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Sequencing the honeybee is seen as important as it is, according to the authors, “…a key model for social behaviour and essential to global ecology through pollination.” In agricultural terms honeybees are vital, “…pollinating 90 major commercial crops in North America alone.” [Check E (2006) Nature 443, 893]. However, pollinating species are in danger; the honeybee population has declined 30% over the past 20 years. Having the genome sequence should enable scientists to breed new strains of honeybee, for example, that are resistant to the varroa mite, a parasite that can destroy an entire bee colony.
From the human health and societal perspectives, the honeybee will serve as a model organism for the study of issues such as immunity, allergic reaction, antibiotic resistance, mental health, longevity, social instincts and behavioural traits [see NIH press release]. The honeybee’s social behaviour is especially intriguing, as it has parallels in everyday human activities. Honeybees are an ideal model organism in which to study social biology, say scientists [see Check]. Investigators will be interested in finding out whether the mechanisms that control bee behaviour can tell us more about human behaviour.
30 October 2006A new report, Genomic Tests for Ovarian Cancer Detection & Management, has been released by the US Agency for Healthcare Research & Quality (AHRQ). Produced in collaboration with the CDC Division of Cancer Control and Prevention and the National Office of Public Health Genomics, the report considers evidence for the benefits of genomic testing in ovarian cancer. Conventional strategies for the detection of ovarian cancer are not very effective, so that there is increasing interest in the use of tests to identify genomic, proteomic or other biological markers of ovarian cancer, typically to identify the presence of risk-associated genes (such as BRCA1 and BRCA2), genetic tumour markers (such as CA-125, cancer antigen 125) or genetic changes that may predict response to therapy in affected women.
A review of published literature found little evidence that genetic tests other than CA-125 or BRCA1/2 had been properly evaluated. The researchers reported that they did not find any studies to indicate reduced mortality or improved quality of life among women with ovarian cancer where genetic tests were used to guide clinical management. There were also few studies on the potential harms of gene-based tests for ovarian cancer, such as “the psychological impact of false-positive tests or delays in treatment that can result from a false-negative test” (see Medical News Today report). An Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group will use the new report to develop recommendations on the potential utility of new genomic and proteomic tests for ovarian cancer detection and management, and to identify gaps in knowledge and the important needs for future research (see press release).
A further four reports on the evidence for genomic tests for specific conditions will be produced as part of the inter-agency collaboration. This series of reports are intended to provide valuable evidence-based guidance to inform clinicians and public health specialists about the appropriate applications of genetic testing for particular diseases.25 October 2006The Economic and Social Research Council (ESRC) has announced continued funding for its three research centres studying the societal and economic context of genomics. CESAGen, EGENIS, INNOGEN, together with the ESRC Genomics Policy and Research Forum and the ESRC Attitudes to Genomics Survey, form the ESRC Genomics Network. Begun in 2002, this new investment will extend the funding of the centres for a further five years, from 2007 to 2012.
Each centre has a different, while related, focus. The Centre for Economic and Social Aspects of Genetics (CESAGen) is a joint collaboration between Lancaster and Cardiff. Over the next few years, researchers will “…address the social, economic and policy aspects of development in genomics,” specifically looking at health service delivery, food and nutrition, behaviour and criminal responsibility and human enhancement. The ESRC Centre for Genomics in Society (EGENIS), located in Exeter, looks at “…the social implications of contemporary genetic science.” Areas to be examined include nutrigenomics, systems biology and gene therapy. The ESRC Centre for Social and Economic Research on Innovation in Genomics (INNOGEN) is also a collaborative effort, between Edinburgh University and the Open University. Researchers investigate “…the evolution of genomics and life sciences and their far-reaching social and economic implications,” working in collaboration with industry, private and public interest groups, policy makers, and citizens.
Adrian Alsop, Director for Research, Training and Development for the ESRC, commented, “We are delighted to announce this second phase of funding for our genomics research centres.…Insights from social science explain how genomic technologies can benefit our health service and realise the potential benefits that they can bring to developing countries.”
