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 Philippa Brice   |   Published 25 November 2009

The second part of the US Genetic Information Nondiscrimination Act (GINA) has now been enacted (see information for researchers and health professionals); Title II, which prohibits genetic discrimination in employment, came into effect on November 21 2009; Title I, which relates to individual health insurance came into effect on May 21 2009, and the final element relating to group health insurance policies will follow soon. The employment provisions apply only to employers with more than 15 workers.

GINA prohibits discrimination in these areas on the basis of genetic information (see previous news); of note, employers and health insurance providers will not only be prohibited from requesting or using genetic test results, or information about requests for or access to genetics services, but also information about family history of disease. This is a major departure because family history has long been used by insurers as an important factor in calculating the risk of disease (or other outcomes) in an individual, and determining the premiums they should pay for coverage on this basis. With the exception of diagnostic tests for highly penetrant genetic disorders, tests for individual genetic variants associated with susceptibility to disease are generally much weaker predictors of risk than family history.

Interestingly, the level of support for GINA suggests that this actuarial fairness model for insurance is deemed by many to be unsatisfactory. This may mean that there is a general preference for the alternative social solidarity model – whereby there is universal access to insurance and the total cost of provision is shared by all as opposed to weighted towards those at greatest risk – which is perhaps surprising in the light of opposition to President Obama’s controversial healthcare reform Bill, which seeks to ensure that affordable health insurance is available to all including people with pre-existing medical conditions (see BBC news). This could be an example of collective genetic exceptionalism, whereby genetic information is afforded special protection compared with other forms of confidential medical data.

It has reportedly been common practice in the past for employers in the US (who typically provide health insurance coverage for employees) to request family history information from their workers, for example providing incentives to complete medical information questionnaires (see New York Times article). However, employers may accidentally learn of genetic or family history information – for example, overhearing employees discuss family illness - without penalty. Indeed, how they could avoid this is not clear. In 2001 a US company was prosecuted for secretly testing workers for a genetic variant potentially associated with increased risk of carpal tunnel syndrome (see LA Times article) but there is otherwise little evidence of genetic discrimination by employers, despite concerns. Opponents have said that GINA may actually have a negative impact on the health of employees, for example by limiting access to health-promotion or disease management programmes.


News story   |   By Dr Sowmiya Moorthie   |   Published 23 November 2009
The Organisation for Economic Co-operation and Development (OECD) launched a public consultation on draft Guidelines for Human Biobanks and Genetic Research Databases (HBGRDs) last year (see previous news). The draft Guidelines were 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.  Comments were invited from any member of the public and a Recommendation on Human Biobanks and Genetic Research Databases was adopted in October 2009 by the OECD Council.

The document defines HBGRDs as “structured resources that can be used for the purpose of genetic research and which include: (a) human biological materials and/or information generated from the analysis of the same; and (b) extensive associated information”. The recommendations provide guidelines for the establishment, governance, management, operation, access, use and discontinuation of HBGRDs and are intended to be applied  broadly. Although primarily targeted at new HBGRDs, the principles contained may also be applied to existing databases and to some extent to those which are established for non-research purposes, such as public surveillance. The document also links with other OECD biotechnology recommendations, such as those relating to quality assurance in molecular genetic testing among others.

The OECD state that these guidelines are intended to be “evolutionary” and relevant scientific and societal developments will lead to their review. Accordingly they state a need to review these Recommendations and Guidelines five years after its adoption in the first instance and periodically thereafter.


News story   |   By Dr Philippa Brice   |   Published 17 November 2009

The new Science and Technology Committee of the UK House of Commons has launched a Bioengineering Inquiry, with a specific focus on ‘how the UK can maintain a globally competitive position in emerging and existing bioengineering research fields’. The specific areas of interest are synthetic biology, stem cells and genetic modification (GM), and in each of these areas the inquiry will consider issues of research, translation and regulation.

The relatively permissive regulatory regime for stem cell research in the UK has allowed it to prosper as a centre of international excellence, but even before the recent changes in the US and Japan relaxing restrictions on research involving human embryonic stem cells (see previous news), there were concerns that the UK could lag behind other global players. In contrast with the UK’s track record in stem cell research, research into many forms of genetic modification suffered significant setbacks following a media-led public backlash against so-called ‘Frankenstein foods’ (see also BBC news feature from 2008). Interest in synthetic biology has been growing in recent years (see previous news).

