In a group paper published in the June 14 issue of Nature and in 28 companion papers published in the June issue of Genome Research, the ENCyclopedia Of DNA Elements (ENCODE) consortium, which is organized by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), reported results of its exhaustive, four-year effort to build a parts list of all biologically functional elements in 1 percent of the human genome. Carried out by 35 groups from 80 organizations around the world, the research served as a pilot to test the feasibility of a full-scale initiative to produce a comprehensive catalog of all components of the human genome crucial for biological function.
"This impressive effort has uncovered many exciting surprises and blazed the way for future efforts to explore the functional landscape of the entire human genome," said NHGRI Director Francis S. Collins, M.D., Ph.D. "Because of the hard work and keen insights of the ENCODE consortium, the scientific community will need to rethink some long-held views about what genes are and what they do, as well as how the genome's functional elements have evolved. This could have significant implications for efforts to identify the DNA sequences involved in many human diseases."
The completion of the Human Genome Project in April 2003 was a major achievement, but the sequencing of the genome marked just the first step toward the goal of using such information to diagnose, treat and prevent disease. Having the human genome sequence is similar to having all the pages of an instruction manual needed to make the human body. Researchers still must learn how to read the manual's language so they can identify every part and understand how the parts work together to contribute to health and disease.
In recent years, researchers have made major strides in using DNA sequence data to identify genes, which are traditionally defined as the parts of the genome that code for proteins. The protein-coding component of these genes makes up just a small fraction of the human genome -- 1.5 percent to 2 percent. Evidence exists that other parts of the genome also have important functions.
However, until now, most studies have concentrated on functional elements associated with specific genes and have not provided insights about functional elements throughout the genome. The ENCODE project represents the first systematic effort to determine where all types of functional elements are located and how they are organized.
In the pilot phase, ENCODE researchers devised and tested high-throughput approaches for identifying functional elements in the genome. Those elements included genes that code for proteins; genes that do not code for proteins; regulatory elements that control the transcription of genes; and elements that maintain the structure of chromosomes and mediate the dynamics of their replication.
