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PubMed2003

Quantitative genetic study of radiographic hand bone size and geometry.

Despite the obvious epidemiological significance of bone size (BS) and geometry (BG) traits as risk factors for osteoporotic fracture, very little is still known concerning the extent of their genetic determination. In the present paper we report the results of quantitative genetic analysis of a number of BG and BS indices, as well as of BMD measurements, obtained on a large pedigree-based sample (296 nuclear families, 1208 individuals) of plain hand radiographs. The families studied were all ethnically Caucasians (Chuvasha) living in small villages along the Volga River (Russia). The sample consisted of 636 men and 572 women, aged 18-91 years. To assess hand bone size we used the outcome of principal component analysis conducted on 48 measurements of metacarpal bones and proximal phalanges (PC-BS). Two BG indices, average metacarpal cortical index and breaking bending resistance index (BBRI), also measured on metacarpal and proximal phalanges were used. Again the outcome of the principal component PC-BBRI was examined in the genetic analysis. PC-BS measurements strongly correlated with body length (r = 0.75, P < 0.001) and weight (r = 0.39, P < 0.001), suggesting that they indeed reflected hand skeleton size. Familial correlations for all studied traits, adjusted for covariates (sex, age, etc.), were all highly significant statistically. For example, parent/offspring correlations ranged between 0.248 (P < 0.001) for phalangeal BMD and 0.385 (P < 0.001) for PC-BBRI. Maximum likelihood estimates of the variance component analysis confirmed these results, indicating that approximately 58 to 66% of the residual variance of the studied traits was attributable to genetic effects. Bivariate analysis clearly revealed that while genetic variation of the phalangeal BMD was independent of the genetic effects influencing hand BS and BG, the latter two were strongly interrelated. A substantial proportion of PC-BS and PC-BBRI variation was due to shared genetic (r(G) = 0.468 +/- 0.063) and environmental (r(E) = 0.704 +/- 0.052) factors.

Adolescent↗
PubMed2004

Quantitative genetic variation in the hematopoietic stem cell and progenitor cell compartment and in lifespan are closely linked at multiple loci in BXD recombinant inbred mice.

The number of bone marrow hematopoietic stem and progenitor cells as defined by the lineage(-), Sca1(++), c-kit(+) (LSK) phenotype and their proliferative capacity in vitro are subject to quantitative genetic variation, and several quantitative trait loci (QTL) have been identified in young mice. Because some traits affecting hematopoiesis also change with age in a mouse strain-dependent fashion, we performed quantitative trait analysis in aged BXD recombinant inbred (RI) mice for the number and frequency of LSK cells, and for their proliferative capacity in vitro. Several novel QTL were identified. The number and frequency of LSK cells in old mice correlated inversely with lifespan. Furthermore, 4 of 7 lifespan QTL overlap with QTL contributing to the number, frequency, or proliferative capacity of LSK cells in young or old mice. Taken together, these data establish a close genetic, and perhaps functional, link between genetic variation in lifespan and characteristics of stem and progenitor cells.

Aging↗
PubMed2001

A quantitative genetic analysis of nuclear-cytoplasmic male sterility in structured populations of Silene vulgaris.

Gynodioecy, the coexistence of functionally female and hermaphroditic morphs within plant populations, often has a complicated genetic basis involving several cytoplasmic male-sterility factors and nuclear restorers. This complexity has made it difficult to study the genetics and evolution of gynodioecy in natural populations. We use a quantitative genetic analysis of crosses within and among populations of Silene vulgaris to partition genetic variance for sex expression into nuclear and cytoplasmic components. We also use mitochondrial markers to determine whether cytoplasmic effects on sex expression can be traced to mitochondrial variance. Cytoplasmic variation and epistatic interactions between nuclear and cytoplasmic loci accounted for a significant portion of the variation in sex expression among the crosses. Source population also accounted for a significant portion of the sex ratio variation. Crosses among populations greatly enhanced the dam (cytoplasmic) effect, indicating that most among-population variance was at cytoplasmic loci. This is supported by the large among-population variance in the frequency of mitochondrial haplotypes, which also accounted for a significant portion of the sex ratio variance in our data. We discuss the similarities between the population structure we observed at loci that influence sex expression and previous work on putatively neutral loci, as well as the implications this has for what mechanisms may create and maintain population structure at loci that are influenced by natural selection.

