Whole-genome sequencing offers additional but limited clinical utility compared with reanalysis of whole-exome sequencing

被引：109

作者：

Alfares, Ahmed ^{[1
]}

Aloraini, Taghrid ^{[2
]}

Al Subaie, Lamia ^{[3
]}

Alissa, Abdulelah ^{[2
]}

Al Qudsi, Ahmed ^{[2
]}

Alahmad, Ahmed ^{[2
]}

Al Mutairi, Fuad ^{[3
,4
]}

Alswaid, Abdulrahman ^{[3
,4
]}

Alothaim, Ali ^{[2
,4
]}

Eyaid, Wafaa ^{[3
,4
]}

Albalwi, Mohammed ^{[2
,4
]}

Alturki, Saeed ^{[2
,4
]}

Alfadhel, Majid ^{[3
,4
]}

机构：

[1] Qassim Univ, Dept Pediat, Coll Med, Qasim, Saudi Arabia

[2] King Abdul Aziz Med City, Dept Pathol & Lab Med, Riyadh, Saudi Arabia

[3] King Abdul Aziz Med City, Dept Pediat, Div Genet, Riyadh, Saudi Arabia

[4] King Saud bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia

来源：

GENETICS IN MEDICINE | 2018年 / 20卷 / 11期

关键词：

consanguinity; detection rate; reanalysis of raw data; whole-exome sequencing; whole-genome sequencing; IDENTIFICATION;

D O I：

10.1038/gim.2018.41

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) are used to diagnose genetic and inherited disorders. However, few studies comparing the detection rates of WES and WGS in clinical settings have been performed. Methods: Variant call format files were generated and raw data analysis was performed in cases in which the final molecular results showed discrepancies. We classified the possible explanations for the discrepancies into three categories: the time interval between the two tests, the technical limitations of WES, and the impact of the sequencing system type. Results: This cohort comprised 108 patients with negative array comparative genomic hybridization and negative or inconclusive WES results before WGS was performed. Ten (9%) patients had positive WGS results. However, after reanalysis the WGS hit rate decreased to 7% (7 cases). In four cases the variants were identified by WES but missed for different reasons. Only 3 cases (3%) were positive by WGS but completely unidentified by WES. Conclusion: In this study, we showed that 30% of the positive cases identified by WGS could be identified by reanalyzing the WES raw data, and WGS achieved an only 7% higher detection rate. Therefore, until the cost of WGS approximates that of WES, reanalyzing WES raw data is recommended before performing WGS.

引用

页码：1328 / 1333

页数：6

共 19 条

[1] A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield [J].

Alfares, Ahmed ;

Alfadhel, Majid ;

Wani, Tariq ;

Alsahli, Saud ;

Alluhaydan, Iram ;

Al Mutairi, Fuad ;

Alothaim, Ali ;

Albalwi, Mohammed ;

Al Subaie, Lamia ;

Alturki, Saeed ;

Al-Twaijri, Waleed ;

Alrifai, Muhammad ;

Al-Rumayya, Ahmed ;

Alameer, Seham ;

Faqeeh, Eissa ;

Alasmari, Ali ;

Alsamman, Abdulaziz ;

Tashkandia, Soha ;

Alghamdi, Abdulaziz ;

Alhashem, Amal ;

Tabarki, Brahim ;

AlShahwan, Saad ;

Hundallah, Khalid ;

Wali, Sami ;

Al-Hebbi, Homoud ;

Babiker, Amir ;

Mohamed, Sarar ;

Eyaid, Wafaa ;

Zada, Abdul Ali Peer .

MOLECULAR GENETICS AND METABOLISM, 2017, 121 (02) :91-95

[2] Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants [J].

Belkadi, Aziz ;

Bolze, Alexandre ;

Itan, Yuval ;

Cobat, Aurelie ;

Vincent, Quentin B. ;

Antipenko, Alexander ;

Shang, Lei ;

Boisson, Bertrand ;

Casanova, Jean-Laurent ;

Abel, Laurent .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (17) :5473-5478

[3] Deploying whole genome sequencing in clinical practice and public health: Meeting the challenge one bin at a time [J].

Berg, Jonathan S. ;

Khoury, Muin J. ;

Evans, James P. .

