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PubMed1983

A genetic analysis of the mandible and maxilla in the rat.

A quantitative genetic analysis of eight osteometric traits from the oral region together with femur length in the rat are described. The relevant questions being examined are (1) the heritability of each trait; (2) the relative contribution of genetic, maternal environmental, and residual environmental effects to the correlation between the oral traits, and (3) genetic and nongenetic components of the correlation between the oral traits and overall body size. Some quantitative genetic aspects of covarying traits is briefly reviewed with special emphasis on allometric variation. Phenotypic regression coefficients from log-transformed data (= allometry coefficients) of oral traits onto femur length are partitioned into components due to genetic, maternal environmental, residual environmental, and total environmental causes. All phenotypic regression coefficients and all but one based on an environmentally determined covariance component are significantly different from zero, suggesting a substantial body size effect in the oral region resulting from nonheritable causes. However, three genetic coefficients from regressions of oral traits to femur length are not different from zero, indicating a genetic correlation with body size in five traits but not in three others. A principal components analysis was carried out on the phenotypic, genetic, and environmental correlations of the eight oral traits to provide a multivariate depiction of the components of covariation in the maxilla and mandible of the rat. General multivariate effects due to body size together with group or special effects are demonstrated for each component of morphogenesis.

Animals↗
PubMed2005

Comparative losses of quantitative and molecular genetic variation in finite populations of Drosophila melanogaster.

Quantitative genetic variation, the main determinant of the ability to evolve, is expected to be lost in small populations, but there are limited data on the effect, and controversy as to whether it is similar to that for near neutral molecular variation. Genetic variation for abdominal and sternopleural bristle numbers and allozyme heterozygosity were estimated in 23 populations of Drosophila melanogaster maintained at effective population sizes of 25, 50, 100, 250 or 500 for 50 generations, as well as in 19 highly inbred populations and the wild outbred base population. Highly significant negative regressions of proportion of initial genetic variation retained on inbreeding due to finite population size were observed for both quantitative characters (b = -0.67 +/- 0.14 and -0.58 +/- 0.11) and allozyme heterozygosity (b = -0.79 +/- 0.10), and the regression coefficients did not differ significantly. Thus, quantitative genetic variation is being lost at a similar rate to molecular genetic variation. However, genetic variation for all traits was lost at rates significantly slower than predicted by neutral theory, most likely due to associative overdominance. Positive, but relatively low correlations were found among the different measures of genetic variation, but their low magnitudes were attributed to large sampling errors, rather than differences in the underlying processes of loss.

Animals↗
PubMed2000

The heritability of polymorphic light eruption.

Polymorphic light eruption is classified as an acquired idiopathic photodermatosis, yet it appears to cluster in families, suggesting a possible genetic component. In this study, we assess the heritability of polymorphic light eruption using the classical twin model. Polymorphic light eruption was investigated by a nurse-administered questionnaire in a sample of 420 pairs of adult female twins from St Thomas' Hospital UK Adult Twin Registry, including 119 monozygotic and 301 dizygotic pairs. Probandwise concordance for the presence and absence of disease was calculated and the heritability of polymorphic light eruption assessed by a quantitative genetic model fitting approach using Mx software. The prevalence of polymorphic light eruption was 21% and 18% in monozygotic and dizygotic twins, respectively. A family history of polymorphic light eruption in first-degree relatives (not including the cotwin) was present in 12% of affected twin pairs (where at least one twin had polymorphic light eruption) compared with 4% of unaffected twin pairs, providing evidence of familial clustering (p < 0.0001). The probandwise concordance for polymorphic light eruption was higher in monozygotic (0.72) than in dizygotic twin pairs (0.30), indicating a strong genetic effect. Quantitative genetic modeling found that a model comprising additive genetic (A) and unique environmental (E) factors provided the most parsimonious fit, although a dominant gene effect could also explain our data. In the AE model, 84% (95% confidence interval 65-94%) of the variance in susceptibility to polymorphic light eruption is attributed to additive genetic factors with the remaining 16% (95% confidence interval 6-35%) to unique environmental effects. These data establish a clear genetic influence in the expression of polymorphic light eruption and provide a basis for examining candidate genes that may be pathogenic in this common condition.

