Genome-wide association study and functional analyses for clinical and subclinical ketosis in Holstein cattle

摘要

Ketosis is one of the most frequent metabolic diseasesin high-yielding dairy cows and is characterizedby high concentrations of ketone bodies in blood, urine,and milk, causing high economic losses. The search forpolymorphic genes, whose alleles have different effectson resistance to developing the disease, is of extremeimportance to help select less susceptible animals.The aims of this study were to identify genomic regionsassociated with clinical and subclinical ketosis(β-hydroxybutyrate concentration) in North AmericanHolstein dairy cattle and to investigate these regionsto identify candidate genes and metabolic pathwaysassociated with these traits. To achieve this, a GWASwas performed for 4 traits: clinical ketosis lactation 1,clinical ketosis lactation 2 to 5, subclinical ketosis lactation1, and subclinical ketosis lactation 2 to 5. Theestimated breeding values from 77,277 cows and 7,704bulls were deregressed and used as pseudophenotypesin the GWAS. The top-20 genomic regions explainingthe largest proportion of the genetic variance were investigatedfor putative genes associated with the traitsthrough functional analyses. Regions of interest wereidentified on chromosomes 2, 5, and 6 for clinical ketosislactation 1; 3, 6, and 7 for clinical ketosis lactation 2to 5; 1, 2, and 12 for subclinical ketosis lactation 1; and20, 11, and 25 for subclinical ketosis lactation 2 to 5.The highlighted genes potentially related to clinical andsubclinical ketosis included ACAT2 and IGF1. Enrichmentanalysis of the list of candidate genes for clinicaland subclinical ketosis showed molecular functions andbiological processes involved in fatty acid metabolism,lipid metabolism, and inflammatory response in dairycattle. Several genomic regions and SNPs related tosusceptibility to ketosis in dairy cattle that were previouslydescribed in other studies were confirmed. Thenovel genomic regions identified in this study aid tocharacterize the most important genes and pathwaysthat explain the susceptibility to clinical and subclinicalketosis in dairy cattle.