The Future of Genomics Is Now: Dr. Thomas C. Spelsberg discusses the clinical implications

ORLANDO, Fla.—The genome project sequenced all three billion base pairs of human DNA, revealing the instructions cells need to build all the proteins in the body. But that was just a warm-up, according to Thomas C. Spelsberg, PhD, of the Mayo Clinic in Rochester, Minn.

“Medical genomics is evolving into individualized medicine,” Dr. Spelsberg said at a guest lecture at the Triological Society’s Combined Sections Meeting held here Feb. 4-7. “You can start looking at disease biomarkers, new targeted drugs, disease subcategories, predispositions to diseases and even pharmacogenomics, which is individualized drug metabolism. This is the future, folks.”

Dr. Spelsberg, the George M. Eisenberg Professor in the department of biochemistry and molecular biology at the Mayo Graduate School of Medicine, explained that medical genomics has given way to transcriptonomics, the study of all the mRNAs (messenger RNAs) that code for proteins. Other areas medical genomics has evolved into include preoteomics, the study of all the proteins in cells or organisms, and metabolomics, the study of the activity of cell proteins and enzymes.

Dr. Spelsberg said the knowledge produced by these emerging fields will enable physicians to customize diagnosis and treatment based on each patient’s genetic endowment. Already, researchers have identified about 10 “obesogenes” involved in the maintenance of body weight. Dr. Spelsberg displayed a photo of two rats side by side. One appeared normal, while the other was enormously fat. The fat mouse, he explained, lacked the gene for leptin, the hormone that triggers a feeling of satiety.

Polymorphisms

But the genes themselves are only part of the story. Genes also mutate or “morph” into polymorphisms that can leave the body more susceptible to dysfunction. Some polymorphisms are inherited, some develop over time. “Identical twins are born with the exact same DNA, but they develop polymorphisms with age and start to look different,” Dr. Spelsberg said. “They grow apart.”

The environment plays a role in developing polymorphisms. “People who live in cities get more polymorphisms,” Dr. Spelsberg said. “They say for every 15 cigarettes you smoke you develop a new polymorphism. Smokers have a lot more polymorphisms compared to nonsmokers. And people who get lots of sun have more polymorphisms in their skin. What they’re finding is that the more polymorphisms you get, the shorter your lifespan will be.”

Even though humans are 99.9 percent identical genetically, that remaining 0.1 percent amounts to three million polymorphisms. Most polymorphisms are nonfunctional, but some—about one in 30—alter the structure of the proteins produced by the cell, producing observable changes. A deeper understanding of how polymorphisms interact reveals subclasses of diseases.