Long-range restriction mapping and linkage analysis of the Prader-Willi chromosome region (PWCR)

Abstract In an attempt to elucidate the relationship between genetic alterations at chromosomal bands 15q11.2–12 and the Prader-Willi syndrome (PWS), we have constructed a long-range restriction map of this region using a combination of pulsed-field gel techniques and the infrequently cutting restriction enzymes Not I, Mlu I, Sal I, Sfi I, Nru I, Sac II, and Bss HII. Four previously reported probes mapping to 15q11.2–12 and known to be deleted in PWS patients were used to construct the physical map of this region. The loci recognized by these four probes have been localized to a 2600-kb partial Sal I restriction fragment and a 3200-kb partial Eco RI restriction fragment. Linkage studies were performed on nine families to estimate the recombination rates between these loci. The calculated lod scores did not indicate significant linkage between any of the four loci. The contrast between the physical distance and the observed recombination frequency suggests that these four loci are located in a recombinational “hot spot”.