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Method R estimates of additive genetic, dominance genetic, and permanent environmental fraction of variance for yield and health traits of Holsteins.

Fractions of variance accounted for by additive genetic, dominance genetic, and permanent environmental effects for milk, fat, and protein yields; somatic cell score; and productive life were estimated from Holstein data used for national genetic evaluations. Contemporary group assignments were determined using the national procedure. Data included 1,973,317 milk and fat records for 812,659 cows, 1,019,421 protein records for 462,067 cows, 468,374 lactation average somatic cell score (SCS) records for 232,909 cows, and 735,256 cows with productive-life records. Variance components were estimated with the JAADOM program, which uses iteration on data and second-order Jacobi iteration for obtaining solutions to the mixed-model equations and Method R for estimation of variance components. Ten different random data subsets were used to estimate parameters for each trait. Estimated additive genetic, dominance genetic, and permanent environmental fractions of variance were 0.34, 0.05, and 0.10 for milk yield; 0.34, 0.05, and 0.11 for fat yield; 0.31, 0.05, and 0.10 for protein yield; and 0.17, 0.01, and 0.16 for lactation average SCS. Estimated additive genetic and dominance genetic fractions of variance were 0.12 and 0.06 for productive life. Mean empirical standard errors of additive genetic, dominance genetic, and permanent environmental variance fractions were 0.003, 0.006, and 0.006.

Animals↗

Estimating the sensitivity of a genetic test using gene-carrier probability estimates and its application in genetic counselling.

BACKGROUND: The estimation of the sensitivity of a genetic test is of practical importance. If a 'gold standard' (an exact test) is not available, an estimate of the probability of being a gene carrier may be useful for an individual. This information could be based on individual pedigree and family-history data, and a known genetic model for the disease of interest. METHODS: We develop a maximum-likelihood estimate of the sensitivity of a genetic test that may be applied in a situation without a 'gold standard', in which an estimate of the probability of being a gene carrier for an individual is available. RESULTS: A maximum-likelihood estimate for the sensitivity can be obtained through an iterative algorithm. We demonstrate the method using data from a project on familial breast cancer. We further present disease-risk estimates incorporating results from a genetic test with different values of sensitivity, and compare these with disease-risk estimates that are solely based on family-history data. DISCUSSION: We provide a systematic methodology to obtain an estimate of sensitivity of a genetic test when only gene-carrier probability estimates from a genetic model are available. Given a negative result from a genetic test, predictions for lifetime and age-specific disease-risk, accounting for test sensitivity, can then be provided in genetic counselling.

Algorithms↗

Community genetic services in Latin America and regional network of medical genetics. Recommendations of a World Health Organization consultation.

The World Health Organization sponsored a Consultation on Community Genetic Services and a Regional Network of Medical Genetics in Latin America in Porto Alegre, Brazil, on June 19, 2003. The main recommendations of the meeting included: (a) the call for government funding of services, research and education in medical genetics; (b) the conduct of epidemiological research on the prevalence and types of birth defects, genetic disorders and genetic predispositions to common diseases; (c) the education of health professionals in genetics; (d) the education of genetic professionals in community health and public health genetics; (e) the fostering of interactions between clinical geneticists, public health personnel, primary health care workers and community organizations, and (f) a better planning of regionalized services to avoid duplication and inefficiency.

Community Networks↗

Genetic epidemiology: bringing genetics to the population--the NAPE Lecture 2001.

OBJECTIVE: To present an overview of the status of genetics of mental disorders and to describe the role of genetic epidemiology in the future of the implementation of the human genome initiative. METHOD: Reviews evidence on familial recurrence risk for major mental disorders and approaches to identify genes for complex disorders. RESULTS: The next decade will witness shifts in approaches of both epidemiology and genetics to address sources of complexity of the mental disorders. Descriptive genetic epidemiology will evolve into analytic genetic epidemiology by shifting the key questions from estimation of the magnitude of mental disorders to identification of risk and protective environmental factors that may be informative for both etiology and prevention. Genetics research will expand to population-based studies for complex disorders and will employ designs and methods that incorporate sources of complexity. CONCLUSION: In summary, the next era of human genetics will witness major shifts in approaches to identify the genes underlying mental disorders. The contributions of genetic epidemiology to translate advances in molecular genetics to public health are discussed.

Genetic Markers↗

Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic Analysis of Idiopathic Thrombophilia.

Although there are a number of well-characterized genetic defects that lead to increased risk of thrombosis, little information is available on the relative importance of genetic factors in thrombosis risk in the general population. We performed a family-based study of the genetics of thrombosis in the Spanish population to assess the heritability of thrombosis and to identify the joint actions of genes on thrombosis risk and related quantitative hemostasis phenotypes. We examined 398 individuals in 21 extended pedigrees. Twelve pedigrees were ascertained through a proband with idiopathic thrombosis, and the remaining pedigrees were randomly ascertained. The heritability of thrombosis liability and the genetic correlations between thrombosis and each of the quantitative risk factors were estimated by means of a novel variance component method that used a multivariate threshold model. More than 60% of the variation in susceptibility to common thrombosis is attributable to genetic factors. Several quantitative risk factors exhibited significant genetic correlations with thrombosis, indicating that some of the genes that influence quantitative variation in these physiological correlates also influence the risk of thrombosis. Traits that exhibited significant genetic correlations with thrombosis included levels of several coagulation factors (factors VII, VIII, IX, XI, XII, and von Willebrand), tissue plasminogen activator, homocysteine, and the activated protein C ratio. This is the first study that quantifies the genetic component of susceptibility to common thrombosis. The high heritability of thrombosis risk and the significant genetic correlations between thrombosis and related risk factors suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.

Adolescent↗

High genetic diversity vs. low genetic differentiation in Nouelia insignis (Asteraceae), a narrowly distributed and endemic species in China, revealed by ISSR fingerprinting.

BACKGROUND AND AIMS: Nouelia insignis Franch., a monotypic genus of the Asteraceae, is an endangered species endemic in Yunnan and Sichuan Provinces of China. Most of the populations are seriously threatened. Some of them are even at the brink of extinction. In this study, the genetic diversity and differentiation between populations of this species were examined in two drainage areas. METHODS: DNA fingerprinting based on inter-simple sequence repeat polymorphisms was employed to detect the genetic variation and population structure in the species. KEY RESULTS: Genetic diversity at species level was high with P=65.05% (percentage of polymorphic loci) and Ht=0.2248 (total genetic diversity). The coefficient of genetic differentiation among populations, Gst, which was estimated by partitioning the total gene diversity, was 0.2529; whereas, the genetic differentiation between populations in the Jinsha and Nanpan drainage areas was unexpectedly low (Gst=0.0702). CONCLUSIONS: Based on the genetic analyses of the DNA fingerprinting, recent habitat fragmentation may not have led to genetic differentiation or the loss of genetic diversity in the rare species. Spatial apportionment of fingerprinting polymorphisms provides a footprint of historical migration across geographical barriers. The high diversity detected in this study holds promise for conservation and restoration efforts to save the endangered species from extinction.

Asteraceae↗

Genetic information leaflets: influencing attitudes towards genetic testing.

PURPOSE: This article explores how a "neutral" genetics information leaflet influenced people's attitudes to be more positive toward predictive genetic testing. This is of concern, given the desire within clinical genetics and population based testing to provide information that informs choice without directing toward, or against, testing. METHOD: Four studies are reported. The first two investigated presentation (glossy and colored vs. black and white), and method of reading (read only vs. read followed by probing questions). The second two investigated content, using "think aloud," "card sort," and delayed recall tasks. RESULTS: Those receiving a glossy leaflet expressed more positive attitudes and more interest in undergoing testing than those receiving a black and white leaflet, and those who were asked questions about what they had read were more positive about genetic testing than those who only read the leaflet. Recall one week later varied from 72% to 28%, depending on type of information. Information that described the advantages of genetic testing or discussed genes and genetic testing in relation to disease were well recalled and rated positively. Attitudes toward information ranged from 100% positive (e.g., what diseases genetic tests are available for) to 0% positive (e.g., the meaning of a positive result). CONCLUSION: These results show that quite small changes within a leaflet can change attitudes toward genetic testing. This is of concern, given the association between attitudes toward a behavior and undergoing that behavior. The form, method of presentation, and content of genetic information leaflets should be evaluated for impact on attitude and decisions before they are used clinically.

Adolescent↗

Understanding of genetic information in higher secondary students in northeast India and the implications for genetics education.