Written submissions are invited by 4th December 2009.



News story   |   By Dr Philippa Brice   |   Published 11 November 2009

The first complete genome sequence of the domestic horse, Equus caballus, has been produced by an international team of researchers. Besides being of obvious interest for evolutionary biology and veterinary science, the researchers say that the 2.7 billion base-pair horse genome is also relevant for the study of human disease. Kerstin Lindblad-Toh of the Horse Genome Project at the US Broad Institute of MIT said: "Horses and humans suffer from similar illnesses, so identifying the genetic culprits in horses promises to deepen our knowledge of disease in both organisms" (see ScienceDaily news).

There are reportedly more than 80 hereditary diseases in horses with similarities to human disorders, including musculoskeletal, neuromuscular, cardiovascular and respiratory diseases (see press release). The research was partly funded by the National Human Genome Research Institute.

Meanwhile, as sequencing costs continue to fall, an international consortium of researchers have launched the Genome 10K Project, an initiative intended to create a ‘zoo’ of genomes from 10,000 vertebrate species to inform the study of evolution (see press release). Perhaps some of these genome sequences might also have relevance to human health.


News story   |   By Dr Philippa Brice   |   Published 11 November 2009

There have been new reports that UK doctors are calling for retention of human tissue for genetic testing in cases of sudden cardiac death among young people, in case of an underlying genetic cardiac condition that could also put relatives at risk. This follows calls for greater awareness among doctors and coroners about inherited cardiac conditions and their role in sudden deaths, and clarity for coroners about their responsibilities in such cases, from the PHG Foundation report Heart to Heart: Inherited Cardiovascular Conditions Services published earlier this year (see previous news).

The BBC has reported the suggestion from one clinical geneticist that until coroners' forms could be changed to deal specifically with consent for the pathologist to retain tissue for DNA extraction and storage in such cases, they should consider taking a tiny tissue sample and approaching relatives for consent, as some coroners already do. Dr Mary Sheppard, of the Royal Society of Medicine said: "If coroners routinely requested consent from the family to retain material for DNA testing at autopsies we would be able to find out far more about how the person died and possibly prevent other deaths in the same family" (see BBC news report). Adrian McNeil of the Human Tissue Authority said it was “alarmed about any public statement that urges practitioners to consider breaking the law governing consent and the taking of tissue for DNA testing”, although of course the doctor had not been advocating retaining or testing tissue against the wishes of relatives.

The PHG Foundation report, the product of an expert Working Group, and which has just won an NHS Partnership Award, called for legislative change and other measures to encourage the retention of tissue samples following sudden cardiac death, as well as clarification of the responsibility of coroners to family members who may be at risk. However, the importance of best practice in gaining consent from family members for investigation of the possible presence of an inherited cardiac condition in the deceased person was also emphasised.


News story   |   By Dr Philippa Brice   |   Published 10 November 2009
The UK Academy of Medical Sciences has launched a new study to examine the use of animals containing human material (such as DNA) in scientific research. They say that consideration of this area is needed in the light of rapid scientific advances ‘to ensure that research into our understanding of diseases and their treatment can take place in the UK within a robust ethical and regulatory framework’ (see press release).

The investigation will consider transgenic animals and animal embryos containing integrated ‘human-like genetic material’, and chimeric animals and animal embryos, containing cells of human origin. For example, this might include mouse models of human diseases such as Down’s Syndrome, which are widely used for medical and pharmaceutical research; human tissues or organs being grown in animals as part of transplantation research; or the controversial hybrid human-animal embryos for stem cell research (see previous news).

The study is expected to take 12-18 months and will consider scientific, ethical, social, regulatory and safety aspects of the creation and use of non-human animals and embryos incorporating human material, including public perceptions of such research. Professor Martin Bobrow CBE, who is to lead the multi-disciplinary expert group who are undertaking the study, reportedly said: "We are trying to work out what is reasonable" (see Associated Press news).

The study is supported by the Home Office, the Medical Research Council and the Wellcome Trust (see responses to study launch). The AMS says the final report will serve to ‘reinforce the UK’s lead in developing policy and legislation in challenging areas of medical science that is recognised world-wide’. More information is available from their website.


News story   |   By Dr Philippa Brice   |   Published 6 November 2009

A new national biobanking initiative is to be established after the Dutch government awarded €22.5m funding for the Biobanking and Biomolecular Resources Infrastructure Netherlands (BBMRI-NL), a network including several academic and other research bodies. The initiative is intended to integrate and enrich existing clinical data and samples to make them more accessible for researchers. Professor Gertjan van Ommen of Leiden University Medical Centre said: “The existing materials are often of high value and quality but underused because of fragmentation” (see eHealthEurope news).

Once established, the initiative will presumably link in with larger networks that seek to connect European biobanks, particularly the European BBMRI, Biobanking and Biomolecular Resources Research Infrastructure (see previous news) or the EuroBiobank. The Netherlands is also reportedly competing with Austria and Luxembourg to host the BBMRI itself, which will enjoy special legal status and tax benefits (see EurActive news). Luxembourg is partnering with the US Translational Genomics Research Institute to form the Integrated Biobank Luxembourg (IBBL), a biomedical hub focusing on diagnostic biomarkers. 

Meanwhile in the US, the Kaiser Permanente biobank (see previous news) is partnering with the University of California, San Francisco (UCSF) to collate and analyse genetic and clinical data from 100,000 older Americans, with an average age of 65 (see Technology Review article). The National Institutes of Health (NIH) awarded $24.8 million over two years for this new study into the genetic and environmental factors influencing health and ageing. Richard Hodes, director of the National Institute on Aging (NIA) which was behind the grant said: “We are very excited about the opportunity to develop this extraordinary database in an older population, to facilitate studies of gene-environment interaction as determinants of health, disease, and longevity” (see press release).


News story   |   By Dr Philippa Brice   |   Published 4 November 2009

A new European initiative has formed for the purpose of promoting the use of diagnostics for personalised medicine. The European Personalised Medicine Diagnostics Association (EPEMED) is a non-profit venture that hopes to recruit commercial and academic research bodies and patient groups (for a membership fee) to collaborate to advance personalised medicine diagnostics in Europe and promote harmonization between countries in terms of ‘value pricing and value reimbursement with a clear regulatory path in Europe for novel diagnostics and/or companion therapeutics’ (see website).

The group also plans to work with other international bodies in the area of personalised medicine and to offer opinions on policies. Founder Alain Huriez said that innovations in molecular diagnostics would offer better patient care in coming years, adding: "It is our responsibility to make sure that these innovations will be made available to European patients and as a result, to make Europe an attractive place for innovations, financial and industrial investments in the area of personalised medicine diagnostics" (see GenomeWeb news).


News story   |   By Dr Caroline Wright   |   Published 3 November 2009

Sense about Science has published Making Sense of Screening, a public guide aimed at addressing misconceptions about how screening works. By working with scientists and clinicians, as well as organisations including the UK National Screening Committee and the PHG Foundation, they hope to bridge the gap between the active debates of the scientific community and the concerns raised by the public.

The guide highlights many of the limitations of population screening, and explains the trade-off between of benefits and harms that is required before establishing a national screening programme. It explains that:

  • Screening rarely benefits all sections of the population and can have negative effects, so it needs to be targeted at those most likely to benefit.
  • Not all diseases are suitable for screening.
  • A positive screening result does not mean you have the disease in question, and a negative result does not mean you will not go on to develop the disease being screened for.

The guide is being launched at a public debate on screening, as part of National Pathology Week. Media interest has focused on concerns that the potential harms of screening have not always been properly explained (see Times article).

Sense about Science is an independent charitable trust focused on responding to the misrepresentation of science on issues that matter to society. This is the second publication from Sense about Science with input from the PHG Foundation; last year, Making Sense of Testing was launched in tandem with the PHG Foundation’s report on The Evaluation of Diagnostic Laboratory Tests and Complex Biomarkers (see previous news).


Research articles

Research article   |   By Dr Sowmiya Moorthie   |   Published 27 November 2009
Genome-wide-association (GWA) studies aim to pinpoint the genetic differences that correlate with and perhaps play a causative role in disease. Genetic variants associated with disease are identified by comparing DNA samples from a group of patients who share a particular disease with samples from those who do not (controls). The data from these studies are usually stored in publicly accessible databases so that they can be used by other researchers. Open access data requires balancing the availability of genomic research and its potential public benefit with ethical principles relating to consent, confidentiality and privacy. Several consortia such as the Wellcome Trust Case Control Consortium and National Institutes of Health have created data sharing policies and regulatory procedures taking into consideration the ethical issues raised by such research. In addition, such issues have been extensively discussed in the literature along with the proposal of models for data sharing. However, this has mainly been in the context of research carried out in higher-income countries and may not be applicable to developing countries, where an increasing number of GWA studies are being conducted.

