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

Cytogenet Cell Genet. 2001;92(1-2):97-102. doi: 10.1159/000056876.

Abstract

Dominant optic atrophy (DOA, gene OPA1) is the commonest form of inherited optic atrophy. Linkage studies have shown that a locus for this disease lies in a 1.4-cM region at chromosome 3q28-->q29 and have suggested a founder haplotype for as many as 95% of the linked families. To aid the identification of candidate genes for this disease, we have constructed a Bacterial Artificial Chromosome (BAC) contig covering approximately 3.3 Mb and encompassing the OPA1 critical region (flanking markers D3S3669 and D3S3562). This physical map corrects errors in the marker order reported in the literature, allowing the OPA1 critical region to be precisely defined. A reassessment 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 the region by radiation hybrid mapping. One known gene (KIAA0567 protein) and 15 ESTs were found to lie within the minimal disease region. Analysis of the sequence data already available from within the OPA1 critical region allowed the identification and mapping of a further 31 ESTs. The work presented in this study provides the basis for the characterisation of candidate genes and the ultimate identification of the gene mutated in DOA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Artificial, Bacterial / genetics
  • Contig Mapping*
  • England
  • Expressed Sequence Tags
  • Female
  • Founder Effect*
  • Genes, Dominant / genetics*
  • Genetic Markers / genetics
  • Haplotypes / genetics*
  • Humans
  • Male
  • Meiosis / genetics
  • Molecular Sequence Data
  • Mutation / genetics
  • Optic Atrophies, Hereditary / genetics*
  • Pedigree
  • Polymorphism, Genetic / genetics
  • Sequence Tagged Sites

Substances

  • Genetic Markers

Associated data

  • GENBANK/AA438507
  • GENBANK/AC016947
  • GENBANK/AC021846
  • GENBANK/AC023596
  • GENBANK/AC024447
  • GENBANK/AC024559
  • GENBANK/AC025847
  • GENBANK/AC026101
  • GENBANK/AC026529
  • GENBANK/AC027042
  • GENBANK/AC027402
  • GENBANK/AC068162