Fine Mapping QTLs Affecting Milk Production Traits on BTA6 in Chinese Holstein with SNP Markers

Our previous studies demonstrated that the region around markers BMS470 and BMS1242 on BTA6 showed a linkage to 305-d milk yield and composition traits in the Chinese Holstein population. We herein focused on such narrow region to fine map milk production QTLs with 15 SNPs across 25 Mb with each SNP in 1 Mb within most regions in a Chinese Holstein population with daughter design. 1 449 Holstein cows and 11 sires were genotyped for such SNPs by using TaqMan probe and RFLP assays. Multipoint linkage analysis across family revealed a QTL affecting milk yield between PPARGC1A C4075T and SLC34A2 T1713C. Meanwhile, within family analysis found three milk yield QTLs （two in CR T60984131G-CEP135 C501T and one in PDLIM5 A106C-OPN T3907, a fat yield QTLin UGDH T1670C-CR T60984131G region, and two protein yield QTLs in TBC1D1 G501C-UGDH T1670C and PPARGC1A C4075T-SLC34A2 T1713C, respectively. Associations between aforementioned significant SNP markers and milk production traits were further implemented. We found significant associations of PPARGC1A C4075T, SLC34A2 T1713C with milk yield （P0.05, P0.01, P0.01）, UGDH T1670C, and CR T60984131G with fat yield （P0.01, P0.01）, and PPARGC1A C4075T, SLC34A2 T1713C, UGDH T1670C and OPN T3907 with protein yield （P0.01, P0.01, P0.01, P0.01）. Our findings implied that QTLs affecting milk production traits on BTA6 were pleictropism or multigenic effect and PPARGC1A and OPN may be the causal mutations behind milk production QTLs on BTA6 in the Chinese Holstein population.

Fine mapping quantitative trait loci affecting milk production traits on bovine chromosome 6 in a Chinese Holstein population

To fine map the previously detected quantitative trait loci （QTLs） affecting milk production traits on bovine chromosome 6 （BTA6）, 15 microsatellite markers situated within an interval of 14.3 cM spanning from BMS690 to BM4528 were selected and 918 daughters of 8 sires were genotyped. Two mapping approaches, haplotype sharing based LD mapping and single marker regression mapping, were used to analyze the data. Both approaches revealed a quantitative trait locus （QTL） with significant effects on milk yield, fat yield and protein yield located in the segment flanked by markers BMS483 and MNB209, which spans a genetic distance of 0.6 cM and a physical distance of 1.5 Mb. In addition, the single marker regression mapping also revealed a QTL affecting fat percentage and protein percentage at marker DIK2291. Our fine mapping work will facilitate the cloning of candidate genes underlying the QTLs for milk production traits.

A post-GWAS replication study confirming the association of C14H8orf33 gene with milk production traits in dairy cattle

Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population.Of these,38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition.By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis,26 genes were found to contain or be near to such SNPs.Among them,the C14H8orf33 gene is merely 87 bp away from the significant SNP,Hapmap30383-BTC-005848.Hence,we report herein genotype-phenotype associations to further validate the genetic effects of the C14H8orf33 gene.By pooled DNA sequencing of 14 unrelated Holstein sires,a total of 18 with seven novel SNPs were identified.Among them,nine SNPs were in the 5′regulatory region,one in exon 6 and the other in the 3′UTR and 3′regulatory region.A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population.The results showed that these SNPs were statistically significant for more than two traits[P<(0.0001–0.0267)].In addition,mRNA expression analyses revealed that C14H8orf33 was ubiquitous in eight different tissues,with a relatively higher expression level in the mammary gland than in other tissues.These findings,therefore,provide strong evidence for association of C14H8orf33 variants with milk yield and milk composition traits and may be applied in Chinese Holstein breeding programs.