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PubMed1990

Quantitative genetic tools for insecticide resistance risk assessment: estimating the heritability of resistance.

Quantitative genetic studies of resistance can provide estimates of genetic parameters not available with other types of genetic analyses. Three methods are discussed for estimating the amount of additive genetic variation in resistance to individual insecticides and subsequent estimation of the heritability (h2) of resistance. Sibling analysis and offspring-parent regression permit direct estimates of h2 by comparing the resistance phenotypes of individuals of known relatedness. Threshold trait analyses, performed on data from selection experiments, provide estimates of realized heritability. Procedures are outlined for predicting changes in resistance to insecticides based on h2 estimates. Quantitative genetic theory is examined as it relates to resistance and resistance as a quantitative trait; quantitative genetic methods also are unique in providing estimates of genetic correlations between traits. Comments are included on estimates of genetic correlation between resistance and phenotypic traits (e.g., development time) and how they may be used to predict changes in the genetic aspects of phenology that result from insecticide applications (i.e., to predict how the reproductive capacity of future generations will differ from that of the treated generation).

Analysis of Variance↗
PubMed2003

Latitudinal divergence of common frog (Rana temporaria) life history traits by natural selection: evidence from a comparison of molecular and quantitative genetic data.

The relative roles of natural selection and direct environmental induction, as well as of natural selection and genetic drift, in creating clinal latitudinal variation in quantitative traits have seldom been assessed in vertebrates. To address these issues, we compared molecular and quantitative genetic differentiation between six common frog (Rana temporaria) populations along an approximately 1600 km long latitudinal gradient across Scandinavia. The degree of population differentiation (QST approximately 0.81) in three heritable quantitative traits (age and size at metamorphosis, growth rate) exceeded that in eight (neutral) microsatellite loci (FST = 0.24). Isolation by distance was clear for both neutral markers and quantitative traits, but considerably stronger for one of the three quantitative traits than for neutral markers. QST estimates obtained using animals subjected to different rearing conditions (temperature and food treatments) revealed some environmental dependency in patterns of population divergence in quantitative traits, but in general, these effects were weak in comparison to overall patterns. Pairwise comparisons of FST and QST estimates across populations and treatments revealed that the degree of quantitative trait differentiation was not generally predictable from knowledge of that in molecular markers. In fact, both positive and negative correlations were observed depending on conditions where the quantitative genetic variability had been measured. All in all, the results suggest a very high degree of genetic subdivision both in neutral marker genes and genes coding quantitative traits across a relatively recently (< 9000 years) colonized environmental gradient. In particular, they give evidence for natural selection being the primary agent behind the observed latitudinal differentiation in quantitative traits.

Animals↗
PubMed1994

Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice.

Experimental analysis of complex quantitative genetic traits, such as essential hypertension, should be greatly facilitated by being able to manipulate the expression of a gene in living animals without altering the nucleotide sequence, chromosomal location, or regulatory elements of the gene. To explore this possibility, we have used targeted gene disruption and duplication to generate mice that are genetically identical [(129 x C57BL6)F1] except for having one, two, or three functional copies of the gene coding for angiotensinogen. The two-copy animals have two normal copies of the angiotensinogen gene; the one-copy and three-copy animals have one normal copy with the other either disrupted or duplicated by gene targeting. The duplicated pair of genes was generated by a special form of gap-repair gene targeting that tandemly duplicates the whole of a gene together with 5' and 3' flanking regions. We find progressively and significantly higher levels of the gene product in the animals having increasing numbers of gene copies: the one-copy animals have steady-state plasma angiotensinogen levels approximately 35% of normal (P < 0.0001), and the three-copy animals have levels approximately 124% of normal (P < 0.004). Detailed information about regulatory sequences is not required for this type of experiment; nor is it necessary to have DNA clones or targeting constructs that cover the whole of the target gene. Varying gene copy numbers by targeting consequently offers a promising approach to quantitative genetics.

Angiotensinogen↗
PubMed2003

The constancy of the G matrix through species divergence and the effects of quantitative genetic constraints on phenotypic evolution: a case study in crickets.

