title: Can a place of origin of the main cystic fibrosis mutations be identified?
abstract: The genetic background of the mutations that most often cause cystic fibrosis (CF) is different from that of non-CF chromosomes in populations of European origin. It is not known whether these haplotype backgrounds could be found at high frequencies in populations in which CF is, at present, not common; such populations would be candidates for the place of origin of CF mutations. An analysis of haplotypes of CF transmembrane conductance regulator, together with their variation in specific CF chromosomes, in a worldwide survey of normal chromosomes shows (1) a very low frequency or absence of the most common CF haplotypes in all populations analyzed and (2) a strong genetic variability and divergence, among various populations, of the chromosomes that carry disease-causing mutations. The depth of the gene genealogy associated with disease-causing mutations may be greater than that of the evolutionary process that gave rise to present-day human populations. The concept of "population of origin" lacks either spatial or temporal meaning for mutations that are likely to have been present in Europeans before the ethnogenesis of present populations; subsequent population processes may have erased the traces of their geographic origin.
authors.affiliation: Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Mateu
authors.forename: Francesc
authors.initials: F
authors.lastname: Calafell
authors.forename: Maria Dolors
authors.initials: MD
authors.lastname: Ramos
authors.forename: Teresa
authors.initials: T
authors.lastname: Casals
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
mesh_terms: D003550:Cystic Fibrosis / Q000208:ethnology* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004641:Emigration and Immigration; D005060:Europe; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D016013:Likelihood Functions; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018401:Sample Size
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator