Cookson Mark R
Laboratory of Neurogenetics, NIA, NIH. 35, Convent Drive, Bethesda, MD, 20892-3707, USA.
Adv Neurobiol. 2017;15:479-489. doi: 10.1007/978-3-319-57193-5_19.
In the past two decades it has become increasingly clear that the risk for many neurodegenerative disorders is at least partially genetic. Assignment of causality for a given gene depends on showing that a particular variant shows either segregation within a family or association with disease across a population. In terms of lifetime risk of disease, the former generally show strong effects compared to the latter. In rare, but interesting, circumstances there are genetic loci that contain different variants that encode either highly penetrant Mendelian disease but also that contribute to risk of sporadic disease. Here, we will discuss the current efforts to complete our understanding of the genetic architecture of neurodegenerative diseases of aging with a particular focus on Parkinson's disease. We will also briefly outline attempts to use systematic approaches to infer relationships between genes associated with the same diseases, which likely demonstrate that in each case there are a relatively small number of underlying biological pathways or processes that may explain pathogenesis.
在过去二十年里，越来越明显的是，许多神经退行性疾病的风险至少部分是由基因决定的。确定某个特定基因的因果关系，取决于证明某个特定变体在家族中呈现分离现象，或者在人群中与疾病存在关联。就疾病的终生风险而言，前者通常比后者表现出更强的影响。在罕见但有趣的情况下，存在一些基因位点，其中包含不同的变体，这些变体既编码高外显率的孟德尔疾病，也会增加散发性疾病的风险。在此，我们将讨论目前为全面了解衰老相关神经退行性疾病的遗传结构所做的努力，特别关注帕金森病。我们还将简要概述尝试运用系统方法来推断与同一种疾病相关的基因之间的关系，这可能表明在每种情况下，都有相对较少的潜在生物学途径或过程可以解释发病机制。
