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DCDC2 is associated with reading disability and modulates neuronal development in the brain
Meng, HY., Smith, SD., Hager, K., Held, M., Liu, J., Olson, RK., Pennington, BF., DeFries, 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, 102(47), 17053-17058. https://doi.org/10.1073/pnas.0508591102
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.
