The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene
The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene
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DOI：
10.1006/geno.1997.5012
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发表时间：
1997-11-15
期刊：
影响因子：
4.4
通讯作者：
Nicholson, GA
中科院分区：
文献类型：
--
作者：
Kennerson, ML;Nassif, NT;Nicholson, GA
染色体17p11.2-p12上CMT1A- rep二元重复序列的两个元素的错位导致两种遗传性周围神经病变，Charcot-Marie-Tooth型1A （CMT1A）和遗传性神经病变，易导致压力性麻痹。这种二元重复包含重复的DNA元件，包括LINES、sin、中等重复频率重复和转座子样元件。COX10基因已被定位到远端CMT1A-REP元件上10 kb的着丝粒，该基因的一部分同时存在于近端和远端CMT1A-REP元件中。我们报道了一种新的cDNA （C170RF1）的分离和鉴定，它将着丝粒映射到近端CMT1A-REP元件并部分位于其内。C170RF1的一部分转录自近端CMT1A-REP元件中存在的COX10部分基因重复的相反链。这一发现表明，C170RF1和COX10是从基因组中相隔1.5 Mb的相同DNA序列的相反链上转录的。RT-PCR分析显示，近端转录本在骨骼肌中表达。序列分析鉴定出一个编码199个氨基酸蛋白的开放阅读框。Zoo blot分析表明，该转录本在非人灵长类动物中是保守的。二元重复序列的存在导致了17号染色体这一区域的不稳定性，然而两个CMT1A-REP元素在黑猩猩和所有人类群体中都存在。在CMT1A-REP二元重复序列的两个元素中表达序列的存在可以解释该重复序列在人类中的维持。(C) 1997学术出版社。
Misalignment between the two elements of the CMT1A-REP binary repeat on chromosome 17p11.2-p12 causes two inherited peripheral neuropathies, Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies. This binary repeat contains repetitive DNA elements that include LINES, SINES, medium reiteration frequency repeats, and a transposon-like element. The COX10 gene has been mapped 10 kb centromeric to the distal CMT1A-REP element, and a portion of this gene is present in both the proximal and the distal CMT1A-REP elements. We report the isolation and characterization of a novel cDNA (C170RF1), which maps centromeric to and partially within the proximal CMT1A-REP element. Part of C170RF1 is transcribed from the opposite strand of the COX10 partial gene duplication present in the proximal CMT1A-REP element. This finding-shows that C170RF1 and COX10 are being transcribed from opposite strands of identical DNA sequences that are separated by 1.5 Mb in the genome. RT-PCR analysis showed the proximal transcript was expressed in skeletal muscle. Sequence analysis identified an open reading frame encoding a 199-amino-acid protein. Zoo blot analysis showed that the transcript is conserved in nonhuman primates. The presence of a binary repeat contributes to the instability of this region of chromosome 17, yet two CMT1A-REP elements are present in the chimpanzee and all human populations. The presence of expressed sequences in both elements of the CMT1A-REP binary repeat could explain the maintenance of this repeat in humans. (C) 1997 Academic Press.