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   |   Published 17 November 2006

The European Commission is currently seeking comments on a draft report into the ethics of clinical trials involving children. Ethical Considerations for Clinical Trials Performed in Children has been prepared by an Ad-Hoc committee looking into developing and implementing guidelines for the Clinical Trials Directive (2001/20/EC) related to good clinical practice in the conduct of clinical trials on medicinal products for human use. The authors of the Clinical Trials Directive recognised a need for investigations involving children, as they are physically and developmentally different than adults. However, as they are a vulnerable population, special issues will arise. “Medicinal products, including vaccines, for children need to be tested scientifically before widespread use.…The clinical trials required for this purpose should be carried out under conditions affording the best possible protection for the subjects. Criteria for the protection of children in clinical trials therefore need to be laid down.”


Broad topics covered include: informed consent; assent from the child; the need for appropriate expertise on ethics committee to review paediatric clinical trials; trial designs; pain, distress and fear minimisation for children involved in trials; and measures of benefit whether directly for the child or those with the same disease or condition. Specific guidance is given on, for example, informed consent (and assent from children) for emergency trials, informed consent (and assent for children) of families from a different cultural background, and differences of opinion between the child and the legal representative. The final recommendations, resulting from this consultation, should be of benefit to ethics committee members, sponsors and investigators who are involved with paediatric clinical trials. The consultation ends 31 January 2007; comments can be sent to

News story   |   Published 15 November 2006

The Caldicott Review of 1997 made several recommendations for good practice in the use and transfer of patient-identifiable information in the NHS. Among these recommendations was that every NHS organisation should appoint a Caldicott ‘Guardian’: a person of board-level seniority who would oversee arrangements for the use and sharing of clinical information held by their organisation. The Department of Health has recently issued a new manual for Caldicott Guardians, updating previous guidance to incorporate requirements arising from recent legislation on data protection, freedom of information and human rights, and the development of new information systems and policy for information governance within the NHS.

The Caldicott Guardian Manual 2006 sets out the roles and responsibilities of Caldicott Guardians, including responsibility for overseeing new flows of information resulting from the development of the NHS Electronic Care Record and similar electronic record systems in other related organisations such as social services. The Caldicott Guardian is also responsible for arrangements for disclosure of information to outside bodies such as the police or researchers. The Cayton review of information governance in the NHS (published earlier this year) recommended the setting up of an information governance steering group within each NHS organisation; the 2006 Caldicott Guardian Manual recommends that the Caldicott Guardian should attend this group in person.

The Manual concludes with a list of organisations and websites providing reliable information and guidance on the legal aspects of information governance and NHS policy in this area.

News story   |   Published 14 November 2006

The Human Genetics Commission has published its response to the Department of Health’s three-year review of the Genetics White Paper. The HGC’s response commends the original objectives of the White Paper, which outlined the Government’s vision for developing genetic services and for integrating genetics into healthcare more generally- a vision that was to be supported by ring-fenced funding.

The HGC highlights the positive impact of the White Paper in developments such as the establishment of the National Genetics Education and Development Centre, and it lists areas of its own work that have been complementary to the aims set out in the White Paper. It also flags up issues that may need particular attention in the future, including the regulation of direct-to-consumer genetic testing, the need to communicate more effectively with the public about large-scale research projects such as Biobank, ensuring equity of provision of genetic services in the NHS, the implications of the National Programme for IT (Connecting for Health) for genetic information, the impact of intellectual property and patenting in genetics, and the future development of antenatal screening programmes.

The HGC’s response also sounds a note of serious concern that the benefits gained from the initial investment in the White Paper programme may be lost through uncertainty about future funding. It questions the rationale for a review after only three years, given the time it takes to develop high-quality projects to the point where results can be evaluated, and expresses concern about “a real possibility that developments would not be sustainable and would dissipate in the next financial year”.

An issue singled out for particular attention is the lack of a “clear mechanism for translating genetic (or indeed any technological) advances from the research laboratory into healthcare practice” and the fact that, as a result “this transfer is not strategic, is slow and is an ad hoc process”. The development process that is an essential part of the transition from research to service, says the Commission, “is not currently addressed by existing funding streams”.

