McGill University and Genome Quebec Innovation Centre, Montreal, Canada.
J Med Genet. 2011 Sep;48(9):580-9. doi: 10.1136/jmedgenet-2011-100223. Epub 2011 Jul 5.
Recent advances in next-generation sequencing technologies have brought a paradigm shift in how medical researchers investigate both rare and common human disorders. The ability cost-effectively to generate genome-wide sequencing data with deep coverage in a short time frame is replacing approaches that focus on specific regions for gene discovery and clinical testing. While whole genome sequencing remains prohibitively expensive for most applications, exome sequencing--a technique which focuses on only the protein-coding portion of the genome--places many advantages of the emerging technologies into researchers' hands. Recent successes using this technology have uncovered genetic defects with a limited number of probands regardless of shared genetic heritage, and are changing our approach to Mendelian disorders where soon all causative variants, genes and their relation to phenotype will be uncovered. The expectation is that, in the very near future, this technology will enable us to identify all the variants in an individual's personal genome and, in particular, clinically relevant alleles. Beyond this, whole genome sequencing is also expected to bring a major shift in clinical practice in terms of diagnosis and understanding of diseases, ultimately enabling personalised medicine based on one's genome. This paper provides an overview of the current and future use of next generation sequencing as it relates to whole exome sequencing in human disease by focusing on the technical capabilities, limitations and ethical issues associated with this technology in the field of genetics and human disease.
新一代测序技术的最新进展带来了医学研究人员研究罕见和常见人类疾病方式的范式转变。以具有成本效益的方式在短时间内生成具有深度覆盖的全基因组测序数据的能力正在取代专注于基因发现和临床测试特定区域的方法。虽然全基因组测序对于大多数应用来说仍然过于昂贵，但外显子组测序——一种仅关注基因组中蛋白质编码部分的技术——将新兴技术的许多优势置于研究人员手中。最近使用这项技术的成功案例，无论遗传背景如何，都发现了少数先证者的遗传缺陷，并正在改变我们对孟德尔疾病的方法，因为很快所有的致病变体、基因及其与表型的关系都将被揭示。预计在不久的将来，这项技术将使我们能够识别个体个人基因组中的所有变体，特别是具有临床相关性的等位基因。除此之外，全基因组测序也有望在诊断和理解疾病方面给临床实践带来重大转变，最终实现基于个体基因组的个性化医疗。本文通过关注与遗传学和人类疾病领域中该技术相关的技术能力、局限性和伦理问题，概述了下一代测序技术在人类疾病中外显子组测序方面的当前和未来用途。