Adult↗
PubMed2004

Genetics and the evolution of primate enamel thickness: a baboon model.

The thickness of mammalian tooth enamel plays a prominent role in paleontology because it correlates with diet, and thicker enamel protects against tooth breakage and wear. Hominid evolutionary studies have stressed the importance of this character for over 30 years, from the identification of "Ramapithecus" as an early Miocene hominid, to the recent discovery that the earliest hominids display molar enamel intermediate in thickness between extant chimpanzees and Australopithecus. Enamel thickness remains largely unexplored for nonhominoid primate fossils, though there is significant variation across modern species. Despite the importance of enamel thickness variation to primate evolution, the mechanisms underlying variation in this trait have not yet been elucidated. We report here on the first quantitative genetic analysis of primate enamel thickness, an analysis based on 506 pedigreed baboons from a captive breeding colony. Computed tomography analysis of 44 Papio mandibular molars shows a zone of sufficiently uniform enamel thickness on the lateral surface of the protoconid. With this knowledge, we developed a caliper metric measurement protocol for use on baboon molars worn to within this zone, enabling the collection of a data set large enough for genetic analyses. Quantitative genetic analyses show that a significant portion of the phenotypic variance in enamel thickness is due to the additive effects of genes and is independent of sex and tooth size. Our models predict that enamel thickness could rapidly track dietary adaptive shifts through geological time, thus increasing the potential for homoplasy in this character. These results have implications for analyses of hominoid enamel thickness variation, and provide a foundation from which to explore the evolution of this phenotype in the papionin fossil record.

Animals↗
PubMed2003

The evolution of trade-offs: geographic variation in call duration and flight ability in the sand cricket, Gryllus firmus.

Quantitative genetic theory assumes that trade-offs are best represented by bivariate normal distributions. This theory predicts that selection will shift the trade-off function itself and not just move the mean trait values along a fixed trade-off line, as is generally assumed in optimality models. As a consequence, quantitative genetic theory predicts that the trade-off function will vary among populations in which at least one of the component traits itself varies. This prediction is tested using the trade-off between call duration and flight capability, as indexed by the mass of the dorsolateral flight muscles, in the macropterous morph of the sand cricket. We use four different populations of crickets that vary in the proportion of macropterous males (Lab = 33%, Florida = 29%, Bermuda = 72%, South Carolina = 80%). We find, as predicted, that there is significant variation in the intercept of the trade-off function but not the slope, supporting the hypothesis that trade-off functions are better represented as bivariate normal distributions rather than single lines. We also test the prediction from a quantitative genetical model of the evolution of wing dimorphism that the mean call duration of macropterous males will increase with the percentage of macropterous males in the population. This prediction is also supported. Finally, we estimate the probability of a macropterous male attracting a female, P, as a function of the relative time spent calling (P = time spent calling by macropterous male/(total time spent calling by both micropterous and macropterous male). We find that in the Lab and Florida populations the probability of a female selecting the macropterous male is equal to P, indicating that preference is due simply to relative call duration. But in the Bermuda and South Carolina populations the probability of a female selecting a macropterous male is less than P, indicating a preference for the micropterous male even after differences in call duration are accounted for.

Animals↗
PubMed2001

Finding the molecular basis of quantitative traits: successes and pitfalls.

Understanding the molecular basis of quantitative genetic variation is a principal goal for biomedicine. Although the complex genetic architecture of quantitative traits has so far largely frustrated attempts to identify genes in humans by standard linkage methodologies, quantitative trait loci (QTL) have been mapped in plants, insects and rodents. However, identifying the molecular bases of QTL remains a challenge. Here, we discuss why this is and how new experimental strategies and analytical techniques, combined with the fruits of the genome projects, are beginning to identify candidate genes for QTL studies in several model organisms.

