Genome-wide association study between copy number variants and hoof health traits in Holstein dairy cattle.

Genome-wide association studies based on SNP have been completed for multiple traits in dairy cattle; however, copy number variants (CNV) could add genomic information that has yet to be harnessed. The objectives of this study were to identify CNV in genotyped Holstein animals and assess their association with hoof health traits using deregressed estimated breeding values as pseudophenotypes. A total of 23,256 CNV comprising 1,645 genomic regions were identified in 5,845 animals. Fourteen genomic regions harboring structural variations, including 9 deletions and 5 duplications, were associated with at least 1 of the studied hoof health traits. This group of traits included digital dermatitis, interdigital dermatitis, heel horn erosion, sole ulcer, white line lesion, sole hemorrhage, and interdigital hyperplasia; no regions were associated with toe ulcer. Twenty candidate genes overlapped with the regions associated with these traits including SCART1, NRXN2, KIF26A, GPHN, and OR7A17. In this study, an effect on infectious hoof lesions could be attributed to the PRAME (Preferentially Expressed Antigen in Melanoma) gene. Almost all genes detected in association with noninfectious hoof lesions could be linked to known metabolic disorders. The knowledge obtained considering information of associated CNV to the traits of interest in this study could improve the accuracy of estimated breeding values. This may further increase the genetic gain for these traits in the Canadian Holstein population, thus reducing the involuntary animal losses due to lameness.

Selection signatures in tropical cattle are enriched for promoter and coding regions and reveal missense mutations in the damage response gene HELB.

BACKGROUND: Distinct domestication events, adaptation to different climatic zones, and divergent selection in productive traits have shaped the genomic differences between taurine and indicine cattle. In this study, we assessed the impact of artificial selection and environmental adaptation by comparing whole-genome sequences from European taurine and Asian indicine breeds and from African cattle. Next, we studied the impact of divergent selection by exploiting predicted and experimental functional annotation of the bovine genome. RESULTS: We identified selective sweeps in beef cattle taurine and indicine populations, including a 430-kb selective sweep on indicine cattle chromosome 5 that is located between 47,670,001 and 48,100,000 bp and spans five genes, i.e. HELB, IRAK3, ENSBTAG00000026993, GRIP1 and part of HMGA2. Regions under selection in indicine cattle display significant enrichment for promoters and coding genes. At the nucleotide level, sites that show a strong divergence in allele frequency between European taurine and Asian indicine are enriched for the same functional categories. We identified nine single nucleotide polymorphisms (SNPs) in coding regions that are fixed for different alleles between subspecies, eight of which were located within the DNA helicase B (HELB) gene. By mining information from the 1000 Bull Genomes Project, we found that HELB carries mutations that are specific to indicine cattle but also found in taurine cattle, which are known to have been subject to indicine introgression from breeds, such as N'Dama, Anatolian Red, Marchigiana, Chianina, and Piedmontese. Based on in-house genome sequences, we proved that mutations in HELB segregate independently of the copy number variation HMGA2-CNV, which is located in the same region. CONCLUSIONS: Major genomic sequence differences between Bos taurus and Bos indicus are enriched for promoter and coding regions. We identified a 430-kb selective sweep in Asian indicine cattle located on chromosome 5, which carries SNPs that are fixed in indicine populations and located in the coding sequences of the HELB gene. HELB is involved in the response to DNA damage including exposure to ultra-violet light and is associated with reproductive traits and yearling weight in tropical cattle. Thus, HELB likely contributed to the adaptation of tropical cattle to their harsh environment.

Genome-wide scan reveals population stratification and footprints of recent selection in Nelore cattle.

BACKGROUND: This study aimed at (1) assessing the genomic stratification of experimental lines of Nelore cattle that have experienced different selection regimes for growth traits, and (2) identifying genomic regions that have undergone recent selection. We used a sample of 763 animals genotyped with the Illumina BovineHD BeadChip, among which 674 animals originated from two lines that are maintained under directional selection for increased yearling body weight and 89 animals from a control line that is maintained under stabilizing selection. RESULTS: Multidimensional analysis of the genomic dissimilarity matrix and admixture analysis revealed a substantial level of population stratification between the directional selection lines and the stabilizing selection control line. Two of the three tests used to detect selection signatures (FST, XP-EHH and iHS) revealed six candidate regions with indications of selection, which strongly indicates truly positive signals. The set of identified candidate genes included several genes with roles that are functionally related to growth metabolism, such as COL14A1, CPT1C, CRH, TBC1D1, and XKR4. CONCLUSIONS: The current study identified genetic stratification that resulted from almost four decades of divergent selection in an experimental Nelore population, and highlighted autosomal genomic regions that present patterns of recent selection. Our findings provide a basis for a better understanding of the metabolic mechanism that underlies the growth traits, which are modified by selection for yearling body weight.

