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 July 2011

A new government report has set out the challenges for regenerative medicine in the UK and a strategy for future development.

Published by the Office for Life Sciences and the Department of Health (DH), the new report provides an overview of the UK’s strengths and weaknesses in regenerative medicine, and sets out a strategy to boost the development and commercialisation of regenerative therapeutics building on existing academic, health service and commercial expertise.


Regenerative medicine is defined in the broadest sense, incorporating stem cell therapeutics, tissue engineering, biomaterials and gene therapy as well as cell-based technologies for drug discovery, toxicity testing and non-regenerative therapeutics.


Given the high costs of such treatments, clear evidence of safety and efficacy are said to be vital for securing ongoing financial investment. Potential benefits in terms of both commercial revenue and improved health outcomes are noted, along with the unique position of the National Health Service (NHS) as a ‘fertile environment’ for the translation of scientific innovation into diagnostics and treatments and calls for the NHS to work more closely with companies to achieve this.


Commitments are also set out for the government to back efforts to generate public and private investment and maintain facilitative regulatory and intellectual property frameworks. The UK Stem Cell Toolkit (see previous news) will be kept up to date to reflect any changes in the regulatory pathway and support research and product development.


Comment: Overall, the report calls for an integrated, national strategy to improve the ‘delivery, infrastructure, regulation and uptake of cell therapy and regenerative medicine’. Plans to capitalise on potential UK strengths in research, a permissive regulatory environment and unique national healthcare system to drive translation echo recent recommendations from the Academy of Medical Sciences (see previous news). The challenge will be in realising these ambitions in the light of current financial restrictions and restructuring in the health service.

Report of a story in the news   |   By Rebecca Bazeley   |   Published 28 July 2011

Civil liberties campaigners have accused the UK government of a U-turn on its pledge to delete the DNA profiles of innocent people.

At the moment, the DNA of anyone who has been arrested in England, Wales and Northern Ireland is held indefinitely on a national database. Under the Protection of Freedoms Bill, currently before Parliament, samples from innocent people will be deleted from the national DNA database (see previous news), but local forensic science laboratories could retain anonymised samples.The Home Office argues that to destroy samples from local laboratories would be difficult because DNA samples of innocent people are stored in ‘batches’ with the DNA of guilty people. Daniel Hamilton, director of the civil liberties group Big Brother Watch, said the anonymised samples would retain their bar code, allowing them to be ‘married up’ with information about individuals.

Our view:

Although DNA is unique to a specific person (with the exception of identical twins), some campaigners fear that human error could result in contamination of samples, errors in data handling and misinterpretation of profiles, leading to potential miscarriages of justice. However, these concerns would be equally valid for the examination of DNA samples from previously convicted criminals.

News story   |   By Dr Gurdeep Sagoo   |   Published 26 July 2011

A paper reporting associations between genetic signatures and exceptional longevity, which attracted widespread media attention when published in July last year, has been retracted.

Genetic Signatures of Exceptional Longevity in Humans was published in the well-known journal Science to much skepticism from the statistical genetics community (see Genetic Future article). Having never moved from online access into the full print edition of journal, Science published a formal Editorial Expression of Concern in November 2010, and just this week the authors of the manuscript have fully retracted the manuscript, saying that “technical errors in the Illumina 610 array and an inadequate quality control protocol introduced false-positive single-nucleotide polymorphisms (SNPs) in our findings”. Many of the issues that led to the non-publication of this manuscript and finally its retraction are well articulated by both Daniel MacArthur, in his original blog piece as well as a more recent one, and by the 23andMe research team in their The Spittoon blog.


Comment: Several issues are raised by the ‘publication’ of this article and its subsequent ‘non-publication’. First, it can be argued that the problems with this study should have been picked up in the peer-review process and that the article should not have got as far as online publication. This highlights one of the problems we face with the peer-review process i.e. it’s not fool-proof (although it is probably still the best external reviewing process we have). Hopefully this is something that Science will look into and ask how this manuscript ‘got through’ the process. Second, what part in the process (if any) did publication bias play? These findings were very exciting and would no doubt be of great interest to the research community. However, a closer inspection by the same research community led to widespread skepticism due to errors that were preventable. Third, despite the efforts of the research community to introduce various reporting guidelines, such as STREGA (see previous news), in a bid to highlight the importance of ensuring that research is done to the highest genetic and epidemiological standards, the importance of replication, replication, replication shouldn’t be forgotten (see previous news).


