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The Genetics of Adult-Onset Neuropsychiatric Disease: Complexities and Conundra?
James L. Kennedy,1Lindsay A. Farrer,2Nancy C. Andreasen,3Richard Mayeux,4Peter St George-Hyslop1*
Genetic factors play a major role in the etiology of adult-onsetneurodegenerative and neuropsychiatric disorders. Several highlypenetrant genes have been cloned for rare, autosomal-dominant,early-onset forms of neurodegenerative diseases. These geneshave provided important insights into the mechanisms of thesediseases (often altering neuronal protein processing). However,the genes associated with inherited susceptibility to late-onsetneurodegenerative diseases, schizophrenia, and bipolar disorderappear to have smaller effects and are likely to interact witheach other (and with nongenetic factors) to modulate susceptibilityand/or disease phenotype. Several strategies have recently beenapplied to address this complexity, leading to the identificationof a number of candidate susceptibility loci/genes.
1 Departments of Psychiatry and Medicine, Centre for Addiction and Mental Health, Centre for Research in Neurodegenerative Diseases, University of Toronto; and Department of Medicine (Division of Neurology), The University Health Network, Toronto, Ontario M5S 3H9, Canada. 2 Departments of Medicine, Neurology, and Genetics & Genomics, Boston University School of Medicine; and Departments of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA. 3 Department of Psychiatry, University of Iowa; and Departments of Psychiatry and Neurology, University of New Mexico, The MIND Institute, Albuquerque, NM 87106, USA. 4 Gertrude H. Sergievsky Center, Taub Institute of Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
* To whom correspondence should be addressed. E-mail: p.hyslop{at}utoronto.ca
High-Resolution Serum Proteomic Profiling of Alzheimer Disease Samples Reveals Disease-Specific, Carrier-Protein-Bound Mass Signatures.
M. F. Lopez, A. Mikulskis, S. Kuzdzal, D. A. Bennett, J. Kelly, E. Golenko, J. DiCesare, E. Denoyer, W. F. Patton, R. Ediger, et al. (2005)
Clin. Chem.
51, 1946-1954
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Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family.
Y. Li, P. Nowotny, P. Holmans, S. Smemo, J. S. K. Kauwe, A. L. Hinrichs, K. Tacey, L. Doil, R. van Luchene, V. Garcia, et al. (2004)
PNAS
101, 15688-15693
|Abstract »|Full Text »|PDF »
Clinical Trials in Late Life: New Science in Old Paradigms.
Neural system-enriched gene expression: relationship to biological pathways and neurological diseases.
J. Zhang, A. Moseley, A. G. Jegga, A. Gupta, D. P. Witte, M. Sartor, M. Medvedovic, S. S. Williams, C. Ley-Ebert, L. M. Coolen, et al. (2004)
Physiol Genomics
18, 167-183
|Abstract »|Full Text »|PDF »
Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease.
J. A. Beck, M. Poulter, T. A. Campbell, J. B. Uphill, G. Adamson, J. F. Geddes, T. Revesz, M. B. Davis, N. W. Wood, J. Collinge, et al. (2004)
Hum. Mol. Genet.
13, 1219-1224
|Abstract »|Full Text »|PDF »
Alzheimer's disease: one disorder, too many genes?.
