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 31 May 2011

A new report from the PHG Foundation sets out a common framework for the evaluation and comparison of different models for predicting the risk of different diseases.


Risk prediction models for common diseases are an important element of public health practice, allowing screening and preventative interventions to be targeted to those at greatest risk of developing disease. As new data emerges, including on potentially predictive new biomarkers, the number of available and updated models increases – but there is no systematic approach to assessing their clinical performance.


Quality standards in risk prediction sets out a practical framework to assess risk prediction models, building on earlier PHG Foundation work on risk prediction for coronary heart disease, and based on the recommendations of international experts in the field. The new approach is based on assessments of three key ‘quality domains’ - the risk prediction model in question, the medical context in which it is to be used, and issues relating to clinical implementation of the model.

Comment: Using the best possible risk prediction model is critical for delivery of optimal health care, not only to identify and treat those at genuinely increased risk of developing serious disease, but also to ensure that others do not receive unnecessary treatments. Targeting treatments with the greatest accuracy avoids waste and minimises side-effects. This new approach to assessing and comparing current, updated and novel risk prediction models is therefore a valuable tool. 

Report of a story in the news   |   By Dr Philippa Brice   |   Published 28 May 2011

A bill that aims to make it easier for researchers to gain permission for research using human embryos and human embryonic stem cells (see previous news) has met fresh opposition from the French government.   

The French National Assembly has voted more than 2:1 against the proposed new measures that, though maintaining a general legal ban on research using human embryos, would make it easier to obtain legal exemptions. The Senate passed the bill following a first reading, and a second reading is scheduled for next month, but if they pass the bill again, the National Assembly decision will reportedly take precedence. A final decision may take months. 

Our view:

Many researchers are keen to press ahead with human embryonic stem-cell research, and will be frustrated by this turn of events. However, as the vote clearly demonstrated, many people in France have profound ethical concerns about the use of human embryos and cell lines, even for medical research, feeling that the ends do not justify the means.

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

The possibility of strict regulation of direct-to-consumer (DTC) genetic tests in the US continues with further warnings from the Food and Drug Administration (FDA) issued to companies.


The FDA began sending warning letters that commercial tests or services might require regulatory approval as medical devices last year (see previous news). Earlier this month a fresh batch of letters went out; Lumigenix offers genetic predisposition testing similar to that of other DTC companies, whereas PQDNA is more unusual in offering solely a service to help consumers understand genetic data and identify information relative to health. Their CEO Andre Gous has said that the FDA could "regulate the industry into de facto oblivion” and that they risk overextending their regulatory reach, adding that it is nonsensical "to consider DNA 'spit tubes' as 'medical devices’".


The third company invited asked by the FDA to make a case for why their products should not be subject to medical device regulation is AIBiotech, which sells the controversial new Sports X Factor Test Kit, which claims to enhance athletic performance in young people by using genetic information to determine how to tailor training, determine how much rest is needed following head injuries, and assess the risk of inherited cardiac conditions. Experts are concerned about the veracity of the medical claims for this test, and potential dangers to children whose parents opt to have them tested. 

Comment: This is a difficult situation; whilst the FDA has a clear legal requirement to regulate medical devices to protect consumers from harm including inaccurate test results or clinical interpretations, attempting to define any type of genetic testing and even interpretation services as medical devices is a stretch. Clearly, some sort of regulatory oversight for medical claims is needed, but so is a common-sense approach. 

Report of a story in the news   |   By Dr Philippa Brice   |   Published 23 May 2011

A new report outlines the findings from a US expert workshop looking at evidence for genetic tests for clinical applications. 

The workshop was hosted by the Institute of Medicine (IoM) in November 2010 and examined these issues with a view to ultimately driving forward translation of genomic research for health by providing evidence of the clinical efficacy of genetic tests. Participants included researchers, health care providers, commercial developers, policy-makers and funders, all considering questions of what evidence was needed, how it was currently generated, whether there were better ways to produce the required evidence, and what barriers existed to prevent this.

Our view:

It was noted that different stakeholders require different sorts of evidence, and that maintaining dialogue between them throughout development and evaluation of new genetic tests was important. The experts recommended that trials to generate evidence were increasingly required, but should be designed with reference to the specific clinical context for testing. Issues relating to clinical practice, health insurance reimbursement for genetic tests, and clinical research were also considered.

