AN INVESTIGATION OF GENETIC-HETEROGENEITY AND LINKAGE DISEQUILIBRIUM IN 161 FAMILIES WITH SPINAL MUSCULAR-ATROPHY

We performed linkage analysis of 161 families with spinal muscular atr ophy (SMA) in which affected individuals suffer from the intermediate or mild form of the disease (Types II or III). Markers for six loci en compassing the chromosome 5q11.2-q13.3 region were typed. The best map location for the disease locus was found to be between D5S6 and MAP1B . The corresponding 1 led unit support interval is confined to this in terval and spans 0.5 cM. The data strongly support the hypothesis of l inkage heterogeneity (likelihood ratio, 1.14 x 10(4)), with 5% of the families unlinked. Four families have a probability of less than 50% o f segregating the SMA gene linked to the region 5q11.2-q13.3. A likeli hood approach to test for linkage disequilibrium revealed no significa nt departure from Hardy-Weinberg equilibrium with any marker under stu dy. (C) 1994 Academic Press, Inc.