectively means that a person with a genetic condition, at significant risk of serious illness or disability, may not donate eggs or sperm for IVF treatment if there is an existing donor without such a condition. It also means that an embryo with a genetic abnormality posing a significant risk of serious illness or disability must not be implanted if there is one available that does not, or is not known to, have the abnormality.

The case raises a number of legal and social questions about perceptions of disability and the parameters of reproductive choice. The ‘medical model’ of disability employed in the Act has been blamed by supporters of the deaf community for undervaluing people with genetic conditions, their contributions to society, and – in the case of the deaf couple – their unique language and culture. It is true that the choice PGD offers to parents is one based on purely medical criteria – while each embryo is equally valuable in human terms. It is also true that the objective of PGD is to provide families with a means of choosing to avoid hardships associated with serious physical limitations - and that parents are not obliged to have their embryos diagnosed prior to implantation. At the point at which the in vitro fertilization has taken place and diagnosis obtained, however, a crucial decision must be made. The decision is not about whether an unhearing child would be better off with hearing. It is about which of the embryos, each legitimate offspring of a couple, will be nurtured and raised, and which will perish. The decision involves an element of discretion that the government is apparently not content to leave entirely to the parents, and which the parents might justifiably consider their personal prerogative.

The legislation currently places some controls on the use of PGD, limiting the genetic characteristics that may be tested for, and thus the information upon which the selection is to be based. These parameters are not presently in question, but within them there is an issue over the right to make the actual selection. The legislation and the goal of medical intervention by PGD are based on a presumption, reiterated in clause 14(4), that the interests of the public are best served by avoidance of genetic abnormality and physical impairment, and propose to prevent any other result. The values that suffuse this presumption are a cause of concern for Tomato and Paula, who argue that their preferences should not be legislated and that the government should not be arbiters of their family life. 

Various arguments are being flung about in the debate as to the right of disabled parents to choose children like themselves. The right to privacy in such intimate matters, the right to family life and the right to equality as well as non-discrimination are being hailed. The public interests against which such individual rights must be balanced, apart from overarching public health questions and economic considerations, are not self-evident. There is unlikely to be a floodgates problem of people seeking to use PGD in this way. Still, the government may be committed in principle to a prohibition of deliberate preference of disabilities, and refocus the debate on whether deafness is outside of the scope of ‘serious disability’ or ‘serious medical condition’. The absence of definitions in the Bill is perhaps by design, providing a degree of flexibility to permit interpretative application in individual cases. Where however ambiguity is informed by a contextual understanding of the intention of the legislators - in this case the accompanying explanation that deafness was being targeted – the legislative interpretation must take it into account. By removing this reference the notes should have less (prejudicial) relevance for the interpretation of ‘serious disability’ in the context of individual PGD assessments involving deafness.

Given the current limitations of the treatment - the prevalence of IVF births is just 1% and PGD has a low success rate and high cost - one has to question the need for any change in the level of regulatory scrutiny regarding preferences in the selection process. While Tomato and Paula remain the exception to the rule, the case-by-case method for addressing such decisions may continue to be the most appropriate way of handling them.

News story   |   By Dr Philippa Brice and Dr Sowmiya Moorthie   |   Published 23 April 2008

New technologies that have a potential to impact on health services are in constant development, and adequate Health Technology Assessment (HTA) systems are needed in order to make evidence-based decisions on the benefits of new clinical tools. A recent report published by the European Observatory on Health Systems and Policies has identified areas which could lead to improvements in HTA systems; Ensuring value for money in health care: The role of health technology assessment in the European Union is based upon a review of HTA organisations and processes across Europe.

The authors concluded that improvements to HTA could be made through a number of mechanisms such as increased transparency and stakeholder involvement, assessment of existing technologies as well as new ones, assessing the timing of evaluations so that decisions can be made quicker and more effectively and the implementation of a system which allows re-evaluation of products based upon new information on clinical and health economics. Some of these recommendations are similar to those published in a report by the House of Commons Health Committee following an inquiry into NICE, the National Institute for Health and Clinical Excellence (see also NICE’s response).

Comment: The importance of the assessment of new biomedical tools and interventions is strongly supported by the PHG Foundation; one of the key strategic objectives is to promote the development of systems and policies for the proper evaluation of new technologies that arise from biomedical research, and many of our projects relate to evaluation of this kind; for example, see our work streams on the Evaluation and regulation of genetic tests and Promoting genetics in mainstream medicine.

Prompt and effective translation of emerging technologies into health service practice requires key steps of evaluation, assessment, appraisal and implementation following on from ‘bench to bedside’ research; the PHG Foundation suggests that in the UK, these stages are not optimally handled, with the Health Technology Assessment (HTA) scheme limited to evaluation and assessment, and not directly linked with policy development (see Genomic Medicine consultation response). Our aim as practitioners of public health genomics is to bridge the current gap between assessment/evaluation and clinical implementation, a gap which creates unnecessary delay at translating potentially valuable new technologies into clinical practice and better health.

