UW joins national push for the $1,000 genome

The National Human Genome Research Institute today announced that the University of Washington is one of eight institutions funded to revolutionize DNA sequencing. Two of the eight institutions are in Seattle. The goal of the federal effort is more rapid sequencing of a person’s genome at a lower price: $1,000 or less. Quicker, less expensive, more accurate methods would make possible the everyday use of DNA sequencing technologies by biomedical researchers and healthcare providers. In making this announcement, the National Institutes of Health is investing $14 million in grants to bolster the availability of genomic tools in research and medicine.

Dr. Jay Shendure, UW associate professor of genome sciences, is the principal investigator on the three-year, $1.8 million award. His group designed faster techniques to sequence the protein-coding portions of the human genome, the exome, and used these techniques to identify the mutations causing rare genetic diseases. Last winter, his team published a study demonstrating a method to figure out the haplotype of an individual’s genome. Haplotype refers to the versions of genes and patterns of variants inherited together along a chromosome from each parent.

More specifically, in a Nature Biotechnology paper published in January 2011, Shendure and his team said: “Haplotype information is essential to the complete description and interpretation of genomes, genetic diversity, and genetic ancestry.” But despite the increasingly routine nature of human genome sequencing, nearly all the data gathered is blind to haplotype, the team said. Improving techniques to obtain haplotypes by re-sequencing genomes will be an aim of his lab’s work under this new grant.

Some technologies have reduced the cost and time for DNA sequencing by several orders of magnitude, said Shendure. Analyzing massive amounts of data simultaneously, however, has come at the sacrifice of quality. Current methods shatter DNA into a jumble of shards. These fragments are then sequenced and re-assembled through sophisticated computational biology. It is akin to tearing apart quilt blocks to see how they are constructed, then piecing them back together in a coherent pattern.

Shendure’s team plans to test new methods for shattering DNA with tags that tell the adjacent order of fragments. This would be somewhat like placing marks on tiles to show how to place them next to each other to reproduce an intricate mosaic. Assembly might also be made easier by a new method to barcode tiny stretches of the genome, and by another method to keep sequence reads in the right lineup.

The researchers plan to integrate these methods to see if they can not only newly assemble the mouse genome of higher quality than the original, and re-sequence a human genome to resolve the person’s haplotype, but also to do each of these in a highly cost-effective manner.

“We are confident that the grantees will continue to make major breakthroughs in the development of technologies that will sequence for $1,000 or less,” said Eric Green, National Human Genome Research Institute director, in a news release issued by the NIH. “As genome sequencing costs continue to decline, researchers and clinicians can increase the scale and scope of their studies. We will continue to fund innovations to accelerate what is known about human health and disease.”

During the past decade, DNA sequencing costs have plunged by more than a thousand-fold. The costs have been driven down in large part by tools, technologies and process improvements emerging from the Human Genome Project. In 2009, a high quality genome sequence of six billion base pairs (the amount of DNA in humans, who receive three billion bases from each parent) cost $100,000. Today, the cost to sequence a human genome is below $20,000.

“With advances in a third generation of sequencing technologies, we’re moving closer to the point when researchers and healthcare providers can routinely and rapidly screen a person’s or a large number of people’s DNA using devices that produce highly accurate data,” said Dr. Jeffrey Schloss, the Institute’s program director for technology development.

In addition to Shendure, researchers and institutions receiving grants today include:

• Mark A. Akeson, University of California, Santa Cruz
• Wayne M. Barnes, Washington University, St. Louis
• Marija Drndic, University of Pennsylvania, Philadelphia
• Mark Korokis, Stratos Genomics, Inc., Seattle
• Stuart Lindsay, Arizona State University, Tempe
• Bharath R. Takulapalli, Arizona State University, Tempe
• Marian Mankos, Electron Optica, Palo Alto
• Steven A. Soper, Louisiana State University A & M College, Baton Rouge

Learn more about the NIH's "$1,000 genome" program