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Association of reading disabilities with regions marked by acetylated H3 histones in KIAA0319

Authors

  • Jillian M. Couto,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
    Current affiliation:
    1. Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, UK.
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  • Izzy Livne-Bar,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Katherine Huang,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Zhaodong Xu,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Tasha Cate-Carter,

    1. Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Yu Feng,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Karen Wigg,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Tom Humphries,

    1. Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Rosemary Tannock,

    1. Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Elizabeth N. Kerr,

    1. Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Maureen W. Lovett,

    1. Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Rod Bremner,

    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
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  • Cathy L. Barr

    Corresponding author
    1. Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
    2. Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
    • Toronto Western Research Institute, Toronto Western Hospital, MP14-302, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8.
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  • How to Cite this Article: Couto JM, Livne-Bar I, Huang K, Xu Z, Cate-Carter T, Feng Y, Wigg K, Humphries T, Tannock R, Kerr EN, Lovett MW, Bremner R, Barr CL. 2009. Association of Reading Disabilities With Regions Marked by Acetylated H3 Histones in KIAA0319. Am J Med Genet Part B 153B:447–462.

Abstract

Reading disabilities (RDs) have been associated with chromosome 6p with recent studies pointing to two genes, DCDC2 and KIAA0319. In this study, markers across the 6p region were tested for association with RD. Our strongest findings were for association with markers in KIAA0319, although with the opposite alleles compared with a previous study. We also found association with markers in VMP, but not with DCDC2. Current evidence indicates that differential regulation of KIAA0319 and DCDC2 contributes to RD, thus we used chromatin immunoprecipitation coupled with genomic tiling arrays (ChIP-chip) to map acetylated histones, a molecular marker for regulatory elements, across a 500 kb genomic region covering the RD locus on 6p. This approach identified several regions marked by acetylated histones that mapped near associated markers, including intron 7 of DCDC2 and the 5′ region of KIAA0319. The latter is located within the 70 kb region previously associated with differential expression of KIAA0319. Interestingly, five markers associated with RD in independent studies were also located within the 2.7 kb acetylated region, and six additional associated markers, including the most significant one in this study, were located within a 22 kb haplotype block that encompassed this region. Our data indicates that this putative regulatory region is a likely site of genetic variation contributing to RD in our sample, further narrowing the candidate region. © 2009 Wiley-Liss, Inc.

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