With First Comparative Look At Human And Mouse DNA, Joint Genome Institute Team Confirms Gene Estimate

The team, led by biomedical scientist Lisa Stubbs of Lawrence Livermore National Laboratory, details its findings — based on comparing human chromosome 19 with similar sections of mouse DNA — in Friday's edition of the journal Science. In addition to Stubbs, the study's analysis was performed by Paramvir Dehal, a UC Davis graduate student, Livermore computer scientist Art Kobayashi and a team of JGI computer scientists and biologists.

The sequencing of the mouse DNA, which was done between April and October of last year, was led by former Joint Genome Institute Director Elbert Branscomb, current JGI Director Trevor Hawkins and sequencing director Paul Predki.

"There had been speculation that aligning the human and mouse DNA sequence might reveal many more genes," Stubbs said. "However, if chromosome 19 is indicative of other chromosomes, the estimate of 30,000 genes is fairly accurate."

Before the comparison of human and mouse DNA, researchers had thought that human chromosome 19 had about 1,100 genes. With the comparative analysis, about 1,200 were found, Stubbs said.

"We've wanted to compare human and mouse DNA to help us find human genes and to figure out how they function," she said. "Another reason is that researchers use mouse models for studying diseases and testing medicines, and to do this properly, it's important to understand the differences and similarities between the two species."

Through their study, the Joint Genome Institute team found apparent additional sections of more than 300 human genes, confirmed the existence of other computer-predicted genes and provided evidence to discard other gene predictions, according to Stubbs. The team discovered "candidate" regulatory sequences for genes throughout chromosome 19. Regulatory sequences tell individual genes when and in which cells to activate.

In the study, the researchers found that about 90 percent of the human genes in chromosome 19 were also located in similar sections of mouse DNA, Stubbs said.

The approximately 10 percent of human or mouse genes that are unique to each other are the type of genes that tend to duplicate, or make extra copies, over time.

These genes include zinc finger genes, which produce proteins that control the activity levels of other genes; olfactory receptor genes, which are responsible for the sense of smell; and the genes encoding receptors for pheromones, which serve as a chemical attractant for mating and other social behavior.

Mouse and human DNA contain different complements of these types of genes because active duplications have created new genes specifically in primates or rodents.

Established in 1996, the JGI is a consortium of scientists, engineers and support staff from three Department of Energy national laboratories — Lawrence Berkeley, Lawrence Livermore and Los Alamos. The institute performed the sequencing for three human chromosomes — 5, 16 and 19.

Other members of the sequencing or sequence analysis teams were: Anne Olsen, Peg Folta, Susan Lucas, Miriam Land, Astrid Terry, Carol Ecale Zhou, Sam Rash, Qing Zhang, Laurie Gordon, Joomyeong Kim, Christopher Elkin, Martin Pollard, Paul Richardson, Dan Rokhsar and Ed Uberbacher.

In the future, the LLNL research team led by Stubbs plans to try to confirm the apparent gene extensions and test the function of the regulatory sequences, determining how and where the genes are activated, Stubbs said.

Founded in 1952, Lawrence Livermore National Laboratory is a national security laboratory, with a mission to ensure national security and apply science and technology to the important issues of our time. Lawrence Livermore National Laboratory is managed by the University of California for the U.S. Department of Energy's National Nuclear Security Administration.