Identification of single nucleotidepolymorphisms of PIK3R1 and DUSP1 genes and their genetic associa

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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.
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