Genomic organization of two novel genes on human Xq28: Compact head to head arrangement of IDH gamma and TRAP delta is conserved in rat and mouse

In this paper we present the entire genomic sequence as well as the cDNA sequence of two new human genes encoding the gamma subunit of the NAD(+)-dependent isocitrate dehydrogenase (H-IDH gamma) and the translocon-associated protein delta subunit (TRAP delta). These genes are located on region q28 of the human X chromosome, approximately 70 kb telomeric to the adrenoleukodystrophy locus (ALD). The sequences of the transcripts of both genes were obtained by searching the EST database with genomic data. Identified ESTs were completely sequenced and assembled to cDNAs comprising the entire coding region. For IDH gamma, several EST clones indicate differential splicing. IDH gamma and TRAP delta are arranged in a compact head to head manner. The nontranscribed intergenic region represents only 133 bp and is embedded in a CpG island. The CpG island obviously functions as a bidirectional promoter to initiate the transcription of both functionally unrelated genes with quite distinct expression patterns. This exceptional gene arrangement prompted us to clone and sequence genomic DNA fragments containing the homologous intergenic regions of rat and mouse. We show that in both species this area is similarly compact and represents less than 249 bp in rat and not more than 164 bp in mouse. In both cases this intergenic region is embedded in a CpG; island and is highly conserved with nucleotide identity values ranging from 70.1% between human and rat to 92.6% between mouse and rat. (C) 1997 Academic Press.