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Transversions have larger regulatory effects than transitions.

Publication ,  Journal Article
Guo, C; McDowell, IC; Nodzenski, M; Scholtens, DM; Allen, AS; Lowe, WL; Reddy, TE
Published in: BMC Genomics
May 19, 2017

BACKGROUND: Transversions (Tv's) are more likely to alter the amino acid sequence of proteins than transitions (Ts's), and local deviations in the Ts:Tv ratio are indicative of evolutionary selection on genes. Whether the two different types of mutations have different effects in non-protein-coding sequences remains unknown. Genetic variants primarily impact gene expression by disrupting the binding of transcription factors (TFs) and other DNA-binding proteins. Because Tv's cause larger changes in the shape of a DNA backbone, we hypothesized that Tv's would have larger impacts on TF binding and gene expression. RESULTS: Here, we provide multiple lines of evidence demonstrating that Tv's have larger impacts on regulatory DNA including analyses of TF binding motifs and allele-specific TF binding. In these analyses, we observed a depletion of Tv's within TF binding motifs and TF binding sites. Using massively parallel population-scale reporter assays, we also provided empirical evidence that Tv's have larger effects than Ts's on the activity of human gene regulatory elements. CONCLUSIONS: Tv's are more likely to disrupt TF binding, resulting in larger changes in gene expression. Although the observed differences are small, these findings represent a novel, fundamental property of regulatory variation. Understanding the features of functional non-coding variation could be valuable for revealing the genetic underpinnings of complex traits and diseases in future studies.

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Published In

BMC Genomics

DOI

EISSN

1471-2164

Publication Date

May 19, 2017

Volume

18

Issue

1

Start / End Page

394

Location

England

Related Subject Headings

  • Transcription Factors
  • Protein Binding
  • DNA
  • Computational Biology
  • Bioinformatics
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 08 Information and Computing Sciences
  • 06 Biological Sciences
 

Citation

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Guo, C., McDowell, I. C., Nodzenski, M., Scholtens, D. M., Allen, A. S., Lowe, W. L., & Reddy, T. E. (2017). Transversions have larger regulatory effects than transitions. BMC Genomics, 18(1), 394. https://doi.org/10.1186/s12864-017-3785-4
Guo, Cong, Ian C. McDowell, Michael Nodzenski, Denise M. Scholtens, Andrew S. Allen, William L. Lowe, and Timothy E. Reddy. “Transversions have larger regulatory effects than transitions.BMC Genomics 18, no. 1 (May 19, 2017): 394. https://doi.org/10.1186/s12864-017-3785-4.
Guo C, McDowell IC, Nodzenski M, Scholtens DM, Allen AS, Lowe WL, et al. Transversions have larger regulatory effects than transitions. BMC Genomics. 2017 May 19;18(1):394.
Guo, Cong, et al. “Transversions have larger regulatory effects than transitions.BMC Genomics, vol. 18, no. 1, May 2017, p. 394. Pubmed, doi:10.1186/s12864-017-3785-4.
Guo C, McDowell IC, Nodzenski M, Scholtens DM, Allen AS, Lowe WL, Reddy TE. Transversions have larger regulatory effects than transitions. BMC Genomics. 2017 May 19;18(1):394.
Journal cover image

Published In

BMC Genomics

DOI

EISSN

1471-2164

Publication Date

May 19, 2017

Volume

18

Issue

1

Start / End Page

394

Location

England

Related Subject Headings

  • Transcription Factors
  • Protein Binding
  • DNA
  • Computational Biology
  • Bioinformatics
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 08 Information and Computing Sciences
  • 06 Biological Sciences