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Maximizing the response of selection with a predefined rate of inbreeding.

A method was derived that maximizes the genetic level of selected animals while constraining their average coancestry to a predefined value. The average coancestry of the selected parents equals the inbreeding level in the next generation, so that rates of inbreeding were controlled. When this method was applied for several generations of selection, stable rates of genetic gain were attained, which indicates that the method could control the short- and long-term effects of selection on inbreeding. At equal rates of inbreeding, genetic gains were 21 to 60% greater than that with selection for BLUP-EBV, because of increased selection differentials. The difference was larger when the desirable rate of inbreeding was smallest. Selection with a constraint on inbreeding required only EBV of, and relationships between, the selection candidates and is therefore easy to apply in practice. The optimal solution is expressed in genetic contributions of selection candidates to the next generation, which is equivalent to numbers of offspring per candidate. These optimal numbers of offspring may be difficult to attain because of female reproductive limitations. The optimal method could be adapted to situations with additional reproductive constraints. The method can also be used to constrain the variance of response by restricting the average prediction error variance of the selected animals.

Animal Husbandry↗

Multivariate analysis of litter size for multiple parities with production traits in pigs: II. Response to selection for litter size and correlated response to production traits.

Litter size and production trait responses to experimental selection for increased litter size in a Landrace pig population are reported. The numbers of sows and litters available for the first cycle of selection were 3,034 and 961, respectively. Selection was carried out using a BLUP repeatability animal model for number of piglets born alive (NBA). The experiment included one selection and one control line, each with three nonoverlapping generations. The selection line (H) consisted of the 160 sows with the highest breeding values and one boar from each of 25 full-sib families with the highest breeding values. The control line (C) consisted of 160 sows and 25 boars randomly chosen. The two subsequent generations in each line were obtained by random selection. A Bayesian analysis of genetic response using a multivariate model was carried out by Gibbs sampler. Marginal posterior distributions were obtained for direct response in NBA, and for correlated response in weight (WT), and backfat thickness (BT) at 175 d of age. The posterior means and posterior standard deviation (PSD) for direct genetic response of NBA ranged from 0.32 (PSD 0.08) in the first parity to 0.64 (PSD 0.08) in the fourth. The posterior means for correlated genetic response in WT and BT were -0.66 kg (PSD 0.36) and 0.20 mm (PSD 0.10), respectively. For WT and BT, the 95% highest posterior density regions (HPD) contain zero-correlated genetic response. Marginal posterior distributions of selection differentials were investigated. The posterior means for standardized selection differentials for NBA in different parities ranged from 0.70 (PSD 0.12) to 0.94 (PSD 0.06) in females for line H, from 0.22 (PSD 0.19) to 0.34 (PSD 0.10) in males for line H, and from 0.08 (PSD 0.08) to 0.13 (PSD 0.07) in females for line C. All available males were used in line C. Results from this experiment showed that selection for increased litter size is effective. Responses to selection were heterogeneous across parities, suggesting that litter size in each parity may have a different genetic background. No correlated genetic response to growth and backfat thickness was observed.

Adipose Tissue↗

Genetic response to selection for weaning weight or yearling weight or yearling weight and muscle score in Hereford cattle: efficiency of gain, growth, and carcass characteristics.

An experiment involving crosses among selection and control lines was conducted to partition direct and maternal additive genetic response to 20 yr of selection for 1) weaning weight, 2) yearling weight, and 3) index of yearling weight and muscle score. Selection response was evaluated for efficiency of gain, growth from birth through market weight, and carcass characteristics. Heritability and genetic correlations among traits were estimated using animal model analyses. Over a time-constant interval, selected lines were heavier, gained more weight, consumed more ME, and had more gain/ME than the control. Over a weight-constant interval, selected lines required fewer days, consumed less ME, had more efficient gains, and required less energy for maintenance than control. Direct and maternal responses were estimated from reciprocal crosses among unselected sires and dams of control and selection lines. Most of the genetic response to selection in all three lines was associated with direct genetic effects, and the highest proportion was from postweaning gain. Indirect responses of carcass characteristics to selection over the 20 yr were increased weight of carcasses that had more lean meat, produced with less feed per unit of gain. At a constant carcass weight, selected lines had 1.32 to 1.85% more retail product and 1.62 to 2.24% less fat trim and 10/100 to 25/100 degrees less marbling than control. At a constant age, heritability of direct and maternal effects and correlations between them were as follows: market weight, 0.36, 0.14, and 0.10; carcass weight, 0.26, 0.15, and 0.03; longissimus muscle area, 0.33, 0.00, and 0.00; marbling, 0.36, 0.07, and -0.35; fat thickness, 0.41, 0.05, and -0.18; percentage of kidney, pelvic, and heart fat, 0.12, 0.08, and -0.76; percentage of retail product, 0.46, 0.05, and -0.29; retail product weight, 0.44, 0.08, -0.14; and muscle score, 0.37, 0.14, and -0.54. Selection criteria in all lines improved efficiency of postweaning gain and increased the amount of salable lean meat on an age- or weight-constant basis, but carcasses had slightly lower marbling scores.

