News

22 December 2008 The European Court of Human Rights (ECHR) has ruled that the retention of fingerprint information, cellular material and DNA profile of two British men in the National DNA database is in violation of Article 8 of the European Convention on Human Rights (see BBC news). The men had appealed for their data to be removed as they had not been convicted of any crime, and approached the European Court of Human Rights after their cases were rejected by the House of Lords. In their judgement, the ECHR was "struck by the blanket and indiscriminate nature of the power of retention in England and Wales’’. In particular, the Court singled out the fact that the existing regime takes no account of age of the subject (contrary to the UN Convention on the Rights of the Child 1989, which asserts the right of every child to be treated with dignity and worth). This was one of the grounds on which the Nuffield Council on Bioethics reached their critical assessment of the existing system (see previous news). The ECHR finding against the UK Government was also on the basis that the system failed to discriminate on the basis of the seriousness of the crime or the likelihood of reoffending as do comparative systems elsewhere in Europe. The Court also noted that the Government had failed to justify continuing with the existing system by describing the number of convictions that would have been lost had the current system not been in place.

The ruling was welcomed by the Nuffield Council on Bioethics, who in their 2007 report The Forensic Use of Bioinformation: ethical issues (see previous news) cautioned against the storage of such information when the alleged offences are minor, or individuals are not ultimately charged or convicted (see press release). The case highlights the sensitivity of retaining DNA samples and data rather than fingerprints, and both the case and the report by the Nuffield Council draw distinctions between the ethical issues raised by the storage of fingerprint data, digitised DNA profiles and biological samples. The ECHR noted that the latter two categories have a stronger potential for future use of personal information than fingerprint information, and are capable of being used "as a means of identifying genetic relationships between individuals" and as such "their retention interferes with the right to the private life of the individuals concerned".

In response to this ruling, the UK Home Secretary has announced the publication of a White Paper on forensics in 2009, with the aim of creating a more proportionate and effective system of retention. The Government have also announced the immediate withdrawal of samples from children aged under 10 years from the database (around 70 samples). The Human Genetics Commission is currently involved in a project aiming to form recommendations on issues relating to the National DNA Database for England and Wales and the Scottish forensic database; the Scottish database differs in that, DNA of unconvicted persons is only retained in the case of adults charged with violent or sexual offences and even then, only for three years, extendable for two more years following consent from a sheriff.

16 December 2008 Screening newborns for certain inherited conditions is undertaken in most countries to provide a means of early identification and treatment of conditions such as phenylketonuria (PKU) and sickle cell anaemia. With the emergence of new high-throughput technologies such as tandem mass spectrometry (MS/MS), the number of conditions that can potentially be screened for has increased and is likely to expand further as genomic technologies develop. MS/MS allows for the detection and quantitation of over 20 different metabolites simultaneously, following simple sample preparation, thereby allowing screening for a number of inherited metabolic disorders to be carried out. In the US, the American College of Medical Genetics (ACMG) has recommended screening to be undertaken for a “core” panel of 29 conditions (see previous news) and 25 secondary conditions. In the UK, newborn screening has not expanded to such and extent and MS/MS is only offered for the detection of phenylketonuria (PKU) and Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD). A health and technology assessment carried out in 2004 concluded that although it could be used for screening a number of other inherited metabolic disorders, lack of evidence about the incidence of these conditions as well as the impact of screening on management of the conditions precluded their inclusion in the newborn screening programme (see previous news).

Screening for a wide panel of disorders, especially when many of them are extremely rare, not fully understood and as yet untreatable raises a number of ethical, legal and social issues (see previous news). This month the President’s Council of Bioethics in the US has released a white paper on expanded newborn screening with the aim to “foster public awareness of the practice, the ethical principles that have guided it until now, and the ethical problems posed by its current and future expansion”. In their report: The Changing Moral Focus of Newborn Screening: An Ethical Analysis by the President's Council on Bioethics, the council examine the ethical implications of offering screening for a wide range of conditions, especially when in many cases there are no treatments available for the detected conditions. Their report concludes that screening for untreatable conditions may do more harm than good and this may be “accentuated once new DNA technologies make it possible to expand screening to target additional diseases and to detect disease susceptibility as well”. As a result they recommend that screening should only be offered for conditions that meet the traditional Wilson-Jungner screening criteria. The report acknowledges that expanded newborn screening can contribute to biomedical knowledge of rare diseases; however, they recommend that where screening is possible for untreatable conditions, this should be offered through pilot studies, so that evidence about the benefits of screening can be gathered. In addition, informed consent should be gained from parents prior to this undertaking.

