Center for Molecular Imaging, Division of Genomics and Bioinformatics, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030.
Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):16957-62. doi: 10.1073/pnas.1315934110. Epub 2013 Sep 30.
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.
下一代测序（NGS）常用于研究遗传疾病的病因。然而，其在医学诊断中的临床应用尚处于早期发展阶段。在本报告中，我们展示了 NGS 在遗传风险评估中的价值，并评估了将该技术引入医学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），并要求每位志愿者提供个人病史、构建三代系谱，并参加全面的教育计划。我们的临床报告仅限于基于罕见有害突变和先前报道与人类疾病相关的基因中的已知致病性变异的疾病风险。我们确定了 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 连锁隐性风险等位基因（3 个基因）。我们将 18 名志愿者的个人疾病史与致病疾病基因联系起来。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。我们向所有志愿者提供了传统的遗传咨询和疾病教育，以口头和书面报告的形式。我们的报告表明，当对基因组结果进行仔细解释并与个体的病历和系谱数据整合时，NGS 是遗传疾病风险的有价值的诊断工具。
