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 29 September 2008

A new paper profiled in the Genomics & Health Weekly Update from the National Office of Public Health Genomics, and published in the CDC’s Mortality and Morbidity Weekly Report reports on the impact of the expanded newborn screening programme in the US. Screening newborns for a much larger panel of different disorders became feasible due to the advent of advanced tandem mass spectrometry (MS/MS). In 2005 the US Department of Health and Human Services’ Maternal and Child Health Bureau (MCHB) commissioned the American College of Medical Genetics (ACMG) to make recommendations about expanded newborn screening, and a panel of 29 ‘core’disorders was proposed (see previous news). The Federal Advisory Committee on Heritable Disorders in Newborns and Children endorsed this panel, and most US states began to implement the expanded newborn screening from 2006.

The new paper,  Impact of Expanded Newborn Screening - United States, 2006, reports that if all 50 states had implemented the ACGM panel as recommended (as opposed to fewer than half in practice), the number of children diagnosed in 2006 would have risen by 32% from 4370 to 6439, based on 2001-2006 data from states with well-established MS/MS screening programmes. It notes that these children “would have had many rare disorders that require local or regional capacity to deliver expertise in screening, diagnosis, and management”, and emphasises the need for public health and health-care delivery systems to build or expand facilities for the clinical management of these rare disorders.

An editorial accompanying the report notes that the increase in cases would be largely due to the increased detection of rare disorders (since all states already screened for the more common conditions such as the haemoglobinopathies), saying that this “underscores the dual challenge of continuing the screening program for the more common disorders while also building the expertise and resources to manage the many rare disorders”. It proposes that ongoing surveillance and evaluation of the diagnosis of affected newborns and their longer-term health outcomes is required to develop better management protocols, noting that provision of screening and follow-up for the rarer disorders remains a challenge.

News story   |   By Dr Sowmiya Moorthie   |   Published 25 September 2008

The Human Microbiome Project (HMP) was launched at the beginning of this year by the US National Institutes of Health (NIH) with the aim of generating resources to enable a better understanding of the various microbes that inhabit the human body and their influence on health and disease (see previous news).


As part of this programme the NIH also aims to address the ethical, legal and social implications of this project in much the same way as it has done with the Human Genome Project (reported by GenomeWeb News). The institute is offering awards to investigate issues such as informed consent, intellectual property rights, and strategies available for public education on the project and its implications for health and society. In addition, it is also interested in identifying what new technologies and clinical applications may result from this research and their subsequent ethical, legal and societal impact.

News story   |   By Dr Sowmiya Moorthie   |   Published 22 September 2008

The Embryo Research Licensing Committee of the Australian National Health and Medical Research Council (NHMRC) issued its first licences, allowing scientists to clone human embryos using somatic cell nuclear transfer (SCNT) in order to obtain stem cells (see press release). The licences have been granted to Sydney IVF and if the company is successful, it would be the first production of stem cells from cloned embryos for therapeutic purposes, as opposed to medical research. A national ban on therapeutic cloning in Australia was lifted in December 2006 (see previous news) and since then several states have also lifted their prohibition on therapeutic cloning (see previous news).

SCNT or therapeutic cloning involves removal of DNA from the nucleus of an unfertilised egg and replacing it with DNA from an adult cell. Although other scientists in countries such as the UK have been granted licences to carry out research using SCNT (see previous news), none have so far been able to extract embryonic stem cells from cloned embryos. If successful, this research could lead to the generation of disease specific and person specific human embryonic stem cells for research. The cloned embryos will be generated from human eggs generated by IVF (in vitro fertilisation) that have been discarded as unsuitable for establishing a pregnancy. Although the technique could in theory also be used for reproductive cloning, this practice is still banned in most countries, and there have been calls for an international law to prohibit it (see previous news).

Keywords : CloningStem Cells

News story   |   By Dr Philippa Brice   |   Published 19 September 2008

Two US medical centres have announced that they will launch the first systematic newborn screening programmes for the inherited disorder fragile X syndrome using a new blood spot test. Fragile X results from the expansion of a CGG repeat sequence on the X chromosome FMR1 gene; normally under 55 repeats, expansion to 55-200 repeats is classed as a pre-mutation (PM) and above 200 repeats is classed as a full mutation (FM). Of individuals with a full mutation, all males and around half of females have the disease, which causes learning disability and behavioural problems, with around 1 in 4000 males and 1 in 8000 female affected in the general population. Males typically show more severe learning disability than females, and Fragile X is the most common inherited form of learning disability.

