Association of the OLR1 gene with milk composition in Holstein dairy cattle

Oxidized low-density lipoprotein receptor (OLR1) is the major protein that binds, internalizes, and degrades oxidized low-density lipoprotein. The role of OLR1 in lipid metabolism and the results of previous whole-genome scan studies prompted the investigation of OLR1 as a candidate gene affecting milk composition traits. Direct cDNA and genomic sequencing of OLR1 revealed 2 single nucleotide polymorphisms (SNP) in exon 4, 5 SNP in intron 4, and 1 in the 3' untranslated region (UTR). Four intragenic haplotypes comprising SNP positions 7,160, 7,161, 7,278, 7,381, 7,409, 7,438, 7,512, and 8,232 were inferred. Haplotype analysis showed that one of the haplotypes was associated with a significant increase in fat yield and fat percentage. Single SNP analysis showed that allele C of SNP 8,232 (in the 3'-UTR) had significant effects on fat yield and fat percentage, whereas SNP 7,160 and 7,161 (in exon 4) had no significant effects. Both single SNP and haplotype analyses indicate that SNP 8,232 in the 3'-UTR is associated with milk fat yield and percentage and it may be in linkage disequilibrium with the functional polymorphism. To provide support for the hypothesis that SNP 8,232 is responsible for OLR1 expression, OLR1 expression levels in individuals bearing different genotypes were assessed. It was found that OLR1 expression was reduced in genotype AA individuals compared with CC and AC individuals, suggesting that A at position 8,232 may be the nucleotide causing decreased OLR1 expression. The 3'-UTR polymorphism found in this study might control translation or stability of OLR1 mRNA.