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 o n chromosome 17p11.2-p12 causes two inherited peripheral neuropathies, Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with li ability to pressure palsies. This binary repeat contains repetitive DN A elements that include LINES, SINES, medium reiteration frequency rep eats, 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 element s. We report the isolation and characterization of a novel cDNA (C170R F1), 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-RE P element. This finding-shows that C170RF1 and COX10 are being transcr ibed from opposite strands of identical DNA sequences that are separat ed by 1.5 Mb in the genome. RT-PCR analysis showed the proximal transc ript was expressed in skeletal muscle. Sequence analysis identified an open reading frame encoding a 199-amino-acid protein. Zoo blot analys is showed that the transcript is conserved in nonhuman primates. The p resence of a binary repeat contributes to the instability of this regi on of chromosome 17, yet two CMT1A-REP elements are present in the chi mpanzee and all human populations. The presence of expressed sequences in both elements of the CMT1A-REP binary repeat could explain the mai ntenance of this repeat in humans. (C) 1997 Academic Press.