Individuals with pre-mutations do not show any form of mental retardation, but female PM carriers are at risk of having children with full mutations, and also have an increased incidence of premature ovarian failure. Male carriers are not at increased risk of transmitting a full mutation to their children, but may develop a neurodegenerative disorder called fragile X–associated tremor/ataxia syndrome (FXTAS) in later life (see previous news); this can more rarely affect female PM carriers too.

Studies have suggested that cascade testing in affected families or universal prenatal screening may be appropriate for Fragile X (see previous news), but there is no screening programme in the UK (see National Screening Committee policy statement); this decision will be reviewed in 2009/10. It has been proposed that newborn screening for the condition, since it would result in identification of PM or FM children who may never, in fact, be affected by the disease, could potentially result in some serious harms for the child and family (see previous news). Even prenatal screening has raised concerns (see previous news).

The new test has been developed by researchers at University of California, Davis M.I.N.D. Institute and the Rush University Medical Center with National Institutes of Health (NIH) funding, and will be used in a pilot study from autumn 2008 on all newborns at the two centres, estimated to reach a total of 30,000 in the coming five years. The test uses a polymerase chain reaction (PCR) based technique to amplify the FMR1 gene expansion region and allows detection of expanded repeat regions. This means that the test will identify pre-mutation carriers as well as those with the full mutation. Senior researcher Dr Randi Hagerman said: “While the newborn screening study is not specifically designed to offer treatment, the diagnosis will open the door to new therapies for infants…Once we have identified affected infants, we will propose treatment options for them.”(see press release).

Comment: There is no cure for Fragile X Syndrome, although drugs may alleviate some of the symptoms, so the prospects of treating affected children are currently very limited. Despite this there are arguable benefits of early diagnosis, paticularly in allowing prompt access to supportive treatment to address behavioural problems, and special educational help. It may also allow the diagnosis of FM or PM status in family members, who may have associated health problems or mild learning disability. However, many would question the ethics of identifying PM or FM infants, since PM status is not associated with any significant health impacts until maturity, whilst FM status does not necessarily mean that an individual will ever show any symptoms of Fragile X; moreover, none of the infants would be capable of giving informed consent for the decision to test.

News story   |   By Dr Sowmiya Moorthie   |   Published 18 September 2008
In the August issue of PLoS Genetics, an article described a new forensic DNA analysis technique which is able to identify the DNA of one individual in the midst of a large sample. The paper by Homer et al. describes how statistical analysis of data from single nucleotide polymorphism (SNP) data sets could be used to resolve individual genotypes [Homer N et al, (2008) PLoS Genet. 4(8), e1000167]. This technique is a major breakthrough for forensic science as it will allow identification of an individual’s DNA even if it only constitutes 0.1% of the whole mixture in the sample. The technique can allegedly also be applied to individual participants in data obtained from genome-wide association (GWA) studies, although identification would require prior knowledge of the SNP profile of the individual concerned, or a close relative. Despite the remote possibility of identification of individual participants in GWA studies, some institutes such as the US National Institutes of Health (NIH) and the Wellcome Trust have, since the publication of the article, restricted access to genetic data on grounds that it throws into question previous consent procedures and approaches to privacy and confidentiality in such research (reported in Science).

GWA studies operate on the basis of the location of many SNPs associated with susceptibility to disease.  The data are usually stored in publicly accessible databases so that they can be used by other researchers, and are generally pooled and summarised in the form of statistical information, in order to ensure that anonymity is maintained. The technique described by Homer et al. opens the possibility of the identification of individual participants. However, in order to achieve this, their SNP profile must be previously known, and this information is generally only available to researchers.

The new statistical approach has implications for data sharing policies, as data from GWA studies has been made publicly available via research databases, websites, journal articles and other publications. Some researchers feel that the NIH/Wellcome Trust restriction on access to data is premature and may impede research (reported by Nature). The NIH is currently working to explore and address the policy implications of this finding and in a letter published in Science, called on others in the scientific community to join in the deliberations [Zerhouni EA et al. (2008) Science  Sep 4: Epub ahead of print]. Issues relating to privacy, confidentiality and consent, have already been raised in the context of personal genomics (see news reviews) and bio banking, and are becoming increasingly important as genetic data proliferates.


