PERSPECTIVES

SCIENCE AND SOCIETY

Genetic profiling of newborns: ethical and social issues

Brenda Almond

Abstract | Identifying genetic factors that could reliably predict health risks for individuals has the potential to bring great health benefits, both for the individuals concerned and for health-care providers. Genetic profiling at birth would allow a persons genome to be analysed at an early stage, and the data electronically stored for future use. However, although this might seem like an attractive proposition, it carries with it serious ethical and social concerns that would need to be addressed if the genetic profiling of newborns were ever to be considered on a population-wide basis.
There are predictions that, over the next few decades, genetic information technologies will revolutionize medicine. As a result of the success of the Human Genome Project, it will be increasingly possible to assess disease risk from genotype. This will bring about a move away from medicine as a practice that follows the traditional pattern of diagnosis and treatment of disease, and its replacement by a new pattern of maintaining health in an apparently symptom-free patient by prediction and prevention1,2. It should also be possible to detect diseases that are already present at an early stage, and to initiate treatment before too much damage has occurred. Early intervention will, it is hoped, reduce the risks that are currently faced by genetically susceptible individuals for a range of chronic diseases including, for example, Alzheimer disease and autoimmune diseases. Clinical practice will also change in other ways, in particular as the new science of pharmacogenetics develops, making it possible to match the genotypes of patients with drug regimes and other treatments3. Some of these possibilities are already taking shape in the form of individualized treatments for leukaemia and some solid cancers, including breast and colon cancer, while new and more effective individualized treatments of other conditions will be possible in the near future4. It is in this context that the UK government decided to enquire into the possibility of neonatal profiling as a potential future health-care strategy. This was based on a vision of health-care provision that would make full use of the potential of new genetic knowledge5, and in which all patients, and their health-care providers, would have access to an electronic record of their personal genetic profile. As a result, two bodies that advise the government of the United Kingdom on aspects of health policy, the Human Genetics Commission (HGC) and the National Screening Committee (NSC), produced a joint report in March 2005 (REF. 6), which set out an analysis of the case for genetic profiling of babies on a population-wide basis. It was clear from the report that such a proposal raised many questions. Some of these were practical, either from a medical or technological perspective; some were financial; others were social, legal or ethical. The balance of judgement in the report was against recommending any immediate initiatives, but it acknowledged the speed of new developments in this area and recommended a return to the subject in 5 years. It considered the proposal of neonatal profiling to be feasible within a timescale of 20 years, and considered that in the long term there could be important medical benefits.

The issues raised in this report have implications not only for the United Kingdom, but for every other nation in which the genetic profiling of newborns is technically and economically feasible. Building on the issues that were raised in this report, I focus here on some important ethical, legal and social objections concerning the genetic profiling of newborns, which might ultimately be more difficult to resolve than the practical problems. The issues I tackle include those of consent, confidentiality and discrimination. To put these ethical and social issues into context, I begin by explaining the idea of profiling, and indicate the respects in which it differs from the established approaches of genetic testing and screening.
Testing and screening a brief overview Genetic testing is offered to individuals, and is used to identify a specific genetic variant or mutation. It might be offered on the basis of a family history that suggests the possibility of an inherited condition, or because symptoms have already appeared. Newborn testing is currently undertaken only for identifiable early-onset conditions for which diagnosis and intervention at an early stage could be crucial, as it is generally considered justifiable to obtain such genetic information only if valid practical measures can be taken at the time7,8 (BOX 1). By contrast, the aim of screening is to identify people from a particular population who could be helped by being identified as at risk of a disease, with the aim of offering further, more specific testing, earlier treatment or life-style advice9. Unlike testing, it is offered to a defined group rather than an individual: for example, all newborns, or all women from a particular age-group. Screening can, of course, be used for general medical reasons, not only for genetic conditions. As an example of the successful application of screening, the use of Guthrie cards for newborn bloodspot screening has been routine clinical practice in the United Kingdom since it was introduced in the 1960s, and is common in many other countries. It is virtually riskfree, involving taking only a drop of blood from a babys heel and testing for some common conditions, including

