A survey of state insurance commissioners concerning genetic testing and life insurance.

Rapid advances in genetic testing have stimulated growing concern about the potential for misuse of genetic data by insurance companies, employers, and other third parties. Thus far, reports of genetically based discrimination in life insurance have been anecdotal. Reasoning that state insurance commissioners were likely to be aware of (1) the extent of current use of and interest in genetic tests by life insurers and (2) consumer complaints about insurance being denied because of genetic condition or because of genetic test results, we conducted a survey of that group. We received responses from 42 of the 51 jurisdictions. Our results suggest (1) that those who regulate the life insurance industry do not yet perceive genetic testing to pose a significant problem in how insurers rate applicants, (2) that life insurers have much legal latitude to require genetic tests, and (3) that so far few consumers have formally complained to commissioners about the use of genetic data by life insurers.     

Actuarial considerations on genetic testing.

In the UK the majority of life insurers employ relatively liberal underwriting standards so that people can easily gain access to life assurance cover. Up to 95% of applicants are accepted at standard terms. If genetic testing becomes widespread then the buying habits of the public may change. Proportionately more people with a predisposition to major types of disease may take life assurance cover while people with no predisposition may take proportionately less. A model is used to show the possible effect. However, the time-scales are long and the mortality of assured people is steadily improving. The change in buying habits may result in the rate of improvement slowing down. In the whole population, the improvement in mortality is likely to continue and could improve faster if widespread genetic testing results in earlier diagnosis and treatment. Life insurers would not call for genetic tests and need not see the results of previous tests except for very large sums assured. In the UK, life insurers are unlikely to change their underwriting standards, and are extremely unlikely to bring in basic premium rating systems that give discounts on the premium or penalty points according to peoples genetic profile. The implications of widespread genetic testing on medical insurance and some health insurance covers may be more extreme.     

Reassessing insurers' access to genetic information: genetic privacy, ignorance, and injustice

Many countries have imposed strict regulations on the genetic information to which insurers have access. Commentators have warned against the emerging body of legislation for different reasons. This paper demonstrates that, when confronted with the argument that genetic information should be available to insurers for health insurance underwriting purposes, one should avoid appeals to rights of genetic privacy and genetic ignorance. The principle of equality of opportunity may nevertheless warrant restrictions. A choice-based account of this principle implies that it is unfair to hold people responsible for the consequences of the genetic lottery, since we have no choice in selecting our genotype or the expression of it. However appealing, this view does not take us all the way to an adequate justification of inaccessibility of genetic information. A contractarian account, suggesting that health is a condition of opportunity and that healthcare is an essential good, seems more promising. I conclude that if or when predictive medical tests (such as genetic tests) are developed with significant actuarial value, individuals have less reason to accept as fair institutions that limit access to healthcare on the grounds of risk status. Given the assumption that a division of risk pools in accordance with a rough estimate of people's level of (genetic) risk will occur, fairness and justice favour universal health insurance based on solidarity.     

A survey of medical directors of life insurance companies concerning use of genetic information.

Rapid advances in our ability to test persons presymptomatically for genetic diseases have generated increasing concern that genetic information will be abused by insurance companies. Reasoning that the insurance companies may have the strongest interest in using genetic data and that the medical directors of those companies with responsibility for rating applicants would be a good source of information on the use of such data, we conducted a large survey of medical directors of North American life insurance companies. We received responses from 27 medical directors. Our results suggest that (1) few insurers perform genetic tests on applicants, but most are interested in accessing genetic test information about applicants that already exists; (2) the degree of insurers' interest in using genetic test results may depend on the face amount of the policy applied for and on the specificity and sensitivity of the test; (3) many companies employ underwriting guidelines with respect to certain genetic conditions but may not always have specific actuarial data in house to support their rating decisions; (4) a considerable degree of subjectivity is involved in most insurers' rating decisions; and (5) some of the medical directors who responded to our survey are not fully informed about certain basic principles of medical genetics.     

