Signatures of selection in Nelore cattle revealed by whole-genome sequencing data.

Nelore cattle breed was farmed worldwide due to its economic importance in the beef market and adaptation to the tropics. In Brazil, purebred Nelore animals (PO) receive a certificate from the breeders' association based on the animal's genealogy and morphological characterization. The top 20 to 30% of the superior animals are eligible to receive the Special Certificate of Identification and Production (CEIP), meaning animals from this category were selected and evaluated in a breeding program to improve economically important traits. We used whole-genome sequencing and approaches based on haplotype differentiation and allelic differentiation to detect regions of selection signatures in Nelore cattle by comparing animals from PO and CEIP categories. From a total of 150 animals, a hierarchical clustering analysis was performed to choose the more unrelated animals from each category (16 PO and 40 CEIP). The hapFLK statistic was performed, and extensions of hapFLK values were investigated considering continuous regions with significant q-values. The Weir and Cockerham's Fst estimator (wcFst) was computed using the GPAT++ software library. The total of 82,326 SNPs with hapFLK values passed the FDR control (q-value<0.05), and 718 segments were target as signatures of selection. A total of 1713 highly differentiated genomic regions were identified based on the segmentFst approach. The signatures of selection were spread across the genome. Annotation of overlapping selection signature regions between the two methods revealed 118 genes in common. A variant located within the 3' region of the BOLA-DRB3 gene was found as a promising candidate polymorphism. Within genomic regions that deserves attention, we found genes previously associated with adaptation to tropical environments (HELB), growth and navel size (HMGA2), fat deposition and domestication (IRAK3), and feed efficiency and postmortem carcass traits (GABRG3). The genes BOLA-DQA2, BOLA-DQB, BOLA-DQA5, BOLA-DQA1, BOLA-DRB3, ENSBTAG00000038397 on chromosome 23 are part of the Bovine Major Histocompatibility Complex (MHC) Class II gene family, representing good candidates for immune response and adaptation to tropical conditions. The BoLA family genes and the interaction of ROBO1 with SLIT genes appeared in the enrichment results. Genomic regions located in intronic regions were also identified and might play a regulatory role in traits under selection in PO and CEIP subpopulations. The regions here identified contribute to our knowledge regarding genes and variants that have an important role in complex traits selected in this breed.

Maiorano AM ，Cardoso DF ，Carvalheiro R ，Júnior GAF ，de Albuquerque LG ，de Oliveira HN ... -  《-》

Copy number variations in BOLA-DQA2, BOLA-DQB, and BOLA-DQA5 show the genomic architecture and haplotype frequency of major histocompatibility complex class II genes in Holstein cows.

Bovine major histocompatibility complex (MHC) class II region contains many genes. The bovine leukocyte antigen (BoLA)-DRB3 was reportedly associated with susceptibility of various phenotypes of infections including bovine leukemia virus-induced lymphoma. However, the association of the remaining genes with various phenotypes has not been clarified due to the complicated genomic structure of the MHC class II region. Thus, in this study, we elucidated the MHC class II genomic structure, including the novel alleles and copy number variations (CNVs). We determined the copy numbers of BOLA-DQA2 (DQA2), BOLA-DQB (DQB2), BOLA-DQA5 (DQA5), BLA-DQB (DQB1), LOC100848815 (DQA1), and BOLA-DRB3 (DRB3) in 127 unrelated Holstein cows by TaqMan copy number assay. The genomes were sequenced using target next-generation sequencing (NGS) based on multiplex polymerase chain reaction. Combining the results of the copy numbers and alleles, we identified the BoLA alleles directly without haplotype estimation. Pairwise linkage disequilibrium (LD) analysis between alleles and genes were performed. The CNVs of DQA2, DQB2, and DQA5 in Holstein cows were detected. The frequency of the whole gene deletion in DQA2, DQB2, and DQA5 was 35.4%, 93.7%, and 93.7%, respectively. After target NGS, we identified 37 alleles in the six genes. Fifteen novel alleles (40.5%) were not registered in the IPD-MHC Database. LD analysis showed strong LD among the DQB2*deletion, DQA5*deletion, and DRB3*27:03 alleles. Our findings will provide important insights into the identification of the BoLA genes associated with various infection-related phenotypes.