Long-term phenotypic evolution can be modeled using the response-to-selection equation of quantitative genetics, which incorporates information about genetic constraints (the G matrix). However, little is known about the evolution of G and about its long-term importance in constraining phenotypic evolution. We first investigated the degree of conservation of the G matrix across three species of crickets and qualitatively compared the pattern of variation of G to the phylogeny of the group. Second, we investigated the effect of G on phenotypic evolution by comparing the direction of greatest quantitative genetic variation within species (g(max)) to the direction of phenotypic divergence between species (Delta(z)). Each species, Gryllus veletis, G. firmus, and G. pennsylvanicus, was reared in the laboratory using a full-sib breeding design to extract quantitative genetic information. Five morphological traits related to size were measured. G matrices were compared using three statistical approaches: the T method, the Flury hierarchy, and the MANOVA method. Results revealed that the differences between matrices were small and mostly caused by differences in the magnitude of the genetic variation, not by differences in principal component structure. This suggested that the G matrix structure of this group of species was preserved, despite significant phenotypic divergence across species. The small observed differences in G matrices across species were qualitatively consistent with genetic distances, whereas ecological information did not provide a good prediction of G matrix variation. The comparison of g(max) and Delta(z) revealed that the angle between these two vectors was small in two of three species comparisons, whereas the larger angle corresponding to the third species comparison was caused in large part by one of the five traits. This suggests that multivariate phenotypic divergence occurred mostly in a direction predicted by the direction of greatest genetic variation, although it was not possible to demonstrate the causal relationship from G to Delta(z). Overall, this study provided some support for the validity of the predictive power of quantitative genetics over evolutionary time scales.

Analysis of Variance↗
PubMed2002

Quantitative genetic analysis of natural populations.

Quantitative genetic studies in natural populations have been rare because they require large breeding programmes or known pedigrees. The relatedness that has been estimated from molecular markers can now be used to substitute for breeding, allowing studies of previously inaccessible species. Many behavioural ecologists have a sufficient number of markers and study species with characteristics that are amenable to this approach. It is now time to combine studies of selection with studies of genetic variation for a more complete understanding of behavioural evolution.

Animals↗
PubMed2001

Quantitative genetics of autogamous F2.

General quantitative genetic properties are derived for the F2 originating from self-fertilisation of hybrid (F1) individuals. These results extend and generalize previous restricted knowledge about this F2. New equations are found for all genotype frequencies, allele frequencies, inbreeding coefficient, genic (additive-genetic) and dominance variances, broadsense and narrowsense heritabilities, and selection potential. The bulk mean is generally lower, and the genotypic variance is generally higher, than those of the F1 and the allogamous F2. Genic and dominance variances for the selfed F2 are very different to the classical counterparts. Their relationships with inbreeding have been investigated, and they are more elaborate than previously considered. The level of inbreeding is constant irrespective of parental combinations, which is different to the inbreeding of an allogamous F2. Selection potential is generally high, and selection advance generally exceeds bulk inbreeding depression. If selection is assisted by dispersion, the autogamous F2 may obtain greater genetic advance than its allogamous counterpart for the same selection pressure. Under conditions of spatially separated F2, swarms, natural selection may be enhanced by selfing.

Alleles↗
PubMed1987

Quantitative genetic variation in an ecological setting.

The machinery was developed to investigate the behavior of quantitative genetic variation in an ecological model of a finite number of islands of finite size, with migration rate m and extinction rate e, for a quantitative genetic model general for numbers of alleles and loci and additive, dominance, and additive by additive epistatic effects. It was necessary to reckon with seven quadratic genetic components, whose coefficients in the genotypic variance components within demes, sigma Gw2, between demes within populations, sigma s2, and between replicate populations, sigma r2, are given by descent measures. The descent measures at any time are calculated with the use of transition equations which are determined by the parameters of the ecological model. Numerical results were obtained for the coefficients of the quadratic genetic components in each of the three genotypic variance components in the early phase of differentiation. The general effect of extinction is to speed up the time course leading to fixation, to increase sigma r2, and to decrease sigma s2 (with a few exceptions) in comparison with no extinction. The general effect of migration is to slow down the time course leading to fixation, to increase sigma Gw2, at least in the later generations, and to decrease sigma s2 (with a few exceptions) in comparison with no migration. Except for these, the effects of migration and extinction on the variance components are complex, depending on the genetic model, and sometimes involve interaction of migration and extinction. Sufficient details are given for an investigator to evaluate numerically the results for variations in the quantitative genetic and ecological models.