NATURE REVIEWS | GENETICS

VOLUME 7 | JANUARY 2006 | 67

2005 Nature Publishing Group

PERSPECTIVES
extensive investment is already being made in research that will bring genetic profiling closer to becoming a reality
congenital hypothyroidism, phenylketonuria (PKU), galactosaemia, haemoglobinopathies (for example, sickle-cell anaemia) and cystic fibrosis. In the case of PKU, which is an enzyme deficiency that causes severe learning difficulties, early action to provide a special diet can mean the child will avoid these adverse consequences. So, for some conditions, newborn screening can make the difference between a baby with a healthy life and one that requires long-term care. For this reason, in 1998 the WHO (World Health Organization) recommended that newborn screening should be mandatory and free of charge where early diagnosis and treatment could benefit children a position that could be interpreted as overriding even parental consent10. Whether this judgement could be extended to profiling is, however, more problematic.
Genetic profiling aims and challenges In its most strict sense, genetic profiling is the analysis of a persons entire genome to reveal their genetic variation. This approach is technically feasible now, through DNA sequencing, but would be prohibitively expensive for general use. At present, it is estimated that it would cost ~614 million to sequence an entire human genome1113. The ultimate goal is to bring this down to under 1,000, although it is not clear when this might be possible13,14. However, if there were a focus on analysing just the fraction of the human genome that is thought to contain medically important genetic variation, the cost would be much less. For example, genotyping all the ~1,000,000

variants catalogued in the International HapMap Project could potentially be carried out for less than 10,000 (REFS 1517), a much more affordable price. The most optimistic but admittedly long-term view is that the cost of sequencing someones DNA and putting it on a CD-ROM could eventually fall dramatically to a point at which it would cost little more than a conventional medical check-up. Apart from current concerns about cost, the potential clinical utility of genetic profiling is not fully established. First, although the genetic basis of many Mendelian (monogenic) diseases is well understood, the relationship between genetic variation and polygenic disorders, which comprise most human genetic disease, is far less clear-cut. Second, the risk of disease that is associated with genetic variants can be modified by the environment and by other genetic factors, which would make a genetic profile difficult to interpret18. For example, the homozygous state for a common mutation of the haemochromatosis (HFE) gene was identified in about 90% of patients of northern European origin with haemochromatosis. However, further studies showed that the vast majority of people who are homozygous for this mutation have no clinical symptoms, and that their risk of severe disease is only about 1% (REFS 1922). A further example is provided by the case of PKU; although this is a genetic disease, the large range of mutations that can cause the disease means that a direct biochemical test can be more accurate than a DNA-based diagnosis. Because of these practical issues, some might argue that it is premature to discuss the ethical and social concerns that would be raised by neonatal profiling, especially when concerns of this sort have already been discussed in the broader context of population screening23. However, extensive investment is already being made in research that will bring genetic profiling closer to

becoming a reality notably projects such as the HapMap and the SNP consortium, which are working towards understanding and cataloguing human genetic variation, specifically with the aim of tackling complex genetic disease15,24. There is therefore good reason to consider the ethical and social acceptability of a potential neonatal geneticprofiling programme at this early stage, even if it will need to be reviewed again when more scientific progress has been made. Here the debate moves on from what is practical or possible to what is desirable or ethically acceptable. Although genetic testing and screening are applied to specific individuals or defined populations, and are undertaken with specific health problems in mind, genetic profiling is a broad net that scoops up whatever might be there to be found. So, although in testing or screening it is known what conditions are being investigated, the results of profiling might be unexpected or surprising. Because of this difference, several ethical and social issues are associated with the genetic profiling of newborns that are distinct from those that have already been explored for genetic testing and screening. These include issues of consent, confidentiality and discrimination, as well as wider issues for society.
The consent issue The issue of consent has a distinctive role here, placed as it is between the more familiar areas of antenatal screening and the diagnostic testing of individuals who are old enough to give their own consent. In the case of neonates, the burden of decision is necessarily placed on the parents. The consent issue therefore has two aspects, the first of which is parental consent itself, raising important questions. For example, how informed can this consent be? And how extensive must it be? Although these questions can also be asked in the case of testing or screening, they are particularly important in the case of profiling because of the complexity of the information that is likely to be generated. The second aspect relates to the child, whose own consent is pre-empted25. As far as the parental issue is concerned, an immediate question is whether generic consent is enough, or whether specific consent would need to be obtained for every condition that profiling might reveal. Because this might be a matter of hundreds or even thousands of conditions if full profiling was possible, specific consent would hardly seem possible. However, such specific consent is considered important with respect to screening: the General Medical Council

