LINKAGE DISEQUILIBRIUM BETWEEN 4 INTRAGENIC POLYMORPHIC MICROSATELLITES OF THE NF1 GENE AND ITS IMPLICATIONS FOR GENETIC-COUNSELING

Four intragenic polymorphic microsatellite markers, AAAT Alu repeat, I VS27AC28.4, ACI27.2, and IVS38GT53.0, located along a 65kb DNA region of the NF1 gene, were used to genotype 64 Spanish families with neurof ibromatosis type 1 (NF1). Linkage disequilibrium between each pair of markers was evaluated. Three of these markers, AAAT Alu repeat, ACI27. 2, and IVS38GT53.0, exhibit linkage disequilibrium between each other. Analysis of extended haplotypes provides further evidence of the dise quilibrium within this region since only 11 haplotypes account for 52% of the total chromosomes. Because of linkage disequilibrium, the info rmativeness of marker combinations for genotyping of NF1 families is d iminished. There was no difference in the overall distribution of alle les between affected and normal chromosomes. An at risk haplotype was not found, as expected for a disease with at least 50% of cases being sporadic.