A recent article in PLoS Medicine, outlines some of the challenges of developing guidelines for data sharing in developing countries, using the Malaria Genomic Epidemiology Network (MalariaGEN) as an example  [Parker et al. (2009) PloS Medicine 6(11) e1000143. doi:10.1371/journal.pmed.1000143]. The key issues that were raised in developing data release policies for MalariaGEN were in relation to the format of data, its acceptable uses and timing of release all of which have implications for local communities as well as individual researchers. Entirely open access to GWA data on individuals along with phenotypic data was considered to be inappropriate, as factors such as ethnicity may allow de-identification of data sets, especially if it related to the frequency of gene variants. With relation to MalariaGEN, an independent data access committee (IDAC) was set-up to mediate data-access, which required signing a legally binding access agreement. The data-sharing policy also allowed for a delay in data release in order to give researchers at study sites in developing countries time to analyse newly available data. This was to address the imbalance in analytic capabilities between developed and developing countries.

The authors state that there is a need for genetic researchers to work together with ethics committees, social scientist and local communities to ensure their views are respected with respect to open access data. In addition they state that ethical data release policies should also ensure that the research aspirations of developing countries are attained, this may be through mechanisms that allow data produced in developing countries to be analysed locally and ensuring that they address local health needs.

 


Research article   |   By Dr Caroline Wright   |   Published 24 November 2009

The discovery that we all carry many small, apparently benign copy number variants in our genomes was a surprise to many people, and suggests that cells are less sensitive to gene dosage (i.e. the number of copies of a gene) than originally believed. Similarly, the old paradigm of simple dominant and recessive mutations – an all or nothing approach to genetics – has also been challenged by numerous discoveries of semi-dominant relationships and mutations associated with increased susceptibility to disease.

 

A simple question therefore remains: what proportion of genes in the human genome are dosage-sensitive? An approximate answer to this question is provided by the first dosage map of a human chromosome, which has been produced by looking for disease causing mutations and copy number variations across chromosome 18 [Cody JD et al. Genet Med (2009) 11: 778-82]. Researchers mined through online resources (such as OMIM and the Database of Genomic Variants) for evidence of disease resulting from a mutation, duplication or deletion in just one copy of chromosome 18. Two hundred fifty-three genes were evaluated and categorised as to whether they showed dosage sensitivity or not. Of these, five were found to be dosage sensitive (haploinsufficient, though one only in the presence of an additional factor), and 81 were found to be dosage insensitive (haplosufficient); no information was available to determine the dosage sensitivity of the remaining 167 genes. Although there is doubtless a continuum of dosage sensitivity, this work suggests that perhaps 5-10% of human genes are dosage sensitive to such an extent that changing the copy number noticeably affects the phenotype.

 

Comment: This map is the first stage towards producing a complete understanding of the dosage-dependence of the entire human genome. In addition to providing a fascinating insight into the regulation and activity of gene products at a quantitative, molecular level, it potentially has enormous utility for interpreting clinical results from high resolution diagnostic technologies such as DNA microarrays. Moreover, because the results have been integrated into an online genomic map, this work can be applied immediately by clinicians and genetic counsellors in caring for individuals with chromosome 18 abnormalities.


Research article   |   By Dr Susmita Chowdhury   |   Published 19 November 2009

Parkinson's disease (PD) is a chronic degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions. Parkinson’s is caused by degeneration of the basal ganglia, an area of the brain, and by low production of the neurotransmitter, dopamine. Most PD patients are over 50, and one in 500 people in the UK suffer from the condition according to the Parkinson’s Disease Society. The common form of  PD (as opposed to much rarer Mendelian forms of Parkinsonism) is a complex disorder caused by multiple genetic and environmental factors. Previously, genome-wide association studies (GWAS) for PD have shown some evidence for association of several genetic variants with disease risk, but not at statistically significant levels.