Box 1 | Criteria for deciding whether a genetic test should take place
The criteria that are particularly relevant here, because they are also applicable to the case of neonatal genetic profiling, are listed below. There should be a link between the genetic variants that are tested for and the disease or disease risk. The individual or, in the case of a child, the person with parental responsibility must give consent. The risk of disease must be modifiable, based on some form of medical intervention or some other life-style change that can benefit the individual or family. Those who are identified as being at increased risk must be likely to follow any recommendations to reduce the risks. The ethical, legal and social implications must have been considered.

68 | JANUARY 2006 | VOLUME 7

www.nature.com/reviews/genetics

2005 Nature Publishing Group

PERSPECTIVES
of the United Kingdom has advised as a general principle that an offer of screening should be accompanied by information on the condition, as well as the likelihood of a positive test result and its meaning26. Even if such information were to be offered in some form, there is a serious question as to how far parents who have no scientific background would understand the complex genetic information they would be given. Also, because the predictive power of any test is less when applied to a healthy population, it is likely that genetic profiling would produce more false positives and false negatives than specific genetic tests that are undertaken in a defined patient group6. This would contribute to the potential confusion of parents. In the case of an adverse finding, discussion would involve not only genetic science, but also principles of epidemiology, requiring some grasp of risks and statistics, and a realistic appreciation of future possible developments in medical treatments. Even for medical professionals, the interpretation of such results is problematic, and could itself become a specialist area27. As far as the child is concerned, because in a sense the information that is generated belongs to the child, there are questions as to whether and which information should be fed back to parents after profiling. One possibility is that the results could simply be kept on file and not divulged to parents at that stage unless they revealed something that needed immediate action. But in a climate in which openness between doctors and patients has become the norm, such a solution would be unlikely to be acceptable to parents. Information that they would, rightly or wrongly, regard as important to them in the care of their child, would seem to have been deliberately and needlessly withheld from them. Another question is how far parental consent is a sufficient justification for testing. It is hardly an exaggeration to say that a major human rights issue might be involved here. To begin with, there is a widely held view that genetic testing has a special status28. There is also an established principle that children should not be tested for medical conditions unless there is some advantage to them for their care during childhood. Otherwise, testing should be postponed until individuals are old enough to give their own informed consent and to understand the implications of a positive diagnosis29. In relation to this, in a report published in 2002, the HGC said: It is ... the role of the state to ensure that children are protected from the wrongful use of parental authority. Genetic testing may differ from other forms of diagnostic procedures in that it may disclose information that the child may subsequently find burdensome.30 Although these remarks are specific to testing, they are perhaps even more relevant to genetic profiling: given that profiling would provide information on many genetic variants that might not provide any medical benefit in the short term, any advantages would currently be limited. The burdensome nature of knowledge about genetic conditions for which no treatment is available applies especially to late-onset disorders, for example Huntington disease31. This could also have implications for other family members who have not been asked for consent to the testing of the new baby, but who might be affected by the discovery of a familial hazard to which they might also be susceptible. But even where a diagnosis is limited to the child alone, the psychological implications of growing up with a risk that could have instead been encountered or come to terms with at a much later stage in life are far from negligible32. Although some young people might be robust enough to live with their diagnosis, for others it might cast a shadow over long-term life plans, including important decisions about marriage and children. It is not possible to balance these disadvantages by assuming that genetic knowledge will motivate behaviour to reduce genetic risks33.
The carrier issue Although it is also applicable to genetic testing and screening, the issue of carrier status raises special considerations in the context of profiling. A recognized difficult by-product of screening is that it reveals the carrier status for many who are not themselves suffering from a condition, and this raises a number of issues. For example, in the case of haemoglobinopathies it has been estimated that for each affected child, between 17 to 100 neonates might be carriers37. Problems that arise from this would be greatly increased by profiling, as it is inevitable that diagnoses that emerge from screening would also emerge from genetic profiling, although such discoveries will not be an issue for individuals until they reach the age when they might consider having a family themselves. In the meantime, however, they could have other adverse affects on the children that are identified in this way, and on their expectations38. For example, this could affect the way that these children are regarded within the family, as parents might not distinguish clearly between carrier and disease status. It might also affect the way that they approach relationships with potential partners as teenagers. Again, any confidentiality they might have preferred will already have been breached unless their parents are extremely careful to maintain silence on the subject with friends, relatives and professionals, such as teachers or temporary carers. For reasons like these, some professional bodies take the view that carrier testing should be postponed until the child is at an age to appreciate the issue and give consent39. However, there are circumstances in which the knowledge of carrier status in a child might affect its parents future reproductive choices, as it could reveal that one or both parents are also carriers, with a risk of transmitting the condition to future children. For example, in the case of Duchenne muscular dystrophy, an X-linked recessive disorder, although early detection of carrier status is of no benefit to the child, it could be helpful to parents. For example, they might want to avoid a subsequent pregnancy or to consider using donor-assisted reproduction to have an unaffected child. In such circumstances, profiling could be seen as offering enhanced reproductive choice, as it could reveal more potential genetic insights than would currently be gained from genetic testing or screening.

