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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Acknowledgments
The authors would like to thank Jesse Hammer for assistance with the graphics, Joanne Currer for her help in preparing the manuscript, and Drs. Luanne Peters and Edward Leiter for their helpful comments on the manuscript. This work was supported by the grants HL 66611 and HL 83069 from the National Institutes of Health, U.S., and by the Cancer Core grant CA 34196 to the Jackson Laboratory.
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Communicated by S. Hohmann.
A. S. Leme, A. Berndt contributed equally.
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Leme, A.S., Berndt, A., Williams, L.K. et al. A survey of airway responsiveness in 36 inbred mouse strains facilitates gene mapping studies and identification of quantitative trait loci. Mol Genet Genomics 283, 317–326 (2010). https://doi.org/10.1007/s00438-010-0515-x
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DOI: https://doi.org/10.1007/s00438-010-0515-x