2 5Q13 SIMPLE TANDEM REPEAT LOCI ARE IN LINKAGE DISEQUILIBRIUM WITH TYPE-1 SPINAL MUSCULAR-ATROPHY

The gene for the common recessive neuromuscular disorder spinal muscul ar atrophy (SMA) has been previously mapped to chromosome 5q. We repor t here linkage disequilibrium analyses of two polymorphic simple tande m repeat (SIR) sequences which map into the critical region of 5q13 co ntaining the SMA gene. The polymorphisms presented are constituents of CATT-1, a complex STR which is present in as many as four or more cop ies per chromosome 5. The PCR can amplify as many as eight CATI-I prod ucts of different sizes from genomic DNA samples due to differing numb ers of CA dinucleotides at each SIR location (sublocus). Oligonucleoti de primers for two of these subloci have been developed for specific P CR assays; a variety of allele sizes can be generated with each assay and, in some cases, no amplification products are detected due to null alleles. The genotyping of 149 SMA type 1 chromosomes and 142 normal chromosomes from Canadian and American kindreds reveals the presence o f significant linkage disequilibrium between the null allele of the su blocus referred to as CATT-40G1 and mutation(s) causing SMA Type 1 (We rdnig - Hoffmann disease). Allele 2 of the second sublocus, CATT-192F7 , is also in linkage disequilibrium with SMA Type 1 although the degre e of this association is less than that found for CATT-40G1. The proxi mal and distal STRs from the critical region, D5S435 and D5S351, showe d no linkage disequilibrium with SMA. The data presented here will ser ve as a framework for future linkage disequilibrium analyses, expediti ng the final stage of the search for the SMA gene.