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

Abstract

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.

Transcriptional Features of Cattle Visceral and Subcutaneous Adipose Tissues: A Study of RNA-seq

“…We found many DEGs that are involved in immune response-related processes. BoLA-DQA1 and BoLA-DQB are two BoLA (bovine leukocyte antigen) class II molecules, which can present antigen to bovine CD4 + T cell lymphocytes and play an important role in immune responses to infectious pathogens [27] [28]. Both BoLA-DQA1 and BoLA-DQB were up-regulated in VAT in our study, together with other pro-inflammatory cytokines and genes such as TNFSF18 and TLR2 [29] [30].…”

Functional immune diversity in reindeer reveals a high Arctic population at risk

“…Haplotypic variation in number of expressed loci both within as well as between populations is quite common when it comes to MHC. For instance in cattle, there is haplotypic variation with one or two DQB genes (Fukunaga et al, 2020). In sheep, there seems to be two DQA and DQB genes (DQA1-DQB1 and DQA2-DQB2), but in some haplotypes the DQA1-DQB1 genes are replaced by DQA2-like and DQB2-like genes (Ballingall et al, 2018b).…”

Genome-Wide Association Analysis Reveals Novel Loci Related with Visual Score Traits in Nellore Cattle Raised in Pasture–Based Systems

“…The BoLA-DBQ gene belongs to the bovine leukocyte antigen ( BoLA ) family and is characterized by a complex structure of linkage disequilibrium and a high degree of genetic variation [ 89 ]. This gene located on Chr23 was largely associated with physiological and immunological mechanisms of resistance against diseases that have a significant impact on animal production [ 90 , 91 ].…”