In the news

  • Newsletter Edition
The PHG Foundation monthly newsletter features news and views about genetics and genetics research, from a public health perspective. The newsletter is written by staff of the PHG Foundation.

In the news

News story   |   By Dr Philippa Brice   |   Published 9 May 2006

The Human Fertilisation and Embryology Authority (HFEA) has issued draft recommendations on widening the number of conditions for which PGD may be used, for discussion at a public meeting of the authority in Belfast tomorrow (10th May). This follows on from a public consultation on widening the scope of PGD launched in November 2005.

PGD or pre-implantation genetic diagnosis in the UK requires a license from the HFEA. All licences granted so far have been for fully (or almost fully) penetrant diseases such as cystic fibrosis and Huntington's disease. However the HFEA recently carried out a consultation on what its policy should be for late onset conditions that are incompletely penetrant and are also (at least to some extent) treatable or preventable, such as familial forms of breast/ovarian and colorectal cancer.

The BRCA1 and BRCA2 mutations are associated with a 40-80% lifetime risk of breast cancer and a 10-50% risk of ovarian cancer, whilst the MMR gene mutations linked with HNPCC carry a lifetime risk of up to 80% for colon cancer in men and 30-60% for endometrial cancer in women. The precise probabilites of a mutation carrier developing disease (penetrance) are difficult to calculate precisely and different studies have produced variable results. PGD has already been approved for two inherited types of cancer, familial adematous polyposis (FAP) colon cancer, and retinoblastoma; these conditions affect children and young adults, although effective treatments are available.

The HFEA's ethics and law committee reportedly recommends it would be appropriate, in principle, to extend the use PGD for cancer genes "because the features of the conditions are not incompatible with them being regarded as serious genetic conditions" (see BBC news report). Former British Fertility Society chair Dr Richard Kennedy commented: “As the precision and success rates of PGD increase, so the choice of avoiding the threat and consequences of cancer becomes legitimate".

However, others have expressed concern at the proposals, especially given that the forms of cancer included are of lower penetrance than previously approved conditions (and hence may never occur even in mutation carriers), and also that surveillance, prophylactic and therapeutic interventions exist to reduce the risk and impact of disease in high-risk individuals. Josephine Quintavalle, director of the group Comment on Reproductive Ethics, said: "PGD is currently nothing more than a weapon of destruction, aimed at the ruthless elimination of any embryo which does not conform to eugenic concepts of perfection…Given the permissive track record of the HFEA, it is hardly surprising that we now see them recommending the inclusion of lower penetrance cancer susceptibility on the growing hit list of undesirable genetic conditions”.

News story   |   Published 26 May 2006

A sperm donor has passed a rare genetic condition, severe congenital neutropenia (SCN), to five children born to four couples in the United States [see reports in BioEdge and the New Scientist]. People with SCN have low counts of white blood cells that kill bacteria. The condition is treatable but it is expensive, approximately $200 (£107) per day. The children will have an increased risk of developing leukaemia and will have a 50% chance of passing the disease to their own children.


Although clinics screen for some genetic diseases, such as cystic fibrosis, SCN is too rare to be included in screening. The circumstances were only discovered when researchers at the University of Michigan noticed an increased number of cases of the disease. In their article in the Journal of Pediatrics, Dr Lawrence Boxer and his colleagues report that when examining the children, they found that each child had the same mutation in the ELA2 gene. All the families had used the same sperm bank for their fertility treatment and the same donor. The clinic staff said that the donor exhibited no symptoms that would have alerted them to a problem. The researchers believe that he must have a condition called gonadal mosaicism, where his sperm would carry the mutation for the disease but the other cells in his body would not. This would explain why he appeared healthy. It is unknown how many other children have been fathered by the donor. The sperm bank has destroyed any of his remaining samples. 


Experts state it would be very expensive to screen for rare diseases such as SCN. Dr Boxer and his colleagues hope their report will help to persuade people to seek counselling before undergoing IVF or donor insemination treatment. 