Perhaps most intriguing is how the authors in their retraction “feel the main scientific findings remain supported by the available data” despite “the specific details of the new analysis change substantially from those originally published online to the point of becoming a new report”. Let’s wait and see what gets published.

News story   |   By Dr Philippa Brice   |   Published 26 July 2011

The Academy of Medical Sciences (AMS) has called for more sensitive oversight of some forms of research involving animals containing human material (ACHM).


A new AMS report has said that, whilst most such research (for example, using genetically modified mice that contain a human gene or genes to study human diseases) does not raise new ethical or regulatory concerns, emerging applications might ‘approach ethical or regulatory boundaries’.  


It is suggested that whilst most forms of research need no additional regulatory oversight, a national expert body should be established to advise the Home Office on potentially sensitive types of ACHM research, such as any biological modifications that could mimic human-like brain functions or external characteristics ‘perceived as uniquely human’, and any form of fertilisation involving human eggs or sperm in an animal. Some extreme forms of research might be prohibited. However, the report also notes the potential value of ACHM research in general, not only to improve human health but also potentially to reduce the use of general animal testing.

Comment: These are sensible proposals, recognising the difference between standard methods of biomedical research using animals and those which present new issues with respect to public acceptability. Maintaining a good system of oversight is a key element in maintaining public trust in research that raises potential ethical concerns. The report also recognises the need for regulatory bodies to work together to avoid gaps, overlaps or inconsistencies in regulation’

Report of a story in the news   |   By Rebecca Bazeley   |   Published 25 July 2011

The South Australian Government has ordered an urgent investigation into its medical laboratory, Medvet, over a major breach of customer confidentiality. 

Invoices identifying the work and home addresses, and in some cases names, of customers purchasing paternity test kits had been made available online and were accessible via Google. People seeking drug and alcohol test kits were also affected. A report in The Australian said industry sources described it as one of the worst privacy lapses and the most serious in a sector that has grown steadily with the increasing use of workplace testing of employees for the presence of alcohol and drugs. Most of test kits had been sent to private addresses. 

Our view:

Early indications are that the breach was a result of poor controls over privacy and were not due to hacking. The leak could lead to legal action against the SA Government, or for individual compensation claims. 

Report of a story in the news   |   By Dr Philippa Brice   |   Published 25 July 2011

The German Bundestag has voted to permit pre-implantation genetic diagnosis (PGD) for couples at high risk of serious genetic diseases. 

PGD will only be allowed where the prospective parents have a genetic predisposition to a serious disease that could be passed to their offspring, resulting in a high probability of miscarriage or stillbirth, or causing significant suffering in surviving children. Ethics committee approval will be required for every potential application, and couples will also be required to receive counselling prior to procedures. Over 320 members voted in favour, with 260 against and eight abstentions. The Christian Democrats are reported to have been broadly opposed to the decision with the Social Democrats in favour. 

Our view:

The German government has voted for the most liberal of the three options under consideration (see previous news), despite widespread concern that it is an affront to the dignity of human embryos and could reduce social acceptance of disability. However, the chosen option is hardly reckless; the ethical safeguards to be put in place and the restriction of the use of PGD only to the most serious medical conditions mean that the technique will be used rarely and only in a careful and considered way to prevent suffering. Moreover, this avoids recourse to termination of pregnancy, which is already legal in such circumstances. 

Report of a story in the news   |   By Dr Sowmiya Moorthie   |   Published 15 July 2011

The US Food and Drug Administration (FDA) held a one day workshop in June to discuss challenges in  assessing the analytical validity when next generation sequencing (NGS) technologies are used for clinical applications.

This multi-stakeholder workshop addressed how sequencing platforms can be analytically evaluated prior to their adoption for clinical uses. Issues that were discussed included the evaluation of instrument accuracy in generating sequences and bioinformatics aspects such as data analysis and storage. The conclusion was that a broad framework should be applied which takes into consideration the different applications of NGS. This framework should consider the requirements for laboratory accreditation, the specific clinical application and confidence in identifying particular variants (i.e. outcome of the test). No timeline was set for the issue of guidance on this matter.

