TMC PULSE

t m c » p u l s e | s e p t e m b e r 2 0 1 5 16 16 F irst, there was Mendel and his peas. In the century-and-a-half that followed, matched pairs of chromosomes were identified, A's and T's and G's and C's were coupled off, X-ray crystallography techniques exposed the double helix structure of DNA, and the code of life was cracked wide open. It was, of course, the Human Genome Project—the international, multi-billion dollar endeavor in which thousands of researchers spent over a decade identifying and mapping the complete set of nucleic acid sequences encoded within the DNA of humans—that ultimately catalyzed all of these scientific breakthroughs into something that could be translated into the world of health care. Today, just 12 years after its completion, some of the great minds of genomics research are bringing that science into clinics throughout the Texas Medical Center. "Back in the 1980s, we knew that there were genetic causes for important human conditions, and we recognized the potential for understanding genetics and genes to really revolutionize the way we tackled therapy and diagnostics and prognostics, but we didn't have the genome, and the technology to get it wasn't there yet," explained Richard Gibbs, Ph.D., director of the Human Genome Sequencing Center at Baylor College of Medicine. "Nevertheless, the visionary quest was launched to sequence the human genome so that we would have this foundation to do all of it—whatever 'it' turned out to be. It was a big breakthrough upon completion, and the question immediately became, 'How do we push the genome into medicine?' because impacting health is really what it's all about." The first genome cost around $3 billion, but by 2009, advances had reduced the cost of mapping an individual's genome to less than $50,000. Researchers then turned to straightforward problems—diagnoses that, based on family history or other hereditary indicators, pointed towards a single genetic cause. Pediatric diseases quickly emerged as one of the most promising fields for genetic application because many of the disorders are inherited and triggered by the mutation of a single gene. The idea was to map the genome of the patient, and often his or her parents as well, to pinpoint what specific gene was missing or modified and how its expression was inherited. "Baylor already had such a strong history of studying single-gene diseases, and we were determined to move this forward, so we worked on refining the tests," said Gibbs. "We were able to simplify the analyses and developed some clever techniques in the lab that pulled out the genes, which are only one percent of DNA anyway, with special hybridization tools." Known as whole exome sequencing, the abbreviated assay dropped the price to $2,000 per genome. Now, Baylor routinely evaluates children with uninterpreted disorders, often providing answers where before, there were none. For individuals like Kristin Phillips, this kind of information is invaluable. Kristin's son, Jacob, was born in May 2009, seemingly healthy as could be. For the first year of his life, he was a cheerful and active baby, reaching all of his developmental milestones effortlessly until he came down with a common virus at 13 months old, during which time he spiked a 105-degree fever and suffered a small seizure. "After Jacob got sick, he wasn't the same," said Phillips. "He was suddenly very colicky and fussy, and his motor skills began deteriorating drastically—within two months, he was falling over on his face and could not longer bear weight on his legs." Phillips and her husband rushed their son to Texas Children's Hospital, where they ran Without the diagnosis, there would have been no hope, no chance for his survival. At least now, through our research, there's that possibility. — KRISTIN PHILLIPS Mother of Jacob, A Texas Children's Hospital and Baylor College of Medicine Patient (Credit: Robbyn Dodd) THROUGHOUT THE TEXAS MEDICAL CENTER, SCIENTISTS ARE TURNING TO DNA FOR ANSWERS TO MEDICINE'S TOUGHEST QUESTIONS. G E N O M I C S R E V O L U T I O N B y A l e x a n d r a B e c k e r T H E

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