profiling would provide information on many genetic variants that might not provide any medical benefit in the short term
Impotent knowledge of this sort could also have damaging effects on family life if parents or other relatives begin to see an apparently healthy child as already in some sense impaired. It might also lead to other family members feeling obliged to discover their own status where a genetic condition is concerned, disrupting stable situations with foreknowledge that has no practical value34. It is for such reasons that the right not to know has been accepted as a principle in other areas of medicine35. It must also be taken into account, then, in relation to a policy that could force knowledge of a present or future genetic condition on someone whose own consent has not been sought, but has been given by proxy by a parent or carer36.

NATURE REVIEWS | GENETICS

VOLUME 7 | JANUARY 2006 | 69

2005 Nature Publishing Group

PERSPECTIVES
Confidentiality and discrimination Broad questions of discrimination and confidentiality relate to the issue of neonatal genetic profiling, which could affect adult life as well as childhood. Safeguards would be needed to protect confidentiality, but it is hard to see how parents could be persuaded to maintain confidentiality in discussion with teachers, family and friends. This is not necessarily a question of welfare considerations, for there need be no assumption that any of these people would misuse the information to the childs disadvantage. Nevertheless, it would be a breach of the childs right to privacy and to medical confidentiality confidentiality that could not easily be reclaimed in adult life. Although these issues also apply to genetic testing and screening where many have already questioned the desirability of achieving a high up-take at the cost of informed choice40 they are particularly relevant here. In particular, there would be much less chance of keeping information from genetic profiling out of the public domain than in the case of more specific medical screening and testing, which parents are more likely to have sought out and to see as a private medical matter with potential adverse implications. There are also unresolved questions about where and with whom the data should be stored. Many would be concerned at the thought that such detailed and intimate information would be placed in an accessible form in their health centre or doctors surgery, particularly knowing that it could then be accessed by office and nursing staff, other doctors and possibly by various state agencies. These fears might also be expressed in relation to other medical records; however, unlike these, profiling results include large quantities of information that might not be judged significant at the time, but for which confidentiality might later become important. Handing a physical object such as a disk to a parent soon after their child is born is hardly a reliable alternative. People move house, children leave home and relationships break down. Eighteen years is a long time to keep track of a small physical object. However this is resolved, once information enters the public domain it is difficult to ensure that it will not be misused, and in adult life it might bring the possibility of unfair discrimination in insurance or employment41. It is a frequently articulated fear that the wider availability of genetic information might lead to the development of a genetic underclass, who are deprived of access to jobs, mortgages and insurance by onerous rules of disclosure and commercial

policies of avoiding bad risks42. However, profiling in infancy would reveal many more latent possibilities than the screening programmes of the past, making these issues all the more pressing. Some hope to counter the possible effects of such discrimination through the recognition of a principle of genetic equity 43, but it is not entirely clear how this might be applied. It is easily confused with the principle of equal treatment for all, but because it is in fact a principle of justice rather than equality meaning that different cases should be treated differently when there are good reasons for doing so it leaves the position morally ambiguous as far as insurers and employers are concerned. In the end, then, there might be no alternative than to continue to rely on the principle of respect for persons and the outlawing of unfair discrimination. What is clear is that universal profiling of apparently healthy infants could add to the number of people who might be at risk of unfair genetic discrimination, and that state agencies, charities and supportgroups will continue to have an important role in meeting the widely recognized need to counter adverse social consequences for people who are diagnosed with a life-affecting genetic condition.
A medicalized society? The proposal of neonatal genetic profiling might also risk medicalizing a basically healthy population, causing parents to anticipate health problems in their children and perhaps leading them to subject their children to unnecessary and damaging