News story   |   By Dr Sowmiya Moorthie   |   Published 15 September 2008
A new public centre, whose aims are to offer stem cells to match a diverse population, was opened on the 11th of September by the Health Secretary Alan Johnson (see press release). The Anthony Nolan Stem Cell Therapy Centre is a combined blood bank and research institute that aims to store stem cells from cord blood for use in transplants as well as carry out pioneering research into new therapies. It is part of the Cord Blood Programme run by the Anthony Nolan Trust. Currently, cord blood stem cells have been used successful in renewing bone marrow and regenerating the immune systems of those with life-threatening illnesses including leukaemia, sickle-cell diseases, and immune deficiencies and it is hoped that research into cord blood transplantation will help many other diseases.

The centre aims to bank 50,000 units of blood by 2013 of which 20,000 will be suitable for transplantation and 30,000 for research. At present donations are being taken from babies born at London’s Kings College hospital and the Trust hopes that it will be able to collect donations from more hospitals in the future. Various commercial companies also operate cord blood banks and there have been concerns that this may divert efforts away from public sector banks such as the NHS Cord Blood Bank (see previous news). The impact of this new public venture on the NHS Cord Blood bank is unclear, however, the Trust says that the complex will “help provide a lifeline for thousands complementing the 12 years' experience of the NHS Cord Blood Bank; and reinforce the UK's role as a research centre of excellence” (see press release).

Keywords : Stem Cells

News story   |   By Dr Sowmiya Moorthie   |   Published 12 September 2008
The US National Academies released an amended version of their guidelines for human stem cell research at the beginning of September (see press release). The guidelines were originally published in 2005 to offer a common set of ethical standards for the responsible conduct of research using human stem cells (see previous news). Following the publications of the 2005 guidelines, the Human Embryonic Stem Cell Research Advisory Committee was established in order to monitor and review them as scientific advances were made in this field. The guidelines were last updated in 2007 and the recent modifications are in order to incorporate research involving induced pluripotent stem (iPS) cells, these are stem cells produced through re-programming somatic (non-embryonic) cells (see previous news).

Previous versions of the guidelines primarily addressed research involving human embryonic (hES) stem cells. The recent version of the guidelines contains a new section providing guidance on the derivation and use of pluripotent and multipotent stem cells and gives guidance on what level of review is needed for various categories of experiments involving iPS cells. Research involving iPS raise the same ethical and policy issues to those raised by the use of hES in some instances but not others, resulting in the need for differing levels of review.

A number of other brief changes have also been made to other sections of the document, such as the recommendation that institutes should carry out periodic audits of their embryonic stem cell research oversight (ESCRO) committees and make the findings available to the public along with informing them about the types of research they are undertaking. They believe this will encourage better management and instil confidence in the research practices of the institutes. Clarifications were also made to other guidelines, including a better description of what “direct expenses” could be reimbursed to women who donate eggs for research.


Keywords : rStem Cells

News story   |   By Dr Philippa Brice   |   Published 10 September 2008

Preliminary results suggest that a new drug may be an effective treatment for cystic fibrosis, which affects some 70,000 people worldwide and is one of the most common single-gene disorders in the UK, with around 8000 sufferers. One in 25 Caucasians are carriers of causative mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which impair chloride transport in cells; the disease occurs in people who inherit two such mutations. Characterised by excessive production of mucus and loss of salt via sweat, CF can cause significant respiratory and gastrointestinal problems, and markedly reduces life expectancy even in developed countries; there is as yet no treatment beyond interventions to reduce the symptoms, although there are ongoing efforts to develop gene therapies to cure the disease (see previous news).

The new drug VX-770 was developed by the Cystic Fibrosis Foundation in collaboration with Vertex Pharmaceuticals; it targets the defective CFTR protein to improve chloride transport. The Cystic Fibrosis Trust supports a group at the University of Bristol in investigating how new drugs restore function to defective CFTR proteins; group leader Dr David Sheppard reported results at the BA Festival of Science indicating that the new drug could cause a near 50% reduction in salt levels in sweat and a 10% improvement in lung function in cystic fibrosis patients. He said: “The early results with VX-770 suggest that drug therapies which target defects at the root of the disease have the potential to improve greatly the quality of life of CF patients” (see press release).

