Mouse gene sequencing accepted

A faculty member in the College of Liberal Arts and Sciences has won approval for the genome sequencing of four mouse species, a project that will open new areas of research.

The sequencing would be performed at a gene sequencing center chosen by the National Institutes of Health (NIH).

Rachel O'Neill, associate professor of molecular and cell biology, is the lead author of a successful proposal to the (NIH) to sequence the genomes of four species of the Peromyscus mouse, including the deer mouse, which is a carrier for Lyme disease and a deadly "hantavirus."

The proposal was accepted after a highly competitive review process. It will lead to gene mapping of four species of a mouse that is widely studied by scientists.

Co-authors on the paper are researchers at the Peromyscus Genetic Stock Center at the University of South Caroline , Baylor College of Medicine's Human Genome Sequencing Center , and the College of Medicine at the University of California at Irvine .

The stock center is the source of most laboratory specimens of the genus and O'Neill has worked with scientists there in studies related to epilepsy.

The research leading to the paper was collaborative and will benefit many scientists whose work is modeled on the Peromyscus mouse.

"We'll be seen as the lead in getting four genomes sequenced in a very competitive process," said O'Neill, referring to all of the authors. "This opens a lot of doors for research opportunities in the future."

More than 100 scientists nationwide conduct Peromyscus research, and 22 investigators wrote support letters for the proposal, saying that the Peromyscus genome sequence data is essential to furthering and expanding their research.

The project will provide data that can be used by researchers who study medical conditions such as autism, epilepsy, diabetes, and cancer, and by scientists who study the evolution of species.

The deer mouse is also a vector, or carrier, for many human pathogens, including the tick that spreads Lyme disease. Learning the components of its immune function will help researchers understand more about this disease and will "spur the movement of the species into the forefront of infectious disease and physiological research," according to the proposal.

In addition, the deer mouse is the main carrier of a hantavirus that causes a rare, deadly respiratory syndrome first recognized in 1993 in the Southwest when an outbreak rapidly killed five otherwise healthy young adults.

"Understanding how the genome works can only aid in figuring out a treatment," said O'Neill.

Acceptance of the genome sequencing proposal by the National Human Genome Research Institute at the NIH puts the project in line for funding by the NHGRI's Congressional appropriation. The NIH uses several gene sequencing centers around the U.S. for such projects.

The cost could potentially be $15 million or more, based on the cost of similar projects. Sequencing the more complex human genome, which was completed in 2003, cost more than $2.7 billion over 12 years, according to the NHGRI.

The NHGRI funded some $130 million in genome sequencing projects in 2006.

O'Neill was notified by the NIH in late September that the proposal to sequence four species of Peromyscus was accepted.

Of the four species of mice to be sequenced, three will be sequenced at "low coverage," or from 60 to 80 percent of the genome, and the deer mouse will be sequenced to "draft assembly" stage, or near completion. Rarely are proposals selected by the NHGRI for complete, or finished, sequencing.

O'Neill has used Peromyscus specimens as models for studying epilepsy, placental defects, and cancer metastasis, as well as study of evolutionary development. She is interested in the evolution of the chromosome and in comparative genomics.

The Peromyscus genus includes the two most abundant native North American mammals, the deer mouse and the white-footed mouse, O'Neill noted in her proposal. The deer mouse, with brown fur on top and white on the underside, is the mouse most often found in houses and garages.

Peromyscus mice are distinctly different from the laboratory house mouse and rats, and they evolved more recently, closer to the time that humans evolved. They are adaptable for research in the field or laboratory and provide good models for studying human diseases, infectious disease vectors, and ecological niche adaptation.

The four mice to be genetically sequenced are the Peromyscus maniculatus (deer mouse), P. leucopus (white-footed mouse), P. californicus ( California mouse) and P. polionotus (Oldfield mouse).