27 febrero 2020

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).

DOI : 10.3389/fgene.2019.01406

Sebastián Reyes, Jaime Andrés Rivas-Pardo

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.

Investigadores Participantes del Centro

Immunogenomics Laboratory

Doctor en Microbiología, Universidad de Santiago, Chile.


Laboratorio de Biología Mecánica

Doctor en Ciencias, Universidad de Chile, Chile



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