Genomewide linkage analysis identifies novel genetic loci for lung function in mice

Claudia Reinhard, Birgit Meyer, Helmut Fuchs, Tobias Stoeger, Gunter Eder, Franz Rüschendorf, Joachim Heyder, Peter Nürnberg, Martin Hrabé De Angelis, Holger Schulz

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Rationale: Pulmonary function, including lung volumes and compliance, may be genetically determined, but few genetic polymorphisms have been identified that control these traits. We used an experimental approach and performed the first whole genome scan for pulmonary function in mice. Objectives and Methods: To identify novel chromosomal regions contributing to lung function, quantitative trait locus linkage analysis was applied in M2 backcross and F2 intercross mice derived from two inbred strains - C3H/HeJ and JF1/ Msf - with extremely divergent phenotypes. Main results: Significant linkages to total lung capacity with LOD (logarithm of the odds) scores up to 6.0 were detected on chromosomes 15 and 17, to dead space volume and lung compliance on chromosomes 5 and 15 (LOD scores higher than 4.0), to lung compliance also on chromosome 19 (LOD score of 5.8), and to diffusing capacity on chromosomes 15 and 17 (LOD scores up to 5.0). The region of interest on chromosome 17 near D17Mit133 contains a syntenic region to human chromosome 6q27, which was recently identified to be linked to lung function in humans. The identified intervals harbor valuable candidate genes, such as the relaxin1 and transforming growth factor β receptor 3 gene, which revealed missense polymorphisms between the parental strains. Conclusion: The study provides evidence for linkage of different measures of lung function on murine chromosomes 5, 15, 17, and 19 and suggests novel candidate genes that may also affect the expression of human pulmonary function.

Original languageEnglish
Pages (from-to)880-888
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume171
Issue number8
DOIs
StatePublished - 15 Apr 2005

Keywords

  • Genetics
  • Linkage mapping
  • Murine lung function
  • Pulmonary diseases

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