procedures44. If this leads to the health of infants being adversely affected, this could be described as creating a kind of Munchausen syndrome by proxy in the population as a whole. Counselling might seem to offer a remedy, but as discussed above, the way that genes affect individuals can be difficult to understand, and the number of diseases that can be successfully treated once identified is limited45. Counselling therefore has limitations in a situation in which the whole population might be deemed, or deem themselves, to be genetically at risk46. So, not only might some children be at risk of unnecessary interventions, but there is also the potential in the longer term for a larger burden on national health services of an influx of the worried well.
Future prospects A key question raised by the issues discussed above is whether neonatal profiling would do more harm than good it is a sound ethical principle that medical professionals should seek to benefit their patients and avoid harming them. It is clear that, despite the possible risks described above, profiling could offer some important advantages. Apart from the opportunity it would provide for disease-prevention and early intervention, more effective medicines and tailor-made dosing regimes are an attractive possibility. They could save a patient from unnecessarily embarking on an unpleasant procedure, such as a preventive surgery, by having much more specific information about their personal risk. Doctors could also prevent adverse reactions

Glossary
Galactosaemia
A rare autosomal recessive disorder. It is an inability to use galactose, which accumulates in the blood. Untreated affected infants fail to thrive and become mentally retarded, but if galactose is eliminated from the diet growth and development can be normal.

Huntingdon disease
(Also known as Huntington chorea.) A rare, inherited disease of the CNS, which is characterized by progressive dementia, abnormal posture and involuntary movements. The typical age of onset is between 30 and 50 years.

Guthrie cards
Cards that are used in several countries in the screening of newborns for more than 30 genetic disorders. Assays for specific analytes are carried out on proteins that have been reconstituted from dried blood spots.

International HapMap Project

A major international research effort to construct a resource that will facilitate future studies that relate human genetic variation to health and disease by understanding the haplotype structure of the human genome.

Haemochromatosis
A hereditary disease that is characterized by improper processing of iron in the body. There is excessive absorption and storage of iron in affected individuals, which leads to damage of many organs, including the liver and endocrine glands.

Munchausen syndrome by proxy

Munchausen syndrome is a psychological disorder that is characterized by the repeated fabrication or causation of disease symptoms or trauma for the purpose of gaining medical attention or treatment. In the case of Munchausen syndrome by proxy, it is a caregiver, usually a parent, who feigns or induces an illness in another person, usually her or his child.

Haemoglobinopathies
Inherited disorders of haemoglobin that affect the properties of red blood cells.

