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 ... -  《-》

Association of polymorphisms in the bovine FASN gene with milk-fat content.

Fatty acid synthase (FASN) is a multifunctional protein that carries out the synthesis of fatty acids so it plays a central role in de novo lipogenesis in mammals. Previously, we defined the genetic structure and expression of the bovine FASN gene. Our mapping studies placed FASN on BTA19 (19q22) where several quantitative trait loci (QTL) affecting milk-fat content and related traits have been described. This study was conducted to identify polymorphisms in the bovine FASN gene and to study their association with milk-fat content. The bovine FASN gene was screened for polymorphisms in two cattle breeds. Sequence analysis revealed several single nucleotide polymorphisms (SNPs), and two of them were analysed: a G>C substitution in the untranslated exon 1 (g.763G>C), altering a potential Sp1 transcription factor-binding site, and an A>G substitution in exon 34 (g.16009A>G), which determines a non-conservative substitution of threonine by alanine. Allele-specific amplification of the SNPs in FASN revealed significant frequency differences for both polymorphisms in Holsteins with high and low breeding values for milk-fat content. The intragenic haplotypes comprising exon 1 (alleles G and C) and exon 34 (alleles A and G) polymorphisms were studied, and the existence of linkage disequilibrium between these SNPs was found (D(CG) = 0.048, P < 0.001). Our results suggest that the FASN gene polymorphisms contribute to variation in milk-fat content. We propose that the bovine FASN gene is a candidate gene for a milk-fat content QTL.

Roy R ，Ordovas L ，Zaragoza P ，Romero A ，Moreno C ，Altarriba J ，Rodellar C ... -  《ANIMAL GENETICS》

The association of bovine PPARGC1A and OPN genes with milk composition in two independent Holstein cattle populations.

Many studies have reported quantitative trait loci on chromosome 6 that affect milk production traits in dairy cattle. Osteopontin (OPN) and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PPARGC1A) are located in the middle of chromosome 6 about 6 Mb apart, which is approximately 12 cM. The objective of this study was to investigate the association of OPN and PPARGC1A variants with milk production traits in 2 independent Holstein cattle populations: the University of Wisconsin (UW) daughter design and the Cooperative Dairy DNA Repository (CDDR) granddaughter design resource populations. For OPN, 891 cows from the UW resource population were genotyped for the C/T polymorphism reported previously in the CDDR population. Additive effects were significant for fat percentage, protein percentage, and fat yield in the UW resource population. These results are consistent with previous studies that have shown significant association of OPN variants with milk composition traits. The association between PPARC1A variants was investigated in UW and CDDR resource populations using 2 single nucleotide polymorphisms. For the UW resource population, additive effects were significantly increased for protein percentage and decreased for milk yield. Dominance effects were not significant for any of the examined traits. For the CDDR population, PPARGC1A was associated with a significant increase in milk protein percentage and in SCS. Thus, in UW and CDDR populations, PPARGC1A was associated with a significant increase in milk protein percentage in contrast to association results previously reported for the German Holstein population.

Khatib H ，Zaitoun I ，Wiebelhaus-Finger J ，Chang YM ，Rosa GJ ... -  《-》

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 ... -  《-》

New SSCP polymorphism within bovine STAT5A gene and its associations with milk performance traits in Black-and-White and Jersey cattle.

Milk protein genes expression in cows' mammary epithelial cells is regulated mostly by the action of prolactin mediated through the STAT5A transcription factor. The STAT5A gene is a potential quantitative trait locus (QTL) and genetic marker of production traits in dairy cattle. The sequence of the bovine STAT5A gene was analysed in this study to investigate if mutations in this sequence might be responsible for quantitative variations in milk yield and composition. Ten PCR fragments representing most important functional domains of STAT5A were screened for polymorphism. Using the SSCP method a new SNP (A/G) was found, located in intron 9 at position 9501 (GenBank AJ237937). The frequencies of alleles were estimated in 186 Black-and-White cows (0.52 and 0.48 for A and G, respectively) and in 138 Jersey cows (0.58 and 0.42 for A and G, respectively). For Black-and-White cows with different STAT5A genotypes no significant associations between STAT5A genotypes and milk performance traits were found. Statistically significant differences in the first and second lactations for milk yield, fat and protein content were found in Jersey cows. Cows with the GG genotype showed the highest milk yield, while cows with genotypes AA and AG showed higher protein contents when compared to cows with the GG genotype. Interestingly, cows with genotype AG showed significantly higher protein yields in comparison to cows with the AA genotype. For fat content, cows with genotype AA showed the highest level of this trait in the 1st and 2nd lactation. Further studies are necessary to evaluate an allele substitution effect in the population of sib-families of STAT5A heterozygous bulls.

Brym P ，Kamiński S ，Ruść A 《JOURNAL OF APPLIED GENETICS》