Development of additional RFLP probes near the locus for Duchenne muscular dystrophy by cosmid cloning of the DXS84 (754) locus

Summary We have isolated 70 kb of sequences surrounding probe 754 (DXS84), linked with Duchenne muscular dystrophy. In addition to the original PstI RFLP detected by 754, BglII and EcoRI RFLPs were detected with the single copy subclone 754.11 and a HindIII RFLP with the subclone 754.6. The BglII and HindIII and HindIII RFLPs both have minor allele frequencies of 40%, as in PstI polymorphism. The EcoRI polymorphism has a minor allele frequency of 23%. Since a linkage disequilibrium is observed between these RFLPs (P<0.001), the BglII and the HindIII RFLPs do not contribute to the heterozygosity. However, the minor allele of the EcoRI RFLP segregates exclusively with the major haplotype of the PstI-BglII-HindIII complex, and consequently 47% of the homozygotes for the haplotype become heterozygous. As a result, the overal heterozygote frequency of the DXS84 locus increases from 50% to 65%.