A dyslexia-associated variant in DCDC2 changes gene expression

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

doi:10.1007/s10519-010-9408-3

A dyslexia-associated variant in DCDC2 changes gene expression

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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 language	English (US)
Pages (from-to)	58-66
Number of pages	9
Journal	Behavior Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1007/s10519-010-9408-3
State	Published - Jan 2011

Funding

Acknowledgments This study was supported by the International Dyslexia Association (R07420 to H.M.), and National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS43530 to J.R.G.). The authors thank Dr. Satish Ghatpandle for kindly providing the cell lines, Dr. Patrick G. Gallagher for scientific suggestions, and Dr. Seiyu Hosono, Dr. Zhi-jia Ye, Dr. Queenie Tan, and Dr. Rong Cong for technical assistance. We also thank Susan Chan for editing the manuscript.

Keywords

Association
DCDC2
Dyslexia
Reading disability
Regulatory region

ASJC Scopus subject areas

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

Access to Document

10.1007/s10519-010-9408-3

Cite this

@article{e7de8c6e3bc34ebc840c835bb093577d,

title = "A dyslexia-associated variant in DCDC2 changes gene expression",

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.",

keywords = "Association, DCDC2, Dyslexia, Reading disability, Regulatory region",

author = "Haiying Meng and Powers, {Natalie R.} and Ling Tang and Cope, {Natalie A.} and Zhang, {Ping Xia} and Ramsay Fuleihan and Christopher Gibson and Page, {Grier P.} and Gruen, {Jeffrey R.}",

note = "Funding Information: Acknowledgments This study was supported by the International Dyslexia Association (R07420 to H.M.), and National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS43530 to J.R.G.). The authors thank Dr. Satish Ghatpandle for kindly providing the cell lines, Dr. Patrick G. Gallagher for scientific suggestions, and Dr. Seiyu Hosono, Dr. Zhi-jia Ye, Dr. Queenie Tan, and Dr. Rong Cong for technical assistance. We also thank Susan Chan for editing the manuscript.",

year = "2011",

month = jan,

doi = "10.1007/s10519-010-9408-3",

language = "English (US)",

volume = "41",

pages = "58--66",

journal = "Behavior Genetics",

issn = "0001-8244",

publisher = "Springer New York",

number = "1",

}

TY - JOUR

T1 - A dyslexia-associated variant in DCDC2 changes gene expression

AU - Meng, Haiying

AU - Powers, Natalie R.

AU - Tang, Ling

AU - Cope, Natalie A.

AU - Zhang, Ping Xia

AU - Fuleihan, Ramsay

AU - Gibson, Christopher

AU - Page, Grier P.

AU - Gruen, Jeffrey R.

N1 - Funding Information: Acknowledgments This study was supported by the International Dyslexia Association (R07420 to H.M.), and National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS43530 to J.R.G.). The authors thank Dr. Satish Ghatpandle for kindly providing the cell lines, Dr. Patrick G. Gallagher for scientific suggestions, and Dr. Seiyu Hosono, Dr. Zhi-jia Ye, Dr. Queenie Tan, and Dr. Rong Cong for technical assistance. We also thank Susan Chan for editing the manuscript.

PY - 2011/1

Y1 - 2011/1

N2 - 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.

AB - 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.

KW - Association

KW - DCDC2

KW - Dyslexia

KW - Reading disability

KW - Regulatory region

UR - http://www.scopus.com/inward/record.url?scp=79952443927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952443927&partnerID=8YFLogxK

U2 - 10.1007/s10519-010-9408-3

DO - 10.1007/s10519-010-9408-3

M3 - Article

C2 - 21042874

AN - SCOPUS:79952443927

SN - 0001-8244

VL - 41

SP - 58

EP - 66

JO - Behavior Genetics

JF - Behavior Genetics

IS - 1

ER -

A dyslexia-associated variant in DCDC2 changes gene expression

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this