Single-nucleotide polymorphisms (SNP) mining and their effect on the tridimensional protein structure prediction in a set of immunity-related expressed sequence tags (EST) in Atlantic salmon (Salmo salar)
Vallejos Vidal, Eva Carolina (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Reyes-Cerpa, Sebastián (Universidad Mayor. Centro de Genómica y Bioinformática)
Rivas-Pardo, Jaime Andrés (Universidad Mayor. Escuela de Biotecnología)
Maisey, Kevin (Universidad de Santiago de Chile. Departamento de Biología Acuícola)
Yáñez, José M. (Universidad de Chile. Facultad de Ciencias Veterinarias y Pecuarias)
Valenzuela, Hector (Universidad de Santiago de Chile. Centro de Biotecnología Acuícola)
Cea, Pablo A. (Universidad de Chile. Facultad de Ciencias)
Castro-Fernandez, Victor (Universidad de Chile. Facultad de Ciencias)
Tort Bardolet, Lluís (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Sandino, Ana María (Universidad de Santiago de Chile. Centro de Biotecnología Acuícola)
Imarai, Mónica (Universidad de Santiago de Chile. Centro de Biotecnología Acuícola)
Reyes-López, Felipe E. (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Fecha:	2020
Resumen:	Single-nucleotide polymorphisms (SNPs) are single genetic code variations considered one of the most common forms of nucleotide modifications. Such SNPs can be located in genes associated to immune response and, therefore, they may have direct implications over the phenotype of susceptibility to infections affecting the productive sector. In this study, a set of immune-related genes (cc motif chemokine 19 precursor [ ccl19 ], integrin β2 (itβ2, also named cd18), glutathione transferase omega-1 [ gsto-1 ], heat shock 70 KDa protein [ hsp70 ], major histocompatibility complex class I [ mhc-I ]) were analyzed to identify SNPs by data mining. These genes were chosen based on their previously reported expression on infectious pancreatic necrosis virus (IPNV)-infected Atlantic salmon phenotype. The available EST sequences for these genes were obtained from the Unigene database. Twenty-eight SNPs were found in the genes evaluated and identified most of them as transition base changes. The effect of the SNPs located on the 5'-untranslated region (UTR) or 3'-UTR upon transcription factor binding sites and alternative splicing regulatory motifs was assessed and ranked with a low-medium predicted FASTSNP score risk. Synonymous SNPs were found on itβ2 (c. 2275G > A), gsto-1 (c. 558G > A), and hsp70 (c. 1950C > T) with low FASTSNP predicted score risk. The difference in the relative synonymous codon usage (RSCU) value between the variant codons and the wild-type codon (ΔRSCU) showed one negative (hsp70 c. 1950C > T) and two positive ΔRSCU values (itβ2 c. 2275G > A; gsto-1 c. 558G > A), suggesting that these synonymous SNPs (sSNPs) may be associated to differences in the local rate of elongation. Nonsynonymous SNPs (nsSNPs) in the gsto-1 translatable gene region were ranked, using SIFT and POLYPHEN web-tools, with the second highest (c. 205A > G; c484T > C) and the highest (c. 499T > C; c. 769A > C) predicted score risk possible. Using homology modeling to predict the effect of these nonsynonymous SNPs, the most relevant nucleotide changes for gsto-1 were observed for the nsSNPs c. 205A > G, c484T > C, and c. 769A > C. Molecular dynamics was assessed to analyze if these GSTO-1 variants have significant differences in their conformational dynamics, suggesting these SNPs could have allosteric effects modulating its catalysis. Altogether, these results suggest that candidate SNPs identified may play a crucial potential role in the immune response of Atlantic salmon.
Nota:	Ajuts: this study was supported by INNOVA-CORFO (No. 09MCSS-6691 and 09MCSS-6698), FONDECYT (No. 1161015; 11150807; 11180705; 11181133), DICYT- USACH, VRIDEI-USACH (USA1899 VRIDEI 021943IB-PAP), and Universidad Mayor startup funds (No. OI101205; SR-C). The authors also thank to the grants from CONICYT-BCH (Chile) Postdoctoral fellowship (No. 74170091; EV-V), International postdoctoral stay 2019 (Universidad de Chile, UCH1566; EV-V) and VRIDEI-USACH (FR-L). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Single-nucleotide polymorphism ; Immune response ; Synonymous SNP ; Nonsynonymous SNP ; Homology modeling ; 3D protein structure ; Molecular dynamics simulation ; Salmo salar
Publicado en:	Frontiers in genetics, Vol. 10 (Feb. 2020) , art. 1406, ISSN 1664-8021

DOI: 10.3389/fgene.2019.01406
PMID: 32174954

18 p, 3.5 MB

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