Jain Nimansha, Chen-Plotkin Alice S
Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Curr Genet Med Rep. 2018 Mar;6(1):11-19. doi: 10.1007/s40142-018-0133-1. Epub 2018 Feb 5.
To review the evidence for genetic modifier effects in the neurodegenerative diseases Huntington's Disease (HD), Frontotemporal Lobar Degeneration (FTLD), Alzheimer's Disease (AD), and Parkinson's Disease (PD).
Increasingly, we understand human disease genetics less through the lens of single-locus/single-trait effects, and more through that of polygenic contributions to disease risk. In addition, specific examples of genetic modifier effects of the chromosome 7 gene on various target genes including those causal for Mendelian classes of FTLD - and - have emerged from both genetic cohort studies and mechanistic examinations of biological pathways.
Here, we summarize the literature reporting genetic modifier effects in HD, FTLD, AD, and PD. We further contextualize reported genetic modifier effects in these diseases in terms of insight they may lend to the concept of a polygenic landscape for the major neurodegenerative diseases.
回顾亨廷顿舞蹈病（HD）、额颞叶痴呆（FTLD）、阿尔茨海默病（AD）和帕金森病（PD）等神经退行性疾病中基因修饰效应的证据。
我们越来越少地通过单基因座/单性状效应来理解人类疾病遗传学，而是更多地通过多基因对疾病风险的贡献来理解。此外，从基因队列研究和生物途径的机制研究中都发现了7号染色体基因对各种靶基因的基因修饰效应的具体例子，这些靶基因包括导致孟德尔型FTLD的那些基因。
在此，我们总结了报道HD、FTLD、AD和PD中基因修饰效应的文献。我们进一步根据这些疾病中报道的基因修饰效应可能为主要神经退行性疾病的多基因格局概念提供的见解，将其置于背景中进行考量。