Laws restricting health insurers' use of genetic information: impact on genetic discrimination

Since 1991, 28 states have enacted laws that prohibit insurers' use of genetic information in pricing, issuing, or structuring health insurance. This article evaluates whether these laws reduce the extent of genetic discrimination by health insurers. From the data collected at multiple sites, we find that there are almost no well-documented cases of health insurers either asking for or using presymptomatic genetic test results in their underwriting decisions, either (a) before or after these laws have been enacted or (b) in states with or without these laws. By using both in-person interviews with insurers and a direct market test, we found that a person with a serious genetic condition who is presymptomatic faces little or no difficulty in obtaining health insurance. Furthermore, there are few indications that the degree of difficulty varies according to whether a state regulates the use of genetic information. Nevertheless, these laws have made it less likely that insurers will use genetic information in the future. Although insurers and agents are only vaguely aware of these laws, the laws have shaped industry norms and attitudes about the legitimacy of using this information.     

Genetic disorders presenting as “schizophrenia”. Karl bonhoeffer's early view of the psychoses in the light of medical genetics

There is overwhelming empirical evidence for the influence of genetic factors in the etiology of schizophrenic psychoses. An appreciable and still increasing number of exogenous factors have been known for decades that are capable of inducing psychoses that present as "schizophrenia" or are more or less similar to it. In this article, genetic disorders--chromosomal abnormalities and Mendelian diseases--are summarized that may be associated with such psychoses. These disorders frequently but not necessarily exhibit additional physical symptoms. Although the majority of schizophrenic psychoses can so far not be explained by exogenous factors or well-defined genetic disorders, the proportion of these etiologies among all cases may be higher than presumed so far, because they evade detection. Data from the literature are discussed in the light of Karl Bonhoeffer's early concept of exogenous reaction types and modern medical genetics.     

Mutuality and solidarity: assessing risks and sharing losses.

Mutuality is the principle of private, commercial insurance; individuals enter the pool for sharing losses, and pay according to the best estimate of the risk they bring with them. Solidarity is the sharing of losses with payment according to some other scheme; this is the principle of state social insurance; essential features of solidarity are comprehensiveness and compulsion. Private insurance is subject to the uberrima fides principle, or utmost good faith; each side declares all it knows about the risk. The Disability Discrimination Act requires insurers to justify disability discrimination on the basis of relevant information, acturial, statistical or medical, on which it is reasonable to rely. It could be very damaging to private insurance to abandon uberrima fides. However, although some genetic information is clearly useful to underwriters, other information may be so general as to be of little use. The way in which mortality rates are assessed is also explained.     

Use of genetic data, employment and insurance: an international perspective

In this paper, I will say first of all a few words on what is novel in the potential exclusionary use of genetic information in the domains of work or insurance and to what extent legal protection specifically relating to genetic discrimination may be justified. Subsequently, I will briefly examine some of the proposed restrictions on the collection of genetic information for purposes of selection and the scope for international consensus on the issue; in doing so, I will deal separately with employment and private insurance. Finally, I will raise the question whether these issues require international handling and which international steps could be envisaged.     

Genetic diversity and disease susceptibility.

The range of genetic diversity within human populations is enormous. Genetic susceptibility to common chronic disease is a significant part of this genetic diversity, which also includes a variety of rare clear-cut inherited diseases. Modern DNA-based genomic analysis can now routinely lead to the identification of genes involved in disease susceptibility, provides the basis for genetic counselling in affected families, and more widely for a genetically targeted approach to disease prevention. This naturally raises problems concerning the use of information on an individual''s decisions, but for employment, and health and life insurance.     

The likely financial effects on individuals,industry and commerce of the use of genetic information.

In this paper I look at the financial implications of genetic testing, particularly in the employment and pensions fields. I have generally not covered life insurance, as that is covered in other papers in this Discussion Meeting. However, the issues are similar, although the emphasis is different. Inevitably there is an element of speculation involved; genetic testing is in its infancy and so we cannot predict either what information we will be able to obtain through genetic testing, nor the uses that may be devised for this information.     

Genetic information and insurance: some ethical issues.