Along with discussing the ethical issues raised by expanded newborn screening policy in the US, this report also raises conceptual issues about the purpose of screening and screening programmes; an issue which has to be dealt with as our options on what we can screen for expands. The expansion of newborn screening programmes appears to have been mainly been dictated by technological advances. However, an important consideration is whether screening for a particular condition can aid in the care and management of the patient. A recent editorial accompanying a report on the impact of expanded newborn screening in the US, called for ongoing surveillance and evaluation of the diagnosis of affected newborns and their longer-term health outcomes to develop better management protocols (see previous news). The report also raises questions about what conditions should be screened for mandatorily by national health systems in an effort to improve public health and how they should be offered. This also has an effect on ensuring informed consent; as screening technologies develop and expand, especially with the inclusion of much rarer conditions, it becomes much harder to ensure that people are aware about the test, the consequences of the results (i.e. false positives and negatives) and are appropriately advised about them.

 

11 December 2008To receive our monthly round-up by email please register here (also gives you access to our Resources section).

Go to monthly round-up

11 December 2008UK campaign groups the Christian Legal Centre (CLC) and Comment on Reproductive Ethics (CORE) have lost their bid against the Human Fertilisation and Embryology Authority (HFEA). They sought leave from the High Court to bring a test case application for judicial review over the HFEA’s approval in principle of the use of animal eggs in the creation of cytoplasmic hybrid embryos for stem cell research (see previous news), and its subsequent decisions to grant licences to researchers Newcastle University and King's College London allowing them to create cytoplasmic hybrid embryos for stem cell research (see previous news).

Challenging these licences, the campaigners asserted that the HFEA had operated outside the current law in deciding to grant licences for research involving the creation of animal human hybrid embryos; the UK Human Fertilisation and Embryology Bill, which has now passed the House of Commons (see previous news) and will come into force in 2009, was still being drawn up at the time. CORE and CLC argued that under the Human Fertilisation and Embryology (HFE) Act 1990 the definition of a human embryo prohibited the creation of animal human hybrids (because they are not human) and that “even if they were not prohibited, the licenses were neither necessary nor desirable in light of recent developments with adult stem cell research where the real progress in finding cures to serious illnesses is being made” (see press release). However, the HFEA maintained it was right to regulate the research because the Human Fertilisation and Embryology (HFE) Act 1990 (which the new Bill amends) stipulated that the regulator was able to interpret guidance as science progressed so as not to slow down research. 

Rejecting the application, High Court judge Mrs Justice Dobbs ruled that it was "totally without merit" (see BBC news). The HFEA said that it was pleased by the court’s decision, adding: "We always believed that we acted lawfully and responsibly when considering these research licence applications" (see HFEA statement). Speaking for the CLC, Andrea Minichiello Williams commented: “It is ironic that the HFEA was set up to be an independent body concerned with fundamental ethical questions and for the protection of public interest. Yet when public interest bodies wish to challenge controversial ethical decisions there is no internal means of doing so, whereas scientists refused a licence can ask the HFEA for reconsideration” (see press release).

9 December 2008Plans to roll out cascade screening for familial hypercholesterolaemia (FH) in Wales have been announced (see BBC news). FH is a common genetic disorder, inherited in an autosomal dominant manner and with an estimated frequency of around 1 in 500 of the UK population (more than 100,000 people).The vast majority of these individuals are currently undiagnosed. The screening programme will test family members of individuals diagnosed as having FH. Early identification of the condition, characterized by significantly raised cholesterol levels, allows preventative interventions - such as diet and lifestyle modifications, and the use of drugs such as statins  - to reduce the risk of premature coronary artery disease.

Minister for Health and Social Services Edwina Hart has reportedly made a commitment that the Welsh Assembly Government would work with the BHF to help fund the setting up and long term costs of a FH service in Wales. This move follows recent guidance issued by the UK National Institute for Health and Clinical Excellence (NICE) which recommended that cascade screening should be systematically implemented in the families of people diagnosed with FH throughout the UK (see previous news).