Our view:

The number of NGS platforms, differences in their performance metrics and the applications they can be used for, ranging from whole genome sequencing to targeted gene sequencing, can make evaluation difficult. In addition, this is a dynamic field meaning that any framework will have to be flexible to changes in the technologies and their applications. As sequencing is already beginning to be used in the clinical setting, considering these issues is an important aspect of ensuring their safe implementation. The PHG Foundation is undertaking a project looking at the impact of new DNA sequencing technologies for health.

News story   |   By Dr Philippa Brice   |   Published 14 July 2011

The US Food and Drug Administration (FDA) has called for feedback on new proposals to govern the regulation of biologically targeted treatments, also referred to as stratified medicines.


Treatments such as these are suitable for use in only a sub-group of patients with a given disease, because they target or otherwise exploit a specific genetic feature of either the patient or the diseased cells. The most common application is in cancer, where for example the breast cancer therapeutic Herceptin (trastuzumab) is only effective in patients with breast tumours that overproduce the HER2 protein. Targeted medicines therefore typically require a ‘companion diagnostic’ test to identify which patients could benefit from the treatment


Now the FDA proposes that new stratified medicines would only gain regulatory approval for use if the relevant companion diagnostic is also approved, with two exceptions: new treatments for serious or life-threatening conditions for which there are no other effective therapeutics and where the new treatment produces significant benefits; and amendments to treatments that have already been approved.

Comment: The FDA hopes to “help stimulate early collaborations between drug and device makers”. Efforts to streamline the regulatory process are desirable, but may not solve one of the other major barriers to the use of stratified medicine: the cost of companion diagnostics, and who should pay. If the diagnostic and therapeutic form a package that may be regarded as the therapeutic then that problem may be masked, but it could also prevent competition from alternative providers and keep prices high. 

News story   |   By Dr Philippa Brice   |   Published 13 July 2011

Researchers have called for women to be better informed about the increased risks of birth defects as a result of smoking during pregnancy.

The researchers analysed a total of 172 research papers that reported the effects of maternal smoking during pregnancy, covering 11.7 million healthy births and 174,000 with birth defects. They estimate that smoking is responsible for several hundred cases each year in the UK. Smoking was associated with an increased risk of 25-50% for a range of birth defects including absent or malformed limbs including clubfoot (talipes), malformations of the skull and face including cleft lip and palate, eye and gastrointestinal defects.


Professor Charles Rodeck of UCL Institute for Women’s Health commented: "The results of this research are of the greatest significance for the health of mothers and babies and for public health policy. If the recommendations are implemented, they will lead to a reduction in the incidence of several common malformations".


Comment: Many birth defects arise from interacting genetic and environmental factors; whilst smoking in pregnancy may not be the sole cause of a birth defect, it can clearly substantially increase risk. This research shows that even in countries such as the UK where the incidence of birth defects is very low compared with global levels, it is still possible to make changes such as information given to mothers that could further reduce the number of babies born with serious physical problems. The new Born Healthy community is calling for action worldwide to tackle birth defects.

Keywords : Birth defects

Report of a story in the news   |   By Dr Philippa Brice   |   Published 13 July 2011

The US Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC) is a government-funded organisation that works to ‘integrate genomics into public health research, policy, and programs’, with a particular focus on interventions against key chronic, infectious, environmental, and occupational diseases in the US. 

The OPHG was founded in the same year as the UK-based PHG Foundation’s predecessor body (the Public Health Genetics Unit), and has played an important role in the development of public health genomics. It is now seeking views on the public health priorities for the field in the US, to inform strategic planning for the next five years. 

Our view:

Input is requested on the most important activities, their expected outcomes, the policies needed to achieve them, potential barriers and solutions, and the roles of different bodies in working towards the desired outcomes. The consultation is open until 1st August.

News story   |   By Dr Philippa Brice   |   Published 12 July 2011

Sequenom, the company that owns most of the intellectual property relating to non-invasive prenatal diagnosis, has signed a three-year deal with DNA sequencing giant Illumina.

Sequenom holds commercialisation rights for techniques of non-invasive prenatal diagnosis based on the identification and analysis of fetal DNA and RNA from maternal blood samples (see previous news), developed by Professor Dennis Lo. The company has been trialling a new test for Down’s Syndrome (trisomy 21) that could offer vastly improved (safer, earlier) diagnostic testing (see previous news); the cost and speed of sequencing are important factors in developing a suitable market-ready product.


Now Illumina will supply sequencing equipment and materials to Sequenom over a three-year period and work with them ‘toward the submission for regulatory approval of an in vitro diagnostic product for the detection of fetal chromosomal abnormalities’ in the US.


Comment: This partnership may signal rapid development of the long-awaited commercial non-invasive test for Down’s Syndrome. Other applications that capitalize on the combination of free fetal DNA detection with cutting-edge sequencing methods could follow; Lo has already shown promising results for the diagnosis of a recessive genetic disorder (see previous news). Application of non-invasive testing within health systems (in addition to any direct-to-consumer testing) could have a major impact on antenatal care; see 2009 PHG Foundation report for overview.


Report of a story in the news   |   By Rebecca Bazeley   |   Published 12 July 2011

Cells discarded during IVF treatment may hold the key to a non-invasive test for genetic abnormalities. The potential test could prove safer and cheaper than current methods. 

Current approaches to preimplantation genetic screening (see previous news), involve taking cells from the embryo, but a team of researchers at the UK’s Oxford University says it is possible to run the same checks on the cumulus cells which form a ‘cloud’ around the fertilised egg. 

The team examined gene expression in cumulus cells from 26 women undergoing genetic screening prior to IVF treatment. They found abnormalities in the cumulus cells that appeared to tally with genetic errors in the eggs they had surrounded.  

Lead researcher Dr Elpida Fragouli said: “It is interesting that several of these genes are involved in vital cellular functions of the cumulus cells and egg they enclose, such as cell signalling and regulation, hormonal response and cell death, and so they may shed light on the genetic origins of chromosome abnormality".  

Researchers say the cumulus cells may tell us more about genetic abnormalities than screening approaches that look only at the chromosomes of the fertilised eggs. They are running further tests to compare results between the two methods. If there is a good correlation, then they plan to run a clinical trial in about a year's time.  

News story   |   By Dr Philippa Brice   |   Published 5 July 2011

A US politician has reintroduced a bill to codify President Barack Obama’s 2009 policy to ease restrictions on federally funded research using human embryonic stem (HES) cells (see previous news). The bill, which in previous forms has passed Congress but was vetoed by the former President George Bush, is supportive of HES cell research. It would formalise the National Institutes of Health (NIH) stem cell research guidelines, and require regular review in the light of scientific progress.


However, the bill is likely to meet with fierce opposition. Even if passed, it would not solve the ongoing legal conflict over interpretation of the Dickey-Wicker law that prohibits federal funding for research that involves the destruction of embryos. This involved an injunction against all such research that was subsequently lifted (see previous news). However, another legal challenge is now underway, Sherley et al. v. Sebelius, in which adult stem cell researchers are claiming that government funding for HES cell research effectively creates a financial incentive for the destruction of more human embryos by increasing demand for HES cell lines.

Comment: Will this legal wrangling over embryonic stem cell research never end? Clearly, public opinion in the US is sharply divided between the potential medical benefits of HES cell research for patients with serious diseases, and the ethical concerns over the use of human embryos – both very important and valid drivers. Rapid progress towards useful therapeutics from the field of adult stem cell research would provide a welcome resolution to this dilemma, but until or unless this happens then the arguments are likely to continue. 

Keywords : FundingLegal IssuesStem CellsUS

Report of a story in the news   |   By Dr Philippa Brice   |   Published 4 July 2011

 A new consensus statement on the value of diagnostic genetic testing for inherited cardiac conditions (ICCs) has been released; these are heart disorders caused by genetic abnormalities, which collectively represent a significant sub-group of cardiac medicine, including arrhythmias and sudden cardiac death.

The scope and clinical benefits of genetic testing for the diagnosis of ICCS and co-ordinated services that include genetics have already been outlined by the PHG Foundation. This new statement outlines recommendations on testing for 13 ICCs, including hypertrophic cardiomyopathy, long QT syndrome and dilated cardiomyopathy, and also provides guidance on genetic testing after sudden cardiac events in certain circumstances, and after sudden unexpected deaths. One of the experts behind the statement, Dr Silvia Priori, said that “genetic testing cannot be viewed as a one-size fits all solution, but its contribution to family screening and management in affected patients should be defined for each disease".  

