title: Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia.
abstract: We conducted a comparative study of multiplexed affinity enrichment sequence methodologies (MBD-seq and MeDIP-seq) in a rodent model of schizophrenia, induced by in utero methylazoxymethanol acetate (MAM) exposure. We also examined related gene expression changes using a pooled sample approach. MBD-seq and MeDIP-seq identified 769 and 1771 differentially methylated regions (DMRs) between F2 offspring of MAM-exposed rats and saline control rats, respectively. The assays showed good concordance, with ~56% of MBD-seq-detected DMRs being identified by or proximal to MeDIP-seq DMRs. There was no significant overlap between DMRs and differentially expressed genes, suggesting that DNA methylation regulatory effects may act upon more distal genes, or are too subtle to detect using our approach. Methylation and gene expression gene ontology enrichment analyses identified biological processes important to schizophrenia pathophysiology, including neuron differentiation, prepulse inhibition, amphetamine response, and glutamatergic synaptic transmission regulation, reinforcing the utility of the MAM rodent model for schizophrenia research.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, TX 78227, USA. Electronic address: jennifer@avagenhealth.com.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Neary
authors.affiliation: Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: perezsm@uthscsa.edu.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perez
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, TX 78227, USA. Electronic address: karap@txbiomed.org.
authors.forename: Kara
authors.initials: K
authors.lastname: Peterson
authors.affiliation: Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: lodged@uthscsa.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lodge
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, TX 78227, USA. Electronic address: mcarless@txbiomed.org.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D008297:Male; D051381:Rats; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D059467:Transcriptome
keywords: DNA methylation; MBD-seq; MeDIP-seq; Methylazoxymethanol acetate; RNA-seq; Schizophrenia