Human Genetics

, Volume 102, Issue 1, pp 79–86

Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method

A study of 38 British Isles pedigrees

Authors

  • M. Votruba
    • Department of Molecular Genetics, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK Tel.: +44-171-608 6932; Fax: +44-171-608 6863; e-mail: mvotruba@hgmp.mrc.ac.uk
  • Anthony T. Moore
    • Moorfields Eye Hospital, London, UK
  • Shomi S. Bhattacharya
    • Department of Molecular Genetics, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK Tel.: +44-171-608 6932; Fax: +44-171-608 6863; e-mail: mvotruba@hgmp.mrc.ac.uk
Original investigation

DOI: 10.1007/s004390050657

Cite this article as:
Votruba, M., Moore, A. & Bhattacharya, S. Hum Genet (1998) 102: 79. doi:10.1007/s004390050657

Abstract

Dominant optic atrophy, a hereditary optic neuropathy causing decreased visual acuity, colour vision deficits, a centro-caecal scotoma and optic nerve pallor, has been mapped to a genetic interval of 1.4 cM between loci D3S3669 and D3S3562 on chromosome 3q28-qter. In order to further refine the critical disease interval, and to test the power of haplotype analysis and linkage disequilibrium mapping, we identified a total of 38 families with dominant optic atrophy, unrelated on the basis of genealogy, from a data base of genetic eye disease families originating from the British Isles. They were studied with 12 highly polymorphic microsatellite markers spanning a region of 12 cM around the dominant optic atrophy locus (OPA1). Allelic frequency analysis [chi-squared test, likeli-hood ratio test (LRT) and P values] and haplotype parsimony analysis showed evidence of a founder effect in 36 of the 38 pedigrees. Six markers (D3S3669, D3S1523, D3S3642, D3S2305, D3S3590 and D3S3562), spanning 1.4 cM across the disease-associated region, demonstrated significant linkage disequilibrium by LRT (P < 0.05). A peak LRT value of 10.86 (P < 0.0005, λ = 0.4) occurred at D3S3669. On linkage disequilibrium multipoint analysis the maximum lod score of 8.01 is achieved at D3S1523, and 95% confidence intervals suggest that OPA1 lies within ca. 400 kb of D3S1523.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998