Our view:

Current provision of genetic testing in Europe is said to be ‘patchy’. Both this observation and the recommendations for testing of patients and families, including post-mortem analysis, closely mirror the findings of the 2009 PHG Foundation Heart to Heart report, which led to the prioritisation of improved services for ICCs in the UK by the Department of Health. Efforts to ensure cardiologists in Europe are properly informed about the value and proper application of genetic testing for different disorders are to be welcomed. 

Report of a story in the news   |   By Rebecca Bazeley   |   Published 1 July 2011

The U.K. Border Agency (UKBA) has scrapped its widely scorned ‘Human Provenance Pilot Project’. The project, which UKBA set up as means to verify the nationality of asylum seekers, was launched in 2009 and greeted with derision by the scientific community (see PHG Foundation news 30 September 2009 ).

DNA testing might reveal a person’s ancestry but can tell us nothing for certain about nationality. UKBA subsequently suspended the project, only to resume tissue collection from asylum seekers on a voluntary basis.   The project was finally closed in March 2011. UKBA does not expect to publish any data from, or evaluation of, the project, which has reportedly cost the government agency £190,000.

Scientists were not surprised to see the project killed. "Given that most population geneticists would have identified the problems very quickly, it is surprising that it ever got off the ground," commented Mark Thomas, a geneticist at University College London.  

Research articles

Analysis of a study published in a science journal   |   By Dr Sowmiya Moorthie   |   Published 27 July 2011
Study: An integrated semiconductor device enabling non-optical genome sequencing
By: et al. (44 authors total)
In: Nature
What this study set out to do:

Demonstrate that quick de novo DNA sequencing is possible using low-cost semiconductor  technology.

How they went about it:

Developed a system for electronic DNA sequencing based on monitoring changes in voltage as nucleotides are incorporated into a DNA strand. This was based on making improvements to the design of ion chips on which the sequencing reaction takes place, the supporting instrumentation and software. The performance of the system was tested by sequencing three bacterial genomes and producing a draft genome sequence of Gordon Moore, who is the co-founder of Intel and author of Moore’s Law.


An integrated circuit able to sequence DNA was produced. Three different bacterial genomes were sequenced and comparison with the reference sequence demonstrated a high accuracy. The system was also able to produce a draft human whole genome sequence.


This study demonstrates it is possible  to produce ion chips which will facilitate low-cost routine human genome sequencing.

Our view:

Although this technology holds promise for low cost sequencing, as stated in the accompanying commentary, wide-spread use will require demonstration of its accuracy. The ability to quickly and accurately sequence genomes is already having a big impact on science (see previous news) and medicine (see previous news). The PHG Foundation is involved in a project looking at the impact of new sequencing technologies for health.

Analysis of a study published in a science journal   |   By Dr Anna Pokorska-Bocci   |   Published 21 July 2011
Study: Increased exonic de novo mutation rate in individuals with schizophrenia
By: et al. (22 authors total)
In: Nature Genetics
What this study set out to do:

To identify genes involved in the pathogenesis of schizophrenia and responsible for its high heritability. 

How they went about it:

Concentrating on non-familial cases of the disease, the researchers sequenced the exomes of 14 schizophrenia patients and their parents. Sequence reads from the patients were compared with that of their parents and control samples. Potentially causative structural variants were excluded using a copy number variant targeted array.


The sequencing and analysis resulted in identification of 73 putative variants, which were then verified by direct PCR amplification and Sanger sequencing in the patients and their respective parents. This validation study confirmed 15 variations to be genuine de novo mutations (DNMs). None of those DNMs was reported in the latest release of the 1000 Genomes Project. The 15 DNMs were identified in 8 of the 14 schizophrenia patients. No causative structural variants were identified.


None of the 15 identified DNMs has been previously reported to be associated with schizophrenia. The rate of de novo mutations reported in this study is significantly higher than the normal DNM rate established from the 1000 Genomes Project data. This new study suggests that DNMs might contribute to the pathogenesis of schizophrenia, explaining at least partly the missing genetic causes of the disease. It also provides a list of new candidate genes to be screened for in schizophrenia patients.

Our view:

These new results contribute to the understanding of the high worldwide incidence of schizophrenia. The identification of new candidate genes involved in the pathogenesis of the disease will not only allow to learn more about some of the biological pathways that are altered in schizophrenia but also about brain development and function in general .