Animals↗

Incidence of splayleg pigs in Nebraska litter size selection lines.

Genetic parameters for the splayleg (SL) condition were estimated from 37,673 records of pigs from six lines derived from a Large White-Land-race base population. Random selection for 22 generations was practiced in Lines C1 and C2. Line C2 was derived from C1 at Generation 8. Selection lines were as follows: 1) Line I, selected 11 generations for an index of ovulation rate and embryonic survival followed by 11 generations of selection for litter size; 2) Line IOL, derived from Line I at Generation 8 and which underwent eight generations of two-stage selection for ovulation rate and number of fully formed pigs per litter followed by four generations of litter size selection; 3) Line COL, derived from Line C1 at Generation 8 and selected eight generations in two stages for ovulation rate and number of fully formed pigs followed by four generations of litter size selection; and 4) Line T, selected 12 generations for increased testis size. From logistic models, it was found that boars were 224% more likely to have SL than gilts (P < 0.01). Decreases in birth weight, dam age at puberty, dam nipple number, and dam embryonic survival, and increases in dam litter size and inbreeding increased the odds of SL (P < 0.05). Direct and maternal heritabilities of SL were 0.07 and 0.16, respectively, and the correlation between direct and maternal effects was -0.24. Correlations between direct genetic effects for SL and number born alive, nipple number, birth weight, age at puberty, and embryonic survival were -0.19, -0.36, 0.23, -0.19, and -0.32, respectively. Except for the correlation of 0.32 between maternal effects for SL and direct effects for number of live pigs, correlations of SL maternal genetic effects with direct genetic effects of other traits were less than 0.11. Annual direct genetic trends (%) for SL in I, IOL, COL, T, C1, and C2 were -0.003 +/- 0.003, 0.121 +/- 0.012, -0.273 +/-0.009, 0.243 +/-0.014, -0.274 +/-0.004, and 0.086 +/-0.008, respectively; annual maternal genetic trends (%) were 0.106 +/-0.004, 0.508 +/-0.019, 0.383 +/-0.015, 0.527 +/-0.024, 0.188 +/-0.005, and 0.113 +/-0.012, respectively. Annual genetic maternal trend in Line I after Generation 12 was 0.339 +/-0.014. Maternal breeding value for SL is expected to increase as a correlated response to selection for increased litter size and increased size of testes.

Animals↗

Selection when traits have different genetic and phenotypic variances in different environments.

Falconer's concept that performance in environment 2 is a different trait from performance in environment 1 allows calculation of expected response in environment 2 if selection is from environment 1. Response to selection in environment 1 and correlated response in environment 2 depend on heritability and phenotypic variance in environment 1, genetic covariance between performance of identical genotypes in the two environments, and selection intensity. If selection is from performance in environment 2, direct response in environment 2 and correlated response in environment 1 also can be calculated. If selection is from animals in both environments and if selected genotypes are expressed randomly in both environments, relative responses in environments 1 and 2 are weighted averages of direct and correlated responses with the weights being p1 and p2, the fractions of animals selected from environments 1 and 2. Fraction selected from one environment determines the selection intensity factor for the direct and correlated responses in that and the other environment. Other terms determining relative responses are independent of fractions selected. A simple approach to finding the optimum fractions, p1 and p2, is to calculate weighted average responses for environments one and two for all combinations of p1 + p2 = p, a fixed fraction.