News story   |   By Dr Ireena Dutta   |   Published 25 May 2006

The UK Clinical Research Collaboration (UKCRC) has produced a ‘map’ of the health research that is funded by Government and charities. Data was obtained from eleven major research funders in the UK, including the Department of Health, the Scottish Executive Health Department, the Wellcome Trust, Cancer Research UK, the Medical Research Council and the British Heart Foundation, and represented a total spend of £950million during the 2004/2005 financial year. The database and related report only included research funding relating to direct financial support of programmes and training awards, and not to indirect research costs such as administration and infrastructure.


The analysis classified research projects both by the disease area they focussed on, and the type of activity they undertook, such as prevention of disease, underpinning research, detection and diagnosis, and development of treatments. The report found that the majority of research programmes concentrated on underpinning research that was aimed at understanding normal functions and processes, and aetiology, which focussed on the risk, cause and development of disease. Over 60% of the total funds were spent on the areas of cancer, neurology, infection and cardiovascular diseases. The report also analysed the geographical distribution of research funds. It found that London was the biggest recipient (33.3%), followed by Cambridge (12.4%) and Oxford (8.9%).


The UKCRC hope to expand their database to include the research funding provided by smaller charities and the commercial sector, in order to create a comprehensive overview of the UK research environment.


The full UKCRC UK Health Research Analysis report can be downloaded from their website.


Keywords : ukFunding

News story   |   By Dr Philippa Brice   |   Published 24 May 2006

The National Institute for Health and Clinical Excellence (NICE) has issued a draft partial update of the clinical practice guideline on Familial breast cancer (CG14), in development for use in the NHS in England and Wales. This is an update to the guidance issued in 2004, and stipulates when MRI (magnetic resonance imaging) should be offered as a surveillance measure in addition to or in place of mammography, as per the original guideline. The 2004 guidelines did not recommend the use of MRI in routine surveillance on the basis of the evidence available at the time, but this has now been reviewed, with the conclusion that MRI screening can increase sensitivity (albeit at the expense of specificity) of tumour detection; other evidence has suggested that the sensitivity of mammographic screening is partially compromised among younger women due to a generally denser breast tissue.

NICE therefore reviewed the effectiveness and cost effectiveness of MRI and MRI with mammography compared with mammography alone as a surveillance measure for women at increased risk of breast cancer.It is proposed that annual MRI screening should be offered to women in different age categories according to the following criteria:

Age under 30

  • Those at exceptionally high risk (i.e. annual risk greater or equal to 1%) for example TP53 mutation carriers.

Age 30-39

  • BRCA1 and BRCA2 mutation carriers
  • Those at 50% risk of carrying a BRCA1 mutation
  • Those with a risk over ten years of greater than 8%
    Those at 50% risk from untested families with at least a 60% risk of a BRCA1 mutation (i.e. a 30% chance of carrying a mutation themselves).

Age 40-49

  • BRCA1 and BRCA2 mutation carriers
  • Those at 50% risk of carrying a BRCA1 mutation
  • Those with a risk over ten years of greater than 20%
    Those with a genetic history suggesting a risk over ten years of greater than 12% where mammography has shown a dense breast pattern

Individuals and organisations not registered as stakeholders are invited to comment on the updated parts of the guidelines via the most appropriate registered stakeholder organisation.

News story   |   By Dr Philippa Brice   |   Published 23 May 2006

The genetic sequence map of human chromosome 1, the last and largest of the 23 chromosomes to be mapped, has been completed and an analysis published in the journal Nature [Gregory SG et al. (2006) Nature 441, 315-321]. A team of over 160 collaborators in the UK and the US has taken nearly ten years to produce the finished sequence. Lead investigator Simon G. Gregory, who led the project whilst at the Wellcome Trust Sanger Centre in the UK, commented: "This achievement effectively closes the book on an important volume of the Human Genome Project" (see press release). This is because, following the release of the draft and ‘complete’ human genome sequences in 2001 and 2003 respectively, chromosome 1 is the last of the chromosomes to be fully annotated, with the positions of genes and other important structural features mapped on to the basic genetic sequence. Now, the focus of the Human Genome Project (HGP) is likely to move increasingly from direct analysis of the genome sequence, towards attempts understand the genetic contribution to health and disease.

