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

Valerio Carelli, Alessandro Achilli, Maria Lucia Valentino, Chiara Rengo, Ornella Semino, Maria Pala, Anna Olivieri, Marina Mattiazzi, Francesco Pallotti, Franco Carrara, Massimo Zeviani, Vincenzo Leuzzi, Carla Carducci, Giorgio Valle, Barbara Simionati, Luana Mendieta, Solange Salomao, Rubens Belfort, Alfredo A. Sadun, Antonio Torroni

Research output: Contribution to journalArticle

135 Citations (Scopus)

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.

LanguageEnglish
Pages564-574
Number of pages11
JournalAmerican Journal of Human Genetics
Volume78
Issue number4
DOIs
Publication statusPublished - 1 Apr 2006
Externally publishedYes

Fingerprint

Leber's Hereditary Optic Atrophy
Pedigree
Mitochondrial DNA
Genetic Recombination
Haplotypes
Electron Transport Complex I
Cytochromes b
Electron Transport
Italy
Mothers
Amino Acids
Mutation

Cite this

Carelli, Valerio ; Achilli, Alessandro ; Valentino, Maria Lucia ; Rengo, Chiara ; Semino, Ornella ; Pala, Maria ; Olivieri, Anna ; Mattiazzi, Marina ; Pallotti, Francesco ; Carrara, Franco ; Zeviani, Massimo ; Leuzzi, Vincenzo ; Carducci, Carla ; Valle, Giorgio ; Simionati, Barbara ; Mendieta, Luana ; Salomao, Solange ; Belfort, Rubens ; Sadun, Alfredo A. ; Torroni, Antonio. / Haplogroup effects and recombination of mitochondrial DNA : Novel clues from the analysis of leber hereditary optic neuropathy pedigrees. In: American Journal of Human Genetics. 2006 ; Vol. 78, No. 4. pp. 564-574.
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Carelli, V, Achilli, A, Valentino, ML, 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 2006, 'Haplogroup effects and recombination of mitochondrial DNA: Novel clues from the analysis of leber hereditary optic neuropathy pedigrees', American Journal of Human Genetics, vol. 78, no. 4, pp. 564-574. https://doi.org/10.1086/501236

Haplogroup effects and recombination of mitochondrial DNA : Novel clues from the analysis of leber hereditary optic neuropathy pedigrees. / Carelli, Valerio; Achilli, Alessandro; Valentino, Maria Lucia; Rengo, Chiara; Semino, Ornella; Pala, Maria; Olivieri, Anna; Mattiazzi, Marina; Pallotti, Francesco; Carrara, Franco; Zeviani, Massimo; Leuzzi, Vincenzo; Carducci, Carla; Valle, Giorgio; Simionati, Barbara; Mendieta, Luana; Salomao, Solange; Belfort, Rubens; Sadun, Alfredo A.; Torroni, Antonio.

In: American Journal of Human Genetics, Vol. 78, No. 4, 01.04.2006, p. 564-574.

Research output: Contribution to journalArticle

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T2 - American Journal of Human Genetics

AU - Carelli, Valerio

AU - Achilli, Alessandro

AU - Valentino, Maria Lucia

AU - Rengo, Chiara

AU - Semino, Ornella

AU - Pala, Maria

AU - Olivieri, Anna

AU - Mattiazzi, Marina

AU - Pallotti, Francesco

AU - Carrara, Franco

AU - Zeviani, Massimo

AU - Leuzzi, Vincenzo

AU - Carducci, Carla

AU - Valle, Giorgio

AU - Simionati, Barbara

AU - Mendieta, Luana

AU - Salomao, Solange

AU - Belfort, Rubens

AU - Sadun, Alfredo A.

AU - Torroni, Antonio

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