News story   |   By Dr Philippa Brice   |   Published 24 May 2011

The UK Supreme Court has ruled in support of an earlier European legal ruling that the records of up to one million individuals should be expunged from the National DNA Database.

The largest forensic DNA database in the world (see previous news) has for some years caused controversy over a number of practices, including the retention of samples and linked data from crime suspects who were subsequently either not charged, or tried but found innocent of any crime. The Supreme Court has now echoed the ruling of the European Court of Human Rights three years ago by concluding that this practice violates parts of the European Human Rights Convention and is therefore unlawful.


The UK government is planning updated provisions in the forthcoming Protection of Freedoms Bill currently before Parliament that will, if it passes into law, prevent retention of samples in circumstances. Until then, police may continue to hold DNA samples of anyone who is arrested, in accordance with the legal framework put in place in 2001.

News story   |   By Dr Philippa Brice   |   Published 23 May 2011

The Nuffield Council on Bioethics has launched a public consultation on ethical, legal, social and policy issues arising from emerging biotechnologies.

The findings will feed into the work of a UK group examining how policy-makers and wider society respond to new forms of biotechnology and engage with the new issues they may present. Existing (but relatively recent) biotechnologies under consideration will include synthetic biology, regenerative medicine, assisted reproductive technologies and genetically modified crops.


Views are sought from all those involved in the development and implementation of such technologies, including examples of other emerging technologies that may pose particular issues, and questions relating to risk assessment and decision-making, regulation, globalisation and public engagement.


The deadline for responses is 15th June 2011, with the findings of the group due to be released in autumn 2012.

Report of a story in the news   |   By Dr Philippa Brice   |   Published 19 May 2011

The 1000 Genomes Project (see previous news) has announced completion of low-coverage whole genome sequencing of over 1,000 DNA samples at the Biology of Genomes meeting in Cold Spring Harbor last week. 

The project aims to create a resource on human genetic variation for use by other researchers, cataloguing common variants in populations from Europe, Asia, Africa and the Americas. The first phase (1167 samples) should be completed later this year, and ultimately the aim is to sequence 2,500 samples from healthy individuals. Whole exome sequencing for 997 samples and SNP genotyping for more than 1,500 have been completed thus far. 

Our view:

It is hoped that the data will refine the ‘reference’ human genome sequence and be of value to many other research efforts, partly by allowing comparisons to see whether newly identified genetic variants are common in different populations or not, and therefore how likely they are to be associated with disease.  

Report of a story in the news   |   By Dr Philippa Brice   |   Published 17 May 2011

A Canadian study will create new and improved resources for investigating the role of genetic mutations in neurological diseases. 

CanEuCre project researchers will develop resources that use the cre-recombinase (Cre) gene to induce novel mutations and model disease states affecting the brain, spinal cord and eye in mice. The work is funded by Genome BC, and links with the EU-funded EUCOMM Tools study, part of international work in developing mouse models of human disease by genetic manipulation. 

Our view:

Lead investigator Dr Elizabeth of the Centre for Molecular Medicine and Therapeutics said that the project would “put in the hands of scientists worldwide the tools needed to explore what every gene in the genome does, both under normal circumstances, and when diseased". It is hoped that the resources will ultimately be used for applied research developing therapeutics for neurological disorders such as Parkinson’s and Alzheimer’s diseases 

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

A new report from has said that the $3.8 billion investment in the Human Genome Project (HGP) has generated $796 billion in economic impact.


The economic modelling study was performed by Battelle, an independent scientific research and development organisation, and sponsored by Life Technologies Corp. It shows that every dollar invested in the US elements of the international HGP has generated $141 in the economy. It is estimated that in 2010 alone, academic and commercial genomic sequencing and research supported 310,000 jobs and generated $67 billion economic output.


This return on investment (ROI) is despite the fact that the major impacts of the HGP have yet to be realised, in terms of health and innovation, and the study authors conclude that the project is ‘arguably the single most influential investment to have been made in modern science’ and a crucial foundation for progress in biomedical research.


The report identifies expected future benefits from the HGP and concomitant developments in human, animal, plant and microbial genomics, including in agriculture and food production, biofuels and environmental measures such as synthetic organisms designed to reverse pollution.

