Reviewed by Bret Stetka, MD

Every cell in our bodies contains 3 billion base pairs, all twisted together in helices of DNA, that make up the human genome. Within those base pairs are the ~21,000 genes that code for the proteins that run our bodies and biological functions. Yet these genes only comprise 1-2% of our genome.

For years scientists referred to the other 98% of DNA in our genome – which doesn’t code for proteins – as “junk.” Many thought it didn’t do much of anything; an evolutionary afterthought.

Yet it’s become clear that much of this supposed junk DNA is actually critical to regulating the function of our protein-coding genes. For example, this non-coding DNA can work to prevent certain genes from producing too much or too little of a particular protein. Errors in or lack of regulation of protein production can contribute to a wide range of disorders.

Regions of the genome that code for proteins are called exons and these exons are interrupted with non-coding sequence called introns. Those regions that don’t code – so the vast majority of our genome – are called intergenic sequence. And given that around 85% of DNA variants that result in disease reside in our exons, doctors have traditionally focused on testing just a few genes or only the exons when trying to diagnose certain diseases.

Testing only for exons and some flanking intronic sequence is called “exome sequencing.” And as PerkinElmer Senior Vice President and Chief Scientific Officer Madhuri Hegde, PhD puts it, “Often doctors go small, ordering only testing for specific genes, or a small collection of genes.”

She explains that traditionally exome sequencing was considerably cheaper than whole genome sequencing. Yet given the astounding advances in gene sequencing, the price of reading an entire genome has plummeted. What’s more, an entire genome can now be sequenced in a matter of hours by a machine not much larger than a microwave.

Hegde explains that typically physicians and other healthcare providers rule out causes one at a time until they arrive at a final diagnosis. “Whole genome sequencing does this ruling out all at once, and has the potential to become the routine, first-line test for many types of patients, which is now reflected in the American College of Medical Genetics and Genomics (ACMG) guidelines,” she says. “This means you have higher diagnostic yield, a faster time to diagnosis, and less likelihood of ending up on an ineffective or wrong treatment.”

Performing broad testing like whole genome sequencing from the beginning of a patient’s diagnostic odyssey also means patients can undergo fewer tests and avoid the inconvenience of scheduling and traveling to multiple doctor appointments. Hegde points out that this is potentially life changing for many patients, given that on average it takes a child four to eight years before being diagnosed with a rare disease.

“You’re potentially improving the patient’s quality of life by early intervention, while being able to create more effective long-term treatment plans and implementing them sooner and creating the ability to participate in clinical trials,” says Hegde, adding that PerkinElmer is one of the few companies offering whole genome tests from a simple and easy to obtain sample consisting of a dried blood spot; a testing methodology that was recently approved in New York State.

“When we’re talking about the newborn population, a dry blood spot sample is routinely collected at birth for newborn screening purposes. Our unique capability to use this sample type to perform whole genome sequencing means you usually don’t have to go back and resample the baby in the NICU,” says Hegde. “I think dried blood spots are also a great option for elderly patients with more fragile skin. They can just undergo a finger stick and avoid the needles and tubes.”

Hegde is also resolute in distinguishing between the “genetic” versus “genomic” view of disease. Genetic testing focuses on testing for a single gene variant, or a small collection of gene variants, that cause a particular disease. Whole genome testing paired with other technologies such as mass spectrometry can combine the genome and its products together to maintain our health or cause disease, thus increasing the likelihood of finding the cause of a patient’s condition.

“This ultimately is the value of knowing the whole genome,” says Hegde. “The intent of our genomic testing technologies is to answer complex questions that can proactively inform people about the care they may need, from newborns, to children, to adults.”