SNP discovery and haplotype analysis in the bovine PRKAA2 gene

Abstract

The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a cellular fuel gauge that regulates metabolic pathways in glucose and fatty acid metabolism and protein synthesis, and recent data demonstrate that it also plays a critical role in systemic energy balance. PRKAA2, the gene that encodes the α2 catalytic subunit of AMPK, showed be involved in the glucose and lipid metabolism. To date, genetic variants in human PRKAA2 have been shown associations with type 2 diabetes (T2D) in several populations, but few studies show a complete description of the variability of bovine PRKAA2. In the present study, we reported the investigation of PRKAA2 genetic polymorphisms in three Chinese indigenous bovine breeds [Qinchuan (n = 328), Nanyang (n = 278), Jiaxian (n = 148)] and yak (n = 57). The screening of all exons including adjacent splice sites of the gene was performed using a PCR-SSCP strategy, and following sequence analysis revealed fifteen single nucleotide polymorphisms (SNPs). Five SNPs were identified in exons, which all generate synonymous mutations, and other identified variations were located in introns. Linkage disequilibrium (LD) coefficients and haplotype frequencies for some SNPs were investigated. In total, six haplotypes were found in the cattle breeds. Two LD blocks were found in Qinchuan cattle and three common haplotypes were identified based on four SNPs, with the most common haplotype (TGCT) occurring at a frequency of 53.7%; three of the four possible haplotypes were found in Nanyang cattle, with the most common haplotype (CT) occurring at a frequency of 56.3%; whereas, no suitable haplotypes were found in Jiaxian cattle and yak. Phylogenetic analysis showed that Qinchuan and Jiaxian were firstly clustered together, and then Nanyang was added to the branch. The yak (Poephagus grunniens) diverged strongly from the branch of the Bos Taurus. These data will provide a background for more extensive characterization of the bovine PRKAA2 gene, its diversity in different cattle breeds, and evolutionary information of Chinese cattle breeds.