E. J. Eisen

Genetic interpretation and analysis of diallel crosses with animals

SummaryA genetic framework was developed for the interpretation of statistical parameters estimated from a diallel experiment among a fixed set of lines. These included average direct genetic, average maternal genetic, general combining ability, reciprocal, and line and specific direct and maternal heterotic effects. The genetic model is based on direct and maternal additive and dominance genetic effects as would be expected in animal species. The model assumes that dominance is the underlying basis of heterosis. As an example, litter size at birth was analyzed from a 5 × 5 diallel cross with mice.

Genotype by environment interactions and genetic correlations involving two environmental factors

SummaryThe concept of the genetic correlation for one trait across environments was extended to two environmental factors B and C. Three additive genetic correlations for the same trait were defined: rG, across both environmental factors; rG(B), across C and within B; and rG(C), across B and within C. As genotype x environment variances increase, the genetic correlations across environments decrease. These three genetic correlations are biased downward in the presence of heterogeneity of genetic variances within environments when they are calculated from the usual analysis of variance (r*G, r*G(B), r*G(C)). Correction factors were derived to remove the bias. The two-way genotype by environment interaction variances can be biased upward or downward by the heterogeneity, but the three-way interaction variance is always biased upward. Correction factors for the interaction variances were also derived. Four additive genetic correlations between two traits (X and Y) were derived: rGxy, across both B and C; rG(B)xy, and rG(C)xy, across one environmental factor and within the other; and rG(BC)xy, within both B and C. These concepts were extended to genetic correlations for dominance and maternal effects. Paternal half-sib and factorial mating designs were used to obtain the various genetic correlations. An example of a paternal half-sib design with beef cattle was used to illustrate the methodology.

Comparison of Growth Functions Within and Between Lines of Mice Selected for Large and Small Body Weight

SummarySeveral criteria have been suggested for comparing different nonlinear growth functions to determine which function gives the best quantitative description of a given set of observed sigmoid growth curves. These criteria were then used to compare the logistic, Gompertz and Bertalanffy functions within and among lines of mice: a control line (C1) and lines selected for large (H6) and small (L6) body weight at six weeks of age.A general comparison of the three growth functions was based on the differences in residual variances of the respective functions fitted to the growth data of individual mice. Since the three functions differ primarily in the fixed proportion of the asymptotic weight at which the inflexion point occurs, the growth function which will provide the minimum residual variance among the three considered is the one which most closely approximates the observed proportion. The results of this comparison indicated that the logistic function gave the best fit for both sexes of the H6 and C1 lines. While no significant differences in residual variances were evident in L6 males, the Bertalanffy function had the smallest residual variance in L6 females.The four derived traits of each growth function analyzed individually were the asymptote (A), age at inflexion (t*), rate at which a logarithmic function of body weight changes with time (k) and mean absolute growth rate with respect to body weight increase (v). The coefficient of variation among individuals within full-sib families was used to compare the relative variability of the analogous traits estimated from the three growth functions. The coefficients of variation of A, t* and k calculated from the logistic function were significantly (P < .01) smaller than those from both the Gompertz and Bertalanffy functions in all three lines, while there were no significant differences in the relative variability of v among the three lines. The genetic and phenotypic correlations between the analogous traits estimated from two different growth functions were sufficiently high in most cases to conclude that the same trait was being measured by the three growth functions. Each derived trait was analyzed for variation in lines, sexes, seasons and respective interactions. The sources of variation generally exhibited similar levels of significance for the analogous traits estimated by the three functions, although a few exceptions were found. These results suggest that although the logistic function provided the best description of the growth data, the same general conclusions about differences within and among the three lines would have been reached with any of the three functions. The four derived traits of the logistic curve were used to describe quantitatively the differences in growth among the H6, L6 and C1 lines.

Body composition and energetic efficiency in two lines of mice selected for rapid growth rate and their F1 crosses.

