31 July 2008Scientific and technical progress has led to the rapid rise in the number of genome wide association (GWA) studies and the identification of multiple gene-disease associations for common diseases. This has also resulted in the increasing commercial availability of tests to determine the presence or absence of gene variants that have shown an association with disease, although the clinical utility of many such tests is highly questionable (see previous news). Proponents of personalised genomics believe that information about genetic risk of common diseases has value as a tool for health. For example, it could potentially refine risk assessment and screening recommendations; the clinical utility of testing individuals for their genetic risk for breast cancer and its role in population screening has been discussed recently (see previous news).

However, common multi-factorial diseases such as depression, cancer and cardiovascular disease typically involve many highly complex gene-gene and gene-environment interactions, so that even when there is robust evidence to support a link between a particular genetic variant and the risk of developing a given disease, it can represent only one factor in a very complex and as yet poorly understood pathological process. There are concerns that individuals may not be able to fully understand and interpret risk information, leading to potential confusion.

In a commentary published in the August issue of Nature Genetics, McBride et al. discuss the central importance of test evaluation in the effective translation of genomic discoveries into health practices; the evaluation of genetic tests and molecular biomarkers is similarly a major work stream at the PHG Foundation. The authors call for a “targeted research programme to support translational genomics” to bridge the gap between gene disease-association research and investigations into public health and clinical utility [McBride CM et al. (2008) Nat Genet. 40(8):939-42]. Questions which need to be answered are proposed to include the best way to relay genomic risk information to patients, how advances in genome-wide sequencing methods change the nature of risk assessments, and how to educate individuals about the limitations of genetic testing. They propose a phased approach to addressing these issues due to the complexity of both the diseases and possible interventions.

The Multiplex Initiative is described as an example of a starting point for this kind of research. This aims of this project are to gain information about the reasons why individuals opt to take genetic tests and their behavioural responses to test results (see previous news). The authors note that rigorous experimentation is needed in order to provide information about whether genetic susceptibility testing should become an accepted standard of care. Other ventures such as the Corriel Personalized Medicine Collaborative are also aiming to address the clinical utility of susceptibility tests (see previous news). Data from such studies will be valuable for informing the transition from basic research to effective clinical practice, and the development of suitable guidelines and regulations on the use of genetic susceptibility tests.

 

24 July 2008Genome wide association (GWA) studies have identified a number of genetic variants associated with common conditions such as cardiovascular disease, diabetes and obesity. Such research has also resulted in an increasing number of genetic tests to determine the presence or absence of such variants, and to some degree predict genetic risk for these common diseases, although the clinical utility of many such tests is non-proven (see previous news). The biological mechanisms through which such genetic variants contribute to risk and how risk data can be utilised to improve health is still unclear. Such information is potentially valuable for developing therapies, as well as improving public health interventions such as population screening programmes (see previous news).

This month the US National Human Genome Research Institute (NHGRI) announced a funding programme which will grant $31million over four years for projects to investigate the relationship between genetic risk and health. The programme will focus on four existing epidemiological studies: National Health and Nutrition Examination Survey (NHANES), CALiCo Consortium, Multiethnic Cohort and Women's Health Initiative. These studies have been collecting medical information from participants for many years and consist of an ethnically diverse population; an important factor as many GWA studies are carried out in people of European descent and other ethnic groups may vary in the frequency of variants they possess. The researchers will investigate 100 genetic variants in 10, 000 participants each year for four years, and this information will be correlated with clinical characteristics, such as weight, cholesterol levels, blood sugar levels or bone density. They will also investigate the interaction between genetic and non-genetic (environmental) factors such as diet and medication and how this interaction influences health outcomes.

A co-ordinating centre funded by the US National Institute of Mental Health will be established to facilitate data access and analysis tools and data generated from each study will be deposited in the public database of Genotypes and Phenotypes (dbGaP). The NHGRI hope that this data will help translate genomic research into strategies to improve human health and “guide other genomic and epidemiologic studies by defining the potentially wide-ranging effects of genetic differences among people” (see press release).

21 July 2008Changing population demography, with an increase in the number of elderly people has led to an increased interest in identifying the factors which influence longevity and healthy aging. Past research into the genetic factors that influence longevity, identified a mutation which appears to be linked to a longer life span (see previous news). However, such mutations are rare, suggesting that other factors may also be involved. Studies have also revealed that many healthy elderly people do not develop conditions such as cardiovascular disease, stroke and diabetes, although they possess genes which increase their susceptibility to these conditions, suggesting the involvement of protective factors.

