The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene.
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.
Kennerson
M L
ML
Molecular Medicine Laboratory, University of Sydney, Concord Hospital, New South Wales, Australia. marinak@med.usyd.edu.au
Nassif
N T
NT
Dawkins
J L
JL
DeKroon
R M
RM
Yang
J G
JG
Nicholson
G A
GA
D000328:Adult; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003576:Electron Transport Complex IV; D005796:Genes / Q000235:genetics; D005807:Genes, Overlapping / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009928:Organ Specificity; D011323:Primates; D012333:RNA, Messenger / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014158:Transcription, Genetic
D008565:Membrane Proteins; D012333:RNA, Messenger; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases