Department of Human Genetics, Graduate School of Medicine, the University of Tokyo.
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(9):657-676. doi: 10.2183/pjab.93.042.
Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.
人类基因组变异可能导致性状和疾病风险的差异。通过综合全基因组分析，如使用下一代测序 (NGS) 技术的全基因组测序 (WGS) 和全基因组关联研究 (GWAS)，可以检测到常见和罕见疾病的致病/易感基因和变异。在这里，除了将 NGS 作为一种全基因组分析方法的应用外，我们还总结了从人类基因组中丰富的遗传变异中鉴定功能疾病因果/易感变异的方法，以及使用 NGS 以及体内和体外功能分析评估其在人类疾病中的功能效应的方法。我们还讨论了功能疾病因果/易感变异在个性化医疗中的临床应用。
