The National Human Genome Research Institute (NHGRI) today announced the first grants in a three-year, $36 million scientific reconnaissance mission aimed at discovering all parts of the human genome that are crucial to biological function. 

In recent years, researchers have made tremendous progress in sequencing the genomes of humans and other organisms. Scientists use DNA sequence data to help find genes, which are the parts of the genome that code for proteins. However, the protein-encoding component of DNA comprises just a small fraction of the genome, accounting for roughly 1.5 percent of the genetic material of humans and other mammals. There is compelling evidence that other parts of the genome must have important functions, but at present there is only very limited information available about how these other parts work. 

"The Human Genome Project has provided us with a wonderful foundation, but obviously having the human genomic sequence is not enough. We must keep on exploring this newfound wealth of knowledge if we are to realize the full potential of genome research to improve human health," says NHGRI Director Francis S. Collins, MD, PhD, who led the public effort to sequence all 3 billion base pairs in human DNA. 

"Our experimental and computational methods are still primitive when it comes to identifying functional elements that are not involved in protein coding. That has to change. So, with NHGRI's support, research teams around the world are embarking on a daunting mission: to build a comprehensive 'parts list' of the human genome by identifying and precisely locating all functional elements in our DNA sequence," Dr. Collins says. 

The new effort, which is called the ENCyclopedia Of DNA Elements (ENCODE) project, will be carried out by an international consortium made up of scientists in government, industry and academia. A major aspect of this initiative is a three-year pilot project in which research groups will work cooperatively to test efficient, high- throughput methods for identifying, locating and fully analyzing all of the functional elements contained in a set of DNA target regions that covers approximately 30 megabases, or about 1 percent, of the human genome. If the pilot effort proves successful, the project will be expanded to cover the entire genome. 

"The ultimate goal of the ENCODE project is to create a reference work that will help researchers fully utilize the human sequence to gain a deeper understanding of human biology, as well as to develop new strategies for preventing and treating disease," says Elise A. Feingold, PhD, the NHGRI program director in charge of the ENCODE project. "Following the model established by the Human Genome Project, data generated by ENCODE researchers will be collected and stored in databases, and will be rapidly and freely available to the entire scientific community.” 

The ENCODE pilot effort is being implemented by a consortium because the wide range of technologies that need to be tested and developed is well beyond the scope of any single scientific team. The DNA target regions were selected to provide a good cross section of different types of genome sequence and to encourage researchers to look for functional elements beyond genes, transcription-factor binding sites and others that are already fairly well characterized. 

"Each member of the consortium will look at all the target regions. Researchers won't be able to come in and just focus on their favorite area of the genome," Dr. Feingold says. "By working together in a highly cooperative manner, we fully expect this consortium to lay the groundwork for a future, large-scale effort." 

In addition to studying the human genome itself, another prominent component of the ENCODE project will be the comparison of genomic sequences from many different animals. "Multi-species comparisons enable us to zero in on DNA sequences that have been highly conserved throughout evolution, which is a strong indicator that these sequences reflect functionally important regions of the human genome," says NHGRI Scientific Director Eric D. Green, MD, PhD, whose team recently published a pioneering study in the journal Nature that compared genomic sequences among 13 vertebrate species.