A dyslexia-associated variant in DCDC2 changes gene expression

Haiying Meng, Natalie R. Powers, Ling Tang, Natalie A. Cope, Ping Xia Zhang, Ramsay L Fuleihan, Christopher Gibson, Grier P. Page, Jeffrey R. Gruen

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Reading disability (RD) or dyslexia is a common neurogenetic disorder. Two genes, KIAA0319 and DCDC2, have been identified by association studies of the DYX2 locus on 6p21.3. We previously identified a 2445 bp deletion, and a compound STR within the deleted region (BV677278), in intron 2 of DCDC2. The deletion and several alleles of the STR are strongly associated with RD (P = 0.00002). In this study we investigated whether BV677278 is a regulatory region for DCDC2 by electrophoretic mobility shift and luciferase reporter assays. We show that oligonucleotide probes from the STR bind nuclear protein from human brain, and that alleles of the STR have a range of DCDC2-specific enhancer activities. Five alleles displayed strong enhancer activity and increased gene expression, while allele 1 showed no enhancer activity. These studies suggest that the association of BV677278 with RD reflects a role as a modifier of DCDC2 expression.

Original languageEnglish (US)
Pages (from-to)58-66
Number of pages9
JournalBehavior Genetics
Volume41
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Dyslexia
gene expression
disability
allele
Alleles
alleles
Gene Expression
Reading
oligonucleotide probes
modifiers (genes)
Oligonucleotide Probes
Nucleic Acid Regulatory Sequences
nuclear proteins
luciferase
Nuclear Proteins
Luciferases
Introns
brain
introns
probe

Keywords

  • Association
  • DCDC2
  • Dyslexia
  • Reading disability
  • Regulatory region

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

Cite this

Meng, H., Powers, N. R., Tang, L., Cope, N. A., Zhang, P. X., Fuleihan, R. L., ... Gruen, J. R. (2011). A dyslexia-associated variant in DCDC2 changes gene expression. Behavior Genetics, 41(1), 58-66. https://doi.org/10.1007/s10519-010-9408-3
Meng, Haiying ; Powers, Natalie R. ; Tang, Ling ; Cope, Natalie A. ; Zhang, Ping Xia ; Fuleihan, Ramsay L ; Gibson, Christopher ; Page, Grier P. ; Gruen, Jeffrey R. / A dyslexia-associated variant in DCDC2 changes gene expression. In: Behavior Genetics. 2011 ; Vol. 41, No. 1. pp. 58-66.
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Meng, H, Powers, NR, Tang, L, Cope, NA, Zhang, PX, Fuleihan, RL, Gibson, C, Page, GP & Gruen, JR 2011, 'A dyslexia-associated variant in DCDC2 changes gene expression', Behavior Genetics, vol. 41, no. 1, pp. 58-66. https://doi.org/10.1007/s10519-010-9408-3

A dyslexia-associated variant in DCDC2 changes gene expression. / Meng, Haiying; Powers, Natalie R.; Tang, Ling; Cope, Natalie A.; Zhang, Ping Xia; Fuleihan, Ramsay L; Gibson, Christopher; Page, Grier P.; Gruen, Jeffrey R.

In: Behavior Genetics, Vol. 41, No. 1, 01.01.2011, p. 58-66.

Research output: Contribution to journalArticle

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AU - Fuleihan, Ramsay L

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AU - Gruen, Jeffrey R.

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