Zhou Lisheng, Ji Jiuxiu, Peng Song, Zhang Zhen, Fang Shaoming, Li Lin, Zhu Yaling, Huang Lusheng, Chen Congying, Ma Junwu
National Key Laboratory for Swine Genetics, Breeding and Production Technology, Jiangxi Agricultural University, Nanchang, 330045, China.
Mamm Genome. 2016 Dec;27(11-12):610-621. doi: 10.1007/s00335-016-9657-4. Epub 2016 Jul 29.
Pigs share numerous physiological and phenotypic similarities with human and thus have been considered as a good model in nonrodent mammals for the study of genetic basis of human obesity. Researches on candidate genes for obesity traits have successfully identified some common genes between humans and pigs. However, few studies have assessed how many similarities exist between the genetic architecture of obesity in pigs and humans by large-scale comparative genomics. Here, we performed a genome-wide association study (GWAS) using the porcine 60 K SNP Beadchip for BMI and other four conformation traits at three different ages in a Chinese Laiwu pig population, which shows a large variability in fat deposition. In total, 35 SNPs were found to be significant at Bonferroni-corrected 5 % chromosome-wise level (P = 2.13 × 10) and 88 SNPs had suggestive (P < 10) association with the conformation traits. Some SNPs showed age-dependent association. Intriguingly, out of 32 regions associated with BMI in pigs, 18 were homologous with the loci for BMI in humans. Furthermore, five closest genes to GWAS peaks including HIF1AN, SMYD3, COX10, SLMAP, and GBE1 have been already associated with BMI in humans, which makes them very promising candidates for these QTLs. The result of GO analysis provided strong support to the fact that mitochondria and synapse play important roles in obesity susceptibility, which is consistent with previous findings on human obesity, and it also implicated new gene sets related to chromatin modification and Ig-like C2-type 5 domain. Therefore, these results not only provide new insights into the genetic architecture of BMI in pigs but also highlight that humans and pigs share the significant overlap of obesity-related genes.
猪在生理和表型上与人类有许多相似之处，因此被认为是研究人类肥胖遗传基础的非啮齿类哺乳动物的良好模型。对肥胖性状候选基因的研究已成功鉴定出人类和猪之间的一些共同基因。然而，很少有研究通过大规模比较基因组学评估猪和人类肥胖的遗传结构之间存在多少相似性。在此，我们使用猪60K SNP芯片对中国莱芜猪群体三个不同年龄的体重指数（BMI）和其他四个体型性状进行了全基因组关联研究（GWAS），该群体在脂肪沉积方面表现出很大的变异性。总共发现35个单核苷酸多态性（SNP）在经Bonferroni校正的5%染色体水平上具有显著性（P = 2.13×10），88个SNP与体型性状存在提示性关联（P < 10）。一些SNP表现出年龄依赖性关联。有趣的是，在与猪BMI相关的32个区域中，有18个与人类BMI的基因座同源。此外，与GWAS峰值最接近的五个基因，包括HIF1AN、SMYD3、COX10、SLMAP和GBE1，已与人类的BMI相关，这使其成为这些数量性状基因座（QTL）非常有前景的候选基因。基因本体（GO）分析结果有力支持了线粒体和突触在肥胖易感性中起重要作用这一事实，这与先前关于人类肥胖的研究结果一致，并且还涉及到与染色质修饰和免疫球蛋白样C2型5结构域相关的新基因集。因此，这些结果不仅为猪BMI的遗传结构提供了新的见解，还突出了人类和猪在肥胖相关基因上存在显著重叠。