Cell Nucleus↗
PubMed1991

Quantitative genetic variation and developmental clocks.

It is well-known that most genetic variation affects quantitative traits, and natural or artificial selection can act to change quantitative features of organisms more rapidly than qualitative ones. Surprisingly, variability is not confined to outbred species, but also occurs in inbred mice at a much higher rate than expected from known mutation rates. The size and shape of organisms and their constituent parts are, at least in part, controlled by the number of cell divisions, and there is published evidence for the existence of developmental clocks, which may count cell divisions. A molecular model for a developmental clock was previously proposed. It depends on the DNA methylation of repeated sequences of DNA, where the methylation of each additional sequence is tied to DNA synthesis and therefore cell division. The number of repeats specifies the number of divisions which will occur before a signal is produced which can activate or inactivate one or more genes. It is known that crossing over occurs between sister chromatids, and where tandemly repeated sequences occur unequal exchange can generate a larger or smaller number of repeats. An example of this is seen in the well-known variability of "minisatellite" sequences in human DNA. Unequal sister chromatid exchange can occur in mitotic and meiotic cells in the germ line, and in the case of developmental clock sequences could generate variation in clock length which in turn would directly affect quantitative traits. These events can be regarded as a special case of molecular drive during evolution.

Animals↗
PubMed1992

Quantitative genetic study on sexual difference in emigration behavior of Drosophila melanogaster in a natural population.

A quantitative genetic analysis was conducted on emigration response behavior using 140 second chromosome lines of Drosophila melanogaster. Fourteen sets of 5 x 5 partial diallel cross experiments were made in the parental generation. The emigration activity per batch of 50 male and 50 female F1 progeny was scored with Sakai's population system. Sexual difference did not appear in the emigration activity in these experiments. A significant genotype x sex x set interaction was detected. The genetic variance components of emigration activity differed between sexes: In males, additive genetic variance of emigration activity was 0.0497 +/- 0.0092 and dominance variance, 0.0018 +/- 0.0046; in females, additive, 0.0373 +/- 0.0076 and dominance, 0.0169 +/- 0.0044. Additive genetic correlation between sexes for the emigration activity was 0.685 +/- 0.150, deviating significantly from unity. These results suggested that the genes affecting emigration activity would operate differently between sexes of D. melanogaster in natural populations.

Animals↗
PubMed2002

Fluctuating environments and the role of mutation in maintaining quantitative genetic variation.

We study a class of genetic models in which a quantitative trait determined by several additive loci is subject to temporally fluctuating selection. Selection on the trait is assumed to be stabilizing but with an optimum that varies periodically and might be perturbed stochastically. The population mates at random, is infinitely large and has discrete generations. We pursue a statistical and numerical approach, covering a wide range of ecological and genetic parameters, to determine the potential of fluctuating environments to maintain quantitative genetic variation. Whereas, in contrast to some recent claims, this potential seems to be rather limited in the absence of recurrent mutation, fluctuating environments might, in combination with it, often generate high levels of additive genetic variation. We investigate how the genetic variation maintained depends on the ecological parameters and on the underlying genetics.

Genetic Variation↗
PubMed1989

[A novel method for determining an integrated character in quantitative genetics].

This paper describes a novel method using maximum entropy principle introduced by Shannon to construct a unique integrated character and gives a comparison between this method and multivariate statistics in quantitative genetics. In multivariate genetic analysis multivariate statistics is usually used for a polygenic system of multiple quantitative traits to form several complex character. Genetic analysis can be implemented through treating these correlated elementary traits by using the technique of principal component analysis or canonical correlation. Differing from the multivariate statistics, this paper presents a new method using maximum-entropy principle to obtain a unique integrated character from a set of correlated quantitative traits. This method has the advantages of simple mathematical structure and process, simple and clear results.

Animals↗
PubMed1989

Behavioral responses to novelty and structural variation of the hippocampus in mice. I. Quantitative-genetic analysis of behavior in the open-field.

