Identification of genetic effects and potential causal polymorphisms of CPM gene impacting milk fatty acid traits in Chinese Holstein.,Animal Genetics

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Identification of genetic effects and potential causal polymorphisms of CPM gene impacting milk fatty acid traits in Chinese Holstein.
Animal Genetics ( IF 2.4 ) Pub Date : 2020-04-16 , DOI: 10.1111/age.12936
L Shi _{1,

2} , L Liu ₃ , X Lv ₃ , Z Ma ₃ , C Li ₁ , Y Li ₃ , F Zhao ₃ , D Sun ₁ , B Han ₁

Affiliation

Our previous GWAS revealed 83 significant SNPs and 20 promising candidate genes associated with milk fatty acid traits in dairy cattle. Out of them, the carboxypeptidase M (CPM ) gene contains a genome‐wide significant SNP, Hapmap49848‐BTA‐106779, which is strongly associated with myristic acid (C14:0; P = 0.0064). Herein, we aimed to confirm the genetic effects of CPM on milk fatty acids in Chinese Holstein. Seven SNPs were detected by re‐sequencing the sequences of entire exons and 3000 bp of up‐/downstream flanking regions of the CPM gene, of which three were in 5′ flanking region, one in the 3′ UTR and three were in the 3′ flanking region. Using the Haploview 4.1, we estimated the LD among the identified SNPs and found two haplotype blocks. With the animal model, we performed the SNP‐ and haplotype‐based association analyses, and observed that these SNPs and haplotype blocks mainly had strong genetic associations with medium‐chain saturated fatty acids (caproic acid, C6:0; caprylic acid, C8:0; capric acid, C10:0; and lauric acid, C12:0) (P < 0.0001–0.0257). In addition, using the Genomatix software, we predicted that three SNPs in the 5′ flanking region of CPM (g.45079507A>G, g.45080228C>A and g.45080335C>G) changed the transcription factor binding sites for PREF (progesterone receptor biding site), ZBRK1 (transcription factor with eight central zinc fingers and an N‐terminal KRAB domain), SOX9 (sex‐determining region Y‐box 9, dimeric binding sites), SOX6 (sex‐determining region Y‐box 6) and FOXP1‐ES (alternative splicing variant of FOXP1, activated in ESCs). Further, the dual‐luciferase reporter assay showed these three SNPs altered the transcriptional activity of CPM gene (P ≤ 0.0006). In summary, using the post‐GWAS strategy, we first confirmed the significant genetic effects of CPM with milk fatty acids in dairy cattle, and identified three potential causal mutations.

更新日期：2020-04-16

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