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Transforming the understanding and treatment of mental illness through research DIVISION OF INTRAMURAL RESEARCH PROGRAMS

Staff Scientists and Clinicians Sevilla Detera-Wadleigh, Ph.D.   Dr. Sevilla Detera-Wadleigh is continuing her investigation on the genetics of mood disorders in the Mood and Anxiety Disorders Program, Experimental Therapeutics Branch, Unit on Genetic Basis for Mood and Anxiety. She joined NIMH following a postdoctoral fellowship at the Laboratory of Biochemistry, at the National Cancer Institute where she worked on the mechanism of action of DNA polymerases. She has an M.S. degree in Biochemistry (The George Washington University) and a Ph.D. degree in Biochemistry (Howard University). Research Interests Dr. Dr. Detera-Wadleigh�s long-standing interest and passion is to contribute to the understanding of the genetic basis of psychiatric disorders, particularly mood disorders and schizophrenia. Currently, she is following up on her findings on 13q and other regions, interrogating genetic variants and mutations on positional candidate genes for their potential contribution to overall susceptibility. Recently she and her colleagues investigated the potential role of DIBD1, a gene disrupted by a translocation breakpoint on 11q23. The reciprocal translocation t(9;11)(p24;q23) co-segregated with bipolar affective disorder in a small family. Dr. Detera-Wadleigh completed a high density genome scan of bipolar disorder that has highlighted several regions in the genome, foremost of which were 13q, 18p and 1q as possible loci encoding bipolar disorder- predisposing genes. Additional highlighted regions were 4p, 7q, 14q, 21q and 22q. These sites have likewise been supported by independent groups. Some of these regions of interest overlap with proposed susceptibility regions for schizophrenia which raises the interesting question of whether some of the risk-conferring genes are shared by schizophrenia and bipolar disorder. She collaborated on the first study that implicated the chromosome 18 pericentromeric region in bipolar disorder. In an effort to pursue this finding she isolated 25 new cDNAs on chromosome 18 and cloned the myo-inositol monophosphatase gene (IMPA2) that maps to 18p11.2. The gene is an interesting functional candidate encoding an enzyme that is perturbed by lithium, a mood stabilizing agent. She also found that variants of IMPA2 showed association with schizophrenia. She initiated the first and largest genome scan meta analysis (GSMA) of bipolar disorder that included 22 genome scans conducted worldwide, both published and unpublished. The goal of the GSMA is to find support for regions previously highlighted in individual scans and detect new regions that may have been missed by smaller samples such as those in individual scans. Representative Selected Recent Publications: Baysal B.E., Willett-Brozick J.E., Badner J.A., Corona W., Ferrell R.E., Nimgaonkar V.J., Detera-Wadleigh S.D.: A mannosyltransferase gene at 11q23 is disrupted by a translocation breakpoint that co-segregates with bipolar affective disorder in a small family. Neurogenetics, 4:43-53, 2002. Detera-Wadleigh S.D., Goldin L.R. Genetics of Affective Disorders. In M.C. King, A. G. Motulsky, J. Rotter (eds) Genetic Basis of Common Disease. Oxford University Press, New York, 2nd ed, pp. 831-849, 2002. Detera-Wadleigh S.D.: Lithium-related genetics of bipolar disorder. Ann. Med., 33:272-285, 2001. Yoshikawa T., M. Kikuchi, Saito K., Watanabe A., Yamada K., Shibuya H., Nankai M., Kurumaji A., Hattori E., Ishiguro H., Shimizu H., Okubo Y., Toru M., Detera-Wadleigh S.D. Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples. Mol. Psychiatry, 6:202-210, 2001. Detera-Wadleigh S.D., Badner J.A., Berrettini W.H., Yoshikawa T., Goldin L.R., Turner G, Rollins D.Y., Moses T., Sanders A.R., Karkera J.D., Esterling L.E., Zeng J., Guroff, J.J., Kazuba, D., Maxwell, M.E., Nurnberger J.I. Jr., Gershon E.S. A high density genome scan detects evidence for a bipolar disorder susceptibility locus on chromosome 13q32, and other potential loci on 1q32 and 18p11.2. Proc. Natl. Acad. Sci. USA 96: 5604-5609, 1999. Address:   Phone:   Email: Fax:   Lab Web Site: http://intramural.nimh.nih.gov/mood/proginfo/etpb.htm     Principal Investigators Scientists & Clinicians DIRP Labs and Branches DIRP Research Areas Staff Scientists/Clinicians Office of the Scientific Director Site Map Participate in Research Contact Us Careers in Research What’s New Functional MRI Core Magnetic Resonance Core Magnetoencephalography Core Microarray Core Non-Human Primate Core Scientific and Statistical Computing Core Transgenic Core Veterinary Medicine Resources (Staff only) Office of the Scientific Director Office of the Clinical Director Office of Fellowship Training Office of Technology Transfer Administrative Services Branch Administrative Services

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The Division of Intramural Research Programs is within the National Institute of Mental Health (NIMH) is a part the National Institutes of Health (NIH), is a component of the U.S. Department of Health and Human Services.