Comment: This is a fascinating insight into direct and indirect positive financial impacts of the HGP, and provides a heartening counterpoint to the usual frustration that the medical benefits are much slower to materialise than originally hoped (largely because the human genome has proved to be vastly more complex than ever imagined). Of course, these estimates are just for the US; burgeoning genomics industries have also developed in the other HGP partner countries (the UK, China, Japan, Germany and France) as well as many more. 

Report of a story in the news   |   By Dr Philippa Brice   |   Published 9 May 2011

A new national genetic research programme has been launched by the US Veterans Affairs (VA) Office of Research and Development. 

The Million Veteran Program (MVP) will create a large-scale database detailing genetic and health data from military veterans, along with information about their lifestyles and military exposures. Data will be made securely available to authorised giovernment and academic researchers for ‘studies to determine which genetic variations are associated with particular health issues’, with a view to developing improved methods for ‘preventing and treating illnesses in Veterans and all Americans’. Participation is voluntary.

Our view:

The VA office is well equipped to create a large-scale and potentially very valuable research resource such as this, having advanced electronic health records for veterans coupled to healthcare providers and genomic research laboratories. No information is given about the nature of uniquely military exposures and health outcomes that may be of particular interest to the VA researchers – one possibility might be research into genetic predisposition to adverse psychological reactions to trauma, for example.

News story   |   By Dr Philippa Brice   |   Published 4 May 2011

A group of scientists have written to Nature expressing their fears that proposals to ban patent protection for embryonic stem cell lines in Europe will harm medical research and progress.


The letter follows a statement from the Advocate General of the Court of Justice of the European Communities saying that patenting of applications using human stem cells is invalid on ethical grounds since they are either derived from, or have the potential to become, human embryos (see previous news). Writing in Nature, the scientists dispute this view and warn that removing patent protection would be a serious blow to biomedical commercialization and clinical application in Europe.


EuroStemCell, a pan-European project bringing together stem cell and regenerative medicine researchers, is spearheading a campaign for signatures in support of this open latter. The International Society for Stem Cell Research has also issued a statement expressing concern that halting patent protection ‘will preclude investment in potentially life-saving treatments’.


Lawyer Julian Hitchcock, Director of CellFate and a PHG Foundation Associate, has criticised the Advocate General’s failure to take account of the scientific facts’ in suggesting that a human body begins to form at the point of fertilisation (see commentary), and that the AG’s position protecting the status of fertilised human embryonic cells or cell lines is actively detrimental to humans affected by degenerative conditions, who might benefit from therapies arising from human embryonic stem cell research.

Comment: Patent protection is certainly a very important financial incentive for investment in biomedical research, which is why moves to block patenting of gene sequences have met stiff opposition (see previous news) and why researchers’ concerns over a potential ban on stem cell patenting are very valid. However, many people also hold strong ethical views about the use of embryos. Greenpeace, who initiated the original German legal case, said that they were not opposed to stem cell research but wanted ‘clarification that the industrial and commercial use of human embryos is not encouraged’.

It should perhaps be noted that the courts’ function is to examine only the relevant legal issues (and both ethical and intellectual property principles are enshrined in law), irrespective of the competing perspectives. 

News story   |   By Dr Philippa Brice   |   Published 4 May 2011

After temporarily blocking an injunction preventing federally funded human embryonic stem (HES) cell research in the US (see previous news), the Court of Appeals for Washington, D.C has now ruled that such research is legal and can continue.


Two of the three panel judges concluded that it was reasonable to interpret the existing law against federal funding for research in which embryos are destroyed as meaning that only research involving the direct destruction of embryos is prohibited from funding.  Last year’s injunction stated that allowing federal funding of research using stem cells originally derived from embryos on the basis that private funding had been used for the original creation of stem cell lines (and concomitant destruction of embryos) was invalid (see previous news).


Comment: The decision is good news for HES cell researchers, although in many ways the damage has been done as uncertainty over federal funding continues; appeals against this most recent ruling could still be lodged. President of the California Institute for Regenerative Medicine (CRIM) Dr Alan Trounson said that "The fight for embryonic stem cell research in the United States is not over", noting also that "A stop-start approach is not good for research".  

The state-funded CRIM is apparently attempting to keep its options open with respect to stem cell research, as it is reportedly considering funding induced pluripotent stem (iPS) cell banking projects. Research using iPS cells is considered by many to offer an ethically acceptable alternative to potential HES cell therapeutics, but there are significant scientific barriers to application, and some also fear that over emphasis on HES cell research could actively hinder funding for the development of iPS cell alternatives. 

