Journal Article

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

Rehm, Heidi L., Wiley, Ken, Jarvik, Gail P., Prows, Cynthia, Muzny, Donna M., Pasham, Divya, Rowley, Robb, Boerwinkle, Eric, Smith, Maureen E., Bland, Harris T., Macbeth, Alyssa, Gordon, Adam, Lennon, Niall, Sleiman, Patrick, Harden, Maegan V., Hu, Jianhong, Venner, Eric, Zhang, Lan, Gibbs, Richard A., Murugan, Mullai, Harrison, Steven M., Balasubramanian, Adithya, Murdock, David, Mahanta, Lisa, Korchina, Viktoriya, Kelly, Melissa A., Zouk, Hana, Kovar, Christie, Chandanavelli, Gauthami

2024

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Biomedical and Life Sciences / Biomedicine / Bone marrow / Bone Marrow Transplantation / Chromosomes / Clinical Laboratory Services / Clinical testing / DNA sequencing / Evaluation / Females / Genetic screening / Genetic testing / Genomes / Genotype / Genotypes / Genotyping / High-Throughput Nucleotide Sequencing / Humans / Laboratories / Life Sciences / Medicine/Public Health / Next-generation sequencing / Next-generation sequencing (NGS) / Nucleotide sequencing / Quality control / Research Note / Sex / Sex concordance / Single-nucleotide polymorphism / SNP genotyping / Stem cell transplantation / Testing laboratories / Transgender persons