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Outcomes of reciprocal invasions between genetically diverse and genetically uniform populations of Daphnia obtusa (Kurz).

Ecological theory predicts that genetic variation produced by sexual reproduction results in niche diversification and provides a competitive advantage both to facilitate invasion into genetically uniform asexual populations and to withstand invasion by asexual competitors. We tested the hypothesis that a large group of diverse clones of Daphnia obtusa has greater competitive advantage when invading into genetically uniform populations of this species than a smaller group with inherently less genetic diversity. We compared competitive outcomes to those of genetically uniform groups of small and large size invading into genetically diverse populations. Genetically diverse invaders of initially large group size increased their representation by more than those of initially small size; in contrast, genetically uniform invaders of initially large group size diminished on average by more than those of initially small size. These results demonstrate an advantage to the genetic variation produced by sexual reproduction, both in invasion and resisting invasion, which we attribute to competitive release experienced by individuals in genetically diverse populations.

Animals↗

Realized sampling variances of estimates of genetic parameters and the difference between genetic and phenotypic correlations.

A data set of 1572 heritability estimates and 1015 pairs of genetic and phenotypic correlation estimates, constructed from a survey of published beef cattle genetic parameter estimates, provided a rare opportunity to study realized sampling variances of genetic parameter estimates. The distribution of both heritability estimates and genetic correlation estimates, when plotted against estimated accuracy, was consistent with random error variance being some three times the sampling variance predicted from standard formulae. This result was consistent with the observation that the variance of estimates of heritabilities and genetic correlations between populations were about four times the predicted sampling variance, suggesting few real differences in genetic parameters between populations. Except where there was a strong biological or statistical expectation of a difference, there was little evidence for differences between genetic and phenotypic correlations for most trait combinations or for differences in genetic correlations between populations. These results suggest that, even for controlled populations, estimating genetic parameters specific to a given population is less useful than commonly believed. A serendipitous discovery was that, in the standard formula for theoretical standard error of a genetic correlation estimate, the heritabilities refer to the estimated values and not, as seems generally assumed, the true population values.

Analysis of Variance↗

Integration of physical, genetic and cytogenetic maps of human chromosome 7: isolation and analysis of yeast artificial chromosome clones for 117 mapped genetic markers.

An important goal for the human genome project is to assemble fully integrated physical, genetic and cytogenetic maps for each human chromosome. Towards that end, we have isolated yeast artificial chromosome (YAC) clones containing 117 of the 119 genetic markers that constitute a recently constructed, detailed genetic map of human chromosome 7. Analysis of these clones reveals numerous examples where adjacent genetic markers have been physically connected, either in individual YACs or in multi-YAC contigs. At present, the 117 genetic markers are contained in fewer than 80 YAC contigs, with most of these contigs uniquely ordered relative to one another based on the genetic map positions of the corresponding markers. These YACs and YAC contigs are estimated to contain approximately 60-85% of the DNA from human chromosome 7. YACs representing 36 genetic markers were mapped by fluorescence in situ hybridization (FISH) to metaphase chromosomes, allowing assignment of these genetic markers to cytogenetic bands along chromosome 7 and placement of the centromere within the genetic map. Together, these studies provide genetically and cytogenetically anchored YAC clones covering the majority of chromosome 7 that will be useful both for the positional cloning of genes and as a framework for assembling a complete YAC-based physical map of the chromosome.

Chromosome Mapping↗

Clinical genetics as clues to the "real" genetics of schizophrenia (a decade of modest gains while playing for time).

