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

International audienceBackground: 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

Accumulation de délétions aléatoires de l’ADN mitochondrial au cours du vieillissement, conséquences sur l’activité mitochondriale musculaire

National audienc

New evidence of a mitochondrial genetic background paradox: Impact of the J haplogroup on the A3243G mutation-0

Impacts on the OXPHOS level, their implications on an individual level, and their impact on the distribution of populations studied within the phylogeny.<p><b>Copyright information:</b></p><p>Taken from "New evidence of a mitochondrial genetic background paradox: Impact of the J haplogroup on the A3243G mutation"</p><p>http://www.biomedcentral.com/1471-2350/9/41</p><p>BMC Medical Genetics 2008;9():41-41.</p><p>Published online 7 May 2008</p><p>PMCID:PMC2409300.</p><p></p