Analysis of genetic diversity in Brown Swiss, Jersey and Holstein populations using genome-wide single nucleotide polymorphism markers

BACKGROUND: Studies of genetic diversity are essential in understanding the extent of differentiation between breeds, and in designing successful diversity conservation strategies. The objective of this study was to evaluate the level of genetic diversity within and between North American Brown Swiss (BS, n = 900), Jersey (JE, n = 2,922) and Holstein (HO, n = 3,535) cattle, using genotyped bulls. GENEPOP and FSTAT software were used to evaluate the level of genetic diversity within each breed and between each pair of the three breeds based on genome-wide SNP markers (n = 50,972). RESULTS: Hardy-Weinberg equilibrium (HWE) exact test within breeds showed a significant deviation from equilibrium within each population (P < 0.01), which could be a result of selection, genetic drift and inbreeding within each breed. Hardy-Weinberg test also confirmed significant heterozygote deficit in each breed over several loci. Moreover, results from population differentiation tests showed that the majority of loci have alleles or genotypes drawn from different distributions in each breed. Average gene diversity, expressed in terms of observed heterozygosity, over all loci in BS, JE and HO was 0.27, 0.26 and 0.31, respectively. The proportion of genetic diversity due to allele frequency differences among breeds (F(st)) indicated that the combination of BS and HO in an ideally amalgamated population had higher genetic diversity than the other pairs of breeds. CONCLUSION: Results suggest that the three bull populations have substantially different gene pools. BS and HO show the largest gene differentiation and jointly the highest total expected gene diversity compared to when JE is considered. If the loss of genetic diversity within breeds worsens in the future, the use of crossbreeding might be an option to recover genetic diversity, especially for the breeds with small population size

Characteristics of linkage disequilibrium in North American Holsteins

<p>Abstract</p> <p>Background</p> <p>Effectiveness of genomic selection and fine mapping is determined by the level of linkage disequilibrium (LD) across the genome. Knowledge of the range of genome-wide LD, defined as a non-random association of alleles at different loci, can provide an insight into the optimal density and location of single-nucleotide polymorphisms (SNPs) for genome-wide association studies and can be a keystone for interpretation of results from QTL mapping.</p> <p>Results</p> <p>Linkage disequilibrium was measured by |D'| and r²between 38,590 SNPs (spaced across 29 bovine autosomes and the X chromosome) using genotypes of 887 Holstein bulls. The average level of |D'| and r²for markers 40-60 kb apart was 0.72 and 0.20, respectively in Holstein cattle. However, a high degree of heterogeneity of LD was observed across the genome. The sample size and minor allele frequency had an effect on |D'| estimates, however, r²was not noticeably affected by these two factors. Syntenic LD was shown to be useful for verifying the physical location of SNPs. No differences in the extent of LD and decline of LD with distance were found between the intragenic and intergenic regions.</p> <p>Conclusions</p> <p>A minimal sample size of 444 and 55 animals is required for an accurate estimation of LD by |D'| and r², respectively. The use of only maternally inherited haplotypes is recommended for analyses of LD in populations consisting of large paternal half-sib families. Large heterogeneity in the pattern and the extent of LD in Holstein cattle was observed on both autosomes and the X chromosome. The extent of LD was higher on the X chromosome compared to the autosomes.</p

Comparison of statistical procedures for estimating polygenic effects using dense genome-wide marker data

In this study we compared different statistical procedures for estimating SNP effects using the simulated data set from the XII QTL-MAS workshop. Five procedures were considered and tested in a reference population, i.e., the first four generations, from which phenotypes and genotypes were available. The procedures can be interpreted as variants of ridge regression, with different ways for defining the shrinkage parameter. Comparisons were made with respect to the correlation between genomic and conventional estimated breeding values. Moderate correlations were obtained from all methods. Two of them were used to predict genomic breeding values in the last three generations. Correlations between these and the true breeding values were also moderate. We concluded that the ridge regression procedures applied in this study did not outperform the simple use of a ratio of variances in a mixed model method, both providing moderate accuracies of predicted genomic breeding values