 

Recently, two independent GWA studies, one led by researchers in Japan [Satake et al.(2009)Nat Genet 15 November doi:10.1038/ng.485] and another by collaborators from USA and Europe [Simón-Sánchez et al. (2009) Nat Genet 15 November doi:10.1038/ng.487] have detected strong links between PD and several genetic variants, and have compared their results.

 

Satake et al. and colleagues studied more than 2,000 Japanese PD cases and 18,000 control subjects. They identified new susceptibility loci on chromosomes 1 and 4, designated the PARK16 and BST1 loci. The genes SNCA and LRRK2 (on chromosomes 4 and 12 respectively) also showed significant association with risk of Parkinson’s. Simón-Sánchez et al. and colleagues studied more than 5,000 PD cases and 8,000 controls of European ancestry and observed strong associations at the SNCA and MAPT gene loci.

 

When the data from the two studies were compared, it was found that variants of PARK16, SNCA and LRRK2 genes were associated with increased risk of Parkinson’s in both Japanese and ancestral European populations, while variants of the BST1 gene and MAPT locus were associated with PD risk only in Japanese and ancestral European populations, respectively. Therefore the authors concluded that the findings reflect “population differences in the genetic heterogeneity of PD aetiology”.

 

There is supporting evidence for how the susceptibility genes identified by the two groups may contribute to the aetiology of Parkinson’s disease. For example, the SNCA gene encodes a protein involved in RNA processing or stability, which is also the main component of Lewy body, a pathological hallmark of typical PD. SNPs in the BST1 gene have been linked with dysfunction of neurones (nerve cells), and the PARK16 region contains functionally interesting candidate genes for PD aetiology. Presently, although medical treatments may improve symptoms of Parkinson’s Disease, there are none that can slow down or halt the disease’s progression. It is hoped that a better understanding of genetic mechanisms underlying this disease including discovery of new susceptibility loci, will lead to strategies that may help to delay or potentially prevent the disease.

Keywords : parkinsons

Research article   |   By Dr Gurdeep Sagoo   |   Published 18 November 2009
Ulcerative colitis is a common form of inflammatory bowel disease (IBD) and is a chronic condition affecting the colon; combined with Crohn’s disease, it affects around 1 in 400 people in the UK (according to the National Association for Colitis and Crohn’s Disease). Over the past two years, several genome wide association studies (GWAS) have expanded the number of genetic factors implicated in IBD pathogenesis, with 32 loci associated with Crohn’s disease and 17 associated with ulcerative colitis. Three research groups have recently published new GWAS studies online in the journal Nature Genetics identifying several new genetic variants.


The study by Asano et al. [Asano et al. (2009) Nat Genet 15 November doi:10.1038/ng.482] reports a two-stage study of Japanese subjects with more than 1,000 ulcerative colitis patients and 3,000 controls. Many SNPs in the MHC region on chromosome 6 showed strong association with IBD. Fifteen SNPs outside this region showing strong association were analysed and three novel susceptibility loci identified: the FCGR2A immunoglobulin receptor gene, the SLC26A3 glycoprotein gene, and a variant on chromosome 13q12.


The second publication by the UK IBD Genetics Consortium and the Wellcome Trust Case Control Consortium 2 [Barrett et al. Nat Genet 15 November doi:10.1038/ng.483] looked at two independent sets of around 2,400 patients with ulcerative colitis and around 5,000 controls. Three new positions on chromosomes 7, 16, and 20 showed significant association with the disease, the authors identified LAMB1, CDH1, and HNF4A as biologically plausible candidate genes in these regions.


The third publication by Imielinski et al. [Imielinski et al. Nat Genet 15 November doi:10.1038/ng.489] reports a GWAS of more than 3,400 European patients with early-onset IBD and almost 12,000 European and North American controls. This study detected associations at 23 of the 32 loci previously implicated in Crohn’s disease and 8 of the 17 previously implicated in ulcerative colitis. It also identified five novel early-onset IBD susceptibility loci on chromosomes 2, 10, 16, 19, and 22. Of the multiple genes in these regions, the authors consider the immunomodulatory cytokine IL27 gene to be the most likely candidate gene involved in disease susceptibility.