1 December 2008 A growing trend in the provision of direct-to-consumer (DTC) genetic testing for ancestry research has led the American Society of Human Genetics (ASHG) to issue new guidance, proposing that the practice needs greater scrutiny and that “it is imperative to explore the complex relationship between genetics, ancestry and race that can complicate the interpretation of these types of tests and their results” (see press release). This assertion is partly because many companies offer testing for both ancestral analysis and health risk assessment; because of the potentially wide-ranging impacts of such testing; and also because of the unaddressed “scientific and non-scientific challenges and implications of DTC ancestry…in the genetic and genomic research arenas from which it originated”.In particular, they draw attention to the different applications of genetic ancestry analysis as a service for individual consumers as compared with in the context of large-scale scientific research on population genetics.

The ASHG statement on ancestry testing noted their major concern that there is no quality assurance system or “even a mechanism to couple market performance with anything relating to accuracy”, although this accuracy could vary to a significant degree depending on the reference population databases used for analysis. The ASHG also notes that even the best databases “reflect a woefully incomplete sampling of human genetic diversity”. In terms of potential health implications of ancestry testing, the ASHG notes the current lack of understanding about how genetic ancestry related to individual and population health, along with a common assumption that racial/ethnic identity may be a key determinant of health outcomes. They urge caution in the interpretation and clinical application of results from ancestry and related DTC genetic tests. The personal and societal implications of testing are noted to be potentially complex, raising a range of political, legal, psychological, social and ethical issues.

President elect of the ASHG Edward McCabe commented: “Consumers, as well as scientists, must remember that ancestry-testing inferences are fallible, and that over-interpretation or misinterpretation can happen…Inaccurate results may be confusing and life-changing, therefore greater efforts are needed to make the limitations of ancestry testing more explicit” (see press release).

The five recommendations of the ASHG are:

Clearer delineation of the current limitations of ancestry determination by industry and academia to make them clearer to consumers, the scientific community, and the public at large; the public should access and take note of information.

Further research to clarify the extent to which the accuracy of genetic ancestry estimation is influenced by the individuals represented in existing databases, geographical patterns of human diversity, marker selection and statistical methods.

Assessment of the complex consequences of ancestry estimation for people, families, and populations, and the development of guidelines to facilitate explanation and/or counselling about ancestry estimation in research, DTC and health care settings.

Conferral of scientists performing and interpreting genetic ancestry tests with experts in the historical, sociopolitical and cultural contexts of such testing.

Establishment of mechanisms for greater accountability of the DTC ancestry testing industry.

Internet-based ancestry testing is available DTC internationally; for example, MyHeritage offers testing including a Y-chromosome test to identify paternal descent, a mitochondrial DNA test to identify maternal descent. FamilyTreeDNA chief executive Bennett Greenspan has reportedly said of their own service: "The biggest problem is finding out your brother isn't your brother or your father isn't your father. But we don't deal with that…you'd be more likely to find out that your great grandfather was adopted or that there was false paternity" (see Guardian news article).

23 December 2008

The gold standard for mutation screening for many years has been amplification of target sequences by polymerase chain reaction (PCR) followed by Sanger sequencing. However, when it comes to conditions where the mutation may be in one of several genes or polygenic conditions where a number of different genes may be involved (e.g. breast cancer), gathering results by this technique can often be labour intensive and time consuming as numerous different genes have to be sequenced. Although a number of parallel sequencing techniques have been developed, along with “front-end” methods to amplify a subset of genes (see previous news), these procedures are still too expensive and complex to be applied in a routine diagnostic or screening setting.

Recently, VIB researchers at the University of Antwerp have developed a new method of detecting mutations and copy number variations that may make diagnosis of inherited diseases quicker (see press release). The technique involves a combination of multiplex PCR (amplification of multiple targets by using more than one set of primers) with high-throughput parallel sequencing, in order to analyse multiple genes simultaneously. In a paper published this month, Goossens et al. describe the use of this technique to identify mutations in seven genes associated with Charcot-Marie Tooth Disease (CMT) – an inherited disorder that affects the peripheral nervous system [Goossens et al 2008 Hum Mutat. 0(1-6)]. The researchers amplified and sequenced seven genes from 31 individuals and compared the mutations detected with the results obtained by traditional PCR-based Sanger sequencing. All the variants that were detected by traditional methods were also identified using the new technique. They were also able to determine the copy number variation (CNV) of two genes associated with CMT (GJB1 and PMP22).