Analysis of a study published in a science journal   |   By Dr Gurdeep Sagoo   |   Published 19 July 2011
Study: Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study
By: et al. (134 authors total)
In: Nature Genetics
What this study set out to do:

The study authors conducted an extensive investigation to identify novel common prostate cancer susceptibility loci

How they went about it:

In the first two stages of this study, researchers used computer-based methods to combine data from their previously published genome-wide association study (GWAS) with another prostate cancer study (CGEMS) in order to identify single nucleotide polymorphisms (SNPs) for further analysis. Stage 3 of the study involved more than 1,300 SNPs being genotyped in nearly 5,000 prostate cancer patients and 5,000 healthy men from the UK and Australia. identified SNPs were then replicated in a further 26,000 cases and 25,000 men in the fourth stage.


Sixteen SNPs across 10 loci were identified in the third stage of this study. Of these ten loci, seven were novel loci that lie in regions that contain plausible causative genes. The SNP on chromosome 5 (rs2242652) is located within an intron of the TERT gene in a region linked to several other cancers. Interestingly, this SNP also showed an association with serum prostate-specific antigen (PSA) that was consistent with its prostate cancer association.


The identification of these seven novel loci brings the total number of known prostate cancer susceptibility loci to 40. These 40 loci are thought to account for around 25% of the familial risk. The top 1% of the population at highest risk are estimated to be at more than a four-fold increase in relative risk compared to the average risk in the general population with potential use of this information including targeted screening and prevention programs.

Our view:

A more than two-fold increase in relative risk for the top 10% of the population and a four-fold increase for the top 1% are no doubt large enough to be clinically useful. However, whether those individuals at the highest genetic risk are also at the highest risk of developing the aggressive form of disease needs further research in order to provide evidence for the clinical utility of screening and prevention programs. The PHG Foundation is a partner in a large European consortium, the Collaborative Oncological Gene-environment Study (COGS), a project that is developing the understanding of both genetic and environmental risk factors for breast, ovarian and prostate cancers, for use in individual risk prediction.

Keywords : cancer_genjournal

Analysis of a study published in a science journal   |   By Dr Philippa Brice   |   Published 20 July 2011
Study: US attitudes toward human embryonic stem cell research
In: Nature Biotechnology
What this study set out to do:

Assess US public opinion on government funding for human embryonic stem (HES) cell research by asking for their views on different applications of stem cell research. 

How they went about it:

Almost 2300 US citizens were interviewed about their views on five key areas said to relate to human embryonic stem cell research, focusing on the source of the cells used and the projected outcomes from the research: cloning animals, cloning humans, curing serious diseases by therapeutic cloning or by using stem cells from an IVF embryo, curing serious diseases using adult stem cells, and cosmetic uses. 


Most participants were opposed to cloning humans, with somewhat higher levels of support for cosmetic applications and cloning animals. Support was much higher for curing serious diseases, at around 70% for all the approaches listed, though somewhat lower for treating less serious diseases such as allergies.


The American public has different attitudes towards the various applications of stem cell research, but there was generally strong support for ‘all that offer hope of curing serious diseases’. Government policy, by ‘deferring to objections from a small (mainly religious) minority’ is suggested to be unethical in limiting funding for HES cell research.

Our view:

Review of public attitudes in shaping policy is a good idea, to place alongside the views of politicians who represent the public. However, the to conclude that public opinion provides an obvious mandate for government funding of HES cell research is a bit of a leap; not only was this specific question not addressed, but there was also possible bias in the questions posed. For example, those about therapeutic cloning refers to stem cells from IVF embryos as ‘amazing’ and having ‘no risk’ of rejection whereas adult stem cells were said to be ‘not well understood, and occasionally the new cells become cancerous’. 

Keywords : CloningStem CellsrFundingjournal

Analysis of a study published in a science journal   |   By Dr Philippa Brice   |   Published 18 July 2011
Study: Parents' Experiences of Expanded Newborn Screening Evaluations
By: et al. (4 authors total)
In: Pediatrics
Link: 10.1542/peds.2010-3413
What this study set out to do:

Evaluate the impact of an abnormal newborn screening result for rare metabolic diseases on parents, specifically those more recently added to US screening panels, and for which the medical implications are less well understood. 

How they went about it:

A total of 44 English-speaking parents without previous experience of metabolic disease whose apparently healthy babies had received abnormal metabolic screening results were interviewed about their experiences shortly after the screening result, and again after diagnostic confirmation. Of the 30 babies, nine had positive diagnoses, eight had negative diagnoses, and thirteen received ‘equivocal confirmatory results’.


Parents were shocked by abnormal results; most had not understood the screening process nor heard of the metabolic disorder in question, and typically researched it on the internet, being frightened by the information they found. Expert consultation was largely considered helpful, though some found the doctors lacked empathy. Waiting for test results was very stressful; those with positive results reported resignation; those with negative results; joy, and those with ambiguous results, confusion. Nearly all parents believed in the value of newborn screening for babies’ health, however. 


The ‘magnitude of parents’ distress while waiting for infants’ confirmatory test results should not be underestimated’ - quicker testing and better support to help parents identify metabolic symptoms in potentially affected babies are needed. Distress was high even though recruitment to the study was biased towards parents with better education and knowledge of science and health.

Our view:

Though very small, this study highlights the problem of accurately explaining newborn screening to parents, caring appropriately for those who receive abnormal results to minimise distress, and supporting those whose babies’ receive equivocal results. Research on the health impacts of disorders of uncertain clinical significance must be a priority, to see whether the medical benefits of newborn screening do (as hoped) outweigh the disadvantages (see previous news). 

Analysis of a study published in a science journal   |   By Dr Sowmiya Moorthie   |   Published 6 July 2011
Study: Integrated genomic analyses of ovarian carcinoma
In: Nature
What this study set out to do:

Carry out detailed molecular analysis of high-grade serous ovarian adenocarcinoma (HGS-OvCa) cells in order to identify and catalogue factors that influence pathophysiology of cancer and outcome of therapy, as well as identify potential therapeutic targets.

How they went about it:

The exomes of normal and tumour cells were captured and sequenced in order to identify genes mutated in the ovarian cancer cells. Microarray techniques were used to investigate gene expression, copy number changes and DNA methylation patterns in tumour cells.


Mutations in single genes as well as a large number of copy number changes contributed to disease. The majority of tumour cells had a mutation in the TP53 – a tumour suppressor gene, mutations in other genes including BRCA1 and BRCA2 are also associated with disease but were not present in all samples. The mutations present in HGS-OvCa are different from those present in other sub-types of ovarian cancer. Gene expression studies identified a number of genes are associated with survival and showed that there are distinct sub-types of the disease.


The identification of molecular sub-types of ovarian cancer is an opportunity for sub-type stratified treatment. Therapies aimed at genes involved in DNA repair may be beneficial as there are defects in the networks of genes involved in this process.

Our view:

Ovarian cancer is a leading cause of death in women and therapy is not always successful. An understanding of the underlying molecular defects that influence response to therapy can lead to better management of the disease and development of new therapies. Although further work is needed to investigate how the different molecular sub-types of cancer can be managed, this study is the initial step that could eventually lead to stratified treatment.

Analysis of a study published in a science journal   |   By Dr Gurdeep Sagoo   |   Published 7 July 2011
Study: Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease.
By: et al. (12 authors total)
In: PLoS Genetics
What this study set out to do:

To identify genetic variation associated with Parkinson’s disease in individuals of European ancestry. 

How they went about it:

The researchers from genetic testing company 23andMe conducted a genome-wide association study (GWAS) in 3,426 patients and 29,624 controls. Interestingly, this study took place ‘online’, with patients recruited through patient groups and tertiary clinics into the 23andMe database with controls coming from the existing customer database. Patients were clinically diagnosed and provided additional information via a web-based survey. 


Two novel associations were identified near the SCARB2 gene on chromosome 4 and SREBF1/RAI1 on chromosome 17. A further six previously identified loci were also replicated with an additional three loci close to a genome-wide significance level. Results were validated in two independent cohorts. 


This study used a novel web-based enrolment to conduct a large-scale GWAS, which resulted in the identification of two novel loci associated with Parkinson’s disease as well as the replication of several known loci. The authors suggest that the results provide support for their novel methodology as well as estimating a sizeable genetic contribution underlying Parkinson’s disease.

