The next generation of complex lung genetic studies.
The next generation of complex lung genetic studies.
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下一代复杂的肺部遗传学研究。
DOI：
10.1164/rccm.201207-1178pp
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发表时间：
2012
影响因子：
24.7
通讯作者：
Schwartz,DavidA
中科院分区：
文献类型：
--
作者：
Yang,IvanaV;Schwartz,DavidA
通过全基因组关联研究确定的常见遗传风险变异解释了复杂疾病中一小部分疾病遗传性。越来越明显的是，每个基因/位点是异质性的，并且人群中多个罕见的独立风险等位基因有助于疾病风险。下一代测序技术已经达到了进行全基因组、全外显子组和靶向区域测序所需的成熟度和低成本，以识别整个人群中的所有罕见风险等位基因，这是通过基因分型不可能实现的任务。设计全基因组、全外显子组和靶向测序项目以鉴定复杂肺部疾病的疾病变体需要四个主要步骤：文库制备、测序、序列数据分析和统计分析。尽管数据分析方法仍在不断发展，但许多已发表的研究已成功识别出与复杂疾病相关的罕见变异。尽管将这些技术应用于肺部疾病面临许多挑战，但罕见变异可能是需要解决的难题的关键部分，以了解复杂肺部疾病的遗传基础，并利用这些信息开发更好的疗法。
Common genetic risk variants identified by genome-wide association studies have explained a small portion of disease heritability in complex diseases. It is becoming apparent that each gene/locus is heterogeneous and that multiple rare independent risk alleles across the population contribute to disease risk. Next-generation sequencing technologies have reached the maturity and low cost necessary to perform whole genome, whole exome, and targeted region sequencing to identify all rare risk alleles across a population, a task that is not possible to achieve by genotyping. Design of whole genome, whole exome, and targeted sequencing projects to identify disease variants for complex lung diseases requires four main steps: library preparation, sequencing, sequence data analysis, and statistical analysis. Although data analysis approaches are still evolving, a number of published studies have successfully identified rare variants associated with complex disease. Despite many challenges that lie ahead in applying these technologies to lung disease, rare variants are likely to be a critical piece of the puzzle that needs to be solved to understand the genetic basis of complex lung disease and to use this information to develop better therapies.