Pulsed‐field gradient‐gel studies around the fragile site

Abstract
Using pulsed‐field gradient‐gel electrophoresis (PFGE) we compared two fragile X (fra(X)) chromosomes from individuals in families that exhibit linkage heterogeneity between fra(X) and coagulation factor IX (F9). The analysis of very large restriction fragments indicated that there is a structural difference in the interval between fra(X) and F9 near the locus DXS105. Differences were observed in the Sfi I partial digestion analysis and in the Mlu I pattern of the DXS105 region. Digestion with Nru I and Sst II also showed differences between these alleles. The analyses suggest that the alleles differ in a region of >200 kb. Analysis of other normal and fra(X) chromosomes will be necessary to determine whether the observed difference is a normal population variant or if it may be resonsible for the linkage heterogeneity observed between these loci.