title: Glycogen branching enzyme (GBE1) mutation causing equine glycogen storage disease IV.
abstract: Comparative biochemical and histopathological evidence suggests that a deficiency in the glycogen branching enzyme, encoded by the GBE1 gene, is responsible for a recently identified recessive fatal fetal and neonatal glycogen storage disease (GSD) in American Quarter Horses termed GSD IV. We have now derived the complete GBE1 cDNA sequences for control horses and affected foals, and identified a C to A substitution at base 102 that results in a tyrosine (Y) to stop (X) mutation in codon 34 of exon 1. All 11 affected foals were homozygous for the X34 allele, their 11 available dams and sires were heterozygous, and all 16 control horses were homozygous for the Y34 allele. The previous findings of poorly branched glycogen, abnormal polysaccharide accumulation, lack of measurable GBE1 enzyme activity and immunodetectable GBE1 protein, coupled with the present observation of abundant GBE1 mRNA in affected foals, are all consistent with the nonsense mutation in the 699 amino acid GBE1 protein. The affected foal pedigrees have a common ancestor and contain prolific stallions that are likely carriers of the recessive X34 allele. Defining the molecular basis of equine GSD IV will allow for accurate DNA testing and the ability to prevent occurrence of this devastating disease affecting American Quarter Horses and related breeds.
authors.affiliation: Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, 295 AS/VM, 1988 Fitch Ave., St. Paul, Minnesota 55108-6009, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Ward
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Valberg
authors.forename: David L
authors.initials: DL
authors.lastname: Adelson
authors.forename: Colette A
authors.initials: CA
authors.lastname: Abbey
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Binns
authors.forename: James R
authors.initials: JR
authors.lastname: Mickelson
mesh_terms: D015061:1,4-alpha-Glucan Branching Enzyme / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003062:Codon; D018388:Codon, Terminator; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005808:Genes, Recessive; D005838:Genotype; D006011:Glycogen Storage Disease Type IV / Q000235:genetics*; D006720:Homozygote; D006736:Horses; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011134:Polysaccharides; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000737:chemistry
chemical_list: D003062:Codon; D018388:Codon, Terminator; D018076:DNA, Complementary; D011134:Polysaccharides; D012333:RNA, Messenger; D014443:Tyrosine; D004247:DNA; D015061:1,4-alpha-Glucan Branching Enzyme