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.
authors.affiliation: Department of Pediatrics, Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Meng
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Smith
authors.forename: Karl
authors.initials: K
authors.lastname: Hager
authors.forename: Matthew
authors.initials: M
authors.lastname: Held
authors.forename: Jonathan
authors.initials: J
authors.lastname: Liu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Olson
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Pennington
authors.forename: John C
authors.initials: JC
authors.lastname: DeFries
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Reilly-Pol
authors.forename: Stefan
authors.initials: S
authors.lastname: Somlo
authors.forename: Pawel
authors.initials: P
authors.lastname: Skudlarski
authors.forename: Sally E
authors.initials: SE
authors.lastname: Shaywitz
authors.forename: Bennett A
authors.initials: BA
authors.lastname: Shaywitz
authors.forename: Karen
authors.initials: K
authors.lastname: Marchione
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Murugan
authors.initials: M
authors.lastname: Paramasivam
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: LoTurco
authors.forename: Grier P
authors.initials: GP
authors.lastname: Page
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000235:genetics; D004410:Dyslexia / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion