The success of fine-scale mapping and genomic selection depends mainly on the strength of linkage disequilibrium (LD) between markers and causal mutations. With Lewontin's measure of LD (known as D'), high levels of LD that extend over several million base pairs have been reported in livestock. However, this measure of LD can be strongly biased upward by small samples and by low allele frequencies. The aim of this study was to characterize the level and extent of LD in Holstein cattle in North America (Canada and the United States for purposes of this study) by using the squared correlation of the alleles at 2 loci (r(2)). The Affymetrix MegAllele GeneChip Bovine Mapping 10K single nucleotide polymorphism (SNP) array was used to genotype 821 bulls, from which 497 were used in the analysis of the extent of LD. A total of 5,564 SNP were used after filtering out SNP with more than 5% of Mendelian inconsistencies, with more than 20% missing genotypes, or with a minor allele frequency of less than 10%. Analysis of syntenic pairs revealed that useful LD (measured as r(2) > 0.3) occurred at distances shorter than 100 kb. Linkage disequilibrium decayed very rapidly, within a few hundred kilobase pairs. In addition, no substantial LD between unlinked loci was found. Using a sliding window analysis, we observed an irregular pattern of LD across the genome. These findings suggest that to capture useful LD, which is required for whole-genome fine mapping and genomic selection, a denser SNP map would be needed.

BackgroundBreeding for enhanced immune response (IR) has been suggested as a tool to improve inherent animal health. Dairy cows with superior antibody-mediated (AMIR) and cell-mediated immune responses (CMIR) have been demonstrated to have a lower occurrence of many diseases including mastitis. Adaptive immune response traits are heritable, and it is, therefore, possible to breed for improved IR, decreasing the occurrence of disease. The objective of this study was to perform genome-wide association studies to determine differences in genetic profiles among Holstein cows classified as High or Low for AMIR and CMIR. From a total of 680 cows with immune response phenotypes, 163 cows for AMIR (81 High and 82 Low) and 140 for CMIR (75 High and 65 Low) were selectively genotyped using the Illumina Bovine SNP50 BeadChip. Results were validated using an unrelated population of 164 Holstein bulls IR phenotyped for AMIR and 146 for CMIR.ResultsA generalized quasi likelihood score method was used to determine single nucleotide polymorphisms (SNP) and chromosomal regions associated with immune response. After applying a 5% chromosomal false discovery rate, 186 SNPs were significantly associated with AMIR. The majority (93%) of significant markers were on chromosome 23, with a similar peak found in the bull population. For CMIR, 21 SNP markers remained significant. Candidate genes within 250,000 base pairs of significant SNPs were identified to determine biological pathways associated with AMIR and CMIR. Various pathways were identified, including the antigen processing and presentation pathway, important in host defense. Candidate genes included those within the bovine Major Histocompatability Complex such as BoLA-DQ, BoLA-DR and the non-classical BoLA-NC1 for AMIR and BoLA-DQ for CMIR, the complement system including C2 and C4 for AMIR and C1q for CMIR, and cytokines including IL-17A, IL17F for AMIR and IL-17RA for CMIR and tumor necrosis factor for both AMIR and CMIR. Additional genes associated with CMIR included galectins 1, 2 and 3, BCL2 and β-defensin.ConclusionsThe significant genetic variation associated with AMIR and CMIR in this study may imply feasibility to include immune response in genomic breeding indices as an approach to improve inherent animal health.

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-Bayesian (via Gibbs sampling) and empirical BLUP (EBLUP) estimation of fixed effects and breeding values were compared by simulation. Combinations of two simulation models (with or without effect of contemporary group (CG)), three selection schemes (random, phenotypic and BLUP selection), two levels of heritability (0.20 and 0.50) and two levels of pedigree information (0% and 15% randomly missing) were considered. Populations consisted of 450 animals spread over six discrete generations. An infinitesimal additive genetic animal model was assumed while simulating data. EBLUP and Bayesian estimates of CG effects and breeding values were, in all situations, essentially the same with respect to Spearman's rank correlation between true and estimated values. Bias and mean square error (MSE) of EBLUP and Bayesian estimates of CG effects and breeding values showed the same pattern over the range of simulated scenarios. Methods were not biased by phenotypic and BLUP selection when pedigree information was complete, albeit MSE of estimated breeding values increased for situations where CG effects were present. Estimation of breeding values by Bayesian and EBLUP was similarly affected by joint effect of phenotypic or BLUP selection and randomly missing pedigree information. For both methods, bias and MSE of estimated breeding values and CG effects substantially increased across generations.breeding value / selection / Bayesian estimation / empirical BLUP / Gibbs sampling

