Detection of multiple quantitative trait loci and their pleiotropic effects in outbred pig populations.

BACKGROUND: Simultaneous detection of multiple QTLs (quantitative trait loci) may allow more accurate estimation of genetic effects. We have analyzed outbred commercial pig populations with different single and multiple models to clarify their genetic properties and in addition, we have investigated pleiotropy among growth and obesity traits based on allelic correlation within a gamete. METHODS: Three closed populations, (A) 427 individuals from a Yorkshire and Large White synthetic breed, (B) 547 Large White individuals and (C) 531 Large White individuals, were analyzed using a variance component method with one-QTL and two-QTL models. Six markers on chromosome 4 and five to seven markers on chromosome 7 were used. RESULTS: Population A displayed a high test statistic for the fat trait when applying the two-QTL model with two positions on two chromosomes. The estimated heritabilities for polygenic effects and for the first and second QTL were 19%, 17% and 21%, respectively. The high correlation of the estimated allelic effect on the same gamete and QTL test statistics suggested that the two separate QTL which were detected on different chromosomes both have pleiotropic effects on the two fat traits. Analysis of population B using the one-QTL model for three fat traits found a similar peak position on chromosome 7. Allelic effects of three fat traits from the same gamete were highly correlated suggesting the presence of a pleiotropic QTL. In population C, three growth traits also displayed similar peak positions on chromosome 7 and allelic effects from the same gamete were correlated. CONCLUSION: Detection of the second QTL in a model reduced the polygenic heritability and should improve accuracy of estimated heritabilities for both QTLs.

Estimation of the time of divergence between Japanese Mishima Island cattle and other cattle populations using microsatellite DNA markers.

We applied the theory of random genetic drift to determine the divergence history of a closed cattle population over the relatively short timescale of several hundred years. The divergence history of the closed population of Mishima Island cattle, a national natural treasure of Japan, was examined, and the results were compared with historical documents. Inbreeding depression in the isolated population was investigated for body size and fertility. Twenty-one DNA microsatellite markers in Mishima Island cattle and 3 major breeds from the mainland were genotyped. For the mainland breeds, all 21 or 20 markers were segregating. However, nearly half the number of loci (9 of 21) was fixed in the Island cattle. The average number of alleles per locus of Island cattle was markedly lower than that in the mainland breeds. These results support the theory that Island cattle have been isolated for a considerable period of time. The number of generations of isolation was estimated as 14.1-22.6, and the year of divergence was calculated as 1778-1846. In view of these findings, we propose that Island cattle diverged from the mainland population at around 1800 and were isolated for about 200 years. These estimates are in agreement with historical documents showing that divergence occurred between 1672 and 1880. The total inbreeding coefficient of the present population was predicted to be in the range of 0.51-0.60. However, historical reports dated over 100 years do not support changes in fertility, so that there is no evidence for inbreeding depression.

Long-term selection using a single trait criterion, non-destructive deformation, in White Leghorns: Effect over time on genetic parameters for traits related to egg production.

Although non-destructive deformation is relevant for assessing eggshell strength, few long-term selection experiments are documented which use non-destructive deformation as a selection criterion. This study used restricted maximum likelihood-based methods with a four-trait animal model to analyze the effect of non-destructive deformation on egg production, egg weight and sexual maturity in a two-way selection experiment involving 17 generations of White Leghorns. In the strong shell line, corresponding to the line selected for low non-destructive deformation values, the heritability estimates were 0.496 for non-destructive deformation, 0.253 for egg production, 0.660 for egg weight and 0.446 for sexual maturity. In the weak shell line, corresponding to the line selected for high non-destructive deformation values, the heritabilities were 0.372, 0.162, 0.703 and 0.404, respectively. An asymmetric response to selection was observed for non-destructive deformation, egg production and sexual maturity, whereas egg weight decreased for both lines. Using non-destructive deformation to select for stronger eggshell had a small negative effect on egg production and sexual maturity, suggesting the need for breeding programs to balance selection between eggshell traits and egg production traits. However, the analysis of the genetic correlation between non-destructive deformation and egg weight revealed that large eggs are not associated with poor eggshell quality.

Antagonistic genetic correlations for milking traits within the genome of dairy cattle.