Since the work of Watson and Crick in the mid-1950s, the science of genetics has become increasingly molecular. The development of recombinant DNA technologies by the agricultural and pharmaceutical industries led to the introduction of genetically modified organisms (GMOs). By the end of the twentieth century, reports of animal cloning and recent completion of the Human Genome Project (HGP), as well techniques developed for DNA fingerprinting, gene therapy and others, raised important ethical and social issues about the applications of such technologies. For citizens to understand these issues, appropriate genetics education is needed in schools. A good foundation in genetics also requires knowledge and understanding of topics such as structure and function of cells, cell division, and reproduction. Studies at the international level report poor understanding by students of genetics and genetic technologies, with widespread misconceptions at various levels. Similar studies were nearly absent in India. In this study, I examine Indian higher secondary students' understanding of genetic information related to cells and transmission of genetic information during reproduction. Although preliminary in nature, the results provide cause for concern over the status of genetics education in India. The nature of students' conceptual understandings and possible reasons for the observed lack of understanding are discussed.

Cells↗

[Statistical genetic analysis of some problem behaviors during sleep in childhood--estimation of genetic and environmental factors influencing multiple health phenomena simultaneously].

This study was conducted to clarify the genetic and environmental factors for some problem behaviors during sleep in childhood, namely sleep talking, half-sleeping, night terrors and nocturnal enuresis. The subjects were 881 pairs of twins, consisting of 609 monozygotic (279 male-male, 330 female-female) and 272 dizygotic (86 male-male, 84 female-female, 102 opposite-sexed). They were all applicants to the junior high school affiliated with Tokyo University from 1981 to 1998. The twins' mothers had previously completed a medical questionnaire and had been interviewed by three to five interviewers. With regard to the above mentioned four traits, they selected one answer from the choices 'often', 'sometimes' 'never' and 'unknown' for each twin. The interviewer checked the answers and, where necessary, explained the meaning of any terms such as "night terrors". Genetic analysis was performed as follows. First the answers were summarized in the form of a 2 x 2 contingency table; 'often' and 'sometimes' were included in one category. Then, tetrachoric correlations of the contingency table were calculated according to zygosity using the program package PRELIS2. Furthermore, covariance structure analysis was performed for several genetic models using the program package LISREL8. The results were as follows. Univariate genetic analysis showed that all four traits were under genetic control. Sleep talking, half-sleeping and night terrors were under strong or moderate genetic control. As to nocturnal enuresis, the genetic effect was moderate and shared environmental factors played an important role. Sex difference was observed in the case of half-sleeping and enuresis. Moreover these traits tended to occur together, and sleep talking, half-sleeping and night terrors shared common genetic and environmental factors in addition to specific genetic and environmental factors.

Child↗

Genetic implications of a simulation model of litter size in swine based on ovulation rate, potential embryonic viability and uterine capacity: I. Genetic theory.

A simulation model of litter size in swine based on ovulation rate, uterine capacity and potential embryo viability was compared to three genetic models to clarify its genetic characteristics. The simulation model is equivalent to independent culling based on fixed levels of potentially viable embryos and uterine capacity. Litter size also can be described by a combination of additive, additive x additive, mean environment x additive, random environment and additive x random environment effects. A third genetic model that can describe the simulation model is the associative effects model, in which litter size is the result of grouping two genotypes. The fixed independent culling levels model predicts that genetic parameters will change as the component means change. This genetic model also predicts that selection on an index of ovulation rate and uterine capacity would improve selection response for litter size. This genetic model predicts asymmetry of correlated responses in ovulation rate and uterine capacity when selecting for high and low litter size. The nonadditive genetic model predicts covariances among relatives that are different from their additive relationships; however, simulated results did not detect any differences. The nonadditive genetic model also predicts that heterosis for litter size will differ among crosses based on the mean environment and on additive x additive genetic interaction. The associative effects model predicts that selection for litter size will always lead to a positive response in litter size.

Animals↗

[Genetic effects on grain shape traits of indica black pericarp rice and their genetic correlations with main mineral element contents in grains].

