Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia

Neary, Jennifer L.; Perez, Stephanie M.; Peterson, Kara R.; Lodge, Daniel J.; Carless, Melanie A.

doi:10.1016/j.ygeno.2017.03.004

Cited by 21 publications

(13 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This verified that all sample libraries were indeed enriched for CpG sites (score > 1) but also that, in saliva samples, CpG-site enrichment was more pronounced than in blood samples (mean scores of 1.36 and 1.16, respectively). The enrichment score is somewhat lower than reported elsewhere for human embryonic stem cells (1.64), human dried blood spots (1.63), and rodent hippocampus (1.4) [43][44][45].…”

Section: Introductioncontrasting

confidence: 71%

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

et al. 2017

View full text Add to dashboard Cite

Abstract:Background: Interrogation of DNA methylation profiles hold promise for improved diagnostics, as well as the delineation of the aetiology for common human diseases. However, as the primary tissue of the disease is often inaccessible without complicated and inconvenient interventions, there is an increasing interest in peripheral surrogate tissues. Whereas most work has been conducted on blood, saliva is now becoming recognized as an interesting alternative due to the simple and non-invasive manner of collection allowing for self-sampling. Results: In this study we have evaluated if saliva samples are suitable for DNA methylation studies using methylated DNA immunoprecipitation coupled to next-generation sequencing (MeDIP-seq). This was done by comparing the DNA methylation profile in saliva against the benchmark profile of peripheral blood from three individuals. We show that the output, quality, and depth of paired-end 50 bp sequencing reads are comparable between saliva and peripheral blood and, moreover, that the distribution of reads along genomic regions are similar and follow canonical methylation patterns. Conclusion: In summary, we show that high-quality MeDIP-seq data can be generated using saliva, thus supporting the future use of saliva in the generation of DNA methylation information at annotated genes, non-RefSeq genes, and repetitive elements relevant to human disease.

show abstract

Section: Introductioncontrasting

confidence: 71%

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

et al. 2017

View full text Add to dashboard Cite

show abstract

“…We have recently discovered alterations in the cannabinoid receptor interacting protein 1 (CNRIP1) in the MAM (methylazoxymethanol acetate) model, and in F2 MAM rats, a novel rodent model of schizophrenia susceptibility (Neary et al, 2017;Perez et al, 2016). F2 MAM rats were obtained by mating MAM-treated rats with control rats, resulting in a proportion of the offspring (~40%) displaying a schizophrenia-like phenotype (Perez et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat

Perez

Donegan

Boley

et al. 2019

Schizophrenia Research

Self Cite

View full text Add to dashboard Cite

Adolescent cannabis use has been implicated as a risk factor for schizophrenia; however, it is neither necessary nor sufficient. Previous studies examining this association have focused primarily on the role of the cannabinoid receptor 1 (CB1R) with relatively little known about a key regulatory protein, the cannabinoid receptor interacting protein 1 (CNRIP1). CNRIP1 is an intracellular protein that interacts with the C-terminal tail of CB1R and regulates its intrinsic activity. Previous studies have demonstrated aberrant CNRIP1 DNA promoter methylation in postmortem in human patients with schizophrenia, and we have recently reported decreased methylation of the CNRIP1 DNA promoter in the ventral hippocampus (vHipp) of a rodent model of schizophrenia susceptibility. To examine whether augmented CNRIP1 expression could contribute to the pathology of schizophrenia, we performed viral-mediated overexpression of CNRIP1 in the vHipp of Sprague Dawley rats. We then tested these rats for behavioral correlates of schizophrenia symptoms, followed by electrophysiology to determine the effects on the dopamine system, known to underlie psychosis. Here, we report that overexpression of vHipp CNRIP1 induces impairments in latent inhibition and social interaction, similar to those observed in individuals with schizophrenia and in rodent models of the disease. Furthermore, rats overexpressing vHipp CNRIP1 displayed a significant increase in ventral tegmental area (VTA) dopamine neuron population activity, a putative correlate of psychosis. These data provide evidence that alterations in CNRIP1 may contribute to the pathophysiology of schizophrenia, as overexpression is sufficient to produce neurophysiological and behavioral correlates consistently observed in rodent models of the disease.

show abstract

“…TENM4 rare variants are also found to be associated with bipolar disorder (Ament et al, 2015). Furthermore, a role of Tenm4 has been implicated in a rodent model of schizophrenia (Neary et al, 2017). These studies taken together were in line with a substantial role of TENM4 in mammalian central nervous system development and functions.…”

Section: Discussionmentioning

confidence: 99%

“…Although TENM4 has not been clinically linked to schizophrenia previously, recent studies have already implicated its possible role in mental illness and cognition. In an epigenetic study, the Tenm4 gene has recently been implicated in a rodent model of schizophrenia (Neary et al, 2017). In addition, TENM4 is associated with bipolar disorder in a recent genome-wide association study with a large sample size (Sklar et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing Identifies TENM4 as a Novel Candidate Gene for Schizophrenia in the SCZD2 Locus at 11q14-21

Xue

Zhu

et al. 2019

Front. Genet.

View full text Add to dashboard Cite

Schizophrenia is a complex psychiatric disorder with high genetic heterogeneity, however, the contribution of rare mutations to the disease etiology remains to be further elucidated. We herein performed exome sequencing in a Han Chinese schizophrenia family and identified a missense mutation (c.6724C>T, p.R2242C) in the teneurin transmembrane protein 4 (TENM4) gene in the SCZD2 locus, a region previously linked to schizophrenia at 11q14-21. The mutation was confirmed to co-segregate with the schizophrenia phenotype in the family. Subsequent investigation of TENM4 exons 31, 32, and 33 adjacent to the p.R2242C mutation revealed two additional missense mutations in 120 sporadic schizophrenic patients. Residues mutated in these mutations, which are predicted to be deleterious to protein function, were highly conserved among vertebrates. These rare mutations were not detected in 1000 Genomes, NHLBI Exome Sequencing Project databases, or our in-house 1136 non-schizophrenic control exomes. Analysis of RNA-Seq data showed that TENM4 is expressed in the brain with high abundance and specificity. In line with the important role of TENM4 in central nervous system development, our findings suggested that increased rare variants in TENM4 could be associated with schizophrenia, and thus TENM4 could be a novel candidate gene for schizophrenia in the SCZD2 locus.

show abstract

Comparative analysis of MBD-seq and MeDIP-seq and estimation of gene expression changes in a rodent model of schizophrenia

Cited by 21 publications

References 102 publications

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing

Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat

Exome Sequencing Identifies TENM4 as a Novel Candidate Gene for Schizophrenia in the SCZD2 Locus at 11q14-21

Contact Info

Product

Resources

About