A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q.
Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by the death of motor neurons in the cortex, brain stem, and spinal cord. Despite intensive research the basic pathophysiology of ALS remains unclear. Although most cases are sporadic, approximately 10% of ALS cases are familial (FALS). Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause approximately 20% of FALS. The gene(s) responsible for the remaining 80% of FALS remain to be found. Using a large European kindred without SOD1 mutation and with classic autosomal dominant adult-onset ALS, we have identified a novel locus by performing a genome scan and linkage analysis. The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus.
Hand
Collette K
CK
Centre for Research in Neuroscience, McGill University and the Montréal General Hospital Research Institute, Montréal, Canada.
Khoris
Jawad
J
Salachas
François
F
Gros-Louis
François
F
Lopes
Ana Amélia Simões
AA
Mayeux-Portas
Veronique
V
Brewer
Carl G
CG
Brown
Robert H
RH
Meininger
Vincent
V
Camu
William
W
Rouleau
Guy A
GA
D000328:Adult; D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D005819:Genetic Markers; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1