2号染色体麻风易感基因鉴定分离

本课题组最近对麻风家系进行了全基因组连锁分析，发现2号染色体上的2p14区域与该病在常染色体隐性遗传模式下达到了全基因组连锁水平（HLOD=3.513），据此确定了一个新的疾病易感位点，结果发表于《PLoS ONE》。这一区域在我们既往开展的全基因组关联研究（GWAS）数据中并无阳性信号，提示该区域可能存在对疾病发生风险影响程度较大的低频变异。本研究拟在业已建立的麻风病资源库中选取符合常染色体隐性遗传模式的麻风家系，利用高通量测序技术对目标区域进行外显子测序，定位该区域中存在的疾病相关遗传变异，继而在大样本量的病例对照中进行验证，并对阳性相关变异的功能进行研究，以期发现麻风病新的易感基因，为发病机制、风险预测及干预措施的制定累积基础。

Recently, we conducted a genome-wide single nucleotide polymorphism (SNP) based linkage analysis and identified a novel loci on 2p14 with genome-wide significant evidence for linkage with a heterogeneity logarithm of odds (HLOD) score of 3.51 (rs1106577) under a recessive model of inheritance, which published in PLoS ONE. There is no overlap between this loci and our previous GWAS which published in New England Journal of Medicine and Nature Genetics，indicating that at least one rare variants with large effect size on this region.This study is to identify new susceptiblity gene/ risk variants on Chr2p14 through targeted exome sequencing with samples of pedigrees in accordance with autosomal recessive model of inheritance, validating the results in large case-control samples, and follow-up function analysis. This study may be helpful for the elucidation of etiology , risk assessment and intervention of this disease. .