Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Annu Rev Med. 2012;63:35-61. doi: 10.1146/annurev-med-051010-162644.
Following the "finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges.
在“完成”了人类 euchromatin 单体型参考基因组序列之后，新型快速且廉价的测序技术迅速发展，使得人类个体化基因组学时代成为可能。个体人类二倍体基因组序列已经生成，每一个序列都有助于我们更好地理解人类基因组中的变异。因此，我们开始认识到从单个核苷酸到结构变异的个体遗传变异的广泛性。然而，将基因组规模的变异转化为具有医学用途的信息还处于起步阶段。这篇综述总结了在临床实施个体基因组信息方面所采取的初步步骤，并描述了全基因组和外显子组测序在确定遗传疾病原因和提出辅助治疗方面的应用。为了解码、解释和优化人类基因组变异所能为我们提供的临床应用，我们需要更好的分析工具和对我们基因组生物学的更深入理解。个体基因组测序最终可能成为一种常见的医学实践手段，提供有助于制定鉴别诊断的信息。本文概述了一些尚存的挑战。
