title: Why is the cystic fibrosis gene so frequent?
abstract: The high incidence of cystic fibrosis (CF) in most European populations (and populations of European descent) can be explained by different hypotheses that can be tested using the available data concerning this disorder. Among the five hypotheses discussed (genetic heterogeneity, high rate of mutation, meiotic drive, drift and heterozygote advantage), only the last is supported by experimental data. The following conclusions can be drawn from the evidence that we have reviewed: (1) CF is a single gene disorder (genetically homogeneous). (2) Haplotypes associated with the CF gene suggest that only a few mutations (the same gene located in 7q13 is always affected) are responsible for the disorder. (3) CF with pancreatic insufficiency is mainly associated with a single haplotype, whereas CF with pancreatic sufficiency is more frequently associated with different haplotypes. (4) A selective advantage consisting of higher resistance to Cl- -secreting diarrhoeas might have favored, in the past, survival of infants heterozygous for the CF gene.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Romeo
authors.forename: M
authors.initials: M
authors.lastname: Devoto
authors.forename: L J
authors.initials: LJ
authors.lastname: Galietta
mesh_terms: D003241:Consanguinity; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics*; D005060:Europe; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans