OAT

OAT (ornithine aminotransferase) is the structural gene whose loss of function causes gyrate atrophy of the choroid and retina, an autosomal recessive disorder, as established by genetic linkage and allelic disequilibrium analysis in a human pedigree (PMID:2893548). The gene maps to human chromosome 10, distinct from related sequences residing on the X chromosome (PMID:2893548). Beyond this gene-disease mapping (PMID:2893548), the enzymatic mechanism, substrate specificity, and structural characterization of the human protein are not represented in the available corpus.

1. 1988 Medium

   Before this work it was unclear which locus harbored the causative defect for gyrate atrophy and whether the OAT structural gene resided on chromosome 10 or the X chromosome where related sequences also map; the study answered this by demonstrating co-segregation and allelic disequilibrium tying the chromosome 10 OAT gene to the disease.

   Evidence RFLP analysis with noncoding single-copy probes and cDNA subclones, pedigree linkage, and chromosomal mapping in human families

   PMID:2893548

   Open questions at the time

   • Does not reconstitute or characterize OAT enzymatic activity in vitro
   • Does not identify the specific causative mutations or their effect on protein function
   • No structural model of the human enzyme established

• The catalytic mechanism, substrate specificity, subcellular handling, and structural basis of disease-causing mutations of human OAT remain uncharacterized in the available corpus.
• No direct in vitro enzymatic reconstitution captured
• No structural characterization of the human enzyme captured
• Genotype-phenotype mechanism linking specific mutations to disease not resolved