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Characterization of the cDNA and genomic DNA sequence encoding for the platelet integrin alpha IIB and beta III in a horse with Glanzmann thrombasthenia.
Abstract: Glanzmann thrombasthenia (GT) is characterized by a defect of platelet aggregation. This autosomal recessive genetic disorder is caused by an abnormality of the platelet glycoprotein receptors alpha IIb or beta III. Recently, we identified a horse with clinical and pathological features of GT. The aim of this study was to describe this case of GT at the molecular level. A point mutation from G to C in exon 2 of ITGA2B causing a substitution of the expected amino acid arginine 72 (Arg(72)) by a proline (Pro(72)) was encountered. This amino acid change may result in abnormal structural conformations that yield an inactive alpha IIb subunit. The genomic DNA analysis showed that this horse was homozygous for the missense mutation. La thrombasthénie de Glanzmann (TG) est une maladie caractérisée par un défaut d’agrégation plaquettaire. C’est une maladie génétique autosomale récessive causée par une anomalie de la sous-unité alpha IIb ou beta III du récepteur plaquettaire. Nous avons identifié récemment un cheval démontrant les caractéristiques clinico-pathologiques de la TG. L’objectif de notre étude était de caractériser au niveau moléculaire ce patient atteint de TG. Une substitution d’une guanine par une cytosine a été mise en évidence au niveau de l’exon 2 d’ amenant à la substitution d’une arginine 72 (Arg) par une proline (Pro). Ce changement d’acide aminé pourrait résulter en une conformation structurelle anormale qui amènerait à une sous-unité αIIb inactive. L’analyse de l’ADN génomique a démontré que ce cheval était homozygote pour cette mutation. (Traduit par les auteurs)
Publication Date: 2012-01-03 PubMed ID: 22210999PubMed Central: PMC3122970 The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Case Reports
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study focuses on characterizing the DNA sequence responsible for Glanzmann thrombasthenia, a genetic disorder that affects blood clotting, in a horse. The researchers identified a single point mutation that led to a crucial amino acid substitution in the platelet protein responsible for the disorder.
Understanding the Research
- The goal of the research was to understand the molecular basis of Glanzmann thrombasthenia (GT), a blood clotting disorder, in a horse diagnosed with the disease. GT is an autosomal recessive genetic disorder, which means that a horse needs to inherit two copies of the faulty gene (one from each parent) to suffer from it.
- The researchers focused on two integral components of platelets (blood cells responsible for clotting), known as glycoprotein receptors alpha IIb or beta III. These proteins act together as a primary receptor for platelet aggregation, or binding together. In horses with GT, these proteins are abnormal, leading to defective platelet function and hence, impaired blood clotting.
- To understand the cause of abnormality, the researchers analyzed the horse’s cDNA and genomic DNA – the coding and non-coding sequences of the horse’s genome.
Findings
- The researchers identified a genetic mutation (a change or ‘mistake’ in the DNA sequence) in the horse with GT. Specifically, they found a point mutation where guanine (G) is replaced by cytosine (C) in exon 2 of the gene ITGA2B. This gene encodes for alpha IIb, one of the two important glycoprotein receptors.
- This single-point mutation caused an amino acid substitution in the protein produced from the DNA. Instead of the usual amino acid arginine 72 (Arg[72]), this mutation resulted in a proline (Pro[72]). The type of amino acids in a protein and their arrangement significantly impacts a protein’s three-dimensional structure, and thus, its function.
- Consequently, this mutation, causing an unexpected amino acid in the protein alpha IIb, might lead to an abnormal protein structure and hence, an inactive alpha IIb subunit.
- The researchers found the horse to be homozygous for this mutation, meaning it carries two copies of the same faulty gene. Since GT is an autosomal recessive disorder, this genetic makeup would indeed result in the horse manifesting the disease.
Overall, the findings provide a molecular-level understanding of GT in horses, which can help in diagnosing and managing this disorder.
Cite This Article
APA
Macieira S, Lussier J, Bédard C.
(2012).
Characterization of the cDNA and genomic DNA sequence encoding for the platelet integrin alpha IIB and beta III in a horse with Glanzmann thrombasthenia.
Can J Vet Res, 75(3), 222-227.
Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q.
MeSH Terms
- Animals
- Base Sequence
- DNA, Complementary / analysis
- DNA, Complementary / genetics
- Female
- Homozygote
- Horse Diseases / genetics
- Horses
- Integrin beta3 / genetics
- Molecular Sequence Data
- Mutation, Missense
- Platelet Membrane Glycoprotein IIb / genetics
- Point Mutation
- Sequence Analysis, DNA / veterinary
- Thrombasthenia / genetics
- Thrombasthenia / veterinary
References
This article includes 18 references
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Citations
This article has been cited 4 times.- Dahlgren AR, Tablin F, Finno CJ. Genetics of equine bleeding disorders. Equine Vet J 2021 Jan;53(1):30-37.
- Satué K, Gardon JC, Muñoz A. Clinical and laboratorial description of the differential diagnoses of hemostatic disorders in the horse. Iran J Vet Res 2020 Winter;21(1):1-8.
- Leite RO, Ferreira JF, Araújo CET, Delfiol DJZ, Takahira RK, Borges AS, Oliveira-Filho JP. Prevalence of the Mutations Responsible for Glanzmann Thrombasthenia in Horses in Brazil. Animals (Basel) 2019 Nov 13;9(11).
- Norris JW, Pombo M, Shirley E, Blevins G, Tablin F. Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia. J Vet Intern Med 2015 Sep-Oct;29(5):1387-94.
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