20 October 2006The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the US National Institutes of Health (NIH) have announced new details of The Cancer Genome Atlas (TCGA) Pilot Project, a $100 million collaborative initiative intended to assess the feasibility of using large-scale genome analysis technologies to identify important genetic changes involved in cancer (see previous news story). The project will be studying lung, brain (glioblastoma), and ovarian cancers.
A network of seven newly selected Cancer Genome Characterization Centers (CGCCs) will use “advanced genome analysis technologies to identify major changes in the genomes of the cancers chosen” (see press release). In addition, a Data Coordinating Center (DCC) to track, check and make publicly accessible data produced by the TCGA has been established, along with a Biospecimen Core Resource (BCR); genome sequencing centres have yet to be selected.
NCI Deputy Director for Advanced Technologies and Strategic Partnerships Dr Anna Barker said: “TCGA will analyze genomic changes in lung, brain, and ovarian cancers with a goal of identifying all alterations in genes for these three tumors - especially those that can serve to differentiate cancer subtypes. The Cancer Genome Characterization Centers will identify genomic aberrations, such as copy number changes and/or chromosomal translocations that will enable the development of targeted diagnostics and therapies for cancer patients, and provide a path to more personalized cancer medicine”.
20 October 2006The NHS Sickle Cell and Thalassaemia Steering Group are holding an event in Westminster to celebrate the fact that screening for the genetic disorder sickle cell anaemia is now offered to all newborn babies in England, and to launch new standards and guidelines for the clinical care of sickle cell diseases in childhood. These have been developed by the UK Forum for Haemoglobin Disorders in conjunction with the NHS steering group, the Sickle Cell Society, the British Society of Haematology, and the Royal College of Paediatrics and Child Health; they provide the first formal clinical quality standards for those receiving treatment for sickle cell disease and “signify a first step in a process designed to integrate screening and care of those affected by sickle cell disorders”.
Sickle-cell disease one of a group of haemoglobinopathies, inherited blood disorders that primarily affect people of Afro-Caribbean origin, but are also present in other populations. Briefly, the guidelines set out measures for the implementation of antenatal and newborn screening, and for the linking of information between the two stages of screening. The programme standards cover issues not only of practical implementation, but also of patient satisfaction. It is intended that the new standards, combined with those for another important genetic haemoglobinopathy, thalassaemia, should provide a foundation for the development of nationwide quality care (see stakeholder briefing); they are supported by the Professional Education for Genetic Assessment and Screening (PEGASUS) scheme, which facilitates training of health professionals involved in antenatal and newborn screening.
Screening for sickle-cell disease, which is performed as part of the standard ‘heel-prick’ neonatal screening procedure, is expected to identify more than 300 affected babies each year in England. Early identification of the disorder minimises complications and mortality in such children, for example by allowing prompt intervention with penicillin to prevent overwhelming infections. Screening programmes are already in place in area of England with the highest prevalence, but it is intended that national coverage will be complete by the middle of 2007 (see BBC news). Early antenatal testing to identify mothers who are carriers of the disease should also be offered; couples found to be at high risk of having an affected child are offered counselling and prenatal diagnosis.
16 October 2006The US Foundation for the National Institutes of Health (FNIH) has announced the first six studies of common diseases selected for whole genome analysis by the Genetic Association Information Network (GAIN). The Genetic Association Information Network is a public-private partnership between the US National Institutes of Health (NIH), the Broad Institute (Massachusetts Institute of Technology and Harvard University) and commercial enterprises including Pfizer, Affymetrix, Perlegen Sciences and Abbott.