Comment: The need for a coherent process to bridge the gap between research and healthcare implementation is also highlighted in the PHGU’s response to the White Paper review, and indeed is the rationale that underlies the approach of public health genetics. Public health genetics is defined as “the responsible and effective translation of genome-based knowledge and technologies for the benefit of population health”. It proceeds by integrating knowledge from basic research in genomics (both scientific and in the arts and humanities) and using this integrated knowledge base to underpin four core sets of activities: informing public policy, developing health care services, education and training, and stakeholder engagement. If sustained funding is not made available for these initiatives, the promised benefits of genomics for health care may indeed not be fully realised.

News story   |   Published 7 November 2006

Two research teams from Newcastle University and Kings College, London, have applied to the Human Fertilisation and Embryology Authority (HFEA) for licenceto create embryos by fusing human DNA with cow eggs, a technique known as nuclear transfer or therapeutic cloning. A third application is expected to be submitted from Edinburgh University. Bovine oocytes would have the nucleus (containing the majority of the bovine DNA) removed before being fused with human cell nuclei; the resulting chimeric human-bovine embryos would be grown for six days, then harvested for stem cells. All embryos would be required to be destroyed by 14 days.

The stem cells would be used for research purposes. The purpose of the application is supposedly to make up for the limited supply of human eggs by using cow eggs instead; genetically, the human-cow embryos would be largely human because only extra-nuclear bovine genetic material would be present. The Newcastle team, led by Dr Lyle Armstrong, wants to analyse the process of cellular genetic reprogramming following nuclear transfer, in the hope of learning how to make embryonic stem cells without an animal egg. Dr Armstrong said: “At the moment we don’t know if the nuclear transfer process works well enough in humans to create useful embryonic stem cells. We need to carry out many tests to establish this and, as animal eggs are freely available, it makes sense to use these as a source of material for our laboratory work” (see Newcastle press release).

Dr Stephen Minger, who leads the King's College application, wants to use the chimeric embryos to continue current work to produce disease-specific stem cells from humans with genetic neurodegenerative diseases. He said that they considered it appropriate to use “non-human oocytes from livestock as a surrogate” rather than human ooctyes from women. Dr Minger also stated: “Once the nucleus of the animal egg is removed it essentially no longer has a species identity and when replaced with a human nucleus, the resulting embryo and cell line will have human genetic identity” (see King’s press release). However, this is not strictly correct, as although the vast majority of genetic identity would be human, heritable extra-nuclear genetic material such as that present in the cellular structures mitochondria would be bovine in origin.

Critics of the plans have slated the application to the HFEA as potentially dangerous, as well as unethical. Calum MacKellar of the Scottish Council on Human Bioethics said: "In this kind of procedure, you are mixing at a very intimate level animal eggs and human chromosomes, and you may begin to undermine the whole distinction between humans and animals…If that happens, it might also undermine human dignity and human rights" (see BBC news report).

News story   |   Published 6 November 2006

The European Commission has announced the adoption of the second set of technical rules, Commission Directive 2006/86/EC, implementing the European Tissues and Cells Directive (Directive 2004/23/EC) (see press release). The new Directive addresses the processing, preservation, storage and distribution of tissues and cells intended for human application. The first set of technical rules, Commission Directive 2006/17/EC, was published in February 2006 and provided rules for the donation, procurement and testing of tissues and cells. According to the Commission, these rules “…will help to ensure a high level of public health protection in all Member States, and prevent the transmission of diseases via donated tissues and cells.”

In this second technical Directive, rules are laid out for the accreditation of tissue establishments and for preparation processes for tissues and cells. Also covered are procedures for notifying competent authorities in Member States of serious adverse reaction events and the conclusions reached after events have been investigated. Ensuring that donations can be traced from donor to recipient is a key requirement in the Tissues and Cell Directive and this new Directive confirms that a single European code will be assigned to donated materials in order that they may be identified wherever they are being used. The Coding System will include, at the minimum, donation information and product details, but no further details on the system are provided. The Human Fertilisation and Embryology Authority, the UK competent authority for reproductive cells, has noted in their Tissues and Cells newsletter that the coding system is not expected to be implemented until September 2008.

Now that this new Directive is in place Member States will be able to finalise their national systems in these areas. Draft regulations to transpose these Directives into UK law, by amending the Human Fertilisation and Embryology Act 1990 and the Human Tissue Act 2004, have been drafted. The consultation on them has been completed and they are now being finalised. It is intended that the final Regulations will be placed before Parliament at the end of 2006 and brought into force by April 2007.