Life is risky, and insurance provides one of the best developed ways of controlling risks. By pooling, and so transferring risks, those who turn out to suffer antecedently uncertain harms can be assured in advance that they will be helped if those harms arise; they can then plan their lives and activities with confidence that they are less at the mercy of ill fortune. Both publicly organized and commercial insurance can organize the pooling of risk in ways that are beneficial for all concerned. They provide standard ways of securing fundamental ethical values such as solidarity and mutuality. Although policy holders do not know or contract with one another, each benefits from the contribution of others to a shared scheme for pooling and so controlling risk. Although there is a limit to the degree to which commercially-based insurance, where premiums depend on risk level, can go beyond mutuality towards solidarity, in practice it too often achieves a measure of solidarity by taking a broad brush approach to pooling risk. However, the ordinary practices of insurance, and in particular of commercial insurance, also raise ethical questions. These may be put in simple terms by contrasting the way in which an insurance market discriminates between different people, on the basis of characteristics that (supposedly) determine their risk level, and our frequent abhorrence of discrimination, in particular on the basis on religious, racial and gender characteristics. Are the discriminations on which insurance practice relies upon as standard acceptable or not? The increasing availability of genetic information, which testing (of individuals) and screening (of populations) may provide, could lend urgency to these questions. Genetic information may provide a way of obtaining more accurate assessment of individual risks to health and life. This information could be used to discriminate more finely between the risk levels of different individuals, and then to alter the availability and the costs of health, life and unemployment insurance to them. Since all of these forms of insurance bear very directly on the way most people live, it will matter to them how (if at all) insurers take account of genetic information. Will use of this information improve or damage the capacity of insurance to provide confidence in the face of uncertain harms, and help if they happen? Will it discriminate in acceptable or in unacceptable ways? Will it support or damage the sorts of mutuality and solidarity various sorts of insurance schemes have successfully institutionalized?     

Statistical Tests of Neutrality of Mutations against Population Growth, Hitchhiking and Background Selection

The main purpose of this article is to present several new statistical tests of neutrality of mutations against a class of alternative models, under which DNA polymorphisms tend to exhibit excesses of rare alleles or young mutations. Another purpose is to study the powers of existing and newly developed tests and to examine the detailed pattern of polymorphisms under population growth, genetic hitchhiking and background selection. It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, F(s), is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations. Background selection gives rise to quite different polymorphic patterns than does logistic population growth or genetic hitchhiking, although all of them show excesses of rare alleles or young mutations. We show that Fu and Li''s tests are among the most powerful tests against background selection. Implications of these results are discussed.     

Genetic tests: between risks and opportunities. The case of neurodegenerative diseases

