title: Estimating the age of CFTR mutations predominantly found in Brittany (Western France).
abstract: BACKGROUND
  Disparities in the spectrum of mutations within the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene are commonly observed in populations from different ethnical and/or geographical origins. The occurrence of CF in Brittany (western France) is one of the highest in populations from Caucasian origin (<1/2000 in specific areas). The W846X(2), 1078delT and G551D mutations, as well as the I1027T polymorphism in cis with the DeltaF508 mutation (currently referred to as p.F508del) are particularly frequent in this area. We investigated the age of the respective variants in the region of interest.
  
  
  METHODS
  Several polymorphic markers surrounding the CFTR gene were genotyped. Allele frequencies as well as mutation rates and other parameters were used to calculate the respective age of the most recent common ancestors in the region of interest by a previously employed, simple likelihood-based method.
  
  
  RESULTS
  Following haplotype reconstruction and simulation, the ages were estimated to be approximately 600, 1000, 1200 and 600 years, respectively (with a 95% confidence interval).
  
  
  CONCLUSIONS
  These datings thus provide historical insights in the context of understanding population migrations. They also underline the usefulness of this method for estimating the age of rare mutations with a limited number of carriers.
authors.affiliation: Inserm, U613, Génétique Moléculaire et Génétique Epidémiologique, Etablissement Français du Sang, 46 rue Félix Le Dantec, BP62025, F-29220, Brest, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Fichou
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Génin
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Maréchal
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrézet
authors.forename: Virginie
authors.initials: V
authors.lastname: Scotet
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D016001:Confidence Intervals; D003550:Cystic Fibrosis / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D044465:White People