Research and Publications

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We are using murine and non-human primate model systems to investigate the dynamics of DNAm (both 5-mC and 5-hmC) in neurodevelopmental health and disease states. Here, we utilize the extensive non-human primate resources available to UW to study the temporal and spatial changes of DNAm throughout neurodevelopment and due to prenatal/early life stresses. Briefly, these studies will test the hypothesis that DNAm confers epigenetic information to DNA and controls gene expression in response to prenatal stress in both mice and Rhesus monkeys. This approach will provide a distinct advantage to previous studies using only murine models, as rhesus monkeys and humans have structural and functional similarities in the neural circuits mediating neuropsychiatric disease. In addition, the monkey model improves our ability to translate our findings to humans and provides opportunities to test hypotheses that cannot be performed in humans; for example, methylome and transcriptome data from relevant brain regions can be assessed and analyzed in relation to behavioral data.

Moreover, these studies will be combined with others to create an interdisciplinary approach of molecular genetic investigations with functional magnetic resonance imaging to generate comprehensive maps of healthy and disease activity in the brain. Together, these studies will provide insight into the connection between epigenetics and prenatal stress-related alterations in behavior, emotion and cognition as they relate to birth defects and emerging psychiatric symptoms.

Ultimately, since many of the autism endophenotypes overlap with those studied in the non-human primate models within the Psychiatry department’s colony, we will compare the overlap of ASD-associated loci and those loci associated with fear, anxiety and depression.

 

Alisch, R. S., Chopra, P., Fox, A. S., Chen, K., White, A.T.J., Roseboom, P. H., Keles, S., Kalin, N.H., 2014, Differentially Methylated Plasticity Genes in the Amygdala of Young Primates Are Linked to Anxious Temperament, an at Risk Phenotype for Anxiety and Depressive Disorders. J Neurosci., 34(47): 15548-15556. PMID: 25411484.

Journal of Neuroscience 2014: Alisch_et_al_Supplementary Table 1
Journal of Neuroscience 2014: Alisch et al. Supplementary Figure 1

Papale, L. A. Zhang, Q., Li, S., Chen, K., Keles, S., Alisch, R.S., 2015, Genome-wide disruption of 5-hydroxymethylcytosine in a mouse model of autism. Hum Mol Genet, doi:10.1093/hmg/ddv411. PMID: 26423458.

The following two links are the complete information of hyper and hypo DhMRs, in .txt format

ftp://ftp.cs.wisc.edu/pub/users/kelesgroup/Keles/Reid_Alisch/paper-homo_male-wt_male/homo_male_naive-wt_male_naive-top-dhmr-hyper.txt
ftp://ftp.cs.wisc.edu/pub/users/kelesgroup/Keles/Reid_Alisch/paper-homo_male-wt_male/homo_male_naive-wt_male_naive-top-dhmr-hypo.txt

The following are a simplified version the above two files, with only location information, in bed format.

ftp://ftp.cs.wisc.edu/pub/users/kelesgroup/Keles/Reid_Alisch/paper-homo_male-wt_male/hyper.bed
ftp://ftp.cs.wisc.edu/pub/users/kelesgroup/Keles/Reid_Alisch/paper-homo_male-wt_male/hypo.bed