One dose of Coumadin could kill Kelley Thomas. Fortunately, scientific advances in genomics are taking the guesswork out of determining an individual’s reaction to a growing number of medications that a person may be prescribed.
“The most popular talk I give on campus is about genomes,” says Thomas, Hubbard professor of genomics at the College of Life Sciences and Agriculture (COLSA) within the University of New Hampshire (UNH). “I show people my own genome and they run right out of the room to buy their genomes,” he says in reference to the personalized digital genotype report, which was produced by an online company that analyzed his mailed-in saliva sample. Their lab staff extracted Thomas's DNA from the cheek cells contained in his saliva and placed it on a chip that reads a fraction of the Single Nucleotide Polymorphisms, or SNPs, found spread across his entire genome. SNPs are the genetic variations in the DNA sequence that give us our biological variety from other living things. As an incomplete, but interesting complement to genetic testing, this type of genotyping can furnish one with a host of information about everything from traits for earwax type to risk for Alzheimer’s disease. And it was through the results of this genomic information that Thomas learned he has the potential for a fatal response to Coumadin.
Besides safeguarding one’s health and preventing disease, people have used information from their genomic mapping to determine the likelihood of genetic traits in offspring, manage expectations for the development of addiction, or find family members who’ve been separated since birth. “The scientific, ethical, and legal issues are mindboggling,” says Rick Cote, chair of the Department of Molecular, Cellular, and Biomedical Sciences at COLSA, about the type of information one can obtain through interpreting this genetic “map” of a person’s physical and behavioral propensities. But the questions go far beyond the personal and touch upon topics that have global significance, like what we learn from sequencing the genomes of organisms that have been genetically modified or inhabit water contaminated by massive oil spills.
“Genomics is an area of genetics that deals with the whole complement of genes in an organism,” says Thomas. As a relatively new aspect of science, genomics is picking up steam and advancing at an exciting rate. Early techniques for sequencing genomes were established in the 1970’s by Fred Sanger and his research team, but the term “genomics” wasn’t coined until the late 1980’s when geneticist Tom Roderick came up with it over a beer during a conversation about mapping the human genome.
One of the most important tools in genomic research is bioinformatics, or the computer analysis of biological data. Thomas, who teaches a computer programming course for biologists, claims that bioinformatics makes it possible for scientists to make sense of the huge amounts of data contained in a genome and allows us to discover subtle patterns, predict gene locations, determine links between gene expressions, develop expectation for reactions to specific medications, and much more.
To get a visual sense of the enormity of the digital information regarding genomes, one can envision that the print-out of a sequenced human genome fills a floor-to-ceiling book case with hefty volumes of data. At a cost of $100B and six years to complete, the initial Human Genome Project was a lengthy and expensive endeavor. Now all kinds of genomes are being mapped much more quickly—sometimes in a matter of days—and for a mere fraction of the cost. “The mapping of the human genome was a turning point,” says Thomas. “Sequencing no longer applies to individual organisms, but also to environments. In the old days, you had to pick through and culture a single microorganism in order to understand its genome. Now, we can sequence multiple organisms and see how their genetic information changes in different environments. You can see what genes are turned on. You can look for specific genes like those controlling nitrogen fixation. Genome sequencing is the go-to approach and has revolutionized biology in the last five years.”
Thomas is the director of the Hubbard Center for Genome Studies at UNH, which was established in 2001 with a strong focus on marine and aquatic organisms. “Kelley’s work exemplifies, as the director of the Hubbard Center and as an individual researcher, broad-based approaches to solving fundamental biological problems,” says Cote. “Traditional life-science approaches—whether studied at the organismal, cellular, or molecular level—served us well in the 20th century to advance biomedical, agricultural, and other areas of research. Nowadays, genome-based experimental approaches are leading the way to fundamental new understandings of such diverse areas as nutrition, human behavior, cancer, and environmental science, not to mention the molecular mechanisms underlying all of evolution.”
“We started the Hubbard Center recognizing that UNH has historically been known for excellence in environmental biology, and that genomics—as it turned out to be true—would be a major contributor,” says Thomas. The resources of the center are in constant use by professors and students from across the University, many of whom are conducting ecosystem research in the areas of soil microbiology and water quality. Other research programs utilize the center to explore cancer biology, host-pathogen interactions, and cellular communication pathways. “One of the real and relatively recent advances in genomics is looking at biodiversity,” says Thomas. “There may be a thousand organisms in a sample of soil that are behaving differently from another patch of soil. You can take the barcode of the genome, sequence it, and know what the community of organisms looks like.”
Thomas has applied for a grant from the National Science Foundation for a new DNA sequencer valued at just over a million dollars. The size of two copy machines pushed together, the sequencer enables researchers to identify a vast number of genetic markers that have applications for everything, such as conceptualizing plant breeding programs, understanding what genes the salt marsh sparrow possesses that allow it to inhabit the salt marsh, and unraveling the subtle changes in DNA that can cause cancer. The acquisition of this instrument would make the Hubbard Center a core facility that provides unique opportunities to scientists in all areas of life science research at UNH. And the grant would also provide critically needed support personnel for the center to assist with the sequencing work and consult with researchers about using the best available genomics and bioinformatics tools. “Genome-enabled biology is here, and it’s a real strength at UNH, but we are beyond our limit to properly support it,” says Thomas. “We need to have an improved, shared infrastructure for genomics and bioinformatics resources.”
At the undergraduate level, the enrollment in the Genetics major has been doubling every year. That is due—in part—to the cutting-edge technology on campus, the use of which gives matriculated students added confidence for working in a lab, or advancing their studies in graduate school, with a strong understanding of genome-enabled biology. “To answer the really big questions, we need to think more broadly,” says Thomas. “At the level of graduate education, we need to produce the next generation of faculty who look at the big picture and use the appropriate experimental approaches to address fundamental questions in the life sciences.”
“This is an exciting time for the Hubbard Center for Genome Studies,” says Thomas who is, along with other faculty from a variety of disciplines, drawing upon its resources to revolutionize their fields. As forward-thinking professors at UNH, they are leading the way to prepare a new generation of researchers who will work seamlessly across disciplines with the common goal of more intimately understanding ourselves and the world in which we live.