Alison Goate, Ph.D. Samuel and Mae S. Ludwig Professor of Genetics in Psychiatry Psychiatry Neurology Genetics Human and Statistical Genetics Program Molecular Genetics and Genomics Program Neurosciences Program
Office Phone: 314-362-8691 Lab Phone: 314-362-8668 Other Phone: 314-747-1711 FAX: 314-747-2983 Box: 8134 Lab Address: G04 Biotechnology Building Email: goate@icarus.wustl.edu Website: http://www.genetics.wustl.edu/molgen/goate.html Keywords: genetics; Alzheimer's disease; Alchohol dependence; nicotine dependence; dementia Short Research Description: Linkage and association studies to uncover genetic susceptibility to neuropsychiatric disease.
Research Abstract: The principal focus of the laboratory is the molecular genetics of neuropsychiatric diseases. The two major research areas are Alzheimer's disease and alcohol dependence, although smaller studies are underway on the genetics of other rare dementias and nicotine dependence. We are using genetic linkage and disequilibrium strategies to identify loci predisposing to these disorders. Our linkage studies in late onset AD have identified evidence for susceptibility loci on chromosomes 9, 10 and 12. The current focus of our AD genetics project is to identify the specific genes on these chromosomes. In addition to our search for novel genes we are also investigating the normal function and regulation of known AD genes including presenilin. We have recently demonstrated that a highly conserved PAL sequence in presenilins and presenilin homologues is essential for normal protease activity and likely part of the active site of these unusual proteases. Linkage studies for alcoholism and related traits have identified evidence for susceptibility loci on chromosomes 4 and 7. Our current focus is the analysis of candidate genes on chromosome 7. Linkage disequilibrium analysis has demonstrated strong association between SNPs in the muscarinic acetylcholine receptor, M2 (CHRM2) and alcohol dependence. An overlapping set of SNPs also shows association with depression, providing evidence of pleiotropy. We are currently investigating the biological basis for the increased risk associated with hapotypes in the CHRM2 gene. Similar analyses have implicated a missense mutation in a bitter taste receptor as a risk factor for alcoholism.
Selected Publications: Grupe A, Li Y, Rowland C, Nowotny P, Hinrichs AL, Smemo S, Kauwe JS, Maxwell TJ, Cherny S, Doil L, Tacey K, van Luchene R, Myers A, Wavrant-De Vrieze F, Kaleem M, Hollingworth P, Jehu L, Foy C, Archer N, Hamilton G, Holmans P, Morris CM, Catanese J, Sninsky J, White TJ, Powell J, Hardy J, O'Donovan M, Lovestone S, Jones L, Morris JC, Thal L, Owen M, Williams J, Goate A. A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. Am J Hum Genet 2006 Jan;78(1):78-88. Hinrichs AL, Wang JC, Bufe B, Kwon JM, Budde J, Allen R, Bertelsen S, Evans W, Dick D, Rice J, Foroud T, Nurnberger J, Tischfield JA, Kuperman S, Crowe R, Hesselbrock V, Schuckit M, Almasy L, Porjesz B, Edenberg HJ, Begleiter H, Meyerhof W, Bierut LJ, Goate AM. Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence. Am J Hum Genet 2006 Jan;78(1):103-111. Li Y, Grupe A, Rowland C, Nowotny P, Kauwe JS, Smemo S, Hinrichs A, Tacey K, Toombs TA, Kwok S, Catanese J, White TJ, Maxwell TJ, Hollingworth P, Abraham R, Rubinsztein DC, Brayne C, Wavrant-De Vrieze F, Hardy J, O'donovan M, Lovestone S, Morris JC, Thal LJ, Owen M, Williams J, Goate A. DAPK1 variants are associated with Alzheimer's disease and allele-specific expression. Hum Mol Genet 2006 Sep 1;15(17):2560-2568. Mukherjee O, Pastor P, Cairns N, Chakraverty S, Kauwe J, Shears S, Behrens M, Budde J, Hinrichs A, Norton J, Levitch D, Taylor-Reinwald L, Gitcho M, Tu P, Grinberg L, Liscic R, Armendariz J, Morris J, Goate A. HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin. Ann Neurol 2006 314-322. Pastor P, Ezquerra M, Perez JC, et al. Novel protective and risk haplotypes spanning the MAPT locus are strongly associated with progressive supranuclear palsy. Ann Neurol 2004 Aug;56(2):249-258.

Last Updated: 06/26/2007