Comment: These three well-conducted GWAS papers provide robust evidence for association between several new genetic variants and susceptibility to IBD. Each study identifies biologically plausible candidate genes involved in autoimmunity or the function of the epithelium. For example, the FCGR2A gene is implicated in susceptibility to other autoimmune diseases, and encodes a receptor that is expressed on the surface of several immune cells, whilst the IL27 gene encodes a cytokine which regulates immune cells, lending further support to the idea that this immune pathway plays a key role in causing intestinal inflammation. These susceptibility genes now require extensive follow-up work to understand their role in the processes that cause IBD, which may lead to new approaches in developing treatments.


Research article   |   By Simon Leese   |   Published 16 November 2009

A study published last week in Nature Neuroscience has described for the first time a mechanism by which stressful events in infancy can alter gene expression in later life Murgatroyd et al. (2009) 8 Nov epub ahead of print.

The research examined epigenetic changes in mice that had been exposed to stress by being separated from their mothers for three hours a day for the first ten days of their lives. It was already known that this causes alterations in hormone levels and the stress responses of the mice that persist in later life. It was also already known that environmental signals in general can cause epigenetic changes to the genome that alter gene expression, and that these changes are often effected by methylation of DNA. Some previous studies have suggested that this form of altered gene regulation may be a factor in some psychiatric disorders.

This study focused on the expression of two regulatory hormones; arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH), both of which are linked to mood and cognitive behaviours. The researchers found that early life stress in the mice caused a surge in stress-associated hormones, altering the methylation of a regulator of the Avp gene resulting in persistent increased expression of AVP and consequent changes in behaviour, such as deficits in memory and a reduced ability to cope with stress. They also found that these behaviours were mostly reversible by the subsequent use of antagonists to block the mice’s AVP receptors. The authors speculate that the behaviours were likely not entirely reversed because other regulators or genes that they had not targeted were also involved.

Comment: Whilst this study is significant in that it is the first to elucidate a mechanism by which stress can alter gene expression, caution must always be exercised when seeking to extrapolate the results of animal studies to humans. It does however seem highly plausible that environmental stresses in humans could cause similar changes to the epigenome; indeed several studies have suggested such effects, such as the thrifty phenotype observed in the children of mothers who have experienced poor nutrition.

There is an established correlation between childhood neglect and psychiatric illness in humans, and this study suggest the possibility that this may not be a purely psychological effect, but may also be influenced by fundamental changes to the expression of some genes. If this proves to be the case, it could open up research into entirely new approaches to the treatment of psychiatric disorders such as depression.


Research article   |   By Dr Philippa Brice   |   Published 13 November 2009
French researchers have reported the results of a new form of gene therapy used to treat patients with the genetic neurodegenerative disease X-linked adrenoleukodystrophy (ALD). Caused by mutations in the ABCD1 gene that prevent the formation of normal ALD protein, patients develop progressive loss of the myelin sheath that protects nerve cells. Death typically occurs before adolescence; the only treatment is a full bone marrow transplant, which requires a matched donor and is in itself a dangerous procedure, and which must also take place early in life before the demyelination progresses too far, since it is irreversible.                      

Now researchers have treated haematopoietic stem cells (blood cell precursors) from two seven-year old ALD patients with an HIV-1 derived lentivirus vector carrying the normal ABCD1 gene [Cartier N et al. (2009) Science. 326(5954):818-23]. The patients had aggressive chemotherapy to suppress normal bone marrow production of haematopoietic stem cells followed by administration of the treated stem cells. Since these stem cells were derived from the patients’ own cells, there was no risk of immune rejection as there would be with imperfectly matched donor cells.

Blood cell analysis suggested that around 15% of the reconstituted blood cells in the patients contained normal, healthy copies of the ABCD1 gene. Brain scans and tests of cognitive function showed a halt in disease progression after 14–16 months that has persisted for a further 12 months. There have been no signs of cancer; the major risk from gene therapy (especially using virus-derived vectors) is of insertional mutagenesis where the vector inserts into a place in the recipient cell’s genome that drives the formation of a tumour (see previous news). Analysis of the sites of vector insertion to date reportedly did not show any signs that the vectors were inserting in any one particular site ie. that there was any preferential replication of cells carrying the insert in a particular position, which might be a precursor of cancer formation.

Comment: This was a very small trial; while promising, it is still early days, and it is possible that over time the therapeutic effect of the gene therapy could deteriorate, or leukaemia develop in either of the two patients. However, without this treatment, the outlook for these two boys (for whom no matched bone marrow donor was available) was extremely bleak; for the moment, at least, they have been cured. Further trials with patients in similar positions are certainly warranted  - and no doubt eagerly sought by the patients’ families.


