A high-density transcript map of the human dominant optic atrophy OPA1 gene locus and re-evaluation of evidence for a founder haplotype

Dominant optic atrophy (DOA, gene OPA1) is the commonest form of inherited optic atrophy. Linkage studies have shown that a locus for this disease lie s in a 1.4-cM region at chromosome 3q28 --> q29 and have suggested a founde r haplotype for as many as 95% of the linked families. To aid the identific ation of candidate genes for this disease, we have constructed a Bacterial Artificial Chromosome (BAC) contig covering approximately 3.3 Mb and encomp assing the OPA1 critical region (flanking markers D3S3669 and D3S3562). Thi s physical map corrects errors in the marker order reported in the literatu re. allowing the OPA1 critical region to be precisely defined. A reassessme nt of the founder effect in the light of the revised marker order suggests that it may not be as significant as had previously been suggested. A high- density transcript map was created by precisely mapping genes and expressed sequence tags (ESTs) from GeneMap'99, that have been loosely assigned to t he region by radiation hybrid mapping. One known gene (KIAA0567 protein) an d 15 ESTs were found to lie within the minimal disease region. Analysis of the sequence data already available from within the OPA1 critical region al lowed the identification and mapping of a further 31 ESTs. The work present ed in this study provides the basis for the characterisation of candidate g enes and the ultimate identification of the gene mutated in DOA. Copyright (C) 2001 S. Karger AG, Basel.