The Evolution of Genetics: Alzheimer's and Parkinson's Diseases.
The Evolution of Genetics: Alzheimer's and Parkinson's Diseases.
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DOI：
10.1016/j.neuron.2016.05.040
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发表时间：
2016-06-15
期刊：
影响因子：
16.2
通讯作者：
Hardy J
中科院分区：
文献类型：
--
作者：
Singleton A;Hardy J
遗传学的发现是目前神经退行性疾病研究的基础。这项工作是由在确定因果突变方面取得的重大进展推动的;然而，将疾病的遗传原因转化为病理生物学理解仍然是一个挑战。第二代遗传学方法的应用允许对疾病的中度和轻度遗传风险因素进行剖析。这需要在两个关键领域进行新的思考：什么构成致病性的证据，以及我们如何将这些发现转化为生物学理解。在这里，我们描述了遗传学的进展和正在进行的进化。我们描述了一种观点，拒绝传统的遗传证据必须是绝对的功能表征之前，并集中在一个多维度的方法整合遗传学，参考数据，和功能的工作。我们还认为，这些挑战不能有效地满足传统的假设驱动的方法，但需要高内容系统范围内的努力。
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 allow 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.