News

24 March 2006The Chancellor of the Exchequer, Gordon Brown, has announced a number of measures this week in his budget statement with implications for science and specifically health research. Perhaps most important was the announcement that a joint £1billion fund for health research will be created and held jointly by the Departments of Health and Trade and Industry. The Government will then seek advice on the best institutional arrangements for the development of a more ‘coherent framework for health research and development under this structure’. This will involve a consultation exercise that will report on the differing options. The Government hopes that these measures will help to align research priorities more closely with wider health benefits and to translate this work into economic benefit for the UK.

The Chancellor also announced a number of other measures to boost innovation and to improve the supply of skilled scientists by promoting training and science education.

Full details of these measures can be found in the ‘Meeting the Productivity Challenge’ section of the Budget.

16 March 2006The UK Biobank project aims to create a massive bank of biological material and linked medical information with a view to facilitating research into the genetic and environmental factors that affect the risk of common complex diseases. It is intended that a total of 500,000 adult volunteers aged between 40-69 will eventually be recruited and their future health outcomes followed; this information combined with genetic and lifestyle data will be available for research.

A pilot centre opened in Altrincham, South Manchester on 13th March, and up to 3000 individuals in the area are being contacted by post and invited to participate in the venture. This will entail a visit to the assessment centre of around an hour for clinical assessments, provision of blood and urine samples, and agreement for UK Biobank to follow their future “medical and other health-related records” (see press release). Alan Langlands, chair of the UK Biobank board, said: "The privacy of participants will be protected throughout the lifetime of the project…The security of patient data has to be guaranteed to have the confidence of the public” (see BBC news report).

The initial recruitment phase is intended to ensure procedure run smoothly before the scheme is rolled-out nationally later in the year, when a total of 8-10 assessment centres across the UK are expected to be in operation at any one time.

UK Biobank is funded by the Department of Health, the Scottish Executive, the Wellcome Trust and the Medical Research Council (MRC).

7 March 2006It has been announced that Manchester will be host to a new embryonic stem cell research initiative. The North West Embryonic Stem Cell Centre (NWESCC) is expected to be completed later in the year and is a joint project between Central Manchester NHS Trust, the University of Manchester, the Patterson Institute for Cancer Research and the University of Liverpool. It is anticipated that the new centre will develop human embryonic stem (hES) cell lines for the treatment of a variety of diseases. Specifically, it will seek to develop methods of culturing and selecting oocytes and embryos for hES cell derivation, establish conditions for deriving hES cells under Good Manufacturing Practice (GMP) culture conditions, develop targets for cancer therapy and direct the differentiation of hES cells into lines suitable for clinical useage. The centre is being funded by both the MRC (£0.5M) and the North West Development Agency (£1.45M).

7 March 2006The European Court of Human Rights (ECHR) has ruled against a UK woman in her case to win the right to use her frozen embryos to have a child after her partner had withdrawn his consent (see BBC news report 03/07/06). Ms Natallie Evans had been undergoing in vitro fertilisation (IVF) procedures with her partner, Mr Howard Johnston, when she was diagnosed with early stage ovarian cancer. Their resulting embryos had been stored in expectation of starting a family at a later time. However, their relationship ended and Mr Johnston subsequently withdrew his consent for Ms. Evans to use the embryos. Ms Evans had taken her case to UK courts claiming that Mr Johnston had been willing to start a family at the time of the IVF treatment and should not be allowed to withdraw his consent. Both the UK Court of Appeal and High Court dismissed her claims. Leave to appeal to the House of Lords was refused.

