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

被引：300

作者：

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 ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Yale Child Res Ctr, Dept Pediat, New Haven, CT 06520 USA

[2] Univ Nebraska, Med Ctr, Munroe Meyer Inst, Omaha, NE 68198 USA

[3] Yale Univ, Sch Med, WM Keck Fdn Biotechnol Resource Lab, New Haven, CT 06511 USA

[4] SoftGenet, State Coll, PA 16803 USA

[5] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA

[6] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[7] Univ Denver, Dept Psychol, Denver, CO 80210 USA

[8] Vet Affairs Med Ctr, Dept Psychiat, West Haven, CT 06516 USA

[9] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA

[10] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06519 USA

[11] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA

[12] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 47期

关键词：

dyslexia; DYX2; disequilibrium; haplotype; doublecortin;

D O I：

10.1073/pnas.0508591102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：17053 / 17058

页数：6

共 36 条

[1] GOLD - Graphical Overview of Linkage Disequilibrium [J].