Chromosome 1, which represents around 8% of the human genome, is dense in genes (3,141 and 991 pseudogenes); these include around one thousand novel genes (see project website). It is thought that many of these are important in human health, and further study of the chromosome may lead to the discovery of novel diagnostics and therapeutics. Several genes involved in disease have already been identified using the annotated chromosome sequence. Dr Brian Schutte of the University of Iowa in the US, who in collaboration with the UK Sanger team located a chromosome 1 gene involved in both a rare human orofacial disease and the common form of cleft lip and palate commented: “Our experience demonstrates two important issues. Firstly, gene discoveries in rare diseases can contribute directly to the understanding of common diseases. Secondly, sequencing efforts accelerate gene discovery of not only rare genetic disorders, but also common diseases that place the greatest burden on our healthcare system".

News story   |   By Dr Philippa Brice   |   Published 23 May 2006

The Human Fertilisation and Embryology Authority (HFEA) has confirmed its decision to permit pre-implantation genetic diagnosis (PGD) for the selection of embryos free from mutations associated with inherited predisposition to breast, ovarian and bowel cancers (see previous news story).

This decision was made in the light of the “aggressive nature of the cancers, the impact of treatment and the extreme anxiety that carriers of the gene can experience” (see HFEA statement), despite the fact that unlike previously approved conditions, not all those with an inherited mutation will develop cancer and others will do so relatively late in life, and that preventative and curative treatments may be available.

However, the HFEA Licence Committee will continue to assess applications individually and will take into account factors including average penetrance and age of onset of the disease, the scope for treatment, and the medical history of the family concerned.

News story   |   Published 23 May 2006

The Nuffield Council on Bioethics has published a consultation paper on the issues surrounding the ethics of public health. A Working Party, established in January 2006 to look at these issues, will consider consultation responses when writing their Report, expected in Autumn 2007. The Working Party’s terms of reference include the aim “[t]o identify and consider ethical, legal and social issues arising when designing measures to improve public health.” Their final Report will contain advice for UK policy makers based on their findings.


The Working Party has set specific questions for which they seek respondents’ opinions and the reasons behind those opinions. For example, respondents are asked if they agree that the interactions of these five factors are the main influences affecting public health: the environment, social and economic factors, lifestyle, genetic background, and preventative and curative health services. If they are, are some more important than others or should other factors be included? Respondents are also asked if they agree that the definition of public health should be, “[W]hat we, as a society, collectively do to assure the conditions for people to be healthy.”


In addition, the consultation focuses specifically on five areas of public health: infectious diseases, obesity, smoking, alcohol and the supplementation of food and water. By use of case studies and questions in each of these areas, the Working Party hopes to highlight the ethical issues and conflicts and solicit opinions. Ethical principles such as autonomy, solidarity, consent and trust as also explored. For example, on the subject of infectious diseases, should there be times when an individual’s civil liberties should be infringed in order to control an infectious outbreak? Can mandatory testing for highly infectious and life-threatening diseases be justified and if so, when? In the areas of obesity, smoking and alcohol, how can the government balance an individual’s right to self-governance (or autonomy) with the need to best utilise scarce public health resources, such as NHS services?


The consultation period ends on 15 September 2006. The Working Party welcomes comments; a copy of the consultation paper and further information can be found on the Nuffield Council of Bioethics website.
Keywords : uk

News story   |   By Simon Leese   |   Published 15 May 2006

A woman is pregnant with what is thought to be the first child in the UK to have been selected to be free of a cancer gene, The Times has reported.

Doctors at University College London (UCL) used preimplantation genetic diagnosis (PGD) to check embryos for the presence of a mutation in the RB1 gene that can lead to the development of the eye cancer retinoblastoma. PGD enables the identification and selection of embryos created by IVF to implant in the mother that are free of an undesirable mutation.

Mutations in the RB1 gene are inherited in an autosomal dominant manner, and so the naturally conceived child of a parent who carries the mutation has a 50% chance of inheriting the gene. Retinoblastoma tumours can be successfully treated if detected early enough, but the required chemotherapy and surgery can result in blindness.