Commercial genetic testing challenges traditional medical practice and the doctor–patient relationship. Neurodegenerative diseases may serve as the practical and ethical testing ground for the application of genomics to medicine.In the age of the Internet, a wealth of information lies at your fingertips—even your genetic ancestry and your fate in terms of health and sickness. A Google search for ‘genetic testing'' immediately comes up with a list of companies offering quick, direct-to-consumer genetic tests (DCGT) for relatively little money. “Claim your kit, spit into the tube and send it to the lab,” states the website of 23andMe—the company whose Personal Genome Service was named the ‘2008 Invention of the Year'' by Time magazine. Six to eight weeks after sending in a sample, customers can log on to the company website and learn about their genetic origins and ancestry if they opted for the ‘Fill in Your Family Tree'' option, or can explore their genetic profile under the “Health Edition” and what it says about personal disease risks and drug responses.The availability of next-generation high-throughput DNA sequencers has enabled companies to sequence the genes of a large number of customers at a low costs and with few personnel23andMe is one of several companies that offer predictive genetic tests covering a range of multifactorial and monogenic disorders (STOA, 2008). This is clearly a revolutionary approach to personalized medicine; it not only allows individuals to learn about genetic risk factors for a variety of diseases, but also does so outside the established medical system. Before the advent of DCGTs, genetic tests were only carried out at specialized medical institutions under controlled conditions, and only on referral from a physician. The decreasing price of DNA sequencing, new technologies for high-throughput sequencing and the growth of the Internet have all helped to reduce the technical, financial and access barriers to genetic testing. It is therefore not surprising that private enterprises moved into this fast-developing market.The availability of next-generation high-throughput DNA sequencers enables companies to sequence the genes of a large number of customers at a low cost and with few personnel. They can therefore offer this service at attractive prices, in the range of a few hundred dollars. The Internet conversely enables accessibility: a few mouse clicks are enough, while completely bypassing the usual checks and balances of organized healthcare. This means that expert advice is often lacking for patients about results that predict inherited risks for diabetes, cancer, neurological disorders and drug response (STOA, 2008).The simple, affordable and rapid service offered by these companies raises concerns about the clinical validity and utility of the tests, as well as the information and support that they offer to properly interpret the results. In June this year, the US Food and Drug Administration (FDA) contacted five companies that sell genetic tests directly to consumers and asked them to prove the validity of their products (Pollack, 2010). The FDA argues that genetic tests are diagnostic tools that must obtain regulatory approval before they can be marketed, but it did not order the companies to stop selling their tests. 23andMe—one of the five companies that were contacted—replied: “We are sensitive to the FDA''s concerns, but we believe that people have the right to know as much about their genes and their bodies as they choose” (Pollack, 2010). Last year, researchers from the J. Craig Venter Institute (San Diego, CA, USA) and the Scripps Translational Science Institute (La Jolla, CA, USA) reported inconsistencies between results obtained from two DCGT companies in an opinion article in Nature and made recommendations for improving predictions (Ng et al, 2009).A balance must be struck between consumer choice, consumer benefit and consumer protection. On one side is the individual''s right to have access to information about his or her health condition and health risks, so as to be able to take preventive measures. On the other side, serious questions have emerged about the lack of proper counselling in a professional setting. Are customers able to correctly understand, interpret and manage the information gained from a genetic test? Are they prepared to deal with the health risk information such a test provides? Are the scientific community and society as a whole ready to change the focus in medicine from morphological and physiological factors to molecular and genetic information?A balance must be struck between consumer choice, benefit and protectionThese concerns become more complicated when companies offer genetic tests for neurodegenerative disorders for which there are no preventive measures or treatments, such as Alzheimer, Parkinson or Huntington diseases. Most of these diseases are severe, debilitating and can lead to stigmatization and possible discrimination for patients. Brain disorders that cause progressive mental decline affect not only the health of the individual, but also their identity, self-consciousness and role within the family and society. As Judit Sándor, Director of the Centre for Ethics and Law in Biomedicine at the Central European University (Budapest, Hungary) put it: “The stigmatization of hereditary diseases in society may lead to ethical and legal consequences that are difficult to grasp. The stigma associated with neurodegenerative diseases would be even harder to bear if the disease is proven to be hereditary by some form of genetic testing.”In this context, 60 experts from a range of disciplines—scientists, clinicians, philosophers, sociologists, jurists, journalists and patients—from Europe, Canada and the USA met at the 2010 workshop ‘Brains In Dialogue On Genetic Testing'' in Trieste, Italy. The meeting was organized by the International School for Advanced Studies, as part of the European project ‘Brains in Dialogue'', which aims to foster dialogue among key stakeholders in neuroscience (www.neuromedia.eu). The use of predictive genetic testing for neurodegenerative diseases was the main focus of the meeting and represents an interesting model for discussing the risks and benefits of DCGTs.Very few neurodegenerative disorders have a typical Mendelian inheritance. The most (in)famous is Huntington disease, which typically becomes noticeable in middle age. Symptoms include progressive choreiform movements, cognitive impairment, mood disorders and behavioural changes. Huntington disease is caused by an increase in the number of CAG repeats in the gene Huntingtin, which can be tested for easily and reliably (Myers, 2004) in order to confirm a diagnosis or predict the disease, in at-risk groups or