Genome-wide association for milk urea concentration in Dual-Purpose Belgian Blue cows.

The objectives of this study were to estimate genetic parameters and identify genomic regions associated with milk urea concentration (MU) in Dual-Purpose Belgian Blue (DPBB) cows. The data were 29,693 test-day records of milk yield (MY), fat yield (FY), protein yield (PY), fat percentage (FP), protein percentage (PP) and MU collected between 2014 and 2020 on 2498 first parity cows (16,935 test-day records) and 1939 second-parity cows (12,758 test-day records) from 49 herds in the Walloon Region of Belgium. Data of 28,266 single nucleotide polymorphisms (SNP), located on 29 Bos taurus autosomes (BTA), on 1699 animals (639 males and 1060 females) were used. Random regression test-day models were used to estimate genetic parameters through the Bayesian Gibbs sampling method using a single chain of 100,000 iterations after a burn-in period of 20,000. SNP solutions were estimated using a single-step genomic best linear unbiased prediction approach. The proportion of genetic variance explained by windows of 25 consecutive SNPs (with an average size of ~2 Mb) was calculated, and regions accounting for at least 1.0% of the total additive genetic variance were used to search for candidate genes. The mean (SD) of MU was 22.89 (10.07) and 22.35 (10.07) mg/dl for first and second parity, respectively. The mean (SD) heritability estimates for daily MU were 0.18 (0.01) and 0.22 (0.02), for first and second parity, respectively. The mean (SD) genetic correlations between daily MU and MY, FY, PY, FP and PP were -0.05 (0.09), -0.07 (0.11), -0.03 (0.13), -0.05 (0.08) and -0.03 (0.11) for first parity, respectively. The corresponding values estimated for second parity were 0.02 (0.10), -0.02 (0.09), 0.02 (0.08), -0.08 (0.06) and -0.05 (0.05). The genome-wide association analyses identified three genomic regions (BTA2, BTA3 and BTA13) associated with MU. The identified regions showed contrasting results between parities and among different stages within each parity. This suggests that different groups of candidate genes underlie the phenotypic expression of MU between parities and among different lactation stages within a parity. The results of this study can be used for future implementation and use of genomic evaluation to reduce MU in DPBB cows.

Development of a genomic tool for breed assignment by comparison of different classification models: Application to three local cattle breeds.

Assignment of individual cattle to a specific breed can often not rely on pedigree information. This is especially the case for local breeds for which the development of genomic assignment tools is required to allow individuals of unknown origin to be included to their herd books. A breed assignment model can be based on two specific stages: (a) the selection of breed-informative markers and (b) the assignment of individuals to a breed with a classification method. However, the performance of combination of methods used in these two stages has been rarely studied until now. In this study, the combination of 16 different SNP panels with four classification methods was developed on 562 reference genotypes from 12 cattle breeds. Based on their performances, best models were validated on three local breeds of interest. In cross-validation, 14 models had a global cross-validation accuracy higher than 90%, with a maximum of 98.22%. In validation, best models used 7,153 or 2,005 SNPs, based on a partial least squares-discriminant analysis (PLS-DA) and assigned individuals to breeds based on nearest shrunken centroids. The average validation sensitivity of the first two best models for the three local breeds of interest were 98.33% and 97.5%. Moreover, results reported in this study suggest that further studies should consider the PLS-DA method when selecting breed-informative SNPs.

Performances of Adaptive MultiBLUP, Bayesian regressions, and weighted-GBLUP approaches for genomic predictions in Belgian Blue beef cattle.

BACKGROUND: Genomic selection has been successfully implemented in many livestock and crop species. The genomic best linear unbiased predictor (GBLUP) approach, assigning equal variance to all SNP effects, is one of the reference methods. When large-effect variants contribute to complex traits, it has been shown that genomic prediction methods that assign a higher variance to subsets of SNP effects can achieve higher prediction accuracy. We herein compared the efficiency of several such approaches, including the Adaptive MultiBLUP (AM-BLUP) that uses local genomic relationship matrices (GRM) to automatically identify and weight genomic regions with large effects, to predict genetic merit in Belgian Blue beef cattle. RESULTS: We used a population of approximately 10,000 genotyped cows and their phenotypes for 14 traits, mostly related to muscular development and body dimensions. According to the trait, we found that 4 to 25% of the genetic variance could be associated with 2 to 12 genomic regions harbouring large-effect variants. Noteworthy, three previously identified recessive deleterious variants presented heterozygote advantage and were among the most significant SNPs for several traits. The AM-BLUP resulted in increased reliability of genomic predictions compared to GBLUP (+ 2%), but Bayesian methods proved more efficient (+ 3%). Overall, the reliability gains remained thus limited although higher gains were observed for skin thickness, a trait affected by two genomic regions having particularly large effects. Higher accuracies than those from the original AM-BLUP were achieved when applying the Bayesian Sparse Linear Mixed Model to pre-select groups of SNPs with large effects and subsequently use their estimated variance to build a weighted GRM. Finally, the single-step GBLUP performed best and could be further improved (+ 3% prediction accuracy) by using these weighted GRM. CONCLUSIONS: The AM-BLUP is an attractive method to automatically identify and weight genomic regions with large effects on complex traits. However, the method was less accurate than Bayesian methods. Overall, weighted methods achieved modest accuracy gains compared to GBLUP. Nevertheless, the computational efficiency of the AM-BLUP might be valuable at higher marker density, including with whole-genome sequencing data. Furthermore, weighted GRM are particularly useful to account for large variance loci in the single-step GBLUP.

Highly effective SNP-based association mapping and management of recessive defects in livestock.

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.