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

Area of Science:

• Genetics
• Pulmonary Medicine
• Quantitative Trait Locus Analysis

Background:

• Pulmonary function traits like lung volumes and compliance can be genetically influenced.
• Few genetic polymorphisms controlling these traits have been identified.
• A whole genome scan was performed in mice to investigate genetic determinants of pulmonary function.

Purpose of the Study:

• To identify novel chromosomal regions associated with lung function.
• To utilize quantitative trait locus (QTL) linkage analysis for this identification.
• To analyze genetically divergent mouse strains (C3H/HeJ and JF1/Msf) with distinct phenotypes.

Main Methods:

• Quantitative trait locus linkage analysis was performed.
• N(2) backcross and F(2) intercross mouse populations were generated from C3H/HeJ and JF1/Msf strains.
• Genome-wide scan was conducted to identify linkages for various pulmonary function parameters.

Main Results:

• Significant linkages for total lung capacity were found on chromosomes 15 and 17 (LOD scores up to 6.0).
• Linkages for dead space volume and lung compliance were detected on chromosomes 5 and 15 (LOD scores > 4.0).
• Lung compliance also showed linkage on chromosome 19 (LOD score 5.8), and diffusing capacity on chromosomes 15 and 17 (LOD scores up to 5.0).
• A region on chromosome 17 is syntenic to human chromosome 6q27, previously linked to lung function.
• Candidate genes including relaxin1 and transforming growth factor beta receptor 3 were identified with missense polymorphisms.

Conclusions:

• The study provides evidence for the linkage of multiple lung function measures to specific murine chromosomes (5, 15, 17, and 19).
• Novel candidate genes potentially influencing pulmonary function in both mice and humans were suggested.
• This research opens avenues for further investigation into the genetic basis of lung function.