RESUMO -O objetivo deste estudo foi investigar, por meio de dados simulados, o efeito da heterogeneidade de variância residual entre grupos de contemporâneos (GC) sobre as avaliações genéticas de bovinos de corte, e comparar o uso de uma avaliação genética ponderada (R≠Iσ e 2 ) em relação à avaliação que pressupõe homogeneidade de variância (R=Iσ e 2 ). A característica estudada foi ganho de peso pós-desmame corrigido para 345 dias, sendo esta simulada com variância fenotípica de 300 kg 2 e herdabilidade igual a 0,4. A estrutura de um conjunto real de dados foi utilizada para fornecer os GC e os pais referentes às observações de cada animal. Effects of Heterogeneity of Residual Variance among Contemporary Groups on Genetic Evaluation of Beef CattleABSTRACT -The objective of this study was to investigate, via simulated data, the effect of heterogeneity of residual variance among contemporary groups (CG) on genetic evaluation of beef cattle, and to compare a weighted genetic evaluation procedure (R≠Iσ e 2 )with one that assumes homogeneity of variances (R = Iσ e 2 ). Different data sets of postweaning weight gain, adjusted to 345 days, were simulated with and without heterogeneity of residual variance, using a phenotypic variance of 300 kg 2 and a true heritability of 0.4. A real data set was used to provide the CG and parents related to each animal observation. Results showed that, when high levels of heterogeneity of residual variance were considered, animals were selected from CG with higher variability, especially with intense selection. With respect to prediction consistency, non parent animals and cows had their predicted breeding values more affected by heterogeneity of residual variance than sires. The weighed factor used reduced, but did not eliminate, the effect of heterogeneity of residual variance. The results of weighted genetic evaluations were similar or superior to those from evaluations that assumed homogeneity of variances. Even when the variances were homogeneous, the weighed genetic evaluations yielded results that were not inferior than those from the usual evaluations, which assumed homogeneity of variances.

Background Genetic progress for fertility and reproduction traits in dairy cattle has been limited due to the low heritability of most indicator traits. Moreover, most of the quantitative trait loci (QTL) and candidate genes associated with these traits remain unknown. In this study, we used 5.6 million imputed DNA sequence variants (single nucleotide polymorphisms, SNPs) for genome-wide association studies (GWAS) of 18 fertility and reproduction traits in Holstein cattle. Aiming to identify pleiotropic variants and increase detection power, multiple-trait analyses were performed using a method to efficiently combine the estimated SNP effects of single-trait GWAS based on a chi-square statistic. Results There were 87, 72, and 84 significant SNPs identified for heifer, cow, and sire traits, respectively, which showed a wide and distinct distribution across the genome, suggesting that they have relatively distinct polygenic nature. The biological functions of immune response and fatty acid metabolism were significantly enriched for the 184 and 124 positional candidate genes identified for heifer and cow traits, respectively. No known biological function was significantly enriched for the 147 positional candidate genes found for sire traits. The most important chromosomes that had three or more significant QTL identified are BTA22 and BTA23 for heifer traits, BTA8 and BTA17 for cow traits, and BTA4, BTA7, BTA17, BTA22, BTA25, and BTA28 for sire traits. Several novel and biologically important positional candidate genes were strongly suggested for heifer (SOD2, WTAP, DLEC1, PFKFB4, TRIM27, HECW1, DNAH17, and ADAM3A), cow (ANXA1, PCSK5, SPESP1, and JMJD1C), and sire (ELMO1, CFAP70, SOX30, DGCR8, SEPTIN14, PAPOLB, JMJD1C, and NELL2) traits. Conclusions These findings contribute to better understand the underlying biological mechanisms of fertility and reproduction traits measured in heifers, cows, and sires, which may contribute to improve genomic evaluation for these traits in dairy cattle.

Heat stress imposes a challenge to the dairy industry, even in northern latitudes. In this study, publicly available weather station data was combined with test-day records for milk, fat, and protein yields to identify the temperature-humidity index (THI) thresholds at which heat load starts affecting milk production traits in Canadian Holstein cows. Production loss per THI unit above the threshold for each trait was estimated. Test-day records from 2010-2019 from 166,749 cows raised in Ontario and from 221,214 cows raised in Quebec were analyzed. Annual economic losses due to heat stress were estimated from the average losses of fat and protein yields based on the annual average of 156 days with THI exceeding the calculated thresholds. Average thresholds for the daily maximum (THI_max) and daily average (THI_avg) THI estimated across lactations in both provinces were THI_max (THI_avg) 68 (64), 57 (50), and 60 (58) for milk, fat, and protein yield, respectively, indicating that milk components are more sensitive to heat stress. An economic loss of about $34.5 million per year was estimated. Our findings contribute to an initial investigation into the impact of heat stress on the Canadian dairy industry and provides a basis for genetic studies on heat tolerance.

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