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The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration

Abstract:
Dyslexia is one of the most prevalent childhood cognitive disorders, affecting ~5% of school-age children. We have identified a risk haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the risk haplotype, the expression of the KIAA0319 gene is reduced but the expression of the other two genes remains unaffected. Using in situ hybridization, we detect a very distinct expression pattern of the KIAA0319 gene in the developing cerebral neocortex of mouse and human fetuses. Moreover, interference with rat Kiaa0319 expression in utero leads to impaired neuronal migration in the developing cerebral neocortex. These data suggest a direct link between a specific genetic background and a biological mechanism leading to the development of dyslexia: the risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319 gene which is required for neuronal migration during the formation of the cerebral neocortex.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/hmg/ddl089

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Human Genetics Wt Centre
Role:
Author
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Institution:
"University of Connecticut, Storrs, USA"
Department:
Department of Physiology and Neurobiology
Role:
Author
More by this author
Institution:
"University College London"
Department:
Neural Development Unit,Institute of Child Health
Role:
Author
More by this author
Institution:
"University College London"
Department:
Wolfson Institute for Biomedical Research
Role:
Author
More by this author
Institution:
"University of Connecticut, Storrs, USA"
Department:
Department of Physiology and Neurobiology
Role:
Author


More from this funder
Funding agency for:
Paramasivam, M
Wang, Y
LoTurco, J
More from this funder
Funding agency for:
Monaco, A


Publisher:
Oxford University Press
Journal:
Human Molecular Genetics More from this journal
Volume:
15
Issue:
10
Pages:
1659-1666
Publication date:
2006-05-01
Edition:
Publisher's version
DOI:
EISSN:
1460-2083
ISSN:
0964-6906


Language:
English
Keywords:
Subjects:
UUID:
uuid:9fe77835-8271-49c7-bbd0-e08485f01b99
Local pid:
ora:3093
Deposit date:
2009-11-25
ARK identifier:

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