Genetic Correlates of Schizophrenia in the Mouse
Schizophrenia is a common psychiatric disorder with a complex etiology involving genes, environment, and their interaction. While there have been many exciting advances in the genetics of schizophrenia over the past years, including the recent identification of vulnerability genes, it is likely that there are many more allelic variants that increase the risk of disease in human populations. Over the past years several neuroanatomical correlates of schizophrenia have been identified in humans. It is suspected that variation in these correlates has a genetic basis and that these genes have pleiotropic effects on schizophrenia. In this project, we are mapping quantitative trait loci (QTLs) affecting select murine neural and behavioral phenotypes homologous to those associated with schizophrenia in humans. Experimental protocols in the mouse allow for far greater power in detecting QTLs than can be practically obtained in human populations. These QTLs will be fine-mapped to sub-cM intervals. We are identifying positional candidate genes and evaluating their potential for affecting schizophrenia using bioinformatics resources, gene expression data, and known sequence variations. Ultimately, variations in the champion candidate genes will be identified in humans and tested for association with schizophrenia. QTLs are being identified in the BXD, LGXSM, and AXB/BXA sets of recombinant inbred strains and validated and fine-mapped using congenic lines.
Dr. John Csernansky, Northwestern University
Dr. Rob Williams, University of Tennessee-Memphis
Dr. Hongxin Dong, Northwestern University
This project is supported through the Silvio Conte Center for Studies of Schizophrenmia and Related Disorders under the direction of Dr. Deanna Barch (NIMH MH071616).
Publications on the Topic
Meng, L., L. Lu, K. M. Murphy, C. M. Yuede, J. M. Cheverud, J. G. Csernansky and H. Dong. 2011. Neuroanatomic and behavioral traits for autistic disorders in age--‐specific restricted index selection mice. Neuroscience, 189: 215-222.
Dong, H, Martin, M, Colvin, J, Ali, Z, Wang, L, Lu, L, Williams, R, Rosen, G, Csernansky, J & Cheverud, J. (2007) 'Quantitative trait loci linked to thalamus and cortex gray matter volumes in BXD recombinant inbred mice', Heredity, vol. 99, no. 1, pp. 62-69. doi:10.1038/sj.hdy.6800965 [pdf]
Martin, M, Dong, V, Vallera, D, Lee, D, Lu, L, Williams, R, Rosen, G, Cheverud, J & Csernansky J. (2006) 'Independent quantitative trait loci influence ventral and dorsal hippocampal volume in recombinant inbred strains of mice', Genes, Brain and Behavior, vol. 5, pp. 614-623. doi:10.1111/j.1601-183X.2006.00215.x [pdf]