Nature Genetics
35, 258 - 263 (2003)
Published online: 19 October 2003; | doi:10.1038/ng1256
Positional cloning of a novel gene influencing asthma from Chromosome 2q14Maxine Allen1, 8, Andrea Heinzmann2, 8, Emiko Noguchi2, 8, Gonçalo Abecasis2, John Broxholme2, Chris P Ponting3, Sumit Bhattacharyya2, Jon Tinsley1, Youming Zhang2, Richard Holt2, E Yvonne Jones2, Nick Lench1, Alisoun Carey1, Helene Jones1, Nicholas J Dickens3, Claire Dimon1, Rosie Nicholls1, Crystal Baker1, Luzheng Xue1, Elizabeth Townsend1, Michael Kabesch4, Stephan K Weiland5, David Carr4, Erika von Mutius4, Ian M Adcock6, Peter J Barnes6, G Mark Lathrop7, Mark Edwards1, Miriam F Moffatt2
& William O C M Cookson21
Oxagen, Milton Park, Oxfordshire, UK. 2
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. 3
MRC Functional Genetics Unit, Dept of Human Anatomy and Genetics, University of Oxford, UK. 4
University Children's Hospital, Munich, Germany. 5
Department of Epidemiology, University of Ulm, Ulm, Germany. 6
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK. 7
Centre National De Genotypage, Evry, France. 8
These authors contributed equally to this work.
Correspondence should be addressed to William O C M Cookson william.cookson@ndm.ox.ac.ukAsthma 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.
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