prenatally. The results have psychological and ethical implications that affect individuals and their families. According to the STOA report on DCGTs, only one company offers a test for Huntington disease.Most neurodegenerative disorders have a more complex set of genetic and environmental risk factors that make it difficult—if not impossible—to predict the risk of disease at a certain age. A small percentage of cases of Alzheimer and Parkinson diseases—usually early-onset—carry specific mutations with a Mendelian inheritance, but genetic factors are also involved in the most common late-onset forms of these diseases (Avramopoulos, 2009; Klein & Schlossmacher, 2006). Nicholas Wood of University College London, UK, commented that: “[t]here has been a revolution in our molecular genetic understanding of Parkinson''s disease. Twenty years ago Parkinson''s disease perhaps was considered the archetype of non-genetic disease. It is now clear that a growing list of genes is primarily responsible for Mendelian forms of Parkinson''s disease. It is also clear from recent studies that, due to reduced penetrance, some of these ‘Mendelian genes'' play a role in the so-called sporadic disease.” Nevertheless, a genetic test based on susceptibility genes would not enable a clear diagnosis—as in the case of Huntington disease—but only an estimate of the individual''s risk of developing the disease later in life, with varying reliability.For Alzheimer disease, genetic testing is usually only recommended for individuals with a family history of early-onset or with immediate relatives who already have the disease. The most common form of late-onset Alzheimer disease has a complex inheritance pattern. The medical establishment does not therefore recommend genetic testing for it, although a polymorphism in the Apolipoprotein E (APOE) gene has been unequivocally associated with Alzheimer disease (Avramopoulos, 2009). The identification of such risk factors through epidemiological studies provides valuable information about the molecular basis of the disease, but the management of this information at the individual level seems difficult for clinicians and patients. Agnes Allansdottir of the University of Siena, Italy, explained these difficulties stating that “research on decision-making processes demonstrates that we humans have severe problems dealing with probabilities.”Sándor expressed concerns that these difficulties could lead to additional discrimination. “Most people know what to do if they have high blood pressure, for instance. However, information coming from a genetic test is much more complex—their reading and interpretation require special expertise,” she said. She pointed out that some groups might be unable to access that expertise, while others might be unable to understand the information. “As a consequence, they will suffer an additional form of discrimination that is the ‘discrimination in the accessibility'' of sensitive and complex medical data, and that affects […] the right to privacy, as well.”…“research on decision-making processes demonstrates that we humans have severe problems dealing with probabilities”It is certainly possible that individuals who do not understand what probabilistic estimates of risk mean will be upset to find out they have a higher risk of developing a certain disorder, even though in absolute terms this risk is marginal. Avoiding this situation is what genetic counselling tries to achieve: to inform patients and help them to interpret the results of genetic tests. For the same reason, genetic testing for most common forms of late-onset Alzheimer or Parkinson disease—both of which are multifactorial—is not recommended, precisely because of the limited predictive value of these tests and the lack of proven preventive measures. However, various companies including deCODEme offer to identify your APOE variant and calculate “your risk of developing late-onset Alzheimer''s Disease” as part of their service.Research has demonstrated that genetic testing may be a useful coping strategy for some at-risk individuals (Gooding et al, 2006), a conclusion that was also reached by the Risk Evaluation and Education for Alzheimer''s Disease (REVEAL) study (Green et al, 2009). Some results showed that knowledge of their APOE genotype and numerical lifetime risk influenced the health-related behaviour of asymptomatic adult children of Alzheimer disease patients. The discovery of increased risk of disease through an education-and-disclosure protocol was associated with a stronger motivation to engage in behaviours that reduce risk, such as changes in medications or vitamin intake, even if their effectiveness is still unclear (Chao et al, 2008). Genotype disclosure did not result in short-term psychological problems, despite the frightening nature of the disease and the lack of therapies for it (Green et al, 2009). These studies highlight the importance of education and counselling in understanding risk and evaluating the means of counteracting it.Yet the ease with which DCGT companies offer tests over the Internet creates a new kind of autonomy for patients. “Genetic information serves often as a key to future decisions. Based on the information, they may rearrange the priorities in their life or change their lifestyle in order to fight against the manifestation of the disease, to decrease its symptoms or simply delay its progress,” Sándor said. “For many people, nothing else is worse than the lack of certainty and thus knowledge, in itself, can be a value.”To know or not to know: that is the question—particularly for neurodegenerative diseases. In addition to the opinions of the experts at the meeting, the public round table, ‘Health and DNA: my life, my genes'', showed that the choice whether to take a test should be a personal decision; certainly nobody should be forced in one direction or another. During the discussion, different opinions and experiences regarding the use of genetic testing were presented by members of the panel and the public. Verena Schmocker, a Swiss woman affected by Parkinson disease, explained why she refused to be tested, despite a strong family history of early-onset Parkinson disease. “I knew already that the disease was in my family, but I didn''t want to take any genetic test. I chose to live my life day by day and live what is there for me to live.” Another woman in the audience explained that she wanted to know her destiny: “[w]hen 15 years ago I was diagnosed with Huntington''s disease I woke up from a nightmare of doubts. I started organizing my life, I got married and got prepared for the future.”In many ways, Huntington disease is an unrepresentative example—not only because it is an untreatable, debilitating Mendelian disease, but also because patients typically receive mandatory and sophisticated patient counselling. Most importantly, as Marina Frontali from the National Research Council (Rome, Italy) highlighted, counselling should enable and respect autonomous decisions by the person at risk, even in light of third-party pressure to take the test, not just by employers or insurance companies, but also by family members. The counselling service for Huntington disease—through a tight collaboration between laypeople and professionals—is a valuable example of the management of genetic testing.…the ease with which DCGT companies offer tests over the Internet creates a new kind of autonomy for patientsThe Eurobarometer 2005 survey showed that EU citizens are generally supportive of the use of genetic data for diagnosis and research, and 64% of the respondents said that they would take a genetic test to detect potential diseases (EC, 2006). In reality, however, attitudes vary between countries: in most cases, people would be willing to take a test only in exceptional circumstances or only if it was highly regulated and controlled. Interestingly, those countries in which people expressed more concern and negative attitudes towards testing were those with higher levels of education and scientific literacy, where the mass media is more attentive to science and technology and where the public and political debate is more advanced. It shows, again, that increasing scientific literacy is not enough to overcome people''s fears and objections to genetic testing; the more they understand the issues, the less likely people are to be enthusiastic about new technologies.These concerns notwithstanding, the number of tests that are available is growing, and genetic testing—whether as part of the healthcare system or through DCGT companies—is becoming a model for preventive medicine and discussions about the impact of genetics on public health (Brand et al, 2008). The advances brought about by genomics will lead to more targeted health promotion messages and disease prevention programmes specifically directed at susceptible individuals and families, or at subgroups of the population, based on their genomic risk profile.The controversial nature of the political discourse concerning science and health often raises controversy, and the integration of genomics into public healthcare, research and policy might therefore be challenging. According to Brand et al (2008), the question is not whether the use of genomics in public health is dangerous, but whether excluding genomic information from public health interventions and withholding the potential of evidence-based prevention might do more harm. The next decade will provide a window of opportunity in which to prepare and educate clinicians, public health professionals, policy-makers and the public for the integration of genomics into healthcare. Brand et al (2008) argue that there is an ethical obligation to meet this challenge and make the best use of the opportunities provided by scientific progress.This, inevitably, requires a legal and regulatory framework to ensure that the benefits are made widely available to the population and, in particular, to protect consumers—today, DCGT by private companies remains a largely unregulated market. In 2008, the Committee of Ministers of the 47 Member States of the Council of Europe adopted the first international legally binding document concerning genetic testing for health purposes (Lwoff, 2009). The Additional Protocol to The Convention on Human Rights and Biomedicine about Genetic Testing for Health Purposes addresses some of the issues raised by genetic testing, from quality and clinical utility, to public information and genetic screening programmes for health purposes (Council of Europe, 2008). According to the Protocol, a health-screening programme that uses genetic tests can only be implemented if approved by the competent body, after independent evaluation of its ethical acceptability and fulfilment of specific conditions. These include the health relevance, scientific validity and effectiveness, availability of appropriate preventive or treatment measures, equitable access to the programme and availability of adequate measures to inform the population about the existence, purpose and accessibility of the screening programme, as well as the voluntary nature of participation in it.Two particular issues were discussed during the development of the Protocol: direct access to tests by individuals; and information and genetic counselling (Lwoff, 2009). The Protocol includes some debated restrictions to DCGT (Borry, 2008), to guarantee the proper interpretation of predictive test results and appropriate counselling to understand their implications. According to Article 7, with few exceptions “[a] genetic test for health purposes may only be performed under individualized medical supervision.” In order to assure quality of information and support for the patient, Article 8 states that “the person concerned shall be provided with prior appropriate information in particular on the purpose and the nature of the test, as well as the implications of its results.” Moreover, for tests for monogenic diseases, tests that aim to detect a genetic predisposition or genetic susceptibility to a disease, or tests to identify the subject as a healthy carrier of a gene responsible for a disease, appropriate genetic counselling should be available. It states that “the form and extent of this genetic counselling shall be defined according to the implications of the results of the test and their significance for the person or the members of his or her family, including possible implications concerning procreation choices.” According to this document, genetic counselling could thus go from being a “very heavy and long” procedure to a “lighter” one, but should be guaranteed in any case. The Protocol has already influenced legislation, but it will apply only in countries that have ratified it, which, so far, is only Slovenia.Companies that offer DCGTs are harbingers of change for personalized medicine. Their increasing popularity—owing not least to the ease with which their services can be obtained over the Internet—shows that the public is willing to pay for this kind of personal information. Nevertheless, healthcare systems and regulators must ensure that developments in this area benefit patients. Experience from genetic testing for neurological diseases—given their particularly severe impact on patients and their families—highlights both the current lack of proper regulation and oversight, as well as the potential health benefits that can be reaped from genetic tests.? Open in a separate windowDonato RamaniOpen in a separate windowChiara Saviane     