Animals↗

Response to divergent selection for early growth of chickens fed a diet deficient in selenium.

Three generations of divergent selection for 21-day growth response to a diet deficient in selenium (-Se) were bred using a meat-type chicken. The Athens-Canadian Randombred (AC) population of chickens served as the base population for this study. Mass selection was used to establish a -Se refractory line (SDR) and a -Se susceptible line (SDS). A genetic control line was maintained during the selection process to facilitate evaluation of the responses of the selected lines. The SDR males and females had an average of 17% increase in weight gain at 21 days of age when fed the -Se diet compared with the control line males and females fed the same diet for the three generations of selection. The SDS line had an average reduction in weight gain of 27% during the same period of selection. A difference of 25 g was observed between the mean body weights of SDR males and females and between the SDS males and females after one generation of selection. By the third generation of selection, the difference between SDR and SDS males had increased to 31 g, whereas the SDR and SDS females differed by 41 g. Early response to selection was asymmetrical because the response was greater in the SDS than in the SDR line. Response to selection, however, generally declined after the first generation. Realized heritability estimates for individual generations for this trait were variable (ranging from -.26 to .95), but cumulative estimates (.15 to .39) for growth through three generations were similar to those reported for chickens and quail.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunocompetences and Marek's disease resistance in three pairs of chicken lines selected for different immunological characters.

Three pairs of chicken lines selected for high (H) and low (L) graft vs. host reaction (GVHR) competences, serum immunoglobulin G (IgG) levels, and antibody responses to Leucocytozoon caulleryi were examined for their immunocompetences and Marek's disease (MD) resistance. The GVHR-H and GVHR-L lines were further divided into two sublines according to their major histocompatibility B genotype. Immune responses to sheep erythrocytes (SRBC), bovine serum albumin (BSA), and a lipopolysaccharide (LPS) were compared between the high and low lines of each pair of selected lines. Significant differences were found in responses to SRBC and LPS in IgG-selected lines and in response to BSA in Leucocytozoon-selected lines. In all three instances antibody titers of the H line were higher than those of the L line. The GVHR competence expressed by the splenomegaly index (SI) was also significantly different between the H and L lines of all three selected-line pairs. The SI values in the GVHR-selected and IgG-selected lines were higher in the H line than in the L line, whereas those in the Leucocytozoon-selected lines were lower in the H line. Differences in MD incidence and in MD mortality were found between the GVHR-selected B11B11 subline and the IgG-selected lines. In both instances the L line was more resistant to MD than the H line.

Animals↗

Water and feed intake, feed efficiency, and abdominal fat levels of dwarf and normal chickens selected under different water:feed ratio environments.

Early feed and water intake, feed efficiency, and abdominal fat weights were investigated in normal and dwarf genotypes previously selected for high 8-wk body weight under .4 and 1.6% dietary salt environments. Progeny from the selected lines were evaluated on a normal .4% salt diet in two experiments following Generations 3 and 4. Progeny of lines selected on the .4% salt environment tended to have higher body weights and feed intake than progeny of lines selected on the 1.6% salt environment. There was evidence that progeny from normal birds previously selected on the 1.6% salt environment had higher initial (0 to 6 days) water:feed ratios than progeny of normal birds previously selected on the .4% salt environment, with ratios approximately 20% greater from 0 to 2 days in Generation 4 progeny. Feed efficiencies were similar within genotype across selection environments. However, feed efficiency of dwarfs appeared to be superior to feed efficiency of normals from 0 to 8 days, whereas at later ages, normals were more efficient. Normal females of lines selected in the 1.6% salt environment had from 13 to 29% less abdominal fat percentages than contemporaries from lines selected on the .4% salt environment at 63 to 66 days of age. Abdominal fat weights of dwarfs, however, were not influenced by the selection environment.

Adipose Tissue↗

Sexual selection for size and symmetry in a diversifying secondary sexual character in Drosophila bipectinata Duda (Diptera: Drosophilidae).

