Association Analyses Between Type 2 Diabetes Genes and Obesity Traits in Pigs
Association Analyses Between Type 2 Diabetes Genes and Obesity Traits in Pigs
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DOI：
10.1038/oby.2008.557
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发表时间：
2009-02-01
期刊：
影响因子：
6.9
通讯作者：
Rothschild, Max F.
中科院分区：
文献类型：
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作者：
Du, Zhi-Qiang;Fan, Bin;Rothschild, Max F.
目的研究人2型糖尿病（T2D）相关候选基因在猪肥胖相关表型中的表达。在由伯克希尔和约克郡两个猪品种构建的参考家系中，实现了脂肪沉积基因的统计关联分析。然后尝试进行广泛的测序以发现致病多态性。T2D发育相关基因TCF7L2、WFS1、FTO、SLC30A8和GCKR分别定位于野猪第14、8、6、4和3号染色体。只有TCF7L2与猪的五个脂肪性状显著相关。进一步的研究表明，一个单倍型（HapB），而不是HapA（同源的区域为人类T2D易感性的单核苷酸多态性（SNP）rs7903146位于），是显着相关的脂肪相关性状。在HapB中，TCF7L2外显子8和内含子10中的2个SNPs与5个脂肪性状显著相关，可能与4个背膘性状和总脂率的加性效应的致病变异体存在连锁不平衡。对于外显子8中的SNP，基因型TT的猪仅具有一种转录异构体（不具有外显子4的转录异构体），并且背膘深度较低。候选基因分析可以为这些基因在人类T2D易感性中的作用提供新的思路，并支持猪可以成为人类肥胖和T2D研究的合适模型。应考虑在其他猪群中进一步复制这项研究，以便探索在猪育种或动物模型研究中利用这些遗传标记的可能性。
To investigate candidate genes involved in human type 2 diabetes (T2D) for obesity-related phenotypes in pigs. Statistical association analyses of genes with fat deposition were realized in a pig reference family constructed by two breeds, Berkshire and Yorkshire. Extensive sequencing was then attempted to discover the causative polymorphism. Genes implied in human T2D development, TCF7L2, WFS1, FTO, SLC30A8, and GCKR, were mapped on Sus scrofa chromosomes 14, 8, 6, 4, and 3, respectively. Only TCF7L2 was significantly associated with five fat traits in pigs. Further investigation demonstrated that one haplotype (HapB), but not the HapA (homologous to the region for human T2D susceptibility where single-nucleotide polymorphism (SNP) rs7903146 is located), is significantly associated with the fat-related traits. In HapB, two SNPs in TCF7L2 exon 8 and intron 10 are significantly associated with five fat traits, and may be in linkage disequilibrium with the causative variant with additive effects on all four backfat traits, and the total lipid percentage. Pigs of genotype TT for the SNP in exon 8 have only one transcript isoform (the one without exon 4), and lower backfat depth. Candidate gene analyses could provide novel ideas about how these genes function in T2D susceptibility in human, and support that the pig can be a suitable model for human obesity and T2D research. Further replication of this research in other pig populations should be considered, so that the possibility of utilizing these genetic markers in pig breeding or in animal model research can be explored.