News story   |   Published 1 November 2006

The Nuffield Council on Bioethics has launched a consultation entitled, Forensic use of bioinformation: ethical issues. The consultation aims “To identify and consider the ethical, social and legal issues raised by current and potential future uses of bioinformation for forensic purposes,” in particular as it relates to DNA and the UK National DNA Database. In addition, Working Group members will make recommendations, based on their findings, on the ethical and legal principles and procedures that should govern the forensic use of this information.

The consultation notes that there have been significant advances within the forensic science field in the collection, interpretation and application of biological information (or ‘bioinformation’) to identify individuals. This identification process is most likely used to determine if a person is who they say they are or if a person has been in a particular place, such as a crime scene, or has had contact with another person or an object. However, while bioinformation may be useful in the investigative process, UK policy requires that additional evidence be presented in court in order to identify a suspect as the source of the bioinformation.

Currently DNA profiles, one example of bioinformation, are collected and stored on the UK National DNA Database. The consultation will be looking for comments regarding the collection of these profiles, the management of the Database and other ethical issues. Specific issues include:

  • The retention of profiles: should those who are not convicted of an offence be allowed to have their profile and samples removed from the Database? Should volunteers be able to have their profiles removed, as is the case in Scotland, and under what circumstances? Should minors have their profiles retained?
  • The use of familial matching: finding a close match on the Database and using that information to locate and test family members in hopes of finding a match to the sample. While this has proven successful in finding perpetrators, it can also reveal sensitive details about family relations and may be seen as an invasion of privacy. Does the prospect of finding a suspect outweigh family privacy concerns?
  • Would placing everyone on the Database from birth be an equitable solution to ethical concerns?

Proponents argue that the DNA Database is vital as it assists in the successful detection and prosecution of criminals. Others worry that that there are not sufficient safeguards in place to protect citizens from violations of their rights. The inventor of DNA fingerprinting, Prof Sir Alec Jeffrey, believes that the Database has moved beyond what was originally envisioned, ‘mission creep’ in his words, and fears that samples taken for one purpose may be used for another in the future [see BBC news story]. The Working Group welcomes comments from the public and other stakeholders. The consultation ends on 30 January 2007; information on how to respond is available on the consultation website.

Research articles

Research article   |   Published 23 November 2006

A new publication in Nature has revealed a surprising degree of genetic variability between humans. Using the International Haplotype Map (HapMap) resource, a consortium of researchers created a map of copy number variable regions (CNVRs), sections of DNA at least 1000 base pairs long that are present in variable copy numbers in different individuals. The CNV regions range from simple tandem repeats to highly complex repeats at multiple sites across the genome, and are known to influence gene expression. They have been implicated in a range of diseases by their action in disrupting coding sequences and perturbing gene dosage (the number of copies of a gene that may be expressed).

DNA from the 270 individuals from four different populations (Nigerian, North Americans of European descent, Japanese and Han Chinese) was screened for copy number variability, with a total of 1,447 CNVRs identified, representing some 12% of the entire genome, a far greater proportion than previous estimates [Redon R et al. (2006) Nature 444, 444-454]. CNVRs were present in 2,908 genes, of which 285 have been linked with disease, as well as highly conserved non-coding sequences.

Presenting their extensive analysis of the CNVRs identified, the researchers conclude that they represent an abundant form of genomic variation and likely to make a substantial contribution to phenotypic (observable) variation in human populations. They propose that future genetic association studies should consider the potential links between CNVRs and disease, and suggest that SNP genotyping data should be enriched by information on copy number variable regions. Co-author Matthew Hurles of the UK Wellcome Trust Sanger Institute commented: "The copy number variation that researchers had seen before was simply the tip of the iceberg, while the bulk lay submerged, undetected. We now appreciate the immense contribution of this phenomenon to genetic differences between individuals" (see press release). The international consortium, which in addition to the Nature paper has published a further three articles in Nature Genetics and Genome Research, is now expanding its studies to include healthy individuals from populations outside the HapMap collection, and attempts to identify CNVRs smaller than 1kb.

Comment: This work reveals that the extent of copy number variation within the human genome is much greater than previously supposed, which immediately thrusts CNV analysis into the limelight as a tool for identifying the genetic factors that influence susceptibility and resistance to disease. The biological and clinical implications of multiple copy number variant regions remain to be seen, but may prove highly significant.

