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W G Hill

Publications and source records attributed to W G Hill.

At least 19 recordsLinked to original sources
PubMed1992

The time of detection of recessive visible genes with non-random mating.

Expressions for the probability and average time of detection of a recessive visible gene in populations where there is partial selfing or partial full-sib mating are presented. A small increase in the proportion of inbred matings greatly reduces the average time until detection and increases the proportion detected. Unless the proportion of inbred matings or the population size is very small, the time and proportion detected are approximately independent of the population size.

Crosses, Genetic↗
PubMed1992

Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model. 1. Lean mass.

Analysis was undertaken using Restricted Maximum Likelihood (REML) with an animal model of the results of selection for 20 generations for predicted lean mass in 10-week-old male mice. There were three replicates, each comprising high, low and unselected control lines. The overall estimates of heritability (h2) and common environmental correlations (c2) from results of the first seven generations were 0.51 +/- 0.03 and 0.21 +/- 0.01, respectively. Analyses of data from different lines and different numbers of generations were undertaken but with all pedigrees and data included, which enabled inferences to be drawn on changes in variance that were not due simply to inbreeding or short-term effects of selection. Estimates of h2 were lower in selected lines than the control, increasingly so in later generations, indicating departure from the infinitesimal model assumption of unlinked additive genes each of very small effect. In addition, values of c2 became higher in high than in control or low selected lines.

Analysis of Variance↗
PubMed1992

Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model. 2. Body weight, body composition and litter size.

Restricted Maximum Likelihood (REML) with an animal model was used to estimate genetic parameters of body weight, body consumption and litter size of lines of mice selected for 20 generations on an index of lean mass at 10 weeks in males, highly correlated with body weight, and for a further 18 generations on body weight at 10 weeks in males and females. Univariate and multivariate estimates of heritability were about 0.5 and those of common environment correlations were about 0.25 for both body weight and composition. Body weight and fat pad weight had genetic and phenotypic correlations of about 0.5. The heritability estimate of litter size was about 0.15 from univariate analysis, rather lower from multivariate, and the estimate of its genetic correlation with body weight was about 0.25. There were reductions in heritability of both body weight and litter size in later generations, even though full pedigrees were fitted and inferences made to the base population, but a plateau in response to selection for increased body weight could not be explained by a complete attenuation of genetic variance.

Animals↗
PubMed1992

Effective size of nonrandom mating populations.

Nonrandom mating whereby parents are related is expected to cause a reduction in effective population size because their gene frequencies are correlated and this will increase the genetic drift. The published equation for the variance effective size, Ne, which includes the possibility of nonrandom mating, does not take into account such a correlation, however. Further, previous equations to predict effective sizes in populations with partial sib mating are shown to be different, but also incorrect. In this paper, a corrected form of these equations is derived and checked by stochastic simulation. For the case of stable census number, N, and equal progeny distributions for each sex, the equation is [formula: see text], where Sk2 is the variance of family size and alpha is the departure from Hardy-Weinberg proportions. For a Poisson distribution of family size (Sk2 = 2), it reduces to Ne = N/(1 + alpha), as when inbreeding is due to selfing. When nonrandom mating occurs because there is a specified system of partial inbreeding every generation, alpha can be substituted by Wright's FIS statistic, to give the effective size as a function of the proportion of inbred mates.

Breeding↗
PubMed1992

Effects of partial inbreeding on fixation rates and variation of mutant genes.

Diffusion methods were used to investigate the fixation probability, average time until fixation and extinction, and cumulative heterozygosity and genetic variance for single mutant genes in finite populations with partial inbreeding. The critical parameters in the approximation are the coefficient of inbreeding due to nonrandom mating (F) and the effective population size (Ne), which also depends on F and the variance of family size. For large Ns, the fixation probability (u) is u = 2(Ne/N)s (F + h - Fh), where N is the population census, s is the coefficient of selection of the mutant homozygote and h is the coefficient of dominance. For Poisson family size (independent Poisson distributions of selfed and nonselfed offspring with partial selfing, and independent Poisson distributions of male and female numbers with partial sib mating), Ne = N/(1 + F), and the time until fixation is approximately equal to Ne/N times the time to fixation with random mating, but this relation does not hold, however, for other distributions of family size. The cumulative nonadditive variance until fixation or loss for dominant genes is reduced with increasing F while for recessive genes it is increased with intermediate values of F. The average time until extinction of deleterious mutations is reduced by increasing F. This reduction, when expressed as a proportion, is approximately independent of the initial gene frequency as well as the selective disadvantage if this is large.