In order to gain a better understanding of the genetic factors which influence longevity, researchers at the Scripps Translational Science Institute in the US, plan to compare genes in 1000 healthy people aged 80 or over, who have never suffered serious illness and don’t take medication, with DNA from people who died from age-related diseases before they reached their 80s (reported by Technology Review). They will compare the sequences of one hundred genes which have been linked with health and ageing. Among them are genes involved in cellular housekeeping activities, DNA repair and cell growth. The hope is that sequence comparison of these genes will allow them to elucidate the molecular basis of the protective effect afforded by certain gene variants leading subsequently to the development of compounds that mimic this process in order to combat age-related illnesses.

 

16 July 2008An ethics task force from the European Society of Human Reproduction and Embryology (ESHRE) is to investigate the application of DNA chip (microarray) technology in embryo screening. Preimplantation genetic screening is used to identify significant chromosomal abnormalities in embryos created by in vitro fertilization (IVF) prior to implantation, with a view to establishing pregnancies with the healthiest embryos to minimize the risk of miscarriage. The British Fertility Society has recently published guidelines on this form of screening (see previous news), which are significantly different from prenatal genetic diagnosis (PGD), used for the definitive diagnosis of specific serious genetic disorders.

Microarray technology makes it feasible to test for the presence of thousands of specific genetic abnormalities or variations simultaneously – but the clinical significance of many is unknown, and might not influence the successful establishment of a pregnancy. Task force chair Professor Guido De Wert, who has launched a consultation process with ten European fertility centres, commented: "One of my concerns is that people who are naive about genetics think that it is easy to pick the best embryo… But even the best geneticists don't know how to interpret how diseases might develop from gene chip information” (see BBC news). The aim of the ESHRE task force is reportedly to assess the potential of ‘gene chips’ for embryo screening and ultimately develop a code of practice to regulate their use. One of the difficulties will be to distinguish between the diagnosis of a specific disease for which the embryo is at high risk due to family history, and screening for numerous other diseases for which the embryo is not at particular risk. Although screening raises additional ethical issues, since both types of tests could easily be performed simultaneously using the same microarray, having different guidelines for each type of test may become impracticable.

 

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8 July 2008Introgen Therapeutics Inc. has become the first company to apply for FDA approval of a gene therapy drug to treat cancer (see press release). Although high profile gene therapy trials reported in the media have largely been for rare inherited diseases such as muscular dystrophy (see previous news), in fact two-thirds of all gene therapy treatments currently in clinical trials are for types of cancer (see Gene Therapy Clinical Trials Worldwide).

Advexin® has been developed to treat recurrent, refractory head and neck cancers and works by using a deactivated cold virus to deliver the p53 tumour suppressor gene into cancer cells. Abnormalities in the p53 gene are associated with many forms of cancer, and restoration of a functional gene can trigger tumour suppression mechanisms without harming healthy cells. The drug has been shown only to work on patients who have low levels of the functional p53 gene; consequently clinical trials incorporated common diagnostic tests to identify patients most likely to benefit from Advexin® treatment. This involved pre-treatment tissue analyses to determine p53 profile status; two-thirds of the patients with head and neck cancers were able to take the drug.

Introgen has requested Priority Review from the FDA, if granted the FDA will have six months from the submission date to take action. This review is generally granted to compounds that provide significant medical benefit compared with existing treatments. Introgen’s submission is based on positive phase II and III trials and if successfully granted Priority Review, could result in a decision by 2009. Introgen’s subsidiary in Europe, Gendux Molecular Limited has also applied for approval from the European Medicines Evaluation Agency (EMEA). Although the submissions are for use of Advexin® to treat head and neck cancers, it may have the potential to treat other types of cancers such as breast and lung cancer and clinical trials are currently underway to assess this.

3 July 2008Regenerative medicine has continued to feature in the headlines recently. The European Science Foundation has announced plans to strengthen the research base in this area, which they define as “the development of stem cell therapies to restore lost, damaged, or ageing cells and tissues in the human body” (see press release). The new REMEDIC initiative, a five-year a research networking programme intended to facilitate information exchange and collaborative research, is supported by organisations from several European countries including Germany, Spain, Switzerland, Austria and the Netherlands. The Canadian government has announced funding of more than $100 million for the Canadian Cancer Stem Cell Consortium (see CBC news), which is to join with the California Institute for Regenerative Medicine (CRIM) in the US for a project on the role of cancer stem cells in disease development (see press release). CRIM has also announced a collaborative partnership with the Australian state of Victoria (see press release).

