Average Effects Of Alleles Research Articles

The Impact of Non-additive Effects on the Genetic Correlation Between Populations.

Average effects of alleles can show considerable differences between populations. The magnitude of these differences can be measured by the additive genetic correlation between populations (). This can be lower than one due to the presence of non-additive genetic effects together with differences in allele frequencies between populations. However, the relationship between the nature of non-additive effects, differences in allele frequencies, and the value of remains unclear, and was therefore the focus of this study. We simulated genotype data of two populations that have diverged under drift only, or under drift and selection, and we simulated traits where the genetic model and magnitude of non-additive effects were varied. Results showed that larger differences in allele frequencies and larger non-additive effects resulted in lower values of . In addition, we found that with epistasis, decreases with an increase of the number of interactions per locus. For both dominance and epistasis, we found that, when non-additive effects became extremely large, had a lower bound that was determined by the type of inter-allelic interaction, and the difference in allele frequencies between populations. Given that dominance variance is usually small, our results show that it is unlikely that true values lower than 0.80 are due to dominance effects alone. With realistic levels of epistasis, dropped as low as 0.45. These results may contribute to the understanding of differences in genetic expression of complex traits between populations, and may help in explaining the inefficiency of genomic trait prediction across populations.

Evolutionary quantitative genetics of nonlinear developmental systems.

In quantitative genetics, the effects of developmental relationships among traits on microevolution are generally represented by the contribution of pleiotropy to additive genetic covariances. Pleiotropic additive genetic covariances arise only from the average effects of alleles on multiple traits, and therefore the evolutionary importance of nonlinearities in development is generally neglected in quantitative genetic views on evolution. However, nonlinearities in relationships among traits at the level of whole organisms are undeniably important to biology in general, and therefore critical to understanding evolution. I outline a system for characterizing key quantitative parameters in nonlinear developmental systems, which yields expressions for quantities such as trait means and phenotypic and genetic covariance matrices. I then develop a system for quantitative prediction of evolution in nonlinear developmental systems. I apply the system to generating a new hypothesis for why direct stabilizing selection is rarely observed. Other uses will include separation of purely correlative from direct and indirect causal effects in studying mechanisms of selection, generation of predictions of medium-term evolutionary trajectories rather than immediate predictions of evolutionary change over single generation time-steps, and the development of efficient and biologically motivated models for separating additive from epistatic genetic variances and covariances.

Fixation probability with multiple alleles and projected average allelic effect on selection

The first-order effect of selection on the probability of fixation of an allele, with respect to an intensity of selection s > 0 in a diploid population of fixed finite size N , undergoing discrete, non-overlapping generations, is shown to be given by the sum of the average effects of that allele on the coefficient of selection in the current generation and all future generations, given the population state in the current generation. This projected average allelic effect is a weighted sum of average allelic effects in allozygous and autozygous offspring in the initial generation, with weights given in terms of expected coalescence times, under neutrality, for the lineages of two or three gametes chosen at random in the same generation. This is shown in the framework of multiple alleles at one locus, with genotypic values determining either viability or fertility differences, and with either multinomial or exchangeable reproduction schemes. In the limit of weak selection in a large population such that N s tends to zero, the initial average allelic effects in allozygous offspring and autozygous offspring have the same weight on the fixation probability only in the domain of application of the Kingman coalescent. With frequency-dependent selection in a linear-game-theoretic context with two phenotypes determined by additive gene action, the first-order effect on the fixation probability is a combination of two effects of frequency-independent selection, one in a haploid population, the other in a diploid population. In the domain of application of the Kingman coalescent as the population size goes to infinity and N s to zero, the first effect is three times more important than the second effect. This explains the one-third law of evolutionary dynamics in this domain, and shows how this law can be extended beyond this domain.

Quantitative trait loci and gene interaction: the quantitative genetics of metapopulations

Genetic population differentiation is typically viewed as differentiation of population means. However, several theories of evolution and speciation postulate that populations differentiate not only with respect to the population means, but also with respect to the effects of alleles within these populations. I develop herein a measure of population differentiation for the 'local average effects' of alleles, where local average effect is defined as the average effect of an allele in a deme measured as a deviation from the metapopulation mean. The differentiation for local average effects has two components, a component attributable to the population mean and a residual component that is attributable to changes in the local average effects independent of the population mean. The variance in local average effects attributable to the population mean is measured as the variance in the mean local average effect of all alleles. The variance in the residual local average effects is measured as the difference between the variance local average effects of individual alleles and the variance in the mean local average effects of all alleles. Differentiation for population means and differentiation for residual local average effects need not be related. I show that when there is only additive gene action, populations can differentiate for population means, but not for residual local average effects. However, if there is gene interaction then populations can also differentiate for local average effects of alleles. The consequence of this differentiation is that the local average effects of alleles change relative to each other such that an allele that is favoured by selection in one population may be removed by selection in other populations. I discuss the evolutionary consequences of differentiation for local average effects, and the interpretation of QTL data in light of this model.