Animals↗
PubMed1992

Quantitative genetic variation in body size of mice from new mutations.

To measure the amount of new genetic variation in 6-week weight of mice arising each generation from mutation, selection lines derived from an initially inbred strain were maintained for 25 generations. An analysis using an animal model with restricted maximum likelihood was applied to estimate a mutational genetic component of variance for the infinitesimal model of many genes of small effect. Assuming that the inbred base population was at a mutation-drift equilibrium, it is estimated that the heritability for body size has increased by 1.0% per generation, with lower and upper confidence limits of 0.6% and 1.6%, respectively. A model which includes a mutational genetic component of variance fits the data much better than one involving only base population genetic variance. A model with no genetic component fits the data very poorly. An environmental covariance of body size of mother and offspring was included in the model and accounts for 10% of the variance. By using information only from the observed response to selection, the estimated increase in heritability from mutation is 0.3% per generation. These values are higher than published estimates for the increase in variance from spontaneous mutations in bristle traits of Drosophila, for which there are extensive data, but similar to estimates for various skeletal traits in mice.

Animals↗
PubMed1991

Mixed model analysis of a selection experiment for food intake in mice.

Data from 23 generations of mice selected for increased and reduced appetite were analysed by Restricted Maximum Likelihood fitting an animal model with litters as additional random effects. Traits considered were food intake between 4 and 6 weeks of age adjusted for 4-week body weight (AFI), the selection criterion, and body weight at 6 weeks (6WW). Selection was carried out within families. A high and a low selection line and a control were maintained in each of three replicates. Analyses were performed for each replicate separately taking subsets of the data spanning different numbers of generations. Overall estimates of heritabilities were 0.15 for AFI, which agreed well with realized heritability estimates, and 0.42 for 6WW. The litter variance, expressed as a proportion of the phenotypic variance, was 0.21 for both traits, yielding intraclass correlations of full-sibs of 0.29 and 0.42, respectively. Similar results were obtained for variances of each trait using univariate and multivariate analyses. From the latter, estimates of correlations between the two traits were 0.46 for additive genetic, -0.19 for litter and 0.31 for residual effects, resulting in a phenotypic correlation of 0.23. Analyses of data from generations 2-7, 8-13 and 14-23 separately showed a marked decrease in genetic variance and heritability in later generations for both traits. Heritabilities of AFI, for instance, were 0.24, 0.10 and 0.07, respectively. These changes could not be attributed to the effects of inbreeding or of selection in an infinitesimal model and suggested that some change in variance due to change in gene frequency had occurred during the course of the experiment.

Analysis of Variance↗
PubMed1991

Analysis of lines of mice selected for fat content. 3. Flux through the de novo lipid synthesis pathway.

The flux through the de novo fatty acid synthesis pathway was estimated in lines of mice which differed substantially in fat content following 26 generations of selection at 10 weeks of age. Previous estimates of lipogenic enzyme activities had indicated an increase in the capacity for lipogenesis in the Fat compared to the Lean line. Therefore the in vivo flux in lipogenesis was measured in both liver and gonadal fat pad (GFP) tissues of males at 5 and 10 weeks of age, using the rate of incorporation of 3H from 3H2O and 14C from acetate and citrate into total lipids. At both ages and in both tissues the Fat line had a higher flux, about 20% increase in the liver and up to three-fold increase (range 1.2- to 3.4-fold) in the GFP. We conclude that direct selection for fatness in mice has resulted in metabolic changes in the rate of de novo fatty acid synthesis, and that the changes are largely detectable before 10 weeks, the age of selection.