Comment: Although this new method still needs validating, if successful it could make diagnosis and screening for many inherited conditions much more rapid (weeks as opposed to months). In addition, with inherited conditions that can be a result of mutations in several genes, where mutation screening is usually only undertaken to identify common variants, this technique may allow screening for a larger number of variants at a fraction of the cost.

19 December 2008

New publications have shed light on some of the genetic factors involved in obesity, (defined as a body mass index or BMI greater than 30 kg/m2). Two papers in Nature Genetics report the association of specific genetic variants with obesity. The first presents the results of a genome-wide association (GWA) study with more than 300,000 single nucleotide polymorphisms (SNPs) typed in around 31,000 individuals. Most of these were Icelandic, along with around 3,000 Dutch, 2,000 European Americans and 1,000 African American subjects; results were combined with previously published results in over 5,500 Danish individuals. A total of 29 genetic variants in 11 chromosomal regions were found to be significantly associated with obesity, including previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, and variants at seven loci not previously connected with obesity [Thorleifsson G et al. Nat. Genet. 2008 14 December | doi:10.1038/ng.274].

Many of the variants identified are near genes highly expressed or known to act in the brain and central nervous system (CNS), and may therefore be involved in the neuronal control of weight regulation. The authors note that this “underscores the importance of genes that regulate food intake over those involved in metabolism”. They also observe that the variants they report are all relatively common in the sampled populations (because the analysis is biased towards identification of these more common variants) and collectively explain only a small proportion of genetic variation in BMI and weight, whilst more rare mutations in the same loci might be involved in the rarer and more extreme cases of genetically-determined obesity.

The second paper is a meta-analysis of fifteen previously published GWAs with a combined total of more than 32,000 individuals looking for genetic variants associated with BMI; the fourteen most promising candidate variants were analysed in an additional fourteen groups with a combined total of more than 59,000 individuals. The results presented by the researchers confirm the involvement previously reported variants in the FTO and MC4R gene loci, along with a further six loci in the TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 genes [Willer CJ et al. Nat. Genet.2008 14 December | doi:10.1038/ng.287].

The researchers acknowledge that the identified loci, their precise positions and the mechanisms by which they influence BMI and obesity will require further analysis. However, as with the first paper, they too note the high representation of genes involved in the central nervous system (CNS) that may be involved in the neuronal control of weight regulation. They also observe that many more genetic variants that influence BMI may well remain as yet undetected, particularly those that are less common or exert smaller individual effects, some of these might lie within the previously identified loci.

A third paper in the New England Journal of Medicine focused on the fat mass and obesity–associated (FTO) gene in Scottish children. The common rs9939609 (A allele) FTO genevariant was found to be associated with increased weight and body-mass index (BMI) in a sample of around 3,000 children, as expected. However, the researchers then focused on a much smaller sub-sample of 76 children to examine links between the variant and adiposity, energy expenditure, and food intake. Itwas found to be associated with increased fat (but not lean) mass, and with increased energy intake independently of body weight [Cecil JE et al. (2008) N Engl J Med. 359(24):2558-66].

Children were given one of three pre-meal snacks providing no energy, a low total energy value, or a high total energy value. Children with the A allele showed significantly greater energy intake at the subsequent test meals than those without it, especially if they had received the zero or low-energy pre-meal snacks, although the mass of food consumed by the A allele children was not increased compared with that of other children. Resting energy expenditure was equivalent for both groups of children, leading the authors to propose that the variant is not linked with any defect in metabolic adaptation to obesity, but rather that it may be involved in the regulation of food choice and intake, such that children with the variant eat more high-calorie foods than those without it. Researcher Professor Colin Palmer reportedly said that these findings “reinforced the idea that soaring obesity rates were closely linked to the widespread availability of cheap, calorie-packed foods” (see BBC news article).

Comment: Obesity is a serious public health concern in the UK and many other countries, where rising levels of obesity are predicted to lead to a huge surge in associated diseases such as metabolic syndrome, type 2 diabetes and cardiovascular disease. England’s Chief Medical Officer Sir Liam Donaldson has spoken of an "obesity timebomb" in the UK (see BBC news article). Whilst the environmental causes of obesity are relatively straightforward, being essentially excess dietary energy intake and inadequate physical activity, the genetic factors that influence it are more complex, although known to exert a significant effect on the risk of obesity. An improved understanding of the underlying genetics of obesity is an important goal for the development and targeting of effective interventions; Willer et al. correctly observe that the discovery of additional genetic variants that influence BMI will “slowly increase predictive power”, but that insight into the underlying biological mechanisms involved in obesity and the design of therapeutic interventions may be more significant in terms of health impact.