Keywords : rRegulatory Framework

News story   |   By Dr Alison Stewart   |   Published 22 April 2008

In 1995 the House of Commons Select Committee on Science and Technology published Human Genetics: the Science and its Consequences, a report which showed for the first that UK politicians were becoming aware of new developments in genetics and their potential impact on health care. Publication of the report was followed, during the second half of the 1990s, by the establishment of the first Government advisory committees devoted to aspects of genetics policy.

More than a decade later, the Human Genome Project is complete and the Commons Science and Technology Committee is defunct, but its counterpart in the House of Lords has appointed a sub-committee to carry out an inquiry into Genomic Medicine, aiming to “provide an assessment of genome technologies and their actual and potential impact on clinical practice in the post-genome era”. The initial consultation stage of the inquiry, which has just closed, asked for evidence on issues ranging from the state of the science to how effectively it is being translated into new clinical tests and interventions, whether the existing regulatory framework is appropriate, and whether ethical, legal and social considerations are being adequately addressed.

In its response to the call for evidence, the PHG Foundation emphasises that, although genomic science is in a robust state, progress is much slower in evaluating the clinical and public health relevance of these scientific advances. There is insufficient recognition of, or resources for, the final stage of translation, which is not a research activity but a process of change management that includes knowledge integration and synthesis, knowledge brokering, stakeholder dialogue and consensus-building, clinical and public policy development, service review and reorganisation, education and training. These activities form the core of the work of public health genomics.

The PHG Foundation calls for a regulatory and policy regime that avoids ‘genetic exceptionalism’, instead treating DNA as one among several types of biomarker that may be used in the diagnosis of disease or estimation of disease risk. It points out that, in the context of common disease, the concept of ‘individualised medicine’ may be misleading. Advances in genomics are unlikely to lead to an ability to provide an individual with a precise, personalised prediction of drug response or disease risk. Rather, genomics will refine our ability to place that person within a band or segment of the population characterised by a particular array of diagnostic features or a particular average disease risk. This process does not differ in principle from the current practice of population stratification based on phenotypic features such as blood pressure or cholesterol levels.

Finally, the Foundation predicts that new service models and professional roles will need to be defined as genetics becomes integrated into mainstream medical practice, and routine genetic aspects of care are devolved to appropriately trained health professionals in other specialties.

The next phase of the House of Lords’ inquiry will be a series of public meetings and oral evidence sessions. The Committee expects to publish its final report, with the accompanying evidence, towards the end of 2008.

News story   |   By Dr Sowmiya Moorthie   |   Published 21 April 2008

The Wellcome Trust Case Control Consortium (WTCC) has received £30 million to begin a new series of genome wide association studies, or GWAs (see press release). The venture, the largest study of genetics behind common diseases, will be funded by the Wellcome Trust and is a follow up to last year’s successful completion of a similar but smaller scale study (see previous news).

The previous study examined DNA samples from 19,000 individuals in order to gain a better understanding of the genetic factors involved in eight complex diseases. The current study involves a much larger sample number of 120,000, which will allow researchers to gain a better understanding of 25 diseases through examining single nucleotide polymorphisms (SNPs) and a comprehensive number of copy number variants (CNVs). Along with improved knowledge with respect to disease genetics, the undertaking will also look at the genetics of learning in children, and individual responses to statins.

News story   |   By Dr Philippa Brice   |   Published 20 April 2008

The Organisation for Economic Co-operation and Development (OECD) has launched a public consultation on draft Guidelines for Human Biobanks and Genetic Research Databases (HBGRDs).

The success of research involving the human genome and resulting applications is dependent on the sharing of knowledge comprised of data, biological samples and information derived from the analysis of those samples. . The OECD guidelines are intended as a tool to assist both OECD and non-OECD economies with the development of policies for the establishment and operation of HBGRDs

The draft Guidelines have been developed by experts from OECD member states, including individuals from national and international HBGRDs, along with policy makers, researchers, lawyers, ethicists, and private sector representatives. They are intended for use by individuals and bodies involved in the governance, management and use of human biobanks and genetic research databases, and aim to provide both key principles and suggested best practices.

The OECD is inviting comments are invited from any member of the public, but there is a particular call for input from “public and private sector entities involved in the establishment, governance, management and use of human biobanks, genetic research databases, and collections; patient groups; researchers; and from experts involved in ethical, social, legal and financial fields” (see Frequently Asked Questions for more information). The deadline for submitting comments is 16 May 2008.

