Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “quantitative genetics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1999

Evidence that multiple genes influence baseline concentrations and diet response of Lp(a) in baboons.

We investigated the response of lipoprotein(a) [Lp(a)] levels to dietary fat and cholesterol in 633 baboons fed a series of 3 diets: a basal diet low in cholesterol and fat, a high-fat diet, and a diet high in fat and cholesterol. Measurement of serum concentrations in samples taken while the baboons were sequentially fed the 3 diets allowed us to analyze 3 Lp(a) variables: Lp(a)(Basal), Lp(a)(RF) (response to increased dietary fat), and Lp(a)(RC) (response to increased dietary cholesterol in the high-fat environment). On average, Lp(a) concentrations significantly increased 6% and 28%, respectively, when dietary fat and cholesterol were increased (P<0.001). As expected, most of the variation in Lp(a)(Basal) was influenced by genes (h(2)=0.881). However, less than half of the variation in Lp(a)(RC) was influenced by genes (h(2)=0.347, P<0. 0001), whereas the increase due to dietary fat alone was not significantly heritable (h(2)=0.043, P=0.28). To determine whether Lp(a) phenotypic variation was due to variation in LPA, the locus encoding the apolipoprotein(a) [apo(a)] protein, we conducted linkage analyses by using LPA genotypes inferred from the apo(a) isoform phenotypes. All of the genetic variance in Lp(a)(Basal) concentration was linked to the LPA locus (log of the odds [LOD] score was 30.5). In contrast, linkage analyses revealed that genetic variance in Lp(a)(RC) was not linked to the LPA locus (LOD score was 0.036, P>0.5). To begin identifying the non-LPA genes that influence the Lp(a) response to dietary cholesterol, we tested, in bivariate quantitative genetic analyses, for correlation with low density lipoprotein cholesterol [LDLC; ie, non-high density lipoprotein cholesterol less the cholesterol contribution from Lp(a)]. LDLC(Basal) was weakly correlated with Lp(a)(Basal) (rho(P)=0.018). However, LDLC(RC) and Lp(a)(RC) were strongly correlated (rho(P)=0. 382), and partitioning the correlations revealed significant genetic and environmental correlations (rho(G)=0.587 and rho(E)=0.251, respectively). The results suggest that increasing both dietary fat and dietary cholesterol caused significant increases in Lp(a) concentrations and that the response to dietary cholesterol was mediated by a gene or suite of genes that appears to exert pleiotropic effects on LDLC levels as well. The gene(s) influencing Lp(a) response to dietary cholesterol is not linked to the LPA locus.

Animals↗
PubMed2006

Male pregnancy and the evolution of body segmentation in seahorses and pipefishes.

The evolution of complex traits, which are specified by the interplay of multiple genetic loci and environmental effects, is a topic of central importance in evolutionary biology. Here, we show that body and tail vertebral numbers in fishes of the pipefish and seahorse family (Syngnathidae) can serve as a model for studies of quantitative trait evolution. A quantitative genetic analysis of body and tail vertebrae from field-collected families of the Gulf pipefish, Syngnathus scovelli, shows that both traits exhibit significantly positive additive genetic variance, with heritabilities of 0.75 +/- 0.13 (mean +/- standard error) and 0.46 +/- 0.18, respectively. We do not find any evidence for either phenotypic or genetic correlations between the two traits. Pipefish are characterized by male pregnancy, and phylogenetic consideration of body proportions suggests that the position of eggs on the pregnant male's body may have contributed to the evolution of vertebral counts. In terms of numbers of vertebrae, tail-brooding males have longer tails for a given trunk size than do trunk-brooding males. Overall, these results suggest that vertebral counts in pipefish are heritable traits, capable of a response to selection, and they may have experienced an interesting history of selection due to the phenomenon of male pregnancy. Given that these traits vary among populations within species as well as among species, they appear to provide an excellent model for further research on complex trait evolution. Body segmentation may thus afford excellent opportunities for comparative study of homologous complex traits among disparate vertebrate taxa.

Animals↗
PubMed1992

Quantitative variability and multilocus polymorphism under epistatic selection.

We study multilocus polymorphism under selection, using a class of fitness functions that account for additive, dominant, and pairwise additive-by-additive epistatic interactions. The dynamic equations are derived in terms of allele frequencies and disequilibria, using the notions of marginal systems and marginal fitnesses, without any approximations. Stationary values of allele frequencies and pairwise disequilibria under weak selection are calculated by regular perturbation techniques. We derive conditions for existence and stability of the multilocus polymorphic states. Using these results, we then analyze a number of models describing stabilizing selection on additive characters, with some other factors, and determine the conditions under which genetic quantitative variability is maintained.

