Human Genome Sequencing at the Population Scale: A Primer on High-Throughput DNA Sequencing and Analysis
Human Genome Sequencing at the Population Scale: A Primer on High-Throughput DNA Sequencing and Analysis
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DOI：
10.1093/aje/kww224
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发表时间：
2017-10-15
影响因子：
5
通讯作者：
Ashley, Euan A.
中科院分区：
文献类型：
--
作者：
Goldfeder, Rachel L.;Wall, Dennis P.;Ashley, Euan A.
大多数人类疾病都有潜在的遗传原因。为了更好地了解基因对疾病的影响及其对医学和公共卫生的影响，研究人员一直在寻找确定单个基因序列的方法，然后是所有基因，现在是完整的人类基因组。大规模并行高通量测序技术将 DNA 剪切成更小的片段，进行测序，然后通过计算重新排序和分析，从而能够以经济实惠的方式对整个人类基因组进行快速且经济的测序。随着测序价格持续下降，越来越多的人接受基因组测序。这可能有助于更好地进行人群水平的疾病亚型和特征描述，以及个体水平的诊断和个性化的治疗和预防计划。在这篇综述中，我们描述了几种大规模并行高通量 DNA 测序技术及其相关的优势、局限性和错误模式，重点关注流行病学研究和精准医学中的应用。我们详细介绍了用于计算处理和解释序列数据的方法，以告知医疗或预防行动。
Most human diseases have underlying genetic causes. To better understand the impact of genes on disease and its implications for medicine and public health, researchers have pursued methods for determining the sequences of individual genes, then all genes, and now complete human genomes. Massively parallel high-throughput sequencing technology, where DNA is sheared into smaller pieces, sequenced, and then computationally reordered and analyzed, enables fast and affordable sequencing of full human genomes. As the price of sequencing continues to decline, more and more individuals are having their genomes sequenced. This may facilitate better population-level disease subtyping and characterization, as well as individual-level diagnosis and personalized treatment and prevention plans. In this review, we describe several massively parallel high-throughput DNA sequencing technologies and their associated strengths, limitations, and error modes, with a focus on applications in epidemiologic research and precision medicine. We detail the methods used to computationally process and interpret sequence data to inform medical or preventative action.