Two quantitative trait loci affecting progressive hearing loss in 101/H mice
Two quantitative trait loci affecting progressive hearing loss in 101/H mice
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DOI：
10.1007/s00335-004-2438-5
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发表时间：
2006-08-01
期刊：
影响因子：
2.5
通讯作者：
Steel, Karen P.
中科院分区：
文献类型：
--
作者：
Mashimo, Tomoji;Erven, Alexandra E.;Steel, Karen P.
虽然最近在识别耳聋相关基因方面取得了显著进展，但由于在人群中研究这种迟发性复杂疾病的难度极大，因此对进行性听力损失（或年龄相关性听力损失）的遗传基础了解甚少。一些近交系小鼠如129 P1/ReJ、C57 BL/6 J、DBA/2 J和BALB/cByJ已被报道表现出与年龄相关的听力损失，并为人类非综合征性进行性耳聋提供了有价值的模型。在这篇文章中，我们表明，101/H小鼠也表现出进行性耳聋与早期发作。对101/H与MAI/Pas和MBT/Pas野生小鼠杂交的F-2群体进行连锁分析，发现至少有两个主要的数量性状基因座（QTL）影响进行性听力损失。第一个QTL，命名为Phl 1，以6.7的最大LOD得分定位到染色体17的着丝粒区域，迄今为止还没有定位到与遗传相关的QTL。第二个QTL，命名为Phl 2，定位于染色体10，并表现出最大LOD得分为5.3。Phl 2的图谱位置靠近已知的与年龄相关的听力损失（阿勒）的QTL，提示等位性的可能性，尽管阿勒突变本身在这些杂交中没有分离。最后，我们发现了Phl 1和Phl 2之间上位相互作用的一些证据。
Although recent progress in identifying genes involved in deafness has been remarkable, the genetic basis of progressive hearing loss (or age-related hearing loss) is poorly understood because of the extreme difficulty in studying such a late-onset, complex disease in human populations. Several inbred strains of mice such as 129P1/ReJ, C57BL/6J, DBA/2J, and BALB/cByJ have been reported to exhibit age-related hearing loss and provide valuable models for human nonsyndromic progressive deafness. In this article we show that 101/H mice also exhibit progressive deafness with early onset. Linkage analysis of F-2 populations derived from crosses between the 101/H and the MAI/Pas and MBT/Pas wild-derived mice suggested at least two major quantitative trait loci (QTLs) that influence progressive hearing loss. A first QTL, designated Phl1, was mapped with a maximum LOD score of 6.7 to the centromeric region of Chromosome 17, where no deafness-related QTL has been mapped so far. A second QTL, designated Phl2, mapped to Chromosome 10 and exhibited a maximum LOD score of 5.3. The map position of Phl2 near the well-known QTL of age-related hearing loss (Ahl) suggested the possibility of allelism, although the Ahl mutation itself did not segregate in these crosses. Finally, we found some evidence of epistatic interaction between Phl1 and Phl2.