Development and Characterization of Reference Materials for Genetic Testing: Focus on Public Partnerships

Abstract

Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs.

Keywords: Assay validation; DNA sequencing; Genetic tests; Genome sequencing; Genomics; Molecular oncology; Next generation sequencing; Quality control; Reference materials.

Fig. 1. Steps in the GeT-RM Process. Information about reference material (RM) needs is obtained from the genetic testing community. Once needs have been identified, appropriate cell lines from the Coriell Cell Repositories are identified or created through collaboration with patient groups and academic laboratories. Coriell prepares and ships cell line-derived DNA samples to clinical genetic testing laboratories and test manufacturers who have volunteered to characterize the blinded samples. Different laboratories are selected to maximize the variety of testing methods used. Laboratories test the DNA samples and report their results back to the CDC for analysis and arbitration of discrepant results. A consensus genotype is assigned to each sample and the results are published, presented at meetings, and provided on the GeT-RM and Coriell websites.