Haplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees.

TitleHaplogroup effects and recombination of mitochondrial DNA: novel clues from the analysis of Leber hereditary optic neuropathy pedigrees.
Publication TypeJournal Article
Year of Publication2006
AuthorsCarelli, V, Achilli, A, Valentino, MLucia, Rengo, C, Semino, O, Pala, M, Olivieri, A, Mattiazzi, M, Pallotti, F, Carrara, F, Zeviani, M, Leuzzi, V, Carducci, C, Valle, G, Simionati, B, Mendieta, L, Salomao, S, Belfort, R, Sadun, AA, Torroni, A
JournalAm J Hum Genet
Volume78
Issue4
Pagination564-74
Date Published2006 Apr
ISSN0002-9297
KeywordsDNA, Mitochondrial, Female, Haplotypes, Humans, Male, Molecular Sequence Data, Optic Atrophy, Hereditary, Leber, Pedigree, Recombination, Genetic
Abstract

The mitochondrial DNA (mtDNA) of 87 index cases with Leber hereditary optic neuropathy (LHON) sequentially diagnosed in Italy, including an extremely large Brazilian family of Italian maternal ancestry, was evaluated in detail. Only seven pairs and three triplets of identical haplotypes were observed, attesting that the large majority of the LHON mutations were due to independent mutational events. Assignment of the mutational events into haplogroups confirmed that J1 and J2 play a role in LHON expression but narrowed the association to the subclades J1c and J2b, thus suggesting that two specific combinations of amino acid changes in the cytochrome b are the cause of the mtDNA background effect and that this may occur at the level of the supercomplex formed by respiratory-chain complexes I and III. The families with identical haplotypes were genealogically reinvestigated, which led to the reconnection into extended pedigrees of three pairs of families, including the Brazilian family with its Italian counterpart. The sequencing of entire mtDNA samples from the reconnected families confirmed the genealogical reconstruction but showed that the Brazilian family was heteroplasmic at two control-region positions. The survey of the two sites in 12 of the Brazilian subjects revealed triplasmy in most cases, but there was no evidence of the tetraplasmy that would be expected in the case of mtDNA recombination.

DOI10.1086/501236
Alternate JournalAm. J. Hum. Genet.
Citation Key10.1086/501236
PubMed ID16532388
PubMed Central IDPMC1424694
Grant ListGGP030039 / / Telethon / Italy