Complete diallel crosses with 7 varieties of indica black pericarp rice were conducted to analyze the genetic effects on grain shape traits such as 100-grain weight, grain length, grain width and length/width and their genetic correlations with main mineral elements of Fe, Zn, Mn and P contents in kernels of parents and their F1s and F2s, by using the full genetic model including seed, cytoplasmic and maternal effects on quantitative traits of seeds in cereal crops. The results indicated that the grain shape traits were controlled by seed direct genetic effects, maternal genetic effects as well as by cytoplasmic effects. The seed direct genetic effects were more important than the maternal genetic effects for grain shape traits, and seed direct additive effects constituted a major part of their genetic effects. The narrow heritabilities of seed direct effects were high for 100-grain weight, grain width and grain length/grain width, while those of seed and maternal effects were intermediate for grain length. Therefore, more attention should be paid to the single seed selection on the 100-grain weight, grain width and grain length/grain width in early generations of hybrid offspring, while in the case of grain length, attention should be paid to single plant selection and single seed selection in late generations. The results also showed that there existed significant genetic correlations of seed direct additive, seed direct dominance, cytoplasm, maternal additive and maternal dominance between most of grain shape traits such as 100-grain weight, grain length, grain width, grain length/grain width and main mineral elements of Fe, Zn, Mn and P contents in grains. The improvement for nutrient quality traits of main mineral elements Fe, Zn, Mn and P contents in indica black pericarp rice could be realized by the indirect selection of grain shape traits in speciality rice quality breeding.

Crosses, Genetic↗

Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.

Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.

Animals↗

Genetic codes as evolutionary filters: subtle differences in the structure of genetic codes result in significant differences in patterns of nucleotide substitution.

The codon-degeneracy model (CDM) predicts that patterns of nucleotide substitution in protein-coding genes are largely determined by the relative frequencies of four-fold (4f), two-fold, and non-degenerate sites, the attributes of which are determined by the structure of the governing genetic code. The CDM thus further predicts that genetic codes with alternative structures will "filter" molecular evolution differentially. A method, therefore, is presented by which the CDM may be applied to the unique structure of any genetic code. The mathematical relationship between the proportion of transitions at 4f degenerate nucleotide sites and the transition-to-transversion ratio is described. Predictions for five individual genetic codes, relative to the relationship between code structure and expected patterns of nucleotide substitution, are clearly defined. To test this "filter" hypothesis of genetic codes, simulated DNA sequence data sets were generated with a variety of input parameter values to estimate the relationship between patterns of nucleotide substitution and best-fit estimates of transition bias at 4f degenerate sites for both the universal genetic code and the vertebrate mitochondrial genetic code. These analyses confirm the prediction of the CDM that, all else being equal, even small differences in the structure of alternative genetic codes may result in significant shifts in the overall pattern of nucleotide substitution.

Codon↗

Single nucleotide polymorphisms in clinical genetic testing: the characterization of the clinical significance of genetic variants and their application in clinical research for BRCA1.

Clinical genetic testing is increasingly employed in the medical management of cancer patients. These tests support a variety of clinical decisions by providing results that indicate risk for future disease, confirmation of diagnoses, and more recently, therapeutic selection and prognosis. Most genetic variation detected during clinical testing involves single nucleotide polymorphisms (SNPs). Continued advances in the technologies of genetic analyses make these tests increasingly sensitive, cost-effective and timely, which contribute to their increased utilization. Conversely, it has proven difficult to characterize the clinical significance of genetic variants that do not obviously truncate the open reading frames of genes. These genetic variants of uncertain clinical significance diminish the value of genetic test results. This article highlights a variety of approaches that have emerged from research in diverse disciplines to solve the problem, including the application of information about common SNPs in multiple methods to better characterize clinically uncertain variants. Hereditary breast/ovarian cancer, and in particular BRCA1, provides a framework for this discussion. BRCA1 is particularly interesting in this respect since clinical genetic testing by direct DNA sequencing for over 50,000 patients in North America has revealed approximately 1500 genetic variants to date. This large data set combined with the clinical significance of BRCA1 have resulted in research groups selecting BRCA1 as a preferred gene to evaluate novel methods in this field. Finally, the lessons learned through work with BRCA1 are highly applicable to many other genes associated with cancer risk.

Breast Neoplasms↗

Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

These cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Cancer Genetic Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Key components include the intake (medical and family histories), psychosocial assessment (assessment of risk perception), cancer risk assessment (determination and communication of risk), molecular testing for hereditary cancer syndromes (regulations, informed consent, and counseling process), and follow-up considerations. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

Critical Pathways↗

Scientific rationality, uncertainty and the governance of human genetics: an interview study with researchers at deCODE genetics.

