GENOMIC ORGANIZATION OF 2 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 cD NA sequence of two new human genes encoding the gamma subunit of the N AD(+)-dependent isocitrate dehydrogenase (H-IDH gamma) and the translo con-associated protein delta subunit (TRAP delta). These genes are loc ated on region q28 of the human X chromosome, approximately 70 kb telo meric to the adrenoleukodystrophy locus (ALD). The sequences of the tr anscripts of both genes were obtained by searching the EST database wi th genomic data. Identified ESTs were completely sequenced and assembl ed to cDNAs comprising the entire coding region. For IDH gamma, severa l EST clones indicate differential splicing. IDH gamma and TRAP delta are arranged in a compact head to head manner. The nontranscribed inte rgenic region represents only 133 bp and is embedded in a CpG island. The CpG island obviously functions as a bidirectional promoter to init iate the transcription of both functionally unrelated genes with quite distinct expression patterns. This exceptional gene arrangement promp ted us to clone and sequence genomic DNA fragments containing the homo logous intergenic regions of rat and mouse. We show that in both speci es this area is similarly compact and represents less than 249 bp in r at and not more than 164 bp in mouse. In both cases this intergenic re gion is embedded in a CpG; island and is highly conserved with nucleot ide identity values ranging from 70.1% between human and rat to 92.6% between mouse and rat. (C) 1997 Academic Press.