Acetates↗
PubMed1991

Analysis of lines of mice selected on fat content. 4. Correlated responses in growth and reproduction.

Lines of mice have been selected for 32 generations for either high or low fat content, resulting in a threefold divergence in the selection criterion (estimated fat content of males at 14 weeks of age). Male mice from both lines were dissected at a series of ages between 4 and 26 weeks and the following traits measured or estimated: body weight, fat content, lean weight, and the weights of several fatpads and internal organs. The lines appeared to have a similar underlying lean weight upon which the Fat line accumulated fat at a faster rate. This accumulation continued unabated in the Fat lines for at least 26 weeks but had effectively ceased by 8 weeks of age in the Lean. The liver and kidneys were slightly larger in the Fat line but there were no differences in the weights of heart, lung or spleen. This detailed phenotypic description of the lines complemented previous reports describing correlated changes in their physiology. The threefold divergence in estimated fat content was less than that in one of its component traits, growth of gonadal fatpad, but was greater than the divergence in other physiological indicators, i.e. the activity of lipogenic enzymes in vitro and direct measurement of lipogenic flux. Testis size in the Fat line was consistently lower than in the Lean although the Fat line was slightly more fecund, apparently due to a higher prenatal survival rate.

Adipose Tissue↗
PubMed1991

Effects of exogenous growth hormone on growth and body composition in genetically selected mice.

The effects of exogenous GH on growth and body composition were investigated in lines of mice selected for high or low body weight (P-lines) or high or low body fat (F-lines). Mice from all lines were given daily injections of recombinant bovine GH or a placebo for 21 days from 4 weeks old. They were killed and various organ weights measured. There was no consistent effect of GH on organ weights. In all lines of mice the rate of weight gain and final weight increased in response to GH. In both lines selected for body fat, GH treatment decreased fat content. The low body weight mice also became less fat, but in the high body weight mice GH treatment increased fat percentage. The results indicate that the differences in growth rate and body composition observed in these lines are not due to differences in responsiveness to GH.

Animals↗
PubMed1990

Analysis of lines of mice selected for fat content. 2. Correlated responses in the activities of enzymes involved in lipogenesis.

Estimates of the activities (Vmax) of six enzymes involved in de novo fat synthesis were made in replicated lines of mice differing in fat content. These lines had been selected high and low for 20 generations with three replicates each of Fat, Control and Lean lines and for a further eight generations high and low as an unreplicated line. The activities of ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS), cytoplasmic malate dehydrogenase (MDH), malic enzyme (ME) and pyruvate kinase (PK) were determined in vitro in both liver and gonadal fatpad tissues taken at ages five and ten weeks. The activities of ACL, ACC, FAS and ME were significantly higher in the Fat than the Lean lines, and the differences were more pronounced at the earlier age and in the gonadal fatpad where activities in the Fat lines were higher by factors of 3.5, 2.4, 2.5 and 3.5 respectively. The activity of PK was unchanged in each tissue. MDH activity was significantly lower in adipose tissue in the Fat lines than the Lean lines at age ten weeks but not at age five weeks or in liver tissue. Results from replicates indicated that random genetic drift affected enzyme activities but nevertheless significant changes in activity were associated with the direction of selection. The changes in enzyme activity reported here are similar to those known to be associated with major mutations causing obesity in mice.

ATP Citrate (pro-S)-Lyase↗
PubMed1989

Quantitative genetic variability maintained by mutation-stabilizing selection balance: sampling variation and response to subsequent directional selection.