Genome-wide association studies can be applied to identify useful SNPs associated with complex traits. Furthermore, regional genomic mapping can be used to estimate regional variance and clarify the genomic relationships within and outside regions but has not previously been applied to milk traits in cattle. We applied both single SNP analysis and regional genomic mapping to investigate SNPs or regions associated with milk yield traits in dairy cattle. The de-regressed breeding values of three traits, total yield (kg) of milk (MLK), fat (FAT), and protein (PRT) in 305 days, from 2,590 Holstein sires in Japan were analyzed. All sires were genotyped with 40,646 single-nucleotide polymorphism (SNP) markers. A genome-wide significant region (P < 0.01) common to all three traits was identified by regional genomic mapping on chromosome (BTA) 14. In contrast, single SNP analysis identified significant SNPs only for MLK and FAT (P < 0.01), but not PRT in the same region. Regional genomic mapping revealed an additional significant region (P < 0.01) for FAT on BTA5 that was not identified by single SNP analysis. The additive whole-genomic effects estimated in the regional genomic mapping analysis for the three traits were positively correlated with one another (0.830-0.924). However, the regional genomic effects obtained by using a window size of 20 SNPs for FAT on BTA14 were negatively correlated (P < 0.01) with the regional genomic effect for MLK (-0.940) and PRT (-0.878). The BTA14 regional effect for FAT also showed significant negative correlations (P < 0.01) with the whole genomic effects for MLK (-0.153), FAT (-0.172), and PRT (-0.181). These negative genomic correlations between loci are consistent with the negative linkage disequilibrium expected for traits under directional selection. Such antagonistic correlations may hamper the fixation of the FAT increasing alleles on BTA14. In summary, regional genomic mapping found more regions associated with milk production traits than did single SNP analysis. In addition, the existence of non-zero covariances between regional and whole genomic effects may influence the detection of regional effects, and antagonistic correlations could hamper the fixation of major genes under intensive selection.

Effects of heat stress on production, somatic cell score and conception rate in Holsteins.

We examined the effects of heat stress (HS) on production traits, somatic cell score (SCS) and conception rate at first insemination (CR) in Holsteins in Japan. We used a total of 228 242 records of milk, fat and protein yields, and SCS for the first three lactations, as well as of CR in heifers and in first- and second-lactation cows that had calved for the first time between 2000 and 2012. Records from 47 prefectural weather stations throughout Japan were used to calculate the temperature-humidity index (THI); areas were categorized into three regional groups: no HS (THI < 72), mild HS (72 ≤ THI < 79), and moderate HS (THI ≥ 79). Trait records from the three HS-region groups were treated as three different traits and trivariate animal models were used. The genetic correlations between milk yields from different HS groups were very high (0.91 to 0.99). Summer calving caused the greatest increase in SCS, and in the first and second lactations this increase became greater as THI increased. In cows, CR was affected by the interaction between HS group and insemination month: with summer and early autumn insemination, there was a reduction in CR, and it was much larger in the mild- and moderate-HS groups than in the no-HS group.

Effect of Long-Term Selection for Non-Destructive Deformation on Egg Shape in White Leghorns.

Several conventional traits, including eggshell thickness, are commonly being improved genetically as a means to increase eggshell strength. At the same time, researchers have come to recognize that factors related to egg geometry, such as egg shape, are important determinants of the variability remaining in eggshell strength, after conventional traits have been considered. Therefore, given that the value of the egg shape index -the egg's width to length ratio-depends highly on the hen strain, it is necessary to examine the relationship between eggshell strength and shape index more closely in a variety of breeds. From this perspective, by using REML methodology under a five-trait animal model, we analyzed a two-way selection experiment for non-destructive eggshell deformation in 31 generations of White Leghorns, to evaluate the effect of selection for eggshell strength on egg shape. In the strong line, which refers to the line that was selected for decreased non-destructive deformation value, the genetic correlation between eggshell breaking strength and shape index was 0.285±0.055, whereas that between non-destructive deformation and shape index was -0.021±0.063. In the weak line, these values were 0.244±0.055 and -0.093±0.060, respectively. The heritability estimates were 0.381±0.033 for non-destructive deformation, 0.349±0.029 for eggshell breaking strength, and 0.544 ±0.027 for shape index in the strong line, and 0.408±0.031, 0.468±0.032, and 0.484±0.028, respectively, in the weak line. The genetic correlation between eggshell breaking strength and shape index suggests that rounder eggs are somewhat more resistant to breakage than more elongated eggs. The moderately high heritability estimates for shape index indicate the potential to improve egg shape through genetic gain.

Quantitative trait loci variation for growth and obesity between and within lines of pigs (Sus scrofa).

The hypothesis that quantitative trait loci (QTL) that explain variation between divergent populations also account for genetic variation within populations was tested using pig populations. Two regions of the porcine genome that had previously been reported to harbor QTL with allelic effects that differed between the modern pig and its wild-type ancestor and between the modern pig and a more distantly related population of Asian pigs were studied. QTL for growth and obesity traits were mapped using selectively genotyped half-sib families from five domesticated modern populations. Strong support was found for at least one QTL segregating in each population. For all five populations there was evidence of a segregating QTL affecting fatness in a region on chromosome 7. These findings confirm that QTL can be detected in highly selected commercial populations and are consistent with the hypothesis that the same chromosome locations that account for variation between populations also explain genetic variation within populations.

Localising loci underlying complex trait variation using Regional Genomic Relationship Mapping.

