title: Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis.
abstract: The acid beta-galactosidase cDNA of Portuguese Water dogs was isolated and sequenced. The entire coding region of the gene consists of 2004 nucleotides encoding a protein of 668 amino acids. Its encoding sequence indicates approximately 86.5% identity at the nucleotide level and about 81% identity at the amino acid level with the encoding region of the human acid beta-galactosidase gene. The deduced amino acid sequence contains a 24-amino-acid putative signal sequence, six possible glycosylation sites, and seven cysteine residues. A homozygous recessive mutation, causing canine GM1-gangliosidosis, was identified at nucleotide G200-->A in exon 2 resulting in an Arg60-->His (mutation R60H) amino acid substitution. The mutation creates a new restriction enzyme site for Pml1. Genotyping 115 dog samples for this acid beta-galactosidase gene alteration readily distinguished affected homozygous recessives (n=5), heterozygous carriers (n=50) and normal homozygotes (n=60). DNA mutation analysis provided a method more specific than enzyme assay of beta-galactosidase for determination of carriers.
authors.affiliation: Department of Neurology, New York University School of Medicine, New York 10016, USA.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Zeng
authors.forename: H
authors.initials: H
authors.lastname: Shibuya
authors.forename: G S
authors.initials: GS
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Alroy
authors.forename: G M
authors.initials: GM
authors.lastname: Pastores
authors.forename: S
authors.initials: S
authors.lastname: Raghavan
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003545:Cysteine / Q000032:analysis; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D004285:Dogs; D016537:Gangliosidosis, GM1 / Q000235:genetics*; D005838:Genotype; D006031:Glycosylation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017385:Sequence Homology; D001616:beta-Galactosidase / Q000737:chemistry / Q000235:genetics*
chemical_list: D001616:beta-Galactosidase; D003545:Cysteine