Genomic analysis and identification of susceptible genes for alopecia areata

在这项研究中，我们已经确定了6号染色体上的一个强候选区域，在HLA-B位点附近（OR: 3.21）。通过使用微卫星标记和snp对该区域进行详细的遗传分析，我们可以成功地将该区域缩小到2兆碱基间隔（Haida Y, Ikeda S, et al .：利用微卫星标记对HLA区域内斑秃的关联研究）。免疫遗传学,2013;65: 553-7.）. 我们进一步对50例斑秃病例的2兆碱基区域进行了测序，并确定了斑秃的强相关单倍型（OR: 3.75）。此外，在这一区域，我们已经在基因的外显子和内含子中发现了多个突变和/或多态性，这些突变经常导致终止密码子突变的形成和基因产物的截断。这些结果表明该基因可能是斑秃的强易感基因。我们现在正在生产这种基因的基因修饰小鼠，并检测这种候选基因在斑秃患者皮肤上的表达。

In this study, we have identified a strong candidate region for alopecia areata on chromosome 6, at around HLA-B locus (OR: 3.21). By detailed genetic analysis of this region using microsatellite markers and SNPs, we could successfully narrow the region to 2 megabase interval (Haida Y, Ikeda S, et al: An association study of Alopecia Areata within the HLA region using microsatellite markers. Immunogenetics, 2013; 65: 553-7.）. We further sequenced this 2 megabase region on 50 alopecia areata cases, and identified a strongly associated haplotype for alopecia areata (OR: 3.75). Moreover, in this region, we have identified multiple mutations and/or polymorphisms in the exons and introns of a gene, that frequently resulted in the formation of stop codon mutations and truncation of gene products. These results indicated that this gene could be a strong susceptible gene for alopecia areata. We are now producing gene modified mice for this gene, and also examining the expression of this candidate gene on the alopecia areata patients’ skin.