Molecular diagnosis of cystic fibrosis in Maritime Canada

Many of the people in Maritime Canada can trace their ancestry to some of the oldest settlements in North America. Consequently, both founder effect and genetic drift can be shown to account for the high frequency of some genetic disorders and virtual absence of others. The birth prevalence rate for cystic fibrosis (CF) in Maritime Canada is similar to other North American regions, but we recognized that similar factors might apply to CF genotypes and thereby impair the accuracy of counselling based on molecular markers. We therefore screened the majority (53%) of our CF population for the commonest mutation (delta F508) and for frequency of haplotypes based on 4 linked RFLPs: XV2C, KM19, J3.11, and MP6d9. The proportion with the delta F508 mutation--100 (76%) of 131 CF chromosomes--was similar to that found in other centres. In comparing frequencies of XV2C and KM19 haplotypes on non-delta F508 CF chromosomes with those from a more heterogeneous Canadian population (Kerem et al.) and a Swiss population (Liechti-Gallati et al.), no statistically significant differences were identified. Extended haplotyping to include MP6d9 and J3.11 alleles revealed 3 new haplotypes, but the overall frequency distribution was not statistically different. We can therefore exclude substantial founder effects in our population. Genotype frequencies and recurrence risks for non-delta F508 CF genotypes can be used in counselling most Maritime Canadian families with cystic fibrosis. Further mutational analysis should focus on chromosomes bearing unique haplotypes and individuals from specific subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)