Genetic Testing Reference Materials Coordination Program

Goals

The goal of GeT-RM is to coordinate a self-sustaining community process to improve the public availability of appropriate and characterized reference materials for:

• Quality control (QC).
• Proficiency testing (PT).
• Test development & validation.
• Research.

Purpose

The purpose of this program is:

• To help the genetic testing community obtain appropriate and characterized reference materials.
• To facilitate and coordinate information exchange between users and providers of QC and reference materials.
• To coordinate efforts for contribution, development, characterization and distribution of reference materials for human genetic testing.

Reference materials are essential for quality control in testing

Reference and quality control (QC) materials are essential for many aspects of genetic testing. Testing these materials alongside patient samples helps laboratories to detect errors from test system failures or user errors. Reference materials are also useful for:

• Test development and validation.
• Lot-testing of new reagent batches.
• Proficiency testing/external quality assessment programs (PT/EQA).

Clinical laboratories currently offer genetic tests for over 10,000 human genetic disorders. However, for most of these tests, characterized reference or QC materials are not publicly available. Without publicly available materials, laboratories must adapt and often use non-public sources of genetic material. In some cases, they must also develop and run assays without adequate controls.

Laboratories often use DNA from residual patient samples as reference material. However, these samples are not readily available or renewable.  Laboratories also use synthetic DNA or DNA isolated from cell lines. This lack of reference materials may affect the quality of available tests and could prevent the development of new genetic tests.

Solving the problem of limited genetic reference materials

The Centers for Disease Control and Prevention (CDC), in partnership with the genetic testing community, established the Genetic Testing Reference Materials (GeT-RM) Program in 2004. The goal of this program is to improve the public availability of well characterized genomic DNA reference materials.

GeT-RM works with a variety of partners, including clinical and research laboratories, in vitro diagnostics (IVD) manufacturers, professional organizations, patient advocacy groups, and the Coriell Institute for Medical Research to identify reference material needs and create publicly available, renewable, well characterized genomic DNA reference materials.

Making validated materials available to the laboratory community

Cell lines with confirmed genotypes are generally the preferred control for DNA-based genetic testing. They are preferred because they resemble actual patient samples. As a result, GeT-RM's efforts focus on this material type. GeT-RM has characterized more than 5800 loci in over 450 cell line-based genomic DNA reference materials. These materials cover a number of heritable genetic disorders, pharmacogenetic, and HLA loci, including:

Heritable Disorders

• Fragile X
• Disorders on the Ashkenazi Jewish Panel
  • Bloom syndrome
  • Canavan disease
  • Fanconi anemia
  • Familial dysautonomia
  • Gaucher disease
  • Mucolipidosis IV
  • Neimann Pick disease
  • Tay Sachs disease
• Spinal muscular atrophy
• Cystic fibrosis
• Huntington disease
• MTHFR-related homocysteinemia
• Alpha1-antitrypsin deficiency
• Multiple endocrine neoplasia
• BRCA1 and BRCA2-related cancers
• Duchenne muscular dystrophy
• Myotonic dystrophy
• Rett syndrome

HLA Loci

• 108 samples for 11 HLA loci

Pharmacogenetic (PGx) Loci

• 9 studies characterized 363 samples for 34 PGx genes and loci including CYP2C9, CYP2C19, CYP3A4, CYP3A5, CYP2D6, TPMT, NUDT15, and DPYD

Each sample was characterized using a variety of methods and test platforms by two or more laboratories. Results were assessed for quality, discordances, and determination of consensus genotype for each sample. These materials are publicly available from the Coriell Institute for Medical Research.

References

Disclaimer

The CDC is not responsible for the validity of mutations in cell lines or any other materials. Inclusion of commercially available materials or reagents on this website does not constitute an endorsement of such materials by the CDC and no endorsement shall be stated or inferred.