Determination of genetic associations between indels in 11 candidate genes and milk composition traits in Chinese Holstein population

We have previously identified 11 promising candidate genes for milk composition traits by resequencing the whole genomes of 8 Holstein bulls with extremely high and low estimated breeding values for milk protein and fat percentages (high and low groups), including FCGR2B, CENPE, RETSAT, ACSBG2, NFKB2, TBC1D1, NLK, MAP3K1, SLC30A2, ANGPT1 and UGDH those contained 25 indels between high and low groups. In this study, the purpose was to further examine whether these candidates have significant genetic effects on milk protein and fat traits. With PCR product sequencing, 13 indels identified by whole genome resequencing were successfully genotyped. With association analysis in 769 Chinese Holstein cows, we found that the indel in FCGR2B was significantly associated with milk yield, protein yield and protein percentage (P = 0.0041 to 0.0297); five indels in CENPE and one indel in MAP3K1 were markedly relevant to milk yield, fat yield and protein yield (P < 0.0001 to 0.0073); polymorphism in RETSAT was evidently associated with milk yield, fat yield, protein yield and protein percentage (P = 0.0001 to 0.0237); variant in ACSBG2 affected fat yield and protein percentage (P = 0.0088 and 0.0052); one indel in TBC1D1 was with respect to fat percentage and protein percentage (P = 0.0224 and 0.0209). Significant associations were shown between indels in NLK and protein yield and protein percentage (P = 0.0012 to 0.0257); variant in UGDH was related to the milk yield (P = 0.0312). The two exonic indels in FCGR2B and CENPE were predicted to change the mRNA and protein secondary structures, and resulted in the corresponding protein dysfunction. Our findings presented here provide the first evidence for the associations of eight functional genes with milk yield and composition traits in dairy cattle.