SummaryCorrelated responses to selection for increased growth rate were compared in two mouse populations (M16 and H6) of distinct genetic origin. Traits studied were body composition, feed intake, constituent gains and energetic efficiency. When compared with their respective controls (ICR and C2) at 6 and 9 weeks of age, body weight increased more in M16 (57%and 69 % of the control mean) than in H6 (40 % and 34%). The M16 showed correlated responses in fat percent of 2.6% (P <.05), 8.4% (P <.01) and 11.2% (P <.01) at 3, 6 and 9 weeks, respectively, whereas corresponding values in H6 were −2.4% (P <.05), 3.3% (P <.05) and 2.09 % (P >.05). The correlated responses in fat percent were 2.7 and 4.7 times higher in M16 than H6 at 6 and 9 weeks. The regression of ln fat weight on ln empty body weight was larger in M16 (P <.05) compared to ICR and larger (P <.01) in H6 compared to C2. Both M16 and H8 exhibited positive correlated responses from 3 to 6 weeks of age in feed intake and gain and efficiency in fat, protein, calories and ash; fat and caloric gain and efficiency exhibited higher correlated responses in M16 than H6. During the 6- to 9-week interval, the M16 population continued to evince positive correlated responses in gains and efficiencies of fat, protein and calories, whereas H6 did not. Several possible explanations are presented to account for the differences in correlated responses between the selected populations. Partitioning of correlated response differences between M16 and H6 into average direct and average maternal genetic effects indicated that average direct genetic effects, favoring M16, were responsible for the major difference between the selected populations. Direct heterosis in F1 crosses of the selected populations were generally not significant, although there was a tendency for fat percent and fat weight to show heterosis.

Sexual dimorphism and direct and maternal genetic effects on body weight in mice

SummaryGenetic and phenotypic parameters for three-, six- and eight-week body weight and for weight gain between three and six weeks of age were estimated from data collected over 14 generations in a randombred control population. Genetic parameters were also estimated for sexual dimorphism in body weight and gain. Heritability estimates were substantial for body weight at all ages and for body weight gain. Additive maternal variances were also large. Estimates of the covariance between direct and maternal genetic effects were negative and substantial for three- and six-week weights and gain. Also the covariance between maternal effects on weaning weight and direct genetic effects on six- and eight-week weights were negative. These results indicate a consistent antagonism between maternal and direct genetic effects in this population.The analysis of sexual dimorphism yielded estimates of 0.87±.09 and 0.71±.14 for the correlation between additive direct effects on males and females for six-week weight and body weight gain respectively. Corresponding heritability estimates were 0.07±.09 and 0.11±.09. Heritability estimates for sexual dimorphism in three- and eight-week weights were negative.

Correlated response in skeletal traits and replicate variation in selected lines of mice.

SummaryCorrelated responses in caudal vertebrae number (VN), lengths of eighth and ninth caudal vertebrae (V8 and V9, respectively), femur length (FL) and femur weight (FW) were evaluated in lines of mice which had been selected for six-week body weight (WK6) and/or six-week tail length (TAIL). Ten males and ten females were randomly sampled from each of ten selected lines (two replicates each of five selection treatments) after seven generations of selection. Sexes and lines were significant (P < .01) sources of variation in all seven traits. Sex x line interactions were unimportant except for V8 and V9. Male mice of both replicate lines selected for increased WK6 and decreased TAIL had shorter vertebrae than females, whereas the reverse was true for all other lines. Multiple regression and canonical correlation analyses indicated a high phenotypic relationship of FL with both WK6 and TAIL. Examination of the correlated responses indicated that FL was the only skeletal trait that showed a substantial correlated response to single trait selection for both WK6 and TA IL. Thus, the genetic relationships among the three traits also appeared to be high. Between replicate variation was not significant for randomly selected control lines. However, about onethird of the statistical tests between selected replicates were significant. This was taken to indicate a joint effect of selection and drift in causing variation between replicate lines. Replicate variation was further examined by canonical variate and generalized distance analyses. The first two canonical variates accounted for most of the generalized variance. Graphically, the first two canonical variables discriminated among selection treatments, whereas the replicates tended to cluster. Thus, although between replicate differences were significant for several traits, the differences were relatively small compared with the variation between lines having different selection criteria.

Comparison of growth curves of mice selected and unselected for postweaning gain.

SummaryMice were sampled from a line selected for increased postweaning weight gain from three to six weeks and from a randombred control line originating from the same base population. Body weights were recorded at each of 14 ages from day 5 to day 98. The Richards and logistic growth functions were fitted to the growth trajectories of each individual mouse by a generalized non-linear least squares procedure. Estimated growth parameters (asymptotic weight, rate, shape of curve, age and weight at inflection, mean absolute growth rate and mean relative growth rate) were computed for each individual. The effects of line, litter within line, sex and line × sex interactions on these estimated parameters were then studied.Both the Richards and logistic functions fitted the data equally well and the plotted trajectories coincided over most of the growth curve. There was excellent agreement between the estimates of asymptotic weight and both age and weight at inflection based on the different functions. However, both functions apparently underestimated the asymptotic weight.Analyses of the line differences showed that selection for postweaning gain increased the mean absolute growth rate over the entire curve but had no effect on the relative growth rate or the shape of the growth curve. Full-sib analyses suggested the presence of considerable genetic variation and some high genetic correlations among the estimated growth parameters.

