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Home / Equine Research Bank / Genomics / Glycogen synthase (GYS1) mutation causes a novel skeletal mu...
Genomics2008; 91(5); 458-466; doi: 10.1016/j.ygeno.2008.01.011

Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis.

Abstract: Polysaccharide storage myopathy (PSSM) is a novel glycogenosis in horses characterized by abnormal glycogen accumulation in skeletal muscle and muscle damage with exertion. It is unlike glycogen storage diseases resulting from known defects in glycogenolysis, glycolysis, and glycogen synthesis that have been described in humans and domestic animals. A genome-wide association identified GYS1, encoding skeletal muscle glycogen synthase (GS), as a candidate gene for PSSM. DNA sequence analysis revealed a mutation resulting in an arginine-to-histidine substitution in a highly conserved region of GS. Functional analysis demonstrated an elevated GS activity in PSSM horses, and haplotype analysis and allele age estimation demonstrated that this mutation is identical by descent among horse breeds. This is the first report of a gain-of-function mutation in GYS1 resulting in a glycogenosis.
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Publication Date: 2008-03-20 PubMed ID: 18358695PubMed Central: PMC2430182DOI: 10.1016/j.ygeno.2008.01.011Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research uncovers a new type of glycogen disease in horses known as polysaccharide storage myopathy (PSSM), which leads to abnormal accumulation of glycogen in skeletal muscle causing muscle damage. The identified cause is a mutation in the gene GYS1, associated with glycogen synthesis, not previously linked to glycogen diseases.

Introduction to the Study

  • The research focuses on defining and understanding Polysaccharide Storage Myopathy (PSSM).
  • PSSM is a newly discovered glycogenosis (a disease caused by the abnormal metabolism of glycogen) in horses.
  • Unlike known human and domestic animal glycogen storage diseases, PSSM leads to abnormal glycogen accumulation in skeletal muscle, resulting in muscle damage when the horse exerts itself.

Genomic Association and Mutation

  • A genome-wide association study was conducted to identify potential genes responsible for PSSM.
  • The study identified GYS1, the gene which encodes for skeletal muscle glycogen synthase (GS), as a candidate gene for PSSM.
  • Upon rigorous DNA sequence analysis, a mutation was observed in the GYS1 gene. This mutation is an alteration from arginine to histidine in a region of GS that is highly conserved and critical to its function.

Functional Analysis and Haplotype Study

  • Functional analysis was carried out to understand the impact of the GYS1 mutation. The study revealed that PSSM horses have an elevated level of GS activity.
  • The research further conducted a haplotype analysis and allele age estimation to consolidate the findings. These analyses confirmed that the GYS1 mutation is passed down identically across different horse breeds, therefore demonstrating that the mutation is identical by descent.

Significance of the Study

  • This research is significant because it is the first to report a gain-of-function mutation (where the altered gene product possesses a new molecular function or a new pattern of gene expression) in the GYS1 gene leading to a form of glycogenosis.
  • The findings of this research expand our understanding of GYS1-related glycogenosis and have implications for better diagnosing and managing this disease in horses.

Cite This Article

APA
McCue ME, Valberg SJ, Miller MB, Wade C, DiMauro S, Akman HO, Mickelson JR. (2008). Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics, 91(5), 458-466. https://doi.org/10.1016/j.ygeno.2008.01.011

Publication

Genomics
ISSN: 1089-8646
NlmUniqueID: 8800135
Country: United States
Language: English
Volume: 91
Issue: 5
Pages: 458-466

Researcher Affiliations

McCue, Molly E
  • Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA. mccų@umn.edu
Valberg, Stephanie J
    Miller, Michael B
      Wade, Claire
        DiMauro, Salvatore
          Akman, Hasan O
            Mickelson, James R

              MeSH Terms

              • Amino Acid Sequence
              • Amino Acid Substitution
              • Animals
              • Gene Frequency
              • Genome
              • Glycogen Storage Disease / enzymology
              • Glycogen Storage Disease / genetics
              • Glycogen Storage Disease / veterinary
              • Glycogen Synthase / genetics
              • Glycogen Synthase / metabolism
              • Haplotypes
              • Horse Diseases / enzymology
              • Horse Diseases / genetics
              • Horses
              • Microsatellite Repeats
              • Molecular Sequence Data
              • Muscle, Skeletal / enzymology
              • Muscle, Skeletal / metabolism
              • Mutation, Missense
              • Polymorphism, Single Nucleotide

              Grant Funding

              • T32 OD010993 / NIH HHS
              • T32 RR018719 / NCRR NIH HHS
              • T32 RR018719-02 / NCRR NIH HHS
              • T32RR018719-02 / NCRR NIH HHS

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