Plant & Animal Genomes XIII Conference

January 15-19, 2005
Town & Country Convention Center
San Diego, CA

Glycogen Branching Enzyme (GBE1) Mutation In American Quarter Horses

Stephanie J Valberg¹ , Tara L Ward¹ , David L Adelson ² , Colette A Abby ² , Matthew M Binns³ , M Cecilia T Penedo⁴ , James R Mickelson ¹

¹  College of Veterinary Medicine, University of Minnesota, St Paul MN 55108 USA

²  Texas A&M University, College Station TX USA

³  The Animal Health Trust, Newmarket UK

⁴  Veterinary Genetics Laboratory, University of California, Davis 95616 USA

Glycogen branching enzyme deficiency (GBED) has recently been reported in the American Quarter Horse. Varied clinical signs included late term abortion, weakness at birth, ventilatory failure, hypoglycemic seizures, contracted tendons, inability to rise, and/or sudden death by 18 weeks of age. The similarity between the abnormal globular and crystalline polysaccharide inclusions in tissues of affected foals to findings in children with glycogen storage disease type IV, led us to suspect that affected foals had a glycogen branching enzyme (GBE) deficiency. GBED was confirmed by a lack of GBE enzyme activity and immuno-reactive GBE protein in affected foal tissues. Glycogen extracts from affected foal tissues were sparsely branched in comparison to control foal glycogen. Pedigree analysis was consistent with an autosomal recessive trait. The equine GBE1 gene was genetically and physically mapped to ECA26 and alleles of microsatellite markers from this region were associated with GBED. The complete equine GBE1 cDNA sequence was obtained by a combination of RT-PCR and direct sequencing from BAC clones. All GBED foals were homozygous for a tyrosine to stop codon mutation at exon 34 of the 699 amino acid GBE protein; all available dams and/or sires of GBED foals were heterozygous. Screening of 350 randomly selected Quarter Horses revealed a mutant allele frequency of approximately 0.045. The GBE1 mutation therefore appears to be fairly common in the Quarter Horse breed and may account for a number of the abortions, stillbirths and weak neonatal foals produced in this and related breeds.