Alison Goate, Ph.D. Professor of Genetics Psychiatry Professor Neurology 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@psychiatry.wustl.edu Website: http://www.genetics.wustl.edu/molgen/goate.html Keywords: genetics; Alzheimer's disease; Alchohol dependence; nicotine dependence; dementia Short Research Description: Genome-wide 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: Kauwe JSK, Cruchaga C, Mayo K, Fenoglio C, Bertelsen S, Nowotny P, Galimberti D, Scarpini E, Morris JC, Fagan AM, Holtzman DM, Goate AM. Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition. Proc Natl Acad Sci U S A 2008 105(23):8050-4. Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Bertelsen S, Fox L, Grucza RA, Horton WJ, Kauwe JS, Morgan JD, Saccone NL, Saconne SF, Xuei X, Breslau N, Budde J, Cloninger CR, Dick DM, Foroud T, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Kuperman S, Madden PA , Nurnberger J Jr., Pomerleau O, Porjesz B, Reyes O, Schuckit M, Swan G, Edenberg HJ, Rice JP, Goate A M. Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 2008; 165(9):1163-71. PMID: 18519524 2008 (In Press). Wang JC, Grucza R, Cruchaga C, Hinrichs AL, Bertelsen S, Budde JP, Fox L, Goldstein E, Reyes O, Saccone N, Saccone S, Xuei X, Bucholz K, Kuperman S, Nurnberger J Jr., Rice JP, Schuckit M, Tischfield J, Hesselbrock V, Porjesz B, Edenberg HJ, Bierut LJ, Goate AM. Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence. Mol Psychiatry 2008 (In Press). Gitcho M, Baloh R, Chakraverty S, Mayo K, Nortn , Levitch D, Hatanpaa K, White C, Bigio E, Caselli R, Baker M, Al-Lozi M, Morris J, Pestronk A, Rademakers R, Goate A, Cairns N. TDP-43 A 315T mutation in familial motor neuron disease. Ann Neurol 2008 63(4):535-8. Mukherjee O, Wang J, Gitcho M, Chakraverty S, Taylor-Reinwald L, Shears S, Kauwe JS, Norton J, Levitch D, Bigio EH, Hatanpaa KJ, White CL, Morris JC, Cairns NJ, Goate A. Molular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. Hum Mutat. 2008 20(4):512-21.

Last Updated: 03/18/2009