Generation of a Public Resource of Mouse Strain Sequences
Lead Research Organisation:
Wellcome Sanger Institute
Department Name: Research Directorate
Abstract
In this project we will decode the genomes of 17 key mouse strains that are used extensively as models of human disease by using DNA sequencing. By having the DNA sequence of these mouse strains we will be able to better understand what makes each mouse strain unique and this will in turn illuminate the basis behind genetic variation and disease susceptibility in humans.
Technical Summary
In this project we will use new sequencing technologies to decode the genomes of 17 key mouse strains. A landmark achievement for biology.
Inbred strains of mice represent a rich genetic resource which can provide genetic data in almost every area of medical research. As each individual in the strain is essentially genetically identical, detailed data can be collected from multiple individuals in multiple experiments but all against the same genetic background. Different inbred strains, of course are phenotypically different and the basis of these differences resides in the genetic (sequence) variation between them. Most laboratory strains of mice are genetic mosaics derived from a limited number of founding substrains of Mus: M. m. musculus, M. m. castaneus, M. m. domesticus and M.m. molossinus. The genetic variation responsible for the trait characteristics of each strain is in part due to the substrain contributions and in part to differences between individual founders. In contrast certain strains of mice, such as SPRETUS/Ei, CAST/Ei and PWK/PhJ have been derived from mice caught in the wild which were then interbred to homozygosity and are representative of a single subspecies. These wild derived strains often have robust resistance to cancer and infectious diseases not seen in lab strains.
Determination of the DNA sequence of inbred mouse strains will generate a catalogue of differences between them, which, in any cross segregating complex phenotypic differences, will provide a limited list of candidate base difference in which the underlying genetic trait may be found. Thus with the sequence of these 17 mouse strains we will have a powerful tool to identify disease genes and to dissect gene function.
Inbred strains of mice represent a rich genetic resource which can provide genetic data in almost every area of medical research. As each individual in the strain is essentially genetically identical, detailed data can be collected from multiple individuals in multiple experiments but all against the same genetic background. Different inbred strains, of course are phenotypically different and the basis of these differences resides in the genetic (sequence) variation between them. Most laboratory strains of mice are genetic mosaics derived from a limited number of founding substrains of Mus: M. m. musculus, M. m. castaneus, M. m. domesticus and M.m. molossinus. The genetic variation responsible for the trait characteristics of each strain is in part due to the substrain contributions and in part to differences between individual founders. In contrast certain strains of mice, such as SPRETUS/Ei, CAST/Ei and PWK/PhJ have been derived from mice caught in the wild which were then interbred to homozygosity and are representative of a single subspecies. These wild derived strains often have robust resistance to cancer and infectious diseases not seen in lab strains.
Determination of the DNA sequence of inbred mouse strains will generate a catalogue of differences between them, which, in any cross segregating complex phenotypic differences, will provide a limited list of candidate base difference in which the underlying genetic trait may be found. Thus with the sequence of these 17 mouse strains we will have a powerful tool to identify disease genes and to dissect gene function.