 

9 December 2008Currently, prenatal diagnosis of recessive autosomal diseases is only possible through invasive testing, such as amniocentesis and chorionic villus sampling, which carries around a 1% risk of miscarriage. However, a new technique developed by Dennis Lo’s laboratory in Hong Kong – based on the presence of cell-free fragments of fetal DNA present in the maternal bloodstream during pregnancy – has raised the possibility that such diseases could potentially be prenatally diagnosed non-invasively [Lun  et al (2008) PNAS 105: 19920-19925].

 

To date, research into the non-invasive prenatal diagnosis of single gene disorders using cell-free fetal DNA has been limited to detection of paternally inherited mutations, which are not otherwise present in the maternal genome. This limits the clinical applications to diagnosis of the inheritance of paternal autosomal dominant diseases, and exclusion of the inheritance of certain autosomal recessive diseases where the maternal and paternal alleles differ. However, in cases where the woman is a heterozygous carrier of a disease – with one normal copy of a gene, and one diseased copy – prenatal diagnosis requires determining whether the maternal disease mutation has been inherited by the fetus.

 

The new technique measures the ‘relative mutation dosage’ of a particular gene in all cell-free DNA in the maternal bloodstream, i.e. the ratio of the diseased to the normal alleles. During pregnancy, the presence of even a small amount of fetal DNA in the maternal bloodstream will affect this ratio, and both an underrepresentation or overrepresentation of the disease allele suggest that the fetus is homozygous (and normal or affected respectively); if the alleles are balanced, then the fetus is a carrier. This allele ratio can be measured using a variety of techniques, the most obvious of which is digital PCR, which allows the number of copies of a particular sequence to be easily counted. However, although this ‘molecular counting’ technique is conceptually simple, it is practically challenging due to the relatively low proportion of fetal DNA versus maternal DNA (less than 10% in early pregnancy). The researchers tackled this problem by exploiting the fact that fetal cell-free DNA fragments are generally shorter than the maternal ones. Using an innovative extension to standard digital PCR, the target gene derived specifically from the fetus was selectively amplified and detected, thus effectively enriching the sample with fetal DNA and increasing the potential affect on the allele ratio.

 

However, despite this technical wizardry, the technique is far from being clinically validated. Although the technique proved to be highly accurate on artificially created test mixtures of male and female blood samples, only 5 out of 10 fetuses at risk of either b-thalassaemia or haemoglobin E were correctly diagnosed at 18-20 weeks by measuring the relative mutation dosage (in the absence of fetal enrichment). When fetal DNA enrichment was combined with this method, 4 out of 5 fetuses were correctly genotyped at 12-14 weeks, using a locus of interest for Down syndrome testing on chromosome 21.

 

Comment: This exciting proof-of-concept study has brought non-invasive prenatal diagnosis of single gene diseases a step closer to clinical application, and most importantly, has offered the first practical method for diagnosing recessive diseases. However, before it could be realistically offered by antenatal services, further laboratory development will be needed to make the technology practicable for use by clinical service laboratories, and extensive clinical evaluation in large cohorts will be required to establish the accuracy of the technique for numerous single gene diseases.

5 December 2008 Patients diagnosed with early stage colon cancer (stage I and II) are usually considered to be cured after surgical removal of the tumour. However, in about 20% of patients, the disease can recur and it is important to identify these patients in order to improve their care. It may soon become possible to predict disease recurrence of colon cancer and individualise therapy through examination of the genomic signature of individual tumours (see press release). Researchers from the Duke Institute of Genome Science and Policy in the US have developed a model based on examining the gene expression pattern of tumour cells, to predict the risk of recurrence in early stage colon cancer patients. In addition, this model may also be useful in predicting the response of tumours to various chemotherapy agents, thereby allowing targeted follow-up strategies or therapy to be employed.