 

Ms Evans lodged her case with the ECHR in February 2005. In her arguments she claimed that there had been a violation of her and her embryos’ rights under the European Convention on Human Rights. She cited Article 8, which protects the right to respect for private and family life and Article 14, which prohibits discrimination. The Court deliberated on whether UK law was ‘compatible’ with the Convention. According to the Court, as there is no international consensus over the regulation of IVF treatment, European Union Member States have been allowed some ‘margin of appreciation’ when creating national law. The UK Human Fertilisation and Embryology Act 1990 makes it illegal for clinics to use embryos in treatment if one party refuses their consent. As this was the position of other Member States the Court decided that the UK had reached a balanced position in its national law, in regards to Article 8. The Court also disagreed with Ms Evans’ assertion “…that the situation of the male and female parties to IVF treatment could not be equated and that a fair balance could in general be preserved only by holding the male donor to his consent.” Ms Evans also could not claim that she had been treated any differently than any other woman in her situation, therefore there was no violation of her Article 14 protection against discrimination. The Court did express sympathy that Ms Evans would not be able to give birth to her own genetically related child.

 

Ms Evans had also argued that her embryos’ rights under Article 2, which protects an individual’s right to life, had been violated. The Court agreed unanimously that this right had not been violated as “Under English law an embryo did not have independent rights or interests and could not claim—or have claimed on its behalf—a right to life…” 

 

Ms Evans now hopes to be able to appeal to the Grand Chamber of the European Court. This must be done within 3 months of the original judgement.  The Grand Chamber will decide “…whether the case raises a serious question affecting the interpretation or application of the Convention or its protocols, or a serious issue of general importance…” If so, they will make a final judgement on the case; if not, original judgement will become final.

6 March 2006Age-related macular degeneration (AMD) is the most common form of visual impairment and blindness in developed countries, affecting around half a million people in the UK alone, and is the leading cause of blindness in people over the age of 60. Macular degeneration is a blanket name for a large number of individual conditions involving damage to the macula, a small area of the retina at the back of the eye. Around 90% of macular degeneration is termed AMD, and typically occurs in people over the age of 50.

 

A new study by researchers from Columbia University Medical Center and the University of Iowa in the US [Gold B et al. (2006) Nature Genetics advanced online publication doi:10.1038/ng1750] reports the identification of two key genetic risk factors that could be involved in three-quarters of all cases of AMD. The pathology of AMD is thought to involve dysfunction of normal inflammatory pathways. An earlier study by the same researchers linked certain common variants in the gene for one component of these pathways, complement factor H or CFH, to a significantly increased risk of AMD [Hageman GS et al. (2005) Proc. Natl. Acad. Sci. USA 102, 7227–7232]. However, as around a third of individuals with the disease-associated Factor H gene variant did not have AMD, they decided to investigate whether variations in genes for other factors from the same pathway that could have a similar effect, complement factor B (BF) and complement component 2 (C2), also played a role in risk of AMD. Factor H is involved in the inhibition of immune responses when infectious agents have been eliminated. It is thought that this process of down regulation is impaired in people with certain variant forms of Factor H, and this poorer control of inflammation may be involved in AMD. Factor B acts in opposition to Factor H, activating the immune response pathway.

 

The genotypes of 548 individuals with AMD and 275 controls with respect to the within the BF and C2 genes were determined, by using SNP (single nucleotide polymorphism) tags. Two pairs of variants were found to be significantly associated with AMD; the BF gene L9H and C2 gene E318D alleles, and the BF gene R32Q allele and C2 gene intron 10 SNP variant rs547154. The analysis was repeated in an independent group of 350 individuals with AMD and 114 controls, and the same findings confirmed. Haplotypes across the C2 and BF genes were examined using pooled data from both patient / control cohorts, a total of almost 1300 people. The common haplotype H1 was found to confer a significant risk for AMD. The H7 haplotype (containing the BF R32Q allele and C2 rs547154 SNP) was conferred a high degree of protection against AMD, whilst the H10 haplotype (containing the C2 E318D and BF L9H alleles) was also significantly protective.

