5号染色体中儿童支气管哮喘易感基因的鉴定

Childhood asthma is a chronic inflammatory disease with a high degree of clinical heterogeneity.Genetic and environmental factors play an important role in the pathogenesis. Although genome-wide association study have found several susceptibility genes of childhood asthma,they explain only a very small proportion of patients. Further identifying susceptibility genes by new methods to clarify asthma genetic basis is still an important project. In recent years, exome sequencing become an effective means to find desease susceptibility genes. several linkage analysis studies have localized asthma susceptibility genes in chromosome 5, but the real causative genes remain unclear. Accordingly, we hypothesized that: in the chromosome 5, the genetic variation in exons of certain genes, especially the rare and new mutations may contribute to the genetic basis of childhood asthma. In this study, all exon sequence in chromosome 5 will be captured by the latest capture technology and were enriched for high-throughput sequencing. Then, the common，rare and new variations associated with childhood asthma were identified and filtered. Further, in a large case-control and family asthma samples，these variations were verified and new susceptibility genes were defined by using the bioinformatics and functional studies combined with clinical data. The study will be of great significance for deep understanding the pathogenesis of childhood asthma and identifying new potential drug targets.

儿童哮喘是一种具有高度临床异质性的慢性炎症性疾病，遗传和环境因素在其发病中起重要作用。尽管近年兴起的全基因组关联研究已发现了多个儿童哮喘易感基因，但它们仅能解释极小一部分患者。应用新的研究方法进一步鉴定易感基因仍是阐明儿童哮喘遗传基础重要的科学问题。近年来，外显子测序成为寻找疾病易感基因有效手段且国内外多项连锁分析研究将哮喘易感基因定位在5号染色体，但该染色体区域真正致病基因仍未明确。5号染色体遗传变异尤其是外显子区域的稀有和新发突变可能贡献儿童哮喘遗传基础。本研究拟通过最新发明的目标区域捕获技术捕获5号染色体全部外显子序列富集后进行高通量测序，初步识别和筛选出与儿童哮喘/性状相关的常见、稀有和新发变异，进一步在大样本病例对照和家系样本内进行验证，利用生物信息学和功能研究结合临床资料确立儿童哮喘新易感基因。该研究对深入理解儿童哮喘的发病机理以及发现潜在的药物靶点具有重要意义.

儿童哮喘是一种具有高度临床异质性的慢性炎症性疾病，遗传因素在其发病中起重要作用。.多项连锁分析研究表明5号染色体基因遗传变异尤其是外显子区域的稀有和新发突变可能贡献儿童哮喘遗传基础。本研究拟通过儿童支气管哮喘家系和散发样本外显子捕获技术捕获5号染色体全部外显子序列富集后进行高通量测序，筛选出5号染色体区域多个基因SNPs位点可能作为儿童哮喘相关易感基因。本研究丰富了儿童哮喘样本遗传资源库的建设。该研究对深入理解儿童哮喘的发病机理以及发现潜在的药物靶点具有重要意义.