In their study, Garman et al. retrieved gene expression data from 52 samples representing clinical stage I and II disease from a publicly available database, and correlated the patterns of gene expression with information on tumour recurrence in order to develop a prognostic model [Garman et al. (2008) PNAS 105(49):19431-19436]. The model they developed was based on examination of the expression pattern of 50 genes and was 90% accurate in predicting risk of recurrence in this initial data set. The model was further validated by examining its predictive power using two independent date sets consisting of 55 and 73 tumours and was able to correctly classify 69.1% of patients in the first cohort and almost all patients in the second. Following on from the identification of those at high-risk of recurrence, the researchers went on to investigate therapeutic strategies for this group. They used colon cancer cell lines to investigate the relationship between the high-risk gene expression phenotype and sensitivity to therapeutic agents, and demonstrated a correlation between the two; furthermore, treatment with certain agents was able to reverse the profile of a tumour from high risk to low risk. However, this was only demonstrated under laboratory conditions using cell lines and clinical trials would need to be undertaken in order to validate the observed effects. 

Comment: Cancer cells usually exhibit many genetic aberrations and a greater understanding of these can be useful in classifying tumours, thereby aiding disease prognosis. In addition, a greater understanding of the biology of individual tumours can lead to targeted therapeutics as well as the identification of new targets for therapy. Using tumour genome expression profiling to guide prognosis and treatment has already been developed and approved for breast cancer (see previous news). Whilst extensive clinical evaluation of such risk prediction models is critical, these types of companion diagnostic tests are likely to become increasingly common and could potentially have an enormous impact on the pharmaceutical and biotech industries.

 

3 December 2008The common disease-common variant (CDCV) hypothesis predicts that common disease-causing alleles, or variants, exist in all human populations that contribute to common diseases. Although each variant will necessarily only have a small effect on disease susceptibility (i.e. a low associated relative risk), numerous researchers have suggested that useful diagnostic or predictive tests may nonetheless be possible by combining multiple variants. To this end, the cumulative effect of common risk variants has been demonstrated for prostate cancer and cardiovascular disease (see previous news), and a scheme for improved targeting of breast cancer screening using common genetic markers has been outlined (see previous news).

 

More recently, researchers have investigated combining 18 common single nucleotide polymorphisms (SNPs) to predict the risk of type 2 diabetes [Meigs JB et al. (2008) NEJM 359(21):2208]. The study examined the extent to which a genotype score (i.e. the total number of risk variants possessed by an individual) could discriminate the risk of diabetes when used either alone or in addition to other clinical risk factors. The clinical performance was measured using a ‘c-statistic’, which represents the discriminatory accuracy of a test, i.e. how well it can distinguish between individuals that will get the disease from those who will not; this value varies from 0.5 (i.e. a useless test, equivalent to guessing randomly) to 1.0 (i.e. a perfect test, where everyone is correctly categorised).

 

There are two very different ways to represent the results of this study. The first is in a fairly positive light. There was a 12% increase in the risk of diabetes per risk allele, resulting in a substantial overall relative risk of 2.6 between people with the highest and lowest genotype scores. Adjusted only for sex, the genotype score produced a c-statistic of 0.581, a statistically significant improvement over a value of just 0.534 without the genetic information, resulting in improved discrimination and reclassification of 4.1% of people primarily from low risk categories into higher-risk ones. Given the increasingly high prevalence of type 2 diabetes (around 4% according to Diabetes UK), as well as the availability of highly effective, safe and well validated preventative measures, this would appear to be potentially a very valuable test.

 

However, the second representation is rather more discouraging. When family history or clinical risk factors were also used, all of which are frequently documented during adulthood, the genotype score did not significantly improve discrimination. The best validated model – based on sex, family history, age, body-mass index, fasting plasma glucose level, systolic blood pressure, high-density lipoprotein cholesterol level and triglyceride level – already offers a high discrimination power of 0.900, and the addition of the genotype score only resulted in a small and non-statistically significant increase of the c-statistic to 0.901. Here, the addition of genetic information to standard risk factors is essentially clinical useless.

 

Comment: This study highlights the importance examining the incremental benefits of genetic susceptibility testing within a particular clinical scenario – what might at first look like a very useful test on its own may in fact offer limited or no value when combined with traditional risk factors. Consideration of genetic tests within a specific clinical context is therefore crucial to realistic evaluation.