Our view:

Initially launched two years ago (see previous news), this study used web-based enrolment and self-reported phenotype data as well as utilising the 23andMe customer database to provide a control population. The authors acknowledge that using self-reported phenotype data is not without its problems, and that the population enroled was biased towards one with a higher socioeconomic status, although they believe that these ascertainment biases would not substantially affect the conclusions unless they differed between the patients and controls (which they do not believe to be the case). The study recruited nearly 3,500 patients and 30,000 controls in 18 months without the need for large-scale multinational collaborations, suggesting that this type of study design may have merit in significantly increasing power and robustness if designed carefully.

Analysis of a study published in a science journal   |   By Dr Philippa Brice   |   Published 1 July 2011
Study: In vivo genome editing restores haemostasis in a mouse model of haemophilia
By: et al. (20 authors total)
In: Nature
What this study set out to do:

Use zinc finger nucleases (ZFNs) to direct highly specific insertion of a gene into DNA (a process called genome editing) to create effective treatment of a genetic disease in mice. 

How they went about it:

A ‘humanised’ mouse model of the genetic disorder haemophilia B was created; these mice had no murine clotting factor IX gene, and only a mutated form of the human gene (hF9). ZFNs designed to target the hF9 gene sequence were joined to a healthy form of the hF9 gene to create a gene therapy vector that was injected into the mice. 


Liver samples from the mice removed after 10 weeks showed that the healthy hF9 gene had been successfully inserted in 1-3% of cells. Those mice that had received the gene showed human Factor IX levels of 2-3% in the blood and partially restored blood clotting amounting to effective treatment of haemophilia. 


ZFNs delivered with an appropriately designed gene-targeting vector can produce gene replacement at a specific position resulting in clinically significant correction of abnormal blood clotting caused by the faulty hF9 gene. Genome editing may therefore be ‘a viable strategy for the treatment of genetic disease’. 

Our view:

One of the major problems with gene therapy is inserting the healthy gene only into the desired  place in the genome, since insertion in other places can disrupt other genes and effectively drive the development of cancer. This phenomenon, known as insertional mutagenesis, has previously caused leukaemia in gene therapy recipients (see previous news). It appears that ZFNs might offer a way of achieving much more specific (and hence safer) insertion of corrective genes; if borne out by further experiments, genome editing could indeed be an exciting advance for gene therapy. 

New reviews and commentaries

Selected new reviews and commentaries, 3 July 2011

Reviews & commentaries : by Dr Philippa Brice

Personalised medicine: lessons from birth defects and single gene disorders

Burton H, Nacul L, Sanderson S. Curr. Pharm. Person. Med. 9(2): 1875-6921


The future of direct-to-consumer clinical genetic tests

Frueh FW et al. Nat Rev Genet. 2011 Jun 1;12(7):511-5. 


Making translation work

Williams RS, Desmond-Hellmann S. Science. 2011 Jun 17;332(6036):1359.


Gene expression: The autism disconnect

Korade Z, Mirnics K. Nature. 2011 Jun 15;474(7351):294-5.


Protein synthesis: Stop the nonsense

Ferré-D'Amaré AR. Nature. 2011 Jun 15;474(7351):289-90.


Genomics. Behavior and the dynamic genome

Bell AM, Robinson GE. Science. 2011 Jun 3;332(6034):1161-2. 


Been there, not done that - melanoma in the age of molecular therapy

Ernstoff MS. N Engl J Med. 2011 Jun 30;364(26):2547-8.


Genome-wide genetic marker discovery and genotyping using next-generation sequencing

Davey JW et al. Nat Rev Genet. 2011 Jun 17;12(7):499-510. 


Health advocacy organizations and evidence-based medicine

Rothman SM. JAMA. 2011 Jun 22;305(24):2569-70.


Global health diplomacy: how foreign policy can influence health

Kickbusch I. BMJ. 2011 Jun 10;342:d3154. doi: 10.1136/bmj.d3154.


Cancer risk assessment in Lynch syndrome: does the gene matter?

Xicola RM, Llor X. bJAMA. 2011 Jun 8;305(22):2351-2. 


Stem cells: iPS cells under attack

Apostolou E, Hochedlinger K. Nature. 2011 Jun 8;474(7350):165-6. 


Induced pluripotent stem cells - a cautionary note

Mummery C. N Engl J Med. 2011 Jun 2;364(22):2160-2. 


Democratizing clinical research

Lloyd K, White J. Nature. 2011 Jun 15;474(7351):277-8.  

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