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31 October 2007Funded by the Wellcome Trust, UK and US researchers are to conduct what is said to be the largest genome-wide association (GWA) study to date for Alzheimer Disease (AD), looking at DNA samples from a total of 14,000 people; 6,000 ‘cases’ with late-onset AD and 8,000 healthy ‘controls’. Project lead Professor Julie Williams of Cardiff University commented: "Alzheimer's is a genetically-complicated story involving many genes, so we need large sample sizes to make sure any genetic links that we find are not mere coincidence… We need to build a complete picture of the different pathways that lead to the disease" (see press release).
The Alzheimer’s Society estimates that number of people in the UK with dementia will exceed one million by 2025; AD is the most common form of dementia (see Facts about dementia).
31 October 2007Scientists at the Beijing Genomics Institute (BGI) in China have announced that they have completed the first complete diploid genome sequence of a Chinese individual (see press release). This comes within months of the first two individual genomes to be sequenced, that of James Watson, Nobel Laureate and co-discoverer of the double helix structure of DNA (see previous news article), and Craig Venter, maverick scientist who lead the private bid to sequence the human genome (see previous news article). It is the first non-Caucasian genome to be sequenced in its entirety, although it has not yet been published in a peer-reviewed journal for international scientific use.
The project was undertaken by BGI’s Shenzhen branch, also known as Shenzhen Huada, a non-profit research organization funded primarily by local governments in partnership with several companies. The institute plans to sequence 99 more Chinese genomes as part of a 100-person project to map DNA polymorphisms in the Chinese population, and is offering wealthy Chinese the opportunity to have their own genome completely sequenced and analyzed for $1.3 million. Another project to sequence the panda genome is also underway at the institute.
30 October 2007The Council of Europe unveiled new guidelines regarding mail order and over-the-counter genetic tests at a conference in Paris at the beginning of October (reported by the Royal Society of Chemistry). The guidelines stipulate that diagnostic, predictive, ‘healthy carrier’ and pharmacogenetic tests should only be used under medical supervision. The move comes at a time when private genetic testing is not only commercially available but also heavily advertised in the US and represents an attempt to circumvent potential ethical quandaries relating to genetic testing, not least the perceived low public understanding of the complex relationship between genes and diseases.
Speaking about private genetic tests, Dr Ron Zimmern, director of the PHG Foundation, was recently quoted on BBC News as saying, “I think it is certainly too early to start offering the test both directly to the public or indeed through a physician. My main problem is that clinical studies that try to see what the predictive value of these tests is at the individual level just have not been done."
The European protocol will require that genetic tests meet generally accepted criteria of scientific and clinical validity. Legislators will scrutinise the text over the next few months before Ministers are asked to approve it, making it available for national ratifications. However, it is unclear how many states will choose to accept the complete, legally binding protocol.
29 October 2007A new report on the increasing health problem of overweight and obesity in the UK has been launched; the report from the UK Government group Foresight, Tackling obesities: future choices, is the product of a two year study by a large group of experts to produce a ‘long-term vision of a sustainable response to obesity in the UK over the next 40 years’ (see Foresight project website). Looking at the causes and predicted progression of obesity, the report predicts that 60% of men and 40% of women in the UK population will be obese by 2050, with the annual cost based on increased morbidity reaching £46 billion. It is proposed that an effective response to this trend towards widespread obesity, rather than being focused solely on individuals, will require cross-cutting societal approaches to increase activity levels and decrease consumption of high-calorie foods in the population as a whole. The role of individual genetic factors in determining resistance or predispostion towards obesity must also be taken into consideration.
The report also considers emerging areas of research such as the field of nutrigenomics (‘the science of personalised nutrition’), and their potential applications in the struggle to reduce levels of obesity, although Dr Siân Astley of the European Nutrigenomics Organisation (NuGO) has reportedly said that nutrigenomics has: "potential to underpin more-targeted more-specific public healthcare advice and perhaps in the future, when we have a better understanding of which if any genes are most important, maybe individualised advice via nutrigenetics and genetic testing" whilst cautioning that the influences of genetics on obesity are multiple, and intimately associated with environmental and behavioural factors (see FoodNavigator report).The UK government has reportedly announced the intention to work at the ‘environmental and organisational level’ to combat the obesity epidemic [Hitchen L (2007) BMJ 335(7624):789].
