Medically reviewed by Susan Kerrigan, MD and Marianne Madsen on February 2, 2023
For patients, realizing they have a genetic predisposition to disease brings with it a host of choices. For their doctors, the dilemma is balancing cost with prevention––can discovering a genetic marker make a difference? Running entire genetic sequences is expensive. This is why the 2021 news that the Helix Laboratory earned FDA Authorization for a whole exome sequencing platform provides new hope to doctors and their patients. So what is the platform and how does it advance genetic therapies?
Genetics History
Genetics is the study of a person’s genes, the ways they interact, and how they behave in various environments. The science of genomics has led researchers to develop diagnostic tests for diseases. Our DNA––deoxyribonucleic acid––holds the body’s instruction manual. DNA directs how our cells operate. Nearly every cell contains a complete copy of the human genome’s three billion DNA base pairs. Sequencing lets researchers uncover the exact order of bases in a strand of DNA.
It’s no longer a novel notion that it’s possible to identify genetic markers predisposing someone for a disease. The challenge is balancing suspicion with certitude when recommending a course of treatment.
Over 200 years ago, John Conrad Otto correctly surmised that hemophilia was more common in certain families. A decade after his hypothesis, in 1813, John Hay demonstrated that men with the disease could pass it on to their grandchildren through their daughters who were unaffected. Although Hay didn’t know it at the time, this is because hemophilia “is caused by recessive mutations in a gene for specific blood clotting factors located on the X-chromosome. Because females normally have two X-chromosomes, but males only have one, females who inherit one mutated copy of the gene are healthy, but males with the mutation will manifest the disease.”
For over a century and a half, researchers continued to find genetic links to diseases culminating with the work of Victor McKusick, who in 1966 created Mendelian Inheritance in Man––a continually updated publication listing every known heritable disease. From James Gusella’s 1983 work locating disease-causing genes through mapping the Huntington’s disease gene to the Human Genome Project which sequenced the entire set of DNA in humans and was essentially completed in 2004, great strides have been made in the field of genetics. During this time and continuing today, genes for alcoholism, early-onset Alzheimer’s, and breast cancer have been identified. The main hurdle for patients in finding out whether they carry these genes has been one of time and expense.
The Whole Exome Sequencing Platform
An exome is part of the human genome. Although the full genome is some three billion nucleotides which are the “letters” of DNA, just 1.5% are translated into proteins. This is important. The proteins are the working players of the body, the coding portions of the genes that get translated into action. These exons or “EXpressed regiONs” are the parts that get translated into protein form. Sequencing the entire human genome is pricey, but by focusing on the functional 1.5%, scientists can more easily identify the genes that predict predispositions for certain diseases.
Helix’s whole exome sequencing platform is capable of examining some 20,000 genes. Because it only deals with the exome, Helix’s sequencing platform can identify genetic markers at a fraction of the cost of sequencing an entire genome. Or as the company’s co-founder, Dr. James Lu, M.D., Ph.D put it, “Being the first company to receive market authorization for such a broad, sequencing-based platform is a major milestone for Helix and for the genomics industry. Our research has shown that many people are at risk for highly actionable genetic conditions that could be prevented with better access to genetic screening. This first-of-its-kind market authorization will greatly accelerate adoption of genomic medicine that can personalize and improve the care that patients receive.”
Even as researchers make great strides in the field, patients need to remember that genetics is not destiny. Environmental and behavioral factors play a role as well. That means no matter how many genes are linked to a predisposition to disease, individuals still have a great deal of control over whether or not they get them.
Written by John Bankston