Ocular Albinism Type 1 - Molecular Biology of Oa1

Molecular Biology of Oa1

Human Oa1 gene has been identified by positional cloning as a 40kb gene mapped to Xp22.3-Xp22.2. Later, a mouse homolog of the human Oa1 gene was also identified and cloned. It codes for a 404 amino acid long protein with up to three potential glycosylation sites. The transcript has been found to be expressing very well in retinal pigment epithelium and skin and to a much lesser extent in brain and adrenal glands.

Mutations in Oa1 have been well characterized and studied using various techniques like southern blot analyses, single-strand conformation polymorphism and sequence analysis. Most of these mutations have been reported to be occurring in the N-terminus and few in the trans-membrane regions but very rarely in the much conserved cytoplasmic C-terminus. Populations belonging to different ethnic groups have been extensively analyzed and a database has been created recording the details of mutations related to OA1. A total of 25 missense, 2 nonsense, 9 frameshift, and 5 splicing mutations have been reported till date. In addition to these mutations, there also occur several deletions in one or many of the exons of Oa1 gene, especially exon 2. These deletions are presumed to be because of unequal crossing-over due to the presence of flanking Alu regions. In some cases, the entire Oa1 gene is deleted along with other contiguous genes. Many different polymorphisms have also been detected, mainly in intron 1.

Tissue-specific control of Oa1 transcription is by a 617bp long E-box region bound by Mitf. Mitf has been shown to regulate expression of many melanosomal genes like TYR and TRP-1 through the E-box motif (CATGTG). Vetrini et al. have used adenoviral vectors to study tissue-specificity of Oa1 transcription through Mitf and observed that this regulation in conserved in human Oa1 gene.