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.

Khatib H ，Leonard SD ，Schutzkus V ，Luo W ，Chang YM ... -  《-》

Additional support for an association between OLR1 and milk fat traits in cattle.

The bovine oxidized LDL receptor 1 (OLR1) was chosen as a candidate gene for association tests with milk composition traits. Genotyping of 773 Italian Brown Swiss for a SNP at position 8232 in OLR1 (NW_215807:g.8232C>A) revealed a frequency of 0.95 for the g.8232C allele. The University of Wisconsin Holstein resource population was genotyped for the OLR1 NW_215807:g.[7160C>T; 7161A>G; 8232C>A] SNPs, and four haplotypes were inferred based on the genotypes of sires and their daughters. Oxidized LDL receptor 1 haplotypes were significantly associated with fat percentage (P = 0.0015). Haplotype [C; A; C] was associated with a significant increase in fat percentage when compared with the other haplotypes.

Khatib H ，Rosa GJ ，Weigel K ，Schiavini F ，Santus E ，Bagnato A ... -  《ANIMAL GENETICS》

Short communication: Association of an OLR1 polymorphism with milk production traits in the Israeli Holstein population.

Previous studies have reported significant associations between haplotypes of the oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) gene and a single nucleotide polymorphism (SNP) in its 3'-untranslated region with milk composition and health traits in different cattle populations. However, to provide a better estimation of the impact and size of the association of OLR1 with production traits, a need exists to validate its genomic association in additional cattle populations. Thus, the objective of this study was to perform association analysis of the OLR1 SNP with milk traits in the Israeli Holstein population. Estimated breeding values of milk composition traits and somatic cell score were obtained for a total of 1,211 Holstein cows, which were genotyped for a SNP in the 3'-untranslated region. Statistical analysis revealed significant association between the OLR1 SNP and protein percentage and somatic cell score. Thus, the validation of association of this SNP with milk traits in independent cattle populations suggests OLR1 as a candidate gene for further functional studies.

Wang X ，Peñagaricano F ，Tal-Stein R ，Lipkin E ，Khatib H ... -  《-》

Association of the protease inhibitor gene with production traits in Holstein dairy cattle.

Positional, comparative candidate gene analysis and previous quantitative trait loci linkage mapping results were used to search for candidate genes affecting milk production and reproduction traits in dairy cattle. The protease inhibitor (PI) gene was chosen for examination, and 5 single nucleotide polymorphisms were detected in coding regions of the gene by direct sequencing of reverse transcription-polymerase chain reaction products from a wide range of cattle tissues. A total of 6 different intragenic haplotypes were identified in North American Holstein population, and these were examined for associations with milk production traits in 24 half-sib families comprising 1007 sons utilizing a granddaughter design. One common haplotype was associated with increased milk and fat yields, increased productive life, and decreased somatic cell score. Another common haplotype was associated with decreased productive life and increased somatic cell score. One rare haplotype was associated with decreased milk, fat, and protein yields and increased milk protein percentage; another rare haplotype was associated with decreased milk yield, increased protein percentage, and decreased productive life. The observation that the PI gene is associated with analogous traits in humans demonstrates the effectiveness of the positional comparative candidate gene analysis that utilizes information about genes present in chromosomal regions with conserved synteny in other species.

Khatib H ，Heifetz E ，Dekkers JC 《JOURNAL OF DAIRY SCIENCE》

Effect of polymorphisms in the FASN, OLR1, PPARGC1A, PRL and STAT5A genes on bovine milk-fat composition.

The aim of our study was to estimate effects of polymorphisms in the ATP-binding cassette G2 (ABCG2), fatty acid synthase (FASN), oxidized low-density lipoprotein receptor 1 (OLR1), peroxysome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A), prolactin (PRL) and signal transducer and activator of transcription 5A (STAT5A) genes on milk production traits and detailed milk-fat composition. Milk-fat composition phenotypes were available for 1905 Dutch Holstein-Friesian cows. First, the presence of each SNP in the Dutch Holstein-Friesian population was evaluated by direct sequencing of the PCR product surrounding the SNP in 22 proven Dutch Holstein-Friesian bulls. The ABCG2 SNP did not segregate in the bull population. Second, we genotyped the cows for the FASN(g.16024G>A), FASN(g.17924A>G), OLR1(g.8232C>A), PPARGC1A(c.1790+514G>A), PPARGC1A(c.1892+19G>A), PRL(g.8398G>A) and STAT5A(g.9501G>A) polymorphisms, and estimated genotype effects on milk production traits and milk-fat composition. FASN(g.17924A>G) and OLR(g.8232C>A) had a significant effect (P < 0.05) on milk-fat percentage. However, we were not able to confirm results reported in the literature that showed effects of all evaluated polymorphisms on milk-fat percentage or milk-fat yield. All polymorphisms showed significant effects (P < 0.05) on milk-fat composition. The polymorphisms in FASN and STAT5A, which had an effect on C14:0 and were located on chromosome 19, could not fully explain the quantitative trait locus for C14:0 that was previously detected on chromosome 19 in a genome-wide scan using linkage analysis.

Schennink A ，Bovenhuis H ，Léon-Kloosterziel KM ，van Arendonk JA ，Visker MH ... -  《-》