News

11 April 2006Last year’s report by the UK Stem Cell Initiative, led by Sir John Pattison, included a recommendation that a UK-wide national Stem Cell Cooperative be created. This Cooperative should aim to “maximise the cross-fertilisation between those involved in the sub-disciplines of UK stem cell research”.

 

The Government, although accepting all of the report’s recommendations, has yet to allocate specific funds for the establishment of a Cooperative. However the Research Councils have collectively established a fund to begin to move this specific recommendation forward. The BBSRC has now launched an online consultation on behalf of the UK Research Councils, the Department of Health, the Office of Science and Innovation, and the Department of Trade and Industry to “provide stem cell researchers with the opportunity to express their opinions on how they would like to see the UK Stem Cell Cooperative established and run”.

 

The consultation is open until the end of May, and seeks responses to questions such as what activities the Cooperative should be involved in, and how it should be run.

 

The online consultation questions and instructions on how to respond can be found on the BBSRC website.

http://www.bbsrc.ac.uk/society/consult/ukstemcells/Welcome.html

 

28 April 2006Researchers have shown that a majority of the public support the use of personally identifiable data by cancer registries for public health research [Barrett, G et al, BMJ online 28/04/06]. They conducted their study to determine the public’s attitude on using personal medical data without individual consent. This has recently become an area of contention. It has been assumed by regulators that people want to be asked their permission for every use of their personal data, in research as well as clinical care. But there has been little research to support this assumption. Public health researchers have claimed that requiring individual consent hinders their research. Therefore researchers “sought the views of the British public on the acceptability of identifiable information being used for public health purposes in the context of a real example,” the National Cancer Registry. Registries across the United Kingdom collect data about people suffering from cancer, using it to monitor trends for people getting cancer and trends in cancer survival, for example.

 

The authors found that 72% of the approximately 3000 people interviewed did not feel it was an invasion of their privacy if their personal data (postcode or name and address) was forwarded to the National Cancer Registry. 81% would support legislation requiring the registration of all cancer cases with the Registry. Also, over 80% of respondents did not feel that receiving a letter from their doctor asking them to participate in a research study was an invasion of their privacy. The authors recognised that this study only addresses one form of public health research using personal data. However, they believe this study suggests, “that the confidential use of identifiable health information for research without individual’s consent has not so far damaged the public’s trust.” 

 

It has been argued that a narrow interpretation of the provisions of the Data Protection Act 1998, which safeguards the processing of personal data, has made it increasingly difficult to conduct public health research. In the cases of studies that require a large number of participants in order to be useful, requiring explicit consent from each person can be time intensive for staff and expensive. Recently, the Academy of Medical Sciences (AMS) published a report on the subject, Personal data for public good: using health information in medical research. The AMS stated their evidence “…shows that advances in this field are increasingly inhibited by inappropriate constraints on the use of personal health data.” The AMS has called for a reinterpretation of the legal framework and engagement with the public on this issue. Barrett and colleagues also call for additional research into public attitudes towards use of their personal medical data in research.

27 April 2006On 25 April 2006, the Human Tissue Authority (HT Authority) launched the framework for licensing certain activities prescribed by the Human Tissue Act. The HT Authority was established in April last year following the enactment of the Human Tissue Act in 2004. This legislation empowers the HT Authority to regulate the removal, storage and use of human material from whole bodies to single cells, from the living and the dead (with limited exceptions). These activities include the storage of human tissue (for research and other purposes regulated by the Act) and post-mortem and anatomical examinations. The HT Authority has published compliance reports that will form the basis for potential licence applications. The HT Authority is also the competent authority for the licensing of therapeutic tissue banks under the European Directive on Tissues and Cells. Anybody storing human tissue or cells for human application is required to have a licence from 7 April 2006.

 

Another plank of the HT Authority’s work will be in relation to the regulation of transplantation, superseding the Unrelated Live Transplants Regulatory Authority (ULTRA). The Act provides for new forms of transplantation between unrelated living donors to take place (by pooling potential donors and recipients, and allowing altruistic or stranger donation to take place). These donations are expected to save or improve the lives of dozens of people a year. It is fitting that the HT Authority announced on 25 April 2006 that its first licences were issued to banks storing tissue for transplants.

