Genome Center receives $26 million to begin sequencing

The Whitehead/MIT Center for Genome Research has received a three year, $26 million grant from the National Institutes of Health (NIH) to begin sequencing specific portions of the human genome.

The Center's effort, along with others in the country, launches the final and most important phase of the Human Genome Project-decoding the exact sequence of the 3 billion DNA letters that make up a human being. Ultimately, sequencing the genome will help researchers identify disease-related genes and result in unprecedented advances in health care.

As the largest federally funded genome center, Whitehead's main charter is to sequence human chromosome 17, using markers from its powerful physical map of the human genome as a scaffold. Completed last December, this comprehensive map comprises more than 16,000 landmarks called sequence tagged sites, or STSs. Each landmark is a short stretch of DNA that tags a unique position in the human genome.

In the coming months, scientists led by Drs. Eric Lander, Trevor Hawkins and Bruce Birren will use the STS markers as a scaffold to align so-called Bacterial Artificial Chromosomes (BACs)-pieces of human DNA cloned in bacteria-in the order in which they exist on chromosome 17. Once the STS markers and the BACs are aligned, the scientists can begin sequencing the individual BACs.

Chromosome 17 comprises 90 megabases, and scientists speculate that it is rich in genes. "Generating the complete sequence of human DNA is the most exciting adventure in modern science," said Dr. Lander, director of the Genome Center. "Sequencing the human genome will give us a new understanding of human development and a broad array of new tools for fighting human disease."

A major player in the Whitehead sequencing effort will be a robot called the Sequatron. This robot is the first fully integrated robotic system for DNA sequencing that is able to carry out DNA purification and sequencing setup without human supervision. Because of the robot, Whitehead's 25-member sequencing team is undertaking tasks that compete with 100-member teams at other sequencing centers.

"The sequatron completely automates the front end of sequencing," said Dr. Hawkins, who heads up the sequencing and automation teams. "It is a five-foot-square unit with a mechanical hand and automated helpers that work at a tremendously fast pace."

"Automation is going to play a key role in the future as we move from the mapping phase of the genome project to the sequencing phase," Dr. Lander said. "Automation was a major factor in allowing us to complete the STS map ahead of schedule and under budget." The Whitehead Genome Center's goal is to build a future-generation sequatron that can generate enough samples to sequence the human genome in three years.

"Understanding the complete set of genes spelled out in human DNA promises to usher in a new era of molecular medicine, with precise new approaches to the diagnosis, treatment and prevention of disease," said Dr. Francis Collins, director of the National Center for Human Genome Research (NCHGR) at NIH, which supports the Whitehead/MIT Center for Genome Research. The Human Genome Project already has led to the discovery of genes responsible for Alzheimer's disease, colon cancer, breast cancer, Lou Gehrig's disease and dozens of other disorders.

As with the physical and genetic mapping projects, all of the information produced by the Whitehead/MIT Center for Genome Research is available free of charge to the public via the World Wide Web at .

A version of this article appeared in MIT Tech Talk on May 1, 1996.

Topics: Genetics, Administration, Biology

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