 

Stem cell researchers in California have called for a relaxation in state legislation to permit financial compensation for women who donate eggs for the creation of human embryonic stem (HES) cell lines (see Nature news). In some US states, it is legal for women to receive payment for donating eggs (ooctyes) for fertility treatments, but not for research purposes, making it difficult for researchers to recruit donors and, they say, stifling the progress of research. In the UK, women may donate eggs for fertility treatment or research in exchange for limited financial compensation (see previous news), or in exchange for a reduction in the price of their own fertility treatment (see previous news).

Meanwhile, a new publication in the journal Cell Stem Cell has claimed that countries with less restrictive regulatory regimes account for a disproportionately high level of scientific publications [Levine AD (2008) Cell Stem Cell2(6): 521-4], supporting concerns cited by many prominent US researchers that without easing of current legislation such as current restrictions on the use of federal funding for stem cell research (see previous news), the country will lag behind in this area of medicine. Countries dubbed ‘overperforming’ in stem cell publications were Singapore, the UK, Israel, China and Australia, whilst ‘underperformers’ included the US, Japan, France and Switzerland (see Nature news). The author concludes that the most highly performing countries had generally permissive policy environments for HES cell research, whilst those lagging behind were characterised by “protracted policy debates and ongoing uncertainty, regardless of their current policy environment”.

Within the UK, there is debate about the regulatory remit of relevant statutory authorities, with the HTA, HFEA and MHRA issuing a position statement on the use of human embryonic stem cells for human application. The potential for more general debate is evidenced by the discussion and media exposure surrounding the passage of the Human Fertilisation and Embryology Bill through Parliament (see previous news), but surveys of public attitudes have suggested that up to 79% of respondents were broadly in favour of the use of human embryos for medical research (see Times article).

Whether the public have a reasonable expectation of how long it might take for major benefits from such research to be realised is less clear, since progress is always publicised. For example, a triumph cancer ‘cure’ from therapeutic cloning has been hailed (see BBC news) following the publication of a paper in the New England Journal of Medicine detailing remission of a malignant melanoma (skin cancer) for a two-year period. Using immune cells produced by the patient’s body, US researchers created CD4 T-lymphocytes directed against a tumour-specific protein, cloned them and produced a massively expanded population of identical cells, which were then reintroduced to the patient [Hunder NN et al. (2008) N Engl J Med. 358(25):2698-703]. Although not all of the tumour cells were producing the corresponding protein, the patient’s immune system was apparently able to respond effectively against all the tumour cells.

This study is published in a respected peer-reviewed journal and does not make misleading claims, but concerns have arisen from the growing phenomenon of unproved ‘stem cell treatments’ being offered via private clinics and commercial websites. The International Society for Stem Cell Research is reportedly developing guidelines to condemn the use of stem cell treatments outside clinical studies (within which stem cell use is subject to regulation including research ethics approval)..These guidelines are intended to protect the safety of patients and combat misleading claims made about stem cell therapies (see Reuters news).

1 July 2008Health minister Lord Darzi has released his report on and strategy for the NHS in England, the NHS Next Stage Review, which is based around delivering quality of care; quality is defined as “clinically effective, personal and safe” (see report summary). It is suggested that that NHS funding for hospitals, GP practices and other bodies will depend on how well they are deemed to have provided accessible, high quality care by patients, although how this will be measured is not decided. This includes increased emphasis on improving health and preventing disease, including implementation of all recommendations from national expert committees for screening programmes.

The report calls for what it terms ‘intelligent regulation’ as a means to safeguard quality, saying that NHS commissioners will benefit from “clearer standards from an expanded NICE” (National Institute for health and Clinical Excellence) to ensure that “clinically and cost effective innovation in medicines and medical technologies is adopted” This echoes the PHG Foundation’s emphasis on the public health genomics principle of the prompt and effective (ie. evidence-based) translation of genome-based knowledge for the benefit of population health.  The report also notes that innovation should not be confined to research but rather is “a broader concept, encompassing clinical practice and service design”, which supports the PHG Foundation’s service development work considering how novel genomic technologies should best be incorporated into NHS services. Strategic health authorities are to have a new legal duty to promote innovation, with access to funds and prizes.

