Interacting genetic loci cause airway hyperresponsiveness
Interacting genetic loci cause airway hyperresponsiveness
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DOI：
10.1152/physiolgenomics.00267.2004
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发表时间：
2005-03-21
影响因子：
4.6
通讯作者：
Beier, DR
中科院分区：
文献类型：
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作者：
Ackerman, KG;Huang, HL;Beier, DR
哮喘的组成部分，这种复杂特征的遗传基础仍然难以捉摸。我们通过将A/J小鼠（具有升高的初始AHR）与C57 BL/6 J小鼠连续回交并选择具有升高的初始AHR表型的小鼠来产生具有升高的初始AHR的重组同源小鼠。第七代回交高反应小鼠保留了三个区域的A/J位点。对123个AHR N8后代的数量性状连锁（QTL）分析表明，AHR表型与任何单个位点无关，但与第2和第6染色体上的位点间的相互作用显著相关。这些发现在染色体置换品系小鼠的独立分析中得到证实。鉴定基因组区域含有与AHR因果相关的基因座，并证明这种特性需要它们之间的相互作用，这对人类哮喘遗传病因学的研究具有重要意义。
component of asthma, and the genetic basis of this complex trait has remained elusive. We created recombinant congenic mice with increased naive AHR by serially backcrossing A/J mice (which have elevated naive AHR) with C57BL/6J mice and selecting for mice with an elevated naive AHR phenotype. The seventh backcross-generation hyperresponsive mice retained A/J loci in three regions. Quantitative trait linkage (QTL) analysis of 123 unselected N8 progeny demonstrated that the AHR phenotype was not associated with any single locus but was significantly associated with an interaction of loci on chromosomes 2 and 6. These findings were confirmed in an independent analysis of chromosome substitution strain mice. The identification of genomic regions containing loci causally associated with AHR and the demonstration that this trait requires their interaction have important implications for the dissection of the genetic etiology of asthma in humans.