Of note, there are well over a thousand different mutations in the CFTR gene known to cause cystic fibrosis; this new therapy targets a particular type of mutation and would therefore be appropriate for only a small proportion of people with the disease, reportedly around 6% of UK patients (see BBC news). Moreover, not only are the reported results preliminary, requiring further trials to generate reliable data, but the drug offers only a potential alleviation of symptoms and not a cure. However, if effective this sort of treatment could significantly improve the quality and expectancy of life for CF patients, and it illustrates well how determining the genetic basis of disease can lead to an understanding of the underlying disease process, and hence to possible therapeutic interventions.

News story   |   By Dr Caroline Wright   |   Published 3 September 2008

Familial hypercholesterolaemia (FH) is an inherited disorder characterised by high plasma cholesterol – specifically low density lipoprotein (LDL) – and early onset cardiovascular disease. Most cases are caused by mutations in the LDL receptor gene, which is involved in removing LDL from the blood. Other causes include mutations in the apoprotein B (ApoB) gene, which affect the binding of LDL to its receptor, and in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, which reduces the number of LDL receptors.


FH is an autosomal dominant disease which results in premature cardiovascular disease, with an age of onset of around 30-40 in heterozygotes and may be fatal during childhood in homozygotes. Due to the severity of the disease, the UK Human Fertilisation and Embryology Authority (HFEA) recently granted a licence permitting pre-implantation genetic diagnosis to select against homozygous embryos (see previous news). The prevalence of heterozygotes is thought to be around 1 in 500 people, whilst homozygotes are much rarer, occurring in only 1 in a million births. Although the severity of the disease is variable, it can be devastating if left untreated, and once diagnosed, a dietary regime combined with statin therapy is very effective at lowering LDL-cholesterol, particularly in heterozygotes.


Following an extensive review and consultation, the UK National Institute for Health and Clinical Excellence (NICE) released updated guidance on the identification and management of FH on 27th August 2008. Of particular interest is the recommendation that cascade screening be systematically implemented in families affected by FH, including “the use of a nationwide, family-based, follow-up system… to enable comprehensive identification of people affected by FH”. The test will include a combination of genetic testing (where the mutation is known) and LDL concentration measurement, to identify affected first-, second- and third-degree relatives of individuals with a clinical diagnosis of FH. Given an estimated 110,000 affected individuals in the UK, and the enormous benefits of early diagnosis and treatment, the guidance also states that the possibility of FH should be considered in anyone with a raised LDL cholesterol level, especially where there is a family history of premature coronary heart disease. Since only around 10% of the total predicted number of cases have already been identified in the UK – some of whom are related – family cascade testing alone is unlikely to uncover all the remaining cases.


Comment: This strategy for population screening of FH based on cascade testing was recommended in a paper in the BMJ in 2007 (see previous news), and a similar programme has been active in the Netherlands for many years (see previous news). Though simple in concept, the necessary cascade system requires very careful design and evaluation. For example, it needs to enable coordination of testing for a whole family by different health professionals in different geographic locations, and to manage and record the different levels of consent that individuals and families have given. For this reason, the programme is unlikely to succeed unless there is an organised system of clinics in place and the relevant IT infrastructure is available. Support will be needed from specialist genetic services, particularly during developmental phases to help set up protocols and provide educational support in working with families based on sound clinical and ethical principles. The work on FH is firmly set within mainstream medicine, but will provide a valuable prototype for developments in other areas of clinical practice where there are also important genetic subsets of disease.

Research articles

Research article   |   Published 5 September 2008
Much recent work in somatic cell nuclear transfer (cloning), including applications to the UK Human Fertilisation and Embryology Authority (HFEA) to permit the production of hybrid human-animal embryos (see previous news), has been for the purposes of creating human embryonic stem cell lines for research into serious human diseases, including genetic diseases. Human embryonic stem (HES) cells are pluripotent, potentially able to give rise to almost any specialised human cell type, allowing study of the whole process of cell differentiation. Stem cells produced from embryos with genetic diseases reproduce the effects of that disease in specialised cells and tissues, and are of value in learning more about it, as well as attempting to devise treatments, whether permitting in vitro screening of potential novel drugs, or developing stem-cell therapies to correct genetic defects. However, the difficulty of creating HES cells due to a limited supply of human embryos or human oocytes (eggs) is a major barrier to research, which was a key factor in the decision of the HFEA earlier this year to permit the creation of human-animal embryos (see previous news), as well as an area of ethical debate.