Alleles↗
PubMed1986

Correlations between relatives in small populations.

Correlations between relatives in small, closed populations can be substantially smaller than predicted by the classical formulas of population genetics. This effect is especially pronounced for relatives whose most recent common ancestor is several generations removed. When the effective population size is small, correlations between even close relatives can be negative. This implies that in small populations conventional estimators of quantitative genetics parameters will be biased and that preferential treatment of close relatives will be less likely to evolve.

Gene Frequency↗
PubMed2000

Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins.

BACKGROUND: Age-related cataracts are a major public health problem. The relative importance of genes and environment in the causation of nuclear cataracts, the most common form of age-related cataracts, is not known. METHODS: We studied 506 pairs of female twins (226 monozygotic and 280 dizygotic) who were 50 to 79 years old (mean, 62). The amount of nuclear cataract in the right and left eyes was determined objectively by analysis of Scheimpflug lens photographs (yielding three measures) and subjectively with use of the Oxford Clinical Cataract Classification and Grading System (yielding one measure). All eight measures (four in each eye) were subsequently combined in one summary measure of nuclear cataract for each woman. A univariate maximum-likelihood model was used to estimate the variance of the genetic and environmental contributions to each of the measures. RESULTS: The different measures of cataract formation were highly correlated (correlation coefficients, 0.71 to 0.94). The mean scores were similar for the right and left eyes and for monozygotic and dizygotic twins. Quantitative genetic modeling of each of the nuclear-cataract scores invariably resulted in a best-fitting model that involved additive genetic effects, unique environmental effects, and age. The common environmental and dominant genetic effects could be removed from the models without significant loss of fit. The overall heritability in the combined nuclear-cataract score (the proportion of the variance explained by genetic factors) was 48 percent (95 percent confidence interval, 42 to 54 percent); age accounted for 38 percent of the variance (95 percent confidence interval, 31 to 44 percent) and unique environmental effects for 14 percent (95 percent confidence interval, 12 to 18 percent). CONCLUSIONS: Genetic effects are important even in such a clearly age-related disease as nuclear cataract, explaining almost 50 percent of the variation in the severity of this disease.

Age Factors↗
PubMed2004

Genetic influences on CHD-death and the impact of known risk factors: comparison of two frailty models.

The importance of some recognized risk factors on genetic influences for coronary heart disease (CHD) needs further clarification. The aim of the present study was therefore to study the impact of known risk factors on genetic influences for CHD-death. Both twin (correlated gamma-frailty) and non-twin models (univariate gamma-frailty) were utilized and compared regarding their suitability for genetic analyses. The study population consisted of twins born in Sweden between 1886 and 1925. As expected, our findings indicate that genetic influences are important for CHD-death. Inclusion of risk factors in the twin-model increased heritability estimates, primarily due to a substantial reduction in non-shared environmental variances. The genetic influences for CHD-death are only marginally mediated through the risk factors among males, but more so among females. Although the outcome phenotype used in the present study is not behavioral, the analyses demonstrate the potential of frailty models for quantitative genetic analyses of categorical phenotypes.

Body Mass Index↗
PubMed2004

A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders.

Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including obsessive-compulsive disorder, panic disorder, major depressive disorder, bipolar disorder, schizophrenia and Alzheimer's disease. As the search for patterns of inheritance and candidate genes of these complex disorders continues, we review relevant findings from quantitative genetic studies and outline the main challenges for the field of psychiatric genetics to focus on in order to more definitively establish the underpinnings of genetic and environmental influences of adult psychopathology.

Adoption↗
PubMed2003

Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries.

Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20-29 and 30-39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.

Adolescent↗
PubMed2001

The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome.

Here we present the first genetic analysis of adiponectin levels, a newly identified adipocyte-derived protein. Recent work has suggested that adiponectin may play a role in mediating the effects of body weight as a risk factor for coronary artery disease. For this analysis we assayed serum levels of adiponectin in 1100 adults of predominantly northern European ancestry distributed across 170 families. Quantitative genetic analysis of adiponectin levels detected an additive genetic heritability of 46%. The maximum LOD score detected in a genome wide scan for adiponectin levels was 4.06 (P = 7.7 x 10(-6)), 35 cM from pter on chromosome 5. The second largest LOD score (LOD = 3.2; P = 6.2 x 10(-5)) was detected on chromosome 14, 29 cM from pter. The detection of a significant linkage with a quantitative trait locus on chromosome 5 provides strong evidence for a replication of a previously reported quantitative trait locus for obesity-related phenotypes. In addition, several secondary signals offer potential evidence of replications for additional previously reported obesity-related quantitative trait loci on chromosomes 2 and 10. Not only do these results identify quantitative trait loci with significant effects on a newly described, and potentially very important, adipocyte-derived protein, they also reveal the emergence of a consistent pattern of linkage results for obesity-related traits across a number of human populations.