 

However, there is hope on the horizon. Firstly, more genetic susceptibility variants will doubtless be discovered, which may ultimately improve the discriminatory power of the genotype score. Secondly, it is currently unclear whether the ability to test people very early, before clinical risk factors have appeared, could be extremely useful for targeting screening and prevention programmes. Finally, even if ultimately genetic testing does prove to be ineffective for predicting or diagnosing disease, the discovery and validation of the genetic basis of disease will undoubtedly improve our understanding of disease aetiology, and may ultimately lead to the development of novel treatments.

8 December 2008

The 6th November issue of Nature has an editorial and a series of special news reports and commentaries on personal genomes:

My genome. So what?

Nature. 2008 Nov 6;456(7218):1.

 

Personal genomes: The case of the missing heritability
Maher B. Nature. 2008 Nov 6;456(7218):18-21.

 

Personal genomes: Standard and pores
Sanderson K. Nature. 2008 Nov 6;456(7218):23-5.

 

Personal genomes: A disruptive personality, disrupted
Nelson B. Nature. 2008 Nov 6;456(7218):26-8.

 

Personal genomes: When consent gets in the way
Taylor P. Nature. 2008 Nov 6;456(7218):32-3. No abstract available.

 

Personal genomes: Misdirected precaution
Prainsack B, Reardon J, Hindmarsh R, Gottweis H, Naue U, Lunshof JE. Nature. 2008 Nov 6;456(7218):34-5.

 

Genetic mapping in human disease.
Altshuler D, Daly MJ, Lander ES. Science. 2008 Nov 7;322(5903):881-8.

Regulation - the real threat to clinical research.
Stewart PM, Stears A, Tomlinson JW, Brown MJ. BMJ. 2008 Oct 16;337:a1732. doi: 10.1136/bmj.a1732.

 

Fresh thinking about the Declaration of Helsinki
Goodyear MD, Eckenwiler LA, Ells C. BMJ. 2008 Oct 17;337:a2128. doi: 10.1136/bmj.a2128.

Recreational genomics; what's in it for you?

Evans JP. Genet Med. 2008 Oct;10(10):709-10

Molecular genetics of myocardial infarction.
Yamada Y, Ichihara S, Nishida T. Genomic Med. 2008 Jan;2(1-2):7-22.

 

The "neuro" in neurogenetics
Landis S, Insel TR. Science. 2008 Nov 7;322(5903):821.

Research ethics: Certificates of confidentiality and compelled disclosure of data
Beskow LM, Dame L, Costello EJ. Science. 2008 Nov 14;322(5904):1054-5.

 
Recreational genomics; what's in it for you?
Evans JP. Genet Med. 2008 Oct;10(10):709-10.

Policy considerations in designing a fragile X population screening program.
Ross LF, Acharya K. Genet Med. 2008 Oct;10(10):711-3.

 
A Decade of Public Health Genomics in the United States: Centers for Disease Control and Prevention 1997-2007.
Khoury MJ, Bowen S, Bradley LA, Coates R, Dowling NF, Gwinn M, Kolor K, Moore CA, St Pierre J, Valdez R, Yoon PW. Public Health Genomics. 2008 Sep 3.

Canada: Public Health Genomics
Little J, Potter B, Allanson J, Caulfield T, Carroll JC, Wilson B. Public Health Genomics. 2009;12(2):112-20.

Danger and opportunity

Nature. 2008 Nov 13;456(7219):141.

17q21 variants and asthma - questions and answers.
Holloway JW, Koppelman GH. N Engl J Med. 2008 Nov 6;359(19):2043-5. Epub 2008 Oct 15.

 

Sharing patients' records to boost medical research

Lancet. 2008 Nov 29;372(9653):1856.

Medical research ethics in China
Wang R, Henderson GE. Lancet. 2008 Nov 29;372(9653):1867-8. Epub 2008 Oct 17.

Bias, spin, and misreporting: time for full access to trial protocols and results
Chan AW (2008) PLoS Med 5(11): e230 doi:10.1371/journal.pmed.0050230

 

Scientists and human rights
Rubenstein L, Younis M. Science. 2008 Nov 28;322(5906):1303.

From Genome-Wide Association Studies to Gene-Environment-Wide Interaction Studies - Challenges and Opportunities.
Khoury MJ, Wacholder S. Am J Epidemiol. 2008 Nov 20. [Epub ahead of print]

read more ...