A model of genetic variation of a quantitative character subject to the simultaneous effects of mutation, selection and drift is investigated. Predictions are obtained for the variance of the genetic variance among independent lines at equilibrium with stabilizing selection. These indicate that the coefficient of variation of the genetic variance among lines is relatively insensitive to the strength of stabilizing selection on the character. The effects on the genetic variance of a change of mode of selection from stabilizing to directional selection are investigated. This is intended to model directional selection of a character in a sample of individuals from a natural or long-established cage population. The pattern of change of variance from directional selection is strongly influenced by the strengths of selection at individual loci in relation to effective population size before and after the change of regime. Patterns of change of variance and selection responses from Monte Carlo simulation are compared to selection responses observed in experiments. These indicate that changes in variance with directional selection are not very different from those due to drift alone in the experiments, and do not necessarily give information on the presence of stabilizing selection or its strength.

Gene Frequency↗
PubMed1989

Analysis of lines of mice selected for fat content. 1. Correlated responses in the activities of NADPH-generating enzymes.

Estimates of the activities (Vmax) of four enzymes that generate the coenzyme NADPH, an absolute requirement for tissue fatty-acid synthesis, and of the concentration of NADP plus NADPH were made in lines of mice differing in fat content. These lines had been selected from the same base population for 20 generations, and 3 high, 3 low replicates and 1 unselected control were used. Analyses were performed on liver and gonadal fat pad (GFP) of males at 5 and 10 weeks of age. In both the liver and the GFP, measurable activities of the four enzymes: glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), isocitrate dehydrogenase (IDH) and malic enzyme (ME) expressed per mg soluble protein were, with minor exceptions, higher in the Fat (F) than in the Lean (L) lines at both ages; the highest ratio being 2.2 for ME in the GFP. The relationships between these measurable activities (Vmax) and in vivo lipogenesis are not however known. When expressed per gram tissue, the ratios for F to L in the GFP were less than 1 in most cases, presumably because of the very different adipocyte numbers and/or sizes between the lines. There were no significant differences between the lines in the concentration of NADP plus NADPH per gram tissue in liver or GFP, suggesting that F lines converted NADP to NADPH faster than L lines. It is predicted that selection on the enzyme activities would be less efficient than direct selection at changing fat content.

Adipose Tissue↗
PubMed1989

Sewall Wright and quantitative genetics.

Some aspects of Wright's great contribution to quantitative genetics and animal breeding are reviewed in relation to current research and practice. Particular aspects discussed are as follows: the utility of his definition of inbreeding coefficient in terms of the correlation of uniting gametes; the maintenance of genetic variation in the optimum model; the inter-relations between past and present animal-breeding practice and the shifting-balance theory of evolution.

Animals↗
PubMed1988

Variances and covariances of squared linkage disequilibria in finite populations.

Analysis of linkage disequilibrium D among restriction sites or bases in DNA sequences, arising from mutations in finite populations, depends on a knowledge of the variance-covariance structure of measures such as D2 between different pairs of sites. This requires evaluation of the eighth moments of gene frequencies among two, three, and four loci, and the necessary methodology is derived here and results are computed. While primary emphasis is placed on disequilibrium arising from mutation or gene conversion, the methodology also allows for the joint effects of only drift and recombination. Numerical results confirm that squared linkage disequilibria can have high variances and covariances.

Base Sequence↗
PubMed1987

Directional selection and variation in finite populations.

Predictions are made of the equilibrium genetic variances and responses in a metric trait under the joint effects of directional selection, mutation and linkage in a finite population. The "infinitesimal model" is analyzed as the limiting case of many mutants of very small effect, otherwise Monte Carlo simulation is used. If the effects of mutant genes on the trait are symmetrically distributed and they are unlinked, the variance of mutant effects is not an important parameter. If the distribution is skewed, unless effects or the population size is small, the proportion of mutants that have increasing effect is the critical parameter. With linkage the distribution of genotypic values in the population becomes skewed downward and the equilibrium genetic variance and response are smaller as disequilibrium becomes important. Linkage effects are greater when the mutational variance is contributed by many genes of small effect than few of large effect, and are greater when the majority of mutants increase rather than decrease the trait because genes that are of large effect or are deleterious do not segregate for long. The most likely conditions for "Muller's ratchet" are investigated.

Analysis of Variance↗