The report promises that the pathway from development to clinical application will be streamlined, NICE’s process for assessing and (if suitable) approving new drugs and treatments speeded up, and that ways to benchmark and monitor uptake of new interventions will be defined. It also proposes the establishment of selected Health Innovation and Education Clusters, bringing together partners from the NHS, academia and industry to pioneer and develop new treatments and models of care, and of Academic Health Science Centres (AHSCs) “to take new discoveries and promote their application in the NHS and across the world”.

The report also sets out a new ‘NHS constitution’ to clarify patient rights and provide measures of increased transparency and clarity with respect to decision-making and accountability.

29 July 2008Zinc-fingers are small DNA-binding proteins that mediate DNA-protein interactions within cells, playing an important role in regulation of DNA expression. Zinc-finger nucleases (ZFNs) are synthetic enzymes that combine zinc-finger peptide domains (which target the protein to attach to specific DNA sequences) and a nuclease domain that will cut double-stranded DNA at the point where the protein is bound. Importantly, ZFNs can be used to create specific genomic modifications via these sequence-specific DNA breaks, encouraging the insertion of new DNA sequences or targeting the region for inactivation or repair via normal cellular mechanisms.

Research teams from six different US and German institutions, all members of the international Zinc Finger Consortium, have now published a new and efficient method for producing ZFNs in the journal Molecular Cell. The new technique, which they have dubbed OPEN (for Oligomerized Pool Engineering) is significantly more efficient than current methods, as well as being much easier and faster to perform [Maeder ML et al. (2008) Mol. Cell 31, 294-301, doi:10.1016/j.molcel.2008.06.016]. Target DNA sequences are used to select ZFNs from an archive of collections (or ‘pools’) of different zinc fingers. The method was used to produce ZFNs that were able to introduce modifications at sites in three different human genes (VEGF-A, HoxB13, and CFTR; mutations in the latter are associated with cystic fibrosis) within human cells, as well as a plant gene and an isolated human EGFP ‘reporter’ gene, with efficiencies ranging from 1%–50%. However, the paper reports that the desired genetic modifications were not introduced at some sites for which ZFNs were produced. It is suggested that this may have been the result of the state of the DNA at a target site (for example, active/unwound or inactive/supercoiled) or the stability of the ZFNs in the cell.

The researchers are now working to create more ‘pools’ of different ZFNs. Crucially, they are making them publicly available via non profit-making distributors for a modest charge, so that other researchers will be able to create special targeted zinc finger nucleases by the new method. Previously, methods for constructing ZFNs have been hugely labour-intensive, and the primary commercial provider has made them available only for selected academic collaborative projects; although they reportedly plan to offer a service to produce custom-made ZFNs, the expected charges will be very high (see Science news).

It is hoped that the availability of this novel method will facilitate all sorts of genome-based research, including the development of gene therapies directed against the mutations that cause single-gene diseases such as cystic fibrosis; the research was supported by the Cystic Fibrosis Foundation, among other bodies.Senior author J. Keith Joung of the Massachusetts General Hospital in Boston commented: “Our method will enable academic researchers to rapidly create high quality ZFNs for genes of interest and will stimulate use of this technology in biological research and potentially gene therapy” (see press release).

Comment: Research news is often dominated by discoveries or achievements, but new and effective methods can have the greatest impact of all if they facilitate rapid progress in many different areas of research simultaneously, as this latest technique may do for genomic research.

25 July 2008The prevalence of a specific infectious disease typically varies in different populations; much of this variation may result from differing social and economic factors, but genetic factors that influence susceptibility and resistance to the infectious agent can also play a significant role, and are of obvious relevance to public health. For example, it has been known for a long time that cellular receptors play a role in viral entry, and that mutations in such receptors can confer increased resistance to infection by HIV-1. HIV-1 enters a type of white blood cell via interactions with the CCR5 surface receptor; around 1% of Caucasians are homozygous for a specific deletion in the CCR5 gene, which confers a significant degree of resistance to HIV-1 infection.