The UCL team was granted the licence to test for retinoblastoma by the Human Fertilisation and Embryology Authority (HFEA)  last year, and this is the first child to be conceived under that licence. Other hereditary cancers that have been licensed for PGD by the HFEA include Familial Adenomatous polyposis coli (FAP) and Li-Fraumeni syndrome, but no pregnancies have been reported thus far from PGD for those conditions in the UK.

It should be emphasised that the current case is not connected to the draft recommendations that the HFEA announced last week, following a 2005 consultation, to use PGD for mutations that increase susceptibility to both breast and colon cancer. Unlike those conditions, retinoblastoma usually develops in early childhood, and the mutation is almost fully penetrant with about 90% of those who inherit the variant going on to develop the condition.

Nevertheless, because retinoblastoma is potentially treatable, this case is seen by some critics as a worrying extension of the use of PGD technology. Supporters however, welcomed the news as offering greater choice and reassurance for parents who have suffered from the condition themselves and who want to ensure that they do not pass it on to their children.

News story   |   Published 15 May 2006

A Board of Appeal of the European Patent Office (EPO) has published the questions it has referred to the Enlarged Board of Appeal of the EPO. Decision on these questions should enable a decision to be made on whether the Wisconsin Alumni Research Foundation (WARF) patent application, Primate Embryonic Stem Cells (EP1640448), should be approved. The application seeks patent protection for A purified preparation of primate embryonic stem cells,” amongst other claims. 


The EPO Examining Division originally rejected the application in 2004, as the method of manufacture described used a human embryo as starting material for the cell culture and necessitated the destruction of that embryo. This contravened Article 53(a) of the European Patent Convention (EPC), which states that European patents will not be granted for biotechnological inventions “the publication or exploitation of which would be contrary to "ordre public" or morality.” In addition, it was rejected based on Rule 23d(c) as inventions cannot involve “uses of human embryos for industrial or commercial purposes.” The applicants appealed; the Examining Division referred the appeal to the Board of Appeal. The Board of Appeal, after consideration, decided to refer questions for decision to the Enlarged Board of Appeal. The Enlarged Board is referred questions “in order to ensure uniform application of the law, or if an important point of law arises,” according to Article 112 of the EPC. The Enlarged Board’s decisions will be binding on the Board that referred the case.


The Enlarged Board has been asked to consider the following questions: 

  • Does Rule 23d(c) EPC apply to an application files before the entry into force of that rule?
  • If the answer to question 1 is yes, does Rule 23d(c) EPC forbid the patenting of claims directed to products (here: human embryonic stem cell cultures) which - as described in the application — at the filing date could be prepared exclusively by a method which necessarily involved the destruction of the human embryos from which the said products are derived, if the said method is not part of the claims?
  • If the answer to question 1 or 2 is no, does Article 53(a) EPC forbid patenting such claims?
  • In the context of questions 2 and 3, is it of relevance that after the filing date the same products could be obtained without having to recur to a method necessarily involving the destruction of human embryos (here: eg derivation from available human embryonic cell lines)?

In the United States WARF has already been granted two patents in this area: one for purifying and isolating primate embryonic stem (ES) cells and the other for purifying and isolating pluripotent human ES cells. This has resulted in WARF having considerable control over access to human ES cells in the United States [see Rabin, S. Nat Biotech 23(7):817-819 for further discussion]. The situation in Europe has yet to be resolved. It is unknown when a decision on these questions will come. According to a communication from the Enlarged Board, the parties have four months from 9 May to respond to the questions themselves. In addition, the President of the EPO has been invited to comment.

News story   |   By Dr Philippa Brice   |   Published 9 May 2006

Prospects for a new form of gene therapy have been presented at the European Society of Human Genetics conference in Amsterdam. Rather than attempting to insert functional copies of a defective gene, a drug is being used to enhance innate genetic compensatory mechanisms to correct the cellular defect.

Researchers from the University of Cologne Institute of Genetics investigated the effects of an epilepsy drug called valproate in patients with spinal muscular atrophy (SMA), a relatively common inherited disease. Affected individuals lack a copy of the SMN1 gene; a second gene, SMN2, produces the same gene product (survival motor neuron protein, SMN) but at much lower levels. The severity of disease is decreased when there are additional copies of the SMN2 gene present, increasing overall SMN production. Valproate was found to raise SMN levels, and in twenty spinal muscular atrophy patients who received the drug, seven showed increased levels of SMN in their blood.


