Assessment of alternative genotyping strategies to maximize imputation accuracy at minimal cost

Background

Commercial breeding programs seek to maximise the rate of genetic gain while minimizing the costs of attaining that gain. Genomic information offers great potential to increase rates of genetic gain but it is expensive to generate. Low-cost genotyping strategies combined with genotype imputation offer dramatically reduced costs. However, both the costs and accuracy of imputation of these strategies are highly sensitive to several factors. The objective of this paper was to explore the cost and imputation accuracy of several alternative genotyping strategies in pedigreed populations.

Methods

Pedigree and genotype data from a commercial pig population were used. Several alternative genotyping strategies were explored. The strategies differed in the density of genotypes used for the ancestors and the individuals to be imputed. Parents, grandparents, and other relatives that were not descendants, were genotyped at high-density, low-density, or extremely low-density, and associated costs and imputation accuracies were evaluated.

Results

Imputation accuracy and cost were influenced by the alternative genotyping strategies. Given the mating ratios and the numbers of offspring produced by males and females, an optimized low-cost genotyping strategy for a commercial pig population could involve genotyping male parents at high-density, female parents at low-density (e.g. 3000 SNP), and selection candidates at very low-density (384 SNP).

Conclusions

Among the selection candidates, 95.5 % and 93.5 % of the genotype variation contained in the high-density SNP panels were recovered using a genotyping strategy that costs respectively, $24.74 and $20.58 per candidate.     

Optimal numbers of matings: the conditional balance between benefits and costs of mating for females of a nuptial gift‐giving spider

In species where females gain a nutritious nuptial gift during mating, the balance between benefits and costs of mating may depend on access to food. This means that there is not one optimal number of matings for the female but a range of optimal mating numbers. With increasing food availability, the optimal number of matings for a female should vary from the number necessary only for fertilization of her eggs to the number needed also for producing these eggs. In three experimental series, the average number of matings for females of the nuptial gift‐giving spider Pisaura mirabilis before egg sac construction varied from 2 to 16 with food‐limited females generally accepting more matings than well‐fed females. Minimal level of optimal mating number for females at satiation feeding conditions was predicted to be 2–3; in an experimental test, the median number was 2 (range 0–4). Multiple mating gave benefits in terms of increased fecundity and increased egg hatching success up to the third mating, and it had costs in terms of reduced fecundity, reduced egg hatching success after the third mating, and lower offspring size. The level of polyandry seems to vary with the female optimum, regulated by a satiation‐dependent resistance to mating, potentially leaving satiated females in lifelong virginity.     

Improved dairy cattle mating plans at herd level using genomic information

From 2012 to 2018, 223 180 Montbéliarde females were genotyped in France and the number of newly genotyped females increased at a rate of about 33% each year. With female genotyping information, farmers have access to the genomic estimated breeding values of the females in their herd and to their carrier status for genetic defects or major genes segregating in the breed. This information, combined with genomic coancestry, can be used when planning matings in order to maximize the expected on-farm profit of future female offspring. We compared different mating allocation approaches for their capacity to maximize the expected genetic gain while limiting expected progeny inbreeding and the probability to conceive an offspring homozygous for a lethal recessive allele. Three mate allocation strategies (random mating (RAND), sequential mating (gSEQ€) and linear programing mating (gLP€)) were compared on 160 actual Montbéliarde herds using male and female genomic information. Then, we assessed the benefit of using female genomic information by comparing matings planned using only female pedigree information with the equivalent strategy using genomic information. We measured the benefit of adding genomic expected inbreeding and risk of conception of an offspring homozygous for a lethal recessive allele to Net merit in mating plans. The influence of three constraints was tested: by relaxing the constraint on availability of a particular semen type (sexed or conventional) for bulls, by adding an upper limit of 8.5% coancestry between mate pairs or by using a more stringent maximum use of a bull in a herd (5% vs 10%). The use of genomic information instead of pedigree information improved the mate allocation method in terms of progeny expected genetic merit, genetic diversity and risk to conceive an offspring homozygous for a lethal recessive allele. Optimizing mate allocation using linear programming and constraining coancestry to a maximum of 8.5% per mate pair reduced the average coancestry with a small impact on expected Net Merit. In summary, for male and female selection pathways, using genomic information is more efficient than using pedigree information to maximize genetic gain while constraining the expected inbreeding of the progeny and the risk to conceive an offspring homozygous for a lethal recessive allele. This study also underlines the key role of semen type (sexed vs conventional) and the associated constraints on the mate allocation algorithm to maximize genetic gain while maintaining genetic diversity and limiting the risk to conceive an offspring homozygous for a lethal recessive allele.     