New research has implicated the red blood cell (RBC) surface Duffy antigen receptor for chemokines (DARC) in susceptibility to HIV-1 (see BBC news). DARC is the RBC receptor for Plasmodium vivax, one of the four most common species that causes human malaria. Individuals who lack a functional DARC (with a DARC −46C/C genotype) including over 90% of West Africans, are resistant to infection by P. vivax; it is thought that the very high population prevalence of this genotype in areas where P. vivax malaria is endemic is the result of a selective evolutionary advantage.

A paper published in Cell Host and Microbe from researchers at University College London and the University of Texas has reported that DARC is also a receptor for HIV-1 attachment and entry to RBCs, which influences blood plasma levels of chemokines (molecular mediators of the immune response) that suppress HIV-1 and promote inflammatory responses. The researchers also report that the DARC-negative genotype is associated with 40% increase in risk of HIV-1 infection among African Americans [He W et al. (2008) Cell Host Microbe. 4(1):52-62], allowing for the influence of different environmental factors, and propose that, based on the prevalence of this genotype in sub-Saharan African populations, it could account for 11% of all HIV-1 cases. However, the DARC-negative genotype is also associated with slower disease progression. The authors conclude that DARC influences HIV/AIDS susceptibility by mediating infection of red blood cells by HIV-1 and immune responses to the virus.

Comment: The processes by which HIV-1 is able to infect different types of human cell and to evade human immune responses are many and complex, and this research merely adds one more piece of evidence to the body of knowledge in this area; it does not represent a breakthrough that could lead to an effective vaccine or curative therapeutic. The epidemiological work should be repeated in native African populations to determine a more accurate assessment of the impact of the DARC-negative genotype on infection rates and disease progression. However, the paper marks the “first genetic risk factor for HIV found only in people of African descent, and sheds light on the differences in genetic makeup that play a crucial role in susceptibility to HIV and AIDS” (see press release), helping to explain at least some of the observed variation in prevalence rates between different populations.

18 July 2008In an open letter published in Genome Biology, a multidisciplinary team of researchers from Stanford University have proposed ten principles to guide the use of racial categories in human genetics research [Lee et al. (2008) Genome Biology 2008, 9 (7), doi:10.1186/gb-2008-9-7-404]. The authors note that following the completion of the Human Genome Project, research exploring human genetic variation has intensified, leading to a debate on whether racial categorisation of genetic data is appropriate or whether it is “a pernicious reification of historically destructive typologies”.

Issues related to research into human genetic variation were explored in a series of seminars and discussions, leading the team to propose the guidelines in the article. Among the principles, the authors declare that they believe that there is “no scientific basis for any claim that the pattern of human genetic variation supports hierarchically organized categories of race and ethnicity” and caution against using genetic explanations for group differences in complex traits.

They also recommend improved education about genetic variation through encouraging funding for interdisciplinary study and urging researchers and other parties engaged in translation of research to collaborate in order to avoid overstatement of the contribution of genetic variation to phenotypic variation. They also recommend including historical and social scientific information when teaching genetics at the secondary and undergraduate levels, so that the past uses of science to promote racism as well as its impact in the future can be understood. In their conclusion the authors recognised that the language used by scientists and those in humanities and social sciences in relation to these issues varied and could create disagreements. They hoped that the principles set out in the article will encourage open interdisciplinary dialogue and “shape future use of categories of race and ethnicity in biomedical research”.

10 July 2008The management of findings incidental to a research agenda involving human subjects is becoming an increasingly important issue, especially in the context of human genomic and genetics research. Studies involving human subjects result, in some instances, in unexpected findings unrelated to the original objectives of the research, such as the discovery of a tumour during a brain imaging study or misattributed paternity or parentage in a genetic family study. These discoveries, known as incidental findings, pose a dilemma for researchers, who must determine whether or not to disclose such information to the individual participant, whose health or well-being may be affected.

The usual practice in genomic research has been to inform participants prior to consent that there will be no disclosure of individual research results, including incidental findings. This procedure has, however, come under recent scrutiny, as genomic research produces a vast quantity of health-related data and information that may be beneficial to participants. The potential for disclosure of results raises new issues, such as, who might be responsible for dealing with any incidental findings, given the sharing of genomic data among researchers, the use of samples in multiple studies and the absence of defined time limits for their use.

