Volume 7, Issue 4, December 2019, Page: 124-131
In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene
Mohamed Mubarak Babeker, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan; Department of Haematology, Omdurman Ahlia University, Khartoum, Sudan
Afra Mohamed Suliman Albakry, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan
Mohammed Nagm Eldin Elsamani, Department of Clinical Biochemistry, Nile College, Khartoum, Sudan
Gihan Mossalami, Department of Haematology, Omdurman Ahlia University, Khartoum, Sudan
Hind Abdelaziz Elnasri, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan
Mona Abdelrahman Mohamed Khaier, Department of Molecular Biology and Bioinformatics, University of Bahri, Khartoum, Sudan
Received: Sep. 30, 2019;       Accepted: Oct. 23, 2019;       Published: Nov. 22, 2019
DOI: 10.11648/j.ijgg.20190704.17      View  471      Downloads  159
Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs. Mutations to this gene are associated with myelofibrosis and essential Thrombocythemia. In essential Thrombocythemia, these mutations lead to the production of Thrombopoietin receptors that are constitutively activated, or constantly turned on, which results in the overproduction of abnormal megakaryocytes. MPL gene was investigated in NCBI database (http://www.ncbi.nlm.nih.gov/) and computational software’s analyzed SNPs. SNPs in the coding region (exonal SNPs) that are non-synonymous (nsSNP) were analyzed by (sift, polyphen, Imutant and PHD-snp) softwares, and then SNPs at un-traslated region at 5’ ends (5UTR) were analyzed too by SNPs Function prediction software. In this study, Bioinformatics’ analysis of MPL gene initiated by SIFTand Polyphen-2server issued to review 197 SNPs and among this SNPs 23 pathological polymorphisms. Among these 23, 20 pathological polymorphisms were found to be very damaging, with higher Polyphen-2score, of the Polyphen-2 server (=1) and SIFT tolerance index of 0.000-0.005. Protein structural analysis was done by modeling of amino acid substitutions using Project Hope. AlsoI-Mutant software used to check their stability and the effect of the native and mutant residues protein and structure for all these pathological polymorphisms. We hope our results will provide useful information that is needed to help researchers to do further studies.
In silico Analysis, MPL gene, SNPs, SIFT, PolyPhen-2, I-Mutant 3.0 and Project Hope
To cite this article
Mohamed Mubarak Babeker, Afra Mohamed Suliman Albakry, Mohammed Nagm Eldin Elsamani, Gihan Mossalami, Hind Abdelaziz Elnasri, Mona Abdelrahman Mohamed Khaier, In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene, International Journal of Genetics and Genomics. Vol. 7, No. 4, 2019, pp. 124-131. doi: 10.11648/j.ijgg.20190704.17
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Elsayed AG, Ranavaya A, Jamil MO. MPL Y252H anMd PL F126fs mutations in essential thrombocythemia: Case series and review of literature. Hematology reports. 2019 Feb 19; 11 (1).
Vainchenker W, Plo I, Marty C, Varghese LN, Constantinescu SN. The role of the thrombopoietin receptor MPL in myeloproliferative neoplasms: recent findings and potential therapeutic applications. Expert review of hematology. 2019 Jun 3; 12 (6): 437-48.
Ballmaier M, Germeshausen M, Schulze H, Cherkaoui K, Lang S, Gaudig A, Krukemeier S, Eilers M, Strauß G, Welte K. C-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood. 2001 Jan 1; 97 (1): 139-46.
Savoia A, Dufour C, Locatelli F, Noris P, Ambaglio C, Rosti V, Zecca M, Ferrari S, Di Bari F, Corcione A, Di Stazio M. Congenital amegakaryocytic thrombocytopenia: clinical and biological consequences of five novel mutations. haematologica. 2007 Sep 1; 92 (9): 1186-93.
Heller PG, Glembotsky AC, Gandhi MJ, Cummings CL, Pirola CJ, Marta RF, Kornblihtt LI, Drachman JG, Molinas FC. Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation. Blood. 2005 Jun 15; 105 (12): 4664-70.
Horikawa Y, Matsumura I, Hashimoto K, Shiraga M, Kosugi S, Tadokoro S, Kato T, Miyazaki H, Tomiyama Y, Kurata Y, Matsuzawa Y. Markedly reduced expression of platelet c-mpl receptor in essential thrombocythemia. Blood. 1997 Nov 15; 90 (10): 4031-8.
Li J, Xia Y, Kuter DJ. The platelet thrombopoietin receptor number and function are markedly decreased in patients with essential thrombocythaemia. British journal of haematology. 2000 Dec; 111 (3): 943-53.
King S, Germeshausen M, Strauss G, Welte K, Ballmaier M. Congenital amegakaryocytic thrombocytopenia: a retrospective clinical analysis of 20 patients. British journal of haematology. 2005 Dec; 131 (5): 636-44.
Germeshausen M, Ballmaier M, Welte K. MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease. Human mutation. 2006 Mar; 27 (3): 296-283.
Walne AJ, Dokal A, Plagnol V, Beswick R, Kirwan M, de la Fuente J, Vulliamy T, Dokal I. Exome sequencing identifies MPL as a causative gene in familial aplastic anemia. Haematologica. 2012 Apr 1; 97 (4): 524-8.
Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, Maffioli M, Caramazza D, Passamonti F, Pardanani A. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014 Jul; 28 (7): 1 472.
Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010 Jun; 24 (6): 1128.
González-Pérez A, López-Bigas N. Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. The American Journal of Human Genetics. 2011 Apr 8; 88 (4): 440-9.
Capriotti E, Fariselli P, Calabrese R, Casadio R. Predicting protein stability changes from sequences using support vector machines. Bioinformatics. 2005 Jan 1; 21 (suppl_2): ii54-8.
Källberg M, Wang H, Wang S, Peng J, Wang Z, Lu H, Xu J. Template-based protein structure modeling using the RaptorX web server. Nature protocols. 2012 Aug; 7 (8): 1511.
Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic acids research. 2010 Jun 21; 38 (suppl_2): W214-20.
Santos LC, Ribeiro JC, Silva NP, Cerutti J, Silva MR, Chauffaille MD. Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia. Revista brasileira de hematologia e hemoterapia. 2011 Dec; 33 (6): 417-24.
Feener EP, Rosario F, Dunn SL, Stancheva Z, Myers MG. Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling. Molecular and cellular biology. 2004 Jun 1; 24 (11): 4968-78.
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