Although a decade has passed since the genetics of schizophrenia was examined for the Schizophrenia Bulletin, the epigenetic puzzle of schizophrenia has not yielded its secrets to any scientific break-through. In this article we review a sample of the highlights relevant to enlightened genetic thinking, i.e., a broad diathesis-stressor framework with multifactorial causation assumed and with provision for the epigenetic interaction of psychosocial as well as neurobiological factors. The clinical genetic epidemiologist needs to know the lifetime morbid risks generated by different definitions of schizophrenia, as well as the consequences for the familial risks generated by the various family, twin, and adoption strategies. Schizophrenia appears to occur through an interaction of a genetic susceptibility with some kind of environmental stress; the stress need not be an environment containing a person with a diagnosis in the schizophrenia spectrum; the genetic factors in schizophrenia have specificity as they do not increase the risk for major affective disorders or delusional disorder. Clearly, schizophrenia is clinically or phenotypically heterogeneous, but whether this variety is paralleled by etiological heterogeneity or to what extent is problematic. Once the existence of an important genetic predisposition to developing schizophrenia has been established, it becomes important to provide a theory (or theories) to account for its mode (modes) of transmission. Psychiatric geneticists have not yet solved the problem, in part because of the difficulty of specifying the appropriate phenotype to analyze and also because of the unknown degree of heterogeneity. Genetic markers are a special category of biological markers. In addition to conventional markers, the advent of "the new genetics" of recombinant DNA has meant that many more genetic markers (probes) are now available and that the day is not far off when the human genome will be extensively mapped. Considerable optimism exists about the future usefulness of genetic markers in detecting major gene effects and resolving problems of heterogeneity in schizophrenia.

Diseases in Twins↗

Direct genetic and postnatal maternal genetic effects on body composition in mice selected for body weight.

Line crossfostering techniques were used to study differences among selected and control lines of mice in direct genetic and postnatal maternal genetic influences on preweaning (day 12) body weight and composition. The lines were selected for high (H6) and low (L6) 6-week body weight and the control line (C2) was maintained by random selection. There were positive correlated responses to selection in both direct genetic and postnatal maternal genetic effects on body weight and weights of all body components (P less than 0.01) except for water and ash weight in H6. The correlated responses in postnatal maternal genetic effects were of the same order of magnitude as those in direct genetic effects. Correlated responses were greater in L6 than in H6. Correlated responses in direct genetic effects were positive (P less than 0.01) for water percent in H6 and ether extract percent in L6, and negative (P less than 0.01) for water percent and lean percent in L6. Correlated responses in postnatal maternal genetic effects were positive for ether extract percent and negative for water percent (P less than 0.01). Correlated responses were far greater in L6 than in H6 and were greater for postnatal maternal genetic effects than for direct genetic effects. Analyses of covariance results indicated line differences in the relative growth rates of the body components.

Analysis of Variance↗

Genetic sonography: a cost-effective method for evaluating women 35 years and older who decline genetic amniocentesis.

OBJECTIVE: To determine whether offering genetic sonography to patients who decline invasive testing can increase the detection rate of trisomy 21 and is cost-effective. METHODS: The detection rate of trisomy 21, the number of pregnancy losses after amniocentesis, and the cost of detecting a single fetus with trisomy 21 were determined in women 35 years and older managed according to the following 3 policies: (1) universal amniocentesis, (2) genetic counseling for maternal age-associated risks for trisomy 21 followed by amniocentesis in patients who elected it, and (3) genetic counseling followed by genetic sonography in patients who originally declined genetic amniocentesis. RESULT: From a population of 40,143 women 35 years and older, the expected number of trisomy 21 fetuses was 349. After genetic counseling, 32% of patients declined invasive testing, resulting in detection of 70% of fetuses with trisomy 21. For universal amniocentesis, the cost to detect 1 fetus with trisomy 21 was $138,036. For the 32% who declined invasive testing after genetic counseling and underwent genetic sonography, the cost to detect a single fetus with trisomy 21 was a function of sensitivity and the screen-positive rate. For screen-positive rates between 5% and 25%, genetic sonography resulted in a cost savings between 14.3% and 18.8% when compared with universal invasive testing and resulted in a considerable increase in detection of fetuses with trisomy 21 (77% to 97%). CONCLUSIONS: A policy of offering genetic sonography followed by amniocentesis to patients 35 years and older who originally decline invasive testing for the diagnosis of trisomy 21 is cost-effective and results in a higher overall detection rate for trisomy 21 without an increased risk of pregnancy loss.

Adult↗

How can the evaluation of genetic tests be enhanced? Lessons learned from the ACCE framework and evaluating genetic tests in the United Kingdom.

