利用传递不平衡分析在多群体中鉴别猪脐疝易感基因

Identification of susceptibility gene for pig umbilical hernia in different populations using transmission disequilibrium test

在本实验室前期利用白色杜洛克×二花脸F2资源家系开展脐疝易感位点全基因组扫描定位的基础上,文章在7号染色体上的SWR1928和10号染色体上的SW830易感标记区域,结合脐疝发病机制在多群体中进行脐疝位置功能候选基因的筛选和易感位点的精细定位。在两个显著关联的微卫星位点区域搜寻到12个位置功能候选基因,采用比较测序法,选取12个候选基因内共计40个SNP位点在白色杜洛克×二花脸资源家系F2/F3脐疝群体中进行基因分型,利用Plink v1.07软件对基因型数据进行质量控制和传递不平衡(Transmission disequilibrium test,TDT)分析。结果表明,IL16(Interleukin 16)基因中的g.708C>T位点和CDC73(Cell division cycle 73)基因中的g.10664G>A位点与脐疝的关联性达到显著水平(P<0.05)。对这两个位点在西方商业猪种脐疝患病家系中进行基因分型和TDT验证分析,发现CDC73基因中的g.10664G>A位点仍与猪脐疝呈显著关联(P<0.05)。同时对CDC73基因中与资源家系脐疝呈弱相关的两个SNP位点g.10546A>G和g.10811A>G在西方商业猪种中进行TDT验证分析,发现这两个SNP位点与商业猪种脐疝发生的关联性达到极显著水平(P<0.01)。根据文章的分析结果,结合脐疝发生的生理机制及CDC73基因的生物学功能,推测CDC73基因可能为猪脐疝发生的易感基因。

A genome-wide scan for pig umbilical hernia （UH） was performed in a White Duroc × Erhualian resource population reported by our previously study, which detected two susceptibility microsatellite markers （SWR1928 on SSC7 and SW830 on SSC10） significantly affecting pig UH. Herein, fine mapping studies and identification of sus-ceptibility genes for UH were performed in two different populations. A total of 40 SNPs in 12 positional candidate genes located on the two significant segments were genotyped in the F2/F3 resource population. Quality control of the genotype data and transmission disequilibrium test （TDT） were conducted using Plink v1.07 software. The results showed thatg.708G〉A inIL16 （interleukin 16） gene andg.10664G〉A inCDC73（cell division cycle 73） gene were significantly associated with pig UH. These two prominent SNPs and another two weakly associated SNPs g.10546A〉G andg.10811A〉GinCDC73 were also undergone the replication TDT test in the outbred commercial popula-tions. All SNPs in theCDC73 gene were confirmed to be significantly associated with pig UH （P〈0.05）, including g. 10546A〉G andg.10811A〉Gwith extreme significant level （P〈0.01）. Based on these results,CDC73 should be a susceptibility gene for pig UH according to its biological functions and the molecular pathogenesis of UH.