Multipoint linkage analysis of the short arm of the human X chromosome in families with X-linked muscular dystrophy

Abstract

Sixteen three generation families from the West of Scotland with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) have been studied using the Xg blood group and seven cloned DNA sequences which recognise DNA polymorphisms on the short arm of the X chromosome (Xp). Linkage has been established between DMD and probe 754 with a maximum lod score (Ž) of 4.47 at a recombination fraction ( \(\hat \theta\) ) of 0.04. DMD has also been linked to probe 99-6 (Ž=3.75, \(\hat \theta\) =0.03). Combining the data in this study with that of previously published work has established linkage between DMD and L1.28 (Ž=4.42, \(\hat \theta\) =0.17) and altered the linkage estimate between BMD and L1.28 (Ž=3.50, \(\hat \theta\) =0.22). An approximate order for the loci has been deduced by the study of recombinant chromosomes in phase known families informative for three or more loci. The proposed order is centromere-L1.28-754-DMD/BMD-99-6-D2-782-Xg. These results conclusively map both DMD and BMD to the central region of Xp and add weight to the original suggestion that they may be allelic.