In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human <i>MPL</i> Gene

Mohamed Mubarak Babeker; Afra Mohamed Suliman Albakry; Mohammed Nagm Eldin Elsamani; Gihan Mossalami; Hind Abdelaziz Elnasri; Mona Abdelrahman Mohamed Khaier

doi:doi:10.11648/j.ijgg.20190704.17

In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene

Mohamed Mubarak Babeker, Afra Mohamed Suliman Albakry, Mohammed Nagm Eldin Elsamani, Gihan Mossalami, Hind Abdelaziz Elnasri, Mona Abdelrahman Mohamed Khaier

Published in International Journal of Genetics and Genomics (Volume 7, Issue 4)

Received: 30 September 2019 Accepted: 23 October 2019 Published: 22 November 2019

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Abstract

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.

Published in	International Journal of Genetics and Genomics (Volume 7, Issue 4)
DOI	10.11648/j.ijgg.20190704.17
Page(s)	124-131
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

In silico Analysis, MPL gene, SNPs, SIFT, PolyPhen-2, I-Mutant 3.0 and Project Hope

References

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[3]	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.
[4]	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.
[5]	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.
[6]	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.
[7]	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.
[8]	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.
[9]	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.
[10]	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.
[11]	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.
[12]	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.
[13]	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.
[14]	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.
[15]	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.
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APA Style

Mohamed Mubarak Babeker, Afra Mohamed Suliman Albakry, Mohammed Nagm Eldin Elsamani, Gihan Mossalami, Hind Abdelaziz Elnasri, et al. (2019). In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene. International Journal of Genetics and Genomics, 7(4), 124-131. https://doi.org/10.11648/j.ijgg.20190704.17

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ACS Style

Mohamed Mubarak Babeker; Afra Mohamed Suliman Albakry; Mohammed Nagm Eldin Elsamani; Gihan Mossalami; Hind Abdelaziz Elnasri, et al. In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene. Int. J. Genet. Genomics 2019, 7(4), 124-131. doi: 10.11648/j.ijgg.20190704.17

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AMA Style

Mohamed Mubarak Babeker, Afra Mohamed Suliman Albakry, Mohammed Nagm Eldin Elsamani, Gihan Mossalami, Hind Abdelaziz Elnasri, et al. In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene. Int J Genet Genomics. 2019;7(4):124-131. doi: 10.11648/j.ijgg.20190704.17

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@article{10.11648/j.ijgg.20190704.17,
  author = {Mohamed Mubarak Babeker and Afra Mohamed Suliman Albakry and Mohammed Nagm Eldin Elsamani and Gihan Mossalami and Hind Abdelaziz Elnasri and Mona Abdelrahman Mohamed Khaier},
  title = {In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene},
  journal = {International Journal of Genetics and Genomics},
  volume = {7},
  number = {4},
  pages = {124-131},
  doi = {10.11648/j.ijgg.20190704.17},
  url = {https://doi.org/10.11648/j.ijgg.20190704.17},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20190704.17},
  abstract = {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.},
 year = {2019}
}

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TY  - JOUR
T1  - In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene
AU  - Mohamed Mubarak Babeker
AU  - Afra Mohamed Suliman Albakry
AU  - Mohammed Nagm Eldin Elsamani
AU  - Gihan Mossalami
AU  - Hind Abdelaziz Elnasri
AU  - Mona Abdelrahman Mohamed Khaier
Y1  - 2019/11/22
PY  - 2019
N1  - https://doi.org/10.11648/j.ijgg.20190704.17
DO  - 10.11648/j.ijgg.20190704.17
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 124
EP  - 131
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20190704.17
AB  - 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.
VL  - 7
IS  - 4
ER  -

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Author Information

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

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Plain Text BibTeX RIS

APA Style

Mohamed Mubarak Babeker, Afra Mohamed Suliman Albakry, Mohammed Nagm Eldin Elsamani, Gihan Mossalami, Hind Abdelaziz Elnasri, et al. (2019). In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene. International Journal of Genetics and Genomics, 7(4), 124-131. https://doi.org/10.11648/j.ijgg.20190704.17

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ACS Style

Mohamed Mubarak Babeker; Afra Mohamed Suliman Albakry; Mohammed Nagm Eldin Elsamani; Gihan Mossalami; Hind Abdelaziz Elnasri, et al. In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene. Int. J. Genet. Genomics 2019, 7(4), 124-131. doi: 10.11648/j.ijgg.20190704.17

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AMA Style

Mohamed Mubarak Babeker, Afra Mohamed Suliman Albakry, Mohammed Nagm Eldin Elsamani, Gihan Mossalami, Hind Abdelaziz Elnasri, et al. In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene. Int J Genet Genomics. 2019;7(4):124-131. doi: 10.11648/j.ijgg.20190704.17

Copy | Download

@article{10.11648/j.ijgg.20190704.17,
  author = {Mohamed Mubarak Babeker and Afra Mohamed Suliman Albakry and Mohammed Nagm Eldin Elsamani and Gihan Mossalami and Hind Abdelaziz Elnasri and Mona Abdelrahman Mohamed Khaier},
  title = {In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene},
  journal = {International Journal of Genetics and Genomics},
  volume = {7},
  number = {4},
  pages = {124-131},
  doi = {10.11648/j.ijgg.20190704.17},
  url = {https://doi.org/10.11648/j.ijgg.20190704.17},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20190704.17},
  abstract = {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.},
 year = {2019}
}

Copy | Download

TY  - JOUR
T1  - In Silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human MPL Gene
AU  - Mohamed Mubarak Babeker
AU  - Afra Mohamed Suliman Albakry
AU  - Mohammed Nagm Eldin Elsamani
AU  - Gihan Mossalami
AU  - Hind Abdelaziz Elnasri
AU  - Mona Abdelrahman Mohamed Khaier
Y1  - 2019/11/22
PY  - 2019
N1  - https://doi.org/10.11648/j.ijgg.20190704.17
DO  - 10.11648/j.ijgg.20190704.17
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 124
EP  - 131
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20190704.17
AB  - 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.
VL  - 7
IS  - 4
ER  -

Copy | Download