The research team developed and refined an algorithm for combined analysis of the previously identified CFH and the newly implicated C2/BF alleles, which showed that several different combinations of these alleles gave some degree of protection from AMD. Among AMD patients, 74% were found to lack any protective haplotype, whilst just over half (56%) of the control group had at least one protective CFH or C2/BF haplotype. Because the two genes have opposing actions, possession of a protective gene variant in one can ameliorate the effect of a risk-associated variant in the other. Analysis of the relative contributions of the two loci to the overall genetic risk component for AMD estimated that the CFH locus accounts for 60-65% and the C2/BF locus for 35-40%.

 

Lead author Rando Allikmets commented: "These findings are significant because they absolutely confirm the roles of these two genes and, consequently, the central role of a specific immune response pathway, in the development of AMD…We now have clear targets for early therapeutic intervention".

 

Comment: These results extend previous understanding of the genetic causes of AMD by identifying an additional gene and risk-associated variants within that gene. If further studies replicate the results of this publication, it will confirm the importance of a specific immune response pathway in the pathogenesis of the disease and probably aid the development of novel therapeutic measures. However, it does not provide all the answers. For example, how does the possession of particular genetic combinations affect onset and development of the disease? How do genetic and environmental risk factors interact to cause AMD? The research team is reportedly now seeking to identify which viral and bacterial infections may trigger the immune responses associated with the disease (see BBC news report).

30 March 2006Comparative genomics: difference of expression. Nielsen R (2006) Nature 440, 161. News and Views piece on the use of species-specific microarrays in the investigation of evolutionary change via alterations in gene expression (PubMed). RNA lost in translation. Tollervey D (2006) Nature 440, 425-426. News and Views piece on a new pathway that monitors mRNAs for errors  (PubMed). Familial mediterranean fever in Arabs. El-Shanti H, Majeed HA and El-Khateeb M (2006) Lancet 367, 1016-1024. Review of FMF, an autosomal recessive autoinflammatory disease with a high prevalence among non-Ashkenazi Jewsish, Armenian, Turkish and Arab populations (PubMed). X linked mental retardation: a clinical guide. Raymond FL (2006) J Med Genet 43, 193-200.Clinical review article (PubMed). MicroRNAs as therapeutic targets. Czech MP (2006) N Engl J Med. 354, 1194-5. Clinical implications of basic research focus review (PubMed).

read more ...

9 March 2006Copies count. Nadeau JH and Lee C (2006) Nature 439, 798-799. News and Views piece on how gene copy number variations may influence susceptibility to common disease.

Genome of an epidemic community-acquired MRSA. Enright MC (2006) Lancet 367, 705-706. Comment on research showing how genetic information passes between staphylocci and implications for human infections; see also The importance of knowing the genomes of pathogens. Editorial (2006) Lancet 36, 704.

Genetic susceptibility to coronary artery disease: from promise to progress. Watkins H and Farrall M (2006) Nature Reviews Genetics 7, 163-173. Review on the impact of genome-wide approaches in developing new prognostic and therapeutic strategies.

Roadmap to embryo implantation: clues from mouse models. Wang H and Dey SK (2006) Nature Reviews Genetics 7, 185-199. Review of current understanding of the molecular-genetic basis of mammalian preimplantation and implantation biology.  

Microarray technology: beyond transcript profiling and genotype analysis. Hoheisel JD (2006) Nature Reviews Genetics 7, 200-210. Review of microarrays and their expanding applications in genome-wide epigenetic analysis and on-chip synthesis.

 

The evolution of spliceosomal introns: patterns, puzzles and progress. Roy SW and Gilbert W (2006) Nature Reviews Genetics 7, 211-221. Review of new research on the evolution of introns.

 

Teaching resources for genetics. Haga SB (2006) Nature Reviews Genetics 7, 223-229. Perspectives guide to online resources about genetics for a range of audiences.

 

Functional mapping - how to map and study the genetic architecture of dynamic complex traits. Wu R and Lin M (2006) Nature Reviews Genetics 7, 229-237. Perspectives piece on the use of a statistical mapping framework to investigate the interplay between gene actions or interactions.

read more ...