A low-marker density implementation of genomic selection in aquaculture using within-family genomic breeding values

Background

Genomic selection can increase genetic gain within aquaculture breeding programs, but the high costs related to high-density genotyping of a large number of individuals would make the breeding program expensive. In this study, a low-cost method using low-density genotyping of pre-selected candidates and their sibs was evaluated by stochastic simulation.

Methods

A breeding scheme with selection for two traits, one measured on candidates and one on sibs was simulated. Genomic breeding values were estimated within families and combined with conventional family breeding values for candidates that were pre-selected based on conventional BLUP breeding values. This strategy was compared with a conventional breeding scheme and a full genomic selection program for which genomic breeding values were estimated across the whole population. The effects of marker density, level of pre-selection and number of sibs tested and genotyped for the sib-trait were studied.

Results

Within-family genomic breeding values increased genetic gain by 15% and reduced rate of inbreeding by 15%. Genetic gain was robust to a reduction in marker density, with only moderate reductions, even for very low densities. Pre-selection of candidates down to approximately 10% of the candidates before genotyping also had minor effects on genetic gain, but depended somewhat on marker density. The number of test-individuals, i.e. individuals tested for the sib-trait, affected genetic gain, but the fraction of the test-individuals genotyped only affected the relative contribution of each trait to genetic gain.

Conclusions

A combination of genomic within-family breeding values, based on low-density genotyping, and conventional BLUP family breeding values was shown to be a possible low marker density implementation of genomic selection for species with large full-sib families for which the costs of genotyping must be kept low without compromising the effect of genomic selection on genetic gain.     

Palliating the impact of fixation of a major gene on the genetic variation of artificially selected polygenes

Selective sweeps of variation caused by fixation of major genes may have a dramatic impact on the genetic gain from background polygenic variation, particularly in the genome regions closely linked to the major gene. The response to selection can be restrained because of the reduced selection intensity and the reduced effective population size caused by the increase in frequency of the major gene. In the context of a selected population where fixation of a known major gene is desired, the question arises as to which is the optimal path of increase in frequency of the gene so that the selective sweep of variation resulting from its fixation is minimized. Using basic theoretical arguments we propose a frequency path that maximizes simultaneously the effective population size applicable to the selected background and the selection intensity on the polygenic variation by minimizing the average squared selection intensity on the major gene over generations up to a given fixation time. We also propose the use of mating between carriers and non-carriers of the major gene, in order to promote the effective recombination between the major gene and its linked polygenic background. Using a locus-based computer simulation assuming different degrees of linkage, we show that the path proposed is more effective than a similar path recently published, and that the combination of the selection and mating methods provides an efficient way to palliate the negative effects of a selective sweep.     

Paternity validation and estimation of genotyping error rate for the BovineSNP50 BeadChip

Incorrect paternity assignment in cattle can have a major effect on rates of genetic gain. Of the 576 Israeli Holstein bulls genotyped by the BovineSNP50 BeadChip, there were 204 bulls for which the father was also genotyped. The results of 38 828 valid single nucleotide polymorphisms (SNPs) were used to validate paternity, determine the genotyping error rates and determine criteria enabling deletion of defective SNPs from further analysis. Based on the criterion of >2% conflicts between the genotype of the putative sire and son, paternity was rejected for seven bulls (3.5%). The remaining bulls had fewer conflicts by one or two orders of magnitude. Excluding these seven bulls, all other discrepancies between sire and son genotypes are assumed to be caused by genotyping mistakes. The frequency of discrepancies was >0.07 for nine SNPs, and >0.025 for 81 SNPs. The overall frequency of discrepancies was reduced from 0.00017 to 0.00010 after deletion of these 81 SNPs, and the total expected fraction of genotyping errors was estimated to be 0.05%. Paternity of bulls that are genotyped for genomic selection may be verified or traced against candidate sires at virtually no additional cost.     