The analysis will seek to identify genetic factors that influence susceptibility to and progression of the selected diseases, by comparing genotypic information from 1,000-2000 normal, healthy volunteers and the 1,000-2000 patients with the condition being studied. It is hoped that the identification of key disease-associated genetic variants will lead to a better understanding of disease pathogenesis and ultimately to the development of new and improved methods of prevention, diagnosis and treatment. The six diseases to be studied are:
These projects were selected following peer, technical and ethical reviews; GAIN will provide the genotyping services and also fund analysis of the new genetic data by the project leaders. Results will be made available to the research community “in keeping with the principles pioneered by the Human Genome Project” (see press release).
Francis S. Collins, chair of the GAIN Steering Committee and director of the National Human Genome Research Institute commented: "GAIN is a critical first step in identifying the genetic factors that influence disease susceptibility and health, and it is essential to choose studies that offer the best possible potential to find these factors in common diseases…I'm extremely pleased that GAIN will also be making the results from such high-quality studies in these very important diseases easily available to all researchers".
5 October 2006The X-Prize Foundation, a US-based organisation that seeks to foster innovation by running high profile competitions to reward novel solutions “to the grand challenges of our time” has launched what is reportedly the largest medical prize in history. The Archon X-Prize for Genomics, worth $10m, will be awarded to the first team of scientists to devise a form of rapid genetic sequencing that allows them to decode 100 human genomes in just ten days. The winning team will be paid to map the genetic sequences of a group of 100 celebrities, benefactors and members of the public.
Despite the massive acceleration in sequencing capacity and speed over the last fifteen years, producing a full human genome sequence still takes several months and costs in excess of a million pounds. However, faster, cheaper sequencing technologies would allow multiple different genomes to be sequenced, and a database of this information could be used to learn more about gene-environment interactions and gene-disease associations. In 2004, the US National Human Genome Research Institute (NHGRI) launched a “$1000 genome” project, providing funding for research intended to develop innovative sequencing technologies to reduce the costs of genome sequencing (see previous news story); the ultimate goal is to reduce the sequencing costs for a mammalian genome to just $1000, with an interim goal of $100,000. This week the NHGRI announced research awards in excess of $13.3 million as part of this initiative (see press release). If whole genome sequencing could be achieved for under $1,000 or less, it is envisaged that it could form part of routine medical assessment and potentially allow personalised health care, whereby prevention and treatment of illness could be tailored to each individual recipient. The new prize underlines further the belief in the value of affordable, rapid genome sequencing for human health and healthcare.
However, there are concerns about the privacy of genomic information, especially if it were to become more widely available, and the potential for discrimination against individuals on the basis of such information. NHGRI head Dr Francis Collins commented: "There are real questions here of the benefits versus the risks. We need appropriate protections for people, and we need the public to engage in a policy debate". It has been suggested that the Archon X-Prize for Genomics might stimulate movement of the US Genetic Non-Discrimination bill, approved by the Senate in 2005 (see previous news story) but currently stalled in the House of Representatives (see BBC news report).
2 October 2006The 2006 Nobel Prize for Medicine has been awarded to the US researchers Dr Andrew Fire (Stanford University) and Dr Craig Mello (University of Massachusetts), for their discovery of RNA interference (RNAi). Published in Nature in 1998, the discovery of RNAi revolutionised understanding of the role of RNA in the regulation of gene expression. In brief, RNA interference is a gene silencing mechanism that prevents expression of transcribed genes (conversion from messenger or mRNA molecules into protein products) via double-stranded RNA molecules; the dsRNAs activates cellular machinery that targets and selectively degrades mRNAs identical to the dsRNA sequence. Targeting specific mRNAs for destruction prevents expression of the corresponding gene.
Animal and plant genomes contain multiple microRNAs (miRNAs) that encode small portions of coding sequence, and which allow the formation of double-stranded RNAs. It is now known that this form of genetic regulation via miRNAs is important in normal cellular processes, and in the growth and development of organisms. RNA interference is also an important basic cellular defence mechanism against viruses (many of which have double-stranded RNA genomes) and mobile genetic elements such as transposons, which move via processes including the formation of double-stranded RNA intermediates and can disrupt important genomic sequences.
