REFINEMENT OF THE SPINAL MUSCULAR-ATROPHY LOCUS BY GENETIC AND PHYSICAL MAPPING

We report the mapping and characterization of 12 microsatellite marker s including 11 novel markers. All markers were generated from overlapp ing YAC clones that span the spinal muscular atrophy (SMA) locus. PCR amplification of 32 overlapping YAC clones shows that 9 of the new mar kers (those set in italics) map to the interval between the two previo us closest flanking markers (D5S629 and D5S557) : cen - D5S6 - D5S125 - D5S435 - D5S1407 - D5S629 - D5S1410 - D5S1411 /D5S1412-D5S1413-D5S14 14-D5Z8-D5Z9-CATT1-D5Z10 Z6-D5S557-D5S1408-D5S1409-D5S637-D5S351-MAP1B -tel. Four of these new markers detect multiple loci in and out of the SMA gene region. Genetic analysis of recombinant SMA families indicat es that D5S1413 is a new proximal flanking locus for the SMA gene. Int erestingly, among the 40 physically mapped loci, the 14 multilocus mar kers map contiguously to a genomic region that overlaps, and perhaps h elps define, the minimum genetic region encompassing the SMA gene(s).