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Detection of structural variation using target captured next-generation sequencing data for genetic diagnostic testing.


ABSTRACT: PURPOSE:Structural variation (SV) is associated with inherited diseases. Next-generation sequencing (NGS) is an efficient method for SV detection because of its high-throughput, low cost, and base-pair resolution. However, due to lack of standard NGS protocols and a limited number of clinical samples with pathogenic SVs, comprehensive standards for SV detection, interpretation, and reporting are to be established. METHODS:We performed SV assessment on 60,000 clinical samples tested with hereditary cancer NGS panels spanning 48 genes. To evaluate NGS results, NGS and orthogonal methods were used separately in a blinded fashion for SV detection in all samples. RESULTS:A total of 1,037 SVs in coding sequence (CDS) or untranslated regions (UTRs) and 30,847 SVs in introns were detected and validated. Across all variant types, NGS shows 100% sensitivity and 99.9% specificity. Overall, 64% of CDS/UTR SVs were classified as pathogenic/likely pathogenic, and five deletions/duplications were reclassified as pathogenic using breakpoint information from NGS. CONCLUSION:The SVs presented here can be used as a valuable resource for clinical research and diagnostics. The data illustrate NGS as a powerful tool for SV detection. Application of NGS and confirmation technologies in genetic testing ensures delivering accurate and reliable results for diagnosis and patient care.

SUBMITTER: Mu W 

PROVIDER: S-EPMC6752280 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Detection of structural variation using target captured next-generation sequencing data for genetic diagnostic testing.

Mu Wenbo W   Li Bing B   Wu Sitao S   Chen Jefferey J   Sain Divya D   Xu Dong D   Black Mary Helen MH   Karam Rachid R   Gillespie Katrina K   Farwell Hagman Kelly D KD   Guidugli Lucia L   Pronold Melissa M   Elliott Aaron A   Lu Hsiao-Mei HM  

Genetics in medicine : official journal of the American College of Medical Genetics 20181219 7


<h4>Purpose</h4>Structural variation (SV) is associated with inherited diseases. Next-generation sequencing (NGS) is an efficient method for SV detection because of its high-throughput, low cost, and base-pair resolution. However, due to lack of standard NGS protocols and a limited number of clinical samples with pathogenic SVs, comprehensive standards for SV detection, interpretation, and reporting are to be established.<h4>Methods</h4>We performed SV assessment on 60,000 clinical samples teste  ...[more]

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