Animals↗
PubMed2001

Detecting genotype x age interaction.

This paper explores several extensions to the variance component method, which incorporate genotype x age interaction effects. We evaluate the performance of these methods for detecting genotype x age interaction in quantitative genetic analyses of a quantitative trait (Q4), contrasting this with false positive detection rates obtained from a phenotype influenced by the same genes but without genotype x age interaction effects (Q3). We then assess the impact on linkage power and false positive rate of allowing a QTL-specific genotype x age interaction in linkage analysis of these same traits.

Adult↗
PubMed2001

How closely correlated are molecular and quantitative measures of genetic variation? A meta-analysis.

The ability of populations to undergo adaptive evolution depends on the presence of quantitative genetic variation for ecologically important traits. Although molecular measures are widely used as surrogates for quantitative genetic variation, there is controversy about the strength of the relationship between the two. To resolve this issue, we carried out a meta-analysis based on 71 datasets. The mean correlation between molecular and quantitative measures of genetic variation was weak (r = 0.217). Furthermore, there was no significant relationship between the two measures for life-history traits (r = -0.11) or for the quantitative measure generally considered as the best indicator of adaptive potential, heritability (r = -0.08). Consequently, molecular measures of genetic diversity have only a very limited ability to predict quantitative genetic variability. When information about a population's short-term evolutionary potential or estimates of local adaptation and population divergence are required, quantitative genetic variation should be measured directly.

Animals↗
PubMed2005

Family level inbreeding depression and the evolution of plant mating systems.

Variation in the magnitude of inbreeding depression (ID) among families may have important consequences for mating system evolution. Experimental studies have shown that such variation is a common feature of natural plant populations. Unfortunately, the genetic and evolutionary significance of family level estimates remains obscure. Almost any kind of genetic variation will generate differences in ID among families, and as a consequence, a non-zero variance in family level ID is not sufficient to distinguish genetic architectures with wholly different implications for mating system evolution. Quantitative genetic methods provide a means to extract more information from ID experiments. Estimates of quantitative genetic variance components directly inform questions about the genetic basis of ID and should ultimately allow tests of alternative theories of mating system evolution.

Biological Evolution↗
PubMed2001

QTL analysis and genomewide mutagenesis in mice: complementary genetic approaches to the dissection of complex traits.

Quantitative genetics and quantitative trait locus (QTL) mapping have undergone a revolution in the last decade. Progress in the next decade promises to be at least as rapid, and strategies for fine-mapping QTLs and identifying underlying genes will be radically revised. In this Commentary we address several key issues: first, we revisit a perennial challenge--how to identify individual genes and allelic variants underlying QTLs. We compare current practice and procedures in QTL analysis with novel methods and resources that are just now being introduced. We argue that there is no one standard of proof for showing QTL = gene; rather, evidence from several sources must be carefully assembled until there is only one reasonable conclusion. Second, we compare QTL analysis with whole-genome mutagenesis in mice and point out some of the strengths and weakness of both of these phenotype-driven methods. Finally, we explore the advantages and disadvantages of naturally occurring vs mutagen-induced polymorphisms. We argue that these two complementary genetic methods have much to offer in efforts to highlight genes and pathways most likely to influence the susceptibility and progression of common diseases in human populations.

Alleles↗
PubMed1994

Naturally occurring variation in bristle number and DNA polymorphisms at the scabrous locus of Drosophila melanogaster.

The association between quantitative genetic variation in bristle number and molecular variation at a candidate neurogenic locus, scabrous, was examined in Drosophila melanogaster. Approximately 32 percent of the genetic variation in abdominal bristle number (21 percent for sternopleural bristle number) among 47 second chromosomes from a natural population was correlated with DNA sequence polymorphisms at this locus. Several polymorphic sites associated with large phenotypic effects occurred at intermediate frequency. Quantitative genetic variation in natural populations caused by alleles that have large effects at a few loci and that segregate at intermediate frequencies conflicts with the classical infinitesimal model of the genetic basis of quantitative variation.