Research article   |   Published 17 November 2006

The response to major physical trauma such as that sustained by people involved in serious car crashes varies widely; some patients will go into irreversible (fatal) organ failure about a week after the injuries were sustained, whilst others recover. Organ failure is a leading cause of death among trauma victims. A recent publication in Proceedings of the National Academy of Sciences (PNAS) reports the results of comparative genomic analysis intended to address why some patients die whilst others survive, something that clinicians are presently unable to predict.

A team of US scientists studied white blood cells (leukocytes) from a small group of severely injured patients with organ failure and healthy controls; these blood cells were chosen because they have been implicated in the inflammatory responses associated with the development of post-injury multiple organ dysfunction syndrome. The researchers found that severe trauma provoked alternative patterns of gene expression and the activation of different biological pathways, with the combined effect of reducing the activity of T-cells [Miller-Graziano C et al. (2006) PNAS 103(42):15564-9]. This prevents crucial T-cell regulation of the body’s immune response, so that the process becomes out of control and effectively destroys tissues and organs.

The authors propose that using genome-wide expression analysis combined with cell-type specific pathway analyses may be of value in revealing pathway alterations in other forms of disease. Study author Carol Miller-Graziano commented: “Our study proves for the first time that it is possible to identify the genetic and protein changes in specific immune cells that play a significant role in determining whether or not trauma is fatal…we believe that the techniques established here can provide insights into many disease that involve human immune system failure” (see press release).

Comment: This research is a step towards a prognostic tool that would allow clinicians to identify patients moving into organ failure, and by providing information about the pathological pathways involved in the process it also creates the possibility of developing protective interventions. A comparison of genetic responses from trauma patients who did not develop organ failure with those who did would have been an interesting additional component to the study. However, given that the expression of many thousands of different genes is altered following injury, these researchers used an intelligent approach based on what was already known about the biological processes involved in organ failure, to home in on the genetic changes in key cellular mediators.

Research article   |   Published 2 November 2006

Inherited mutations in the BRCA1 and BRCA2 genes are associated with strong predisposition to breast and ovarian cancer; lifetime risk is around 85% for mutation carriers. Women at high risk of the disease based on their family history require high levels of surveillance to identify tumours in the early stages; the identification of a familial breast cancer associated mutation makes it possible to test unaffected relatives. Those who test positive for the mutation receive the option of increased levels of surveillance or prophylactic interventions, whilst those who test negative are discharged from surveillance.

However, a new study in the Journal of Medical Genetics suggests that the risk of disease for family members who lack the familial BRCA1/2 mutation may nevertheless remain elevated. The UK researchers examined a total of 277 families with pathogenic BRCA1/2 mutations; 49% of the women (258 in all) tested negative for the family mutation, but 28 of these developed breast cancer and a further four, ovarian cancer. Overall, 6.4% of the family members who did not possess the familial mutation developed breast cancer by the age of 50, compared with just 2% of the general population, leading the researchers to conclude that the relative risk of breast cancer for these family members was raised [Smith, A et al. (2006) J Med Genet Online First, doi:10.1136/jmg.2006.043091].

This apparent discrepancy is proposed to be the result of phenocopies within families – that is, individuals who share the same phenotype (breast cancer) but not the same genetic cause. The risk of breast cancer is known be influenced by additional genes besides BRCA1/2. Another less likely possibility would be the presence of more than one pathogenic BRCA1/2 mutation in the same family. The authors conclude that women from high-risk families who do not carry familial BRCA1/2 mutations should nevertheless be considered at moderate risk of breast cancer, and receive increased levels of surveillance accordingly. Lead author Professor Gareth Evans of the Department of Medical Genetics at St Mary's Hospital in Manchester commented: "We would suggest these women should be considered for annual breast screening between the ages 40 and 49 in the UK…rather than being treated like the general population where compulsory screening begins at 50" (see BBC news report).

Comment: It was already known that other genes besides BRCA1 and BRCA2 must contribute to genetic risk of breast/ovarian cancer; women with a strong family history of the disease are known to be at high risk even if no pathogenic mutation is identified within the family. The findings of this study are an important reminder that multiple genetic factors may be at work even within families where pathogenic or potentially pathogenic BRCA1/2 mutations have been found, and this should inform the management of all family members.