News story   |   By Dr Sowmiya Moorthie   |   Published 18 April 2008

South Africa’s first Centre for Proteomic and Genomic Research (CPGR) has been officially opened (see news article). Based within the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, the centre houses a number of genomic and proteomic technology platforms which will be used to provide support and solutions to scientific communities both in industry and academia. The centre is also engaged in a number of research activities relating to both human and plant sciences such as identification of diagnostic markers for diseases like malaria and leukaemia, understanding the correlation between human genetic variation and drug response and the search for markers of pathogen resistance in maize.

Founded in 2006 through a grant provided by South Africa’s Department of Science and Technology, CPGR will contribute significantly to biotechnology in South Africa thereby helping to tackle many health problems faced by the country, as well as being a source of information about genomics for the public at large. It is hoped that public engagement and education about genomics and proteomics will assist in establishing adequate regulatory and evaluation systems for genomic and proteomic technologies (see keynote address by Minister Mangena).

News story   |   By Carol George and Dr Philippa Brice   |   Published 15 April 2008

There have been several recent international developments in stem cell regulation. On Friday 11 April, the Bundestag (lower house) of the German Parliament voted 346-228 to ease current legal restrictions on human embryonic stem (HES) cell research (see BBC news). Previously, German researchers have only been able to use HES cells harvested before January 2002, but now they will be free to use cells created up to May 2007. Germany has in general adopted a conservative approach towards controversial lines of medical research, but this latest move reflects concerns that their international scientific reputation could suffer if research is hindered by excessive regulatory burden.

Meanwhile, the UK National Stem Cell Network, which last week hosted its inaugural Annual Science Meeting in Edinburgh, has warned that the current status of the UK as a world leader in stem cell research will be in jeopardy in the absence of an increase in research funding in excess of £100 million. Professor Roger Pedersen said that the UK was at risk of being eclipsed by Germany and the US, both of which are investing heavily in this area (see Times Higher article).

A survey of public opinion on controversial work using human-animal hybrid embryos in the UK (see previous news) has suggested that 50% of respondents were in favour of the work, and of proposed legal amendments to facilitate such research (see The Times article)., A legal challenge has howeverbeen mounted by the UK Christian Legal Centre (CLC) against the decision of the Human Fertilisation and Embryology Authority (HFEA) to licence such research (see press release), on grounds that the 1990 Human Fertilisation and Embryology Act does not permit the creation of human-animal embryos. The 1990 Act has yet to besuperseded by amendments proposed by the Human Fertilisation and Embryology Bill, which are currently before Parliament.

In the US, a stem cell research advisory panel to the Food and Drug Administration (FDA) has been meeting recently to consider appropriate safeguards for potential use in clinical trials regarding new stem cell therapies on human subjects (see WebMD news). It is not clear whether these will be more rigorous than those applied to normal drug trials.

News story   |   By Dr Philippa Brice and Dr Sowmiya Moorthie   |   Published 10 April 2008

The Australian Capital Territories (ACT) legislative assembly is the latest Australian government body to lift its prohibition on human therapeutic cloning and pass the Human Cloning and Embryo Research Amendment Act 2008 (see press release). The state governments of Victoria (see previous news), Queensland (see ABC news), New South Wales (see previous news) and Western Australia (see ABC news) passed similar legislation last year, following the decision of the Australian federal government to lift its prohibition on cloning of embryos for stem cell research in December 2006 (see previous news). Reproductive cloning remains banned by federal, state and territorial law across Australia.

Keywords : CloningLegal Issues

News story   |   By Dr Philippa Brice   |   Published 8 April 2008

The UK Prime Minister Gordon Brown has announced a compromise whereby Labour Members of Parliament (MPs) will be permitted a free ‘conscience’ vote on selected elements on the Human Fertilisation and Embryology Bill currently before Parliament (see previous news); however, they are expected to support the Bill as a whole and not block its progress (see Ananova news).

Following this decision, and with less than a month until the Bill is scheduled to reach the House of Commons, UK scientists announced that they had successfully created the first human-animal hybrid embryos (see BBC news). It has been stressed that results are only preliminary findings, and have yet to be subject to the normal peer-review process, but the researchers reported the successful creation of embryos from the fusion of bovine egg cells from which the genetic material had been removed with human genetic material, to create embryos that were (in genetic terms) 99.9 per cent human and 0.1 per cent cow. The embryos survived for three days in the laboratory, but it is hoped that this period can be extended to at least six days for optimal research conditions; the legal limit is fourteen days. Professor John Burn, Head of the Institute of Human Genetics at Newcastle University where the work was carried out commented: “Cells grown using animal eggs cannot be used to treat patients on safety grounds but they will help bring nearer the day when new stem cell therapies are available” (see press release).

Work involving the creation of hybrid embryos is regulated by the UK Human Fertilisation and Embryology Authority (HFEA), which earlier this year granted licensed centres at Newcastle University and King's College London to create human admixed embryos as sources of embryonic stem cells for medical research purposes (see previous news).

