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

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

Autor Carelli, V Google Scholar
Achilli, A. Google Scholar
Valentino, M. L. Google Scholar
Rengo, C. Google Scholar
Semino, O. Google Scholar
Pala, M. Google Scholar
Olivieri, A. Google Scholar
Mattiazzi, M. Google Scholar
Pallotti, F. Google Scholar
Carrara, F. Google Scholar
Zeviani, M. Google Scholar
Leuzzi, V Google Scholar
Carducci, C. Google Scholar
Valle, G. Google Scholar
Simionati, B. Google Scholar
Mendieta, Luana Autor UNIFESP Google Scholar
Salomão, Solange Rios Autor UNIFESP Google Scholar
Belfort, Rubens Junior Autor UNIFESP Google Scholar
Sadun, A. A. Google Scholar
Torroni, A. Google Scholar
Instituição Univ Pavia
Univ So Calif
Univ Bologna
Columbia Univ
Natl Neurol Inst Carlo Besta
Univ Roma La Sapienza
Univ Padua
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Idioma Inglês
Data 2006-04-01
Publicado em American Journal of Human Genetics. Chicago: Univ Chicago Press, v. 78, n. 4, p. 564-574, 2006.
ISSN 0002-9297 (Sherpa/Romeo, fator de impacto)
Editor Univ Chicago Press
Extensão 564-574
Fonte http://dx.doi.org/10.1086/501236
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000236755900004
URI http://repositorio.unifesp.br/handle/11600/28799

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