Genetical Research

Do ΔF508 heterozygotes have a selective advantage?

a1 Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK


In this paper the fitness of the ΔF508 heterozygote is assessed and the age of the ΔF508 mutation in the cystic fibrosis locus is estimated. Data from three microsatellite loci are applied. The analysis is performed conditional on the present-day frequency of the ΔF508 mutation and based on assumptions about the demographic history of the European population and the mutation rate in the three microsatellite loci. It is shown that the data gives evidence of positive selection (up to 2–3% per ΔF508 heterozygote), but also that data could be explained by negative selection of roughly the same order of magnitude. The age of the ΔF508 mutation is subsequently estimated; it is found that the mutation is at least 580 generations old, but could be much older depending on the microsatellite mutation rate and the exact number of substitutions experienced in the history of the three microsatellite loci.

(Received November 28 2000)
(Revised March 21 2001)

c1 Tel: +44 (0)1865 27 28 70. Fax: +44 (0)1865 27 25 95. e-mail: