Association of reading disabilities with regions marked by acetylated H3 histones in KIAA0319.
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.
Couto
Jillian M
JM
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Livne-Bar
Izzy
I
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Huang
Katherine
K
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Xu
Zhaodong
Z
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Cate-Carter
Tasha
T
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Feng
Yu
Y
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Wigg
Karen
K
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Humphries
Tom
T
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Tannock
Rosemary
R
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Kerr
Elizabeth N
EN
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Lovett
Maureen W
MW
Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Bremner
Rod
R
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Barr
Cathy L
CL
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.
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
D020413:3' Untranslated Regions; D005819:Genetic Markers; D006657:Histones; C500377:KIAA0319 protein, human; D009419:Nerve Tissue Proteins