Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder.

TitleIdentification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder.
Publication TypeJournal Article
Year of Publication2005
AuthorsHudson, G, Keers, S, Yu-Wai-Man, P, Griffiths, P, Huoponen, K, Savontaus, M-L, Nikoskelainen, E, Zeviani, M, Carrara, F, Horvath, R, Karcagi, V, Spruijt, L, de Coo, IFM, Smeets, HJM, Chinnery, PF
JournalAm J Hum Genet
Volume77
Issue6
Pagination1086-91
Date Published2005 Dec
ISSN0002-9297
KeywordsAlleles, Chromosome Mapping, Chromosomes, Human, X, Cohort Studies, DNA, Mitochondrial, Female, Gene Frequency, Genetic Markers, Haplotypes, Heterozygote, Homozygote, Humans, Linear Models, Linkage Disequilibrium, Male, Microsatellite Repeats, Mitochondrial Diseases, Optic Atrophy, Hereditary, Leber, Pedigree, Penetrance, Phenotype, Point Mutation, Polymorphism, Restriction Fragment Length, Sex Factors, Statistics, Nonparametric
Abstract

Mitochondrial DNA (mtDNA) mutations are a major cause of human disease. A large number of different molecular defects ultimately compromise oxidative phosphorylation, but it is not clear why the same biochemical defect can cause diverse clinical phenotypes. There is emerging evidence that nuclear genes modulate the phenotype of primary mtDNA disorders. Here, we define an X-chromosomal haplotype that interacts with specific MTND mutations to cause visual failure in the most common mtDNA disease, Leber hereditary optic neuropathy. This effect is independent of the mtDNA genetic background and explains the variable penetrance and sex bias that characterizes this disorder.

DOI10.1086/498176
Alternate JournalAm. J. Hum. Genet.
Citation Key10.1086/498176
PubMed ID16380918
PubMed Central IDPMC1285165
Grant List / / Wellcome Trust / United Kingdom