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
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 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
- Glanzmann E. Hereditäre hämorrhagische Thrombasthenie. Ein Beitrag zur Pathologie de Blutplättchen.. J Kinderkr 1918;88:1–42.
- Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa complex.. Blood 1988 Apr;71(4):831-43.
- George JN, Caen JP, Nurden AT. Glanzmann's thrombasthenia: the spectrum of clinical disease.. Blood 1990 Apr 1;75(7):1383-95.
- French DL. The molecular genetics of Glanzmann's thrombasthenia.. Platelets 1998;9(1):5-20.
- Nurden AT. Inherited abnormalities of platelets.. Thromb Haemost 1999 Aug;82(2):468-80.
- Macieira S, Rivard GE, Champagne J, Lavoie JP, Bédard C. Glanzmann thrombasthenia in an Oldenbourg filly.. Vet Clin Pathol 2007 Jun;36(2):204-8.
- Livesey L, Christopherson P, Hammond A, Perkins J, Toivio-Kinnucan M, Insalaco T, Boudreaux MK. Platelet dysfunction (Glanzmann's thrombasthenia) in horses.. J Vet Intern Med 2005 Nov-Dec;19(6):917-9.
- Christopherson PW, Insalaco TA, van Santen VL, Livesey L, Bourne C, Boudreaux MK. Characterization of the cDNA Encoding alphaIIb and beta3 in normal horses and two horses with Glanzmann thrombasthenia.. Vet Pathol 2006 Jan;43(1):78-82.
- Christopherson PW, van Santen VL, Livesey L, Boudreaux MK. A 10-base-pair deletion in the gene encoding platelet glycoprotein IIb associated with Glanzmann thrombasthenia in a horse.. J Vet Intern Med 2007 Jan-Feb;21(1):196-8.
- French DL, Seligsohn U. Platelet glycoprotein IIb/IIIa receptors and Glanzmann's thrombasthenia.. Arterioscler Thromb Vasc Biol 2000 Mar;20(3):607-10.
- Bédard J, Brûlé S, Price CA, Silversides DW, Lussier JG. Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa cells of dominant follicle in cattle.. Mol Reprod Dev 2003 Feb;64(2):152-65.
- Sambrook J, Russell DW. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press; 2001.
- Tanaka S, Hayashi T, Hori Y, Terada C, Han KS, Ahn HS, Bourre F, Tani Y. A Leu55 to Pro substitution in the integrin alphaIIb is responsible for a case of Glanzmann's thrombasthenia.. Br J Haematol 2002 Sep;118(3):833-5.
- Loftus JC, Halloran CE, Ginsberg MH, Feigen LP, Zablocki JA, Smith JW. The amino-terminal one-third of alpha IIb defines the ligand recognition specificity of integrin alpha IIb beta 3.. J Biol Chem 1996 Jan 26;271(4):2033-9.
- Yaron A, Naider F. Proline-dependent structural and biological properties of peptides and proteins.. Crit Rev Biochem Mol Biol 1993;28(1):31-81.
- Losonczy G, Rosenberg N, Boda Z, Vereb G, Kappelmayer J, Hauschner H, Bereczky Z, Muszbek L. Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia.. Haematologica 2007 May;92(5):698-701.
- Calvete JJ, Mann K, Alvarez MV, López MM, González-Rodríguez J. Proteolytic dissection of the isolated platelet fibrinogen receptor, integrin GPIIb/IIIa. Localization of GPIIb and GPIIIa sequences putatively involved in the subunit interface and in intrasubunit and intrachain contacts.. Biochem J 1992 Mar 1;282 ( Pt 2)(Pt 2):523-32.
- Rosenberg N, Yatuv R, Sobolev V, Peretz H, Zivelin A, Seligsohn U. Major mutations in calf-1 and calf-2 domains of glycoprotein IIb in patients with Glanzmann thrombasthenia enable GPIIb/IIIa complex formation, but impair its transport from the endoplasmic reticulum to the Golgi apparatus.. Blood 2003 Jun 15;101(12):4808-15.
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.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
