Positional cloning of a novel gene influencing asthma from Chromosome 2q14
Positional cloning of a novel gene influencing asthma from Chromosome 2q14
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DOI：
10.1038/ng1256
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发表时间：
2003-11-01
期刊：
影响因子：
30.8
通讯作者：
Cookson, WOCM
中科院分区：
文献类型：
--
作者：
Allen, M;Heinzmann, A;Cookson, WOCM
哮喘是儿童和年轻人的常见疾病。四份独立报告将哮喘和相关表型与 2q14 和 2q32 之间不明确的间隔联系起来（参考文献 1-4），并且两项小鼠基因组筛选将支气管高反应性与与 2q14 同源的区域联系起来（参考文献 5,6）。我们发现并复制了哮喘与 D2S308 微卫星之间的关联，该微卫星位于 2q14 上 IL1 簇远端 800 kb 处。我们对周围区域进行了测序，并构建了全面的、高密度的单核苷酸多态性 (SNP) 连锁不平衡 (LD) 图谱。 SNP 关联仅限于 3.6 kb 的单个基因 (DPP10) 的初始外显子，该基因延伸超过 1 Mb 的基因组 DNA。 DPP10 编码二肽基肽酶 (DPP) 的同源物，可将末端二肽从细胞因子和趋化因子中裂解出来，它为哮喘治疗提供了一个潜在的新靶点。
Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1 4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 ( refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy.