Schrodi Steven J
Marshfield Clinic Research Foundation, Center for Human GeneticsMarshfield, WI, USA; Computation and Informatics in Biology and Medicine, University of Wisconsin-MadisonMadison, WI, USA.
Front Genet. 2016 Jun 8;7:106. doi: 10.3389/fgene.2016.00106. eCollection 2016.
Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant.
人类遗传学理论模型的发展以及这些模型与实验和统计评估的整合对科学进步至关重要。本文观点认为，加大疾病遗传学理论研究力度，辅助实验和统计工作，将加速对复杂疾病分子病因的揭示。特别是，开发新的、现实的疾病遗传学模型将有助于阐明复杂疾病的发病机制，这些模型所预测的遗传数据模式将能够对疾病遗传学预测的多个方面进行同步、更全面的统计检验，从而更好地识别疾病基因座。我所说的理论人类遗传学，涵盖所有致力于对疾病性状背后的遗传结构进行建模的研究，以及对这些模型所产生的原理和动态的研究。因此，理论疾病遗传学工作的范围包括构建和分析描述疾病易感等位基因如何（1）产生、（2）在家庭和人群中传递以及（3）在基因组和环境因素中与其他风险和保护等位基因相互作用以产生疾病状态的模型。理论工作有助于深入了解与连锁、传递和关联研究以及群体遗传学的实证结果相一致的可行疾病遗传模型。此外，了解现实疾病模型下预期的遗传数据模式将使发现疾病易感等位基因和常见疾病中重要的其他遗传因素的方法更加强大。尽管疾病遗传学理论起着关键作用，但此类研究并不特别活跃。
