In 1995 the UW Genome Center joined the International Human Genome Sequencing Consortium in an effort to identify the 30,000 to 35,000 genes that produce the molecular blueprint of a human. Since then, professors Dr. Maynard Olson, in genome sciences and medicine, and Dr. Phil Green, in genome sciences, have made significant contributions to the Human Genome Project.

“The challenge of the Human Genome Project is how to take all of these tiny pieces of what can be thought of as a jigsaw puzzle and put them together without making a lot of mistakes,” explained Olson.

Olson directs the UW Genome Center. Trained as a chemist at the California Institute of Technology and Stanford University, Olson recognized early on that human genome technology might eventually be used to prevent and treat diseases such as cancer.

Olson’s pioneering research includes developing a yeast artificial cloning system and introducing new mapping methods and markers. He has led efforts to develop the yeast artificial chromosome (YAC) system for analyzing large blocks of DNA imported into yeast from any organism. The technology, which became the basis of physical maps of all mammals, allows scientists to study large portions of the human genome and has proved indispensable for researchers tracking genetic markers.

Methods from the Human Genome Project are applied to many areas, including comparing the human genome to those of other living things, and analyzing genomes of infectious agents to learn how they are programmed to adapt and survive. A researcher cultures bacteria for a genetic study.

“Since the outset of modern genome sequencing, the limiting factor has been the reconciliation of discrepancies in the sequence,” said Olson. “There’s a delicate balance between sweeping discrepancies under the rug and resolving them appropriately. Expert interpretation is required. Phil Green and I have been working for many years to improve the automation to resolve this issue.”

Green first became involved with genomic sequencing after receiving a Ph.D. in mathematics from the University of California, Berkeley, and working in a private biotechnology firm. At the UW, Green has designed mathematical, statistical, and computer models for analyzing the genomes of humans and other organisms. His software programs PHRAP and PHRED are used worldwide to analyze genomic data. In 2001 Green, who is a Howard Hughes Medical Institute investigator, was elected to the National Academy of Sciences.

Now Green is working on software to automate the finishing process of the genome. His goal is to produce reasonably accurate product that can stand the test of time. In 10 to 15 years Green hopes researchers will be able to feed any genome sequence into a computer and come out with a reliable list of genes and other biologically important parts of the sequence. Green and his colleagues are well on their way with Caenorhabditis elegans, a small, soil-dwelling nematode whose biology shares with humans a surprising number of essential characteristics and problems. C. elegans also has a known genome sequence.

“Our predictions are getting there,” said Green. “About 80 percent of the time we can get the gene exactly right. We’re interested in comparing other genomes to the human genome.”

Olson has received a five-year $15 million grant from the National Human Genome Research Institute (NHGRI) to create a center to study the differences among people’s genomes and how those differences may affect an individual’s health. The long-term goal of the research is to bring down the cost for genome sequencing in hopes of making an individual’s genome part of his or her medical record. Olson’s collaborators on the grant include Green, Dr. Joe Felsenstein, professor of genome sciences; Dr. Matthew Stephens, assistant professor of statistics; and Dr. Elizabeth Thompson, professor of statistics.

The UW College of Engineering also received a five-year grant of $15 million from NHGRI to develop devices to monitor and analyze cellular processes. Knowledge of this kind may help in the diagnoses and treatment of diseases such as cancer.

“We’re to a point where we can get to more interesting computational analyses because they’re more closely related to biology,” said Green. “Ultimately that’s the whole purpose of getting the genome sequence.”