The limited proportion of complex trait variance identified in genome-wide association studies may reflect the limited power of single SNP analyses to detect either rare causative alleles or those of small effect. Motivated by studies that demonstrate that loci contributing to trait variation may contain a number of different alleles, we have developed an analytical approach termed Regional Genomic Relationship Mapping that, like linkage-based family methods, integrates variance contributed by founder gametes within a pedigree. This approach takes advantage of very distant (and unrecorded) relationships, and this greatly increases the power of the method, compared with traditional pedigree-based linkage analyses. By integrating variance contributed by founder gametes in the population, our approach provides an estimate of the Regional Heritability attributable to a small genomic region (e.g. 100 SNP window covering ca. 1 Mb of DNA in a 300000 SNP GWAS) and has the power to detect regions containing multiple alleles that individually contribute too little variance to be detectable by GWAS as well as regions with single common GWAS-detectable SNPs. We use genome-wide SNP array data to obtain both a genome-wide relationship matrix and regional relationship ("identity by state" or IBS) matrices for sequential regions across the genome. We then estimate a heritability for each region sequentially in our genome-wide scan. We demonstrate by simulation and with real data that, when compared to traditional ("individual SNP") GWAS, our method uncovers new loci that explain additional trait variation. We analysed data from three Southern European populations and from Orkney for exemplar traits - serum uric acid concentration and height. We show that regional heritability estimates are correlated with results from genome-wide association analysis but can capture more of the genetic variance segregating in the population and identify additional trait loci.

Economic effects of using sexed semen in Japanese dairy herds.

Dairy farm agricultural income should increase when sexed semen is used instead of unsexed semen. This study simulated three scenarios: using unsexed semen (N), using X sperm of Holstein and unsexed semen of Japanese Black (H), and using X sperm of Holstein and Y sperm of Japanese Black (HJ). Two management scenarios were considered: conventional management (CONV); and the use of Japanese Black semen with surplus cows to produce F(1) s where sufficient replacement female Holstein calves were obtained for maintenance (MAINT). In CONV, the agricultural incomes of H and HJ were 610,000-2,400,000 yen higher than that of N. The agricultural income increased when the difference in the prices between Holstein males and average F(1) male/female calves was 34,000-50,000 yen, that between Holstein male and female calves was 80,000-110,000 yen, and that between F(1) male and female calves was 50,000-90,000 yen. Therefore, the agricultural income can be increased by using sexed semen to select calves of a more valued breed and sex.

Transformation of QTL genotypic effects to allelic effects.

The genotypic and allelic effect models are equivalent in terms of QTL detection in a simple additive model, but the QTL allelic model has the advantage of providing direct information for marker-assisted selection. However, the allelic matrix is four times as large as the genotypic IBD matrix, causing computational problems, especially in genome scans examining multiple positions. Transformation from genotypic to allelic effects, after estimating the genotypic effects with a smaller IBD matrix, can solve this problem. Although the validity of transformation from genotypic to allelic effects has been disputed, this work proves that transformation can successfully yield unique allelic effects when genotypic and allelic IBD matrixes exist.

Further mapping of quantitative trait loci for postnatal growth in an inter-sub-specific backcross of wild Mus musculus castaneus and C57BL/6J mice.

We performed a quantitative trait locus (QTL) analysis of eight body weights recorded weekly from 3 weeks to 10 weeks after birth and two weight gains recorded between 3 weeks and 6 weeks, and between 6 weeks and 10 weeks in an inter-sub-specific backcross population of wild Mus musculus castaneus mice captured in the Philippines and the common inbred strain C57BL/6J ( M. musculus domesticus ), to elucidate the complex genetic architecture of body weight and growth. Interval mapping identified 17 significant QTLs with main effects on 11 chromosomes. In particular, the main effect of the most potent QTL on proximal chromosome 2 increased linearly with age, whereas other QTLs exerted effects on either the early or late growth period. Surprisingly, although wild mice displayed 60% of the body size of their C57BL/6J counterparts, the wild-derived allele enhanced growth at two QTLs. Interestingly, five of the 17 main-effect QTLs identified had significant epistatic interaction effects. Five new epistatic QTLs with no main effects were identified on different chromosomes or regions. For one pair of epistatic QTLs, mice that were heterozygous for the wild-derived allele at one QTL and homozygous for that allele at another QTL exhibited the most rapid growth in all four possible genotypic combinations. Out of the identified QTLs, several showed significant sex-specific effects.

QTL detection and allelic effects for growth and fat traits in outbred pig populations.

Quantitative trait loci (QTL) for growth and fatness traits have previously been identified on chromosomes 4 and 7 in several experimental pig populations. The segregation of these QTL in commercial pigs was studied in a sample of 2713 animals from five different populations. Variance component analysis (VCA) using a marker-based identity by descent (IBD) matrix was applied. The IBD coefficient was estimated with simple deterministic (SMD) and Markov chain Monte Carlo (MCMC) methods. Data for two growth traits, average daily gain on test and whole life daily gain, and back fat thickness were analysed. With both methods, seven out of 26 combinations of population, chromosome and trait, were significant. Additionally, QTL genotypic and allelic effects were estimated when the QTL effect was significant. The range of QTL genotypic effects in a population varied from 4.8% to 10.9% of the phenotypic mean for growth traits and 7.9% to 19.5% for back fat trait. Heritabilities of the QTL genotypic values ranged from 8.6% to 18.2% for growth traits, and 14.5% to 19.2% for back fat. Very similar results were obtained with both SMD and MCMC. However, the MCMC method required a large number of iterations, and hence computation time, especially when the QTL test position was close to the marker.