Identification of single nucleotide polymorphisms in bovine CARD15 and their associations with health and production traits in Canadian Holsteins

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor-2 (TLR2) and Caspase Recruitment Domain 15 (CARD15) are important pattern recognition receptors that play a role in the initiation of the inflammatory and subsequent immune response. They have been previously identified as susceptibility loci for inflammatory bowel diseases in humans and are, therefore, suitable candidate genes for inflammatory disease resistance in cattle. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the bovine <it>TLR2 </it>and <it>CARD15 </it>and evaluate the association of these SNPs with health and production traits in a population of Canadian Holstein bulls.</p> <p>Results</p> <p>A selective DNA pool was constructed based on the estimated breeding values (EBVs) for SCS. Gene segments were amplified from this pool in PCR reactions and the amplicons sequenced to reveal polymorphisms. A total of four SNPs, including one in intron 10 (c.2886-14A>G) and three in the exon 12 (c.3020A>T, c.4500A>C and c.4950C>T) were identified in <it>CARD15</it>; none were identified in <it>TLR2</it>. Canadian Holstein bulls (n = 338) were genotyped and haplotypes were reconstructed. Two SNPs, c.3020A>T and c.4500A>C, were associated with EBVs for health and production traits. The SNP, c.3020A>T, for example, was associated with SCS EBVs (p = 0.0097) with an allele substitution effect of 0.07 score. When compared to the most frequent haplotype Hap12(AC), Hap22(TC) was associated with increased milk (p < 0.0001) and protein (p = 0.0007) yield EBVs, and hap21(TA) was significantly associated with increased SCS EBV(p = 0.0120). All significant comparison-wise associations retained significance at 8% experimental-wise level by permutation test.</p> <p>Conclusion</p> <p>This study indicates that SNP c.3020A>T might play a role in the host response against mastitis and further detailed studies are needed to understand its functional mechanisms.</p

Accuracy of genomic selection in simulated populations mimicking the extent of linkage disequilibrium in beef cattle

<p>Abstract</p> <p>Background</p> <p>The success of genomic selection depends mainly on the extent of linkage disequilibrium (LD) between markers and quantitative trait loci (QTL), the number of animals in the training set (TS) and the heritability (h²) of the trait. The extent of LD depends on the genetic structure of the population and the density of markers. The aim of this study was to calculate accuracy of direct genomic estimated breeding values (DGEBV) using best linear unbiased genomic prediction (GBLUP) for different marker densities, heritabilities and sizes of the TS in simulated populations that mimicked previously reported extent and pattern of LD in beef cattle.</p> <p>Results</p> <p>The accuracy of DGEBV increased significantly (p < 0.05) with the increase in the number of bulls in the TS (480, 960 or 1920), trait h²(0.10, 0.25 or 0.40) and marker densities (40 k or 800 k). Increasing the number of animals in the TS by 4-fold and using their phenotypes to estimate marker effects was not sufficient to maintain or increase the accuracy of DGEBV obtained using estimated breeding values (EBVs) when the trait h²was lower than 0.40 for both marker densities. Comparing to expected accuracies of parent average (PA), the gains by using DGEBV would be of 27%, 13% and 10% for trait h²equal to 0.10, 0.25 and 0.40, respectively, considering the scenario with 40 k markers and 1920 bulls in TS.</p> <p>Conclusions</p> <p>As reported in dairy cattle, the size of the TS and the extent of LD have major impact on the accuracy of DGEBV. Based on the findings of this simulation study, large TS, as well as dense marker panels, aiming to increase the level of LD between markers and QTL, will likely be needed in beef cattle for successful implementation of genomic selection.</p

Polymorphisms in the gene encoding bovine interleukin-10 receptor alpha are associated with Mycobacterium avium ssp. paratuberculosis infection status

