Genetic variations in mice comprehensively catalogued
15 September 2011
An international team, led by researchers at the Wellcome Trust Sanger Institute and the University of Oxford, identified 56.6 million unique sites of variation in the mouse genome known as single nucleotide polymorphisms (SNPs). Many of these sites are associated with important biological differences in the mice, including diseases such as diabetes and heart disease.
The Sanger Institute's Dr David Adams, who led the project, said: "We are living in an era where we have thousands of human genomes at our fingertips. The mouse, and the genome sequences we have generated, will play a critical role in understanding how genetic variation contributes to disease and will lead us towards new therapies."
Inbred strains of mice are widely used in biology to further our understanding of human disease. All the mice in a single strain are essentially genetically identical but the strains have different genes and, as a result, different biological characteristics (phenotypes). These differences model variation between individual humans. The challenge for scientists is to relate the genetic differences to the phenotypic differences.
"In some cases it has taken 40 years - an entire working life - to pin down a gene in a mouse model that is associated with a human disease, looking for the cause," said Dr Thomas Keane, lead author on one of two papers published this week in 'Nature' explaining the work. "Now with our catalogue of variants the analysis of these mice is breathtakingly fast.
"We know where all the variants are, so the questions today are 'What do they do, and can we explain the phenotypic differences between different strains of mice?'"
Researchers will be able to search the catalogue for relevant genetic mutations using a computer mouse instead of having to breed and test lots of real mice. It will reduce the number of animals required for each study and make research in this area much faster.
The catalogue can be used to investigate 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. It will be invaluable in associating variation in a particular trait with differences in people's DNA.
Co-leader of the study Professor Jonathan Flint, from the Wellcome Trust Centre for Human Genetics, said: "This study is a first step in a long path that moves from understanding what the genome is, to what it does."
Professor Ian Jackson, joint head of Medical and Development Genetics at the Medical Research Council Human Genetics Unit, added: "This resource, made possible through huge recent advances in sequencing technology, is transforming our understanding of how DNA sequence variation relates to gene function, and ultimately its association with biology and human health."
The project, funded by the Wellcome Trust and the Medical Research Council with additional support from the Juvenile Diabetes Research Foundation, will be extended by sequencing further mouse strains, encompassing changes found in mouse cancers, and investigating the effect of these variants on gene function. It could eventually involve the sequencing of hundreds of mouse strains, something that would have seemed impossible just a few years ago.
Image: Knockout mice. Credit: Jenny Nichols, Wellcome Images.
References
Keane TM et al. Sequence variants among 17 mouse genomes: effect on phenotypes and gene regulation. Nature 2011 (epub ahead of print).
Yalcin B et al. Sequence based characterization of structural variation in the mouse genome. Nature 2011 (epub ahead of print).