28 October 2007The Human Genome Epidemiology Network (HuGENet™), which is an international collaborative venture to investigate the role of human genome variation in population health, has launched a new resource for genome epidemiologists (see HuGE news). HuGE Navigator is a searchable and continuously updated knowledge base of human gene-disease associations; it also includes information on gene-gene and gene- environment interactions, population prevalence of genetic variants, and the evaluation of genetic tests. The new HuGE Navigator replaces older database search tools as well as offering additional functions for researchers.
25 October 2007Researchers presented work at the recent American Society for Reproductive Medicine conference on the use of RNA interference (RNAi) as a contraceptive tool (see BBC news). There is general interest in producing alternatives to the contraceptive pill as novel forms of birth control, particularly because the hormonal-based pills have unwanted side-effects in some women, and are contraindicated in others, such as those at increased risk of deep-vein thrombosis.
The new method is based on using RNA complementary to that produced to allow expression of a gene active in egg cells just prior to ovulation; blocking expression of the gene is said to prevent the formation of the egg cell’s outer membrane, to which sperm cells must bind in order to allow conception. However, thus far the technique has only been developed in mice, and trials in humans are a very long way off. Moreover, it is not yet known what the side-effects of this application of RNAi might be.
23 October 2007The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), announced recently that is to expand two of its ongoing initiatives. One of these is intended to broaden knowledge of the human genome by, for example, identifying individual genes, their location and how they are regulated. The other addresses the ethical, legal and social questions associated with the acceptance and use genetic research in medicine and public health.
Genes themselves, which are the protein-coding component of DNA, make up only around 1.5% of the human genome. It appears likely that many non-coding regions of the genome also have important functions in health and disease affecting, for example, gene expression, but relatively little is known about the locations of these functional elements or how they work.
In 2003 NHGRI initiated the initial phases of the ENCyclopedia Of DNA Elements (ENCODE) project in which a worldwide consortium of scientists developed and tested a range of computational and informational techniques to identify the functional elements in human DNA. Together they developed a suite of approaches, focusing efforts on ~1% (30mB) of the human genome.
The ENCODE project has now been extended with the announcement of grants totalling more than $80 million to 16 centres over the next four years. The new funding will build on the pilot studies, providing an accurate 'annotation' of the whole human genome and expanding knowledge of human genes. Dr Francis Collins, NHGRI director, said: "The ENCODE pilot produced findings that are reshaping many long-held views about our genome. ENCODE's effort to survey the entire genome will uncover even more exciting surprises, providing us with a more complete picture of the biological roots of human health and disease" (see press release).
Central to the goal of safely and effectively moving discoveries into the clinic is understanding the ethical, legal and social implications of this type of research. To address this NHGRI is adding two new centres to the Centers for Excellence in Ethical, Legal and Social Implications Research Initiative (see press release). Grants totalling over $12 million will be awarded to the University of North Carolina-Chapel Hill and the University of Pennsylvania in Philadelphia who will focus on issues that relate to the applications and uses of genomic research, technologies and information. Teams at each centre include experts in bioethics, law, behavioural and social sciences, clinical research, theology, public policy, and genetic and genomic research.
23 October 2007The second instalment of the human HapMap has been published in Nature by a team of over 200 international scientists [The International HapMap Consortium (2007), Nature 449: 851-862]. The International HapMap is “a multi-country effort to identify and catalogue genetic similarities and differences in human beings”. The project takes its name from the term haplotype, which refers to a set of closely linked alleles that are often inherited together due to physical proximity on the chromosome. The human haplotype map describes the variation seen in 270 individuals from America, Japan, China and West Africa, providing a key resource for biomedical researchers.
The International HapMap consortium was launched in 2002 and since the publication of the first phase in 2005 (see previous news story), with around a million single nucleotide polymorphisms (SNPs), the data have been extensively used in genome-wide studies of disease association; a search for ‘HapMap’ brings up over 350 citations in PubMed. The new, more thorough, high resolution version, HapMap2, contains over 3.1 million SNPs with a density of around one per kilobase. Over 32,000 recombination hotspots have been identified, accounting for around 60% of recombination events of the human genome but only 6% of the sequence. The new version also contains more diversity between individuals than was originally expected, consistent with recent literature describing huge structural variation in the genome (see previous news story).
An indication of how genome-wide association studies will be extended with HapMap2 is presented in the same issue of Nature [Sabeti et al. (2007) Nature 449: 913-918]. Three examples of population-specific selection based on geographical location are identified, involving genes linked to Lassa virus in West Africa, skin pigmentation in Europe and hair follicle development in Asia.