70 | JANUARY 2006 | VOLUME 7

www.nature.com/reviews/genetics

2005 Nature Publishing Group

PERSPECTIVES
to drugs by adjusting dosages to the patient according to their genetic profile. There are also financial considerations: savings to health-care costs for the population might be expected and the pharmaceutical industry could look to gain significantly from the development of individualized medicines. This provides an incentive to pursue these possibilities and could mean that, from a financial point of view, the initial costs would be justified. The proposal of neonatal genetic profiling therefore provides a prime example of a potential conflict between public gains and individual interests. Individual interests here might be construed in terms of both the possibility of valid consent to testing and the balance between personal advantage and disadvantage. However, the consent principle, which has such a significant role in this debate, does not only apply at the microlevel, where what is at issue is the autonomy of individual patients; it would also raise a major issue of public intervention in individual health care if profiling were to be made standard practice at birth. The disadvantages of neonatal profiling might have to be accepted if there were a strong argument of necessity. But the collection of data in this way and at this time (at birth) is not the only possibility. Some of the objections might be met if profiling were postponed until a later stage, either on request, for example, or universally at the age of 18. It is also worth considering that, given the low predictive reliability of genetic testing and the psychological impact on families of any adverse information they receive, environmental and health-improvement strategies might, after all, be more effective than genetic profiling in raising the quality of health and health care in the population23. These are the aspects that the UK government will need to consider if it accepts the recommendation in the report that it commissioned to return to the issue in 5 years time. Other governments might also want to consider the options that are offered by the possibility of genetic profiling, as many countries have similar technologies at their disposal and all have a strong interest in optimizing the delivery of health care. In each case, it will not be a straightforward matter of calculating the ratio of costs to benefits, but rather a case of coming to terms with some complex and difficult ethical, social and legal issues.
Brenda Almond is at the Social Values Research Centre, University of Hull, Hull HU6 7RX, UK. e-mail: brenda.almond@freedom255.co.uk doi: 10.1038/nrg1745
1. 2. 3. Bell, J. Predicting disease using genomics. Nature 429, 453456 (2004). Bentley, D. R. Genomes for medicine. Nature 429, 440445 (2004). GeneWatch UK. Pharmacogenetics: better, safer medicines? Briefing Number 23 [online], <http://www. genewatch.org/Publications/Briefs/Brief23.pdf> (2003). Evans, W. E. & Relling, M. V. Moving towards individualized medicine with pharmacogenomics. Nature 429, 464468 (2004). Department of Health. Our Inheritance, Our Future Realising the potential of genetics in the NHS.HMSO document [online], <http://www.dh.gov. uk/assetRoot/04/01/92/39/04019239.pdf> (2003). Human Genetics Commission. Profiling the newborn: a prospective gene technology? Human Genetics Commission document [online], <http://www.hgc. gov.uk/UploadDocs/Contents/Documents/Final%20D raft%20of%20Profiling%20Newborn%20Report%2 003%2005.pdf> (2005). Clarke, A. The genetic testing of children. Working Party of the Clinical Genetics Society (UK). J. Med. Genet. 31, 785797 (1994). Kroese, M., Zimmern, R. L. & Sanderson, S. Genetic Tests and their evaluation: Can we answer the key questions? Genet. Med.6, 475480 (2004). Green, N. S. & Pass, K. N. Neonatal screening by DNA microarray: spots and chips. Nature Rev. Genet. 6, 147151 (2005). Laberge, C., Kharaboyan, L. & Avard, D. Newborn screening, banking, and consent. HumGen GenEdit archives [online], <http://www.humgen.umontreal.ca/ int/GE/en/2004-3.pdf> (2004). Shendure, J. et al. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309, 17281732 (2005). Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376380 (2005). Kling, J. The search for a sequencing thoroughbred. Nature Biotechnol. 23, 13331335 (2005). US National Institutes of Health. NHGRI seeks next generation of sequencing technologies. NIH News Release [online], <http://www.genome. gov/12513210> (14 October 2004). The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 12991320 (2005). US National Institutes of Health. Additional genotyping for the human haplotype map. NIH Research Funding Announcement [online], <http:// grants.nih.gov/grants/guide/rfa-files/RFA-HG-04-005. html> (16 April 2004). Hirschhorn, J. N. & Daly, M. J. Genome-wide association studies for common diseases and complex traits. Nature Rev. Genet. 