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Genetic sex validation for sample tracking in next-generation sequencing clinical testing

  • Jianhong Hu,
  • Viktoriya Korchina,
  • Hana Zouk,
  • Maegan V. Harden,
  • David Murdock,
  • Alyssa Macbeth,
  • Steven M. Harrison,
  • Niall Lennon,
  • Christie Kovar,
  • Adithya Balasubramanian,
  • Lan Zhang,
  • Gauthami Chandanavelli,
  • Divya Pasham,
  • Robb Rowley,
  • Ken Wiley,
  • Maureen E. Smith,
  • Adam Gordon,
  • Gail P. Jarvik,
  • Patrick Sleiman,
  • Melissa A. Kelly,
  • Harris T. Bland,
  • Mullai Murugan,
  • Eric Venner,
  • Eric Boerwinkle,
  • Debra J. Abrams,
  • Samuel E. Adunyah,
  • Ladia H. Albertson-Junkans,
  • Berta Almoguera,
  • Paul S. Appelbaum,
  • Samuel Aronson,
  • Sharon Aufox,
  • Lawrence J. Babb,
  • Hana Bangash,
  • Melissa A. Basford,
  • Meckenzie Behr,
  • Barbara Benoit,
  • Elizabeth J. Bhoj,
  • Sarah T. Bland,
  • Kenneth M. Borthwick,
  • Erwin P. Bottinger,
  • Deborah J. Bowen,
  • Mark Bowser,
  • Murray Brilliant,
  • Adam H. Buchanan,
  • Andrew Cagan,
  • Pedro J. Caraballo,
  • David J. Carey,
  • David S. Carrell,
  • Victor M. Castro,
  • Rex L. Chisholm,
  • Wendy Chung,
  • Christopher G. Chute,
  • Brittany B. City,
  • Ellen Wright Clayton,
  • Beth L. Cobb,
  • John J. Connolly,
  • Paul K. Crane,
  • Katherine D. Crew,
  • David R. Crosslin,
  • Renata P. da Silva,
  • Jyoti G. Dayal,
  • Mariza De Andrade,
  • Josh C. Denny,
  • Ozan Dikilitas,
  • Alanna J. DiVietro,
  • Kevin R. Dufendach,
  • Todd L. Edwards,
  • Christine Eng,
  • David Fasel,
  • Alex Fedotov,
  • Stephanie M. Fullerton,
  • Birgit Funke,
  • Stacey Gabriel,
  • Vivian S. Gainer,
  • Ali Gharavi,
  • Joe T. Glessner,
  • Jessica M. Goehringer,
  • Adam S. Gordon,
  • Chet Graham,
  • Heather S. Hain,
  • Hakon Hakonarson,
  • John Harley,
  • Margaret Harr,
  • Andrea L. Hartzler,
  • Scott Hebbring,
  • Jacklyn N. Hellwege,
  • Nora B. Henrikson,
  • Christin Hoell,
  • Ingrid Holm,
  • George Hripcsak,
  • Alexander L. Hsieh,
  • Elizabeth D. Hynes,
  • Darren K. Johnson,
  • Laney K. Jones,
  • Yoonjung Y. Joo,
  • Sheethal Jose,
  • Navya Shilpa Josyula,
  • Anne E. Justice,
  • Elizabeth W. Karlson,
  • Kenneth M. Kaufman,
  • Jacob M. Keaton,
  • Eimear E. Kenny,
  • Dustin L. Key,
  • Atlas Khan,
  • H. Lester Kirchner,
  • Krzysztof Kiryluk,
  • Terrie Kitchner,
  • Barbara J. Klanderman,
  • David C. Kochan,
  • Emily Kudalkar,
  • Benjamin R. Kuhn,
  • Iftikhar J. Kullo,
  • Philip Lammers,
  • Eric B. Larson,
  • Matthew S. Lebo,
  • Ming Ta Michael Lee,
  • Kathleen A. Leppig,
  • Chiao-Feng Lin,
  • Jodell E. Linder,
  • Noralane M. Lindor,
  • Todd Lingren,
  • Cong Liu,
  • Yuan Luo,
  • John Lynch,
  • Bradley A. Malin,
  • Brandy M. Mapes,
  • Maddalena Marasa,
  • Keith Marsolo,
  • Elizabeth McNally,
  • Frank D. Mentch,
  • Erin M. Miller,
  • Hila Milo Rasouly,
  • Shawn N. Murphy,
  • Melanie F. Myers,
  • Bahram Namjou,
  • Addie I. Nesbitt,
  • Jordan Nestor,
  • Yizhao Ni,
  • Janet E. Olson,
  • Aniwaa Owusu Obeng,
  • Jennifer A. Pacheco,
  • Joel E. Pacyna,
  • Thomas N. Person,
  • Josh F. Peterson,
  • Lynn Petukhova,
  • Cassandra Pisieczko,
  • Siddharth Pratap,
  • Megan J. Puckelwartz,
  • Alanna K. Rahm,
  • James D. Ralston,
  • Arvind Ramaprasan,
  • Luke V. Rasmussen,
  • Laura J. Rasmussen-Torvik,
  • Dan M. Roden,
  • Elisabeth A. Rosenthal,
  • Maya S. Safarova,
  • Avni Santani,
  • Juliann M. Savatt,
  • Daniel J. Schaid,
  • Steven Scherer,
  • Baergen I. Schultz,
  • Aaron Scrol,
  • Soumitra Sengupta,
  • Gabriel Q. Shaibi,
  • Ning Shang,
  • Himanshu Sharma,
  • Richard R. Sharp,
  • Yufeng Shen,
  • Rajbir Singh,
  • Jordan W. Smoller,
  • Duane T. Smoot,
  • Ian B. Stanaway,
  • Justin Starren,
  • Timoethia M. Stone,
  • Amy C. Sturm,
  • Agnes S. Sundaresan,
  • Peter Tarczy-Hornoch,
  • Casey Overby Taylor,
  • Lifeng Tian,
  • Sara L. Van Driest,
  • Matthew Varugheese,
  • Lyam Vazquez,
  • David L. Veenstra,
  • Digna R. Velez Edwards,
  • Miguel Verbitsky,
  • Kimberly Walker,
  • Nephi Walton,
  • Theresa Walunas,
  • Firas H. Wehbe,
  • Wei-Qi Wei,
  • Scott T. Weiss,
  • Quinn S. Wells,
  • Chunhua Weng,
  • Marc S. Williams,
  • Janet Williams,
  • Leora Witkowski,
  • Laura Allison B. Woods,
  • Julia Wynn,
  • Yanfei Zhang,
  • Jodell Jackson,
  • Cynthia Prows,
  • Lisa Mahanta,
  • Heidi L. Rehm,
  • Richard A. Gibbs,
  • Donna M. Muzny

摘要

Objective

Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups.

Results

Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors (49.09%), samples from transgender participants (3.64%) and stem cell or bone marrow transplant patients (7.27%) along with undetermined sample mix-ups (40%) for which sample swaps occurred prior to arrival at genome centers, however the exact cause of the events at the sampling sites resulting in the mix-ups were not able to be determined.