Unfortunately, at this stage it is not clear whether or not the increased protein levels were the result of SMN2 gene expression specifically in motor neurons, which is where it is required for a therapeutic effect. However, researchers are optimistic; Professor Brunhilde Wirth said: "The long-term outcome could be both improved therapy to enable a better quality of life for SMA patients, and also the introduction of neonatal screening so that therapy could be started before the first symptoms appear" (see BBC news report). Dr Fred Kavalier, of the British Society of Human Genetics, commented: "This work shows that it may be possible to influence the behaviour of genes with drugs".

Keywords : euGene Therapyneuro

News story   |   By Dr Philippa Brice   |   Published 9 May 2006
The US Health and Human Services Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) has released a report, Coverage and Reimbursement of Genetic Tests and Services. SACGHS provides policy advice to the NIH Department of Health and Human Services on the complex medical, ethical, legal, and social issues arising from the development and use of genetic technologies, including genetic tests.

The new report outlines current provision of genetic testing services and policies concerning coverage and reimbursement, making recommendations for improving the present system in both the public and private sectors. This includes establishing a task group to develop guidelines for coverage decision-making, with a particular focus on the issue of testing for very rare genetic diseases. The group would also assess current evidence to establish the analytical validity, clinical validity, and clinical utility of available genetic tests, and identify any areas in which further evidence is required (see OrphaNews report).

News story   |   By Dr Philippa Brice   |   Published 2 May 2006

A new international phase II clinical trial led by Breakthrough Breast Cancer and Cancer Research UK is to look at the effect of a novel form of drug treatment for metastatic hereditary breast cancer. More than three-quarters of all cases of familial breast cancer occur in individuals with mutations in the BRCA1 or BRCA2 genes, in whom the tumours are often more advanced than in other breast cancer patients, and around a quarter will have a recurrence of cancer following initial treatment.

 The new four-year BRCA trial will monitor around 150 women from the UK, Europe, America and Australia, who have BRCA1 or BRCA2 mutations and in whom an initial breast cancer has been followed by recurrence at another site in the body, other than the lymph glands. Standard chemotherapy with docetaxel will be compared with the use of carboplatin, a platinum-based drug currently used for the treatment of ovarian (but not breast) cancer, for toxicity, response and time to progression.

 This is the first trial to treat a specific genetically-defined subpopulation of breast cancer patients; knowledge of the normal functions of the BRCA1/2 proteins in DNA repair suggested that tumours with mutations in the BRCA genes might be particularly sensitive to platinum-based drugs, which induce cross-linking between DNA molecules, and studies have supported this theory. The use of carboplatin may therefore prove to be effective in the treatment of BRCA1/2 tumours and, since the patient’s normal tissues retain functional copies of the BRCA proteins, the drug should in theory target the tumour cells specifically, reducing the toxic side-effects.

Researcher Dr Andrew Tutt from Guy's and St Thomas' Hospital said: "This genetically tailored chemotherapy treatment, carboplatin, acts in a much more focused manner than standard chemotherapy…While standard chemotherapy can affect any rapidly growing cell, these platinum drugs seem to be much more effective in destroying the cancerous BRCA cells. We hope this will mean improved quality of life and survival for women with this rare but important form of genetic breast cancer" (see BBC news report).

Research articles

Research article   |   By Dr Philippa Brice   |   Published 30 May 2006

Cystic fibrosis (CF) is a childhood- onset life-limiting illness (currently, average life expectancy is less than 25 years, although this figure is rising as treatments improve) associated with high morbidity (ill-health) that affects the respiratory and digestive systems. CF is caused by defects in the CFTR gene on chromosome 7; because the condition is a single-gene (Mendelian) disorder, it has the potential to be treated by gene therapy, provision of functional copies of the CFTR gene into the bodies of affected individuals. The actual and potential risks associated with any form of gene therapy generally require that clinical trials must be performed initially inadults.