Research article   |   By Dr Caroline Wright   |   Published 9 November 2009

Following numerous tantalising announcements earlier in the year, US company Complete Genomics Inc. has now published the results of three complete genomes, which were sequenced for an average cost of $4,400 each using its third generation sequencing platform [Drmanac R et al. (2009) Science doi: 10.1126/science.1181498]. The company is one of the front runners in the race to achieve the coveted $1,000 genome, and previously announced that it “plans to sequence 10,000 human genomes in 2010” (see previous news). Although the current price-tag excludes the platform itself and any associated infrastructure, the consumables cost between $1,726 and $8,800 for these genomes, which were sequenced at a coverage ranging from 45- to 87-fold per genome respectively.

The individuals sequenced included two from the HapMap population – a Caucasian male and a Yoruban female – and an individual previously sequenced as part of the Personal Genome Project. The sequencing revealed around 2.9-4 million single nucleotide polymorphisms (SNPs) per genome, of which around 10-20% were novel, as well as 250-500 thousand short insertions and deletions.

The technology uses patterned nanoarrays upon which the DNA self-assembles, thus vastly increasing the sequence content per run relative to earlier technologies. Moreover, unlike second generation “sequencing by synthesis” methods, which sequentially sequence chains of DNA, this method independently sequences each base and therefore avoids accumulation of errors. Validation of one genome suggests an error rate of around one per hundred thousand basepairs, which translates into around 30 thousand errors per genome. Although this is still unsuitable for clinical use, where a high level of diagnostic accuracy is required, it is likely to be applicable both to research for whole-genome-wide association studies and in the direct-to-consumer genomics market.


New reviews and commentaries

Selected new reviews and commentaries, 1 November 2009

Reviews & commentaries : by Dr Philippa Brice

Gene therapy deserves a fresh chance
Nature. 2009 Oct 29;461(7268):1173.

The DNA-damage response in human biology and disease.

Jackson SP, Bartek J. Nature. 2009 Oct 22;461(7267):1071-8.

Genetics of motor neuron disorders: new insights into pathogenic mechanisms
Dion PA, Daoud H, Rouleau GA. Nat Rev Genet. 2009 Nov;10(11):769-82.

Human genetics: Hit or miss?
Chi KR. Nature. 2009 Oct 8;461(7265):712-4.

Finding the missing heritability of complex diseases.
Manolio TA et al. Nature. 2009 Oct 8;461(7265):747-53.

Genomics of Emerging Infectious Disease
Collection of open-access articles on how genomics can revolutionize our understanding of emerging infectious disease.

Public access to genome-wide data: five views on balancing research with privacy and protection
P3G Consortium et al. PLoS Genet. 2009 Oct;5(10):e1000665. Epub 2009 Oct 2.

Megascience. 'Omics data sharing.
Field D et al. Science. 2009 Oct 9;326(5950):234-6.

China: Public Health Genomics
Zheng S, Song M, Wu L et al. Public Health Genomics. 2009 Sep 22. [Epub ahead of print]

Genetics. Life after GWA studies.
Dermitzakis ET, Clark AG. Science. 2009 Oct 9;326(5950):239-40.

The era of genome-wide association studies: opportunities and challenges for asthma genetics.
Zhang G, Goldblatt J, Lesouëf P. J Hum Genet. 2009 Oct 9 [Epub ahead of print]

Alzheimer's disease beyond APOE
van Es MA, van den Berg LH. Nat Genet. 2009 Oct;41(10):1047-8.

Genome-wide association studies in Alzheimer's disease.
Bertram L, Tanzi RE. Hum Mol Genet. 2009 Oct 15;18(R2):R137-45.

Looking for a target on every tumor
Kaiser J. Science. 2009 Oct 9;326(5950):218-20.

DNA damage, aging, and cancer.
Hoeijmakers JH. N Engl J Med. 2009 Oct 8;361(15):1475-85.

The genetics of inbreeding depression.
Charlesworth D, Willis JH. Nat Rev Genet. 2009 Nov;10(11):783-96.

Rethinking how DNA methylation patterns are maintained.
Jones PA, Liang G. Nat Rev Genet. 2009 Nov;10(11):805-11.

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