Multiple mating increases cocoon hatching success in the earthworm Eisenia andrei (Oligochaeta: Lumbricidae)

In simultaneous hermaphrodites with reciprocal mating, multiple mating may be a male strategy that conflicts with female interests, and therefore an intra‐individual sexual conflict regarding the number of matings may be expected. The evolutionary outcome of this sexual conflict will depend on the costs and benefits that extra mating entails for each sexual function. In the present study, we investigated the costs and benefits of multiple mating on cocoon number, cocoon mass, and cocoon hatching success in the redworm Eisenia andrei, a simultaneous hermaphrodite with reciprocal insemination, by manipulating the number of matings with different partners. We did not detect any reduction in the female reproductive output (number and mass of cocoons) with increasing number of mating partners. However, we found that multiple mating showed benefits for female reproduction that increased the hatching success of the cocoons. This effect may be a result of increased quantity and/or diversity of sperm in the spermathecae of multiple mated earthworms. Further studies are required to clarify the mechanism underlying the increased cocoon hatching success when redworms engage in multiple matings. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ?? , ??–??.     

A life-history perspective on strategic mating effort in male scorpionflies

In species with high male mating effort, there is a trade-offbetween mating effort spent in a current mating and resourcesleft for future matings. Consequently, to maximize their reproductivesuccess, males have to invest strategically, saving resourcesin matings with low reproductive gain for future, more valuablematings. However, as males age, the expected future reproductivesuccess constantly declines. Thus, the importance of resource rationing may drastically change during a lifetime. Males ofthe scorpionfly Panorpa cognata offer females a costly nuptialgift before copulation, which functions as male mating effort.Resources for the production of these salivary masses are severelylimited for males in poor condition. We found that males investedmore in copulations with high-quality females than in copulationswith low-quality females. However, males ceased to discriminateas they became older. Old males, with a relative small numberof expected future matings, did not invest differentially incopulations with high- versus low-quality females. In copulationswith low-quality females, males invested more in late thanin initial matings, whereas in matings with high-quality females,time of mating had no influence on mating effort. These resultsimply that males adaptively change their resource allocationstrategy during the course of the season. Initial matings seemto be characterized by male prudence; in later matings, malesseem to adopt a more opportunistic mating strategy.     

Rearing Temperature Influences Adult Response to Changes in Mating Status

Rearing environment can have an impact on adult behavior, but it is less clear how rearing environment influences adult behavior plasticity. Here we explore the effect of rearing temperature on adult mating behavior plasticity in the butterfly Bicyclus anynana, a species that has evolved two seasonal forms in response to seasonal changes in temperature. These seasonal forms differ in both morphology and behavior. Females are the choosy sex in cohorts reared at warm temperatures (WS butterflies), and males are the choosy sex in cohorts reared at cooler temperatures (DS butterflies). Rearing temperature also influences mating benefits and costs. In DS butterflies, mated females live longer than virgin females, and mated males live shorter than virgin males. No such benefits or costs to mating are present in WS butterflies. Given that choosiness and mating costs are rearing temperature dependent in B. anynana, we hypothesized that temperature may also impact male and female incentives to remate in the event that benefits and costs of second matings are similar to those of first matings. We first examined whether lifespan was affected by number of matings. We found that two matings did not significantly increase lifespan for either WS or DS butterflies relative to single matings. However, both sexes of WS but not DS butterflies experienced decreased longevity when mated to a non-virgin relative to a virgin. We next observed pairs of WS and DS butterflies and documented changes in mating behavior in response to changes in the mating status of their partner. WS but not DS butterflies changed their mating behavior in response to the mating status of their partner. These results suggest that rearing temperature influences adult mating behavior plasticity in B. anynana. This developmentally controlled behavioral plasticity may be adaptive, as lifespan depends on the partner’s mating status in one seasonal form, but not in the other.     

