Molecular Testing


You’ve probably heard of mail-order genetic DNA test kits. By providing a saliva sample, you can receive a DNA analysis of the particular code in your cells that makes you unique. This consumer-oriented diagnostic test, which one startup refers to as a genetic “service,” has taken the world by storm in recent years.

But John Howe, Ph.D., director of the Yale School of Medicine’s molecular diagnostics laboratory, explains that these home kits cannot provide the level of detail and information that patients receive from a place like the Yale Center for Genomic Analysis.

What is the molecular diagnosis?

Molecular diagnostics, also called molecular pathology, involves taking DNA or RNA, the unique genetic code found in our cells and analyzing the sequences for red flags that may signal the potential onset of a specific disease. The field has expanded rapidly in recent years. “When I came to the department of laboratory medicine in 1992, there were only a few molecular diagnostic tests,” Howe says. “But now there are molecular tests in most areas of pathology.”

The four areas of molecular diagnostics at Yale Medicine include:

  • Infectious diseases (including microbiology and virology)
  • hematopathology
  • Genetics
  • solid tumor

What are examples of common molecular diagnostic tests?

Testing is typically done to determine whether or not patients have a genetic mutation associated with a specific disease, either as an inherited or acquired mutation. Hereditary diseases can be evaluated in the prenatal, neonatal, and adult stages of life.

For example, a common inherited disease is cystic fibrosis (CF). If a newborn is found to have two mutations in the gene associated with CF, the baby is more likely to have the condition. The child can then receive treatment for the disease, which can prolong her life.

Doctors can perform a molecular test for a common inherited hereditary cancer. For example, in breast cancer, they can screen for specific inherited mutations in the BRCA1 and BRCA2 genes, which may increase a patient’s risk of breast and ovarian cancer. Acquired gene mutations can be tested for in some cases, such as chronic myeloid leukemia (CML). A patient can then start therapy as soon as possible.

Tests can also be done to determine if a person has become resistant to a specific drug and needs to change the course of a treatment regimen. For example, a patient with HIV may be monitored using a quantitative molecular test to determine whether or not the amount of viral load has increased significantly, which is a sign of resistance to treatment. The patient’s HIV DNA can then be sequenced to determine if a mutation known to be associated with resistance is found.

Why is next-generation sequencing an important scientific breakthrough?

Genome sequencing refers to understanding the order of approximately 3 billion DNA bases (nucleotides) in a genome that make up a person’s complete DNA. “After the first genetic sequencing of the human genome, there was an explosion in DNA sequencing innovation, which spawned the development of next-generation sequencing,” says Howe. of testing opportunities.

Next-generation sequencing, also known as massively parallel sequencing, is a term used to describe modern sequencing technologies. Next-generation sequencing uses a unique format in which a wide range of biological phenomena, such as mRNA expression and methylation status, can be tested.

What next for the field of molecular diagnostics?

“We are in the early stages of understanding what those DNA sequence changes that indicate disease mean and why they occurred,” Howe says. “We have all this additional information, and now we have to figure out what to do with it: how best to use and apply this new knowledge.”

Research scientists are using this wealth of new information to try to focus more deeply on the understanding of various diseases. “The more we really understand about diseases, the more refined diagnosis and treatment can become,” Howe says.

What makes Yale Medicine’s approach to molecular diagnostics unique?

“We have physicians, both pathologists, and oncologists, who want our department to stay on the cutting edge of new developments in molecular diagnostic tests so they can make more therapeutic options available to their patients,” Howe says. “This is what really led the lab to develop tumor gene panels using next-generation sequencing.”

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