Research articles

Research article   |   By Dr Caroline Wright   |   Published 28 April 2008

Initial results from two gene therapy trials to treat a rare congenital eye disorder are extremely encouraging, producing a significant improvement in retinal function, particularly in one of the six patients (reported by BBC News).


The first trial started one year ago at London's Moorfields Eye Hospital and University College London (see previous news story). Functional copies of the RPE65 gene were injected into the retina of three young adults with Leber's congenital amaurosis, a rare form of inherited childhood blindness caused by mutations in the RPE65 gene leading to abnormal detection of light by the retina, for which there is currently no treatment. The results, published in the New England Journal of Medicine [Bainbridge JWB et al. (2008) NEJM, doi: 10.1056/NEJMoa0802268], indicate that the technique is safe and potentially enormously beneficial; although the treatment had limited effect on two of the subjects, one patient experienced a significant improvement in visual performance, particularly in low light, despite previously having advanced retinal degeneration.


The results of this trial are published back-to-back with the results of a second, more recent trial carried out on another three patients at the Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine [Maguire AM et al. (2008) NEJM, doi: 10.1056/NEJMoa0802315]. Just six months on, all three patients showed evidence of improved retinal function.


Comment: Although individually rare, there are over 70 groups of genetic conditions affecting the eye and processes of vision and around 1500 people each year in the UK will be affected by these disorders. National statistics and surveys show that each year in the UK, about 400 people will be diagnosed as blind or severely visually impaired as the result of an inherited (genetic) disorder. Genetic factors are also involved in common eye diseases that can lead to blindness, such as age-related macular degeneration (‘AMD’), glaucoma and cataract. These results provide some of the first clinical evidence that gene therapy might achieve its elusive promise of safe and effective treatments for genetic diseases. It is also worth noting that even modest improvements in visual function can have a marked effect on the quality of life for patients.


With increasing ability now to diagnose these conditions using genetic tests, coupled with the development of new targeted treatments such as gene therapy, which are based on a detailed molecular understanding of the conditions, it is now more important than ever that patients are managed in specialised services. With this in mind, the PHG Foundation has been working with key stakeholders on a Genetics in ophthalmology project, commissioned by the UK Genetic Testing Network (UKGTN). The new report, Genetic Ophthalmology in Focus, which will be released next week, sets out the findings of an expert working group on how NHS ophthalmology services need to adapt to take advantage of the opportunities offered by genetic science.

Research article   |   By Dr Caroline Wright   |   Published 8 April 2008

Behind the recent plethora of genome-wide association studies identifying common risk variants for multifactorial diseases, is the assumption that an individual’s overall risk of developing a particular disease is related to the cumulative effect of multiple gene variants. This idea is often known as the common disease common variant hypothesis (CDCV). However, until recently, there has been limited evidence that the number of risk variants possessed by an individual correlates with their phenotype or risk of getting a disease.


Since multiple risk variants are now known for some specific complex diseases, it should be possible to test this idea, and recently two independent studies have shown that – at least in principle – the hypothesis is valid.


The first study, published in the New England Journal of Medicine, assessed the cumulative effect of 16 previously identified single nucleotide polymorphisms (SNPs) at five different chromosomal locations against the risk of developing prostate cancer [Zheng et al.(2008) NEJM 358(9):910]. Each of these SNPs individually have odds ratios of less than 1.65. However, the presence of high risk variants in all five regions combined with family history (with an odds ratio of 2.2) explains nearly half of all cases of prostate cancer, with an overall odds ratio of 9.5.


The second study, published in the same journal a month later, assessed the cumulative effect of 11 previously identified SNPs at nine different locations against the risk of cardiovascular disease [Kathiresan et al. (2008) NEJM 358(12): 1240]. The risk variants were compared with plasma levels of low-density lipoproteins (LDL) and high-density lipoprotein (HDL), which are associated with the risk of cardiovascular disease. They found that, as the number of risk variants increased, the level of LDL in the blood increased whilst the level of HDL decreased, in-line with a higher overall risk of cardiovascular disease. During the follow-up period, the number of risk variants also correlated with the incidence of cardiovascular events.


Comment: Although these studies have relatively small sample sizes and both use naïve additive models to combine the effect of multiple risk variants, they nonetheless represent the first real indication that risk stratification of the population, using common genetic susceptibility variants, might be possible. Whether or not genetic testing of this kind could ultimately be useful for improving public health is still under debate.

Research article   |   By Dr Philippa Brice   |   Published 7 April 2008

A recent review in the journal Paediatrics sets out a useful summary of pertinent ethical, legal and social issues for expanding newborn screening programmes. In the UK, there is a national Newborn Screening Programme which uses bloodspot samples to screen for the single-gene disorders phenylketonuria (PKU), congenital hypothyroidism, sickle cell disease and cystic fibrosis; the latest addition to the programme is screening for MCADD (see previous news). Many other countries have similar schemes, although the range of conditions screened for varies; in the US, it has been proposed that is should include a minimum of 29 disorders (see previous news), and potentially many more - including conditions for which there are as yet no effective interventions .

