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Background  Previously, phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1 ) and dual specificity phosphatase 1 ( DUSP1 ) were identified as promising candidate genes for milk production traits due to their being differentially expressed between the dry period and the peak of lactation in livers of dairy cows. Hence, in this study, the single nucleotide polymorphisms (SNPs) of  PIK3R1  and  DUSP1  genes were identified and their genetic associations with milk yield, fat yield, fat percentage, protein yield, and protein percentage, were investigated using 1067 Chinese Holstein cows from 40 sire families.    Results  By re-sequencing the entire coding region and 2000 bp of the 5′ and 3′ flanking regions of the two genes, one SNP in the 5′ untranslated region (UTR), three in the 3′ UTR, and two in the 3′ flanking region of  PIK3R1  were identified, and one in the 5′ flanking region, one in the 3′ UTR, and two in the 3′ flanking region of  DUSP1  were found. Subsequent single-locus association analyses showed that five SNPs in  PIK3R1 , rs42590258, rs210389799, rs208819656, rs41255622, rs133655926, and rs211408208, and four SNPs in  DUSP1 , rs207593520, rs208460068, rs209154772, and rs210000760, were significantly associated with milk, fat and protein yields in the first or second lactation ( P  values ≤ 0.0001 and 0.0461). In addition, by the Haploview 4.2 software, the six and four SNPs in  PIK3R1  and  DUSP1  respectively formed one haplotype block, and the haplotype-based association analyses showed significant associations between their haplotype combinations and the milk traits in both two lactations ( P  values ≤ 0.0001 and 0.0364). One SNP, rs207593520(T/G), was predicted to alter the transcription factor binding sites (TFBSs) in the 5′ flanking region of  DUSP1 . Further, the dual-luciferase assay showed that the transcription activity of allele T in rs207593520 was significantly higher than that of allele G, suggesting the activation of transcriptional activity of  DUSP1  gene by allele T of rs207593520. Thus, the rs207593520 SNP was highlighted as a potential causal mutation that should be further verified.    Conclusions  We demonstrated novel and significant genetic effects of the  PIK3R1  and  DUSP1  genes on milk production traits in dairy cows, and our findings provide information for use in dairy cattle breeding.

Identification of single nucleotide polymorphisms of PIK3R1 and DUSP1 genes and their genetic associations with milk production traits in dairy cows