A survey of airway responsiveness in 36 inbred mouse strains facilitates gene mapping studies and identification of quantitative trait loci

被引：28

作者：

Leme, Adriana S. ^{[2
]}

Berndt, Annerose ^{[1
]}

Williams, Laura K. ^{[2
]}

Tsaih, Shirng-Wern ^{[1
]}

Szatkiewicz, Jin P. ^{[1
]}

Verdugo, Ricardo ^{[1
]}

Paigen, Beverly ^{[1
]}

Shapiro, Steven D. ^{[2
]}

机构：

[1] Jackson Lab, Bar Harbor, ME 04609 USA

[2] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA

来源：

MOLECULAR GENETICS AND GENOMICS | 2010年 / 283卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Mice; Genetics; Asthma; HYPERRESPONSIVENESS; MODELS; ASTHMA; HYPERREACTIVITY; DISEASE; LINKAGE;

D O I：

10.1007/s00438-010-0515-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：317 / 326

页数：10

共 33 条

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