Alleles↗
PubMed2005

The quantitative genetics of transcription.

Quantitative geneticists have become interested in the heritability of transcription and detection of expression quantitative trait loci (eQTLs). Linkage mapping methods have identified major-effect eQTLs for some transcripts and have shown that regulatory polymorphisms in cis and in trans affect expression. It is also clear that these mapping strategies have little power to detect polygenic factors, and some new statistical approaches are emerging that paint a more complex picture of transcriptional heritability. Several studies imply pervasive non-additivity of transcription, transgressive segregation and epistasis, and future studies will soon document the extent of genotype-environment interaction and population structure at the transcriptional level. The implications of these findings for genotype-phenotype mapping and modeling the evolution of transcription are discussed.

Chi-Square Distribution↗
PubMed1990

Genetic variation for oviposition behavior in Drosophila melanogaster. I. Quantitative genetic analysis of insertion behavior.

The genetic basis of egg insertion behavior was analyzed in two Drosophila melanogaster strains (N and E strain), which were homozygous for the Slow allele of the alcohol dehydrogenase locus. The E strain had been selected for increased tolerance to ethanol. This study originated from the observation that nearly all of the eggs laid by females of the E strain were inserted, while in the control strain (N strain) which was kept on regular food, considerable variation for egg insertion occurred. Crosses between the E and the N strains were made, and quantitative genetic tests were performed. It was shown that the inheritance of egg insertion is polygenic, some of the genes are probably sex linked, and in-laying is partly dominant over on-laying. The heritability of the trait, derived from mother-daughter regression analysis, was .59 +/- .18. The repeatability was high. Bidirectional selection in the E strain was unsuccessful, but an asymmetrical response to selection was obtained in the N strain and in lines derived from crosses between the N and the E strains. Selection for in-laying was more successful than for on-laying. The realized heritability in the former lines was .35 +/- .10.

Alcohol Dehydrogenase↗
PubMed1999

Quantitative genetics of energy balance--lessons from animal models.

Evidence for quantitative genetic variation in components of energy balance in animals is overwhelming. Much of this evidence is drawn from livestock species and relevant rodent models, especially long-term selection lines. This mini-review summarizes findings from several animal studies that have characterized quantitative genetic variation in energy intake and energy expenditure. Applications of this information toward understanding and treatment of human obesity are explored.

Animals↗
PubMed1999

Population and quantitative genetics of regulatory networks.

I evolved boolean regulatory networks in a computer simulation. I varied mutation, recombination, the size of the network, and the number of connections per node. I measured the performance of networks and the heritability and epistasis of genetic effects. Networks of intermediate connectivity performed best. The distinction between metabolic and quantitative genetic additivity explained some of the variation in performance. Metabolic additivity describes the interaction between changes in a single network, whereas quantitative genetic additivity measures the consistency of phenotypic effect caused by gene substitution in randomly chosen members of the population. I analysed metabolic additivity by the distribution of epistatic effects of pairs of mutations in individual networks. I measured quantitative genetic additivity by heritability. Highly connected networks had greater metabolic additivity for perturbations to individual networks, but had lower additivity when measured by the average effect of a gene substitution (heritability). The lower heritability of highly connected nets appeared to reduce the effectiveness of recombination in searching evolutionary space.

Animals↗
PubMed2001

Quantitative genetics and mouse behavior.

Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.

Animals↗
PubMed1999

Quantitative genetics in conservation biology.

Most of the major genetic concerns in conservation biology, including inbreeding depression, loss of evolutionary potential, genetic adaptation to captivity and outbreeding depression, involve quantitative genetics. Small population size leads to inbreeding and loss of genetic diversity and so increases extinction risk. Captive populations of endangered species are managed to maximize the retention of genetic diversity by minimizing kinship, with subsidiary efforts to minimize inbreeding. There is growing evidence that genetic adaptation to captivity is a major issue in the genetic management of captive populations of endangered species as it reduces reproductive fitness when captive populations are reintroduced into the wild. This problem is not currently addressed, but it can be alleviated by deliberately fragmenting captive populations, with occasional exchange of immigrants to avoid excessive inbreeding. The extent and importance of outbreeding depression is a matter of controversy. Currently, an extremely cautious approach is taken to mixing populations. However, this cannot continue if fragmented populations are to be adequately managed to minimize extinctions. Most genetic management recommendations for endangered species arise directly, or indirectly, from quantitative genetic considerations.