The Nobel citation issued by the Swedish Karolinska Institute stated: "This year's Nobel Laureates have discovered a fundamental mechanism for controlling the flow of genetic information" (see press release). The discovery has already lead to a wide range of research applications, using specifically designed dsRNA molecules to silence specific genes; there are also prospects for harnessing the process as a therapeutic tool to treat genetic disorders, viral infections and a range of other diseases.
3 October 2006Somatic cell nuclear transfer (SCNT) or reproductive cloning, was the technique used to create ‘Dolly’ the sheep, and is based on the transfer of a nucleus from an adult cell into an oocyte from which the nucleus has been removed. However this process is usually very inefficient, with a success rate of between 1-5%. It had previously been thought that this was due to the use of donor nuclei from somatic cells, as the use of nuclei from embryonic stem cells achieved a cloning efficiency that was five to ten times higher.
In a new report by Sung et al., the authors challenge this viewpoint. The researchers compared cloning efficiency between cells from the haematopoietic cell lineage at different stages of differentiation. The least differentiated were haematopoietic stem cells (HSCs), a type of adult stem cell, followed by haematopoietic progenitor cells (HPCs) and then fully differentiated granulocytes. They found that cloning efficiency increased as the level of differentiation also increased, with the highest rate of blastocyst development seen from cells that had granulocyte donor nuclei. Furthermore the group demonstrated that live mouse pups could be produced via SCNT from these terminally differentiated adult cells, the first time that this has been reported.
Comment:
The implications of this work remain unclear, although they do appear to demonstrate that it is not necessary, and may well be experimentally detrimental, to use adult stem cells as nuclei donors in SCNT. However there is also evidence that demonstrates that using donor nuclei from embryonic stem cells results in the most successful SCNT. This study will need to be replicated using human cells in order to fully evaluate its impact, but it does provide the potential for developing new SCNT techniques that do not require the harvesting of adult stem cells, but can use fully differentiated cells as nuclei donors instead.
Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer L-Y Sung et al. Nature Genetics Published online 1 October 2006 doi:10.1038/ng1895
26 October 2006A new publication by Humphries et al. in the Journal of Molecular Medicine examines the association between two common variants in the TCF7L2 gene and type 2 diabetes (T2D). This study follows up earlier work conducted by Grant et al. in Icelandic, Danish and European-American populations (see our rapid response to this earlier study). Humphries et al. investigate the role of these two variants in three well established cohort studies of European White, Indian Asian and Afro-Caribbean origin.
The study used both prospective and case-control designs to compare the risk association between the different genotypes in T2D cohorts of the three ethnic groups with non-diabetic ethnically-matched subjects. Subjects were adjusted for age, body mass index, systolic blood pressure, triglyceride and C-reactive protein levels. One of the two gene variants (IVS3C>T) was found to nearly double the risk of T2D, and the other (IVS4G>T) was found to have a smaller, but still significant effect across all three groups. The authors speculate that the mechanism by which the TCF7L2 gene affects T2D risk may be due to alterations in Wnt signalling, since TCF7L2 is a transcription factor in this pathway, but the study did not investigate this.
Comment: The study is well presented and provides external replication of the earlier findings by Grant et al. in three additional population groups further strengthening the support for the possible role of the TCF7L2 gene in T2D. The authors report possible limitations in their study, such as the small number of individuals who developed T2D, and also stress that the data presented for the Afro-Caribbean subset should only be regarded as preliminary. In addition to this they also report that further research is warranted into both the risk variants within the TCF7L2 gene and the mechanism by which the risk of T2D is altered. Once the risk variants and molecular pathway/s by which they act have been identified, specific treatments can be tailored to the carriers of the causal defect(s), and although these studies provide very exciting evidence for the role of TCF7L2, at this stage the prospect of treatments is still somewhat distant.
This article was written by Gurdeep Sagoo and Simon Leese.