News story   |   By Dr Philippa Brice   |   Published 1 May 2011

A new overview of the ENCODE (Encyclopedia Of DNA Elements) project has been published.


The overall goal of the project (see previous news) is to identify and understand the functional regions of the human genome – a task that grows in magnitude as more is learned about the complexity of regulation and control of the genome. Gene-coding regions represent a very small proportion of the whole human genome sequence; it is not yet known what proportion regulatory regions comprise, although more than two million potential elements have already been identified by the project.


Released in PLoS Biology, the new guide to the resources and data arising from the ENCODE project details completion of the mapping of two major groups of genomic elements: all gene sequences (both coding genes that specify proteins, and non-coding genes that specify functional RNA molecules), and all regions known to control gene expression.

ENCODE researchers are working to combine their findings with those from other major research initiatives such as the 1000 Genomes project (see previous news) and the NIH Roadmap Epigenomics program (see previous news). Their hope is that combining data on functional genomic elements with information about genetic and epigenetic variation and different human phenotypes will improve our understanding of the relationships between genetics, health and disease. The overview provides examples of how these data can be used to interpret human genome data such as associations between genetic variants and diseases, and guide further research. 

Research articles

Analysis of a study published in a science journal   |   By Dr Philippa Brice   |   Published 30 May 2011
Study: Transcriptomic analysis of autistic brain reveals convergent molecular pathology
By: et al. (10 authors total)
In: Nature
What this study set out to do:

To establish whether the brains of people with autism spectrum disorder (ASD) shared common genetic changes and molecular pathology that might arise from multiple genetic and environmental causes.

How they went about it:

Post-mortem brain tissue samples from 19 individuals with ASD and 17 unaffected controls were analysed for gene expression in regions of the brain previously implicated in ASD. Samples from the cerebral cortex region showed significantly different patterns of genetic activity and were examined further using a technique called gene co-expression network analysis. 


Both control and autistic brain samples showed a good degree of global similarity with transcriptome patterns from previously analysed normal human brains. However, between different parts of the cerebral cortex where normal brains showed different patterns of gene activity, autistic brains had a very similar pattern in both regions. 


There are consistent differences in gene activity between the brains of autistic and normal individuals. Two networks of functionally related genes were found to be significantly associated with autism; one included several known autism susceptibility genes, whereas the other included genes involved in immune and inflammatory responses. This provides evidence for convergent molecular abnormalities in ASD. 

Our view:

This study provides a remarkable insight into how different genetic and environmental factors might contribute to a common pathology; the gene network involved in immune responses has not been implicated in previous GWAS as an important heritable risk factor for ASD and so is suggested to be either a secondary or environmentally mediated contributor to abnormal brain function. Obviously, the study was very small, and independent replication of these findings is needed, but they are nevertheless exciting both in opening up new avenues of research for ASD and also possible application to other complex diseases with significant genetic components.

Analysis of a study published in a science journal   |   By Dr Sowmiya Moorthie   |   Published 26 May 2011
Study: Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2
By: et al. (37 authors total)
In: Nature Genetics
What this study set out to do:

Cystic fibrosis (CF) is a recessive disorder caused by mutations in the CFTR gene; the main organs affected are the lungs and digestive system. The severity of lung disease in CF varies and cannot be explained by CFTR mutations; this study wanted to identify additional genetic factors that may influence disease severity.

How they went about it:

Individuals with CF enrolled in three different studies were genotyped. Two of these cohorts, Genetic Modifier Consortium (GMC) and Canadian Consortium for Genetic Studies (CCGS) consisted of unrelated individuals and the cystic fibrosis Twin and Sibling Study (TSS) consisted of related individuals. In order to identify candidate loci, a genome-wide association (GWA) study was carried out on genotype data of the unrelated individuals as a whole and then only those with one particular CFTR mutation – a  homozygous deletion. Family based linkage analysis as well as GWA was carried out on the genotype data of the related individuals.