Adiponectin↗
PubMed1993

A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms.

We studied 4042 Vietnam era veteran monozygotic and dizygotic male twin pairs to determine the effects of heredity, shared environment, and unique environment on the liability for 15 self-reported posttraumatic stress disorder symptoms included in the symptom categories of reexperiencing the trauma, avoidance of stimuli related to the trauma, and increased arousal. Quantitative genetic analysis reveals that inheritance has a substantial influence on liability for all symptoms. Symptoms in the reexperiencing cluster and one symptom in the avoidance and numbing cluster are strongly associated with combat exposure, and monozygotic pairs are more highly concordant for combat exposure than dizygotic pairs. By fitting a bivariate genetic model, we show that there are significant genetic influences on symptom liability, even after adjusting for differences in combat exposure; genetic factors account for 13% to 30% of the variance in liability for symptoms in the reexperiencing cluster, 30% to 34% for symptoms in the avoidance cluster, and 28% to 32% for symptoms in the arousal cluster. There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms.

Asia, Southeastern↗
PubMed2002

A quantitative assay for telomere protection in Saccharomyces cerevisiae.

Telomeres are the protective ends of linear chromosomes. Telomeric components have been identified and described by their abilities to bind telomeric DNA, affect telomere repeat length, participate in telomeric DNA replication, or modulate transcriptional silencing of telomere-adjacent genes; however, their roles in chromosome end protection are not as well defined. We have developed a genetic, quantitative assay in Saccharomyces cerevisiae to measure whether various telomeric components protect chromosome ends from homologous recombination. This "chromosomal cap" assay has revealed that the telomeric end-binding proteins, Cdc13p and Ku, both protect the chromosome end from homologous recombination, as does the ATM-related kinase, Tel1p. We propose that Cdc13p and Ku structurally inhibit recombination at telomeres and that Tel1p regulates the chromosomal cap, acting through Cdc13p. Analysis with recombination mutants indicated that telomeric homologous recombination events proceeded by different mechanisms, depending on which capping component was compromised. Furthermore, we found that neither telomere repeat length nor telomeric silencing correlated with chromosomal capping efficiency. This capping assay provides a sensitive in vivo approach for identifying the components of chromosome ends and the mechanisms by which they are protected.

Chromosomes, Fungal↗
PubMed1987

Robustness of path analysis of family resemblance against deviations from multivariate normality.

Path analysis is one of several methods available for quantitative genetic analysis, providing for both tests of hypotheses and estimates of relevant parameters. Central to the theory is the assumption that the observations follow a multivariate normal distribution within families. The purpose of the present investigation is to assess the effects of a certain type of departures from multivariate normality using quantitative family data on lipid and lipoprotein levels. The results show that even large departures produce reasonably unbiased parameter estimates. Whereas moderate departures lead to few inferential errors in hypothesis testing, gross departures from multivariate normality may have considerable effects on likelihood ratio tests.

Environment↗
PubMed2001

Modeling genetic architecture: a multilinear theory of gene interaction.

The map from genotype to phenotype is an exceedingly complex function of central importance in biology. In this work we derive and analyze a mathematically tractable model of the genotype-phenotype map that allows for any order of gene interaction. By assuming that the alterations of the effect of a gene substitution due to changes in the genetic background can be described as a linear transformation, we show that the genotype-phenotype map is a sum of linear and multilinear terms of operationally defined "reference" effects at each locus. The "multilinear" model is used to study the effect of epistasis on quantitative genetic variation, on the response to selection, and on genetic canalization. It is shown how the model can be used to estimate the strength of "functional" epistasis from a variety of genetic experiments.

Analysis of Variance↗
PubMed2007

Genetic correlations between mandibular molar cusp areas in baboons.

Primate evolutionary studies rely significantly on dental variation given the large role that teeth play in how an organism interacts with its environment (animal and plant) and conspecifics. Variation in cusp size has been shown to vary among primate taxa, although most studies to date focused on extant and extinct hominoids. Here we test the assumed hypothesis that a significant proportion of this variation in baboons is due to the additive effects of genes. We perform quantitative genetic analyses on variation in two-dimensional (2-D) mandibular molar cusp size in a captive pedigreed breeding population of baboons (Papio hamadryas) from the Southwest National Primate Research Center. These analyses show that variation in cusp size is heritable and sexually dimorphic. Additionally, we tested for genetic correlations between cusps on the same crown, between morphological homologues along the tooth row, and between cusp area and crown buccolingual width. We find that four of the six cusp pairs on the first molar have a genetic correlation of one, save for the metaconid-hypoconid and entoconid-hypoconid, which are not statistically different from zero. The second and third molars have lower genetic correlations, although the metaconid-hypoconid correlation is similarly estimated at zero and the entoconid-protoconid correlation is estimated to be one. This cross pattern of genetic and no genetic correlation does not immediately accord with the known pattern of development and/or calcification. We propose two explanative hypotheses.