23 October 2006A new advance online publication in Nature Medicine outlines work in developing gene expression signatures that predict sensitivity to chemotherapeutic drugs [Potti A et al. (2006) Nature (Advance Online Publication) doi:10.1038/nm1491]. The choice of chemotherapeutic regimen for the treatment of cancers is a complex one; finding the optimum drug or drug combination that will combat the precise tumour in an individual patient with maximal efficacy and minimal side-effects is a key factor in the success of treatment. Biological treatments tailored to the genetic nature of the tumour such as Herceptin® (Trastuzumab), an antibody-based therapeutic that recognises and specifically targets breast tumours expressing the HER2 protein, are starting to emerge, and there is increasing interest in using genomic information to permit more effective chemotherapy too.
A team of researchers from Duke University in the US studied previously published gene expression information on clinical responses to chemotherapy (sensitivity or resistance to the drug docetaxel) to develop a specific gene expression pattern, or signature, that could predict responses to docetaxel. This was combined with independent data on the sensitivity of different cancer cell lines to the drug, and the predictive ability of the docetaxel response signature found to exceed 80%. The researchers then performed a similar process to develop gene expression profiles to predict responses to a range of other cytotoxic chemotherapeutic drugs, including 5-fluorouracil (5-FU), paclitaxel and cyclophosphamide. These too were found to have a predictive accuracy in excess of 80% for response to the specific drug in question. Since combinations of chemotherapeutic drugs are commonly used to treat tumours, the group also used data from studies that used different combinations of drugs for the treatment of breast cancer; they produced genomic signatures that could distinguish well between responders and non-responders for most individual drugs. Combination signatures to predict response to the combined chemotherapy showed “statistically significant” capacities to distinguish between responders and non-responders.
The researchers conclude that genomic signatures of chemosensitivity have the capacity to predict therapeutic response in individuals receiving either single agent or combination chemotherapy. They also report that gene expression signatures can be used to identify the activation of specific oncogenic pathways within a tumour, information that could direct the choice of chemotherapeutic drugs and other targeted therapeutic drugs in order to avoid drug resistance and maximise therapeutic impact.
Comment: This work is preliminary and would require validation in much larger datasets before the gene expression signatures could be used as a reliable guide to any form of cancer therapy. However, as a proof-of-concept the results are encouraging, suggesting that personalised cancer medicine may be feasible, opening up prospects for rational treatment decisions based on genetic information.
3 October 2006The major histocompatibility complex (MHC) is a set of genes on chromosome 6 that are highly polymorphic; multiple alternative genetic variants (alleles) are present in human populations. Many of the Human Leukocyte Antigen or HLA genes within the MHC region play a crucial role in the human immune system; specifically, in the processes by which the body distinguishes ‘self’ and foreign or ‘non-self’ cells or agents and targets the latter for destruction. HLA variation is a key factor in determining individuals’ susceptibility to multiple infectious and autoimmune diseases, such as malaria, SARS, TB, diabetes, multiple sclerosis, psoriasis and Crohn’s disease. No other region of the human genome has been associated with susceptibility to so many diseases. However, identifying the exact genetic variants associated with disease is extremely difficult due to the high degree of genetic diversity in human populations with respect to this region, and a high level of variation in linked, neighbouring alleles that effectively masks that of the causal alleles.
A new publication in Nature Genetics sets out a detailed map of human genetic variation in the form of haplotypes across the extended MHC region, intended to form a resource for future genetic association studies [de Bakker PI et al. (2006) Nat Genet. 38,1166-1172]. The international team of researchers determined the genetic sequences and mapped more than 7500 single nucleotide polymorphisms (SNPs) in the MHC region from 361 individuals, derived from four population groups (African, European, Chinese and Japanese ancestry). The team identified useful ‘tag’ SNPs that effectively capture most of the common variation in the MHC region, and suggest that analysis of these selected SNPs within the HLA genes may not only be of use for disease association studies, but also as an improvement to current methods of HLA typing; this is the process by which some of the key human leukocyte antigens are identified for matching between donors and transplant recipients, to minimise the probability of transplant rejection due the recognition as ‘non-self’ by the recipient’s body.