As a first step towards a multivariate quantitative-genetic analysis of covariations between heritable variation in hippocampal structure and mouse behavior, a univariate analysis of the genetic architecture of behavioral responses to novelty is presented. For several components of exploratory behavior considerable amounts of genetic variation were found and an evolutionary history of stabilizing selection for intermediate levels of exploration was inferred. Comparison of these results with those from a previous study indicated that even a relatively small diallel cross, involving 4-5 inbred strains, may provide useful genetic information on a specific sample of animals. Larger numbers of strains are needed to provide precise estimates of genetic parameters in a population.

Animals↗
PubMed2005

Marker-based quantitative genetics in the wild?: the heritability and genetic correlation of chemical defenses in eucalyptus.

Marker-based methods for estimating heritability and genetic correlation in the wild have attracted interest because traditional methods may be impractical or introduce bias via G x E effects, mating system variation, and sampling effects. However, they have not been widely used, especially in plants. A regression-based approach, which uses a continuous measure of genetic relatedness, promises to be particularly appropriate for use in plants with mixed-mating systems and overlapping generations. Using this method, we found significant narrow-sense heritability of foliar defense chemicals in a natural population of Eucalyptus melliodora. We also demonstrated a genetic basis for the phenotypic correlation underlying an ecological example of conditioned flavor aversion involving different biosynthetic pathways. Our results revealed that heritability estimates depend on the spatial scale of the analysis in a way that offers insight into the distribution of genetic and environmental variance. This study is the first to successfully use a marker-based method to measure quantitative genetic parameters in a tree. We suggest that this method will prove to be a useful tool in other studies and offer some recommendations for future applications of the method.

Australian Capital Territory↗
PubMed2004

The quantitative genetics of floral trait variation in Lobelia: potential constraints on adaptive evolution.

Although pollinator-mediated natural selection has been measured on many floral traits and in many species, the extent to which selection is constrained from producing optimal floral phenotypes is less frequently studied. In particular, negative correlations between flower size and flower number are hypothesized to be a major constraint on the evolution of floral displays, yet few empirical studies have documented such a trade-off. To determine the potential for genetic constraints on the adaptive evolution of floral displays, I estimated the quantitative genetic basis of floral trait variation in two populations of Lobelia siphilitica. Restricted maximum likelihood (REML) analyses of greenhouse-grown half-sib families were used to estimate genetic variances and covariances for flower number and six measures of flower size. There was significant genetic variation for all seven floral traits in both populations. Flower number was negatively genetically correlated with four measures of flower size in one population and three measures in the other. When the genetic variance-covariance matrices were combined with field estimates of phenotypic selection gradients, the predicted multivariate evolutionary response was less than or opposite in sign to the selection gradient for flower number and five of six measures of flower size, suggesting genetic constraints on the evolution of these traits. More generally, my results indicate that the adaptive evolution of floral displays can be constrained by trade-offs between flower size and number, as has been assumed by many theoretical models of floral evolution.

Adaptation, Biological↗
PubMed2000

Quantitative genetic variation in Daphnia: temporal changes in genetic architecture.

Nonadditive genetic variation and genetic disequilibrium are two important factors that influence the evolutionary trajectory of natural populations. We assayed quantitative genetic variation in a temporary-pond-dwelling population of Daphnia pulex over a full season to examine the role of nonadditive genetic variation and genetic disequilibrium in determining the short-term evolutionary trajectory of a cyclic parthenogen. Quantitative traits were influenced by three factors: (1) clonal selection significantly changed the population mean phenotype during the course of the growing season; (2) sexual reproduction and recombination led to significant changes in life-history trait means and the levels of expressed genetic variation, implying the presence of substantial nonadditive genetic variation and genetic disequilibrium; and (3) Egg-bank effects were found to be an important component of the realized year-to-year change. Additionally, we examined the impact of genetic disequilibria induced by clonal selection on the genetic (co)variance structure with a common principal components model. Clonal selection caused significant changes in the (co)variance structure that were eliminated by a single bout of random mating, suggesting that a build-up of disequilibria was the primary source of changes in the (co)variance structure. The results of this study highlight the complexity of natural selection operating on populations that undergo alternating phases of sexual and asexual reproduction.

Animals↗
PubMed1990

Quantitative genetic analysis of longitudinal trends in height: preliminary results from the Louisville Twin Study.

