Animal Genetics and Breeding Division, ICAR-National Dairy Research Institute, Karnal, Haryana, India.
PLoS One. 2023 May 19;18(5):e0277156. doi: 10.1371/journal.pone.0277156. eCollection 2023.
The purpose of this study was to identify genetic variants in the promoter and 5'UTR regions of bovine leucine amino peptidase three (LAP3) gene and analysed their associations with estimated breeding values (EBVs) of milk production traits and clinical mastitis in Sahiwal and Karan Fries cattle. Eleven SNPs were identified within the region under study of the LAP3 gene, including seven promoter variants (rs717156555: C>G, rs720373055: T>C, rs715189731: A>G, rs516876447: A>G, rs461857269: C>T, rs136548163: C>T, and rs720349928: G>A) and four 5'UTR variants (rs717884982: C>T, rs722359733: C>T, rs481631804: C>T and rs462932574: T>G). Out of them, 10 SNPs variants were found in both Sahiwal and Karan Fries cattle, with one SNP variant (rs481631804: C>T) being unique to Karan Fries cattle. Seven of these identified SNPs were chosen for association analyses. Individual SNP based association analysis revealed that two SNPs (rs720373055: T>C and rs720349928: G>A) were significantly associated with EBVs of lactation milk yield (LMY), 305-day milk yield (305dMY), and one significant association of SNP rs722359733: C>T with lactation length (LL) was observed. Haplotype based association analysis indicated that diplotypes are significantly associated with EBVs of LMY, 305dMY, and LL, individuals with H1H3 (CTACGCT/GCGTACG) being linked to higher lactation performance than other diplotypes. Further logistic regression analysis revealed that, animals with diplotype H1H3 was less susceptible to the incidence of clinical mastitis than other cows, as the odds ratio for the non-incidence of clinical mastitis was found to be low. Altogether, variations in the LAP3 gene promoter could be used as a genetic marker, most notably diplotype H1H3, may greatly benefit the simultaneous improvement of mastitis resistance and milk yield traits in dairy cattle. Moreover, bioinformatics analysis predicted that the SNPs rs720373055: T>C, rs715189731:A>G and rs720349928: G>A is located in the core promoter region and in TFBs, play key role in regulation of studied phenotypes.
本研究旨在鉴定牛亮氨酸氨基肽酶三（LAP3）基因启动子和 5'UTR 区域的遗传变异，并分析其与萨希瓦尔牛和卡兰弗里牛产奶性状和临床乳腺炎估计育种值（EBVs）的关联。在 LAP3 基因研究区域内共鉴定出 11 个 SNPs，包括 7 个启动子变异（rs717156555：C>G、rs720373055：T>C、rs715189731：A>G、rs516876447：A>G、rs461857269：C>T、rs136548163：C>T 和 rs720349928：G>A）和 4 个 5'UTR 变异（rs717884982：C>T、rs722359733：C>T、rs481631804：C>T 和 rs462932574：T>G）。其中，10 个 SNP 变异在萨希瓦尔牛和卡兰弗里牛中均有发现，一个 SNP 变异（rs481631804：C>T）仅存在于卡兰弗里牛中。选择其中的 7 个 SNP 进行关联分析。基于个体 SNP 的关联分析表明，两个 SNP（rs720373055：T>C 和 rs720349928：G>A）与泌乳奶产量（LMY）、305 天奶产量（305dMY）的 EBV 显著相关，还观察到 SNP rs722359733：C>T 与泌乳期长度（LL）的一个显著关联。基于单倍型的关联分析表明，单倍型与 LMY、305dMY 和 LL 的 EBVs 显著相关，与其他单倍型相比，H1H3（CTACGCT/GCGTACG）个体与更高的泌乳性能相关。进一步的逻辑回归分析表明，与其他奶牛相比，具有 H1H3 单倍型的动物对临床乳腺炎的发病率较低，非临床乳腺炎发病率的比值比发现较低。总的来说，LAP3 基因启动子的变异可以作为遗传标记，特别是单倍型 H1H3，可以极大地促进奶牛乳腺炎抗性和产奶量性状的同时改良。此外，生物信息学分析预测 SNP rs720373055：T>C、rs715189731:A>G 和 rs720349928：G>A 位于核心启动子区域和 TFBs 中，在研究表型的调节中发挥关键作用。
