Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene.

Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem DNA duplication in chromosome 17p11.2-p12, while hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this locus. The 1.5-Mb CMT1A monomer unit duplicated in CMT1A and deleted in HNPP is flanked by two 24-kb direct repeats termed the CMT1A-REPs. Recently, sequence analysis of the CMT1A-REPs revealed that they contain an internal exon of the COX10 gene. To characterize COX10, encoding human heme A:farnesyltransferase, the genomic region was isolated and the gene structure and expression profile were determined. COX10 spans approximately 135 kb and consists of seven exons. Exons I-V are telomeric to the 1.5-Mb CMT1A monomer unit, whereas exon VII is located within this 1.5-Mb region. Exon VI is contained within the distal CMT1A-REP. All splice sites conform to the GT/AG rule. Analysis of the putative promoter region of the COX10 gene indicates that it lacks conventional TATA and CAAT boxes, but it does have several potential transcription factor-binding sites. This gene is expressed in multiple tissues with highest expression observed in the heart, skeletal muscle, and testis.