Advances in genetic technology are increasing the availability of genetic tests, not only for rare single gene disorders, but also for common diseases such as breast and colo-rectal cancer. Before there can be widespread uptake of these tests, they must be evaluated to confirm the benefits of their use. But how should genetic tests be evaluated, given the speed at which new tests are emerging? One highly influential approach is the analytic validity, clinical validity, clinical utility and ethical, legal and social issues (ACCE) framework, which has provided a benchmark for the evaluation of genetic tests. The approach has been adopted and adapted by the United Kingdom Genetic Testing Network, with the help of the Public Health Genetics Unit in Cambridge, to evaluate new genetic tests for use in the National Health Service. We discuss a number of conceptual, methodological, and practical issues concerning the evaluation of genetic tests, based on lessons learned from applying the ACCE framework and from the UK experience, and make a number of recommendations to further strengthen the evaluation of genetic tests.

Genetic Carrier Screening↗

Effect of genetic groups on estimates of additive genetic variance.

This study examined the effect of genetic grouping on REML estimates of additive genetic variance with an animal model with selected base populations. A simulated population of 40 animals (20 males and 20 females) was followed under selection or random mating conditions for 10 generations. Each population was replicated 20 or 50 times. Genetic grouping reduced estimates of additive genetic variance in populations with selected base animals, whereas grouping had little effect on the estimate in unselected populations. The effect of genetic grouping varied according to the quantity and kind of information that was missing (percentage of deleted data and pattern of deletion). When genetic grouping was completely random, the estimates were unaffected. Because including genetic groups in the model for analysis affected the estimates of additive genetic variance, the question should be considered of what value or values for heritability should be used for genetic evaluation when grouping is used to account for prior selection.

Animals↗

Genetic privacy and the law: an end to genetics exceptionalism.

While the proliferation of human genetic information promises to achieve many public benefits, the acquisition, use, retention, and disclosure of genetic data threatens individual liberties. States (and to a lesser degree, the federal government) have responded to the anticipated and actual threats of privacy invasion and discrimination by enacting several types of genetic-specific legislation. These laws emphasize the differences between genetic information and other health information. By articulating these differences, governments afford genetic data an "exceptional" status. The authors argue that genetic exceptionalism is flawed for two reasons: (1) strict protections of autonomy, privacy, and equal treatment of persons with genetic conditions threaten the accomplishment of public goods; and (2) there is no clear demarcation separating genetic data from other health data; other health data deserve protections in a national health information infrastructure. The authors present ideas for individual privacy protections that balance the societal need for genetic information and the claims for privacy by individuals and families.

Databases, Nucleic Acid↗

Genetic diversity and genetic burden in humans.

We discuss categories of genetic diversity in humans. Neutral diversity, population differences in frequencies of genetic markers that we think are invisible to natural selection, provides a passive record of population history but is otherwise of little interest in human biology. Genetic variation related to disease can be separated into mutational noise and variation due to selection, either ongoing selection else effects of a past environment. We distinguish consequences of genetic diversity for fitness, relevant to evolution, and consequences for well-being, relevant to medicine and public health. We call genetic variation that causes impairment of health or well-being of individual humans "apparent genetic burden" and variation that has effects on fitness but not well-being "unapparent genetic burden". We use "burden" to distinguish these notions from the classical concept of "genetic load" that refers to effects on population fitness, a concept formulated by Morton et al. [Morton, N.E., Crow, J.F., Muller, H.J., 1956. An estimate of the mutational damage in man from data on consanguineous marriages. Proc. Natl. Acad. Sci. U.S.A. 42, 855-863]. We distinguish adapted genes and adapted genotypes: an adapted gene is a gene that increases fitness of its bearer either in heterozygous or homozygous state or both, while an adapted genotype is a genotype that increases fitness of its bearer but is not transmitted intact to future generations. Balanced polymorphisms in which the heterozygote is superior in fitness may generate most adapted genotypes. In the face of major rapid environmental change adapted genotypes appear first but over time they are replaced by adapted genes. The presence of adapted genotypes is a good indication of recent environmental change: for example, there are apparently many polymorphisms in domestic animals of this nature, responses to domestication, and many fewer in wild animals (and in humans).

Alleles↗

Are genetic influences on peptic ulcer dependent or independent of genetic influences for Helicobacter pylori infection?

