Can a place of origin of the main cystic fibrosis mutations be identified?

The genetic background of the mutations that most often cause cystic fibros is (CF) is different from that of non-CF chromosomes in populations of Euro pean origin. It is not known whether these haplotype backgrounds could be f ound at high frequencies in populations in which CF is, at present, not com mon; such populations would be candidates for the place of origin of CF mut ations. 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 t he most common CF haplotypes in all populations analyzed and (2) a strong g enetic variability and divergence, among various populations, of the chromo somes 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 c oncept of "population of origin" lacks either spatial or temporal meaning f or mutations that are likely to have been present in Europeans before the e thnogenesis of present populations; subsequent population processes may hav e erased the traces of their geographic origin.