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A GWA study reveals genetic loci for body conformation traits in Chinese Laiwu pigs and its implications for human BMI

机译:GWA研究揭示了中国莱芜猪身体构象特征的遗传位点及其对人BMI的影响

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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 x 10(-5)) and 88 SNPs had suggestive (P 10(-4)) 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.
机译:猪与人具有许多生理和表型相似性,因此已被认为是非啮齿类哺乳动物中研究人类肥胖遗传基础的良好模型。对肥胖性状候选基因的研究已成功鉴定出人与猪之间的一些常见基因。然而,很少有研究通过大规模的比较基因组学评估猪和人肥胖的遗传结构之间存在多少相似性。在这里,我们使用猪60 K SNP Beadchip进行了全基因组关联研究(GWAS),用于中国莱芜猪群体中BMI和三个不同年龄的其他四个构象特征,这表明脂肪沉积存在很大差异。总共发现35个SNP在Bonferroni校正的5%染色体水平上具有显着意义(P = 2.13 x 10(-5)),并且88个SNP与构象性状具有暗示性关联(P <10(-4))。 。一些SNP显示出年龄依赖性的关联。有趣的是,在猪中与BMI相关的32个区域中,有18个与人中BMI的基因座同源。此外,人类中的BMI已经与GWAS峰最接近的五个基因包括HIF1AN,SMYD3,COX10,SLMAP和GBE1,这使其成为这些QTL的非常有希望的候选者。 GO分析的结果为线粒体和突触在肥胖易感性中起重要作用提供了有力的支持,这与先前关于人类肥胖的发现是一致的,并且还暗示了与染色质修饰和Ig样C2型有关的新基因组。 5个域。因此,这些结果不仅为猪的BMI遗传结构提供了新的见解,而且还强调了人与猪之间存在肥胖相关基因的显着重叠。

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