Survey of schizophrenia and bipolar disorder candidate genes using chromatin immunoprecipitation and tiled microarrays (ChIP-chip)

Erika Pedrosa, Joseph Locker, Herbert M. Lachman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)341-352
Number of pages12
JournalJournal of Neurogenetics
Volume23
Issue number3
DOIs
StatePublished - Jan 2009

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Chromatin Immunoprecipitation
Bipolar Disorder
Schizophrenia
Histones
Lysine
Chromatin
Histone Code
Alleles
Genes
Antibodies
Regulator Genes
Psychiatry
Technology
DNA
Brain
Surveys and Questionnaires

Keywords

  • Asperger
  • Association
  • Autism
  • Dysbindin
  • Neuregulin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Genetics

Cite this

Survey of schizophrenia and bipolar disorder candidate genes using chromatin immunoprecipitation and tiled microarrays (ChIP-chip). / Pedrosa, Erika; Locker, Joseph; Lachman, Herbert M.

In: Journal of Neurogenetics, Vol. 23, No. 3, 01.2009, p. 341-352.

Research output: Contribution to journalArticle

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