title: A splice mutation in the PHKG1 gene causes high glycogen content and low meat quality in pig skeletal muscle.
abstract: Glycolytic potential (GP) in skeletal muscle is economically important in the pig industry because of its effect on pork processing yield. We have previously mapped a major quantitative trait loci (QTL) for GP on chromosome 3 in a White Duroc × Erhualian F2 intercross. We herein performed a systems genetic analysis to identify the causal variant underlying the phenotype QTL (pQTL). We first conducted genome-wide association analyses in the F2 intercross and an F19 Sutai pig population. The QTL was then refined to an 180-kb interval based on the 2-LOD drop method. We then performed expression QTL (eQTL) mapping using muscle transcriptome data from 497 F2 animals. Within the QTL interval, only one gene (PHKG1) has a cis-eQTL that was colocolizated with pQTL peaked at the same SNP. The PHKG1 gene encodes a catalytic subunit of the phosphorylase kinase (PhK), which functions in the cascade activation of glycogen breakdown. Deep sequencing of PHKG1 revealed a point mutation (C>A) in a splice acceptor site of intron 9, resulting in a 32-bp deletion in the open reading frame and generating a premature stop codon. The aberrant transcript induces nonsense-mediated decay, leading to lower protein level and weaker enzymatic activity in affected animals. The mutation causes an increase of 43% in GP and a decrease of>20% in water-holding capacity of pork. These effects were consistent across the F2 and Sutai populations, as well as Duroc × (Landrace × Yorkshire) hybrid pigs. The unfavorable allele exists predominantly in Duroc-derived pigs. The findings provide new insights into understanding risk factors affecting glucose metabolism, and would greatly contribute to the genetic improvement of meat quality in Duroc related pigs.
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Junwu
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Huanban
authors.initials: H
authors.lastname: Ma
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Xie
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Yuyun
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Yuanmei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, Nanchang, P.R. China.
authors.forename: Lusheng
authors.initials: L
authors.lastname: Huang
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D055106:Genome-Wide Association Study; D006003:Glycogen / Q000235:genetics* / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D008460:Meat; D018482:Muscle, Skeletal; D010641:Phenotype; D010764:Phosphorylase Kinase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D034421:Sus scrofa / Q000235:genetics
chemical_list: D022821:RNA Splice Sites; D006003:Glycogen; D010764:Phosphorylase Kinase