Frequency of phenotype-genotype discrepancies at the apolipoprotein E locus in a large population study

Apolipoprotein E (apoE) genotypes were determined in a random subset of 1041 subjects enrolled in the Framingham Offspring Study by using DNA amplification followed by restriction isotyping. The results were compared with the apoE phenotypes previously assessed by isoelectric focusing. Discrepancies in apoE allele assignment were found in 98 subjects (9.4%). Both genotype and phenotype were reassessed in these subjects. Genotype misclassification was observed in 20 subjects, whereas the initial phenotype assignment was modified in 46 subjects. No concordance between apoE phenotype and genotype remained in 32 subjects (3.07%). Both methods resulted in similar apoE allele frequencies. Furthermore, no differences were observed regarding the average allelic effect on total cholesterol, LDL cholesterol, or HDL cholesterol concentrations; however, a significant difference was noted on triglyceride concentrations. Our results indicate that most discrepancies between genotype and phenotype assessment of apoE polymorphism were due to sample mishandling, data entry, and technical difficulties rather than true discordances.

EPISTASIS AND THE INCREASE IN ADDITIVE GENETIC VARIANCE: IMPLICATIONS FOR PHASE 1 OF WRIGHT'S SHIFTING-BALANCE PROCESS.

Central to Wright's shifting-balance theory is the idea that genetic drift and selection in systems with gene interaction can lead to the formation of "adaptive gene complexes." The theory of genetic drift has been well developed over the last 60 years; however, nearly all of this theory is based on the assumption that only additive gene effects are acting. Wright's theory was developed recognizing that there was a "universality of interaction effects," which implies that additive theory may not be adequate to describe the process of differentiation that Wright was considering. The concept of an adaptive gene complex implies that an allele that is favored by individual selection in one deme may be removed by selection in another deme. In quantitative genetic terms, the average effects of an allele relative to other alleles changes from deme to deme. The model presented here examines the variance in local breeding values (LBVs) of a single individual and the covariance in the LBVs of a pair of individuals mated in the same deme relative to when they are mated in different demes. Local breeding value is a measure of the average effects of the alleles that make up that individual in a particular deme. I show that when there are only additive effects the covariance between the LBVs of individuals equals the variance in the LBV of an individual. As the amount of epistasis in the ancestral population increases, the variance in the LBV of an individual increases and the covariance between the LBVs of a pair of individuals decreases. The divergence in these two values is a measure of the extent to which the LBV of an individual varies independently of the LBVs of other individuals. When this value is large, it means that the relative ordering of the average effects of alleles will change from deme to deme. These results confirm an important component of Wright's shifting-balance theory: When there is gene interaction, genetic drift can lead to the reordering of the average effects of alleles and when coupled with selection this will lead to the formation of the adaptive gene complexes.

Diallel analysis of the latent period of stripe rust in wheat

A half diallel was made amongst five wheat (Triticum aestivum L.) genotypes of which one was susceptible, while the others had adult-plant resistance, to stripe rust (Puccinia striiformis West.). The five parent and ten F1 progeny were grown in the glasshouse and were inoculated with three rust pathotypes at the seedling stage. The latent period was measured on the first leaf. Two procedures were used to analyze the half diallel. Both methods showed that the average effects of alleles were of much greater importance than was dominance in conditioning resistance in response to two of the pathotypes, while for the third pathotype dominance was important. Resistance was conditioned by partial dominance for two pathotypes whereas for the third it was determined by full dominance. Broad-sense heritabilities range from 60-73% and the number of genes involved was different (from 1 to 4), depending on the pathotype.

Second-order approximations for selection coefficients at polygenic loci. II. Pleiotropy.

