title: Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis.
abstract: Recently, point mutations in superoxide dismutase 1 (SOD1) have been shown to lead to a subset of autosomal dominantly inherited familial amyotrophic lateral sclerosis (ALS). These findings have led to the hypothesis that defects in oxygen radical metabolism may be involved in the pathogenesis of ALS. Therefore, we decided to analyze other enzymes involved in oxygen radical metabolism for possible involvement in other forms of ALS. We report here analysis of two genes encoding the molybdenum hydroxylases aldehyde oxidase (AO) and xanthine dehydrogenase/oxidase (XDH) for involvement in ALS. Of particular interest, one gene identified as encoding aldehyde oxidase is shown to map to 2q33, a region recently shown to contain a gene responsible for a familial form of ALS with autosomal recessive inheritance (FALS-AR). The AO gene appears to be located within 280,000 bp of simple sequence repeat marker D2S116, which shows no recombination with the FALS-AR locus. The AO gene is highly expressed in glial cells of human spinal cord. In addition, we mapped a gene for XDH to 2p22, a region previously shown to contain a highly homologous but different form of XDH. Neither of these XDH genes appears to be highly expressed in human spinal cord. This evidence suggests that AO may be a candidate gene for FALS-AR.
authors.affiliation: Eleanor Roosevelt Institute, Denver, Colorado 80206, USA.
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: E
authors.initials: E
authors.lastname: Mezey
authors.forename: K P
authors.initials: KP
authors.lastname: Clancy
authors.forename: G
authors.initials: G
authors.lastname: Harta
authors.forename: R M
authors.initials: RM
authors.lastname: Wright
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Brownstein
authors.forename: D
authors.initials: D
authors.lastname: Patterson
mesh_terms: D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D005808:Genes, Recessive; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014968:Xanthine Dehydrogenase / Q000235:genetics*; D014969:Xanthine Oxidase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase