title: Association of reading disabilities with regions marked by acetylated H3 histones in KIAA0319.
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.
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Jillian M
authors: JM
authors: Couto
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Izzy
authors: I
authors: Livne-Bar
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Katherine
authors: K
authors: Huang
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Zhaodong
authors: Z
authors: Xu
authors: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Tasha
authors: T
authors: Cate-Carter
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Yu
authors: Y
authors: Feng
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Karen
authors: K
authors: Wigg
authors: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Tom
authors: T
authors: Humphries
authors: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Rosemary
authors: R
authors: Tannock
authors: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Elizabeth N
authors: EN
authors: Kerr
authors: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Maureen W
authors: MW
authors: Lovett
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Rod
authors: R
authors: Bremner
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.|Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Cathy L
authors: CL
authors: Barr
mesh_terms: D020413:3' Untranslated Regions; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000648:ultrastructure; D004410:Dyslexia / Q000235:genetics*; D005192:Family Health; D005819:Genetic Markers; D014644:Genetic Variation; D006239:Haplotypes; D006657:Histones / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D015810:Linkage Disequilibrium; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D020413:3' Untranslated Regions; D005819:Genetic Markers; D006657:Histones; C500377:KIAA0319 protein, human; D009419:Nerve Tissue Proteins