Alleles of a polymorphic ETV6 binding site in DCDC2 confer risk of reading and language impairment
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Alleles of a polymorphic ETV6 binding site in DCDC2 confer risk of reading and language impairment. / Powers, Natalie R; Eicher, John D; Butter, Falk; Kong, Yong; Miller, Laura L; Ring, Susan M; Mann, Matthias; Gruen, Jeffrey R.
I: American Journal of Human Genetics, Bind 93, Nr. 1, 11.07.2013, s. 19-28.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Alleles of a polymorphic ETV6 binding site in DCDC2 confer risk of reading and language impairment
AU - Powers, Natalie R
AU - Eicher, John D
AU - Butter, Falk
AU - Kong, Yong
AU - Miller, Laura L
AU - Ring, Susan M
AU - Mann, Matthias
AU - Gruen, Jeffrey R
N1 - Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
PY - 2013/7/11
Y1 - 2013/7/11
N2 - Reading disability (RD) and language impairment (LI) are common learning disabilities that make acquisition and utilization of reading and verbal language skills, respectively, difficult for affected individuals. Both disorders have a substantial genetic component with complex inheritance. Despite decades of study, reading and language, like many other complex traits, consistently evade identification of causative and functional variants. We previously identified a putative functional risk variant, named BV677278 for its GenBank accession number, for RD in DCDC2. This variant consists of an intronic microdeletion and a highly polymorphic short tandem repeat (STR) within its breakpoints. We have also shown this STR to bind to an unknown nuclear protein with high specificity. Here, we replicate BV677278's association with RD, expand its association to LI, identify the BV677278-binding protein as the transcription factor ETV6, and provide compelling genetic evidence that BV677278 is a regulatory element that influences reading and language skills. We also provide evidence that BV677278 interacts nonadditively with KIAA0319, an RD-associated gene, to adversely affect several reading and cognitive phenotypes. On the basis of these data, we propose a new name for BV677278: "READ1" or "regulatory element associated with dyslexia 1."
AB - Reading disability (RD) and language impairment (LI) are common learning disabilities that make acquisition and utilization of reading and verbal language skills, respectively, difficult for affected individuals. Both disorders have a substantial genetic component with complex inheritance. Despite decades of study, reading and language, like many other complex traits, consistently evade identification of causative and functional variants. We previously identified a putative functional risk variant, named BV677278 for its GenBank accession number, for RD in DCDC2. This variant consists of an intronic microdeletion and a highly polymorphic short tandem repeat (STR) within its breakpoints. We have also shown this STR to bind to an unknown nuclear protein with high specificity. Here, we replicate BV677278's association with RD, expand its association to LI, identify the BV677278-binding protein as the transcription factor ETV6, and provide compelling genetic evidence that BV677278 is a regulatory element that influences reading and language skills. We also provide evidence that BV677278 interacts nonadditively with KIAA0319, an RD-associated gene, to adversely affect several reading and cognitive phenotypes. On the basis of these data, we propose a new name for BV677278: "READ1" or "regulatory element associated with dyslexia 1."
KW - Alleles
KW - Base Sequence
KW - Binding Sites
KW - Case-Control Studies
KW - Dyslexia
KW - Genetic Association Studies
KW - Haplotypes
KW - HeLa Cells
KW - Humans
KW - Language Development Disorders
KW - Language Tests
KW - Linkage Disequilibrium
KW - Microsatellite Repeats
KW - Microtubule-Associated Proteins
KW - Molecular Sequence Data
KW - Phylogeny
KW - Polymorphism, Genetic
KW - Promoter Regions, Genetic
KW - Protein Binding
KW - Proto-Oncogene Proteins c-ets
KW - Repressor Proteins
KW - Risk Factors
U2 - 10.1016/j.ajhg.2013.05.008
DO - 10.1016/j.ajhg.2013.05.008
M3 - Journal article
C2 - 23746548
VL - 93
SP - 19
EP - 28
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -
ID: 88583170