GENETICS IN MEDICINE, 2011, 13 (06) :499-504

[4] Reducing INDEL calling errors in whole genome and exome sequencing data [J].

Fang, Han ;

Wu, Yiyang ;

Narzisi, Giuseppe ;

O'Rawe, Jason A. ;

Jimenez Barron, Laura T. ;

Rosenbaum, Julie ;

Ronemus, Michael ;

Iossifov, Ivan ;

Schatz, Michael C. ;

Lyon, Gholson J. .

GENOME MEDICINE, 2014, 6

[5]

Gilissen C, 2014, NATURE, V511, P344, DOI [10.1038/nature13394, 10.3389/fnhum.2013.00444]

[6] Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders [J].

Lee, Hane ;

Deignan, Joshua L. ;

Dorrani, Naghmeh ;

Strom, Samuel P. ;

Kantarci, Sibel ;

Quintero-Rivera, Fabiola ;

Das, Kingshuk ;

Toy, Traci ;

Harry, Bret ;

Yourshaw, Michael ;

Fox, Michelle ;

Fogel, Brent L. ;

Martinez-Agosto, Julian A. ;

Wong, Derek A. ;

Chang, Vivian Y. ;

Shieh, Perry B. ;

Palmer, Christina G. S. ;

Dipple, Katrina M. ;

Grody, Wayne W. ;

Vilain, Eric ;

Nelson, Stanley F. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2014, 312 (18) :1880-1887

[7] Comparison of Exome and Genome Sequencing Technologies for the Complete Capture of Protein-Coding Regions [J].

Lelieveld, Stefan H. ;

Spielmann, Malte ;

Mundlos, Stefan ;

Veltman, Joris A. ;

Gilissen, Christian .

HUMAN MUTATION, 2015, 36 (08) :815-822

[8] Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists [J].

Li, Marilyn M. ;

Datto, Michael ;

Duncavage, Eric J. ;

Kulkarni, Shashikant ;

Lindeman, Neal I. ;

Roy, Somak ;

Tsimberidou, Apostolia M. ;

Vnencak-Jones, Cindy L. ;

Wolff, Daynna J. ;

Younes, Anas ;

Nikiforova, Marina N. .

JOURNAL OF MOLECULAR DIAGNOSTICS, 2017, 19 (01) :4-23

[9] Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test [J].

Lionel, Anath C. ;

Costain, Gregory ;

Monfared, Nasim ;

Walker, Susan ;

Reuter, Miriam S. ;

Hosseini, S. Mohsen ;

Thiruvahindrapuram, Bhooma ;

Merico, Daniele ;

Jobling, Rebekah ;

Nalpathamkalam, Thomas ;

Pellecchia, Giovanna ;

Sung, Wilson W. L. ;

Wang, Zhuozhi ;

Bikangaga, Peter ;

Boelman, Cyrus ;

Carter, Melissa T. ;

Cordeiro, Dawn ;

Cytrynbaum, Cheryl ;

Dell, Sharon D. ;

Dhir, Priya ;

Dowling, James J. ;

Heon, Elise ;

Hewson, Stacy ;

Hiraki, Linda ;

Inbar-Feigenberg, Michal ;

Klatt, Regan ;

Kronick, Jonathan ;

Laxer, Ronald M. ;

Licht, Christoph ;

MacDonald, Heather ;

Mercimek-Andrews, Saadet ;

Mendoza-Londono, Roberto ;

Piscione, Tino ;

Schneider, Rayfel ;

Schulze, Andreas ;

Silverman, Earl ;

Siriwardena, Komudi ;

Snead, O. Carter ;

Sondheimer, Neal ;

Sutherland, Joanne ;

Vincent, Ajoy ;

Wasserman, Jonathan D. ;

Weksberg, Rosanna ;

Shuman, Cheryl ;

Carew, Chris ;

Szego, Michael J. ;

Hayeems, Robin Z. ;

Basran, Raveen ;

Stavropoulos, Dimitri J. ;

Ray, Peter N. .

GENETICS IN MEDICINE, 2018, 20 (04) :435-443

[10] Clinical sequencing: is WGS the better WES? [J].

Meienberg, Janine ;

Bruggmann, Remy ;

Oexle, Konrad ;

Matyas, Gabor .

HUMAN GENETICS, 2016, 135 (03) :359-362

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