Blair I P, Hulme D, Dawkins J L, Nicholson G A
Molecular Medicine Laboratory, University of Sydney, Concord Hospital, New South Wales, Australia.
Genomics. 1998 Jul 15;51(2):277-81. doi: 10.1006/geno.1998.5373.
Hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant peripheral neuropathy, involving sensory and motor neurons. The disease involves distal sensory loss, distal muscle wasting and weakness, and variable neural deafness. The HSN-I locus has been mapped to a 3- to 4-cM genetic interval on chromosome 9q22.1-q22.3. As part of a positional cloning effort to identify the HSN-I gene, we have generated a YAC based transcript map that spans approximately 8 Mb between D9S318 and D9S1786. This transcript map encompasses both the HSN-I critical interval and the locus for multiple self-healing squamous epithelioma (MSSE, previously named ESS1). Forty two ESTs and six characterized genes have been localized across 10 YAC clones, within a framework of 19 genetic linkage markers. Three other characterized genes were localized immediately adjacent to this interval. We have accurately mapped two recently identified genes: NINJ1 was anchored to D9S12II, and the localization of the NOR1 gene was significantly refined. We have also investigated NOR1 and several other characterized genes that localize to chromosome 9q22 for a pathogenic role in HSN-I. This map provides candidate genes for HSN-I and MSSE and is an important step toward completing a functional map of this gene-rich interval.
遗传性感觉神经病I型（HSN-I）是一种常染色体显性周围神经病，累及感觉和运动神经元。该病表现为远端感觉丧失、远端肌肉萎缩和无力，以及不同程度的神经性耳聋。HSN-I基因座已被定位到9号染色体q22.1-q22.3上一个3至4厘摩的遗传区间。作为定位克隆HSN-I基因工作的一部分，我们构建了一个基于酵母人工染色体（YAC）的转录图谱，该图谱跨越D9S318和D9S1786之间约8兆碱基对的区域。这个转录图谱既包含HSN-I关键区间，也包含多发性自愈性鳞状上皮瘤（MSSE，以前称为ESS1）的基因座。42个表达序列标签（EST）和6个已鉴定的基因已定位在10个YAC克隆上，位于19个遗传连锁标记的框架内。另外3个已鉴定的基因定位在这个区间的紧邻区域。我们已精确地定位了两个最近鉴定的基因：NINJ1定位于D9S12II，并且显著优化了NOR1基因的定位。我们还研究了NOR1和其他几个定位于9号染色体q22的已鉴定基因在HSN-I中的致病作用。这个图谱为HSN-I和MSSE提供了候选基因，是朝着完成这个富含基因区间的功能图谱迈出的重要一步。