 

The approach of the HT Authority has been to build on the work of other regulatory agencies – thus the fee structure for licences for therapeutic use reflect the extent to which establishments are already accredited by regulatory bodies such as the Medicines and Healthcare Products Regulatory Agency (MHRA) (and the licence fees vary proportionately ranging from £4500 to £250). The licence fees for other activities to be licensed by the HT Authority from 1 September 2006 are likely to adopt a similarly proportionate approach – building on current regulatory inspections.

 

Although the HT Authority has provided welcome advice to applicants, the entire scope of the regulatory framework remains unclear, because the Codes of Practice that will provide detailed guidance on the implementation of the Act are awaiting final approval from Ministers and Parliament. Also the regulations governing some of the exceptions to the requirement for licensing have not yet been published. Without these being available it is difficult to assess the full impact of the licensing regime on potential applicants. The requirement for licences to be site, purpose and person specific will require those holding tissue to consider carefully how responsibility for compliance should be apportioned between organisations. This will almost certainly require reviewing standard operating procedures, contracts, and training needs at personal and organisational levels.

24 April 2006The Ohio Supreme Court in the US ruled this month that parents may sue on the basis of medical malpractice in the event of negligent genetic counselling or the negligent failure to diagnose a severe or fatal condition in the fetus that would have caused them to seek an abortion. This decision arose in response to the suit of couple whose eight year-old son was born with trisomy 22, a genetic condition that means he is severely disabled.

 The child’s parents sought genetic counselling and testing prior to his conception, which indicated that the mother had a balanced translocation of chromosomes 11 and 22, putting her at risk of having children with more serious chromosomal disorders. The mother therefore underwent a chorionic villus sampling (CVS) test during pregnancy, which reportedly indicated that the fetus was a female with the same balanced translocation as the mother, which would not cause significant disability. Subsequent ultrasound tests reportedly showed normal fetal development. The parents alleged that because fetal karyotype appeared to match that of the mother, the CVS procedure had sampled maternal rather than fetal tissue. They claimed that the Children’s Hospital Medical Center in Cincinnati had  “negligently performed and interpreted the diagnostic tests and that they were negligent in their failure to recommend further tests that would have revealed Matthew’s genetic abnormality” (see law report) with the result that they were denied the option to terminate the severely affected pregnancy. They claimed damages for the costs of pregnancy and delivery, of raising and supporting a disabled child, and for the emotional and physical suffering associated with having a severely disabled child.

 However, although the court allowed the claim for ‘wrongful birth’ to stand, it ruled that only those costs associated with pregnancy and birth could be claimed for, overruling a lower court decision that the parents could sue for the additional costs of raising their disabled child over those for raising a normal child. Courts have been reluctant to countenance such claims on policy grounds, particularly claims for ‘wrongful life’ – where an unhealthy child born following negligent genetic counselling or testing argues that he or she has been damaged by being born at all. This reluctance also extends to claims by parents for the financial burden of caring for a severely disabled child where the cause of the disability is genetic in origin. However damages for ongoing care costs as part of a ‘wrongful birth’ suit have been awarded by a few US states where the disabling condition arose during delivery.

24 April 2006Research Councils UK (RCUK) has published its Science in Society strategy. The RCUK, a partnership of eight research councils that are funded through the UK Office of Science and Technology, has recognised the importance of engaging the public with scientific research and researchers. Their ‘highlights booklet’ shows past achievements and details particularly successful projects; the strategy document sets out future plans in this area.

 

The strategy consists of four aims. The first is to identify public attitudes towards the conduct of research and to foster debate. This will involve launching a programme of public engagement activities on various topics of cross-Council relevance. This programme should help the Councils identify upcoming trends and issues on which to focus in the future. The second aim is to engage with young people, encouraging them to follow careers in research and development. The Council will be developing a programme of Continuing Professional Development for science teachers, “encouraging them to transmit their enthusiasm to their students.” Strategic partnerships with other organisations will provide extra-curricular activities for post-primary students to encourage continued participation in science. A three-yearly external, independent review of the Councils’ activities in education will seek to validate their efforts in relation to the STEM (science, technology, engineering and maths) curriculum being taught in schools as well as other STEM-related activities.

 

The third aim focuses on encouraging researchers to interact with the public. This will include funding, training and best practice support to enable researchers funded by the Councils to actively engage with the public. The Councils will strive to support and reward their efforts, for example by setting up, with the Higher Education Funding Council for England (HEFCE) and other partners, a reward scheme for public engagement activity. Finally, the fourth aim is to increase awareness of Research Council funded research and the ‘scientific process’ among non-specialist audiences. Current activities, such as involvement in regional science festivals and National Science Week, will continue and be expanded. There are plans to determine the possibility of conducting a large-scale media project in collaboration with the BBC.