A Method of Screening for Genes of Major Effect

This paper describes a method for screening animal populations on an index of calculated probabilities of genotype status at an unknown single locus. Animals selected by such a method might then be candidates in test matings and genetic marker analyses for major gene detection. The method relies on phenotypic measures for a continuous trait plus identification of sire and dam. Some missing phenotypes and missing pedigree information are permitted. The method is an iterative two-step procedure, the first step estimates genotype probabilities and the second step estimates genotypic effects by regressing phenotypes on genotype probabilities, modeled as true genotype status plus error. Prior knowledge or choice of major locus-free heritability for the trait of interest is required, plus initial starting estimates of the effect on phenotype of carrying one and two copies of the unknown gene. Gene frequency can be estimated by this method, but it is demonstrated that the consequences of using an incorrect fixed prior for gene frequency are not particularly adverse where true frequency of the allele with major effect is low. Simulations involving deterministic sampling from the normal distribution lead to convergence for estimates of genotype effects at the true values, for a reasonable range of starting values, illustrating that estimation of major gene effects has a rational basis. In the absence of polygenic effects, stochastic simulations of 600 animals in five generations resulted in estimates of genotypic effects close to the true values. However, stochastic simulations involving generation and fitting of both major genotype and animal polygenic effects showed upward bias in estimates of major genotype effects. This can be partially overcome by not using information from relatives when calculating genotype probabilities-a result which suggests a route to a modified method which is unbiased and yet does use this information.     

The evolution of polyandry: multiple mating and female fitness in insects

Theory suggests that male fitness generally increases steadily with mating rate, while one or a few matings are sufficient for females to maximize their reproductive success. Contrary to these predictions, however, females of the majority of insects mate multiply. We performed a meta-analysis of 122 experimental studies addressing the direct effects of multiple mating on female fitness in insects. Our results clearly show that females gain directly from multiple matings in terms of increased lifetime offspring production. Despite a negative effect of remating on female longevity in species without nuptial feeding, the positive effects (increased egg production rate and fertility) more than outweigh this negative effect for moderate mating rates. The average direct net fitness gain of multiple mating was as high as 30-70%. Therefore, the evolutionary maintenance of polyandry in insects can be understood solely in terms of direct effects. However, our results also strongly support the existence of an intermediate optimal female mating rate, beyond which a further elevated mating rate is deleterious. The existence of such optima implies that sexual conflict over the mating rate should be very common in insects, and that sexually antagonistic coevolution plays a key role in the evolution of mating systems and of many reproductive traits. We discuss the origin and maintenance of nuptial feeing in the light of our findings, and suggest that elaborate and nutritional ejaculates may be the result of sexually antagonistic coevolution. Future research should aim at gaining a quantitative understanding of the evolution of female mating rates. Copyright 2000 The Association for the Study of Animal Behaviour.     

Rapid Range Expansion Is Not Restricted by Inbreeding in a Sexually Cannibalistic Spider

Few studies investigated whether rapid range expansion is associated with an individual''s short-term fitness costs due to an increased risk of inbred mating at the front of expansion. In mating systems with low male mating rates both sexes share potential inbreeding costs and general mechanisms to avoid or reduce these costs are expected. The spider Argiope bruennichi expanded its range recently and we asked whether rapid settlement of new sites exposes individuals to a risk of inbreeding. We sampled four geographically separated subpopulations, genotyped individuals, arranged matings and monitored hatching success. Hatching success was lowest in egg-sacs derived from sibling pairs and highest in egg-sacs derived from among-population crosses, while within-population crosses were intermediate. This indicates that inbreeding might affect hatching success in the wild. Unlike expected, differential hatching success of within- and among-population crosses did not correlate with genetic distance of mating pairs. In contrast, we found high genetic diversity based on 16 microsatellite markers and a fragment of the mitochondrial COI gene in all populations. Our results suggest that even a very recent settlement secures the presence of genetically different mating partners. This leads to costs of inbreeding since the population is not inbred.     

