Analysis of the human ornithine aminotransferase gene family.

Ornithine aminotransferase is a mitochondrial matrix enzyme that is deficient in patients with gyrate atrophy, an autosomal recessive disease of the eye. Southern blots of human DNA probed with a previously characterized OAT cDNA showed a complex pattern of gene fragments, suggesting a gene family. Hybridization of these blots with 5' and 3' OAT cDNA probes indicated that there are at least three to four copies of the OAT (approximately 22 kbp) and OAT-related gene sequence(s). We have isolated and partially characterized human OAT gene clones from total genomic and X-chromosome DNA libraries. Sequence analysis confirmed the following previously reported findings on the functional OAT gene: 11 exons, ten introns, an atypical TATA box (TTTAA), two CCAAT boxes, several GC-rich binding sites, 5' sequence homologous to SV40 enhancer core sequence (GTGGA/GA/GA/GG) and promoter region of three urea cycle enzymes (GTATCCTGCCCTC). In addition, we extended the OAT gene sequence in both the 5' and 3' directions and found its promoter region also contained a sequence homologous to the progesterone receptor (TGTTCA/TCC/T), several of the glucocorticoid responsive element (AGAACA), a cyclic AMP-responsive element (TGACGTCG), and recognition motifs for transcription factors AP-2, NF1 and Sp1. Partial sequence analyses of X-chromosome clones demonstrated an intron-less pseudogene with 77% identity to the functional OAT gene. These results demonstrate that the OAT gene is a gene family that contains both functional and related OAT gene sequence(s).