Prioritizing single-nucleotide variations that potentially regulate alternative splicing

Mingxiang Teng, Yadong Wang, Guohua Wang, Jeesun Jung, Howard Edenberg, Jeremy R. Sanford, Yunlong Liu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Recent evidence suggests that many complex diseases are caused by genetic variations that play regulatory roles in controlling gene expression. Most genetic studies focus on nonsynonymous variations that can alter the amino acid composition of a protein and are therefore believed to have the highest impact on phenotype. Synonymous variations, however, can also play important roles in disease pathogenesis by regulating pre-mRNA processing and translational control. In this study, we systematically survey the effects of single-nucleotide variations (SNVs) on binding affinity of RNA-binding proteins (RBPs). Among the 10,113 synonymous SNVs identified in 697 individuals in the 1,000 Genomes Project and distributed by Genetic Analysis Workshop 17 (GAW17), we identified 182 variations located in alternatively spliced exons that can significantly change the binding affinity of nine RBPs whose binding preferences on 7-mer RNA sequences were previously reported. We found that the minor allele frequencies of these variations are similar to those of nonsynonymous SNVs, suggesting that they are in fact functional. We propose a workflow to identify phenotype-associated regulatory SNVs that might affect alternative splicing from exome-sequencing-derived genetic variations. Based on the affecting SNVs on the quantitative traits simulated in GAW17, we further identified two and four functional SNVs that are predicted to be involved in alternative splicing regulation in traits Q1 and Q2, respectively.

Original languageEnglish
Article numberS40
JournalBMC Proceedings
Volume5
Issue numberSUPPL. 9
DOIs
StatePublished - 2011

Fingerprint

Alternative Splicing
Nucleotides
RNA-Binding Proteins
Exome
Phenotype
Education
Workflow
RNA Precursors
Protein Binding
Gene Frequency
Gene expression
Exons
Genes
Genome
RNA
Gene Expression
Amino Acids
Processing
Chemical analysis
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Prioritizing single-nucleotide variations that potentially regulate alternative splicing. / Teng, Mingxiang; Wang, Yadong; Wang, Guohua; Jung, Jeesun; Edenberg, Howard; Sanford, Jeremy R.; Liu, Yunlong.

In: BMC Proceedings, Vol. 5, No. SUPPL. 9, S40, 2011.

Research output: Contribution to journalArticle

Teng, Mingxiang ; Wang, Yadong ; Wang, Guohua ; Jung, Jeesun ; Edenberg, Howard ; Sanford, Jeremy R. ; Liu, Yunlong. / Prioritizing single-nucleotide variations that potentially regulate alternative splicing. In: BMC Proceedings. 2011 ; Vol. 5, No. SUPPL. 9.
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