title: DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS.
abstract: Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; 12-23% are associated with mutations in the Cu/Zn superoxide dismutase gene (SOD1). All ALS-linked SOD1 mutations present with a dominant pattern of inheritance apart from the aspartate to alanine mutation in exon 4 (D90A). This mutation has been observed in dominant, recessive and apparently sporadically cases. SOD1(D90A/D90A) ALS cases have a very slow disease progression (>10 years), raising the hypothesis that modifier genes linked to SOD1 ameliorate the phenotype of recessively inherited SOD1(D90A/D90A) mutations. Previous sequence analysis of a conserved haplotype region around the SOD1 gene did not reveal any functional polymorphisms within known coding or putative regulatory regions. In the current study we expanded the previous analyses by sequencing the entire SOD1 conserved haplotypic region. Although many polymorphisms were identified, none of these variants explain the slowly progressive phenotype observed in patients with recessive SOD1(D90A) mutations. This study disproves the hypothesis that there is a tightly linked genetic protective factor specifically located close to the SOD1 gene in SOD1(D90A) mediated ALS.
authors: Massachusetts General Hospital, 114 16th Street, Navy Yard, Charlestown, MA 02129, USA. wendy.broom@gmail.com
authors: Wendy J
authors: WJ
authors: Broom
authors: Daniel V
authors: DV
authors: Johnson
authors: Manuel
authors: M
authors: Garber
authors: Peter M
authors: PM
authors: Andersen
authors: Niall
authors: N
authors: Lennon
authors: John
authors: J
authors: Landers
authors: Chad
authors: C
authors: Nusbaum
authors: Carsten
authors: C
authors: Russ
authors: Robert H
authors: RH
authors: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D017124:Conserved Sequence; D018450:Disease Progression; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D055815:Young Adult
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1