<p>Abstract</p> <p>Background</p> <p>Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by <it>Mycobacterium avium </it>ssp. <it>paratuberculosis </it>(MAP). Since this pathogen has been implicated in the pathogenesis of human IBDs, the goal of this study was to assess whether single nucleotide polymorphism (SNPs) in several well-known candidate genes for human IBD are associated with susceptibility to MAP infection in dairy cattle.</p> <p>Methods</p> <p>The bovine candidate genes, <it>interleukin-10 (IL10), IL10 receptor alpha/beta (IL10RA/B), transforming growth factor beta 1 (TGFB1)</it>, <it>TGFB receptor class I/II (TGFBR1/2)</it>, and <it>natural resistance-associated macrophage protein 1 (SLC11A1) </it>were sequenced for SNP discovery using pooled DNA samples, and the identified SNPs were genotyped in a case-control association study comprised of 242 MAP negative and 204 MAP positive Holstein dairy cattle. Logistic regression was used to determine the association of SNPs and reconstructed haplotypes with MAP infection status.</p> <p>Results</p> <p>A total of 13 SNPs were identified. Four SNPs in <it>IL10RA </it>(984G > A, 1098C > T, 1269T > C, and 1302A > G) were tightly linked, and showed a strong additive and dominance relationship with MAP infection status. Haplotypes AGC and AAT, containing the SNPs <it>IL10RA </it>633C > A, 984G > A and 1185C > T, were associated with an elevated and reduced likelihood of positive diagnosis by serum ELISA, respectively.</p> <p>Conclusions</p> <p>SNPs in <it>IL10RA </it>are associated with MAP infection status in dairy cattle. The functional significance of these SNPs warrants further investigation.</p

Estimation of Genetic Parameters of Heat Tolerance for Production Traits in Canadian Holsteins Cattle.

Understanding how cows respond to heat stress has helped to provide effective herd management practices to tackle this environmental challenge. The possibility of selecting animals that are genetically more heat tolerant may provide additional means to maintain or even improve the productivity of the Canadian dairy industry, which is facing a shifting environment due to climate changes. The objective of this study was to estimate the genetic parameters for heat tolerance of milk, fat, and protein yields in Canadian Holstein cows. A total of 1.3 million test-day records from 195,448 first-parity cows were available. A repeatability test-day model fitting a reaction norm on the temperature-humidity index (THI) was used to estimate the genetic parameters. The estimated genetic correlations between additive genetic effect for production and for heat tolerance ranged from -0.13 to -0.21, indicating an antagonistic relationship between the level of production and heat tolerance. Heritability increased marginally as THI increased above its threshold for milk yield (0.20 to 0.23) and protein yield (0.14 to 0.16) and remained constant for fat yield (0.17). A Spearman rank correlation between the estimated breeding values under thermal comfort and under heat stress showed a potential genotype by environmental interaction. The existence of a genetic variability for heat tolerance allows for the selection of more heat tolerant cows

Identification of unique ROH regions with unfavorable effects on production and fertility traits in Canadian Holsteins

Background: The advent of genomic information and the reduction in the cost of genotyping have led to the use of genomic information to estimate genomic inbreeding as an alternative to pedigree inbreeding. Using genomic measures, effects of genomic inbreeding on production and fertility traits have been observed. However, there have been limited studies on the specific genomic regions causing the observed negative association with the trait of interest. Our aim was to identify unique run of homozygosity (ROH) genotypes present within a given genomic window that display negative associations with production and fertility traits and to quantify the effects of these identified ROH genotypes. Methods: In total, 50,575 genotypes based on a 50K single nucleotide polymorphism (SNP) array and 259,871 pedigree records were available. Of these 50,575 genotypes, 46,430 cows with phenotypic records for production and fertility traits and having a first calving date between 2008 and 2018 were available. Unique ROH genotypes identified using a sliding-window approach were fitted into an animal mixed model as fixed effects to determine their effect on production and fertility traits. Results: In total, 133 and 34 unique ROH genotypes with unfavorable effects were identified for production and fertility traits, respectively, at a 1% genome-wise false discovery rate. Most of these ROH regions were located on bovine chromosomes 8, 13, 14 and 19 for both production and fertility traits. For production traits, the average of all the unfavorably identified unique ROH genotypes effects were estimated to decrease milk yield by 247.30 kg, fat yield by 11.46 kg and protein yield by 8.11 kg. Similarly, for fertility traits, an average 4.81-day extension in first service to conception, a 0.16 increase in number of services, and a - 0.07 incidence in 56-day non-return rate were observed. Furthermore, a ROH region located on bovine chromosome 19 was identified that, when homozygous, had a negative effect on production traits. Signatures of selection proximate to this region have implicated GH1 as a potential candidate gene, which encodes the growth hormone that binds the growth hormone receptor. This observed negative effect could be a consequence of unfavorable alleles in linkage disequilibrium with favorable alleles. Conclusions: ROH genotypes with unfavorable effects on production and fertility traits were identified within and across multiple traits on most chromosomes. These identified ROH genotypes could be included in mate selection programs to minimize their frequency in future generations

