A Dyslexia-Associated Variant in DCDC2 Changes Gene Expression

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 ....

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Bibliographic Details
Published in:	Behavior genetics Vol. 41; no. 1; pp. 58 - 66
Main Authors:	Meng, Haiying, Powers, Natalie R., Tang, Ling, Cope, Natalie A., Zhang, Ping-Xia, Fuleihan, Ramsay, Gibson, Christopher, Page, Grier P., Gruen, Jeffrey R.
Format:	Journal Article
Language:	English
Published:	Boston Springer US 01-01-2011 Springer Nature B.V
Subjects:	Achievement tests Alleles Behavioral Science and Psychology Brain Brain - metabolism Cell Line Chromosome Deletion Clinical Psychology Dyslexia Dyslexia - genetics Electrophoretic Mobility Shift Assay Enhancer Elements, Genetic Gene expression Gene Expression - genetics Genes Genetic Linkage Genetic Variation - genetics Haplotypes Health Psychology Humans Introns - genetics Medicine Microsatellite Repeats - genetics Microtubule-Associated Proteins - genetics Oligonucleotide Probes Original Research Pediatrics Proteins Psychology Public Health Reading comprehension Reading disabilities Regulatory Sequences, Nucleic Acid - genetics Spelling Variants Australia United States > US Colorado Germany Reading disability Dyslexia Association Regulatory region
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 H. Meng and N. R. Powers contributed equally to this work. Edited by Elena Grigorenko and Brett Miller.
ISSN:	0001-8244 1573-3297
DOI:	10.1007/s10519-010-9408-3