Evidence of positive selection for a glycogen synthase (gys1) mutation in domestic horse populations

Annette M. McCoy, Robert Schaefer, Jessica L Petersen, Peter L. Morrell, Megan A. Slamka, James R. Mickelson, Stephanie J. Valberg, Molly E. Mccue

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A dominantly inherited gain-of-function mutation in the glycogen synthase (GYS1) gene, resulting in excess skeletal muscle glycogen, has been identified in more than 30 horse breeds. This mutation is associated with the disease Equine Polysaccharide Storage Myopathy Type 1, yet persists at high frequency in some breeds. Under historical conditions of daily work and limited feed, excess muscle glycogen may have been advantageous, driving the increase in frequency of this allele. Fine-scale DNA sequencing in 80 horses and genotype assays in 279 horses revealed a paucity of haplotypes carrying the mutant allele when compared with the wild-type allele. Additionally, we found increased linkage disequilibrium, measured by relative extended haplotype homozygosity, in haplotypes carrying the mutation compared with haplotypes carrying the wild-type allele. Coalescent simulations of Belgian horse populations demonstrated that the high frequency and extended haplotype associated with the GYS1 mutation were unlikely to have arisen under neutrality or due to population demography. In contrast, in Quarter Horses, elevated relative extended haplotype homozygosity was associated with multiple haplotypes and may be the result of recent population expansion or a popular sire effect. These data suggest that the GYS1 mutation underwent historical selection in the Belgian, but not in the Quarter Horse.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalJournal of Heredity
Volume105
Issue number2
DOIs
StatePublished - Oct 1 2014

Fingerprint

Glycogen Synthase
Haplotypes
Horses
Mutation
Population
Alleles
Glycogen
Horse Diseases
Linkage Disequilibrium
Muscular Diseases
DNA Sequence Analysis
Gene Frequency
Polysaccharides
Skeletal Muscle
Genotype
Demography
Muscles
Genes

Keywords

  • Polysaccharide Storage Myopathy
  • equine
  • gain of function
  • glycogen synthase
  • selection

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

McCoy, A. M., Schaefer, R., Petersen, J. L., Morrell, P. L., Slamka, M. A., Mickelson, J. R., ... Mccue, M. E. (2014). Evidence of positive selection for a glycogen synthase (gys1) mutation in domestic horse populations. Journal of Heredity, 105(2), 163-172. https://doi.org/10.1093/jhered/est075

Evidence of positive selection for a glycogen synthase (gys1) mutation in domestic horse populations. / McCoy, Annette M.; Schaefer, Robert; Petersen, Jessica L; Morrell, Peter L.; Slamka, Megan A.; Mickelson, James R.; Valberg, Stephanie J.; Mccue, Molly E.

In: Journal of Heredity, Vol. 105, No. 2, 01.10.2014, p. 163-172.

Research output: Contribution to journalArticle

McCoy, AM, Schaefer, R, Petersen, JL, Morrell, PL, Slamka, MA, Mickelson, JR, Valberg, SJ & Mccue, ME 2014, 'Evidence of positive selection for a glycogen synthase (gys1) mutation in domestic horse populations', Journal of Heredity, vol. 105, no. 2, pp. 163-172. https://doi.org/10.1093/jhered/est075
McCoy, Annette M. ; Schaefer, Robert ; Petersen, Jessica L ; Morrell, Peter L. ; Slamka, Megan A. ; Mickelson, James R. ; Valberg, Stephanie J. ; Mccue, Molly E. / Evidence of positive selection for a glycogen synthase (gys1) mutation in domestic horse populations. In: Journal of Heredity. 2014 ; Vol. 105, No. 2. pp. 163-172.
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