The emerging problem with newborn screening is that technical capability is outstripping proven clinical utility. The key reason for including a condition in newborn screening panels is where early detection allows intervention to minimize or prevent harm; for example, restricting dietary intake of phenylalanine prevents the severe mental retardation associated with PKU. However, the clinical benefits of diagnosis are not always so clear-cut; the value of early cystic fibrosis diagnosis has been fiercely debated, although evidence has accumulated to support it. Some suggest that diagnosis of a serious disease is of value in itself, if only because it prevents unnecessary additional testing; others say that to provide information that lacks clinical utility is pointless, and even cruel.

With rapidly developing techniques for high-throughput analysis such as tandem mass spectroscopy (MS/MS), it has become increasingly feasible to test for multiple genetic diseases. The US-based authors of the new paper use Fragile X syndrome as a prototype of an untreatable condition which cost-effective screening may soon become available (see previous news). Fragile X is the most common inherited form of learning disability; care of affected families is complicated by the fact that female carriers of ‘pre-mutation’ alleles are not usually significantly affected themselves, and may or may not transmit a full blown mutation allele to their offspring. The authors identify several key areas of concern [Bailey DB et al. Pediatrics 2008;121(3):e693-704].

Psychosocial harm to the family of the affected child – for example, increased levels of parental anxiety or weakened parental bonding with the child – is identified as a potential problem. This could also be serious where a phenotypically normal child might be identified as affected, or as a carrier for a disease; in such instances the possibility of discrimination or stigmatisation is noted. The prospect of effectively overwhelming genetics services by increasing referrals and demand for genetic counselling and screening of family members is raised; the necessity for properly informed consent for expanded screening would not only increase the burden for providers, but could potentially also reduce participation in standard screening programmes. The authors suggest that consultation with “scientists, policy makers, ethicists, practitioners, and other citizens” is required to consider the underlying aims of newborn screening, and to establish a national newborn screening research network.

Comment: This paper raises the interesting suggestion that we are in a process of moving from the traditional public health model for screening as a means to prevent irreversible and serious harm, to a new model whereby screeningis a service that provides wider but less immediate or obvious benefits. The authors propose that given “low levels of genetic literacy combined with public ambivalence and perhaps skepticism about the value of genetic information”, the public health community should try to engage with the public on this issue. Certainly, this is an arena where practitioners of public health genomics should have a voice; the importance of achieving “responsible and effective application” of biomedical advances for health – and the necessity to weigh potential benefits against possible harms in so doing – is well illustrated by this example.

Research article   |   By Dr Philippa Brice   |   Published 4 April 2008

A new paper in the BMJ reports results from a trial of the new technique for non-invasive prenatal diagnosis, utilizing cell-free fetal DNA present in the maternal blood. The technique has various potential applications including prenatal genetic testing and screening; in this instance, the test is being considered as an alternative to standard procedures for pregnant women with Rhesus-negative blood.

The Rhesus (RhD) factor is one of multiple blood cell surface markers, including the best known A/B/O blood group markers. Around 85% of the UK population are RhD-positive, having these markers; the remainder are RhD-negative, and do not have them. Knowledge of blood-group status is important because transfusion of donor blood with cell surface markers (such as RhD-positive blood) to a recipient who lacks them (RhD-negative) can cause an immune reaction to be mounted against the foreign cells, in a similar manner to rejection of tissue transplants.

The same problem can arise when a RhD-negative mother gives birth to a RhD-positive baby; mixing of the maternal and fetal circulation around birth can ‘alert’ the maternal immune system to the Rhesus antigens, so that any subsequent RhD-negative fetuses are at high risk of developing serious haemolytic disease at or before birth. To avoid this, all RhD-negative pregnant women are offered anti-RhD immunoglobulin (antibodies, effector molecules of immune responses) to effectively block any RhD-positive fetal cells that enter the maternal circulation and prevent the maternal immune system from recognizing them, an intervention that is highly effective in preventing haemolytic disease of the newborn.

However, around 38% of RhD-negative mothers will actually be carrying a RhD-negative fetus and so receive the immunoglobulin treatment unnecessarily. It would be preferable to avoid this, not only on the basis of the cost but also because the administration is uncomfortable and there are concerns associated with the potential for contamination via human blood products. Dr Geoff Daniels of the NHS Blood and Transplant International Blood Group Reference Laboratory, who led the study said: "It's good practice not to give treatment to people who don't need it" (see BBC news). The trial used free fetal DNA analysis (genotyping) to determine the blood group of the fetus during pregnancy, with a reported 95.7% success rate when compared with the actual blood group determined at birth [Finning K et al. BMJ, doi:10.1136/bmj.39518.463206.25 (published 3 April 2008)]. Since this technique is suitable for high-throughput analysis, the authors propose that it is a feasible approach to prevent unnecessary anti-RhD administration for almost all RhD-negative mothers.

