Genomic marathon is worth it

Imagine a project so vast that you could work on it for 20 years, spend $4 billion and still have only just moved it off the starting line. Would you ever finish?

Those questions have for years faced the massive effort to understand human genetic material. The Human Genome Project cost roughly $3.8 billion from 1998 to 2003, and a central message afterward was that “we have but scratched the surface in our understanding.” The ENCODE project picked up where the Human Genome Project left off in 2003, seeking to understand which bits of the genome have an active role in human biology despite their not being genes.

While the 20,000 or genes discovered during the Human Genome Project are a central part of the “blueprint for human biology,” ENCODE has helped to confirm that genes represent less than 2 percent of the genome. Genes, it turns out, are surrounded by vast stretches of code, some of which control when, where and how genes turn on and off.

Teams of ENCODE researchers recently published 30 research papers that represent an early round of results, according to an article in the journal Nature. But how far have we come after adding ENCODE’s seven years and $185 million to our monumental investment in the Human Genome Project?

We asked Michelle Amaral, Ph.D., study navigator in the UAB School of Medicine’s Department of Genetics, for her perspective as part of the next generation of genomic researchers. She thinks ENCODE is worth the investment based on its contributions to date and its potential.

In part thanks to ENCODE, doctors today can assess the impact of small variations in a person’s genome on several diseases, and tailor their treatment accordingly. Amaral mentioned Bruce Korf, M.D., Ph.D., chair of the Department of Genetics, as an example of a UAB genomics researcher whose work is already contributing to both personalized medicine and advances against rare diseases.

What’s taking so long? 

More than 400 ENCODE scientists had completed roughly 1,600 experiments on 150 different cell types in time for the recent ENCODE publications. Despite this frenzy of activity, however, efforts to map the function of the entire human genome are about halfway there, with an in-depth description of the genome’s function just 10 percent complete, according to experts quoted in the Nature article.

“Each person’s DNA code consists of about 3 billion chemical units,” says Amaral in way of explaining the “slow” pace. “Sorting them into genes, gene triggers and gene networks is like trying to piece a foreign alphabet into sentences, stories and libraries of stories, and without knowing the grammar rules.”

From another angle, the ENCODE consortium has already done great things. It has assigned a rough function to about 80 percent of the human genome, although critics argue some of this functional DNA is really junk. It has identified the DNA binding sites for about 120 transcription factors, proteins that control when genes switch on and off to express proteins. And it has mapped genome regions “carpeted” with molecules called methyl groups that confer still more precise control over gene expression.

These mechanisms for genetic fine-tuning may explain why humans are so complex, despite having fewer genes than grapes.

Furthermore, ENCODE has identified thousands of points on the genome where a single-letter (single-molecule) difference in the code contributes to a genetic disease, with 90 percent of them falling outside of genes.

Those interested in learning more should visit the ENCODE project website, the National Human Genome Research Institute ENCODE site, or follow ENCODE on Facebook or Twitter.

UAB genomics retreat

UAB faculty, trainees and students will have a chance to learn more about the field, share work and network at the UAB Genomic Medicine Retreat on Tuesday, Sept. 25. The event will be held in UAB’s Alumni Auditorium.

UAB speakers will include Drs. Korf and Amaral, as well as Lynn Holt, program director for the Genetic Counseling Program, Elliot Lefkowitz, Ph.D., associate professor in Department of Microbiology, and Jonas Almeida, professor in the Department of Pathology. Dan Roden, M.D., professor of Medicine and Pharmacology at Vanderbilt University will also speak. Registration is required and may be completed here.

The list of retreat sponsors reveals the power of the genomics collaboration under way at UAB: the Center for Clinical and Translational Science, Heflin Center for Genomic Science and the Comprehensive Cancer Center.