Comment: Whilst the relevance of the HapMap project to human health was initially unclear when the first phase was published, there is now little doubt that it provides an invaluable tool to researchers trying to understand the genetic basis of disease susceptibility. The higher resolution HapMap2 characterises human genetic variation much more extensively than the original, tripling of the number of genetic markers included, significantly increasing its utility for detection of rare disease determinants. This may be critical for understanding the effect of genome variations on public health.
22 October 2007The European Patent Office (EPO) has rejected an appeal by US company Myriad Genetics and the University of Utah, and upheld an earlier decision to revoke some claims of patent EP705902 relating to the BRCA1 gene and its applications (see press release). Myriad was originally granted the patent in 2001, later transferring it to the University of Utah Research Foundation whilst retaining exclusive licensing rights; the patent claims the isolated BRCA1 gene, the BRCA1 protein, and possible therapeutic applications and diagnostic kits based on the gene.
There was widespread objection to the extent of this claim among European researchers, since it granted an effective monopoly to Myriad which they believed unjustified; six bodies filed objections, leading to a decision by the EPO in 2005 to substantially amend the patent, retaining only the claims relating to a specific nucleic acid probe and vectors containing gene sequences. The EPO has now rejected an appeal by Myriad and the University of Utah, and amended the patent, meaning that European laboratories retain the right to perform diagnostic tests for mutations in the BRCA1 gene sequence, which are associated with increased susceptibility to breast and ovarian cancer.
The EPO has yet to examine the appeals made by Myriad Genetics and the University of Utah against decisions to revoke patent EP699754 in 2004 (see previous news) and amend EP705903 in 2005 (see previous news); both of these patents also relate to the BRCA1 gene.
20 October 2007A new trial of prospective gene therapy to treat the genetic disease Duchenne muscular dystrophy (DMD) is about to begin in London. DMD is inherited in an X-linked recessive pattern, meaning that it affects predominantly males, around 1 in every 3500 live male births. The inherited mutation prevents the production of dystrophin protein, which leads to progressive muscle wasting beginning in early childhood. Affected children gradually lose mobility; the condition becomes increasingly serious as the wasting affects heart and respiratory function, leading to premature death by the early twenties.
There is as yet no effective treatment for the condition.It is hoped that by delivering a specially targeted genetic ‘patch’ in the form of antisense oligonucleotides, production of some functional dystrophin will be possible, and disease progression could be slowed. Animal trials of the drug have proved highly successful. Professor Francesco Muntoni of Imperial College London said: "Maybe this will not be a complete cure, but it could definitely buy a lot of time for these children" (see BBC news).
Funding for the trial was awarded by the Department of Health in 2004, as part of the £50 million allocated in the 2003 Genetics White Paper (see previous news).
18 October 2007A UK consortium is to undertake a genome-wide association study to identify genes that are associated with osteoarthritis (see press release). The 2-year arcOGEN project involves eight UK centres and has received £2.2 million in funding from the Arthritis Research Campaign (arc).
According to arc, osteoarthritis affects about 8 million people in the UK making it the most common joint disease in the UK. Potentially it can affect any joint, causing severe pain and stiffness as the cartilage at the ends of bones wears away, and no treatments are currently available. Osteoarthritis of the knee and hip is the main cause of mobility problems in the elderly, with joint replacement the only option for many as the disease progresses.
The disease often runs in families. This indicates that it is likely to have a considerable genetic component, although lifestyle factors such as obesity are also known to have a role. It appears likely that several (possibly many) genes act together to increase a person's susceptibility, with each individual gene having a relatively small effect. In order to identify gene variants that predispose to the disease, this large study will scan the genomes of 8000 affected individuals, comparing the results with existing data from 6000 healthy volunteers.
The results of the study will be made freely available and are expected to provide a resource that will help identify many of the biological pathways that are involved disease development and progression. As such, the results are likely to be of considerable interest to pharmaceutical companies who could use the data to develop potential therapeutics. Ultimately, it might lead to new drugs to either prevent disease onset or delay its progression. arc also expresses the hope that the study will lead to additional breakthroughs such as genetic tests to predict who is likely to develop osteoarthritis and how severely they will be affected - the intention being that this information is used to offer treatment or life-style advice on how to reduce the risk.