Results of intrapopulation studies of sexual selection and genetic variation and covariation underlying elements of the sex comb of Drosophila bipectinata are presented. The magnitude of the sex comb, a sexual ornament, varies significantly among Australasian populations, motivating research into the evolutionary mechanisms responsible for its incipient diversification. The comb is composed of stout black teeth on the front legs of males arranged in three distinct segments: C1, C2, and C3. Significant sexual selection in field populations in northeastern Queensland, Australia, was detected for increasing C2 and body size, and simultaneously for reducing comb positional fluctuating asymmetry. In contrast, sexual selection was not detected for other comb segments, nor for sternopleural bristle number or symmetry. Selection intensities for C2 and comb positional fluctuating asymmetry were similar in magnitude, and although they were opposite in sign, values across twelve sampling dates, or selection episodes, were uncorrelated. Heritability estimates for C2 were high and significant across years, whereas heritability estimates for comb positional asymmetry were small, and generally nonsignificant. The major sex comb segments (C1 and C2) were significantly and positively correlated genetically, indicating the potential for correlated evolution of these components of the comb under sexual selection. The original finding of a significant positive genetic correlation between the magnitude of this sex trait and its positional asymmetry indicates that the counteracting and independent selection pressures detected could contribute to the maintenance of genetic variation sustaining sexual selection. The study documents the simultaneous presence of sexual selection in nature and of heritable genetic variation underlying expression of the sex comb, fundamental conditions necessary for its adaptive diversification. Drosophila bipectinata may be a valuable model for studies of adaptive diversification and incipient speciation by sexual selection.

Adaptation, Biological↗

An exact form of the breeder's equation for the evolution of a quantitative trait under natural selection.

Starting with the Price equation, I show that the total evolutionary change in mean phenotype that occurs in the presence of fitness variation can be partitioned exactly into five components representing logically distinct processes. One component is the linear response to selection, as represented by the breeder's equation of quantitative genetics, but with heritability defined as the linear regression coefficient of mean offspring phenotype on parent phenotype. The other components are identified as constitutive transmission bias, two types of induced transmission bias, and a spurious response to selection caused by a covariance between parental fitness and offspring phenotype that cannot be predicted from parental phenotypes. The partitioning can be accomplished in two ways, one with heritability measured before (in the absence of) selection, and the other with heritability measured after (in the presence of) selection. Measuring heritability after selection, though unconventional, yields a representation for the linear response to selection that is most consistent with Darwinian evolution by natural selection because the response to selection is determined by the reproductive features of the selected group, not of the parent population as a whole. The analysis of an explicitly Mendelian model shows that the relative contributions of the five terms to the total evolutionary change depends on the level of organization (gene, individual, or mated pair) at which the parent population is divided into phenotypes, with each frame of reference providing unique insight. It is shown that all five components of phenotypic evolution will generally have nonzero values as a result of various combinations of the normal features of Mendelian populations, including biparental sex, allelic dominance, inbreeding, epistasis, linkage disequilibrium, and environmental covariances between traits. Additive genetic variance can be a poor predictor of the adaptive response to selection in these models. The narrow-sense heritability sigma2A/sigma2P should be viewed as an approximation to the offspring-parent linear regression rather than the other way around.

Biological Evolution↗

[Study on application of the general selection index].

Several problems associated with selection strategies of breeder rams are discussed using the general selection index. Selection objective is to improve the aggregate breeding value of clean-fleece weight, number of lambs and body weight. Staple length is the assistant trait of selection. Aggregate, restrictive and optimal selection indices are constructed with the information of ram individual and the ram's half-sib sisters and half-sib daughters. The restrictive selection maintains the genetic gain of body weight unchanged. The optimal selection keeps the genetic gain of the clean-fleece weight at 0.4 kg in one generation (20% retention). The selection effects of the three indices are compared. Furthermore, two related problems are discussed. First, if each single trait of the three objective traits is selected to permit the genetic gain of the trait to be as large as possible in a short time, the largest gain of the aggregate breeding value is obtained when the trait is clean-fleece weight. Secondly, when the number of ram's relatives is more than enough, the selection effect of increasing the number is very limited. However, increasing the ram's half-sib daughters is more favorable than increasing the ram's half-sib sisters.

Animals↗

Influencing prolificacy of sows by selection for physiological factors.

