Personalized genomic disease risk of volunteers
Personalized genomic disease risk of volunteers
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DOI：
10.1073/pnas.1315934110
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发表时间：
2013-10-15
影响因子：
11.1
通讯作者：
Caskey, C. Thomas
中科院分区：
文献类型：
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作者：
Gonzalez-Garay, Manuel L.;McGuire, Amy L.;Caskey, C. Thomas
下一代测序（NGS）通常用于研究遗传疾病的原因。然而，它在临床实践中用于医疗诊断的实用性仍处于早期发展阶段。在这份报告中，我们展示了NGS的遗传风险评估的价值，并评估了将这项技术应用于医疗实践的局限性和障碍。我们对81名志愿者进行了全外显子组测序（WES），对于每名志愿者，我们要求他们提供个人病史，构建了一个三代系谱，并要求他们参加一个全面的教育计划。我们将我们的临床报告仅限于基于罕见的破坏性突变和先前报告与人类疾病相关的基因中的已知致病性变异的疾病风险。共鉴定出271个隐性风险等位基因（214个基因）、126个显性风险等位基因（101个基因）和3个X-隐性风险等位基因（3个基因）。我们在18名志愿者中将个人病史与致病基因联系起来。此外，通过将家族史纳入我们的遗传分析，我们确定了另外五种遗传性疾病。传统的遗传咨询和疾病教育提供口头和书面报告给所有志愿者。我们的报告表明，当基因组结果被仔细解释并与个人的医疗记录和谱系数据相结合时，NGS是一种有价值的遗传疾病风险诊断工具。
Next-generation sequencing (NGS) is commonly used for researching the causes of genetic disorders. However, its usefulness in clinical practice for medical diagnosis is in early development. In this report, we demonstrate the value of NGS for genetic risk assessment and evaluate the limitations and barriers for the adoption of this technology into medical practice. We performed whole exome sequencing (WES) on 81 volunteers, and for each volunteer, we requested personal medical histories, constructed a three-generation pedigree, and required their participation in a comprehensive educational program. We limited our clinical reporting to disease risks based on only rare damaging mutations and known pathogenic variations in genes previously reported to be associated with human disorders. We identified 271 recessive risk alleles (214 genes), 126 dominant risk alleles (101 genes), and 3 X-recessive risk alleles (3 genes). We linked personal disease histories with causative disease genes in 18 volunteers. Furthermore, by incorporating family histories into our genetic analyses, we identified an additional five heritable diseases. Traditional genetic counseling and disease education were provided in verbal and written reports to all volunteers. Our report demonstrates that when genome results are carefully interpreted and integrated with an individual's medical records and pedigree data, NGS is a valuable diagnostic tool for genetic disease risk.