将常染色体显性进行性感觉神经性听力损失（DFNA5）相关基因精细定位到一个2厘摩区域，并排除了一个在内耳中表达的候选基因。

Refined mapping of a gene for autosomal dominant progressive sensorineural hearing loss (DFNA5) to a 2-cM region, and exclusion of a candidate gene that is expressed in the cochlea.

作者信息

Van Laer L, Van Camp G, van Zuijlen D, Green E D, Verstreken M, Schatteman I, Van de Heyning P, Balemans W, Coucke P, Greinwald J H, Smith R J, Huizing E, Willems P

机构信息

Department of Medical Genetics, University of Antwerp, Belgium.

出版信息

Eur J Hum Genet. 1997 Nov-Dec;5(6):397-405.

PMID:9450185

Abstract

A gene for an autosomal dominant form of progressive sensorineural hearing loss (DFNA5) was previously assigned by us to a 15-cM region on chromosome 7p15. In this study, the DFNA5 candidate region was refined to less than 2 cM, and completely cloned in a YAC contig. The HOXA1 gene located in 7p15 was considered to be a good candidate gene for DFNA5 as it harbours mutations leading to developmental defects of the inner ear in mice. However, the refinement of the candidate region of DFNA5 excludes the HOXA1 gene as a candidate for DFNA5. We cloned a novel candidate gene (CG1, candidate gene 1), which is expressed in human fetal cochlea, from the DFNA5 candidate region. The complete cDNA sequence of CG1, encoding a 423 amino acid protein of unknown function, was determined. Mutation analysis of the CG1 gene in DFNA5 patients, however, could not reveal a disease-causing mutation.

摘要

我们先前已将一种常染色体显性进行性感觉神经性听力丧失（DFNA5）的基因定位到7号染色体p15区域上一个15厘摩的区间。在本研究中，DFNA5候选区域被精确定位到小于2厘摩，并在一个酵母人工染色体（YAC）重叠群中完全克隆出来。位于7p15的HOXA1基因被认为是DFNA5的一个良好候选基因，因为它携带的突变会导致小鼠内耳发育缺陷。然而，DFNA5候选区域的精确定位将HOXA1基因排除在DFNA5候选基因之外。我们从DFNA5候选区域克隆了一个新的候选基因（CG1，候选基因1），该基因在人类胎儿耳蜗中表达。确定了CG1的完整cDNA序列，其编码一个功能未知的含423个氨基酸的蛋白质。然而，对DFNA5患者的CG1基因进行突变分析未能发现致病突变。