Allele frequency and likely impact of the glycogen branching enzyme deficiency gene in Quarter Horse and Paint Horse populations.

Glycogen Branching Enzyme Deficiency (GBED), a fatal condition recently identified in fetuses and neonatal foals of the Quarter Horse and Paint Horse lineages, is caused by a nonsense mutation in codon 34 of the GBE1 gene, which prevents the synthesis of a functional GBE protein and severely disrupts glycogen metabolism. The aims of this project were to determine the mutant GBE1 allele frequency in random samples from the major relevant horse breeds, as well as the frequency with which GBED is associated with abortion and early neonatal death using the tissue archives from veterinary diagnostic laboratories. The mutant GBE1 allele frequency in registered Quarter Horse, Paint Horse, and Thoroughbred populations was 0.041, 0.036, and 0.000, respectively. Approximately 2.5% of fetal and early neonatal deaths in Quarter Horse-related breeds submitted to 2 different US diagnostic laboratories were homozygous for the mutant GBE1 allele, with the majority of these being abortions. Retrospective histopathology of the homozygotes detected periodic acid Schiff's (PAS)-positive inclusions in the cardiac or skeletal muscle, which is characteristic of GBED, in 8 out of the 9 cases. Pedigree and genotype analyses supported the hypothesis that GBED is inherited as a simple recessive trait from a single founder. The frequency with which GBED is associated with abortion and neonatal mortality in Quarter Horse-related breeds makes the DNA-based test valuable in determining specific diagnoses and designing matings that avoid conception of a GBED foal.