|Mouse Genome Will Help Identify Causes of Environmental
Research on the DNA of 15 mouse strains commonly used in biomedical
studies is expected to help scientists determine the genes related
to susceptibility to environmental disease. The body of data is now
publicly available in a catalog of genetic variants, which displays
the data as a mouse haplotype map, a tool that separates chromosomes
in to many small segments, helping researchers find genes and genetic
variations in mice that may affect health and disease. The haplotype
map appearing online in the July 29th issue of Nature is
the first published full descriptive analysis of the “Mouse Genome
Resequencing and SNP Discovery Project” conducted by the National
Institute of Environmental Health Sciences (NIEHS), part of the National
Institutes of Health.
“These data allow researchers to compare the genetic makeup of
one mouse strain to another, and perform the necessary genetic
analyses to determine why some individuals might be more susceptible
to disease than another. This puts us one step closer to understanding
individual susceptibility to environmental toxins in humans. We
also hope that pharmaceutical companies developing new treatments
for environmental diseases will find these data and this paper
as a valuable resource,” said David A. Schwartz. M.D., NIEHS Director.
The paper describes in detail the laborious and technology-driven
approaches that were used to identify 8.27 million high quality
SNPs distributed among the genomes of 15 mouse strains. Single
Nucleotide Polymorphisms, or SNPs (known as snips), are single
genetic changes, or variations, that can occur in a DNA sequence.
Much of the project was conducted through a contract between the
National Toxicology Program at NIEHS and Perlegen Sciences, Inc.
of Mountain View Calif.
“The database of mouse genetic variation should facilitate a wide
range of important biological studies, and helps demonstrate the
utility of this array technology approach,” said David R. Cox,
M.D., Ph.D., chief scientific officer at Perlegen Sciences, Inc.
The Perlegen scientists used C57BL/6J the first mouse strain to
undergo DNA sequencing as their standard reference to conduct the
re-sequencing on the four wild-derived and eleven classical mouse
strains. The technology used, the oligonucleotide array, was also
used to discover common DNA variation in the human genome.
The arrays looked at about 1.49 billion bases (58 percent) of
the 2.57 billion base pair of their standard reference strain.
The data were then used to develop the haplotype map which contains
“The data will be a valuable resource to many, including the National
Toxicology Program,” Schwartz says. The National Toxicology Program
(NTP) is an interagency program, headquartered at NIEHS, with the
mission to coordinate, conduct and communicate toxicological research
across the U.S. government.
“The NTP is looking forward to exploring the responses of these
strains of mice to various environmental agents,” said John Bucher,
Ph.D., the new associate director of the NTP.
Frank M. Johnson, Ph. D., an NTP research geneticist and one of
the authors of the Nature paper, adds that systematically characterizing
even more mouse strains for susceptibility to toxins will not only
help with genetic analysis, but better position researchers to
do intervention studies.
The data are publicly available on the National Center for Biotechnology
Information Web site at http://www.ncbi.nlm.nih.gov/SNP/ and at
a Web site developed by Perlegen at http://mouse.perlegen.com which
allows researchers to download SNPs, genotypes, and LR-PCR primer
pairs, which are currently mapped to NCBI Build 36.
In addition to the NTP and Perlegen Sciences scientists, other
key collaborators on the project include researchers from the Department
of Computer Science and Department of Human Genetics, University
of California, Los Angeles; the Department of Computer Science
and Engineering, University of California, San Diego; The Jackson
Laboratory, Bar Harbor, Maine; Broad Institute of Harvard and MIT;
and the Center for Human Genetic Research, Massachusetts General
The National Institute of Environmental Health Sciences (NIEHS),
a component of the National Institutes of Health, supports research
to understand the effects of the environment on human health. For
more information on environmental health topics, please visit our
website at http://www.niehs.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.