Gradient of distribution in Europe of the major CF mutation and of its associated haplotype. European Working Group on CF Genetics (EWGCFG).
In this collaborative European study, a total of 4871 cystic fibrosis (CF) chromosomes and 3539 normal chromosomes have been characterized for the haplotypes defined by the 2 extragenic polymorphic sequences revealed by XV2c and KM19. The association between one of these haplotypes (B haplotype) and the most frequent CF mutation, delta F508, suggests for the latter a single origin and a subsequent diffusion according to a South East-North West gradient. The linkage disequilibrium data between CF and the B haplotype in different European populations are compatible with a relatively more recent appearance of the mutation in Northern Europe whereas in Southern Europe a longer history of the same mutation would have allowed time for recombination with other haplotypes. This model is also compatible with a selective advantage of carriers but does not account for (1) the excess of B haplotypes observed among both normal and non-delta F508 CF chromosomes; (2) the correlation between the B haplotype and the severity of the phenotypic effect caused by CF mutations, as measured by pancreatic insufficiency and meconium ileus.
D003550:Cystic Fibrosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008471:Meconium Aspiration Syndrome / Q000150:complications; D008957:Models, Genetic; D009154:Mutation; D010182:Pancreatic Diseases / Q000150:complications