 

Professor Ian Diamond, chair of the RCUK, has said in a press release, “The Research Councils invest large amounts of public money in research that affects everyone’s lives. By working together to actively engage with the public, who ultimately pay for the research we fund, we aim to raise awareness of science and innovation and find out what matters to them.”

24 April 2006A new international collaboration between four leading Scottish universities (Aberdeen, Dundee, Edinburgh and Glasgow), NHS Scotland (Grampian, Greater Glasgow, Lothian and Tayside) and the pharmaceutical multinational Wyeth Pharmaceutical has been launched. The Translational Medicine Research Collaboration is funded by Wyeth (around £33 million over five years) and Scottish Enterprise (up to £17.5 million), and will focus on developing novel tests for the diagnosis and monitoring of diseases such as cancer, heart disease and depression using biomarkers. Biomarkers (proteins or other cellular products that can be measured in minimally invasive ways, such as in blood or urine samples) can be used to follow the progress of patients during treatment.

The Collaboration will also involve efforts to facilitate the rapid transfer of new drugs and other treatments from the laboratory into the clinic, and on pharmacogenetics, seeking to identify good and poor responders to specific drugs to enable clinicians to use the safest and most effective drug for a given patient and condition. The Collaboration will comprise a central core Research Laboratory (based at the University of Dundee) linked to centres of excellence in each of the four University Medical Schools for clinical research. The initiative also builds on the development of a new Clinical Research Centre network across the four universities and the NHS regions. The Scottish Enterprise funding will be used to set up a new company to act as a link between the participating organisations (see BBC news report)

Executive Vice President of Wyeth Research Frank Walsh said: "The Translational Medicine Research Collaboration represents a truly novel concept in industry-academic-government partnership, and we are delighted to be the major pharmaceutical partner in this relationship. Translational Medicine is key to the successful development of the next generation of innovative medicines which will truly make a difference for patients the world over" (see news report).

6 April 2006The Medical Research Council (MRC) and the Wellcome Trust have released a new report, ‘Access to Collections of Data and Materials for Health Research.’ The report, written by Dr William W. Lowrance, reviews “…various issues surrounding research access to population-based collections of data and materials in the UK.” The funding organisations commissioned Dr Lowrance to provide information on the extent to which current access arrangements for these collections were standardised, whether there was scope for greater standardisation, the possibility of a model governance structure and whether there was scope to develop guidelines in this area.

 

Dr Lowrance reviewed the access arrangements for a variety of collections, supported by the MRC and the Wellcome Trust, separately or in partnership. Those collections included UK Biobank, the Southampton Women’s Survey and Generation Scotland, as well as many more. The author reports that current access arrangements are not standardised but have much in common. There is scope for greater standardisation, for example in standardising core terms of access and material transfer agreements. Oversight committees oversee most collections; a model governance structure might be built using these as examples. The author reports that, “clarification and revised guidance are urgently needed on aspects of consent, confidentiality and anonymisation.” Other guidance is also needed.

 

The author put forward many arguments for why increased access to these collections of data and materials would be valuable. Input from other researchers could add informational value to collections, increasing the return on investment and increasing the possible health benefits. Access can promote scientific openness, enabling replication of studies while reducing duplication of effort. The need for new samples may be minimised as existing ones can be better exploited. As collections are used, their ‘richness’ increases as they are analysed in new and different ways. However, the author concludes, if access is to be increased, the following must be done:

• The original promises made to participants must be kept
• The public and scientific integrity of the project must not be jeopardised
• The interests of the developers and custodians of the resource must be protected and their hard work and goodwill rewarded
• Developers and custodians must be fairly compensated for costs incurred in providing access
• Intellectual property must be managed judiciously

 

25 April 2006Pharmacogenetics, the study of genetic determinants of drug response, is hoped to represent a means of reducing adverse side effects and increasing efficacy of drug treatments, by tailoring them to individual recipients. A new paper published in Nature proposes that for this goal of ‘personalised medicine’, which requires the ability to predict how different individuals will respond to a particular drug/dose combination, pharmacogenomics alone is not sufficient, as it does not take into account important environmental influences on drug metabolism [Clayton TA et al. (2006) Nature 440, 1073-7].The authors set out a novel  'pharmaco-metabonomic' approach to personalized drug treatment, which uses a combination of metabolite profiling and chemometrics to model and predict the responses of individual subjects.

