Detection of mobile elements insertions for routine clinical diagnostics in targeted sequencing data

Molecular Genetics & Genomic Medicine

Isabell Cordts¹  German Demidov²  Sorin Armeanu‐Ebinger²  Ulrike Faust²  Christopher Schroeder²  Stephan Ossowski²  Joohyun Park²  Tobias B. Haack²  Cristiana Roggia²  Maria Blandfort³ 

[1] Department of Neurology Klinikum Rechts der Isar, Technical University Munich Munich Germany;Institute of Medical Genetics and Applied Genomics University of Tübingen Tübingen Germany;Neuropediatrics and Medical Genetics Landau Germany;

关键词: genetic diagnostics;    mobile elements insertions;    structural variants;    targeted sequencing;   

DOI  :  10.1002/mgg3.1807

来源: DOAJ

【 摘 要 】

Abstract Background Targeted sequencing approaches such as gene panel or exome sequencing have become standard of care for the diagnosis of rare and common genetic disease. The detection and interpretation of point mutations, small insertions and deletions, and even exon‐level copy number variants are well established in clinical genetic testing. Other types of genetic variation such as mobile elements insertions (MEIs) are technically difficult to detect. In addition, their downstream clinical interpretation is more complex compared to point mutations due to a larger genomic footprint that can not only predict a clear loss of protein function but might disturb gene regulation and splicing even when located within the non‐coding regions. As a consequence, the contribution of MEIs to disease and tumor development remains largely unexplored in routine diagnostics. Methods In this study, we investigated the occurrence of MEIs in 7,693 exome datasets from individuals with rare diseases and healthy relatives as well as 788 cancer patients analyzed by panel sequencing. Results We present several exemplary cases highlighting the diagnostic value of MEIs and propose a strategy for the detection, prioritization, and clinical interpretation of MEIs in routine clinical diagnostics. Conclusion In this paper, we state that detection and interpretation of MEIs in clinical practice in targeted NGS data can be performed relatively easy despite the fact that MEIs very rarely occur in coding parts of the human genome. Large scale reanalysis of MEIs in existing cohorts may solve otherwise unsolvable cases.

【 授权许可】

Unknown