However, a new report in the Journal of Medical Ethics questions whether it is in fact unethical to deny children access to participation in appropriate clinical trials from which they might derive clinical benefit. Indeed, the benefit might be substantially greater (and scientifically easier to demonstrate) in children, as gene therapy could prevent the onset of significant lung disease. Lead researcher Dr Adam Jaffé told the BBC: "We could be denying children life enhancing treatment on inadequate grounds...The main aim is to halt the decline in lung damage, which begins soon after birth so it makes sense to start treatment in early childhood” (see BBC news report). The authors, based at Great Ormond Street Hospital and the Institute of Child Health in London, the second largest paediatric centre for CF in the UK, present the results of a questionnaire they gave to the parents of children with CF treated at their unit [Jaffé A, Prasad SA, Larcher V and Hart S (2006) J Med Ethics 32, 361-364].

They note first that any medical research and treatment involving children “must balancethe competing duties to produce more benefit than harm and allowingthe children to exercise as much self determination (autonomy)in decision making as they are capable of or want”, with the additional point that children with a serious and chronic illness may be more competent to make decisions about their own care than would be expected from age alone. Parentshave ethical and legal rights to make decisions on behalf oftheir child, provided that they act in the child’s bestinterests. After consideration of some of the potential risks and benefits of gene therapy for cystic fibrosis in children, the authors turn to the opinions of the parents, representing a total of 80 children aged 0-17.

Overall, 82% of the parents considered gene therapy to be the most important area of researchin CF; of these, 56% hoped for a cure, 31% for alleviation of symptoms and 10%for both. Significantly, 99% of respondentsfelt it was ethically sound for children to be given the opportunityto be involved in gene therapy trials, provided that they werecarefully run, with safety issues as the priority, and 91% said that they would consider consentingto their child’s participation in a CF gene therapy trial.The authors propose that their results “may be helpful to gene therapy regulatory bodies whenconsidering the design of future clinical trials”, although they also warn of the necessity to protect children with CF and their parents from unnecessary harm.

Commentary: The researchers are themselves careful to record the limitations of their relatively small study, perhaps most notably that they did not make the risks of gene therapy explicit for the purposes of the questionnaire and that those most in favour of gene therapy trials were probably more likely to have responded to the questionnaire. However, the work does suggest that the standard approach to clinical trials, whereby adults are the initial trial subjects, should be reconsidered in situations where the conditions are serious, and the potential benefit to trial participants is greater for younger patients.
Keywords : journalGene Therapy

Research article   |   By Dr Ireena Dutta   |   Published 26 May 2006

Stem cells have the unique capabilities of being able to self-renew to maintain their own population and differentiate to produce cells with specialist functions. Although self-renewal is an essential in terms of sustaining a pool of cells from which old and dying cells can be replaced, the ability of stem cells to proliferate indefinitely has implicated them as having a significant role in the development of cancers. Many phenotypic and functional similarities have been found between ‘normal’ stem cells and those involved in cancers. For example, leukaemia-initiating cells (also called leukaemic stem cells), express cell markers that are similar to normal haemopoietic stem cells (HSC), and the Hedgehog, Wnt and Notch signalling pathways can promote both cancer cell proliferation and normal stem cell renewal. There is still much discussion regarding the origin of cancer stem cells and if they arise from normal stem cells, however whatever their source they undoubtedly share many of the properties of stem cells. This is an important issue when considering the development of cancer therapies, as it may prove difficult to produce treatments that target only cancer cells without also destroying normal stem cells that are needed by the body.


Two research papers have produced evidence that it may in fact be possible to differentiate between these cell populations. Yimaz et al., and Zhang et al., have investigated the role of the Pten tumour suppressor gene in haematopoietic stem cells. Pten encodes a phosphatase that negatively regulates signalling via the phosphatidylinositol-3-OH kinase (PI(3)K) pathway and inhibits proliferation and cell signalling. Both authors created transgenic mice in which Pten had been conditionally deleted. These mice went on to develop leukaemias, including acute myeloid leukaemia and lymphoblastic leukaemia. They also reported that the Pten deletion led to an eventual depletion of HSCs through the inhibition of self-renewal. Therefore although normal HSCs were not able to maintain themselves in the absence of Pten, leukaemic stem cells were. In order to investigate the further Yilmaz et al., used rapamycin to inhibit one of the effectors of the PI(3)K pathway that Pten is a part of. mTOR kinase activity is inhibited by rapamycin, and this drug has also been used in the treatment of human leukaemias. The authors found that rapamycin inhibited the generation of leukaemic stem cells, and also rescued Pten-deficient HSCs, allowing them to reconstitute cell lineages in irradiated mice. Zhang et al., also analysed the localisation of HSCs with the Pten deletion, and reported that the deletion led to significantly increased HSC mobilisation to the peripheral blood and spleen, rather than these cells remaining in the bone marrow niche.


Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells OH Yilmaz et al. (2006) Nature 441, 475-482.


PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention J Zhang et al (2006) Nature 441, 518-522



This research provides an insight into how cancer stem cells differ from normal stem cells. Although neither of the papers is able to offer an elucidation of the actual mechanism by which the Pten deletion acts to cause a depletion of HSCs and the promotion of leukaemic disorders, this research has identified a relevant pathway. It has previously been thought that oncogenic mutations that give cells the ability to self-renew utilise the same pathways as normal stem cells, whether or not the mutations arise in stem cells or other cell types. This work has identified a key difference in the way in which malignant and normal stem cells behave in the absence of Pten, and may therefore contribute to the design of new cancer treatments or the potential improvement of existing therapies.

Keywords : Stem Cells

New reviews and commentaries

New reviews and commentaries, 30 May 2006

Reviews & commentaries : by Dr Philippa Brice

What is a gene? Pearson H (2006) Nature 441, 398-401. News feature article re-evaluating the concept of a gene as a discrete protein coding sequence and reviewing emerging evidence on the varied role of RNA in information transfer (PubMed).


Ethnicity and adverse drug reactions. Eliasson E (2006) BMJ 332, 1163-1164. Article accompanying meta-analysis of ethnicity and ADRs for cardiovascular drugs, considering the prospects for ‘personalised’ drug treatments (PubMed).


A new human genotype prone to variant Creutzfeldt-Jakob disease. Wilson K and Ricketts MN (2006), BMJ 332, 1164-1165. Article accompanying research report identifying a human genotype that may be associated with an increased predisposition towards vCJD,with a caveats that the results must be interpreted with caution (PubMed).


A broad band of silence. Smith JS and Costello JF (2006) Nature Genetics 38, 504 – 506. News and views article on recent research showing that transcriptional silencing in cancer can be unexpectedly diffuse, by identifying a large domain of epigenetic modification on chromosome 2 in colorectal cancer (PubMed).


Molecular genetics of Rett syndrome: when DNA methylation goes unrecognised. Bienvenu T and Chelly J (2006). Nat Rev Genet. 7, 415-426. Review looking at how mutations in the MECP2 gene cause altered interpretation of DNA methylation leading to specific disease phenotypes (PubMed)


Gene drive systems for insect disease vectors. Sinkins SP and Gould F (2006) Nat Rev Genet. 7, 427-435. Review on systems for spreading genes that can block the transmission of insect-borne pathogens such as malaria parasites, focusing on naturally occurring mobile genetic elements and their potential for exploitation (PubMed).


The quest for genetic determinants of human longevity: challenges and insights. Christensen K, Johnson TE and Vaupel JW (2006) Nat Rev Genet. 7, 436-448. Review of progress and prospects in the hunt for genetic variants associated with human lifespan, proposing that larger-scale studies and new analytical methods may provide the key to success (PubMed).


Inborn errors of metabolism: the flux from Mendelian to complex diseases. Lanpher B, Brunetti-Pierri N and Lee B (2006) Nat Rev Genet. 7, 449-459. Review looking at inborn errors of metabolism, emphasising the role of environmental factors combined with genetic mutastions in disease pathogenesis and considering how dynamic measurement of metabolic fluxes, in combination with genetic and environmental factors, may enhance diagnosis and therapeutic interventions (PubMed).

read more ...