Animals↗
PubMed1991

A genetic-correlational study of hippocampal structural variation and variation in exploratory activities of mice.

Our previous work provided evidence that hippocampal opioid peptides form an important neurochemical substrate underlying the gene-dependent exploratory behavior of mice. A prominent hippocampal opioid is dynorphin B, which resides in the mossy fibers exclusively. In order to seek support for causal relationships between dynorphinergic hippocampal mechanisms and exploration, a quantitative-genetic method was chosen. For this purpose, mice from the inbred strains C57BL/6, DBA/2, BLN, and CPB-K were used. Their hippocampal mossy fiber projections were visualized by means of immunohistochemistry, using a highly specific anti-dynorphin B antiserum. The additive-genetic correlations that were estimated suggest pleiotropic gene effects on locomotion, rearing-up, wall-leaning, and several intra- and infrapyramidal mossy fiber (iipMF) variables. Long iipMF, in particular, were found to be associated with high exploratory activity.

Animals↗
PubMedDate not supplied

Prospects for development of genetic markers for resistance to gastrointestinal parasite infection in sheep.

Selection of sheep for resistance to internal parasites represents a viable option for future parasite control. Many phenotypic measures are available for determining the level of infection in individual sheep, although no phenotypic markers are available which allow prediction of an individual's resistance status. Genetic markers are therefore the best way to incorporate parasite resistance into selection programmes. With the recent development of genetic maps, several experiments are underway to search for markers linked to parasite-resistance genes in sheep. It can be predicted confidently that markers associated with resistance will be discovered within 12 months. Markers useful as selection criteria will be available within 5 years, although considerable quantitative genetic analysis needs to be done to find the best way to utilise marker information in selection programmes. In future, methods for differential DNA analysis or mRNA expression will lead to isolation of the genes involved.

Animals↗
PubMed2001

A genetic interpretation of ecologically dependent isolation.

Hybrids may suffer a reduced fitness both because they fall between ecological niches (ecologically dependent isolation) and as a result of intrinsic genetic incompatibilities between the parental genomes (ecologically independent isolation). Whereas genetic incompatibilities are common to all theories of speciation, ecologically dependent isolation is a unique prediction of the ecological model of speciation. This prediction can be tested using reciprocal transplants in which the fitness of various genotypes is evaluated in both parental habitats. Here we expand a quantitative genetic model of Lynch (1991) to include two parental environments. We ask whether a sufficient experimental design exists for detecting ecologically dependent isolation. Analysis of the model reveals that by using both backcrosses in both parental environments, environment-specific additive genetic effects can be estimated while correcting for any intrinsic genetic isolation. Environment-specific dominance effects can also be estimated by including the F1 and F2 in the reciprocal transplant. In contrast, a reciprocal transplant comparing only F1s or F2s to the parental species cannot separate ecologically dependent from intrinsic genetic isolation. Thus, a reduced fitness of F1 or F2 hybrids relative to the parental species is not sufficient to demonstrate ecological speciation. The model highlights the importance of determining the contribution of genetic and ecological mechanisms to hybrid fitness if inferences concerning speciation mechanisms are to be made.

Adaptation, Physiological↗
PubMed2006

Genetic and environmental factors affecting self-rated health from age 16-25: a longitudinal study of Finnish twins.

We analyzed genetic and environmental determinants of self-rated health and its change from adolescence to early adulthood. Questionnaires were mailed to Finnish twins born 1975-1979 at ages 16, 17, 18 1/2 and, on average, 25 years of age (N=2465 complete twin pairs). The data were analyzed using quantitative genetic methods for twin data by the Mx statistical package. Heritability of self-rated health was greatest at age 16 (63%, 95% confidence intervals (CI) 56-67%, men and women together) and declined steadily to age 25 (33%, 95% CI 25-41%). The residual variation was due to unshared environments. Health ratings at different ages were modestly correlated (r=0.33-0.61). These correlations were mainly due to genetic factors, but unshared environment also contributed to them. An important challenge for further research is to identify environmental influences contributing to self-rated health independently of, or in interaction with, genetic factors.

Adolescent↗