Comment: This study contributes further evidence that genotyping using fetal genetic material from the maternal bloodstream has clinical utility, in this instance as a potential alternative to current antenatal care for RhD-negative women. The PHG Foundation is currently undertaking a flagship project on cell-free fetal nucleic acid analysis, to work with stakeholders to produce strategic recommendations for appropriate implementation of the technique into different clinical services, including the outstanding requirements for evidence, and necessary safeguards. For this particular application, one of the key issues is what would constitute an acceptable false-negative rate for the technique; in this study it was found to be below 0.2% (3 out of approaching 1900 cases), representing the number of women from whom immunoglobulin treatment would have been inappropriately withheld, had administration been based on the fetal genotyping results. The cost-efficacy of the technique when compared with blanket administration of immunoglobulin is also a factor that must be considered; the capacity for high throughput testing makes it more likely to be an affordable measure.

Research article   |   By Dr Caroline Wright   |   Published 3 April 2008

Lung cancer is the most common cause of cancer death worldwide. It is also the most preventable, since, according to the World Health Organisation, smoking causes around 90% of all cases. Assessing the impact of genetic variants on smoking-related diseases is important for public health and understanding gene-environment interactions. 


A massive genome-wide association study published in the journal Nature has identified a gene variant associated with nicotine dependence, lung cancer and peripheral arterial disease [Thorgeirsson et al. (2008) Nature 452:638]. The paper is published back-to-back with another independent study focussing on lung cancer patients, which identified almost the same risk locus [Hung et al. (2008) Nature 452:633]. Another genome-wide analysis with a similar finding is simultaneously published in the journal Nature Genetics [Amos et al. (2008) Nat. Genet. :10.1038/ng.109:10.1038/ng.109].


The biggest study, run by the Icelandic company deCODE genetics, involved nearly 11,000 smokers in Iceland and 32,000 lung cancer patients and controls from around the world. By testing over 300,000 single nucleotide polymorphisms (SNPs), they were able to identify a common variant present in around half the population associated with lung cancer and peripheral arterial disease. The risk variant is located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25, which plays an important role in neurotransmission. Each copy of this SNP confers approximately a 30-40% increase in risk of lung cancer and a 20% increase in risk of peripheral arterial. The risk variant was also found to be associated with the number of cigarettes smoked per day, suggesting a link to nicotine dependence.


A typical smoker with two copies of this risk variant has a 1 in 4 lifetime risk of developing lung cancer; in contrast, a non-smoker (who has smoked fewer than 100 cigarettes) has less than a 1% chance of developing the disease (see news in Nature and New Scientist). The strength of the association comes from the enormous power of the combined studies, which involved over 50,000 people, and their independent replication of the same risk locus with a relatively large effect size. According to their website, the company’s personal genome profile service, deCODEme, will offer the test for this gene variant immediately. However, cancer campaigners stress that smoking is still by far the number-one risk factor for lung cancer.

Research article   |   By Dr Maria Adams   |   Published 2 April 2008

An increasing number of studies are taking place with the aim of identifying the genetic basis of common conditions that have a have a major public health impact such as cardiovascular disease, various cancers and obesity. Such studies are expected to increase understanding of disease processes and lead to more effective treatment options, but it is likely that it will take time before such clinical benefits are achieved.


Another area of medicine that is likely to benefit from genomic and biomolecular advances is the development of more accurate ways to diagnose and screen for various conditions, based on genetic and biomarker profiles. It is hoped that this latter approach will provide less invasive, more convenient routes to diagnosis and treatment. It is also much closer to clinical application and, in some cases, is actually in clinical trials, as demonstrated in three studies reported earlier this week.


One study combines analysis of gene expression patterns in biopsy samples from a fatal brain tumour called glioblastoma multiforme (GMB) with detailed imaging of patients’ brains using magnetic resonance imaging (MRI) [Diehn M et al. (2008) PNAS PMID: 18362333 epub ahead of print]. GMB is untreatable and most patients die within 15 months of diagnosis. At present, diagnosis and treatment is guided largely by biopsy of the tumour followed by microscopic examination of tumour cells. However this current approach has two major flaws: (1) it involves potentially dangerous brain surgery; and (2) individual tumours often behave very differently, even though their cells look similar.


As an alternative, GMB can also be visualised using non-invasive magnetic resonance imaging (MRI) to identify different tumour characteristics. A team of US researchers have combined MRI with gene-expression studies of individual tumours to correlate patterns of gene expression that are associated with a specific appearance on MRI scans. For example, increased activity of genes associated with hypoxia and the formation of new blood vessels (which is thought to be needed for tumour growth) is associated with a particular appearance on MRI; the authors propose that the corresponding MRI characteristics can act as a surrogate biomarker to identify which tumours might respond well to anti-angiogenic therapy (which stops the formation of new blood vessels). It is also suggested that other imaging techniques could be combined with gene mapping approaches (see news article).


