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Mouse Haplotype Map Published

By Robin Mackar
September 2007

Modern mouse strains evolved from a single ancestor approximately one million years ago. They are ancestors of mice inter-bred for coat color in Japan and Victorian England as
Modern mouse strains evolved from a single ancestor approximately one million years ago. They are ancestors of mice inter-bred for coat color in Japan and Victorian England as "fancy" mice to serve as pets. In the 20th century, breeding programs in the United States produced the classical inbred mouse strains.

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 into 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 NIEHS.

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 help 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 40,898 segments.

"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. 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.

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 Exit NIEHS Website and at a Web site developed by Perlegen at 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 researchers, other key collaborators on the project included scientists from the University of California - Los Angeles; University of California - San Diego; The Jackson Laboratory, Broad Institute of Harvard and MIT; and the Center for Human Genetic Research, Massachusetts General Hospital.

Citation: Frazer KA, Eskin E, Kang HM, Bogue MA, Hinds DA, Beilharz EJ, Gupta RV, Montgomery J, Morenzoni MM, Nilsen GB, Pethiyagoda CL, Stuve LL, Johnson FM, Daly MJ, Wade CM, Cox DR. ( Exit NIEHS Website 2007. A sequence-based variation map of 8.27 million SNPs in inbred mouse strains. Nature. (doi:10.1038/nature06067)

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