MAPPING OF 2 NEW MARKERS WITHIN THE SMALLEST INTERVAL HARBORING THE SPINAL MUSCULAR-ATROPHY LOCUS BY FAMILY AND RADIATION HYBRID ANALYSIS

The locus responsible for the childhood-onset proximal spinal muscular atrophies (SMA) has recently been mapped to an area of 2-3 Mb in the region q12-q13.3 of chromosome 5. We have used a series of radiation h ybrids (RHs) containing distinct parts of the SMA region as defined by reference markers. A cosmid library was constructed from one RH. Thir teen clones were isolated and five of these were mapped within the SMA region. Both RH mapping and fluorescence in situ hybridization analys is showed that two clones map in the region between loci D5S125 and D5 S351. One of the cosmids contains expressed sequences. Polymorphic din ucleotide repeats were identified in both clones and used for segregat ion analysis of key recombinant SMA families. One recombination betwee n the SMA locus and the new marker 9Ic (D5S685) indicates that 9Ic is probably the closest distal marker. The absence of recombination betwe en the SMA locus and marker Fc (D5S684) suggests that Fe is located cl ose to the disease gene. These new loci should refine linkage analysis in SMA family studies and may facilitate the isolation of the disease gene.