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

Author:

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

Abstract

Abstract 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.

Funder

NHGRI

Publisher

Springer Science and Business Media LLC

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