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

doi:10.1073/pnas.0508591102

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

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344 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 language	English (US)
Pages (from-to)	17053-17058
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	47
DOIs	https://doi.org/10.1073/pnas.0508591102
State	Published - Nov 22 2005

Keywords

DYX2
Disequilibrium haplotype
Doublecortin
Dyslexia

ASJC Scopus subject areas

General

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10.1073/pnas.0508591102

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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

Meng, H, Smith, SD, Hager, K, Held, M, Liu, J, Olson, RK, Pennington, BF, DeFriess, JC, Gelernter, J, O'Reilly-Pol, T, Somlo, S, Skudlarski, P, Shaywitz, SE, Shaywitz, BA, Marchione, K, Wang, Y, Paramasivam, M, LoTurco, JJ, Page, GP & Gruen, JR 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, vol. 102, no. 47, pp. 17053-17058. https://doi.org/10.1073/pnas.0508591102

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title = "DCDC2 is associated with reading disability and modulates neuronal development in the brain",

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.",

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AU - Meng, Haiying

AU - Smith, Shelley D.

AU - Hager, Karl

AU - Held, Matthew

AU - Liu, Jonathan

AU - Olson, Richard K.

AU - Pennington, Bruce F.

AU - DeFriess, John C.

AU - Gelernter, Joel

AU - O'Reilly-Pol, Thomas

AU - Somlo, Stefan

AU - Skudlarski, Pawel

AU - Shaywitz, Sally E.

AU - Shaywitz, Bennett A.

AU - Marchione, Karen

AU - Wang, Yu

AU - Paramasivam, Murugan

AU - LoTurco, Joseph J.

AU - Page, Grier P.

AU - Gruen, Jeffrey R.

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AB - 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.

KW - DYX2

KW - Disequilibrium haplotype

KW - Doublecortin

KW - Dyslexia

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

Abstract

Keywords

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