A combination of walk-back and optimum contribution selection in fish: a simulation study

The aim of this paper was to study the performance of a novel fish breeding scheme, which is a combination of walk-back and optimum contribution selection using stochastic simulation. In this walk-back selection scheme, batches of different sizes (50, 100, 1000, 5000 and 10 000) with the phenotypically superior fish from one tank with mixed families were genotyped to set up the pedigree. BLUP estimated breeding values were calculated. The optimum contribution selection method was used with the rate of inbreeding (ΔF) constrained to 0.005 or 0.01 per generation. If the constraint on ΔF could not be held, a second batch of fish was genotyped etc. Compared with the genotyping of all selection candidates (1000, 5000 or 10 000), the use of batches saves genotyping costs. The results show that two batches of 50 fish were often necessary. With a batch size of 100, genetic level was 76–92% of the genetic level achieved for schemes with all fish being genotyped and thus candidates for the optimum contribution selection step. More parents were selected for schemes with larger batches, resulting in a higher genetic gain, especially when all selection candidates were genotyped. There was little extra genetic gain in genotyping of 1000 fish instead of 100 for the larger schemes of 5000 and 10 000 candidates. The accuracy of breeding values was similar for all batch sizes (~0.30), but higher (~0.5) when all candidates were included. Since only the phenotypically most superior fish were genotyped, BLUP-EBV were biased. Compared with genotyping of all selection candidates, the use of batches saves genotyping costs, while simultaneously maintaining high genetic gains.     

Studies on assortative mating. III. The effects of incomplete penetrance in assortative mating systems

Four models of positive and negative assortative mating systems, exclusive or partial, in relation to phenotypes determined by a pair of autosomal alleles with dominance but with incomplete penetrance of the dominant allele in heterozygous state, are presented. By introducing the parameter of incomplete penetrance in the models of assortative matings, matings between individuals with identical genotypes will occur within the negative systems, as well as matings between individuals with different genotypes within the positive assortative mating systems. Thus, incomplete penetrance has the effect of retarding equilibrium on an assortative mating system, making this equilibrium equivalent to a system with a lower degree of assortative mating, where the penetrance equals 1 or 0. Another conclusion of biological interest drawn from the mathematical analysis presented in this paper is that for any value of the penetrance, the frequency of 0.5 for recessive individuals is also typical of exclusive or partial negative assortative mating systems at equilibrium.     

A blocking Gibbs sampling method to detect major genes with phenotypic data from a diallel mating

Diallel mating is a frequently used design for estimating the additive and dominance genetic (polygenic) effects involved in quantitative traits observed in the half- and full-sib progenies generated in plant breeding programmes. Gibbs sampling has been used for making statistical inferences for a mixed-inheritance model (MIM) that includes both major genes and polygenes. However, using this approach it has not been possible to incorporate the genetic properties of major genes with the additive and dominance polygenic effects in a diallel mating population. A parent block Gibbs sampling method was developed in this study to make statistical inferences about the major gene and polygenic effects on quantitative traits for progenies derived from a half-diallel mating design. Using simulated data sets with different major and polygenic effects, the proposed method accurately estimated the major and polygenic effects of quantitative traits, and possible genotypes of parents and progenies. The impact of specifying different prior distributions was examined and was found to have little effect on inference on the posterior distribution. This approach was applied to an experimental data set of Loblolly pine (Pinus taeda L.) derived from a 6-parent half-diallel mating. The result indicated that there might be a recessive major gene affecting height growth in this diallel population.     

Costs and benefits of polyandry in a sexually cannibalistic mantis

Mating with more than one male often provides direct or indirect benefits to female fitness but can also increase the chance of injury and death. Costs of mating are expected to increase linearly with increasing mating number. But how such costs interact with benefits to determine the net payoff of mating multiply is not well understood. Using the highly cannibalistic Springbok mantis, Miomantis caffra, a species where females are stabbed in the abdomen by males during violent premating struggles that males initiate to avoid being cannibalized, we took an experimental approach to assess the economics of polyandry under the risk of external, male-inflicted injury. We predicted that females that mate multiply would be more likely to show abdominal injuries, have higher prereproductive mortality, produce fewer offspring and be more likely to engage in pre-mating cannibalism to avoid unwanted matings. In line with our predictions, we found that the likelihood of abdominal injury was highest among females that mated at least once, and prereproductive death was highest among females that mated twice or three times. Virgin females completely avoided these costs and produced some offspring parthenogenetically but not enough to provide a net benefit. Although mating was better than not mating, there was no singularly optimal mating number: females that mated once and three times produced similarly high numbers of offspring from the first ootheca, which resulted in an intermediate trough in offspring production at two matings. We also found little evidence that cannibalism was deployed as a mate-avoidance strategy: females consistently attacked and consumed males regardless of how many times they mated or how long they were housed with males. Our results suggest the possibility of two distinct mating strategies in M. caffra, where females either mate at a lower frequency to minimize costs or at a higher frequency to maximize benefits. We discuss possible explanations for this bimodal pattern in offspring production.     

