THE HUMAN COX10 GENE IS DISRUPTED DURING HOMOLOGOUS RECOMBINATION BETWEEN THE 24 KB PROXIMAL AND DISTAL CMT1A-REPS

The CMT1A-REPs are two large directly repeating DNA sequences located on chromosome 17p11.2-p12 flanking the region duplicated in patients w ith Charcot-Marie-Tooth disease type 1A (CMT1A) and deleted in patient s with hereditary neuropathy with liability to pressure palsies (HNPP) , We have sequenced two cosmids, c74F4 and c15H12, which contain the e ntire proximal and distal CMT1A-REPs and determined that these repeats are similar to 99% identical across a 24011 bp region, In addition, b oth contain an exon of the human heme A:faunesyltransferase gene (COX1 0), Hybridization studies revealed that COX10 spans the distal CMT1A-R EP, while the proximal CMT1A-REP contains an isolated COX10 'pseudo-ex on', There is also a COX10 hybridization signal on chromosome 10 which appears to represent a processed pseudogene, We propose that the dist al CMT1A-REP represents the progenitor copy of COX10 exon VI which was duplicated with surrounding intronic sequences during mammalian genom e evolution and that the HNPP deletion results in a COX10 null allele.