Non-invasive testing for more common conditions such as diabetes also receives a boost with the identification of 1116 proteins that are secreted in human saliva [Denny P et al. (2008) J Proteome Res, PMID: 18361515, epub ahead of print]. The studies authors estimate that as many as 20% of the proteins present in saliva are also found in blood, including several proteins with known roles in Alzheimer’s, Huntington’s and Parkinson’s diseases as well as several cancers and diabetes. Saliva-based tests are already well established for detecting human immunodeficiency virus (HIV) and hepatitis infections. Identifying the range of saliva proteins should provide new targets for diagnosing and monitoring disease in saliva rather than blood or urine (see also associated news report).


These two studies outline the potential of biomolecular tests for providing potentially safer, more convenient diagnostics; a third study highlights the potential for increased sensitivity of primary screening for cervical cancer. Published in the Journal of the National Cancer Institute, this clinical trial of almost 45 000 women shows that testing for human papillomavirus (HPV) DNA in cervical cells is more effective at detecting precancerous cervical lesions than the current ‘gold standard’ of the Pap test [Ronco G et al. (2008) PMID: 18364502, epub ahead of print]. Infection with HPV accounts for virtually all cases of cervical cancer. The HPV test identified almost twice as many women with premalignant lesions requiring treatment than conventional testing in women in the 35-60 age group. Furthermore, it does not increase the incidence of false-positives (i.e. women who test positive, but do not have such lesions) in this age group. DNA-based testing also identifies more potential cases in younger women (25-34 years), although it appears that a significant number of these infections are likely to resolve naturally. Because of this the authors propose that it is more appropriate to rescreen younger women 12 months after the initial DNA test rather than refer them directly for further investigation.


These examples give some idea of the breadth of the possible impact of genomic applications in clinical medicine within the next few years. With the increasing number of large, high-powered studies to identify disease-gene associations and potential avenues for therapeutic development, it is easy to loose sight of the better-advanced potential for genomic medicine in other areas, such as diagnostic and/or prognostic testing and screening programmes.



Research article   |   By Dr Sowmiya Moorthie and Dr Philippa Brice   |   Published 1 April 2008

Recent work has highlighted the role genetics plays in shaping our personality and consequently our psychological status. Numerous studies have already shown the influence of genetics on individual personality and behaviour, and also on mental health and the risk of specific psychiatric disorders. According to the mental health charity Mind, one in four people suffer from mental health problems at some point in their lives. An understanding of the prevalence of mental health problems, as well as new diagnostics and therapies, are important in managing health care resources; provision of adult mental health services alone cost the NHS 4.5 billion in 2004/05.

A recent study compared personality traits in identical and non-identical twins in order to determine the extent genes influence personality traits [Weiss A et al. (2008), Psychol. Sci. 19(3), 205-10]. This work suggested that many personality traits including emotional stability, social and physical activity and constraint were influenced by genetics. Another recent paper in the Archives of General Psychiatry showed that variations in a specific gene called RGS2 could be linked with personality traits, specifically those relating to anxiety [Smoller et al. (2008), Arch. Gen. Psychiatry, 65(3), 298-308]. A better understanding of the genetic factors involved in psychiatric disorders and their associated biological pathways, is a valuable step towards a better understanding of these diseases, and could potentially lead to novel diagnostics, or therapeutic interventions.

The identification of individual genetic factors also opens up the possibility of developing susceptibility testing for these diseases. A ‘predictive’ genetic test for bipolar disorder is already being marketed in the US by Psynomics, and more are likely to emerge. One recent study also claims that it is could even be possible to diagnose depression by monitoring the level of a single biomarker, the GS alpha protein [Donati RJ et al. (2008), J. Neurosci. 28(12), 3042-50]; the researchers found that GS alpha protein localization differed between depressive suicides and controls (non-suicide individuals without any overt psychological disorder. Studies by the same group using animal and cell culture models have also shown that anti-depressants were able to restore normal localisation of the protein; leading the authors to propose that GS alpha could serve as a biomarker for depression and for monitoring the effectiveness of anti-depressants.