Animals↗
PubMed2006

Quantitative genetics of speciation: additive and non-additive genetic differentiation between Drosophila madeirensis and Drosophila subobscura.

The role of dominance and epistasis in population divergence has been an issue of much debate ever since the neoDarwinian synthesis. One of the best ways to dissect the several genetic components affecting the genetic architecture of populations is line cross analysis. Here we present a study comparing generation means of several life history-traits in two closely related Drosophila species: Drosophila subobscura, D. madeirensis as well as their F1 and F2 hybrids. This study aims to determine the relative contributions of additive and non-additive genetic parameters to the differentiation of life-history traits between these two species. The results indicate that both negative dominance and epistatic effects are very important in the differentiation of most traits. We end with considerations about the relevance of these findings for the understanding of the role of non-additive effects in speciation.

Animals↗
PubMed1984

Quantitative genetics and developmental constraints on evolution by selection.

It has often been argued that the principles of random mutation and selection are insufficient to account for macroevolutionary phenomena, such as the origin of morphological novelty and directionality in evolution. A third, epigenetic, principle is said to be required and this principle is thought not to be included in microevolutionary theory. The third principle has most recently been identified as internal selection and/or non-random phenotypic effects of mutation. It is shown that the genetic variance/covariance matrix of quantitative genetic theory measures developmental constraints due to internal selection and non-random mutation. The genetic variance/covariance matrix causes the response to selection to deviate from the optimal rate and direction as specified by the selection gradient, which measures direct selection on the phenotypes. Therefore, microevolutionary theory takes account of developmental constraints on evolution by natural selection through the genetic variance/covariance matrix. Theories for predicting the pattern of genetic variance and covariance from stabilizing selection and the phenotypic effects of mutation are discussed.

Biological Evolution↗
PubMed2005

Estimation of quantitative genetic parameters.

This paper gives a short review of the development of genetic parameter estimation over the last 40 years. This shows the development of more statistically and computationally efficient methods that allow the fitting of more biologically appropriate models. Methods have evolved from direct methods based on covariances between relatives to methods based on individual animal models. Maximum-likelihood methods have a natural interpretation in terms of best linear unbiased predictors. Improvements in iterative schemes to give estimates are discussed. As an example, a recent estimation of genetic parameters for a British population of dairy cattle is discussed. The development makes a connection to relevant work by Bill Hill.

Analysis of Variance↗
PubMed1995

Multivariate quantitative genetics of anthropometric traits from the Boas data.

The use of multivariate quantitative trait information to address questions of population relationships and evolutionary issues has a long-standing history in human anthropometry. Previous analyses have usually rested on a number of explicit or implicit assumptions that allow phenotypic information to be used as a proxy for quantitative genetic information. One (usually implicit) assumption is that the additive genetic variance-covariance matrix (G) among traits is proportional to the phenotypic variance-covariance matrix (P). In this study we discuss the implications of this assumption, demonstrating that if it is true that G = h2P, where h2 is some constant of proportionality, then (1) the biological (phenotypic) Mahalanobis distance will be proportional to genetic distance, (2) phenotypic and genetic allometry coefficients will be equal, and (3) evolutionary models will become simplified. We then use a multivariate quantitative genetic analysis of 12 anthropometric traits in 5 tribes to demonstrate that G = h2P for at least a portion of the Boas data.

Adult↗
PubMed1998

A quantitative genetic approach towards volatile anesthetic mechanisms in C. elegans.

Quantitative genetics is the study of the heritability of continuous traits such as height or IQ. Quantitative trait loci (QTLs) represent the genes that are responsible for these quantitative traits. Sensitivity to the volatile anesthetic halothane is a genetically controlled quantitative trait in the nematode C. elegans. The QTLs that are responsible for the 12-fold range in halothane EC50 in these strains map to a few places with at least one major effect locus on chromosome V. Congenic strains for chromosome V confirmed these loci and offer the means to finely map them for positional cloning.

Anesthetics, Inhalation↗