6, 95108 (2005). Holtzman N. A. & Marteau, T. M. Will genetics revolutionize medicine? N. Engl. J. Med. 343, 141144 (1999). Beutler, E. et al. Penetrance of the 845G>A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 359, 211218 (2002). Beutler, E. The HFE Cys282Tyr mutation as a necessary but not sufficient cause of hereditary hemochromatosis. Blood 101, 33473350 (2003). Feder, J. N. et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genet. 13, 399408 (1996). Jazwinska, E. C. et al. Haemochromatosis and HLA-H. Nature Genet. 14, 249251 (1996). EUROGAPP PROJECT 19992000 Public and Professional Policy Committee (PPPC). Population genetic screening programmes: proposed recommendations of the European Society of Human Genetics. Eur. J. Hum. Genet. 8, 9981000 (2000). Carlson, C. S. et al. Mapping complex disease loci in whole-genome association studies. Nature 429, 446452 (2004). Holm, S. Informed consent and the bio-banking of material from children. Genomics Society Policy 1, 1626 (2005). General Medical Council. Seeking patients consent: the ethical considerations. Genetic Medical Council web page on consent [online], <http://www.gmc-uk.org/guidance/library/consent. asp> (1999). 27. Burke, W. & Emery, J. Genetics education for primarycare providers. Nature Rev. Genet. 3, 561566 (2002). 28. World Health Organization. Proposed international guidelines on ethical issues in medical genetics and genetics services. WHO Human Genetics Programme [online], <http://www.who.int/genomics/publications/ en/ethicalguidelines1998.pdf> (1998). 29. United Nations Educational, Scientific and Cultural Organization. Draft International Declaration on Human Genetic Data. Submission to the General Conference, 32nd session [online], <http://unesdoc. unesco.org/images/0013/001312/131204e.pdf> (2003). 30. Human Genetics Commission. Inside information: balancing interests in the use of personal genetic data. Human Genetics Commission document [online], <http://www.hgc.gov.uk/UploadDocs/ DocPub/Document/insideinformation_summary.pdf> (2002). 31. Sevick, M. A. et al. Genetic testing of children for lateonset disease. Camb. Q. Healthc. Ethics 14, 4756 (2005). 32. Michie, S. & Marteau, T. M. Predictive genetic testing in children: the need for psychological research. Br. J. Health Psychol. 1, 314 (1996). 33. Marteau, T. M. & Lerman, C. Y. Genetic risk and behavioural change. BMJ 322, 10561059 (2001). 34. Fryer, A. Inappropriate genetic testing of children. Arch. Dis. Childhood 83, 283285 (2000). 35. Genetic Interest Group. GIG responses to the UK Clinical Genetics Society report The genetic testing of children. J. Med. Genet. 32, 490494 (1995). 36. McLean, S. A. M. in The Genetic Testing of Children (ed. Clarke, A.) 1726 (Bios Scientific, Oxford, 1998). 37. Laird, L., Dezateux, C. & Anionwu, E. N. Neonatal screening for sickle cell disorders: what about the carrier infants? BMJ 313, 407411 (1996). 38. Marteau, T. & Anionwu, E. N. in The Troubled Helix: Social and Psychological Implications of the New Genetics (eds Marteau, T & Richard, M. P. M.) 123 139 (Cambridge Univ. Press, 1996).. 39. Clark, A. The genetic testing of children. Working Party of the Clinical Genetics Society (UK). J. Med. Genet. 31, 785797 (1994). 40. Austoker, J. Gaining informed consent for screening. BMJ 319, 722723 (1999). 41. Billings PR, et al. Discrimination as a consequence of genetic testing. Am. J. Hum. Genet. 50, 476482 (1992). 42. GeneWatch UK. Bar-coding babies: good for health? Briefing Number 27 [online], <http://www.genewatch. org/Publications/Briefs/brief27.pdf> (2004). 43. Sulston, J. & Harris, J. Genetic equity. Nature Rev. Genet. 5, 796800 (2004). 44. Melzer D. & Zimmern, R. Genetics and medicalisation. BMJ 324, 863864 (2002). 45. European Diagnostic Manufacturers Association Public Relations Committee. Genetic testing, Position paper. EDMA web site [online], <http://www.edmaivd.be/Position_papers/Genetic_Testing_PP_FINAL_ 24Oct03.doc> (24 October 2003). 46. Petersen, A. Counselling the genetically at risk: the poetics and politics of non-directiveness. Health Risk Soc. 1, 253265 (1999).

4.

5.

6.

7.

8.

9.

10.

11.

12.

13. 14.

15.

16.

17.

18.

19.

20.

Competing interests statement

The author declares no competing financial interests.

21.

DATABASES
The following terms in this article are linked online to: Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query. fcgi?db=gene HFE OMIM: http://www.ncbi.nlm.nih.gov/entrez/query. fcgi?db=OMIM Alzheimer disease | congenital hypothyroidism | cystic fibrosis | Duchenne muscular dystrophy | galactosaemia | Huntington disease | phenylketonuria

22. 23.

24.

FURTHER INFORMATION
Human Genetics Commission homepage: http://www.hgc. gov.uk/Client/index.asp?ContentId=1 Human Genome Project: http://www.ornl.gov/sci/ techresources/Human_Genome/home.shtml International HapMap Project: http://www.hapmap.org The SNP Consortium web site: http://snp.cshl.org UK National Screening Committee homepage: http://www.nsc.nhs.uk Access to this interactive links box is free online

25.

26.

NATURE REVIEWS | GENETICS

VOLUME 7 | JANUARY 2006 | 71

2005 Nature Publishing Group