January 2009: Volume 35, Number 1

CDC Program Aims to Develop Genetic Testing Reference Materials

Clinical labs now offer more than 1,300 genetic tests, but for the vast majority of these tests, no publicly available, characterized reference or QC materials are available. Consequently, labs must improvise to obtain these reagents and, in some cases, develop and run assays without adequate controls. DNA from leftover patient samples, synthetic DNA, or DNA isolated from cell lines are often used for this purpose.

“Without adequate standards, it is difficult for laboratories to develop and validate genetic tests and to maintain the quality of these tests over time,” said Lisa Kalman, PhD, health scientist in the division of laboratory systems, at CDC’s National Center for Preparedness, Detection and Control of Infectious Diseases.

To address this need, CDC initiated efforts to develop appropriate and well-characterized reference materials for labs that perform genetic testing, and in 2004, the agency established the Genetic Testing Reference Materials Coordination Program (GeT-RM) in partnership with the genetics community. The goal of this program is to coordinate a self-sustaining community process to improve the availability of characterized genomic DNA materials for QC, PT, test development/validation, and research, said Kalman, who is the program’s coordinator. GeT-RM also aims to facilitate information exchange between users and providers of reference materials.

Although the program is coordinated by CDC, all of the actual work, including decisions about reference material priorities, specimen collection, material development and characterization occurs through voluntary collaborations with labs, Kalman explained. Based on the input from numerous stakeholders, cell lines with confirmed genotypes were identified as the preferred source of control DNA for genetic testing because they most closely resemble an actual patient specimen.

Recently, GeT-RM completed characterization of DNA reference materials from more than 90 cell lines for a number of genetic disorders, including fragile X, disorders on the Ashkenazi Jewish panel (Bloom syndrome, Canavan disease, Fanconi anemia, familial dysautonomia, Gaucher disease, mucolipidosis IV, Neimann Pick disease and Tay Sachs disease), cystic fibrosis, Huntington disease, MTHFR-related homocysteinemia, alpha1-antitrypsin deficiency, multiple endocrine neoplasia, and BRCA1 and BCRA2-related cancers. Each of these genomic DNA materials was tested in three to10 clinical genetic labs using a variety of genetic assays, including DNA sequence analysis. Information about these materials is available on the GeT-RM website and labs may obtain these materials from the Coriell Cell Repositories website. The program’s website provides a comprehensive source of reference material information. Information is grouped into three subject areas: inherited genetic diseases and pharmacogenetics; molecular oncology; and infectious disease. Information about available reference materials, including applicable characterization studies and results are also provided.

GeT-RM’s current efforts include characterization of DNA reference material for Duchenne muscular dystrophy, as well as a large-scale study of DNA from 100 cell lines for polymorphisms in five pharmacogenetic loci. According to Kalman, the program also intends to deal with the need for reference material in other areas of molecular genetic testing, including molecular oncology, cytogenetics, infectious diseases, and biochemical genetics.