Genomic prediction with epistasis models: on the marker-coding-dependent performance of the extended GBLUP and properties of the categorical epistasis model (CE).

BACKGROUND: Epistasis marker effect models incorporating products of marker values as predictor variables in a linear regression approach (extended GBLUP, EGBLUP) have been assessed as potentially beneficial for genomic prediction, but their performance depends on marker coding. Although this fact has been recognized in literature, the nature of the problem has not been thoroughly investigated so far. RESULTS: We illustrate how the choice of marker coding implicitly specifies the model of how effects of certain allele combinations at different loci contribute to the phenotype, and investigate coding-dependent properties of EGBLUP. Moreover, we discuss an alternative categorical epistasis model (CE) eliminating undesired properties of EGBLUP and show that the CE model can improve predictive ability. Finally, we demonstrate that the coding-dependent performance of EGBLUP offers the possibility to incorporate prior experimental information into the prediction method by adapting the coding to already available phenotypic records on other traits. CONCLUSION: Based on our results, for EGBLUP, a symmetric coding {-1,1} or {-1,0,1} should be preferred, whereas a standardization using allele frequencies should be avoided. Moreover, CE can be a valuable alternative since it does not possess the undesired theoretical properties of EGBLUP. However, which model performs best will depend on characteristics of the data and available prior information. Data from previous experiments can for instance be incorporated into the marker coding of EGBLUP.

Study of whole genome linkage disequilibrium in Nellore cattle.

BACKGROUND: Knowledge of the linkage disequilibrium (LD) between markers is important to establish the number of markers necessary for association studies and genomic selection. The objective of this study was to evaluate the extent of LD in Nellore cattle using a high density SNP panel and 795 genotyped steers. RESULTS: After data editing, 446,986 SNPs were used for the estimation of LD, comprising 2508.4 Mb of the genome. The mean distance between adjacent markers was 4.90 ± 2.89 kb. The minor allele frequency (MAF) was less than 0.20 in a considerable proportion of SNPs. The overall mean LD between marker pairs measured by r(2) and |D'| was 0.17 and 0.52, respectively. The LD (r(2)) decreased with increasing physical distance between markers from 0.34 (1 kb) to 0.11 (100 kb). In contrast to this clear decrease of LD measured by r(2), the changes in |D'| indicated a less pronounced decline of LD. Chromosomes BTA1, BTA27, BTA28 and BTA29 showed lower levels of LD at any distance between markers. Except for these four chromosomes, the level of LD (r(2)) was higher than 0.20 for markers separated by less than 20 kb. At distances < 3 kb, the level of LD was higher than 0.30. The LD (r(2)) between markers was higher when the MAF threshold was high (0.15), especially when the distance between markers was short. CONCLUSIONS: The level of LD estimated for markers separated by less than 30 kb indicates that the High Density Bovine SNP BeadChip will likely be a suitable tool for prediction of genomic breeding values in Nellore cattle.

Association of ADIPOQ, OLR1 and PPARGC1A gene polymorphisms with growth and carcass traits in Nelore cattle.

In beef cattle farming, growth and carcass traits are important for genetic breeding programs. Molecular markers can be used to assist selection and increase genetic gain. The ADIPOQ, OLR1 and PPARGC1A genes are involved in lipid synthesis and fat accumulation in adipose tissue. The objective of this study was to identify polymorphisms in these genes and to assess the association with growth and carcass traits in Nelore cattle. A total of 639 animals were genotyped by PCR-RFLP for rs208549452, rs109019599 and rs109163366 in ADIPOQ, OLR1 and PPARGC1A gene, respectively. We analyzed the association of SNPs identified with birth weight, weaning weight, female yearling weight, female hip height, male yearling weight, male hip height, loin eye area, rump fat thickness, and backfat thickness. The OLR1 marker was associated with rump fat thickness and weaning weight (P < 0.05) and the PPARGC1 marker was associated with female yearling weight.