title: New evidence of a mitochondrial genetic background paradox: impact of the J haplogroup on the A3243G mutation.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1Université Bordeaux 1, Laboratoire d'Anthropologie des Populations du Passé, UMR 5199 PACEA, 33400 Talence, France. d.pierron@anthropologie.u-bordeaux1.fr
authors.forename: Denis
authors.initials: D
authors.lastname: Pierron
authors.forename: Christophe
authors.initials: C
authors.lastname: Rocher
authors.forename: Patricia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Martin-Négrier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allouche
authors.forename: Cécile
authors.initials: C
authors.lastname: Batandier
authors.forename: Benedicte
authors.initials: B
authors.lastname: Mousson de Camaret
authors.forename: Catherine
authors.initials: C
authors.lastname: Godinot
authors.forename: Agnes
authors.initials: A
authors.lastname: Rotig
authors.forename: Delphine
authors.initials: D
authors.lastname: Feldmann
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanne-Chantelot
authors.forename: Benoit
authors.initials: B
authors.lastname: Arveiler
authors.forename: Erwann
authors.initials: E
authors.lastname: Pennarun
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Marc
authors.initials: M
authors.lastname: Crouzet
authors.forename: Pascal
authors.initials: P
authors.lastname: Murail
authors.forename: Didier
authors.initials: D
authors.lastname: Thoraval
authors.forename: Thierry
authors.initials: T
authors.lastname: Letellier
mesh_terms: D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004272:DNA, Mitochondrial / Q000235:genetics*; D005602:France; D006239:Haplotypes; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics; D009154:Mutation; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012356:RNA, Transfer, Leu / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D004247:DNA