Encoding the human genome

The public got its first look at extensive genome research from the UW when the Encyclopedia of DNA Elements (ENCODE) released its findings to the public Sept. 5.

The UW has a rich history and promising future in genome studies. One of the five main data-generating centers for the Encyclopedia of DNA Elements (ENCODE) was in the UWs Genome Studies Department in the William H. Foege Building. Its findings were published in 30 articles spread across three science journals: Nature, Genome Biology, and Genome Research.

Planning for ENCODE started in 2003, just after the human genome was sequenced, but the project truly took off in 2007. The majority of the findings recently published came from work done between 2007 and 2012.

Some of the research for ENCODE involved what turns different kinds of cells on and off. Early in the project, researchers realized that each switch is different for each type of cell for example, the instructional on-switches for blue eyes and breast cancer are not the same.

In order to conduct the research, John Stamatoyannopoulos, M.D., UW associate professor and ENCODE researcher since 2003, had to create new technology. Stamatoyannopoulos and his team at the StamLab in the Foege Building were able to successfully map which genomes within a group regulate other genomes.

After treating the genomes with a chemical called nuclease, they discovered that little DNA fragments are released from these switches. The DNA splits directly where the regulatory genomes are located. Scientists can then collect them and use massive parallel sequencing to sequence and map hundreds of millions of these DNA pieces.

Scientists can then reconstruct exactly where the regulatory proteins are sitting in the switches. The reconstruction is full of connections and secondary, or tertiary, connections that end up looking like a neural network map.

The way these switches work, just to conceptualize it, is basically a string of letters, and you can think of them like a sentence, Stamatoyannopoulos said. The sentence is made up of words. These regulatory proteins come in and make these letters into specific words. Once these proteins all dock at a specific site, the gene is turned on.

Across the hall from the Stamlab is the Akey Lab, where Joshua Akey, Ph.D. and associate professor of genome sciences, and graduate student Benjamin Vernot worked on the history of human genomes.

They superimposed the ENCODE data with 52 known genome sequences gathered from geographically diverse areas and asked themselves basic questions such as whether or not an average individual has more protein-coding variation or variation that influences gene expression levels in populations. Understanding how patterns and variation are spread out among individuals and populations, or even species, and finding the evolutionary forces that act upon the sequence variation is what a population geneticist like Akey does.

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Encoding the human genome