Positional cloning of a novel gene influencing asthma from chromosome 2q14.
Allen M., Heinzmann A., Noguchi E., Abecasis G., Broxholme J., Ponting CP., Bhattacharyya S., Tinsley J., Zhang Y., Holt R., Jones EY., Lench N., Carey A., Jones H., Dickens NJ., Dimon C., Nicholls R., Baker C., Xue L., Townsend E., Kabesch M., Weiland SK., Carr D., von Mutius E., Adcock IM., Barnes PJ., Lathrop GM., Edwards M., Moffatt MF., Cookson WO.
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.