Alleles↗
PubMed2004

Evolution and stability of the G-matrix on a landscape with a moving optimum.

In quantitative genetics, the genetic architecture of traits, described in terms of variances and covariances, plays a major role in determining the trajectory of evolutionary change. Hence, the genetic variance-covariance matrix (G-matrix) is a critical component of modern quantitative genetics theory. Considerable debate has surrounded the issue of G-matrix constancy because unstable G-matrices provide major difficulties for evolutionary inference. Empirical studies and analytical theory have not resolved the debate. Here we present the results of stochastic models of G-matrix evolution in a population responding to an adaptive landscape with an optimum that moves at a constant rate. This study builds on the previous results of stochastic simulations of G-matrix stability under stabilizing selection arising from a stationary optimum. The addition of a moving optimum leads to several important new insights. First, evolution along genetic lines of least resistance increases stability of the orientation of the G-matrix relative to stabilizing selection alone. Evolution across genetic lines of least resistance decreases G-matrix stability. Second, evolution in response to a continuously changing optimum can produce persistent maladaptation for a correlated trait, even if its optimum does not change. Third, the retrospective analysis of selection performs very well when the mean G-matrix (G) is known with certainty, indicating that covariance between G and the directional selection gradient beta is usually small enough in magnitude that it introduces only a small bias in estimates of the net selection gradient. Our results also show, however, that the contemporary G-matrix only serves as a rough guide to G. The most promising approach for the estimation of G is probably through comparative phylogenetic analysis. Overall, our results show that directional selection actually can increase stability of the G-matrix and that retrospective analysis of selection is inherently feasible. One major remaining challenge is to gain a sufficient understanding of the G-matrix to allow the confident estimation of G.

Adaptation, Biological↗
PubMed1985

In situ hybridization--visualization and quantitation of genetic expression in mammalian brain.

In situ hybridization techniques have been developed that quantitate the relative levels of specific mRNAs in individual cell types of a heterogeneous tissue, the mammalian brain. Here, we discuss those special procedures and precautions necessary for hybridizing radiolabeled probes to developing and adult brain mRNAs. The probes discussed include double-stranded recombinant DNA, as well as single-stranded DNA, RNA, and polyuridylate. We detail the procedure for determining the relative numbers of hybrids formed and computing the ratio of specific mRNAs to total polyadenylated mRNA and discuss the importance of this ratio for comparison of relative levels of specific mRNAs within and among cell types in an individual brain or between brains.

Animals↗
PubMed2003

From plant genomics to breeding practice.

New alleles are constantly accumulated during intentional crop selection. The molecular understanding of these alleles has stimulated new genomic approaches to mapping quantitative trait loci (QTL) and haplotype multiplicity of the genes concerned. A limited number of quantitative trait nucleotides responsible for QTL variation have been described, but an acceleration in their rate of discovery is expected with the adoption of linkage disequilibrium and candidate gene strategies for QTL fine mapping and cloning. Additional layers of regulatory variation have been studied that could also contribute to the molecular basis of quantitative genetics of crop traits. Despite this progress, the role of marker-assisted selection in plant breeding will ultimately depend on the genetic model underlying quantitative variation.

Breeding↗
PubMed2002

Precision and high-resolution mapping of quantitative trait loci by use of recurrent selection, backcross or intercross schemes.

Dissecting quantitative genetic variation into genes at the molecular level has been recognized as the greatest challenge facing geneticists in the twenty-first century. Tremendous efforts in the last two decades were invested to map a wide spectrum of quantitative genetic variation in nearly all important organisms onto their genome regions that may contain genes underlying the variation, but the candidate regions predicted so far are too coarse for accurate gene targeting. In this article, the recurrent selection and backcross (RSB) schemes were investigated theoretically and by simulation for their potential in mapping quantitative trait loci (QTL). In the RSB schemes, selection plays the role of maintaining the recipient genome in the vicinity of the QTL, which, at the same time, are rapidly narrowed down over multiple generations of backcrossing. With a high-density linkage map of DNA polymorphisms, the RSB approach has the potential of dissecting the complex genetic architecture of quantitative traits and enabling the underlying QTL to be mapped with the precision and resolution needed for their map-based cloning to be attempted. The factors affecting efficiency of the mapping method were investigated, suggesting guidelines under which experimental designs of the RSB schemes can be optimized. Comparison was made between the RSB schemes and the two popular QTL mapping methods, interval mapping and composite interval mapping, and showed that the scenario of genomic distribution of QTL that was unlocked by the RSB-based mapping method is qualitatively distinguished from those unlocked by the interval mapping-based methods.