The potential to improve prolificacy, with major emphasis on selection for components of litter size, ovulation rate and prenatal survival, and selection for physiological factors are reviewed. Response to selection for physiological factors is superior to direct selection if physiological factors have moderate heritabilities and moderate to high genetic correlations with the trait to be improved. There are very few estimates of the genetic parameters needed to calculate the relative efficiency of direct and indirect selection. Testis size is highly heritable and positively correlated genetically with ovulation rate in both mice and pigs and may be potentially useful in an index with litter size to improve ovulation rate and prenatal survival. Selection for growth, ovulation rate or litter size has increased ovulation rate in mice, but the physiological explanations are different. Selection for litter size in a line of pigs previously selected for ovulation rate was effective; the realized heritability was 0.18 +/- 0.06. Potential improvements in litter size from index selection for ovulation rate and prenatal survival are discussed and compared to direct selection for litter size.

Animals↗

[Selection of laboratory rats for fertility components in synchronized estrus using Suisynchron-Praemix. 2. Results of litter development].

The following results were obtained from experimental studies into selection of laboratory rats for fertility and random mating with oestrus being synchronised by means of Suisynchron-Prämix, through eight generations: --Success of selection without synchronised oestrus was higher than that with synchronised oestrus by selection according to the basic index and with one and the same selection intensity. --Litter size and weight were higher in the selected variants, as a result of increased potential fertility (rate of ovulation). --In the population with selection and synchronised oestrus a negative relationship was found to exist between the directly correlated selection results regarding fertility parameters, on the one hand, and the effect of synchronisation, on the other. --Both the rates of ovulation and litter parameters were lower in the population with selection and synchronised oestrus, as a result of synchronisation. --The effect of synchronised oestrus on the population with selection and synchronised oestrus was partially eliminated owing to selection for fertility.

Animals↗

[The temperature dependence of selection efficiency and the expression of the genes controlling the rate of embryonic development in Drosophila melanogaster].

We have already shown that selection of heterogeneous D. melanogaster populations for the rate of embryogenesis at 32 degrees C may produce populations, in which 50% of the larvae are hatched 20-40 min earlier, i.e., 2-4% more rapidly than, in the control. Highly inbred strains were obtained from the selected populations and develop 5-7% more rapidly than the control populations. Here we studied separately the effects of temperature on the efficiency of selection and expression of the selected genotype. With this in view, multiple (9-15 rounds) selection of the first 10% of the larvae was performed at 17, 25, and 32 degrees C and the mean duration of embryogenesis (hatching of 50% larvae) at these three temperatures was determined in the entire selected population. Selection proved to be almost equally efficient at all temperatures. On the contrary, expression of the selected genotypes markedly depended on temperature: the rate of embryogenesis of the selected populations exceeded that in the control at 17 degrees C by 1.1%, at 25 degrees C by 2.5%, and at 32 degrees C by 3.5%. In the inbred strains this dependence was even more pronounced: 1.2%, 2.7%, and 5.7%, respectively. The temperature dependence of expression of the genes collected by selection and coding for accelerated development means that these genes affect the rate of development as the function of temperature by changing the angle of the curve inclination. Possible mechanisms of this phenomenon are discussed.

Animals↗

The antibiotic selective process: concentration-specific amplification of low-level resistant populations.

The biochemistry and genetics of antibiotic resistance are far better known than the equally important events underlying the selection of resistant populations. The hidden selection of low-level resistant variants may be a key process in the emergence of high-level antibiotic resistance. Different low-level resistant bacterial subpopulations may be specifically selected by different low antibiotic concentrations. The space in the environment (human body) where a given selective concentration exists represents the selective compartment. For pharmacokinetic reasons, low antibiotic concentrations occur in a larger selective compartment and persist longer than high antibiotic concentrations. The specific selection of low-level variants by low concentrations of antibiotic can be reproduced in experimental in vitro models using mixtures of susceptible and low-level resistant populations. We demonstrated this in Escherichia coli strains harbouring TEM-1, TEM-12 and TEM-10 beta-lactamases challenged by cefotaxime, and also Streptococcus pneumoniae strains with various levels of penicillin resistance challenged by amoxicillin or cefotaxime. In both cases, four hours of antibiotic challenge produced selective peaks of low-level resistant variant populations at low-level antibiotic concentrations. We conclude that variants with small decreases in antibiotic susceptibility may be fully selectable under in vivo circumstances; on the other hand, low-level antibiotic concentrations may have a considerable selective effect on the emergence of antibiotic resistance.