Pharmaco-metabonomics is defined in the paper as 'the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures'. Metabonomics, also referred to as metabolomics, has already been established as the process of metabolic profiling. In this study, the researchers used nuclear magnetic resonance (NMR) spectroscopy to examine the composition of rat ‘biofluids’ (in this instance urine, although blood plasma, faecal fluid or saliva might also be used) and identify and quantify key metabolites. They set out to test the theory that the pre-dose metabolic profile of an individual animal contains sufficient information to allow the prediction of aspects of drug metabolism and toxicity in that animal, without prior knowledge of the animal's genomic profile.

Urine samples from 65 rats were collected before and after the administration of a single dose of paracetamol, and metabolic profiles determined for all samples. Variation in the levels of paracetamol-related metabolites in the urine following drug administration was modelled relative to the pre-dose metabolite profiles, as was liver damage subsequent to drug delivery. Based on these data, which indicated that the ratio of paracetamol glucuronide to paracetamol (G/P) was most convincingly predictive of post-dose metabolite levels, they constructed a predictive model of metabolic response to paracetamol. A validated model for predicting post-dose liver damage was not produced, although the authors did show an association between this (in terms of the levels of three key compounds) and the pre-dose profiles.

The authors propose that this pharmaco-metabonomic approach might form the basis of a ‘future population-screening tool for selecting individuals according to their suitability for treatment with particular drugs, drug classes or drug dose’”. They note that the identification of novel biomarkers that are predictive of individual drug responses would be of value, and call for further investigation into the potential application of the technique to humans, among whom a far greater degree of genetic and environmental variation would be expected than for laboratory rats. They also envisage that optimal personalization of drug treatments may eventually involve both pharmaco-metabonomics and pharmacogenomics, whilst stressing that the applications of the former might be wider, possibly predicting individual responses to broader ‘medical, dietary, microbiological or physiological challenges’.

Comment: The authors of this paper imply that a widespread belief in the utility of genotypic factors in the assessment of probable drug responses, without consideration of environmental factors, exists; this seems unlikely, as every clinician is well aware of the necessity to consider comorbidities, comedications and other relevant issues when prescribing a drug regime. This aside, this study adds to a growing body of evidence that metabonomics may well have value in the pursuit of individualised treatments. As with pharmacogenomic profiling, for general use it would be necessary to have full profiles performed and the information stored well in advance of that data being required, however, since in general it is not practical to delay the prescription of a drug until such an analysis has been completed.

3 April 2006Researchers at Dundee University's Human Genetics Department, working in collaboration with others in Glasgow, Dublin, Seattle and Copenhagen, have identified mutations that cause a common skin disorder and predispose individuals to eczema and a related form of asthma. This work has been published in two consecutive papers in the March and April editions of Nature Genetics.

The first paper confirms the genetic cause of hereditary ichthyosis vulgaris [Smith FJ (2006) Nat Genet. 38, 337-42]. This condition, which causes the skin to become dry and scaly, is one of the most frequent single-gene disorders in humans with an estimated UK incidence of 1 in 250 children. It is an autosomal dominant genetic disorder that develops in early childhood. Around 120,000 people within the UK have a severe form of the condition, and around 5 million have a milder form. Existing evidence already strongly suggested that the filaggrin gene (FLG) was involved in ichthyosis vulgaris. Filaggrin (filament aggregating protein) is a key protein in the formation of the outer layers of the skin, especially the outermost protective barrier, which prevents water loss and blocks entry of infectious and allergenic agents. However, the long and repetitive DNA sequence of the FLG gene has previously impeded analysis.

The researchers looked at the FLG gene from seven unrelated ichthyosis vulgaris families and eight further isolated cases (for which no family history was available) from Ireland, Scotland and the USA. Using advanced forms of sequencing, they were able to identify a nonsense mutation, R501X, in affected individuals. Some patients with severe phenotypes were found to be homozygous for R501X, whilst others with milder phenotypes were all heterozygous for the mutation. Only two heterozygotes were identified with no clinical phenotype, leading to an estimate of 90% penetrance, although the authors caution that this figure may be an overestimate. Further sequence analysis of all the heterozygotes led to the identification of a second mutation, 2282del4. R501X/2282del4 compound heterozygotes showed severe phenotypes similar to those of the R501X homozygotes. Both mutations cause premature termination of the filaggrin protein. Analysis of skin samples from an R501X homozygote and an R501X/2282del4 compound heterozygote showed an identical loss of functional filaggrin protein, although a severely truncated version of the protein was present.

