Genomewide linkage analysis identifies novel genetic Loci for lung function in mice.
BACKGROUND
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.


OBJECTIVE
To identify novel chromosomal regions contributing to lung function, quantitative trait locus linkage analysis was applied in N(2) backcross and F(2) intercross mice derived from two inbred strains-C3H/HeJ and JF1/Msf-with extremely divergent phenotypes.


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 beta receptor 3 gene, which revealed missense polymorphisms between the parental strains.


CONCLUSIONS
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.
Reinhard
Claudia
C
Ingolstaedter Landstrasse 1, 85764 Neuherberg/Munich, Germany. reinhard@gsf.de
Meyer
Birgit
B
Fuchs
Helmut
H
Stoeger
Tobias
T
Eder
Gunter
G
Rüschendorf
Franz
F
Heyder
Joachim
J
Nürnberg
Peter
P
de Angelis
Martin Hrabé
MH
Schulz
Holger
H
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008170:Lung Compliance / Q000235:genetics*; D008176:Lung Volume Measurements; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020125:Mutation, Missense / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011653:Pulmonary Diffusing Capacity / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D013045:Species Specificity; D014109:Total Lung Capacity / Q000235:genetics*