Parent-offspring genotyped trios unravelling genomic regions with gametic and genotypic epistatic transmission bias on the cattle genome

Several biological mechanisms affecting the sperm and ova fertility and viability at developmental stages of the reproductive cycle resulted in observable transmission ratio distortion (i.e., deviation from Mendelian expectations). Gene-by-gene interactions (or epistasis) could also potentially cause specific transmission ratio distortion patterns at different loci as unfavorable allelic combinations are under-represented, exhibiting deviation from Mendelian proportions. Here, we aimed to detect pairs of loci with epistatic transmission ratio distortion using 283,817 parent-offspring genotyped trios (sire-dam-offspring) of Holstein cattle. Allelic and genotypic parameterization for epistatic transmission ratio distortion were developed and implemented to scan the whole genome. Different epistatic transmission ratio distortion patterns were observed. Using genotypic models, 7, 19 and 6 pairs of genomic regions were found with decisive evidence with additive-by-additive, additive-by-dominance/dominance-by-additive and dominance-by-dominance effects, respectively. Using the allelic transmission ratio distortion model, more insight was gained in understanding the penetrance of single-locus distortions, revealing 17 pairs of SNPs. Scanning for the depletion of individuals carrying pairs of homozygous genotypes for unlinked loci, revealed 56 pairs of SNPs with recessive epistatic transmission ratio distortion patterns. The maximum number of expected homozygous offspring, with none of them observed, was 23. Finally, in this study, we identified candidate genomic regions harboring epistatic interactions with potential biological implications in economically important traits, such as reproduction

Genome-wide association study for milk production and conformation traits in Canadian Alpine and Saanen dairy goats.

Increasing the productivity of Canadian dairy goats is critical to the competitiveness of the sector; however, little is known about the underlying genetic architecture of economically important traits in these populations. Consequently, the objectives of this study were as follows: (1) to perform a single-step GWAS for milk production traits (milk, protein, and fat yields, and protein and fat percentages in first and later lactations) and conformation traits (body capacity, dairy character, feet and legs, fore udder, general appearance, rear udder, suspensory ligament, and teats) in the Canadian Alpine and Saanen breeds; and (2) to identify positional and functional candidate genes related to these traits. The data available for analysis included 305-d milk production records for 6,409 Alpine and 3,434 Saanen does in first lactation and 5,827 Alpine and 2,632 Saanen does in later lactations; as well as linear type conformation records for 5,158 Alpine and 2,342 Saanen does. Genotypes were available for 833 Alpine and 874 Saanen animals. Both single-breed and multiple-breed GWAS were performed using single-trait animal models. Positional and functional candidate genes were then identified in downstream analyses. The GWAS identified 189 unique SNP that were significant at the chromosomal level, corresponding to 271 unique positional candidate genes within 50 kb up- and downstream, across breeds and traits. This study provides evidence for the economic importance of several candidate genes (e.g., CSN1S1, CSN2, CSN1S2, CSN3, DGAT1, and ZNF16) in the Canadian Alpine and Saanen populations that have been previously reported in other dairy goat populations. Moreover, several novel positional and functional candidate genes (e.g., RPL8, DCK, and MOB1B) were also identified. Overall, the results of this study have provided greater insight into the genetic architecture of milk production and conformation traits in the Canadian Alpine and Saanen populations. Greater understanding of these traits will help to improve dairy goat breeding programs