BACKGROUND: Genetic factors play a role or roles in the etiology of peptic ulcer disease and the acquisition of Helicobacter pylori infection. OBJECTIVE: To evaluate the relative importance of genetic and environmental influences as well as the importance of H. pylori on peptic ulcer disease. DESIGN: Cross-sectional study on monozygotic (MZ) and dizygotic (DZ) twins, reared apart or together. PARTICIPANTS: Twins of the subregistry of the Swedish Twin Registry included in the Swedish Adoption/Twin Study of Aging. MEASUREMENTS: Peptic ulcer disease and H. pylori status were assessed in MZ and DZ twin pairs reared apart or together. A total of 258 twin pairs had information regarding H. pylori status and history of peptic ulcer. Helicobacter pylori status was assessed as the presence of anti-H. pylori IgG. RESULTS: The intraclass correlations for peptic ulcer disease for MZ twins reared apart and together and DZ twins reared apart and together were 0.67, 0.65, 0.22, and 0.35, respectively, which indicates that genetic effects are important for liability to peptic ulcer. The correlation coefficient for MZ twins reared apart (0.67) provides the best single estimate of the relative importance of genetic effects (heritability) for variation in liability to peptic ulcer disease, and structural model fitting analyses confirmed this result (heritability, 62%). The cross-twin cross-trait correlations for MZ and DZ twins were examined to determine whether genetic effects for peptic ulcer were shared with or independent of genetic influences for H. pylori. The cross-correlations for MZ and DZ twins were almost identical (0.25 and 0.29, respectively), suggesting that familial environmental rather than genetic influences mediate the association between peptic ulcer disease and H. pylori infection. CONCLUSIONS: Genetic influences are of moderate importance for liability to peptic ulcer disease. Genetic influences for peptic ulcer are independent of genetic influences important for acquiring H. pylori infection.

Adult↗

Moderate genetic influences on plasma levels of plasminogen activator inhibitor-1 and evidence of genetic and environmental influences shared by plasminogen activator inhibitor-1, triglycerides, and body mass index.

Both genes and environmental factors have been reported to influence plasma levels of plasminogen activator inhibitor-1 (PAI-1). However, the relative importance of genetic influences (i.e., heritability) on plasma PAI-1 levels has not yet been investigated. Furthermore, PAI-1 levels are correlated with body mass index (BMI) and triglycerides. These correlations could reflect genetic and/or environmental factors in common to PAI-1, triglycerides, and BMI. We applied multivariate genetic analysis methods to assess the relative importance of genetic and environmental influences on plasma PAI-1 levels and to test the significance of genetic and/or environmental influences shared by PAI-1, triglycerides, and BMI in 217 pairs of middle-aged and elderly twins, of whom 113 pairs were reared apart and 121 pairs were women. The heritability estimate for PAI-1 levels was 42%. Individual-specific environmental factors explained 36% of the variance for PAI-1 levels. The remaining variance of PAI-1 was explained by rearing and residual-familial environmental factors. Furthermore, a genetic correlation of 1.00 between PAI-1 and triglycerides, a rearing environmental correlation of 1.00 between PAI-1 and BMI, a residual-familial environmental correlation of 1.00 between PAI-1 and triglycerides, and a genetic correlation of 0.63 between PAI-1 and BMI, were found. In conclusion, the present results suggest that genetic influences on plasma PAI-1 are moderate. Genetic and shared rearing or residual-familial environmental factors shared by PAI-1, BMI, and triglycerides explain the phenotypic association between these measures. It appears that all the genetic influences for PAI-1 are more or less shared with those for triglycerides and BMI.

Adoption↗

Assessment of Genetic Correlations Between Tobacco or Alcohol Use and Neurodegenerative Diseases Using East Asian Genetic Ancestry Genome-Wide Association Study Results.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.

Female↗

Implementation and evaluation of a genetics curriculum to improve obstetrician-gynecologist residents' knowledge and skills in genetic diagnosis and counseling.

OBJECTIVE: This study was undertaken to develop, implement, and evaluate a genetics curriculum for obstetrician-gynecologist residents. STUDY DESIGN: We prospectively evaluated the effect of a genetics curriculum on obstetrician-gynecologist residents' knowledge and skills. Residents completed a needs assessment and pretest. Educational intervention included 2 3-hour didactic sessions with 1 hour of lecture followed by case discussion and 1 3-hour session of experiential learning using standardized patients who evaluated residents' knowledge and skills in taking family history, drawing genetic pedigrees, and counseling patients. Posttest scores were compared with pretest scores. RESULTS: Needs assessment was completed by all 40 obstetrics and gynecology residents and identified limited and variable genetics education in medical school. Twenty-eight of 40 residents attended the entire educational intervention and completed the pretest and posttest, and 25 of 28 showed improved test scores. Residents stated that they were more confident in their ability to take a family history, record a 3-generation pedigree, and counsel patients about genetic conditions after completion of the genetics curriculum. CONCLUSION: This multifaceted genetics curriculum improved residents' knowledge of genetics as well as their confidence in applying genetic concepts as assessed by the pretest and posttest and by their comments in the debrief session.

