New evidence of a mitochondrial genetic background paradox: impact of the J haplogroup on the A3243G mutation. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue BMC Medical Genetics Année : 2008

New evidence of a mitochondrial genetic background paradox: impact of the J haplogroup on the A3243G mutation.

Pascal Reynier
Benedicte Mousson de Camaret
  • Fonction : Auteur
Marc Crouzet
  • Fonction : Auteur

Résumé

Background: The A3243G mutation in the tRNALeu gene (UUR), is one of the most common pathogenic mitochondrial DNA (mtDNA) mutations in France, and is associated with highly variable and heterogeneous disease phenotypes. To define the relationships between the A3243G mutation and mtDNA backgrounds, we determined the haplogroup affiliation of 142 unrelated French patients – diagnosed as carriers of the A3243G mutation – by control-region sequencing and RFLP survey of their mtDNAs. Results: The analysis revealed 111 different haplotypes encompassing all European haplogroups, indicating that the 3243 site might be a mutational hot spot. However, contrary to previous findings, we observed a statistically significant underepresentation of the A3243G mutation on haplogroup J in patients (p = 0.01, OR = 0.26, C.I. 95%: 0.08–0.83), suggesting that might be due to a strong negative selection at the embryo or germ line stages. Conclusion: Thus, our study supports the existence of mutational hotspot on mtDNA and a "haplogroup J paradox," a haplogroup that may increase the expression of mtDNA pathogenic mutations, but also be beneficial in certain environmental contexts.

Dates et versions

halshs-00433459 , version 1 (19-11-2009)

Identifiants

Citer

Denis Pierron, Christophe Rocher, Patricia Amati-Bonneau, Pascal Reynier, Marie-Laure Martin-Négrier, et al.. New evidence of a mitochondrial genetic background paradox: impact of the J haplogroup on the A3243G mutation.. BMC Medical Genetics, 2008, 9:41, 1-13 (page number not for citation purposes). ⟨10.1186/1471-2350-9-41⟩. ⟨halshs-00433459⟩
194 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More