Until recently, there had been a lack of guidance as to when it might be appropriate to disclose incidental findings to participants and how it is to be done. A set of recommendations has now been published, however, with regard to the management of incidental findings arising from genomic, genetics and other research involving human subjects [Wolf SM et al. (2008) J. Law Med Ethics 36(2): 219-48]. Included in the Summer 2008 issue of the Journal of Law, Medicine and Ethics dedicated to a symposium on incidental findings, the recommendations are the result of a two year project funded by the US National Human Genome Research Institute (NHGRI).

The authors recommend that researchers anticipate the discovery of incidental findings, and consider specifically the potential for incidental findings in future analyses of archived DNA.  They should plan to verify and evaluate a suspected incidental finding, with an expert consultant if necessary, and develop strategic criteria for reporting these findings, such as likely health or reproductive importance. It was recommended that the handling of incidental findings be addressed with participants during the consent process, and that an administrative pathway for dealing with incidental findings should be created and monitored by investigators and Institutional Review Boards (IRBs). Further recommendations addressed incidental findings involving paediatric and adolescent participants and adult participants without decisional capacity. The authors conclude that the responsible handling of incidental findings “requires clarity about the difference between research and clinical care” and suggest that more research is necessary to determine the prevalence of incidental findings and their impact on research participants.

7 July 2008Sudden cardiac death (SCD) in younger athletes is typically the result of structural or electrical defects of the heart, many of which are the result of inherited (genetic) cardiovascular disorders. Unfortunately it is common for death to occur without any previous symptoms in apparently healthy athletes, which has led to the suggestion that screening, including physical examination, electrocardiography (ECG), and the taking of a family history, is advisable to prevent sudden cardiac death in this group. The cost effectiveness and utility of cardiovascular screening of athletes has been a subject of some debate, with the American Heart Association recommending against universal ECG screening in athletes whilst the European Society of Cardiology and the International Olympic Committee advocate it [Drezner JA, Khan K BMJ 2008;337:a309].

A new paper published in the BMJ reports on a national study of more than 30,000 Italian athletes, with a mean age of 30, screened by resting and exercise electrocardiography prior to participation in athletic events over a five-year period. Cardiovascular screening and demonstration of clinical eligibility to compete is a legal requirement in Italy; researchers from the Institute of Sports Medicine in Florence looked at the results of cardiovascular evaluation of prospective participants between 2002 and 2006 [Sofi F et al. BMJ 2008;337:a346].

Resting ECG patterns showed abnormalities in 6% of the athletes, but the majority of these were found to be ‘innocent’ (not of clinical significance). Exercise ECG patterns showed abnormalities in 4.9% of the athletes, including a total of 1227 in whom resting ECG patterns had been normal. Altogether, a total of 196 participants (0.6% of the total) were judged ineligible to participate in competitive sports, and of these a total of 159 were disqualified on the basis of cardiac findings. 126 of these (79.2%) had shown innocent or negative findings with resting ECG, but disease-associated abnormalities with exercise ECG. Although this research has been discussed in the context of young athletes, these individuals were generally older than those with normal ECG patterns, and age over 30 was found to be significantly associated with an increased risk of disqualification on the basis of abnormal exercise ECG findings.

The authors conclude that exercise ECG screening before participation in sporting events can identify those with cardiac abnormalities who are at risk of sudden cardiac death, and propose that follow-up studies should be performed in the expectation of demonstrating that disqualification of such individuals from participation would reduce the incidence of cardiovascular events among athletes. They note, however, that the diagnostic accuracy of the ECG screening was not demonstrated, since the results of subsequent medical investigations were not available.

Overall, 81% of athletes barred from sporting events on medical grounds were found to have cardiovascular disorders associated with a substantially increased risk of SCD. Notably, of these 159 individuals found to have cardiac abnormalities, family history of sudden cardiac death and physical examination had suggested problems in only six cases, and resting ECG patterns were normal in 126 cases. The use of exercise electrocardiography in addition to medical examination and assessment of family history as part of screening therefore made a substantial improvement on the detection rate of serious cardiovascular disorders, with a low rate of false positives.

