LINKAGE DISEQUILIBRIUM ANALYSIS OF CHILDHOOD-ONSET SPINAL MUSCULAR-ATROPHY (SMA) IN THE FRENCH - CANADIAN POPULATION

Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy, t he most common neuromuscular disorder in childhood. The gene responsib le for childhood SMA has been mapped to the q11.2 - q13.3 region of ch romosome 5. We have extended our linkage studies of SMA in the French- Canadian population to include microsatellite markers at the D5S125, D 5S351, D5S435, JK53CA1/2 and MAP1B loci. These markers span about 4 cM of the SMA candidate region. We observed significant evidence for lin kage between SMA and all the markers tested. The analysis of recombina nt chromosomes provide evidence for the following genetic order: D5S12 5-D5S435-MAP1B-3'-JK53CA112 and places D5S351 proximal to JK53CA1/2. F urthermore, we confirm the current localization of the SMA gene distal to D5S435. Finally, we provide demonstration of significant linkage d isequilibrium between childhood-onset SMA and four of the five marker loci, D5S125, D5S435, D5S351 and JK53CA1/2. Analysis of SMA-region hap lotypes suggests that there may be a predominant SMA allele that is pr esent on about 17% of SMA chromosomes in this sample of the French - C anadian population. We conclude that the observed linkage disequilibri um is likely due to genetic drift among regions of Quebec, consistent with this population's early history.