Division of Nephrology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Departments of Internal Medicine and Genetics, Yale University School of Medicine, New Haven, CT, USA.
Pediatr Nephrol. 2018 May;33(5):745-761. doi: 10.1007/s00467-017-3698-0. Epub 2017 Jun 29.
The genesis of whole exome sequencing as a powerful tool for detailing the protein coding sequence of the human genome was conceptualized based on the availability of next-generation sequencing technology and knowledge of the human reference genome. The field of pediatric nephrology enriched with molecularly unsolved phenotypes is allowing the clinical and research application of whole exome sequencing to enable novel gene discovery and provide amendment of phenotypic misclassification. Recent studies in the field have informed us that newer high-throughput sequencing techniques are likely to be of high yield when applied in conjunction with conventional genomic approaches such as linkage analysis and other strategies used to focus subsequent analysis. They have also emphasized the need for the validation of novel genetic findings in large collaborative cohorts and the production of robust corroborative biological data. The well-structured application of comprehensive genomic testing in clinical and research arenas will hopefully continue to advance patient care and precision medicine, but does call for attention to be paid to its integrated challenges.
全外显子测序作为一种强大的工具，可以详细描述人类基因组的蛋白质编码序列，其起源是基于下一代测序技术的可用性和人类参考基因组的知识。儿科肾脏病学领域充满了分子上未解决的表型，这使得全外显子测序的临床和研究应用成为可能，从而能够发现新的基因，并对表型分类错误进行修正。该领域的最新研究告诉我们，当与传统的基因组方法（如连锁分析和其他用于集中后续分析的策略）结合使用时，新型高通量测序技术可能会产生很高的效果。它们还强调了在大型协作队列中验证新的遗传发现以及产生强有力的佐证生物学数据的必要性。综合基因组测试在临床和研究领域的良好应用有望继续推进患者护理和精准医学，但确实需要关注其综合挑战。
