ORNITHINE AMINOTRANSFERASE (OAT): EVIDENCE FOR A DISPERSED GENE FAMILY WITH MEMBER(S) LOCALIZED TO Xp11.1 – Xp21.1

Abstract

OAT is a homotetrameric, mitochondrial matrix enzyme deficient in the autosomal recessive retinal degeneration, gyrate atrophy of the choroid and retina. We have cloned and sequenced a near full length human OAT cDNA. We used this to probe genomic DNA digested with various restriction enzymes and found up to 15 OAT-hybridizing fragments (OAThf). They map to 2 locations: 1/3 are on chromosome 10 (10-OAThf) and represent the OAT structural gene; 2/3 are on Xp11.1-21.1 (X-OAThf). Examination of primate DNAs show that this division of X- and autosomal-OAThf has existed for at least 25 million yrs. The X-OAThf do not hybridize to a near full-length cDNA for ornithine transcarbamylase, another ornithine-metabolizing enzyme mapping to Xp21.1. We isolated OAT-hybridizing genomic clones from chromosomes 10 and X. Preliminary sequence analysis of one X clone shows discrete blocks of high nucleotide homology (92%) to OAT cDNA with in-frame stop codons and typical intron-exon junctions indicating that it is a non-processed pseudogene of either OAT or another DAT-related gene. Comparison of the sequences of clones from 10 and X shows similar but not identical positioning of intron-exon junctions. These results suggest that the OAT structural gene on 10 is a member of a small dispersed gene family with a non-processed pseudogene and probably other members all localized to Xp11.1 to Xp21.1.