The GWA study on all unrelated individuals identified seven genetic regions with possible association. A significant association between lung disease severity and a single nucleotide polymorphism (SNP) on chromosome 11 was detected when the analysis was restricted to those individuals with the homozygous deletion. This association was also confirmed in the cohort of related individuals with the same deletion. Analysis on data from the TSS cohort identified a locus at chromosome 20 associated with lung disease severity.  Both these regions contain genes that modify lung function.


The use of two different approaches provided complementary findings and a method that can be applied to identify other modifying genes related to CF. Further studies are needed to investigate the candidate genes at the regions identified and their role in influencing the severity of lung disease, as well as to investigate other genetic regions identified in this study

Our view:

Along with the identification of two genetic regions related to lung disease severity in CF, this research also provides a methodology that could potentially be used to study modifier genes involved in other monogenic disorders. The rarity of many monogenic disorders often means that sample sizes are too small for their use in GWA studies, but the collaborative approach used here overcomes this problem to a certain degree. This study also highlights the fact that although monogenic disorders are generally attributed to a single gene, the reality is in fact more complex.

Analysis of a study published in a science journal   |   By Dr Gurdeep Sagoo   |   Published 23 May 2011
Study: Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes.
By: et al. (20 authors total)
In: Nature Genetics
What this study set out to do:

The study authors looked at whether a genetic variant (SNP rs4731702) in the KLF14 gene, associated with both type 2 diabetes and cholesterol levels, alters the expression levels of other genes.

How they went about it:

The researchers looked for associations between rs4731702 and the expression levels of over 16,000 genes in fat samples from a cohort of 776 healthy female twins of European descent (from the multiple tissue human expression resource study). Ten genes were then followed up in an additional 589 fat samples from the Icelandic deCODE study, along with further functional lab-based work.


The authors found that rs4731702 was associated with gene expression levels in fat tissue for many genes. Of these they then focused on the expression levels of ten genes (TPMT, ARSD, SLC7A10, C8orf82, APH1B, PRMT2, NINJ2, KLF13, GNB1 and MYL5) on various metabolic phenotypes (including BMI and levels of HDL cholesterol, trigylcerides, fasting insulin and HOMA-IR). Expression levels of six of these genes were in turn associated with BMI and HDL cholesterol, five with triglycerides and fasting insulin levels, and four with HOMA-IR (an index measure of insulin sensitivity). 


The study authors concluded that their data provided convincing evidence of the involvement of KLF14 on risk of metabolic disease. KLF14 is associated with HDL cholesterol and type 2 diabetes and exerts regulatory influence on other genes that influence metabolic disease risk such as APH1B (associated with HDL and triglycerides), MSRA (associated with waist circumference and triglycerides) and several other genes (associated cholesterol, BMI and triglycerides). 

Our view:

This work not only provides a hypothesis-driven framework for further investigative work but also highlights the complexity that underlies common complex diseases such as type 2 diabetes and obesity. This study shows how a single gene may influence disease risk both through its own actions and by regulating the actions of other genes, which in turn also influence disease risk. The next step will be to identify how these genes work in obese people and how this can be used to develop treatments.

Analysis of a study published in a science journal   |   By Dr Sowmiya Moorthie   |   Published 18 May 2011
Study: Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
By: et al. (16 authors total)
In: Nature Genetics
What this study set out to do:

Previous studies on autism spectrum disorder (ASD) have suggested that sporadic cases may be caused by new (de novo) mutations, as opposed to inherited mutations. The aim of this study was to identify specific de novo mutations in sporadic ASD cases.

How they went about it:

The genomes of families with sporadic ASD (i.e. parents and child) as well as controls were analysed to identify genetic variants unique to sporadic ASD. ArrayCGH was used to identify large copy number variants followed by exome sequencing. Comparison with parental sequences as well as data from the dbSNP database, 1000 Genomes Project and other genome sequences was used to filter out variants not unique to children with ASD. 


ArrayCGH did not identify any large de novo copy number changes except in one individual, which was not thought to be causal for ASD. In total 21 de novo changes were identified in individuals with ASD, many within gene coding regions. Eleven mutations were predicted to affect protein function. In four cases the mutations were within genes that have previously been shown to be associated with autism, epilepsy and intellectual disability, suggesting they may be the causal mutations. However, the researchers also identified rare inherited variants that may be linked with autism in these individuals.


New mutations that may be associated with autism can be identified through trio studies. However,  inherited variants were also found, suggesting that other genetic factors may impact disease symptoms or severity, and more research is needed to understand how different genetic and environmental factors interact.