Comment: Senior author Dr John Rioux of the Universite de Montreal said: "This new map will be a key resource for researchers to use to find genes affecting health, disease, and responses to medications" senior author (see press release). Researchers in Canada and the Canada and the US have already begun efforts to use the new, publicly available resource (available from the Montreal Laboratory in Genetics and Genomic Medicine of Inflammation) to identify genetic risk factors for common immune-mediated diseases. This work complements and extends data from the International Haplotype Map or HapMap project, and is a prime example of how large-scale sequencing and analysis projects can provide the starting point for research that will, hopefully, generate reliable and useful information on the links between specific genetic variants and disease susceptibility.
17 October 2006Investments in Cancer Genomics: Who Benefits and Who Decides. Foster MW, Mulvihill JJ and Sharp RR (2006) Am J Public Health [Epub ahead of print]. Piece on decision-making for the US Cancer Genome Atlas project, and how public involvement and rigorous policy analysis allow a fair allocation of scientific resources (PubMed).
The post-Human Genome Project mindset: race, reliability, and health care. Kimmelman J (2006) Clin Genet. 70, 427-32. Essay report from a workshop on genetic diversity and science communication, arguing that there are two different views of human genetics, typified by an increasing interest in genetic differences, and a recognition of the difficulty in translating genetic research into medical or public health applications (PubMed).
Assessing risk assessment: genetic testing and screening for complex disease. Cox S (2006) Clin Genet. 70, 438-44. Essay report from a workshop on genetic diversity and science communication, considering the need to consider the ways in which risk is constructed, perceived and communicated in different contexts, and the implications of this (PubMed).
Public health. Genomics and medicine at a crossroads in Chernobyl. Ginsburg GS, Angrist M and Cook-Deegan R, Science 314, 62-3. Policy forum article proposing that the imminent construction work at the site of the Chernobyl nuclear disaster provides a “unique opportunity to examine the genome, environmental exposures, and their interaction and impact on human health” by combining genomic research with public health measures for the ground workers (PubMed).
Mendelian and complex genetics of susceptibility and resistance to parasitic infections. Campino S, Kwiatkowski D, Dessein A (2006) Semin Immunol. 18, 411-22. Seminar piece on the challenges in discovering the complex genetic basis of susceptibility and resistance to parasitic infectious diseases, involving multiple interacting host and parasite genes combined with environmental factors (PubMed).
16 October 2006The genetics of health. Nadeau JH and Topol EJ (2006) Nat Genet. 38, 1095-8. Commentary suggesting that the genetics of health (as opposed to the genetics of disease) is a neglected area of research, and proposing that disease-free individuals known to be at increased genetic risk of disease should be tested for modifier genes and protective alleles (PubMed).
Body of research - ownership and use of human tissue. Charo RA (2006) N Engl J Med. 355, 1517-9. Perspective piece on the issue of whether or not we can be said to own our own bodies, and implications for research and other uses of human tissues (PubMed).
NHS maternity units should not encourage commercial banking of umbilical cord blood. Edozien LC (2006) BMJ 333, 801-4. Analysis and comment article arguing that the increasingly common practice of private cord blood banking should be curbed (PubMed).
Multiple sclerosis: putting two and two together. Trowsdale J (2006) Nat Med. 12, 1119-21. News and views article on recently revealed epigenetic effects in multiple sclerosis tissue damage (PubMed).
(Re)modeling the transcriptional enhancer. Halfon MS (2006) Nat Genet. 38, 1102-1103. News and views article on recent applications of computer modelling to predict how genetic regulatory elements function, with unexpected results (PubMed).
New evidence that DNA encodes its packaging. Ercan S and Lieb JD (2006) Nat Genet. 38, 1104-5. News and views article on recent research showing the influence of DNA sequence on the packaging of DNA into nucleosomes, which has suggested the existence of nucleosome positioning signatures within the DNA of some genes (PubMed).