Technology development in human genetics is fraught with uncertainty, controversy and unresolved moral issues, and industry scientists are sometimes accused of neglecting the implications of their work. The present study was carried out to elicit industry scientists' reflections on the relationship between commercial, scientific and ethical dimensions of present day genetics and the resources needed for robust governance of new technologies. Interviewing scientists of the company deCODE genetics in Iceland, we found that in spite of optimism, the informants revealed ambiguity and uncertainty concerning the use of human genetic technologies for the prevention of common diseases. They concurred that uncritical marketing of scientific success might cause exaggerated public expectations of health benefits from genetics, with the risk of backfiring and causing resistance to genetics in the population. On the other hand, the scientists did not address dilemmas arising from the commercial nature of their own employer. Although the scientists tended to describe public fear as irrational, they identified issues where scepticism might be well founded and explored examples where they, despite expert knowledge, held ambiguous or tentative personal views on the use of predictive genetic technologies. The rationality of science was not seen as sufficient to ensure beneficial governance of new technologies. The reflexivity and suspension of judgement demonstrated in the interviews exemplify productive features of moral deliberation in complex situations. Scientists should take part in dialogues concerning the governance of genetic technologies, acknowledge any vested interests, and use their expertise to highlight, not conceal the technical and moral complexity involved.

Fear↗

Toward cultural competence in cancer genetic counseling and genetics education: lessons learned from Chinese-Australians.

PURPOSE: In societies such as Australia with a strong multicultural makeup, culturally determined attitudes to genetics, testing, and counseling may be incompatible with current genetics service provision. METHODS: An ethnographic investigation using purposive sampling to increase subject diversity was used to explore the range of beliefs about kinship and inheritance using Chinese-Australians as a case. Participants comprised a sample of 15 Chinese-Australians who had been recruited through several community-based organizations. RESULTS: The level of acculturation does not correlate with holding beliefs about inheritance, kinship, and causes of hereditary cancer that are based on "Western" biomedical or traditional concepts. Mismatch between beliefs may exist within families that can impact participation in cancer genetic testing. Family history taking that underpins the surveillance, management, and referral to genetic counseling where there is a strong family history of breast, ovarian, or colorectal cancer can also be impacted unless recognition is made of the patrilineal concept of kinship prevalent in this Chinese-Australian community. CONCLUSION: This community-based study confirmed and validated views and beliefs on inheritance and kinship and inherited cancer attributed to senior family members by Chinese-Australians who attended cancer genetic counseling. Barriers to communication can occur where there may be incompatibility within the family between "Western" and traditional beliefs. The findings were used to develop strategies for culturally competent cancer genetic counseling with Australian-Chinese patients. These include nonjudgmental incorporation of their belief systems into the genetic counseling process and avoidance of stereotyping. They have also influenced the development of genetics education materials to optimize family history taking.

Adult↗

Multivariate quantitative genetics and the lek paradox: genetic variance in male sexually selected traits of Drosophila serrata under field conditions.

Single male sexually selected traits have been found to exhibit substantial genetic variance, even though natural and sexual selection are predicted to deplete genetic variance in these traits. We tested whether genetic variance in multiple male display traits of Drosophila serrata was maintained under field conditions. A breeding design involving 300 field-reared males and their laboratory-reared offspring allowed the estimation of the genetic variance-covariance matrix for six male cuticular hydrocarbons (CHCs) under field conditions. Despite individual CHCs displaying substantial genetic variance under field conditions, the vast majority of genetic variance in CHCs was not closely associated with the direction of sexual selection measured on field phenotypes. Relative concentrations of three CHCs correlated positively with body size in the field, but not under laboratory conditions, suggesting condition-dependent expression of CHCs under field conditions. Therefore condition dependence may not maintain genetic variance in preferred combinations of male CHCs under field conditions, suggesting that the large mutational target supplied by the evolution of condition dependence may not provide a solution to the lek paradox in this species. Sustained sexual selection may be adequate to deplete genetic variance in the direction of selection, perhaps as a consequence of the low rate of favorable mutations expected in multiple trait systems.

Animals↗