As highlighted in an article in Science, we are likely to see an increase in the number of genetic tests available on the market [Couzin J (2008), Science 319(5861), 274-7]. However, although many psychiatric disorders seem to have significant genetic contributions, they are nevertheless complex diseases influenced by the interplay of many different genetic and environmental factors. Testing to identify the presence of a particular genetic variant that has been associated with a given psychiatric disease does not necessarily provide reliable or indeed useful information about an individual’s susceptibility towards that disease (see previous news). Moreover, recent findings suggest that the genetics of psychiatric diseases may be much more complex than previously supposed. Another new paper in Science reports a study of gene variants associated with autism spectrum disorder, which concluded not only that there were very many of these variants, but also that some were individually very rare [Sebat J et al. (2008) Science 316 (5823), 445 - 449]. This echoes earlier findings in other mental health disorders, and the authors propose that different variations in the hundreds of genes that play a role in normal development and function of the brain might lead to multiple different outcomes, and that each individual with the same psychiatric disorder might well have different genetic contributions to the development of that disease. So in fact, testing for a limited number of specific genetic variants may be of no utility at all in terms of predicting psychiatric disease risk. Even were it feasible to test for genetic factors that conferred a substantially increased risk of such diseases, such testing would raise multiple ethical and regulatory issues, including the usual concerns over potential discrimination with respect to employment or insurance. The potential harms from these sorts of tests are therefore significant, especially when delivered direct to consumers.

So, if susceptibility testing is unlikely, what is the potential benefit of new findings in the genetics of mental health disorders? New tools to identify psychiatric diseases or monitor the efficacy of treatment would be valuable; it might even one day become feasible to determine different underlying pathological pathways in different patients, and tailor therapeutics accordingly (see ScienceNOW news).

New reviews and commentaries

Selected new reviews and commentaries, 3 April 2008

Reviews & commentaries : by Dr Philippa Brice

Genetic tests for common diseases: new insights, old concerns.

Melzer D et al. BMJ. 2008 Mar 15;336(7644):590-3

From genetic privacy to open consent.

Lunshof JE et al. Nat Rev Genet. 2008 Apr 1; [Epub ahead of print]

Research ethics and the challenge of whole-genome sequencing.

McGuire AL, Caulfield T, Cho MK. Nat Rev Genet. 2008 Feb;9(2):152-6.

Heritability in the genomics era - concepts and misconceptions.

Visscher PM, Hill WG, Wray NR. Nat Rev Genet. 2008 Apr;9(4):255-66.

Quiet as a mouse: dissecting the molecular and genetic basis of hearing.

Brown SD, Hardisty-Hughes RE, Mburu P. Nat Rev Genet. 2008 Apr;9(4):277-90.

Comparing whole genomes using DNA microarrays.

Gresham D, Dunham MJ, Botstein D. Nat Rev Genet. 2008 Apr;9(4):291-302.

The road to genome-wide association studies.

Kruglyak L. Nat Rev Genet. 2008 Apr;9(4):314-8.

Public-private partnership in cord blood banking.

Fisk NM, Atun R.BMJ. 2008 Mar 22;336(7645):642-4.

Adding pathogens by genomic subtraction.

MacConaill L, Meyerson M. Nat Genet. 2008 Apr;40(4):380-2.

Epigenetics at the epicenter of modern medicine

Feinberg AP JAMA 2008 Mar;299(11):1345-50

Reducing glutamate signaling pays off in fragile X.

Bassell GJ, Gross C. Nat Med. 2008 Mar;14(3):249-50.

Epigenetics in cancer.

Esteller M. N Engl J Med. 2008 Mar 13;358(11):1148-59

Medicine. Blood-matching goes genetic.

Quill E. Science. 2008 Mar 14;319(5869):1478-9

Bioethics beyond the lifespan.

Churchill LR. Lancet. 2008 Mar 29;371(9618):1066-7.

The involvement of DNA-damage and -repair defects in neurological dysfunction.

Kulkarni A, Wilson DM 3rd. Am J Hum Genet. 2008 Mar;82(3):539-66.

DNA data. Proposal to 'Wikify' GenBank meets stiff resistance.

Pennisi E. Science. 2008 Mar 21;319(5870):1598-9.

Genetic testing and breach of patient confidentiality: Law, ethics, and pragmatics

Minkoff H & Ecker J Am J Obstet Gynecol2008 Mar [Epub ahead of print]

What's new in: "Genetics in childhood epilepsy"

Lagae L  Eur J Pediatr2008 Mar [Epub ahead of print]

Evaluating laboratory diagnostic tests.

Walley T BMJ. 2008 Mar 15;336(7644):569-70.

The gene detective.

Coombes R. BMJ. 2008 Mar 15;336(7644):586-7.

The 28th March issue of Science is a special issue focusing on gene regulation, with articles including:

MicroRNAs make big impression in disease after disease.

Couzin J. Science. 2008 Mar 28;319(5871):1782-4.

Genetic risk. With new disease genes, a bounty of questions.

Couzin J. Science. 2008 Mar 28;319(5871):1754-5.

Gene regulation by transcription factors and microRNAs.

Hobert O. Science. 2008 Mar 28;319(5871):1785-6.

Multilevel regulation of gene expression by microRNAs.

Makeyev EV, Maniatis T. Science. 2008 Mar 28;319(5871):1789-90.

Gene regulation in the third dimension.

Dekker J. Science. 2008 Mar 28;319(5871):1793-4.

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