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Molecular genetic analysis has allowed the elucidation of the etiology of many single-gene, neurodegenerative syndromes. However, as yet, it has had little direct impact on our understanding of the etiology in cases with more complex modes of inheritance. With the completion of the sequence of the human genome, it should be possible to start to attack these more complex problems. In this article, we review the genetic methods that may be used to dissect the etiologies of these diseases and outline what types of clinical samples will be needed for this quest.