Analysis of linkage relationships between genetic markers around the fragile X locus with special reference to the daughters of normal transmitting males.

Genetic linkage data from loci around the fragile X locus at Xq27.3 are analysed in the light of the hypothesis of Pembrey et al. (1985) concerning the generation of the fragile X mutation. Recombination between the four loci 52A, F9, fragile X, and ST14 is significantly decreased in meioses giving rise to the affected grandsons of normal transmitting males, when compared to families where there are no apparent normal transmitting males. There are at least two possible explanations for this phenomenon. Either the established fragile site at Xq27.3 promotes increased recombination in the distal part of the X chromosome as a secondary event, unrelated to the mechanism of formation of the fragile site itself, or an event involving recombination at or around Xq27.3 is the mechanism of formation of the full fragile X mutation, and the decreased recombination seen amongst flanking marker loci in meioses giving rise to the affected grandsons of normal transmitting males is the result of interference.