I determine the second-order approximation for the phenotypic distribution of an arbitrary number of quantitative traits, ignoring the effects of epistasis and linkage disequilibrium, conditioned on the presence of a specified genotype at one underlying locus of small effect. Using this approximation, I determine formulae for the effects of selection at a single locus with random mating under either Gaussian stabilizing selection, or correlated selection with truncation selection for one character. These formulae apply for arbitrary phenotypic distributions, yet even with multivariate Gaussian distributions of phenotypic effects the formula for correlated selection includes a correction to the standard formula in Falconer (1989). I demonstrate that this approximation has an error that is third order in the allelic or genotypic effects, independent of the form of the phenotypic distribution. I show also that the approximation of analogous form for the phenotypic distribution conditioned on the presence of a specified allele at a single locus is also correct to second order. Both approximations allow for dominance and are consistent in the sense that computing marginal fitnesses from approximations based on genotypic deviations and those based on average allelic effect yield the same answers.

Influence of serum paraoxonase polymorphism on serum lipids and apolipoproteins.

One hundred and sixty-three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P less than 0.01). The subjects with PON A had significantly higher LDL cholesterol (P less than 0.05) and lower Apo A-II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P less than 0.05) and LDL (P less than 0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A-II levels (P less than 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P less than 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P less than 0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P less than 0.001) and ApoB (P less than 0.001), while it had lowering influence on total cholesterol (P less than 0.05) and LDL cholesterol (P less than 0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A-II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins.

Second-order approximations for selection coefficients at polygenic loci

I determine the second-order approximation for the phenotypic distribution of a quantitative trait, ignoring the effects of epistasis and linkage disequilibrium, conditioned on the presence of a specified genotype at one underlying locus of small effect. I demonstrate that this approximation has an error that is third order in the allelic or genotypic effects, independent of the form of the phenotypic distribution. I also show that the approximation of analogous form for the phenotypic distribution conditioned on the presence of a specified allele at a single locus is also correct to second order. Both approximations allow for dominance and are consistent in the sense that computing marginal fitnesses from approximations based on genotypic deviations and those based on average allelic effect yield the same answers. Surprisingly, the second-order approximations derived here yield the same approximation for dynamics at a single locus as first-order approximations used earlier thus justifying earlier stability computations based on these first-order approximations.

Apolipoprotein E polymorphism in The Netherlands and its effect on plasma lipid and apolipoprotein levels.

By isoelectric focusing of delipidated sera followed by immunoblotting we studied the apolipoprotein (apo) E polymorphism in 2018 randomly selected 35-years-old males from three different areas in the Netherlands. Comparison of the APOE allele (E*2, E*3, and E*4) frequencies estimated in this study with those reported for several other population samples showed that there are marked differences between the Dutch population and the populations of Japan, New Zealand, Finland, and the United States. These differences in APOE allele frequencies appeared to be mainly due to differences in frequencies of the E*2 allele (decreased in Japan and Finland; increased in New Zealand) and the E*4 allele (increased in Finland; decreased in Japan and the United States). No difference in APOE allele frequencies was found between the Dutch population and the populations of West Germany and Scotland. Measurements of plasma cholesterol and apo B and E concentrations showed that the E*4 allele is associated with elevated plasma cholesterol and apo B levels and with decreased apo E concentrations, whereas the opposite is true for the E*2 allele. In the Dutch population, the sum of average allelic effects of the common APOE alleles on plasma cholesterol and apo B levels is 6.8% and 14.2%, respectively, of the total population mean. The total average allelic effect on plasma apo E concentrations was more pronounced (50.1%), suggesting that the APOE alleles primarily affect apo E concentrations rather than plasma cholesterol and apo B levels. This hypothesis is sustained by the observation that for plasma apo E levels the genetic variance associated with the APOE gene locus contributed about 18% to the total phenotypic variance. For plasma cholesterol and apo B this contribution was only 1.4% and 2.3% and is relatively low as compared with that reported for other population samples.

Quantitative genetics of net blotch resistance in barley

Abstract A half diallel was made amongst 5 barley (Hordeum vulgare L.) genotypes (Zephyr, Hassan, Mata, Kaniere, and Manchuria) which varied in resistance to net blotch disease, caused by the fungus Drechslera teres (Sacc.) Shoem. The 5 parents and 10 F1 progeny were grown to physiological maturity in a controlled environment. All genotypes were inoculated first at 14 days after sowing and thereafter 10 times at about weekly intervals. The procedures of Mather and Jinks were used to analyse the half diallel 89 days after sowing. Net blotch infection was measured on top canopy, bottom canopy, flag leaf (leaf number = 1) and second leaf. Infection of detached leaf segments in petri dishes was also analysed. This test provides a simple and rapid technique for net blotch assessment. All analyses showed that average effects of alleles were of much greater importance than dominance in controlling resistance. Epistasis and/or correlated gene distributions were trivial. Resistance was conditioned by a partially d...