A preliminary series of quantitative genetic models was applied to a subset of longitudinal height data, spanning birth to maturity, gathered from twin families in the Louisville Twin Study. Descriptive Cholesky factor parameterization was found to give more satisfactory results than did a system of constraints based on a model of developmental transmission of a time-constant and time-specific factors. The results from application of two autosomal sex-limitation models are contrasted with those from a model specifying both autosomal and sex-chromosomal patterns of inheritance. The latter model was more conducive to parameter reduction. Although these models do not constitute conclusive tests of autosomal sex-limitation versus sex-linkage, the more parsimonious model is consistent with previous research suggesting a stature locus on the long arm of the Y chromosome. Heritability of height is estimated at about 90% or greater from 6 years of age on. Substantial and fairly constant longitudinal genetic correlations are found from 3 years of age on. Shared environmental effects unrelated to parental height were seen for birth length, corrected for gestational age, to height at 3 years of age, but these are not satisfactorily differentiated from possible twin effects in the present sample. The genetic consequences of assortative mating are emphasized since failure to take assortment into account can lead to overestimation of shared environmental effects and under-estimation of genetic effects. The results indicate that about 20% of within-gender variability for mature height can be attributed to the genetic consequences of assortment, even though the phenotypic marital correlation of 0.22 is quite modest. The importance of testing the assumption of multivariate normality underlying the application of the method of maximum-likelihood is also highlighted.

Body Height↗
PubMed2005

Molecular and quantitative genetic divergence among populations of house mice with known evolutionary histories.

Evolutionary biologists have long been interested in the processes influencing population differentiation, but separating the effects of neutral and adaptive evolution has been an obstacle for studies of population subdivision. A recently developed method allows tests of whether disruptive (ie, spatially variable) or stabilizing (ie, spatially uniform) selection is influencing phenotypic differentiation among subpopulations. This method, referred to as the F(ST) vs Q(ST) comparison, separates the total additive genetic variance into within- and among-population components and evaluates this level of differentiation against a neutral hypothesis. Thus, levels of neutral molecular (F(ST)) and quantitative genetic (Q(ST)) divergence are compared to evaluate the effects of selection and genetic drift on phenotypic differentiation. Although the utility of such comparisons appears great, its accuracy has not yet been evaluated in populations with known evolutionary histories. In this study, F(ST) vs Q(ST) comparisons were evaluated using laboratory populations of house mice with known evolutionary histories. In this model system, the F(ST) vs Q(ST) comparisons between the selection groups should reveal quantitative trait differentiation consistent with disruptive selection, while the F(ST) vs Q(ST) comparisons among lines within the selection groups should suggest quantitative trait differentiation in agreement with drift. We find that F(ST) vs Q(ST) comparisons generally produce the correct evolutionary inference at each level in the population hierarchy. Additionally, we demonstrate that when strong selection is applied between populations Q(ST) increases relative to Q(ST) among populations diverging by drift. Finally, we show that the statistical properties of Q(ST), a variance component ratio, need further investigation.

Animals↗
PubMed1995

Quantitative genetic variation photoinduced by 8-methoxypsoralen in yeast.

The variation in cell mass production within cultured populations of Saccharomyces cerevisiae derived from untreated cells and from cells treated with 8-methoxypsoralen plus near-UV light (8MOP-NUV) was determined. Spontaneous mutation was not significant source of variation, since no genetic component of variance was detected in the untreated population. Following mutagenesis significant levels of genetic variation were found, showing that 8MOP-NUV was effective in inducing quantitative genetic variation among clonal populations of the yeast. The magnitudes of the estimates of the heritability and of the genetic coefficient of variation, indicate that, in phenotypic selection, greater genetic progress can be expected after mutagenic treatment than with untreated populations. The highest estimate of genetic gain was obtained at the intermediate survival level.

Analysis of Variance↗
PubMed1998

Quantitative genetic analysis of internalising and externalising problems in a large sample of 3-year-old twins.