一个具选择、突变、迁移的群体的遗传差分模型

假设一个群体是由“单位点—双基因”的个体所组成的,在该群体内存在选择、突变、迁移、生死等效应的作用。本文给出了在上述假设下并满足:(1)世代重叠,选择、突变、迁移、生死等效应的作用均在世代遗传之间完成;(2)群体适当大,个体间交配随机,符合孟德尔式遗传;(3)没有任何意外的灾祸等约定的群体遗传的数学模型。通过模型分析,我们能够进一步用数学语言来解释一些生命现象。模型分析指出:虽然某些群体不满足Hardy-Weinberg定律所叙述的条件,但可能具有和Hardy-Weinberg定律的结论相似的结果。该文中还就几个主要参数的变化讨论了群体遗传和进化的某些性质,如平衡等。最后,我们给出了该模型的一个数值例子。     

Voluntary disclosure of BRCA1 mutation test results

This study assessed the probability that individuals tested for a BRCA1 gene mutation share their test results with family members, co-workers, and insurers. Members of a large kindred known to be at-risk for carrying a BRCA1 gene mutation were tested and they learned their results from a genetic counselor. During a follow-up interview, 4 months later, subjects were asked with whom they had shared their results. Respondents were most likely to have communicated results to family members, followed by co-workers, and insurers. Carrier status affected their willingness to disclose results to insurers. High rates of disclosure to family members should promote awareness of hereditary cancer risk. Selective disclosure to co-workers and insurers may promote information asymmetries that could affect employment and insurance markets.     

Civilian and military genetics: nondiscrimination policy in a post-GINA world

Evidence is emerging of a growing societal consensus about appropriate and inappropriate uses of genetic information. The Genetic Information Nondiscrimination Act of 2008 provides new legal protections to Americans by prohibiting the discriminatory use of genetic information by health insurers and employers. Additionally, the United States military recently created new policies for fair use of genetic information in the determination of benefits for servicemen and servicewomen leaving military service. Although critical issues remain, such as the potential for genetic information to be used to deny people other forms of insurance, and how the military will use genetic medicine overall, significant progress has been made.     

Competition as a source of constraint on life history evolution in natural populations

Competition among individuals is central to our understanding of ecology and population dynamics. However, it could also have major implications for the evolution of resource-dependent life history traits (for example, growth, fecundity) that are important determinants of fitness in natural populations. This is because when competition occurs, the phenotype of each individual will be causally influenced by the phenotypes, and so the genotypes, of competitors. Theory tells us that indirect genetic effects arising from competitive interactions will give rise to the phenomenon of ‘evolutionary environmental deterioration'', and act as a source of evolutionary constraint on resource-dependent traits under natural selection. However, just how important this constraint is remains an unanswered question. This article seeks to stimulate empirical research in this area, first highlighting some patterns emerging from life history studies that are consistent with a competition-based model of evolutionary constraint, before describing several quantitative modelling strategies that could be usefully applied. A recurrent theme is that rigorous quantification of a competition''s impact on life history evolution will require an understanding of the causal pathways and behavioural processes by which genetic (co)variance structures arise. Knowledge of the G-matrix among life history traits is not, in and of itself, sufficient to identify the constraints caused by competition.     

Beyond Mendel: an evolving view of human genetic disease transmission

Methodological and conceptual advances in human genetics have led to the identification of an impressive number of human disease genes. This wealth of information has also revealed that the traditional distinction between Mendelian and complex disorders might sometimes be blurred. Genetic and mutational data on an increasing number of disorders have illustrated how phenotypic effects can result from the combined action of alleles in many genes. In this review, we discuss how an improved understanding of the genetic basis of multilocus inheritance is catalysing the transition from a segmented view of human genetic disease to a conceptual continuum between Mendelian and complex traits.