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Genomic analyses and biological validation of candidate genes for rectal temperature as an indicator of heat stress in Holstein cattle
Authors:Hanpeng Luo  Xiang Li  Lirong Hu  Wei Xu  Qin Chu  Aoxing Liu  Gang Guo  Lin Liu  Luiz F Brito  Yachun Wang
Affiliation:1. Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture of China, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, China;2. Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, 100097, Beijing, China;3. Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, 8830, Tjele, Denmark;4. Beijing Sunlon Livestock Development Company Limited, 100029, Beijing, China;5. Beijing Dairy Cattle Center, 100192, Beijing, China;6. Department of Animal Sciences, Purdue University, West Lafayette, IN 47907
Abstract:Heat stress is a major cause of welfare issues and economic losses to the worldwide dairy cattle industry. Genetic selection for heat tolerance has a great potential to positively affect the dairy industry, as the gains are permanent and cumulative over generations. Rectal temperature (RT) is hypothesized to be a good indicator trait of heat tolerance. Therefore, this study investigated the genetic architecture of RT by estimating genetic parameters, performing genome-wide association studies, and biologically validating potential candidate genes identified to be related to RT in Holstein cattle. A total of 33,013 RT records from 7,598 cows were used in this study. In addition, 1,114 cows were genotyped using the Illumina 150K Bovine BeadChip (Illumina, San Diego, CA). Rectal temperature measurements taken in the morning (AMRT) and in the afternoon (PMRT) are moderately heritable traits, with estimates of 0.09 ± 0.02 and 0.04 ± 0.01, respectively. These 2 traits are also highly genetically correlated (r = 0.90 ± 0.08). A total of 10 SNPs (located on BTA3, BTA4, BTA8, BTA13, BTA14, and BTA29) were found to be significantly associated with AMRT and PMRT. Subsequently, gene expression analyses were performed to validate the key functional genes identified (SPAG17, FAM107B, TSNARE1, RALYL, and PHRF1). This was done through in vitro exposure of peripheral blood mononuclear cells (PBMC) to different temperatures (37°C, 39°C, and 42°C). The relative mRNA expression of 2 genes, FAM107B and PHRF1, significantly changed between the control and heat stressed PBMC. In summary, RT is heritable, and enough genetic variability exists to enable genetic improvement of heat tolerance in Holstein cattle. Important genomic regions were identified and biologically validated; FAM107B and PHRF1 are the main candidate genes identified to influence heat stress response in dairy cattle.
Keywords:animal resilience  Chinese Holstein cattle  genome-wide association study  gene expression  heat stress
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