Title | Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Hudson, 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 |
Journal | Am J Hum Genet |
Volume | 77 |
Issue | 6 |
Pagination | 1086-91 |
Date Published | 2005 Dec |
ISSN | 0002-9297 |
Keywords | Alleles, 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. |
DOI | 10.1086/498176 |
Alternate Journal | Am. J. Hum. Genet. |
Citation Key | 10.1086/498176 |
PubMed ID | 16380918 |
PubMed Central ID | PMC1285165 |
Grant List | / / Wellcome Trust / United Kingdom |