CMT1A重复断点在CMT1A-REP重复序列的700 bp区间内成簇。

Clustering of CMT1A duplication breakpoints in a 700 bp interval of the CMT1A-REP repeat.

作者信息

Yamamoto M, Keller M P, Yasuda T, Hayasaka K, Ohnishi A, Yoshikawa H, Yanagihara T, Mitsuma T, Chance P F, Sobue G

机构信息

Department of Neurology, Nagoya University School of Medicine, Japan.

出版信息

Hum Mutat. 1998;11(2):109-13. doi: 10.1002/(SICI)1098-1004(1998)11:2<109::AID-HUMU2>3.0.CO;2-E.

DOI:10.1002/(SICI)1098-1004(1998)11:2<109::AID-HUMU2>3.0.CO;2-E

PMID:9482573

Abstract

The CMT1A-REP repeat is proposed to mediate unequal crossover leading to a 1.5 Mb duplication in chromosome 17p11.2-12 associated with Charcot-Marie-Tooth neuropathy type 1A (CMT1A). There is an apparent recombinational "hotspot" in the CMT1A-REP repeat since the majority of crossover breakpoints for CMT1A are located within a 1.7 kb interval. Further to characterize the crossover breakpoint region, we constructed PCR primers that specifically amplify the duplication breakpoint junctions in a series of Japanese and Caucasian CMT1A patients. We mapped the breakpoints in 89% of patients within a 700 bp interval of the CMT1A-REP repeat. This 700 bp region is 1.3 kb telomeric to a previously described mariner-like transposable element. Our observations further define the location of crossovers for CMT1A and provide additional evidence that this region is a recombinational "hotspot" within the CMT1A-REP repeat.

摘要

CMT1A重复序列被认为介导了不等交换，导致17号染色体p11.2 - 12区域出现1.5 Mb的重复，这与1A型遗传性运动感觉神经病（CMT1A）相关。CMT1A重复序列中存在一个明显的重组“热点”，因为CMT1A的大多数交换断点位于一个1.7 kb的区间内。为了进一步表征交换断点区域，我们设计了PCR引物，可特异性扩增一系列日本和高加索CMT1A患者中的重复断点连接。我们在CMT1A重复序列的一个700 bp区间内定位了89%患者的断点。这个700 bp区域位于一个先前描述的类水手转座元件的端粒方向1.3 kb处。我们的观察结果进一步明确了CMT1A交换的位置，并提供了额外证据，证明该区域是CMT1A重复序列内的一个重组“热点”。