Mapping quantitative trait loci for hearing loss in Black Swiss mice
Mapping quantitative trait loci for hearing loss in Black Swiss mice
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DOI：
10.1016/j.heares.2005.11.006
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发表时间：
2006-02-01
期刊：
影响因子：
2.8
通讯作者：
Noben-Trauth, K
中科院分区：
文献类型：
--
作者：
Drayton, M;Noben-Trauth, K
在常见的近交系小鼠品系中，听力损失是一种非常普遍的数量性状，主要由 Cdh23(753A) 变体和许多其他品系特异性基因座的等位基因控制。在这里，我们研究了非近交系听力损失的遗传基础。 Swiss Webster、CF-1、NIH Swiss、ICR 和 Black Swiss 品系的小鼠表现出渐进性感音神经性听力障碍的听力特征。特别是，CF-1、Black Swiss 和 NIH Swiss 小鼠表现出早发性听力损伤，ICR 和 Swiss Webster 小鼠表现出迟发性听力损失，而 NMRI 小鼠则具有正常听力。通过数量性状位点 (QTL) 作图，确定了瑞士黑小鼠听力损失的两个重要 QTL：一个 QTL 映射到染色体 (chr) 10（名为 ahl5，LOD 8.9，峰值关联 35-42 cM），第二个 QTL 定位于 chr 18（ahl6，LOD 3.8，38-44 cM）。 Ahl5 和 ahl6 分别占回交变异的 61% 和 32%。钙粘蛋白 23 (Cdh23) 和原钙粘蛋白 15 (Pedh15) 在 ahl5 的 95% 置信区间内作图，在编码外显子中具有核苷酸多态性，但这些似乎与听力表型无关。 Cdh23 基因座的单倍型分析证明了黑瑞士人和常见近交系之间的系统发育关系。 (c) 2005 Elsevier B.V. 保留所有权利。
In common inbred mouse strains, hearing loss is a highly prevalent quantitative trait, which is mainly controlled by the Cdh23(753A) variant and alleles at numerous other strain-specific loci. Here, we investigated the genetic basis of hearing loss in non-inbred strains. Mice of Swiss Webster, CF-1, NIH Swiss, ICR, and Black Swiss strains exhibited hearing profiles characteristic of progressive, sensorineural hearing impairment. In particular, CF-1, Black Swiss, and NIH Swiss mice showed early-onset hearing impairment, ICR and Swiss Webster mice expressed a delayed-onset hearing loss, and NMRI mice had normal hearing. By quantitative trait locus (QTL) mapping, two significant QTLs were identified underlying hearing loss in Black Swiss mice: one QTL mapped to chromosome (chr) 10 (named ahl5, LOD 8.9, peak association 35-42 cM) and a second QTL localized to chr 18 (ahl6, LOD 3.8, 38-44 cM). Ahl5 and ahl6 account for 61% and 32% of the variation in the backcross, respectively. Cadherin 23 (Cdh23) and protocadherin 15 (Pedh15), mapping within the 95% confidence interval of ahl5, bear nucleotide polymorphisms in coding exons, but these appear to be unrelated to the hearing phenotype. Haplotype analyses across the Cdh23 locus demonstrated the phylogenetic relationship between Black Swiss and common inbred strains. (c) 2005 Elsevier B.V. All rights reserved.