Fukunaga K ，Yamashita Y ，Yagisawa T 《-》

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

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. 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. 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.

Naval-Sánchez M ，Porto-Neto LR ，Cardoso DF ，Hayes BJ ，Daetwyler HD ，Kijas J ，Reverter A ... -  《-》

Evidence of positive selection towards Zebuine haplotypes in the BoLA region of Brangus cattle.

The Brangus breed was developed to combine the superior characteristics of both of its founder breeds, Angus and Brahman. It combines the high adaptability to tropical and subtropical environments, disease resistance, and overall hardiness of Zebu cattle with the reproductive potential and carcass quality of Angus. It is known that the major histocompatibility complex (MHC, also known as bovine leucocyte antigen: BoLA), located on chromosome 23, encodes several genes involved in the adaptive immune response and may be responsible for adaptation to harsh environments. The objective of this work was to evaluate whether the local breed ancestry percentages in the BoLA locus of a Brangus population diverged from the estimated genome-wide proportions and to identify signatures of positive selection in this genomic region. For this, 167 animals (100 Brangus, 45 Angus and 22 Brahman) were genotyped using a high-density single nucleotide polymorphism array. The local ancestry analysis showed that more than half of the haplotypes (55.0%) shared a Brahman origin. This value was significantly different from the global genome-wide proportion estimated by cluster analysis (34.7% Brahman), and the proportion expected by pedigree (37.5% Brahman). The analysis of selection signatures by genetic differentiation (F st ) and extended haplotype homozygosity-based methods (iHS and Rsb) revealed 10 and seven candidate regions, respectively. The analysis of the genes located within these candidate regions showed mainly genes involved in immune response-related pathway, while other genes and pathways were also observed (cell surface signalling pathways, membrane proteins and ion-binding proteins). Our results suggest that the BoLA region of Brangus cattle may have been enriched with Brahman haplotypes as a consequence of selection processes to promote adaptation to subtropical environments.

Goszczynski DE ，Corbi-Botto CM ，Durand HM ，Rogberg-Muñoz A ，Munilla S ，Peral-Garcia P ，Cantet RJC ，Giovambattista G ... -  《-》

Identification and diversity of bovine major histocompatibility complex class II haplotypes in Japanese Black and Holstein cattle in Japan.

Bovine leukocyte antigen (BoLA), the major histocompatibility complex of cattle, is one of the most polymorphic gene clusters. We genotyped a population of 109 Japanese Black and 39 Holstein cattle to analyze their BoLA class II haplotypes, BoLA-DRB3 locus, 5 BoLA-DQA loci, and 5 BoLA-DQB loci. We identified 26 previously reported DRB3 alleles, 22 previously reported and 3 new DQA alleles, and 24 previously reported and 6 new DQB alleles. A dendrogram was constructed based on the predicted amino acid sequences of the α1 or β1 domains encoded by BoLA-DQA or -DQB alleles, which revealed that DQA alleles were clustered into 5 loci, whereas DQB alleles could not be clearly assigned to specific DQB loci. The BoLA-DRB3-DQA-DQB haplotypes were sorted by sequential analytical processes, and 42 distinct haplotypes, including 11 previously published haplotypes and 31 novel haplotypes, were defined. Strong linkage disequilibrium was present in the BoLA genes. We also compared DRB3-DQA1 haplotype frequencies between 507 Japanese Black and 143 Holstein cattle. Thirty-nine DRB3-DQA1 haplotypes were identified, including 29 haplotypes from Japanese Black and 22 haplotypes from Holstein cattle. The majority of the haplotypes could be identified in both breeds, although several haplotypes were identified in only a single breed. This is the first report presenting a detailed study of the BoLA class II haplotype in Japanese Black and Holstein cattle in Japan.

Miyasaka T ，Takeshima SN ，Sentsui H ，Aida Y ... -  《-》