For a quantitative genetic study of pre-school problem behaviours, we have collected data with the Child Behavior Checklist for 2 and 3-year-old children (CBCL 2/3). Questionnaires were completed by mothers of 3620 twin pairs: 633 monozygotic males, 581 dizygotic males, 695 monozygotic females, 519 dizygotic females and 1192 dizygotic opposite sex twin pairs. The genetic and environmental influences on the Externalising and Internalising Problem scales were estimated, simultaneously with sex differences and sibling interaction effects. Genetic factors explained most of the observed variance for both Externalising and Internalising Problems. Cooperative sibling interactions were found for Externalising Problems, indicating that twins reinforce each other's behaviour. Sex differences in genetic architecture were found for Externalising Problems. Genetic factors explained 75% of the variance in girls and 50% in boys. Shared environmental influences were only of importance in boys. For both problem scales, non-shared environmental factors accounted for 25 to 32% of the variance. The observed variances of Internalising Problems could be adequately explained by genetic and nonshared environmental factors, with genetic factors accounting for 68% of the variance.

Child Behavior↗
PubMed1981

Only authorized persons admitted: the quantitative genetics of health and disease.

The scope of quantitation in genetics ranges from traits that are defined by quantity to those that can be quantitated not at all, or only with difficulty and on artificial scales of specious interpretability. Since disease is a complex process, there is a serious risk that a projection of it on an arbitrary system of measurements may be insensitive or frankly misleading. A hypothetical but plausible example (the "brittle model") of a purely genetic trait (but one with zero heritability) is presented. In addition an illustration is given that competition in pathways to an endpoint (such as death) may lead to a counterintuitive reversal of the positive skewness in the component processes (the "bingo model"). These paradoxical results reflect the perils of inadequate descriptors and an irrational reliance on stock methods of looking at the inheritance of disease. Well-known studies by Brown and Goldstein, Knudson, Paigen. Armitage and Doll, and Moolgavkar are cited as examples of how medical geneticists might rationally approach the genetics of common and complicated diseases.

Decision Theory↗
PubMed1997

Quantitative genetic analysis of susceptibility to hookworm infection in a population from rural Zimbabwe.

Overdispersion is a common feature of population distribution patterns for hookworm infection in humans. Genetic factors may be partially responsible for this observed increased susceptibility in a fraction of the exposed population. However, the hypothesis that there are genetic components to susceptibility to this infectious disease has not been tested explicitly. The purpose of this study is to quantify the influence of genetic factors on patterns of hookworm infection in a rural population in Zimbabwe. A quantitative measure of hookworm load, number of hookworm eggs per gram of feces, as determined by the Kato thick smear technique, was available for 289 individuals. Of these, 279 individuals were members of 62 nuclear families and 10 were independent individuals. We analyzed the hookworm data in combination with the pedigree structure of the sampled individuals using quantitative genetic analysis techniques. Using this variance decomposition approach, we estimated the heritability of hook worm load to be 0.37 +/- 0.09 (p < 0.0001). This significant heritability indicates that 37% of the variation (after correcting for the effects of covariates) in hookworm eggs per gram observed in this population is attributable to genetic factors. The results suggest that further investigation and characterization of the genetic components influencing susceptibility to hookworm infection are warranted.

Adolescent↗
PubMed2004

Quantitative genetics of functional characters in Drosophila melanogaster populations subjected to laboratory selection.

What are the genetics of phenotypes other than fitness, in outbred populations? To answer this question, the quantitative-genetic basis of divergence was characterized for outbred Drosophila melanogaster populations that had previously undergone selection to enhance characters related to fitness. Line-cross analysis using first-generation and second-generation hybrids from reciprocal crosses was conducted for two types of cross, each replicated fivefold. One type of cross was between representatives of the ancestral population, a set of five populations maintained for several hundred generations on a two-week discrete-generation life cycle and a set of five populations adapted to starvation stress. The other type of cross was between the same set of ancestral-representative populations and another set of five populations selected for accelerated development from egg to egg. Developmental time from egg to eclosion, starvation resistance, dry body weight and fecundity at day 14 from egg were fit to regression models estimating single-locus additive and dominant effects, maternal and paternal effects, and digenic additive and dominance epistatic effects. Additive genetic variation explained most of the differences between populations, with additive maternal and cytoplasmic effects also commonly found. Both within-locus and between-locus dominance effects were inferred in some cases, as well as one instance of additive epistasis. Some of these effects may have been caused by linkage disequilibrium. We conclude with a brief discussion concerning the relationship of the genetics of population differentiation to adaptation.

Animals↗