Selection for components related to body composition in mice: direct responses

SummaryReplicated within full-sib family single-trait selection was conducted for 10 generations in mice for (1) high or low 12-week epididymal fat pad percentage (100 x epididymal fat pad weight/body weight) or (2) high or low 12-week hind carcass percentage (100 x hind carcass weight/body weight). Pooled realized heritabilities based on high, low and divergent selection were 0.66±0.09, 0.65±0.13 and 0.66±0.05 for epididymal fat pad percentage and 0.48±0.08, 0.33±0.08 and 0.40±0.04 for hind carcass percentage. The pooled realized genetic correlation (rGR) between epididymal fat pad percentage and hind carcass percentage based on divergence was −0.67±0.04. Other estimates of (rGR) were: epididymal fat pad percentage with body weight (0.57±0.05); epididymal fat pad percentage with epididymal fat pad weight (1.17±0.05); hind carcass percentage with body weight (−0.61±0.09); hind carcass percentage with hind carcass weight (−0.05±0.11). Indirect measures of fat and lean tissue percentages were highly heritable, and (rGR) between them would be desirable from the standpoint of analogous types of traits in livestock. In the same context, undesirable (rGR)s were found between epididymal fat pad percentage and body weight and between hind carcass percentage and body weight.

Maturing patterns of organ weights in mice selected for rapid postweaning gain.

SummaryCorrelated responses to selection for increased 3–6 week postweaning gain in male mice were estimated for seven internal organs (testes, spleen, liver, kidneys, heart, small intestine (S intest) and stomach) weighed at specific degrees of maturity in body weight (37.5, 50.0, 62.5, 75.0, 87.5 and 100%). Correlated responses in organ weights were generally large, but the magnitude and direction of response depended upon whether 1) comparisons were made at the same age, degree of maturity or body weight and 2) absolute or proportional organ weights were used. The selected line (M16) weighed more and had larger organ weights than controls (ICR) when compared at either the same degree of maturity or the same age, indicating positive genetic correlations between body weight and the respective organ weights. Positive correlated responses were found in spleen weight/body weight at all degrees of maturity and in liver and S intest weights as a proportion of body weight at some degrees of maturity. Testes, kidneys, heart and stomach weights as a proportion of body weight had negative correlated responses, though this was consistent only for kidneys across all degrees of maturity. Correlated responses in organ weights adjusted for body weight by covariance analysis were positive for spleen, S intest and stomach and negative for testes and kidneys. Based on the constrained quadratic model, degree of maturity in organ weight relative to degree of maturity in body weight responded positively for testes, kidneys and S intest and negatively for spleen and liver. Selection for increased growth caused negative correlated responses in allometric growth of testes, kidneys, S intest and stomach.

Effect of genetic background on growth of mice hemizygous for wild-type or dwarf mutated bovine growth hormone transgenes

The effects of a high-growth genetic background on the growth of mice hemizygous for one of two growth hormone transgenes were examined. Male mice hemizygous for wild-type (W) and dwarf mutant (M) bovine growth hormone (bGH) transgenes were crossed with females of a high-growth selected (S) and control (C) line as follows: W x S, W x C, M x S and M x C. Body weights of progeny were recorded weekly from 2 to 10 weeks of age. F1 progeny were classified as carriers (P) or non-carriers (N) of the transgene by assaying tail DNA for bGH using the polymerase chain reaction and agarose gel electrophoresis. A deficiency in the number of f1 progeny carrying the W (P<0.05) and M (P<0.01) bGH transgene was most likely due to differential prenatal and early postnatal mortality. Bodyweight means of wild-type transgenic mice were larger (P < 0.05) than those of non-transgenic littermates by 3 weeks of age in a C background in contrast to 5 weeks in S. The wild-type bGH transgene increased adult body weights more in the C (155%) than in the S (136%) background, indicating transgene expression by selection background interaction (P < 0.05). However, the growth response to the wild-type transgene in the S background was still large. The dwarf mutant transgene had a greater effect on growth reduction in the S (70%) than in the C (84%) background, thus causing transgene expression by selection background interaction (P < 0.05). Gender by wild-type transgene effect interactions (P < 0.001) for adult body weight were caused by the transgene reducing the gender difference for body weight in C and eliminating it in S. The dwarf mutant caused a larger negative effect on growth in males than in females, resulting in a gender by dwarf mutant transgene interaction (P < 0.001) for adult body weights. Results indicate that the effect of a GH transgene on growth can be affected both by a high-growth genetic background and the gender of progeny.