Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French-Canadian population.
Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy, the most common neuromuscular disorder in childhood. The gene responsible for childhood SMA has been mapped to the q11.2-q13.3 region of chromosome 5. We have extended our linkage studies of SMA in the French-Canadian population to include microsatellite markers at the D5S125, D5S351, D5S435, JK53CA1/2 and MAP1B loci. These markers span about 4 cM of the SMA candidate region. We observed significant evidence for linkage between SMA and all the markers tested. The analysis of recombinant chromosomes provide evidence for the following genetic order: D5S125-D5S435-MAP1B-3'-JK53CA1/2 and places D5S351 proximal to JK53CA1/2. Furthermore, we confirm the current localization of the SMA gene distal to D5S435. Finally, we provide demonstration of significant linkage disequilibrium between childhood-onset SMA and four of the five marker loci, D5S125, D5S435, D5S351 and JK53CA1/2. Analysis of SMA-region haplotypes suggests that there may be a predominant SMA allele that is present on about 17% of SMA chromosomes in this sample of the French-Canadian population. We conclude that the observed linkage disequilibrium is likely due to genetic drift among regions of Quebec, consistent with this population's early history.
Hôpital Sainte-Justine, Montréal, Quebec, Canada.
L R
LR
Simard
G
G
Prescott
C
C
Rochette
K
K
Morgan
B
B
Lemieux
J
J
Mathieu
S B
SB
Melançon
M
M
Vanasse
D017668:Age of Onset; D002170:Canada; D002648:Child; D005260:Female; D005602:France / Q000208:ethnology; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011995:Recombination, Genetic; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*