TY - JOUR
T1 - Survey of schizophrenia and bipolar disorder candidate genes using chromatin immunoprecipitation and tiled microarrays (ChIP-chip)
AU - Pedrosa, Erika
AU - Locker, Joseph
AU - Lachman, Herbert M.
N1 - Funding Information:
This work was supported by grants from the Juvenile Bipolar Research Foundation and NIMH (MH073164). The authors thank the Human Fetal Tissue Repository at the Albert Einstein College of Medicine for tissue and the Human Genetics Core Facility.
PY - 2009/1
Y1 - 2009/1
N2 - It has been difficult to identify disease-causing alleles in schizophrenia (SZ) and bipolar disorder (BD) candidate genes. One reason is that responsible functional variants may exist in unidentified regulatory domains. With the advent of microarray technology and high throughput sequencing, however, it is now feasible to screen genes for such regulatory domains relatively easily by using chromatin immunoprecipitation-based methodologies, such as ChIP-chip and ChIP-seq. In ChIP-chip, regulatory sequences can be captured from chromatin immunoprecipitates prepared with antibodies against covalently modified histones that mark certain regulatory domains; DNA extracted from such immunoprecipitates can then be used as microarray probes. As a first step toward demonstrating the feasibility of this approach in psychiatric genetics, we used ChIP-chip to identify regulatory domains in several candidate genes: NRG1, DTNBP1, DISC1, DAO, DAOA, PDE4B, and COMT. Immunoprecipitates were generated with antibodies to histone H3 acetylated at lysine 9 (H3K9Ac) and histone H3 monomethylated at lysine 4 (H3K4me1), which mark promoters and some enhancers, using fetal brain chromatin as a substrate. Several novel putative regulatory elements, as well as the core and proximal promoters for each gene, were enriched in the immunoprecipitates. Genetic variants within these regions would be of interest to study as potential disease-associated alleles.
AB - It has been difficult to identify disease-causing alleles in schizophrenia (SZ) and bipolar disorder (BD) candidate genes. One reason is that responsible functional variants may exist in unidentified regulatory domains. With the advent of microarray technology and high throughput sequencing, however, it is now feasible to screen genes for such regulatory domains relatively easily by using chromatin immunoprecipitation-based methodologies, such as ChIP-chip and ChIP-seq. In ChIP-chip, regulatory sequences can be captured from chromatin immunoprecipitates prepared with antibodies against covalently modified histones that mark certain regulatory domains; DNA extracted from such immunoprecipitates can then be used as microarray probes. As a first step toward demonstrating the feasibility of this approach in psychiatric genetics, we used ChIP-chip to identify regulatory domains in several candidate genes: NRG1, DTNBP1, DISC1, DAO, DAOA, PDE4B, and COMT. Immunoprecipitates were generated with antibodies to histone H3 acetylated at lysine 9 (H3K9Ac) and histone H3 monomethylated at lysine 4 (H3K4me1), which mark promoters and some enhancers, using fetal brain chromatin as a substrate. Several novel putative regulatory elements, as well as the core and proximal promoters for each gene, were enriched in the immunoprecipitates. Genetic variants within these regions would be of interest to study as potential disease-associated alleles.
KW - Asperger
KW - Association
KW - Autism
KW - Dysbindin
KW - Neuregulin
UR - http://www.scopus.com/inward/record.url?scp=68649109624&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68649109624&partnerID=8YFLogxK
U2 - 10.1080/01677060802669766
DO - 10.1080/01677060802669766
M3 - Article
C2 - 19225952
AN - SCOPUS:68649109624
SN - 0167-7063
VL - 23
SP - 341
EP - 352
JO - Journal of Neurogenetics
JF - Journal of Neurogenetics
IS - 3
ER -