A splice mutation in the PHKG1 gene causes high glycogen content and low meat quality in pig skeletal muscle.
A splice mutation in the PHKG1 gene causes high glycogen content and low meat quality in pig skeletal muscle.
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DOI：
10.1371/journal.pgen.1004710
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发表时间：
2014-10
期刊：
影响因子：
4.5
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Ma J;Yang J;Zhou L;Ren J;Liu X;Zhang H;Yang B;Zhang Z;Ma H;Xie X;Xing Y;Guo Y;Huang L
骨骼肌的糖酵解潜力（GP）在养猪业中具有重要的经济意义，因为它影响猪肉的加工产量。我们在白色杜洛克×二花脸杂种F2中定位了GP的一个主要数量性状基因座（QTL）。我们在此进行了系统遗传分析，以确定潜在的表型QTL（pQTL）的因果变异。我们首先在F2杂交和F19苏太猪群体中进行了全基因组关联分析。然后基于2-LOD滴法将QTL精修至180-kb间隔。然后，我们使用来自497只F2动物的肌肉转录组数据进行表达QTL（eQTL）作图。在QTL区间内，只有一个基因（PHKG 1）具有cis-eQTL，该基因与pQTL在相同的SNP处达到峰值。PHKG 1基因编码磷酸化酶激酶（PhK）的催化亚基，其在糖原分解的级联激活中起作用。PHKG 1的深度测序揭示了内含子9的剪接受体位点中的点突变（C>A），导致开放阅读框中的32-bp缺失并产生提前终止密码子。异常转录物诱导无义介导的衰变，导致受影响动物的蛋白质水平降低和酶活性减弱。该突变导致猪肉GP增加43%，持水力下降>20%。这些效应在F2和苏太猪以及杜洛克×（长白猪×约克郡）杂种猪中是一致的。不利等位基因主要存在于杜洛克猪。这一发现为了解影响葡萄糖代谢的危险因素提供了新的见解，并将大大有助于杜洛克猪近缘种肉质的遗传改良。糖原累积病（Glycogen storage diseases，GSD）是一组以过多糖原累积为特征的遗传性疾病，主要由糖原释放葡萄糖所必需的特定酶的异常引起。GSD样条件已在多种物种中描述。猪是研究人类GSD的重要模型。此外，受GSD影响的猪通常会产生最终pH值较低的劣质猪肉（所谓的“酸性肉”），并且由于过量糖原的死后降解而导致加工产量减少。到目前为止，只有一个致病变异，PRKAG 3 R225 Q，已被确定为GSD在猪。在这里，我们报告了在PHKG 1基因的功能缺失突变，导致糖原分解的缺陷，从而导致GSD和酸肉杜洛克母猪。通过诊断性DNA测试消除种猪中的不良突变将大大降低GSD的发生率，并显着提高猪的猪肉质量和生产力。
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. Glycogen storage diseases (GSD) are a group of inherited disorders characterized by storage of excess glycogen, which are mainly caused by the abnormality of a particular enzyme essential for releasing glucose from glycogen. GSD-like conditions have been described in a wide variety of species. Pigs are a valuable model for the study of human GSD. Moreover, pigs affected by GSD usually produce inferior pork with a lower ultimate pH (so-called “acid meat”) and less processing yield due to post-mortem degradation of the excess glycogen. So far, only one causal variant, PRKAG3 R225Q, has been identified for GSD in pigs. Here we reported a loss-of-function mutation in the PHKG1 gene that causes the deficiency of the glycogen breakdown, consequently leading to GSD and acid meat in Duroc-sired pigs. Eliminating the undesirable mutation from the breeding stock by a diagnostic DNA test will greatly reduce the incidence of GSD and significantly improve pork quality and productivity in the pig.
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影响因子：
3.7
作者：
Corominas J;Ramayo-Caldas Y;Puig-Oliveras A;Pérez-Montarelo D;Noguera JL;Folch JM;Ballester M
通讯作者：
Ballester M
影响因子：
4.5
作者：
Ghazalpour A;Bennett B;Petyuk VA;Orozco L;Hagopian R;Mungrue IN;Farber CR;Sinsheimer J;Kang HM;Furlotte N;Park CC;Wen PZ;Brewer H;Weitz K;Camp DG 2nd;Pan C;Yordanova R;Neuhaus I;Tilford C;Siemers N;Gargalovic P;Eskin E;Kirchgessner T;Smith DJ;Smith RD;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
120.7
作者：
Pearson, Thomas A.;Manolio, Teri A.
通讯作者：
Manolio, Teri A.
DOI：
10.1007/978-1-60761-759-4_15
发表时间：
2010-01-01
期刊：
CANCER SUSCEPTIBILITY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gaildrat, Pascaline;Killian, Audrey;Tosi, Mario
通讯作者：
Tosi, Mario