Anti-Bacterial Agents↗

Quantifying the magnitude of baseline covariate imbalances resulting from selection bias in randomized clinical trials.

Selection bias is most common in observational studies, when patients select their own treatments or treatments are assigned based on patient characteristics, such as disease severity. This first-order selection bias, as we call it, is eliminated by randomization, but there is residual selection bias that may occur even in randomized trials which occurs when, subconsciously or otherwise, an investigator uses advance knowledge of upcoming treatment allocations as the basis for deciding whom to enroll. For example, patients more likely to respond may be preferentially enrolled when the active treatment is due to be allocated, and patients less likely to respond may be enrolled when the control group is due to be allocated. If the upcoming allocations can be observed in their entirety, then we will call the resulting selection bias second-order selection bias. Allocation concealment minimizes the ability to observe upcoming allocations, yet upcoming allocations may still be predicted (imperfectly), or even determined with certainty, if at least some of the previous allocations are known, and if restrictions (such as randomized blocks) were placed on the randomization. This mechanism, based on prediction but not observation of upcoming allocations, is the third-order selection bias that is controlled by perfectly successful masking, but without perfect masking is not controlled even by the combination of advance randomization and allocation concealment. Our purpose is to quantify the magnitude of baseline imbalance that can result from third-order selection bias when the randomized block procedure is used. The smaller the block sizes, the more accurately one can predict future treatment assignments in the same block as known previous assignments, so this magnitude will depend on the block size, as well as on the level of certainty about upcoming allocations required to bias the patient selection. We find that a binary covariate can, on average, be up to 50% unbalanced by third-order selection bias.

Analysis of Variance↗

The multigenic structure of the MHC locus contributes to positive selection efficiency: a role for MHC class II gene-specific restriction.

The study of T cell positive selection in the thymus has long been focused on the specificity of the MHC-TCR interactions, making use of genetically manipulated mice that display TCR specificities or selecting peptides of limited diversity. However, little is known on the role of the MHC molecules irrespective of the peptide specificity and the implications of MHC multigenic structure in thymic positive selection have not been addressed. Here, we investigated the effect of MHC class II genetic configuration on the positive selection efficiency of naturally generated pre-selection repertoires in the mouse thymus. Analysis of positively selected thymocyte populations in MHC-congenic and -transgenic mice revealed that expression of I-E molecule in the thymic cortex increases positive selection efficiency of CD4 cells by approximately 50%. We show that increments in positive selection attributable to either the I-A and I-E genes are not due to increased MHC class II expression in the thymic cortex and are not affected by the number of MHC alleles. Collectively, our findings imply that MHC class II gene-restricted TCR specificities significantly contribute to positive selection efficiency, introducing the notion that multigenic structure of the MHC locus serves to increase selection of non-overlapping TCR repertoires.

Animals↗

New spatial localization method using pulsed high-order field gradients (SHOT: Selection with High-Order gradienT).

A new spatial localization method using an additional set of high-order magnetic field gradients is described. The method uses a nonlinear part of high-order magnetic field gradient patterns which allows us to select a volume in conjunction with the selective radiofrequency (RF) pulse. Unlike the other existing volume selection methods such as ISIS or SPARS, the proposed selection method requires only one RF-gradient pulse pair to select a volume in two directions. The center of the selected volume can be moved to any arbitrary location within the body by the addition of precalculated lower order gradients which are simultaneously pulsed with the high-order gradient. The method also has the potential for localized spectroscopy from the FID signal which can be realized by using oscillating second- and first-order gradients for 3D selection with a single RF pulse. By using the proposed localization method, it is possible to design more flexible pulse sequences, e.g., the shorter echo-time spectroscopic pulse sequence. We have designed and constructed a six-loop r2 (or x2 + y2) gradient coil for initial application. By simultaneously applying this second-order gradient and proper x, y, and/or z gradients, 2D selections were achieved in arbitrarily selected positions in conjunction with a single selective RF pulse. Phantom and animal experiments have been performed and the results appear promising, especially in areas of NMR spectroscopic imaging applications where spatial localization is essential.

Animals↗