Pentao L, Wise C A, Chinault A C, Patel P I, Lupski J R
Institute for Molecular Genetics, College of Medicine, Houston, Texas 77030.
Nat Genet. 1992 Dec;2(4):292-300. doi: 10.1038/ng1292-292.
We have constructed a 3.1 megabase (Mb) physical map of chromosome 17p11.2-p12, which contains a submicroscopic duplication in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). We find that the CMT1A duplication is a tandem repeat of 1.5 Mb of DNA. A YAC contig encompassing the CMT1A duplication and spanning the endpoints was also developed. Several low copy repeats in 17p11.2-p12 were identified including the large (> 17 kb) CMT1A-REP unit which may be part of a mosaic repeat. CMT1A-REP flanks the 1.5 Mb CMT1A monomer unit on normal chromosome 17 and is present in an additional copy on the CMT1A duplicated chromosome. We propose that the de novo CMT1A duplication arises from unequal crossing over due to misalignment at these CMT1A-REP repeat sequences during meiosis.
我们构建了17号染色体p11.2 - p12区域的一个3.1兆碱基对（Mb）的物理图谱，该区域在1A型遗传性运动感觉神经病（CMT1A）患者中存在亚显微重复。我们发现CMT1A重复是一段1.5 Mb DNA的串联重复。还构建了一个包含CMT1A重复并跨越其端点的酵母人工染色体（YAC）重叠群。在17p11.2 - p12区域鉴定出了几个低拷贝重复序列，包括大的（> 17 kb）CMT1A - REP单元，它可能是镶嵌重复的一部分。CMT1A - REP在正常的17号染色体上位于1.5 Mb CMT1A单体单元的两侧，并且在CMT1A重复染色体上额外存在一个拷贝。我们提出，新发的CMT1A重复是由于减数分裂期间这些CMT1A - REP重复序列的错配导致不等交换而产生的。
