Yale researchers have received a $4.9 million dollar grant as part of the Encyclopedia Of DNA Elements (ENCODE) program, a $36 million international initiative aiming to identify and analyze sequences of the human genome.

The National Human Genome Research Institute (NHGRI) will fund a three-year pilot program to experiment with various technologies and techniques to determine the function of base sequences in the human genome. The program will focus on only one percent of the human genome, but if successful it will expand its focus after three years.

“The idea behind the ENCODE grant is that now that they finished the genome, they have all the bases; they want to understand what the different regions of the genome do,” Mark Gerstein, Williams Professor of Molecular Biophysics and Biochemistry, said. “Are they genes, or are they things that regulate genes? What [NHGRI] decided to do was to pick a small region of the genome — they’re going to do a battery of different tests to try to understand in detail what is going on.”

Once the sequences have been analyzed, they may lead to more effective gene therapy and a greater understanding of genetic mutations.

The Yale research team is led by Michael Snyder, professor and chairman of the Department of Molecular, Cellular and Developmental Biology. The team also includes Gerstein and Sherman Weissman, Sterling Professor of Genetics.

“[The study] will have a lot of benefit in showing how we develop from a single cell,” Snyder said. “Also, when you have an idea what the genes and proteins do, you’ll have some idea of what happens when they go wrong — If you have a mutation in a gene you’d really like to know what that gene does to control the deleterious effects of that gene.”

The team will apply technology it developed in Yale laboratories to study the genome of yeast. This technology has already been extended to study the human genome, funded by a Yale Center of Excellence in Genome Science Grant (CEGS).

“[The ENCODE work to be done at Yale] stems from some pioneering technology we established in our lab for analyzing regulating sequences in yeast,” Snyder said. “We’ve been able to extend [technology along those lines] to human cells…technology we’ll be able to use in this ENCODE project.”

Scientists in government, industry and teaching institutions are involved in the international program. Other universities that are participating in the program include Stanford, the University of Virginia and the University of Washington. Each institution will approach the sequence using different technologies to determine which will be the most effective in analyzing the genetic code, and will keep in close contact to compare findings.

“Everyone is bringing different expertise to the project and working on the same sequence with different technology and approaches,” Elise Feingold, Ph.D., the NHGRI program director in charge of the ENCODE project, said. “We’ll be working together. There will be common data base that everyone will submit their data to, along with regular meetings where everyone can share their results and their experiences.”

Snyder said the enormity of the task demands the work of many scientists, and the opportunity for comparison of results during research will be valuable.

“We will all be applying different technologies to bear on the problem,” Snyder said. “There will be a little bit of overlap which is good to compare how we’re doing relative to one another. There is so much to learn — you can have many, many labs working on this, and not learn everything. There will be a lot of synergy to learn as much as possible.”