Our view:

Research has shown that autism spectrum disorders have a strong heritable component, however, identification of the genetic factors involved has been difficult (see previous news). This paper contributes to our understanding of the genetic basis of autism, but also highlights the need for a better understanding of the biology as well as the role of environmental factors in order to better understand this multifactorial condition.

Analysis of a study published in a science journal   |   By Dr Susmita Chowdhury   |   Published 11 May 2011
Study: Polygenic susceptibility to prostate and breast cancer: implications for personalized screening
In: British Journal of Cancer
What this study set out to do:

To model a personalised screening strategy for breast and prostate cancer based on genetic risk and age, and compare it with a screening strategy based on age alone.

How they went about it:

The researchers compared screening approaches based on age (all men aged 47–79 offered prostate cancer screening; all women aged 47–79 offered breast cancer screening) with novel personalised screening approaches based on both age and genetic risk profiles. The number of people eligible to receive screening and the expected number of cancer cases that would be detected for each case were considered.


Under the personalized screening strategy, 16% fewer men would be eligible for prostate cancer screening and 3% fewer cases would be detected, though there would be an increase in cases detected in younger men (<55yrs). Similarly, the personalised strategy would result in 24% fewer women being eligible for breast cancer screening and 14% fewer cases would be detected.


Personalized screening strategies based on age and genetic risk would potentially improve efficiency, substantially reducing the number of people receiving screening with only a small decrease in the overall number of cancer cases detected. Detection of the more aggressive prostate cancers in younger men would improve. Besides being more cost-effective, reducing the number of people screened using this approach would also reduce the harms associated with screening, such as false-positive results, overdiagnosis and unnecessary treatment.

Our view:

Despite limitations such as the necessity to make certain assumptions in modeling the available data, this study shows that it is feasible to use genetic information (in the form of polygenic risk profiles) to improve screening of the general population for cancer. It would be interesting to see the effect of including other factors in risk estimates, such as lifestyle factors, mammographic data and new genetic markers. Policies are unlikely to change overnight to embrace personalised screening; in addition to further research, many ethical, legal and social issues related to genetic testing and risk prediction would require careful consideration. Nevertheless, this work may be laying the foundations for future use of genetic information to improve cancer detection and survival. 

Analysis of a study published in a science journal   |   By Dr Sowmiya Moorthie   |   Published 10 May 2011
Study: ESR1 Is Co-Expressed with Closely Adjacent Uncharacterised Genes Spanning a Breast Cancer Susceptibility Locus at 6q25.1
By: et al. (11 authors total)
In: PLoS Genetics
What this study set out to do:

Previous studies had shown that SNPs at a locus on chromosome 6 are associated risk of breast cancer; the aim of this study was to identify the causative genetic variant within this region and understand how it influences risk of oestrogen receptor α-positive (ER+ve) breast cancer.

How they went about it:

In order to identify genes that were correlated with the ESR1 gene, mRNA in tumour samples from 104 women with ER+ve breast cancer were analysed. Gene expression data from publicly available normal and breast cancer datasets were used to validate findings, and the biological effects of relevant genes were investigated further by manipulating their expression in cell cultures.


The levels of three genes (C6ORF96, C6ORF97, and C6ORF211) were correlated with ESR1 expression both before and after treatment with oestrogen synthesis inhibitors. Investigation of the function of these genes showed that C6ORF211 promotes proliferation (growth) of cultured cells, and is correlated with proliferation in breast tumours, whereas C6ORF97 inhibits proliferation.


Although these genes are linked to the oestrogen receptor, their behavior is independent of it, suggesting that they may mediate or modify its biological effects. They may also act in conjunction with SNPs in this region to influence breast cancer risk; however, this has yet to be established. The exact biological relationship between ESR1 and these genes is yet to be discovered, but they could be potential targets for future therapies.

Our view:

Breast cancer is the most common cancer in women in the UK and an understanding of the biological factors involved is important in directing existing treatments and developing new ones. This study identifies new factors that may play a role in the disease, but further work is needed to understand their exact role in breast cancer and their potential as targets for therapy.

Analysis of a study published in a science journal   |   By Dr Gurdeep Sagoo   |   Published 5 May 2011
Study: Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1.
By: et al. (25 authors total)
In: Nature Genetics
What this study set out to do:

To identify genetic loci associated with open angle glaucoma (OAG) blindness.

How they went about it:

The researchers performed a genome-wide association study covering nearly 300,000 SNPs in 590 individuals with advanced OAG and 3,956 healthy controls of European descent. This was followed up with further genotyping in 892 cases and 4,582 controls from three replication cohorts, also of European descent, along with further lab-based functional work.


The initial discovery cohort linked two genomic regions on chromosomes 1q24 (near the TMCO1 gene) and 9p21 (in the CDKN2B-AS1 gene) with OAG at genome-wide significance. The top SNPs at these two locations also showed association at less stringent statistical significance levels in the replication cohorts. Functional studies showed that TMCO1 and CDKN2B-AS1 may play a role in glaucoma through retinal ganglion cell death.


Carriers of one or more risk allele at the two genes identified by the researchers in this study impart a three-fold increase in risk for advanced OAG. Identification of the CDKN2B-AS1 gene on chromosome 9p21, as well as increased expression of both CDKN2A and CDKN2B (also located on 9p21) in a rat glaucoma model, highlight the importance of this genomic region in the genetic risk of OAG.

Our view:

Glaucoma can lead to complete blindness if left untreated but if caught early can be treated to slow down any further loss of sight. However, because OAG progresses very slowly patients often do not notice the loss of peripheral vision until the disease is advanced. If those at increased risk of developing OAG can be identified early, treatment can be given in a timely manner to minimize the loss of sight caused by OAG. The findings from this study could lead to improved risk prediction and even diagnosis, suggesting plausible biochemical pathways involved in OAG. More research is needed though to confirm exactly which genes are involved, as the authors themselves suggest that the ALDH9A1 gene rather than TMCO1 could be responsible for the observed association.

New reviews and commentaries

Selected new reviews and commentaries, 3 May 2011

Reviews & commentaries : by Dr Philippa Brice

Direct-to-consumer testing: if consumers are not anxious, why are policymakers?

Caulfield T. Hum Genet. 2011 Apr 11.


Scientists see promise and challenges in translating genomics to the clinic.

Kuehn BM. JAMA. 2011 Apr 6;305(13):1285-6.


Whole-genome sequencing: a step closer to personalized medicine.

Pasche B, Absher D. JAMA. 2011 Apr 20;305(15):1596-7. 


Genomics, Biobanks, and the Trade-Secret Model.

Mitchell R et al. Science. 2011 Apr 15;332(6027):309-310.


Next-generation association studies for complex traits.

Zeggini E. Nat Genet. 2011 Mar 29;43(4):287-8.


Cell biology. Are telomere tests ready for prime time?

Leslie M. Science. 2011 Apr 22;332(6028):414-5. 


Frightening risk of Marfan syndrome, and potential treatment, elucidated.

Couzin-Frankel J. Science. 2011 Apr 15;332(6027):297


Inherited cardiomyopathies.

Watkins H, Ashrafian H, Redwood C. N Engl J Med. 2011 Apr 28;364(17):1643-56.


Genetics. Minor splicing, disrupted.

Pessa HK, Frilander MJ. Science. 2011 Apr 8;332(6026):184-5. 


Ex vivo gene transfer and correction for cell-based therapies.

Naldini L. Nat Rev Genet. 2011 May;12(5):301-15.


State-of-the-art gene-based therapies: the road ahead.

Kay MA. Nat Rev Genet. 2011 May;12(5):316-28.


Current prospects for RNA interference-based therapies.

Davidson BL, McCray PB Jr. Nat Rev Genet. 2011 May;12(5):329-40.


Heart failure: advances through genomics.

Creemers EE, Wilde AA, Pinto YM. Nat Rev Genet. 2011 May;12(5):357-62.


When science and the media mix.

Reddy C. Science. 2011 Apr 1;332(6025):13.


No second thoughts about data access.

Nat Genet. 2011 May;43(5):389.


The lawyer's brief on ethics.

Sokol DK. BMJ. 2011 Apr 27;342:d1815.


Regenerative medicine: DIY eye.

Ali RR, Sowden JC. Nature. 2011 Apr 7;472(7341):42-3. 


Newborn screening: how are we travelling, and where should we be going?

Wilcken B. J Inherit Metab Dis. 2011 Apr 16. [Epub ahead of print] 

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