Associations of POU1F1 gene polymorphisms and protein structure changes with growth traits and blood metabolites in two Iranian sheep breeds

2014 ◽  
Vol 93 (3) ◽  
pp. 831-835 ◽  
Author(s):  
MOSTAFA SADEGHI ◽  
ALI JALIL-SARGHALE ◽  
MOHAMMED MORADI-SHAHRBABAK
Keyword(s):  
Protein Structure ◽  
Gene Polymorphisms ◽  
Growth Traits ◽  
Blood Metabolites ◽  
Pou1f1 Gene ◽  
Sheep Breeds ◽  
Structure Changes

scholarly journals THU0017 ATTEMPTS TO LINK EXONIC GENE POLYMORPHISMS TO SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)-ASSOCIATED PROTEIN MODIFIED FUNCTIONALITY: A STRUCTURAL BIOLOGY APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 221.1-222
Author(s):  
E. Eliopoulos ◽  
G. Goulielmos ◽  
M. Matalliotakis ◽  
D. Vlachakis ◽  
T. Niewold ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Protein Structure ◽  
Molecular Modeling ◽  
Nucleic Acid ◽  
Molecular Mechanics ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Association Studies ◽  
Systemic Lupus ◽  
Molecular Graphics

Background:Gene association studies and genome wide association studies (GWAS) have played a primary role in depicting genetic contributions to systemic lupus erythematosus (SLE) development, while accommodating the exonic polymorphisms on the protein structure level, when available, enhances our understanding of protein function modification or depletion. Linking human genetics with therapeutic targets requires the biological function of the causal gene and variant to be known.Objectives:To investigate recently identified SLE-associated functional gene polymorphisms, such asPARP1,ITGAM, TNFAIP3, NCF1, PON1, IFIH1, SH2B3andTYK2[1-4] by correlation to protein structure and function.Methods:Three-dimensional (3D) homology modeling and molecular mechanics/dynamics studies were applied for the localization of the polymorphisms under study on the respective proteins. The mutants were constructed using molecular modeling with the program Maestro (Schrodinger, LLC), which was also used to analyze the conformational changes caused by the mutation. All figures depicting 3D models were created using the molecular graphics program PyMOL V.2.2 [5].Results:Modeling revealed that rs1136410 SNP encodes the less common polymorphism Val762Ala onPARP1that reduces enzymatic activity of Poly(ADP-ribose) polymerase 1 (Figure 1),ITGAMpolymorphism rs1143679 (Arg77His) on Integrin alpha M, component of the macrophage-1 antigen complex affects protein surface recognition,TNFAIP3rs2230926 polymorphism encodes Cys instead of Phe at residue 127 of the ubiquitin editing A20 protein, while rs201802880 polymorphism of the neutrophil cytosolic factor 1 (NCF1) gene modifies the function of the cytosolic subunit of neutrophil NADPH oxidase with the mutation Arg90His.PON1is involved in the oxidative stress process that cause tissue damage observed in SLE and anti-phospholipid syndrome (APS). ThePON1Gln192Arg mutation (rs662 SNP) affects shape and recognition of the ligand recognition site as part of the evolutionary process, whileIFIH1(rs35667974) helicase C domain1 mutant I923V is located on an essential RNA beta loop interacting directly with the nucleic acid (Figure 2). Finally, the rs3184504 SNP ofSH2B3gene generates mutant Arg262Trp on SH2 adapter protein 3, acting as a signaling pathway involved in autoimmune disorders, while inTYK2 gene, one of the Janus kinases, the rs35018800 producing mutant Ala928Val modifies the ADP binding site.Figure 1.Details of the Val762 interaction where V762A mutation occurs in PARP1protein.Figure 2.Nucleic acid interacting IFIH1 helicase beta-loop where I923V mutation occurs (in purple).Conclusion:Based on several examples, we have tried to define a rational link from SLE-associated gene polymorphisms to structure and to modified function, including metagenomic analysis of SNPs, protein crystallography, protein molecular modeling, molecular mechanics and dynamics. Locating, shaping and understanding the target protein interaction interface plays a decisive role in most cases and provides clues for further pharmacological or medical actions [6].References:[1]Hur JW et al (2006). Rheumatology 45:711-7[2]Maiti AK et al (2014). Hum Mol Genet 23:4161-76[3]Shimane K et al (2010). Arthritis Rheum. 62:574-9[4]Linge P et al (2019). Ann Rheum Dis. 2019 Nov 8. pii: annrheumdis-2019-215820[5]Schrödinger LLC: The PyMOL Molecular Graphics System 2016 version 2.2. Available from: pymol.org/2/support.html[6]Plenge RM et al (2013). Nat Rev Drug Discov 12:581–94Disclosure of Interests:None declared

scholarly journals Identification of MEF2B and TRHDE Gene Polymorphisms Related to Growth Traits in a New Ujumqin Sheep Population

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159504 ◽  
Author(s):  
Li Zhang ◽  
Xiaomeng Ma ◽  
Junli Xuan ◽  
Huihua Wang ◽  
Zehu Yuan ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Growth Traits ◽  
Sheep Population

scholarly journals CAST/MspI gene polymorphism and its impact on growth traits of Soviet Merinoand Salsk sheep breeds in the South European part of Russia

2016 ◽  
Vol 40 ◽  
pp. 399-405 ◽  
Author(s):  
Ivan FedIvan GORLOV ◽  
Nadezhda Vasilevna SHIROKOVA ◽  
Alexander Vasilevich RANDELIN ◽  
Valeriya Nikolaevna VORONKOVA ◽  
Natalya Ivanovna MOSOLOVA ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Growth Traits ◽  
European Part ◽  
The South ◽  
Sheep Breeds ◽  
European Part Of Russia

Environmental and Genetic Effects on Early Growth Traits in Moghani Sheep Breeds

2007 ◽  
Vol 10 (15) ◽  
pp. 2595-2598 ◽  
Author(s):  
A. Lavvaf ◽  
A. Noshary ◽  
A. Keshtkaran
Keyword(s):  
Growth Traits ◽  
Early Growth ◽  
Genetic Effects ◽  
Sheep Breeds

scholarly journals Mapping Protein Structure Changes with Cysteine Labeling Kinetics Measured by Mass Spectrometry

2013 ◽  
Vol 104 (2) ◽  
pp. 168a
Author(s):  
Brian C. Chase ◽  
Joe Swift ◽  
J. David Pajerowski ◽  
Hsin-Yao Tang ◽  
David Speicher ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Structure Changes ◽  
Cysteine Labeling

Association of allelic polymorphisms of IGFALS gene with growth traits in Makouei and Ghezel sheep breeds

2020 ◽  
Vol 52 (6) ◽  
pp. 3027-3034
Author(s):  
Fatemeh Alizadeh ◽  
Fatemeh Moradian ◽  
Ayoub Farhadi
Keyword(s):  
Growth Traits ◽  
Sheep Breeds

scholarly journals Association of IGF 1 gene polymorphisms with some morphometric traits of Nigerian indigenous sheep breeds

2018 ◽  
Vol 34 (1) ◽  
pp. 97 ◽  
Author(s):  
A. O. Raji ◽  
A. Mohammed ◽  
J. U. Igwebuike ◽  
C. Alphonsus
Keyword(s):  
Gene Polymorphisms ◽  
Morphometric Traits ◽  
Sheep Breeds ◽  
Indigenous Sheep
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