The Evolution of Genetics: Alzheimer's and Parkinson's Diseases.
Genetic discoveries underlie the majority of the current thinking in neurodegenerative disease. This work has been driven by the significant gains made in identifying causal mutations; however, the translation of genetic causes of disease into pathobiological understanding remains a challenge. The application of a second generation of genetics methods allows the dissection of moderate and mild genetic risk factors for disease. This requires new thinking in two key areas: what constitutes proof of pathogenicity, and how do we translate these findings to biological understanding. Here we describe the progress and ongoing evolution in genetics. We describe a view that rejects the tradition that genetic proof has to be absolute before functional characterization and centers on a multi-dimensional approach integrating genetics, reference data, and functional work. We also argue that these challenges cannot be efficiently met by traditional hypothesis-driven methods but that high content system-wide efforts are required.
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA. Electronic address: singleta@mail.nih.gov.
Andrew
A
Singleton
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
John
J
Hardy
D000544:Alzheimer Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005826:Genetics, Medical / Q000639:trends*; D006801:Humans; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D012107:Research Design / Q000639:trends
Alzheimer’s disease; Exome sequencing; Genetics; Genome-wide association; Parkinson’s disease