Clinical Competence↗

Exploring the discourse between genetic counselors and Orthodox Jewish community members related to reproductive genetic technology.

OBJECTIVE: Genetic technology is complex, relatively new and involves sensitive issues pertaining to personhood and reproduction. While ethno cultural barriers to genetic care are well documented, little attention has been devoted to understanding religious beliefs pertaining to genetic services. This study evaluated the discourse between genetic counselors and Orthodox Jewish community members' perceptions of reproductive genetic technology. METHODS: A cross section of the Orthodox Jewish community was sampled through purposeful and snowball recruitment for in-depth interviews with key informants. RESULTS: Genetic counselors felt apprehensive about serving the Orthodox Jewish population and were unaware of social norms, religious and cultural practices unique to this population. Similarly, Orthodox Jewish consumers exhibited major misgivings about genetic testing. Importantly, stereotypic expectations by both counselors and consumers exacerbated existing communication difficulties. CONCLUSION: Cultural differences and poor communication between genetic counselors and Orthodox Jewish community members impeded the ability of the Orthodox Jewish community to utilize genetic services. PRACTICE IMPLICATIONS: This work illuminates complex issues pertaining to medical encounters between providers and patients with ideological, social and cultural differences. In particular, issues of access to care and transcultural competence in serving religious minority groups, such as Orthodox Jews are presented. On the whole, this group is largely unrecognized in the minority health literature in spite of barriers and challenges that they face. Findings of this study may have application to other cloistered and highly observant religious groups when dealing with reproductive technology and other populations with diverse values, beliefs and behaviors pertaining to reproductive health.

Attitude of Health Personnel↗

Genetic counseling in primary care: longitudinal, psychosocial issues in genetic diagnosis and counseling.

Primary care clinicians have an essential role in genetic counseling.This role is distinct from the usual role of genetic counselors. First,primary care clinicans are often involved in the early stages of identifying who may benefit from genetic assessment, helping patients to decide when it is appropriate to pursue genetic information, and preparing them for consultation. Second, the styles of counseling and guidance common in generalist practice are different from the nondirective approach espoused in genetic counseling. Third, primary care clinicians often have a working knowledge of the patient's family, the context in which genetic information has its impact. They are likely to care for family members in addition to the identified patient,and may be well-positioned to adopt a family-based approach to managing genetic risk. Finally, primary care involves a longitudinal perspective, in which genetic information (the family history, for example) takes on new meaning and sometimes more urgency, as diseases progress, family members are newly diagnosed, and patients enter new phases of the life cycle. Patient continuity will play a pivotal role in the care and long-term management for individuals found to be at risk for genetic illness.

Genetic Counseling↗

Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

Adipose Tissue↗

Genetic diversity and genetic differentiation in Daphnia metapopulations with subpopulations of known age.

If colonization of empty habitat patches causes genetic bottlenecks, freshly founded, young populations should be genetically less diverse than older ones that may have experienced successive rounds of immigration. This can be studied in metapopulations with subpopulations of known age. We studied allozyme variation in metapopulations of two species of water fleas (Daphnia) in the skerry archipelago of southern Finland. These populations have been monitored since 1982. Screening 49 populations of D. longispina and 77 populations of D. magna, separated by distances of 1.5-2180 m, we found that local genetic diversity increased with population age whereas pairwise differentiation among pools decreased with population age. These patterns persisted even after controlling for several potentially confounding ecological variables, indicating that extinction and recolonization dynamics decrease local genetic diversity and increase genetic differentiation in these metapopulations by causing genetic bottlenecks during colonization. We suggest that the effect of these bottlenecks may be twofold, namely decreasing genetic diversity by random sampling and leading to population-wide inbreeding. Subsequent immigration then may not only introduce new genetic material, but also lead to the production of noninbred hybrids, selection for which may cause immigrant alleles to increase in frequency, thus leading to increased genetic diversity in older populations.

Aging↗