DCDC2 is associated with reading disability and modulates neuronal development in the brain.
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.
Meng
Haiying
H
Department of Pediatrics, Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Smith
Shelley D
SD
Hager
Karl
K
Held
Matthew
M
Liu
Jonathan
J
Olson
Richard K
RK
Pennington
Bruce F
BF
DeFries
John C
JC
Gelernter
Joel
J
O'Reilly-Pol
Thomas
T
Somlo
Stefan
S
Skudlarski
Pawel
P
Shaywitz
Sally E
SE
Shaywitz
Bennett A
BA
Marchione
Karen
K
Wang
Yu
Y
Paramasivam
Murugan
M
LoTurco
Joseph J
JJ
Page
Grier P
GP
Gruen
Jeffrey R
JR
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