The combined allele frequency of the mutant alleles in the corresponding Caucasian populations was found to be relatively high at 3.7%. A semi-dominant mode of inheritance of the mutations is proposed, with incomplete penetrance, whereby heterozygotes have absent to mild ichthyosis vulgaris whilst homozygotes or compound heterozygotes for the mutant allele/s have moderate to severe disease. It is suggested that, since the number of repeats within the human FLG gene is known to vary between individuals (10–12 repeats), the presence of an expanded allele with more repeats might mitigate the effect of a mutation in the other allele.

The second paper [Palmer CN et al. (2006) Nat Genet. 38, 441-446] investigates the relationship between the filaggrin mutations and another skin condition, atopic dermatitis (eczema). Eczema is one component of atopic diathesis, an inherited predisposition towards eczema, asthma, hayfever and allergic sinusitis, or a combination of these. Up to half of individuals with ichthyosis vulgaris have some form of atopic diathesis, and 8% of eczema patients also have ichthyosis vulgaris, making the newly identified mutations strong candidates for involvement in eczema.

Eczema was found to be prevalent among individuals from the study with FLG mutations, affecting 44% of those with mild ichthyosis vulgaris (all heterozygotes) and 76% of those with severe disease (homozygotes or compound heterozygotes). None of those without a mutation had eczema and the association between the mutant alleles and eczema in this small population of 29 individuals was found to be significant. Six of these individuals also had asthma but this association was not statistically significant. The authors conclude that atopic dermatitis is inherited as a semidominant trait in these families, with high penetrance in homozygotes or compound heterozygotes, and reduced penetrance in heterozygotes, and propose that filaggrin mutations are a frequent predisposing factor in eczema.

They next analysed a group of 52 Irish children with atopic dermatitis diagnosed by a dermatologist; the combined allele frequency for FLG R501X and 2282del4 was 33%, compared with 4.2% in an unselected control population of 189 Irish individuals. This indicated a highly significant dominant risk for atopic dermatitis conferred by the mutant alleles. A large group of 604 Scottish schoolchildren and adolescents with physician-diagnosed asthma and 1,008 controls with unknown disease status were then analysed; around half of the asthma patients also had a history of atopic dermatitis. The combined allele frequency for FLG R501X and 2282del4 was 15.7%, compared with 9.6% in the control population, suggesting a dominant risk for asthma conferred by both alleles. Notably, within the asthma patient group, 72% of those with an FLG mutant allele had eczema, compared with only 46% of those without any mutant allele. The authors propose that the association between FLG variants and predisposition to asthma exists only for the subtype of asthma linked directly to eczema, and not to isolated forms of asthma. Similar results were obtained from a study of 372 Danish children.

It is proposed that the defective skin barrier caused by filaggrin mutations may increase exposure to allergenic agents, initiating chronic systemic allergic responses and leading to atopic (allergic) reactions via the skin and mucosal surfaces including the lung epithelium. The authors anticipate the discovery of additional FLG mutations involved in predisposition to atopic dermatitis and asthma in Western European populations, perhaps permitting the expression of less severely truncated forms of filaggrin protein, and potentially also in neighbouring genes. They also suggest that the FLG mutants should be studied in relation to other atopic diseases, such as food allergies and bronchial hyperreactivity.

Comment: This research provides evidence of a presumed but hitherto unconfirmed genetic association between the FLG gene and ichthyosis vulgaris, which ties in with the pathophysiological features of the disease. Further, it provides a genetic basis for the observed associations between ichthyosis vulgaris and eczema, and eczema and asthma, and gives insight into the potential pathological mechanisms that may be involved in these diseases. These associations could eventually provide novel routes for therapeutic interventions to prevent and treat the diseases; current treatment of eczema and ichthyosis vulgaris currently relies on skin creams and anti-inflammatory drugs. Lead researcher Professor Irwin McLean of Dundee University commented: "We see this as the dawn of a new era in the understanding and treatment of eczema and the type of asthma that goes with eczema as well” (see BBC news report). A ‘News and Views’ article accompanying the second publication observes that it represents a new line of research in asthma genetics, which has hitherto focused on candidate genes with effects on the immune system, and also poses the question of whether increased exposure to environmental agents that affect the skin may be responsible for the increased incidence of asthma and atopic disease in Western countries in recent years [Hudson TJ (2006) Nat Genet. 38, 399-400].

