Linkage disequilibrium and CF allele segregation analysis in cystic fibrosis families in Northern Ireland

Abstract

Linkage disequilibrium and cystic fibrosis (CF) allele segregation were analysed in 46 CF families in Northern Ireland. The smaller (+) allele of the KM19/PstI polymorphism and the larger (-) allele of the XV-2c/TaqI polymorphism showed marked linkage disequilibrium with CF. This information can be used to alter the risk of an individual being a carrier of CF away from the expected population risk of 1 in 20. The high-risk genotypes K+K+ or X-X- have a risk of 1 in 10 and the low-risk genotypes K-K- or X+X+ have a risk of 1 in 50. A study of the segregation of CF alleles in the 46 families, using KM19 and Xv-2c, showed preferential inheritance of the paternal (79%), as opposed to the maternal (21%), CF allele by the heterozygous carriers. A mechanism that might explain this observation is discussed.