New reviews and commentaries

New reviews and commentaries 23 November 2006

Reviews & commentaries

Aspects of Genetic Susceptibility to Human Infectious Diseases. Hill AV (2006) Annu Rev Genet 40: 469-86. Review looking at the host genetic factors that influence susceptibility to major infectious diseases of humans, and prospects for identifying new genes using large-scale genome-wide association scans (PubMed).


Refusing to provide a prenatal test: can it ever be ethical? Duncan RE, Foddy B and Delatycki MB (2006) BMJ 333(7577):1066-1068. Ethical debate article using scenario of a couple requesting prenatal testing for Huntingdon’s disease, with arguments for and against testing along with a discussion (PubMed).


The cardiofaciocutaneous syndrome. Roberts A et al. (2006) J Med Genet. 43(11): 833-42. Review of this sporadic syndrome and the underlying genetic mutations that cause it and related conditions (PubMed).


Connecting the dots using gene-expression profiles. Gullans SR (2006) N Engl J Med. 355(19): 2042-4.Clinical implications of research article on attempts to create a ‘connectivity map’ of gene expression data, to facilitate discovery of new links between biological pathways and diseases (PubMed).


Cord blood banking: what are the real issues? Chan S (2006) J Med Ethics 32(11): 621-2. Editorial following on from the July RCOG report on this issue, calling for active pursuit of the potential medical benefits from creating a bank of donated cord blood samples (PubMed).

Genome-wide tagging for everyone. Need AC and Goldstein DB (2006) Nat Genet. 38(11):1227-8. News and views piece calling for a standardized platform for whole-genome association studies (PubMed).

Transcription in the loop. Gondor A and Ohlsson R (2006) Nat Genet. 38(11):1229-30. News and views piece on the role of chromatin folding in gene expression (PubMed).

read more ...

New reviews and commentaries 13 November 2006

Reviews & commentaries

The genetic dissection of essential hypertension. Cowley AW Jr (2006) Nat Rev Genet. 7(11):829-40. Review on insights into the pathology of hypertension provided by associated genes (PubMed).

Genetics of global gene expression. Rockman MV and Kruglyak L (2006) Nat Rev Genet. 7(11):862-72. Overview of the applications of genetic analysis of global gene expression (PubMed).

Bridging the regeneration gap: genetic insights from diverse animal models. Alvarado AS and Tsonis PA (2006) Nat Rev Genet. 7(11):873-84. Review on the use of genetic analysis of the regenerative potential of different organisms, and potential applications of this knowledge for regenerative medicine and stem-cell biology (PubMed).

A gene-centric approach to genome-wide association studies. Jorgenson E and Witte JS (2006) Nat Rev Genet. 7(11):885-91. Perspective proposing that current approaches to genomic association studies may miss key gene variants and arguing in favour of an alternative approach (PubMed).

Gavin Rylands de Beer: how embryology foreshadowed the dilemmas of the genome. Horder TJ (2006) Nat Rev Genet. 7(11):892-8. Historical profile proposing that the work of de Beer influences current thought on the genome genome, evolution and developmental biology (PubMed).

Genetics of ischemic stroke: future clinical applications. Wang MM (2006) Semin Neurol. 26(5):523-30. Review (PubMed).

Clinical implications of Parkinson's disease genetics. Lorincz MT (2006) Semin Neurol. 26(5):492-8. Review (PubMed).

Genetic basis for sleep regulation and sleep disorders. Raizen DM, Mason TB and Pack AI (2006) Semin Neurol. 26(5):467-83. Review (PubMed).

Genetics of Parkinson's disease and parkinsonism. Hardy J, Cai H, Cookson MR, Gwinn-Hardy K and Singleton A (2006) Ann Neurol. 60(4):389-98. Review (PubMed).

The routinisation of genomics and genetics: implications for ethical practices. Foster MW, Royal CD and Sharp RR (2006) J Med Ethics 32(11):635-8. Discussion article on the emerging ethical challenges posed by the increasing use of genetic information within society (PubMed).

Ethical and clinical practice considerations for genetic counselors related to direct-to-consumer marketing of genetic tests. Wade CH and Wilfond BS (2006) Am J Med Genet C Semin Med Genet. 42(4):284-92. Discussion article (PubMed).

read more ...