Opportunities for female choice in the bed bug Cimex lectularius

Bed bugs are cited as exemplars of sexual conflict because mating can only occur via traumatic insemination. However, past antagonistic coevolution between the sexes does not necessarily preclude current female choice. Here, we investigate opportunities for precopulatory female choice in bed bugs. We examined whether females seek out mating opportunities when they gain the most benefit: when females are virgin and/or have recently fed. But, we found that female mating and feeding status had little effect on female attraction to males and male odor. To determine whether females approach male harborages (home crevices) to seek matings in nature, we investigated where matings occurred among unfamiliar pairs of bed bugs. We found that, despite female attraction to male odor, matings were most likely to take place in the female's harborage rather than the male's harborage. We also examined the effect of feeding on male and female ability to mate. Whereas previous research reported that engorgement impaired female ability to refuse matings, we found that male feeding status had a larger effect on the success of mating encounters than female feeding status. Fed males had poor mating success, suggesting that males may be faced with a trade‐off between mating and feeding.     

An algorithm for efficient constrained mate selection

Background

Mate selection can be used as a framework to balance key technical, cost and logistical issues while implementing a breeding program at a tactical level. The resulting mating lists accommodate optimal contributions of parents to future generations, in conjunction with other factors such as progeny inbreeding, connection between herds, use of reproductive technologies, management of the genetic distribution of nominated traits, and management of allele/genotype frequencies for nominated QTL/markers.

Methods

This paper describes a mate selection algorithm that is widely used and presents an extension that makes it possible to apply constraints on certain matings, as dictated through a group mating permission matrix.

Results

This full algorithm leads to simpler applications, and to computing speed for the scenario tested, which is several hundred times faster than the previous strategy of penalising solutions that break constraints.

Conclusions

The much higher speed of the method presented here extends the use of mate selection and enables implementation in relatively large programs across breeding units.     

No Effect of Male Courtship Intensity on Female Remating in the Butterfly <Emphasis Type="Italic">Pieris napi</Emphasis>

In Pieris napi, female fitness increases with number of matings, but wild females mate at an unexpectedly low rate. From a sexual conflict perspective this could be because males manipulate female remating, or alternatively, because wild females experience costs associated with remating which are not applicable under laboratory conditions. To get an indication which sex controls remating and/or the different sexes’ relative costs and benefits of remating, we here test whether female mating frequency is affected by male courtship intensity. We found no effect on female mating frequency or lifespan. This indicates that (i) females control remating and their optimal mating frequency is lower compared to males, or (ii) males can manipulate female remating. We argue that both these alternatives may apply simultaneously to P. napiand that they are inseparable.     

Cost of mating in male Menochilus sexmaculatus (Fabricius) (Coleoptera: Coccinellidae)

Mating and reproduction not only provide benefits but can also incur substantial costs. An increasing number of recent studies have indicated that mate searching, mating, and ejaculate production requires large amount of energy which can result in high cost to males. Here, we examine the effect of number of matings of males and mating duration on mating and reproductive success in Menochilus sexmaculatus (Coleoptera: Coccinellidae) by subjecting them to 3 consecutive matings of 30, 60, 90 min, and complete mating (a) with no interval and (b) with interval of 24 hr between the matings. The results reveal a reduction in reproductive performance for both the setup and reduction is more when mating is consecutive without gap. This shows that between subsequent matings males require time to recuperate the sperm/ejaculate. As a male engages in a greater number of matings, the time it takes to begin mating when paired with a female increases and the overall duration of mating decreases. However, frequent mating attempts made by males result in reduction in their body weight. Thus, in this ladybird beetle mating and related physiological process consume lots of energy and the body weight of males tend to decrease which further modifies their reproductive performance. The study helps us to identify the cost of mating from male's perspective and indicates that males need to rejuvenate between the matings.