Separating chromosomes improves genetic test results

A new process that helps unmask genetic mutations by separating chromosomes so they can be studied individually may improve the diagnostic yield of some genetic tests, according to findings of a Colon Cancer Family Registry study published today in the Journal of the American Medical Association.

Conventional gene sequencing analyzes chromosome simultaneously. In this process, normal copies of DNA sequences on one-half of the pair can mask or hide genetic mutations or deleted DNA sequences on the other allele. As a result, conventional sequencing can sometimes miss a genetic mutation or deletion associated with a hereditary disease.

In the colon cancer study, which was led by Graham Casey, Ph.D., from the Cleveland Clinic Department of Cancer Biology, genes known to be involved in mismatch repair and thought to have many different variations were analyzed using Conversion Technology and Conversion Analysis(TM) to separate the chromosomes. Evaluating the alleles separately led to a significant increase in mutations identified, compared with DNA sequencing alone.

Study co-author Stephen Thibodeau, Ph.D., co-director of the Molecular Genetics Laboratory at Mayo Clinic, believes the results show significant promise for Conversion Technology in gene-based test development. Mayo Medical Laboratories, reference laboratory for Mayo Clinic and a leader in gene-based testing, has licensed the technology for these proprietary processes from GMP Companies, Inc. and plans to use them to develop and enhance genetic tests.

"Conversion Technology has the potential to improve the accuracy of gene-based tests. For many genetic disorders, a variety of different types of mutations can be found to cause disease. Additionally, these mutations can often occur anywhere within the gene being analyzed," says Dr. Thibodeau. "In some cases, the identification of gene mutations can be difficult to detect with conventional methods. This study highlights the potential to identify disease-causing mutations in a higher proportion of patients being studied."

Upon transfer, validation and implementation, Conversion Technology will be first utilized in the Mayo Clinic Molecular Genetics Laboratory, which tests for over 40 genetic disorders. Mayo plans to apply the technology to assays for individuals at risk for specific inherited diseases, including some types of hereditary colon cancer.

These tests, which will use a routine blood sample, are expected to be more sensitive than current competitive offerings. When separated, alleles may be analyzed individually using genetic probes that identify gene sequences. This technology is applicable to a gene, a chromosome, or to the entire human genome. The technology will also be made available as a resource to other clinical and research laboratories both within and outside of Mayo Clinic for various clinical, research and validation applications.