A survey of airway responsiveness in 36 inbred mouse strains facilitates gene mapping studies and identification of quantitative trait loci |
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Authors: | Adriana S Leme Annerose Berndt Laura K Williams Shirng-Wern Tsaih Jin P Szatkiewicz Ricardo Verdugo Beverly Paigen Steven D Shapiro |
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Institution: | (1) Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA;(2) The Jackson Laboratory, Bar Harbor, ME 04609, USA; |
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Abstract: | Airway hyper-responsiveness (AHR) is a critical phenotype of human asthma and animal models of asthma. Other studies have
measured AHR in nine mouse strains, but only six strains have been used to identify genetic loci underlying AHR. Our goals
were to increase the genetic diversity of available strains by surveying 27 additional strains, to apply haplotype association
mapping to the 36-strain survey, and to identify new genetic determinants for AHR. We derived AHR from the increase in airway
resistance in females subjected to increasing levels of methacholine concentrations. We used haplotype association mapping
to identify associations between AHR and haplotypes on chromosomes 3, 5, 8, 12, 13, and 14. And we used bioinformatics techniques
to narrow the identified region on chromosome 13, reducing the region to 29 candidate genes, with 11 of considerable interest.
Our combined use of haplotype association mapping with bioinformatics tools is the first study of its kind for AHR on these
36 strains of mice. Our analyses have narrowed the possible QTL genes and will facilitate the discovery of novel genes that
regulate AHR in mice. |
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