Positional cloning of a novel gene influencing asthma from chromosome 2q14

Maxine Allen, Andrea Heinzmann, Emiko Noguchi, Gonçalo Abecasis, John Broxholme, Chris P Ponting, Sumit Bhattacharyya, Jon Tinsley, Youming Zhang, Richard Holt, E Yvonne Jones, Nick Lench, Alisoun Carey, Helene Jones, Nicholas J Dickens, Claire Dimon, Rosie Nicholls, Crystal Baker, Luzheng Xue, Elizabeth TownsendMichael Kabesch, Stephan K Weiland, David Carr, Erika von Mutius, Ian M Adcock, Peter J Barnes, G Mark Lathrop, Mark Edwards, Miriam F Moffatt, William O C M Cookson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)258-63
Number of pages6
JournalNature Genetics
Volume35
Issue number3
DOIs
Publication statusPublished - Nov 2003

Keywords

  • Amino Acid Sequence
  • Asthma
  • Chromosomes, Human, Pair 2
  • Cloning, Molecular
  • Genotype
  • Humans
  • Microsatellite Repeats
  • Sequence Homology, Amino Acid

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