Neurosciences & Mental Health (SickKids Research Institute)
Genetics & Development Division (Krembil Research Institute)
Developmental Dyslexia (specific reading disabilites), working memory, learning, behaviour research, neuropsychiatric disorders, genetic basis of disease, enhancers, gene regulation, CRISPR/Cas9, immune mediated disorders, epigenetics
Drs. Rod Bremner, Jeff Wrana, Dafna Gladman, Joan Withers, Robert Inman, Maureen Lovett, Sharon Guger, Elizabeth Kerr, Bing Ren, Perry Paschou, Paul Sandor.
We are currently preforming genetic studies of psychiatric and cognitive disorders including genome-wide association studies. We follow up the findings from the association studies to identify the genes within these genomic regions by fine mapping and functions studies. We are focusing functional studies on gene regulatory regions, specifically enhancers and super-enhancers. We have developed the technology to perform high throughput studies in large regions of DNA using a DNA “barcode” that uniquely tags DNA amplified from each individual chromosome from hundreds of patient’s DNAs. The barcode design allows us to simultaneously test hundreds of regions for hundreds of patient’s DNAs and detect which DNA change influences gene expression. We are also using CRISPR/Cas9 in select regions to delete regions of the genome in cells and analyzing the consequences of these deletions using RNA-sequencing.
The focus of my research is on gene identification for complex traits and the determination of how DNA changes influence gene function and contribute to risk. My early work focused on determining how specific genes in the immune system were regulated. However, for the past 23 years, my work has been on the genetics of behaviour, specific aspects of cognition, and psychiatric and neurological disorders including attention-deficit hyperactivity disorder (ADHD), childhood-onset anxiety disorders, childhood-onset depression, reading disabilities (developmental dyslexia), and Tourette syndrome. Large genetic studies for these traits have been successful in identifying the position of genes contributing to these disorders and many of the identified genes overlap indicating shared genetic susceptibility across disorders. Interestingly, some of the genes implicated in psychiatric disorders are involved in the immune system. The results from the genetic studies provide overwhelming evidence that changes in gene expression are indicated for disease susceptibility for complex traits, and further that genome-wide association studies implicate genetic variation in specific types of regulatory element, enhancers and super-enhancers, in genetic risk. We are currently preforming functional studies of gene regulatory regions in associated regions for disease using CRISPR/Cas9 editing of cells to study function and high-throughput methods to study the role of genetic variation in gene regulation.
Select Recent Publications
Schmitt AD, Hu M, Jung I, Xu Z, Qiu Y, Tan CL, Li Y, Lin S, Lin Y, Barr CL, Ren B. A compendium of chromatin contact maps reveals spatially active regions in the human genome. Cell Rep. 2016 Nov 15; 17(8):2042-2059. doi: 10.1016/j.celrep.2016.10.061.
Barr CL, Misener VL. Decoding the non-coding genome: elucidating genetic risk outside the coding genome. Genes Brain Behav. 2016 Jan;15(1):187-204. Review.
Lek et al., Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016 Aug 17; 536(7616):285-91. doi: 10.1038/nature19057.
Alexander J, Potamianou H, Xing J, Deng L, Karagiannidis I, Tsetsos F, Drineas P, Tarnok Z, Rizzo R, Wolanczyk T, Farkas L, Nagy P, Szymanska U, Androutsos C, Tsironi V, Koumoula A, Barta C, TSGeneSEE, Sandor P, Barr CL, Tischfield J, Paschou P, Heiman GA and Georgitsi M. Targeted re-sequencing approach of candidate genes implicates rare potentially functional variants in Tourette syndrome etiology. Front Neurosci. 2016 Sep 21; 10:428. eCollection 2016. http://dx.doi.org/10.3389/fnins.2016.00428
Liu F, Hon GC, Villa GR, Turner KM, Ikegami S, Yang H, Ye Z, Li B, Kuan S, Lee AY, Zanca C, Wei B, Lucey G, Jenkins D, Zhang W, Barr CL, Furnari FB, Cloughesy TF, Yong WH, Gahman TC, Shiau AK, Cavenee WK, Ren B, Mischel PS. EGFR mutation promotes glioblastoma through epigenome and transcription factor network remodeling. Mol Cell. 2015 Oct 15;60(2):307-18.
Xie W, Barr CL, Kim A, Yue F, Lee AY, Eubanks J, Dempster EL, Ren B. Base-resolution analyses of parent-of-origin and sequence dependent allele specific DNA methylation in the mouse genome. Cell. 2012 Feb 17; 148(4):816-31.
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/pubmed/?term=Barr+CL
Cross-Appointed to Physiology
Senior Scientist, Krembil Research Institute, UHN
Senior Scientist, The Hospital for Sick Children (SickKids)
Professor, Department of Psychiatry, Physiology, Institute of Medical Science
Student Name: Kaitlyn Price (MSc. Candidate)
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Student Name: Emma Reble (MSc. Candidate)
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Student Name: Aidan Dineen (Postdoctoral Fellow)
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