Incorporating CNV analysis improves the yield of exome sequencing for rare monogenic disorders-an important consideration for resource-constrained settings.
Incorporating CNV analysis improves the yield of exome sequencing for rare monogenic disorders-an important consideration for resource-constrained settings.
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DOI：
10.3389/fgene.2023.1277784
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发表时间：
2023
影响因子：
3.7
通讯作者：
Lombard, Zane
中科院分区：
文献类型：
--
作者：
Louw, Nadja;Carstens, Nadia;Lombard, Zane
关键词：
外显子组测序（ES）是许多罕见单基因疾病的首选诊断测试。它允许在单个测试中检测基因组编码外显子区域中的单核苷酸变体（SNV）和拷贝数变体（CNV），并且这种双重分析是一种有价值的方法，特别是在资源有限的情况下。单核苷酸变异已得到很好的研究;然而，将拷贝数变异分析工具纳入变异识别管道尚未作为常规诊断测试实施，染色体微阵列仍更广泛地用于检测拷贝数变异。研究表明，结合单拷贝数变异分析可以导致高达58%的诊断产率，从单核苷酸变异的管道增加多达18%的产量。重要的是，这是在只考虑计算成本的情况下实现的，而不会产生任何额外的测序成本。这篇简短的综述概述了外显子组数据的拷贝数变异分析以及目前对这类分析的建议。我们还介绍了资源有限环境下罕见单基因疾病研究标准实践的概述。我们提出的证据表明，将拷贝数变异检测工具整合到标准外显子组测序分析管道中可以提高诊断产率，并且应该被认为是一个显着有益的补充，具有相对低的成本影响。在代表性不足的人群和有限的资源环境中进行常规实施将促进CNV数据集的生成和共享，并为在基因组医学中建立这一利基的核心中心提供动力。
Exome sequencing (ES) is a recommended first-tier diagnostic test for many rare monogenic diseases. It allows for the detection of both single-nucleotide variants (SNVs) and copy number variants (CNVs) in coding exonic regions of the genome in a single test, and this dual analysis is a valuable approach, especially in limited resource settings. Single-nucleotide variants are well studied; however, the incorporation of copy number variant analysis tools into variant calling pipelines has not been implemented yet as a routine diagnostic test, and chromosomal microarray is still more widely used to detect copy number variants. Research shows that combined single and copy number variant analysis can lead to a diagnostic yield of up to 58%, increasing the yield with as much as 18% from the single-nucleotide variant only pipeline. Importantly, this is achieved with the consideration of computational costs only, without incurring any additional sequencing costs. This mini review provides an overview of copy number variant analysis from exome data and what the current recommendations are for this type of analysis. We also present an overview on rare monogenic disease research standard practices in resource-limited settings. We present evidence that integrating copy number variant detection tools into a standard exome sequencing analysis pipeline improves diagnostic yield and should be considered a significantly beneficial addition, with relatively low-cost implications. Routine implementation in underrepresented populations and limited resource settings will promote generation and sharing of CNV datasets and provide momentum to build core centers for this niche within genomic medicine.
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影响因子：
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DOI：
10.1161/circgen.120.003108
发表时间：
2021-03
期刊：
Circulation. Genomic and precision medicine
影响因子：
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作者：
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通讯作者：
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