New reviews and commentaries, 18 May 2006

Reviews & commentaries : by Dr Philippa Brice

Quantifying the health benefits of genetic tests: the importance of a population perspective. Khoury MJ, Jones K and Grosse SD (2006) Genet Med. 8(3), 191-5. Commentary proposing an analytical framework to assess the health benefits of genetic testing for disease susceptibility (PubMed).

Quantifying the health benefits of genetic tests: A clinical perspective. Scheuner MT and Rotter JI (2006) Genet Med. 8(3), 141-2. Editorial on the previous article, suggesting various additions, including the contention that genotypic information alone has the potential to reduce disease risk even in the absence of genotype-specific interventions (PubMed)

The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Modell SM and Lehmann MH (2006) Genet Med. 8(3), 143-55. Review on genetic disorders affecting cardiac ion channels, including genetic investigation and complexities such as ethnic polymorphisms (PubMed).

Informed choice for screening: implications for evaluation. Irwig L, McCaffery K, Salkeld G and Bossuyt P (2006) BMJ 332,1148-50. ‘Screening and choice’ commentary on reasons for and methods of obtaining ‘consumer priorities’ (PubMed).

Common susceptibility genes for cancer: search for the end of the rainbow. Baker SG and Kaprio J (2006) BMJ 332, 1150-2. Somewhat pessimistic commentary on the prospects for identifying novel cancer susceptibility genes (PubMed).

The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: an update. Grosse SD, Khoury MJ, Greene CL, Crider KS and Pollitt RJ (2006) Genet Med. 8, 205-12. Review of MCADD deficiency epidemiology (PubMed).

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New reviews and commentaries, 9 May 2006

Reviews & commentaries : by Dr Philippa Brice
The fragile X syndrome: exploring its molecular basis and seeking a treatment. Bardoni B, Davidovic L, Bensaid M and Khandjian EW (2006) Expert Rev Mol Med. 8, 1-16. Review looking particularly at the function of the Fragile-X Mental Retardation Protein and how its absence in patients may result in the clinical phenotypes of the disease, with prospects for therapeutic interventions (PubMed).

Will UK Biobank pay off? Watts G (2006) BMJ 332, 1052. Update on progress and controversies around the UK Biobank project (PubMed).

Medical progress: Hematopoietic stem-cell transplantation. Copelan EA (2006) N Engl J Med 354, 1813-1826. Review (PubMed). Chromosome guardians on duty. Megee P (2006) Nature 441, 35-37. News and Views article summarising recent research into the function of shugoshins, proteins that regulate chromosome adhesion and separation during cell replication (PubMed).

Embracing the complexity of genomic data for personalized medicine. West M, Ginsburg GS, Huang AT and Nevins JR (2006) Genome Res. 6, 559-66. Perspective article arguing that the massive complexity of genomic data, rather than being a barrier to utility, is actually a highly valuable resource for developing improved clinical tools; however, it requires integrated analytical approaches (PubMed).

A SLAMS dunk for cancer regulators. Kumar-Sinha C and Chinnaiyan AM (2006) Nat Biotechnol. 24, 524-6. News and Views article on a novel technique being used to identify genetic regulators of cancer by combining microarray data on global gene expression, and DNA copy number: stepwise linkage analysis of microarray signatures (SLAMS) (PubMed).

Replicators lessen transcriptional silencing. Schildkraut CL and Guan Z (2006) Nat Biotechnol. 24, 523-4. News and Views article on a new approach to prevent transcriptional silencing of transgenes, such as those delivered in gene therapy, by using human DNA sequences that control initiation of replication (PubMed).

Iron metabolism meets signal transduction. Anderson GJ and Frazer DM (2006) Nat Genet. 38, 503-4. News and views piece on the molecular pathogenesis of juvenile hameochromatosis, caused by mutations in the haemojuvelin gene (PubMed).

A broad band of silence. Smith JS and Costello JF (2006) Nat Genet. 38, 504-6. News and views piece on recent research that showed unexpectedly diffuse transcriptional silencing via CpG methylation in colon cancer (PubMed).

mtDNA clock runs out for dopaminergic neurons. Manfredi G (2006) Nat Genet. 38, 507-8. News and views piece on the possible role of damage to the mitochondrial genome in the decay of dopaminergic neurons, ageing and Parkinson’s disease (PubMed).

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