Animals↗
PubMed1999

Estimating the genetic architecture of quantitative traits.

Understanding and estimating the structure and parameters associated with the genetic architecture of quantitative traits is a major research focus in quantitative genetics. With the availability of a well-saturated genetic map of molecular markers, it is possible to identify a major part of the structure of the genetic architecture of quantitative traits and to estimate the associated parameters. Multiple interval mapping, which was recently proposed for simultaneously mapping multiple quantitative trait loci (QTL), is well suited to the identification and estimation of the genetic architecture parameters, including the number, genomic positions, effects and interactions of significant QTL and their contribution to the genetic variance. With multiple traits and multiple environments involved in a QTL mapping experiment, pleiotropic effects and QTL by environment interactions can also be estimated. We review the method and discuss issues associated with multiple interval mapping, such as likelihood analysis, model selection, stopping rules and parameter estimation. The potential power and advantages of the method for mapping multiple QTL and estimating the genetic architecture are discussed. We also point out potential problems and difficulties in resolving the details of the genetic architecture as well as other areas that require further investigation. One application of the analysis is to improve genome-wide marker-assisted selection, particularly when the information about epistasis is used for selection with mating.

Algorithms↗
PubMed1998

Genetic components of variation in Nemophila menziesii undergoing inbreeding: morphology and flowering time.

The standard approaches to estimation of quantitative genetic parameters and prediction of response to selection on quantitative traits are based on theory derived for populations undergoing random mating. Many studies demonstrate, however, that mating systems in natural populations often involve inbreeding in various degrees (i.e. , self matings and matings between relatives). Here we apply theory developed for estimating quantitative genetic parameters for partially inbreeding populations to a population of Nemophila menziesii recently obtained from nature and experimentally inbred. Two measures of overall plant size and two of floral size expressed highly significant inbreeding depression. Of three dominance components of phenotypic variance that are defined under partial inbreeding, one was found to contribute significantly to phenotypic variance in flower size and flowering time, while the remaining two components contributed only negligibly to variation in each of the five traits considered. Computer simulations investigating selection response under the more complete genetic model for populations undergoing mixed mating indicate that, for parameter values estimated in this study, selection response can be substantially slowed relative to predictions for a random mating population. Moreover, inbreeding depression alone does not generally account for the reduction in selection response.

Asteraceae↗
PubMed2000

Quantitative developmental genetic analysis reveals that the ancestral dipteran wing vein prepattern is conserved in Drosophila melanogaster.

Quantitative complementation tests provide a quick test of the hypothesis that a particular gene contributes to segregating phenotypic variation. A set of wild-type alleles is assayed for variation in their ability to complement the degree of dominance of the quantitative effect of a loss of function allele. Analysis of 15 loci known to be involved in wing patterning in Drosophila melanogaster suggests that the genes decapentaplegic, thickveins, EGFR, argos and hedgehog, each of which are involved in secreted growth factor signaling, may contribute to wing shape variation. The phenotype of one deficiency, Df(2R)Px2, which removes blistered/Plexate, is also highly sensitive to the wild-type genetic background and at intermediate expressivity reveals six ectopic veins. These form in the same locations as a projection of the ancestral pattern of dipteran wing veins on- to the D. melanogaster wing. This atavistic phenotype indicates that the wing vein prepatterning mechanism can be conserved in highly derived species, and implies that homoplasic venation patterns may be produced by derepression of vein primordia.

Animals↗