DCDC2 is associated with reading disability and modulates neuronal development in the brain

Haiying Meng, Shelley D. Smith, Karl Hager, Matthew Held, Jonathan Liu, Richard K. Olson, Bruce F. Pennington, John C. DeFriess, Joel Gelernter, Thomas O'Reilly-Pol, Stefan Somlo, Pawel Skudlarski, Sally E. Shaywitz, Bennett A. Shaywitz, Karen Marchione, Yu Wang, Murugan Paramasivam, Joseph J. LoTurco, Grier P. Page, Jeffrey R. Gruen

Research output: Contribution to journalArticle

297 Scopus citations

Abstract

DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD.

Original languageEnglish (US)
Pages (from-to)17053-17058
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number47
DOIs
StatePublished - Nov 22 2005

Keywords

  • DYX2
  • Disequilibrium haplotype
  • Doublecortin
  • Dyslexia

ASJC Scopus subject areas

  • General

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    Meng, H., Smith, S. D., Hager, K., Held, M., Liu, J., Olson, R. K., Pennington, B. F., DeFriess, J. C., Gelernter, J., O'Reilly-Pol, T., Somlo, S., Skudlarski, P., Shaywitz, S. E., Shaywitz, B. A., Marchione, K., Wang, Y., Paramasivam, M., LoTurco, J. J., Page, G. P., & Gruen, J. R. (2005). DCDC2 is associated with reading disability and modulates neuronal development in the brain. Proceedings of the National Academy of Sciences of the United States of America, 102(47), 17053-17058. https://doi.org/10.1073/pnas.0508591102