Comment: The authors note the absence of follow-up data and analysis for this study, and it certainly has inherent limitations. For example, further investigative testing was only performed on individuals who screened positive; without performing the same clinical work-up on a group of people who had negative screening results, it is not possible to provide overall figures for the performance of the screening test. In particular we do not know the final sensitivity of the test, and thus do not know how many cases were missed, and we do not know whether any of the cases who screened negative were real negatives or, possibly had just been missed by the screening (negative predictive value)

The cost of the screening programme in Italy is reportedly estimated at around estimated €30 (£24) per participant, although without evidence that the actual numbers of sudden cardiac deaths are reduced (and by how many) as a result of this screening, the cost implications for health services cannot be accurately calculated. However, this recent study lends weight to the argument that exercise ECG screening of athletes is of value. Alison Cox of the charity Cardiac Risk in the Young, which carries out ECG screening in the UK commented: "The test we do costs £35, but when you consider the cost of the pair of trainers that the athlete is wearing, it seems a small price to pay for a test that could save your life" (see BBC news).

The PHG Foundation is currently working with UK experts and stakeholders in cardiac genetic disease to assess need and review current services with a view to developing recommendations for providing appropriate and accessible cardiac genetics services within the NHS (see Promoting genetics in mainstream medicine for more information).

 

2 July 2008In the last few weeks there has been a wealth of articles focusing on rare inherited diseases:

Issues in genetic testing for ultra-rare diseases: background and introduction.
Ledbetter DH, Faucett WA. Genet Med. 2008 May;10(5):309-13. 

Developing a national collaborative study system for rare genetic diseases.
Watson MS et al. Genet Med. 2008 May;10(5):325-9.

New quality assurance standards for rare disease testing.
Grody WW, Richards CS. Genet Med. 2008 May;10(5):320-4.

Making rare diseases a public-health and research priority.

Lancet. 2008 Jun 14;371(9629):1972

 

Rare diseases: what's next?
Remuzzi G, Garattini S. Lancet. 2008 Jun 14;371(9629):1978-9.

Why rare diseases are an important medical and social issue.
Schieppati A et al.  Lancet. 2008 Jun 14;371(9629):2039-41

Gene therapy of inherited diseases.
Fischer A, Cavazzana-Calvo M. Lancet. 2008 Jun 14;371(9629):2044-7. 

Gene patenting and licensing: the role of academic researchers and advocacy groups.
Ledbetter DH. Genet Med. 2008 May;10(5):314-9.

Common and rare variants in multifactorial susceptibility to common diseases
Bodmer W, Bonilla C. Nat Genet. 2008 Jun;40(6):695-701.

Pharmacogenetic testing: not as simple as it seems.
Haga SB, Burke W.Genet Med. 2008 Jun;10(6):391-5.

Genetic exceptionalism. Too much of a good thing?
Evans JP, Burke W. Genet Med. 2008 Jun 18. [Epub ahead of print]

Keeping Pace with the Times - The Genetic Information Nondiscrimination Act of 2008
Hudson KL, Holohan MK, Collins FS. N Engl J Med. 2008 Jun 19;358(25):2661-3.

The genetics of multiple sclerosis: SNPs to pathways to pathogenesis
Oksenberg JR, Baranzini SE, Sawcer S, Hauser SL. Nat Rev Genet. 2008 Jul;9(7):516-26.

Genetic susceptibility to cancer: the role of polymorphisms in candidate genes
Dong LM et al. JAMA. 2008 May 28;299(20):2423-36.

Genetic Predisposition to Breast Cancer: Past, Present, and Future
Turnbull C, Rahman N. Annu Rev Genomics Hum Genet. 2008 Jun 10.

From Darwin's finches to canaries in the coal mine - mining the genome for new biology.
Hunter DJ, Altshuler D, Rader DJ. N Engl J Med. 2008 Jun 26;358(26):2760-3.

This time it's personal
Nature. 2008 Jun 5;453(7196):697
See also:
Francis Collins interview. Departing U.S. genome institute director takes stock of personalized medicine.

Kaiser J. Science. 2008 Jun 6;320(5881):1272

Neuroblastoma - linking a common allele to a rare disease.
Kushner BH, Cheung NK. N Engl J Med. 2008 Jun 12;358(24):2635-7.

To thwart disease, apply now

Nature. 2008 Jun 12;453(7197):823.

Systems biology. The scale of prediction.
Baliga NS. Science. 2008 Jun 6;320(5881):1297-8.

Genomics: Protein fossils live on as RNA
Sasidharan R, Gerstein M. Nature. 2008 Jun 5;453(7196):729-31

Exploiting the proteome to improve the genome-wide genetic analysis of epistasis in common human diseases
Pattin KA, Moore JH. Hum Genet. 2008 Jun 13. [Epub ahead of print]

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