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TranSNPs: A class of functional SNPs affecting mRNA translation potential revealed by fraction-based allelic imbalance.

ABSTRACT: Few studies have explored the association between SNPs and alterations in mRNA translation potential. We developed an approach to identify SNPs that can mark allele-specific protein expression levels and could represent sources of inter-individual variation in disease risk. Using MCF7 cells under different treatments, we performed polysomal profiling followed by RNA sequencing of total or polysome-associated mRNA fractions and designed a computational approach to identify SNPs showing a significant change in the allelic balance between total and polysomal mRNA fractions. We identified 147 SNPs, 39 of which located in UTRs. Allele-specific differences at the translation level were confirmed in transfected MCF7 cells by reporter assays. Exploiting breast cancer data from TCGA we identified UTR SNPs demonstrating distinct prognosis features and altering binding sites of RNA-binding proteins. Our approach produced a catalog of tranSNPs, a class of functional SNPs associated with allele-specific translation and potentially endowed with prognostic value for disease risk.

SUBMITTER: Valentini S

PROVIDER: S-EPMC8666669 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Coding/functional SNPs change the biological function of a gene and, therefore, could serve as "large-effect" genetic markers. In this study, we used two bioinformatics pipelines, GATK and SAMtools, for discovering coding/functional SNPs with allelic-imbalances associated with total body weight, muscle yield, muscle fat content, shear force, and whiteness. Phenotypic data were collected for approximately 500 fish, representing 98 families (5 fish/family), from a growth-selected line, and the muscle transcriptome was sequenced from 22 families with divergent phenotypes (4 low- versus 4 high-ranked families per trait).GATK detected 59,112 putative SNPs; of these SNPs, 4798 showed allelic imbalances (>2.0 as an amplification and <0.5 as loss of heterozygosity). SAMtools detected 87,066 putative SNPs; and of them, 4962 had allelic imbalances between the low- and high-ranked families. Only 1829 SNPs with allelic imbalances were common between the two datasets, indicating significant differences in algorithms. The two datasets contained 7930 non-redundant SNPs of which 4439 mapped to 1498 protein-coding genes (with 6.4% non-synonymous SNPs) and 684 mapped to 295 lncRNAs. Validation of a subset of 92 SNPs revealed 1) 86.7-93.8% success rate in calling polymorphic SNPs and 2) 95.4% consistent matching between DNA and cDNA genotypes indicating a high rate of identifying SNPs with allelic imbalances. In addition, 4.64% SNPs revealed random monoallelic expression. Genome distribution of the SNPs with allelic imbalances exhibited high density for all five traits in several chromosomes, especially chromosome 9, 20 and 28. Most of the SNP-harboring genes were assigned to important growth-related metabolic pathways.These results demonstrate utility of RNA-Seq in assessing phenotype-associated allelic imbalances in pooled RNA-Seq samples. The SNPs identified in this study were included in a new SNP-Chip design (available from Affymetrix) for genomic and genetic analyses in rainbow trout.

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TranSNPs: A class of functional SNPs affecting mRNA translation potential revealed by fraction-based allelic imbalance.

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