Sometimes a patient is hospitalized with a severe illness that cannot be diagnosed with standard medical tests and imaging. In these rare cases, an answer that explains these puzzling symptoms might be buried in a person’s genes.
Your genes act as sentences in an instruction manual that tell the body how to function. Genes guide the production of molecules called proteins that are necessary for creating the body’s cells, tissues, and organs, as well as for maintaining their function and operation. Genes, however, only make up 1 to 2 percent of your entire “genome,” a term that refers to all of your DNA. This small portion of the genome that makes up actual genes with instructions for making proteins is called the “exome.” In the past decade, physicians and researchers have relied on whole exome sequencing (WES) to uncover new genetic mutations linked to diseases because the procedure was less expensive and required less storage space than sequencing a person’s entire genome.
However, as sequencing costs and data storage requirements have continued to drop, whole genome sequencing (WGS) has become more feasible, though it still is not a widely offered service. Whole genome sequencing translates all of the 3 billion DNA base pairs that make up an entire human genome into a file made up of letters. Doctors and researchers then use tools to scan and analyze these letters (which represent the person’s entire genome) for mutations, or typos, in the genes.
“The vast majority of DNA mutations that lead to illness are found in the exome, making WES an excellent test to look for both known and unknown genetic diseases,” says Saquib Lakhani, MD, clinical director of Yale Medicine’s Pediatric Genomics Discovery Program (PGDP). However, Dr. Lakhani points out that whole genome sequencing can be helpful when a person’s life depends on how quickly a diagnosis can be found and if WES has been tried and did not provide any helpful answers.
At Yale Medicine, our team of physicians, geneticists, and researchers work together to solve complex medical problems that may have an underlying genetic component. Currently, whole genome sequencing is only available through a referral from a patient’s doctor.