A new paper in Cell reports the production of induced pluripotent stem (iPS) cells from patients and carriers of ten different serious disorders, to facilitate further medical research.Most of these diseases were Mendelian (single-gene) disorders, including Duchenne (DMD) and Becker muscular dystrophy (BMD), Huntington disease, Gaucher disease (GD) type III and adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID). In addition, cell lines were generated from individuals with the chromosomal disorder Down syndrome (trisomy 21) and the complex (multifactorial) conditions Parkinson disease and juvenile diabetes mellitus [Park I et al. (2008) Cell 134 (3) 1-10, doi:10.1016/j.cell.2008.07.041]

The US researchers used a variation on a relatively new technique, first reported in 2007 (see previous news) that effectively reprogrammes adult somatic cells (which are specialised cell-types with very limited capacity to form other cell types) to become pluripotent. The method uses combinations of transcription factors (proteins involved in the regulation of gene expression) previously linked with pluripotency  [Park IH et al. (2008) Nat Protoc. 3(7):1180-6], an easier procedure than the production of HES cells and one which does not require the use of human embryos or unfertilized eggs.

The Harvard Stem Cell Institute, where much of the research was carried out, is to establish a facility for the production of other disease-specific iPS cell lines, with a view to making them available to other medical researchers. Senior author George Daley commented: “The cell lines available from the iPS Core will allow stem cell researchers around the world to explore possible gene therapies for some conditions, and will aid in the development of drugs for others” (see press release).

Comment: The critical importance of HES cells in medical research has been a key factor in determining the relatively permissive UK regulatory regime; in the US, federal funding for stem cell research is restrictive, not allowing the creation of new HES cell lines and favouring research into the creation of stem cells from adult cells instead (see previous news). There has been mounting pressure from the scientific research community against these restrictions, due to the limited evidence that adult cells could be used to create stem cells; however, evidence is now mounting that it is possible. Whether these approaches will prove robust enough to eventually remove the need for research using HES cells is not yet clear, but certainly these latest results are a step towards more accessible and ethically non-controversial sources of stem cells.

Research article   |   By Dr Philippa Brice   |   Published 2 September 2008
Breast cancer cases in younger women are more often the more aggressive type than for older women, showing poorer response to treatment. A recent publication looking at patterns of gene expression in breast cancer cells has linked a subset of breast cancers with similar patterns to a younger age at diagnosis, and a poorer prognosis. Writing in the Journal of Clinical Oncology, the researchers report a study of nearly 800 early-stage breast cancers, where microarray (DNA chip) data was compared between young (age 45 and below) and old (age 65 and above) groups [Anders CK et al. (2008) J Clin Oncol. 26(20):3324-30].

A characteristic pattern of gene expression was associated with the young breast cancer patients. This was not a pattern of specific individual genes, but rather groups of genes sharing similar functions such as cellular signalling and survival. These tumours also showed a different pattern of cell-surface receptors; for example, showing lower expression of the estrogen receptor (ER) but higher levels of the human epidermal growth factor receptor 2 (HER-2) than tumours in the older age-group. The authors propose that their results indicate that breast cancer in some young women may be biologically distinct from other breast tumours, arising from different oncogenic pathways and being characterised by a decreased sensitivity to hormones, and a poorer prognosis. They call for further research in order to develop improved preventative and therapeutic options for women with this form of breast tumour.

Senior author Kimberly Blackwell commented: "Clinicians have long noted that the breast cancers we see in women under the age of 45 tend to respond less well to treatment and have higher recurrence rates than the disease we see in older women, particularly those over the age of 65…by understanding this, we may be able to develop better and more targeted therapies to treat these younger women" (see press release).

Comment: Microarray-based analysis has revealed information about many kinds of tumours that suggests that groups of tumours that may appear similar in terms of clinical and histopathological features can have very different genetic signatures, and that these underlying patterns of gene expression can potentially allow more accurate diagnosis, prognosis and management, perhaps even specifically tailored treatments. This paper does no more than open up a possible line of further enquiry; the data is not sufficient to reliably conclude, as the authors suggest, that breast cancer in younger women is a different disease from that seen in older women. A commentary accompanying the report proposes more realistically that: Ultimately, we may move away from the concept of disease asa discrete entity that is largely comparable across patientsto one in which the unique molecular features of each tumorand the biology of the patient, including pharmacogenomic differences,must be considered to guide a more personalized therapy” [Peppercorn J, Partridge AH (2008) J Clin Oncol. 26(20):3303-5].