Abstract
Current theories of a heterozygote advantage for CF carriers of frequent CFTR mutations include increased survival from diarrheal diseases, genetic drift, and hitchhiking (Romeo et al. 1989; Sereth et al. 1993; Gabriel et al. 1994; Macek et al. 1997a). The presence of a common ancient CF mutation in African, Saudi Arab, and Greek populations suggests that this mutation too may have been selected.
This study demonstrates that the 3120+1GRIGHTWARDS ARROWA mutation shares the same extragenic CS.7-KM.19 "risk" haplotype with the other frequent and ancient CF mutations-ΔF508, N1303K, and G542X (Dörk et al. 1992; Morral et al. 1993)-but that it differs from these latter mutations with respect to intragenic CFTR markers. The extragenic CS.7-KM.19 "risk" haplotype recently has been associated with a selective advantage to the postnatal survival of female carriers without a family history of CF (Macek et al. 1997a).
In summary, our present analysis provides the first evidence for a common origin of CF among African, Arab, Greek, and African American populations. The shared extra- and intragenic 3120+1GRIGHTWARDS ARROWA-associated haplotype is most easily explained by the assumption of a single origin for this mutation. 3120+1GRIGHTWARDS ARROWA appears to be an ancient mutation that may be more common than previously thought, in populations of the tropical and subtropical belt, where CF probably is an underdiagnosed disorder.