16 October 2007The UK media has widely reported on the disapproving reaction of scientists to the news that a private US company is to market a service to harvest and store stem cells from excess IVF embryos. Company StemLifeLine, which revealed the new service at the American Society for Reproductive Medicine conference in the US this week, markets itself to parents with the slogan "Think of our service as an investment for the future". It offers parents having in vitro fertilization (IVF) treatment the option to pay to store stem cells from embryos that are not implanted, which could potentially be used in the future to treat disease in their children.
However, stem cell scientists have condemned the service as exploitation, saying that the £8,500 charge is unfairly preying on the fears of parents, and saying that the claim that stem cell lines created "may one day" help create therapies for living children who prove to be good immunological matches for the tissue created from the embryonic siblings is not justified. UK stem cell expert Professor Stephen Minger of King's College London commented: "My worry is that this is a commercial service that is being promoted to companies when the science is really not there to justify it” (see BBC news).
This service goes a step further than current commercial stem-cell banking initiatives, which offer to store cord blood from the umbilicus of newborn babies as a potential source of immunologically identical stem cells, which could be used for some future treatments of that newborn. Such companies operate in the UK, although their services have been criticized (see previous news). The Human Fertilisation and Embryology Authority (HFEA), which regulates the use of embryos created by IVF, has reportedly said that a service using frozen embryos would be unlikely to gain approval in the UK, since licensing requires that the proposed application is both necessary and desirable. The UK already has a national stem cell bank maintained for research purposes, and a public cord blood bank.
16 October 2007The second parasitic genome to be elucidated in recent weeks (see previous news story) has been reported in the journal Science [Morrison, HG. (2007) Science 317, 1921-6].
The unicellular intestinal parasite Giardia lamblia (also known as G. intestinalis and G. duodenalis) occurs worldwide. Transmitted via animal and human faeces, it is recognised as a major cause of diarrhoea in humans and is one of the most common causes of waterborne disease both in the USA as well as less affluent nations. However despite the major health risks associated with Giardia, the basic biology of this parasite is not well understood.
In addition to the major health burden associated with this organism, Giardia intrigues scientists for another reason: taxonomists consider that it occupies a position very close to the transition between eukaryote and prokaryote phylogenies and so is a valuable model from which to gain basic insights into genetic adaptations that led to the formation of eukaryotic cells.
As stated by the authors, ‘This genome sequence will not only be valuable for investigatingthe evolution of eukaryotes, but will also be applied to thesearch for new therapeutics for this parasite’.
Comment: Several existing drugs are available for treating giardiasis. However, since these must be given repeatedly to combat recurring infection from contaminated water, improving access to clean drinking water is likely to have a more direct impact on the incidence of this disease in many parts of the world.
12 October 2007Three multinational pharmaceutical companies have entered into a partnership with the UK government to develop human embryonic stem cells for use in toxicity testing (reported in Reuters). Stem Cells for Safer Medicine (SC4SM), a non-profit British company to be headed by Philip Wright, science director at the Association of the British Pharmaceutical Industry, will be the first major public-private collaboration in stem cell research. Drug giants GlaxoSmithKline, AstraZeneca and Roche have each contributed £0.1 million to help fund the first year's work, whilst the British government is contributing £0.75 million; other drug companies are expected to join soon.
Within its 5 year programme, the consortium will focus on converting stem cells into specific differentiated cell lines for toxicity testing; it will not directly investigate the therapeutic use of stem cells to treat disease. This type of research falls under the broad heading of “animal-on-a-chip” technology, and could significantly reduce the need for animal testing by providing alternatives for evaluating drug toxicity. Reduction in live animal testing is desirable on practical and commercial grounds as well as ethical grounds. Around 10% of the 3 million animals used for testing in the UK in 2006 were used for toxicity testing by the pharmaceutical industry (see Statistics of Scientific Procedures on Living Animals Great Britain 2006) and the number is likely to increase dramatically as a result of the recent European Union legislation regarding the regulation of chemicals (REACH).
More than 90% of new drugs entering into clinical trials fail to get to market, either due to lack of effectiveness or adverse side-effects not predicted during pre-clinical development. SC4SM will initially focus on producing liver cells (hepatocytes) from stem cells, as unexpected liver toxicity is the biggest single reason why new drugs fail during clinical trials. In the longer term, the consortium will investigate differentiating stem cells into various other cell types including heart cells (cardiomyocytes).
11 October 2007The National Institutes of Health (NIH) is making a vast collection of genetic and clinical data freely available to researchers. Called the SNP Health Association Resource (SHARe), it will allow researchers to access extensive phenotype and genotype information from several of the large cohort studies that are funded by the