24 April 2006New genes in inflammatory bowel disease: lessons for complex diseases? Gaya DR et al. (2006) Lancet 367, 1271-1284. Review of recent advances in understanding the genetics underlying Crohn´s disease and ulcerative colitis.

Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. Evans DG, Birch JM, Ramsden RT, Sharif S and Baser ME (2006) J Med Genet. 43, 289-94. Review article looking at the risks associated with radiation therapy for genetic conditions that predispose affected individuals to tumours, such as neurofibromatosis and von Hippel-Lindau disease (PubMed).

Chromatin unbound. Vijg J and Suh Y (2006) Nature 2440, 874-875. News and views piece on a possible role of a novel protein family in genome maintenance, balancing longevity and ageing mechanisms (PubMed).

Human subjects, third parties, and informed consent: a brief historical perspective of developments in the United States. Pelias MK (2006) Community Genet. 9, 73-77. Review of the evolution of the concept of informed consent fro biomedical research in the US (PubMed).

An integrated view of protein evolution. Pál C, Papp B and Lercher MJ (2006) Nat Rev Genet. 7, 337-48. Review of the insights into protein evolution obtained using genomic technologies (PubMed).

Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Crosnier C, Stamataki D and Lewis J (2006) Nat Rev Genet. 7, 349-359. Review looking at how genetic studies of the intestinal stem-cell system have provided insights into the niche and the differentiation processes (PubMed).

High-throughput RNAi screening in cultured cells: a user's guide. Echeverri CJ and Perrimon N (2006) Nat Rev Genet. 7, 373-84. Review of cell-based RNA interference screens (PubMed).

Family-based designs in the age of large-scale gene-association studies. Laird NM and Lange C (2006) Nat Rev Genet. 7, 385-94. Review on the advantages of family-based designs for detecting genetic associations in studies of complex disease (PubMed).

Inherited epigenetic variation — revisiting soft inheritance. Richards EJ (2006) Nat Rev Genet. 7, 395-401. Perspectives article on the implications of inherited epigenetic variation for current theories of inheritance and evolutionary change, in the light of evidence that environmental influences can affect epigenetic status (PubMed).

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4 April 2006Human monogenic disorders - a source of novel drug targets. Brinkman RR (2006) Nat Rev Genet. 7, 249-60. Review article on the prospects for drug discovery using Mendelian genetics (PubMed).

Genetic medicines: treatment strategies for hereditary disorders. O'Connor TP and Crystal RG (2006) Nat Rev Genet. 7, 261-76. Review article on the use of therapies that modify gene expression as treatments for monogenic disorders, including barriers to clinical application (PubMed).

Mendelian disorders deserve more attention. Antonarakis SE and Beckmann JS (2006) Nat Rev Genet. 7, 277-82. Personal perspective on the danger of overlooking Mendelian disorders in favour of multifactorial diseases, since research into the former is likely to be of value in understanding the latter (PubMed).

Genetic susceptibility to infectious disease: lessons from mouse models of leishmaniasis. Lipoldova M and Demant P (2006) Nat Rev Genet. 7, 294-305. Review (PubMed).

Genetics of Parkinson disease: paradigm shifts and future prospects. Farrer MJ (2006) Nat Rev Genet. 7, 306-18. Review article detailing how genetic research is providing improved diagnosis and novel therapeutic strategies for Parkinsin disease (PubMed).

From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research. Solter D (2006) Nat Rev Genet. 7, 319-27. Timeline looking at the history of stem cell research in the light of its increasingly prominent media profile (PubMed).

NPHS2 gene, nephritic syndrome and focal segmental glomerulosclerosis: a HuGE review. Franceschini N (2006) Genet Med. 8, 63-75. Review on nephrotic syndrome, a form of kidney disease, and its association with NPHS2 gene variants (PubMed).

Stops along the RAS pathway in human genetic disease. Bentires-Alj M, Kontaridis MI and Neel BG (2006) Nat Med.12, 283-285. News and Views piece on how mutations in the RAS-MAPK cellular pathway provide a common underlying mechanism for a range of related human 'neuro-cardio-facial-cutaneous' (NCFC) syndromes (PubMed).

Roots and stems: stem cells in cancer. Polyak K, Hahn WC (2006) Nat Med.12, 296-300. Perspective on putative cancer stem cells, populations of self-renewing cells with tumourigenic potential that may be present in tumours (PubMed).

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