Researchers develop mouse genetic blueprint

An overview of variants called from 17 mouse genomes relative to the reference. 

Four wild strains (CAST/EiJ, WSB/EiJ, PWK/PhJ and SPRET/EiJ) are shown in a circle with tracks indicating the relative density of single nucleotide polymophisms (SNPs), structural variants (SVs) and uncallable regions.

Transposable element insertions (TEs), a subset of the SV calls, are shown as a separate track. Corresponding tracks are shown for each of the 13 classical laboratory strains to the right of the circle.

Links crossing the circle indicate regions on the reference where the wild strain is closest to the reference. (Credit: From Keane et al. Mouse genomic variation and its effect on phenotypes and gene regulation.

Nature, 2011; 477 (7364): 289 DOI: 10.1038/nature10413)

Researchers have developed a valuable mouse genetic blueprint that will accelerate future research and understanding of human genetics.

The international team, led by researchers at the Wellcome Trust Sanger Institute and the University of Oxford, explains in two papers published in Nature on Sept. 14, 2011 how they decoded and compared the genome sequence of 17 mouse strains.

In creating this unique resource, the biggest catalogue for any vertebrate model organism, the team found an astonishing 56.7 million unique sites of variation (known as SNPs) between the strains, in addition to other more complex differences.

Among these they identified sequence differences associated with over 700 biological differences, including markers for diseases such as diabetes and heart disease, so linking genes with medically important individual differences.

The catalogue, which was funded principally by the Medical Research Council and the Wellcome Trust, can be used by researchers to understand the genetic basis of individual variation, and to ask fundamental questions about how genes function and make us more or less likely to have particular diseases.

Inbred strains of mice are invaluable sources of genetic information. Every animal within each inbred strain is essentially genetically identical, but each strain is different from the others both in their genes and across a huge range of medically and biologically important characteristics.

"We are living in an era where we have thousands of human genomes at our finger tips," says Dr Adams, from the Wellcome Trust Sanger Institute, who led the project.

"The mouse, and the genome sequences we have generated, will play a critical role in understanding of how genetic variation contributes to disease and will lead us towards new therapies."

As a direct result of the project, researchers will place less reliance on breeding mice to find mutations; using this resource they will be able to find mutations much more quickly by the click of a digital mouse to search for the data on their computer.

These strains of mice are used in every corner of biology to further our understanding of human disease, and there is much more to discover. With the variants to hand, the challenge moves to understanding the biological consequences.