Researchers at the Wellcome Trust Sanger Institute and the University of Oxford have developed a valuable mouse genetic blueprint that will accelerate future research and understanding of human genetics. The international team led by Dr Adams, from the Wellcome Trust Sanger Institute have decoded and compared the genome sequence of 17 mouse strains.
With this breakthrough, a major ground has been laid for the identification of genes responsible for important traits, including diseases that afflict both mice and humans. The genome sequence will be used to ascertain and find a permanent cure for the genetically prevailing diseases in the world. The study was partially funded by the National Science Foundation.
The 17 strains of mice included the most common strains used in lab studies of human diseases. By enabling scientists to list all DNA differences between the 17 strains, the new genome sequences will speed the identification of subsets of mutations and genes that contribute to disease.
“Mouse genomes are complex patchworks of different histories. In our study we compared DNA sequences of four wild-derived mouse strains (three sub-species of mice and one separate mouse species) in order to reconstruct their evolutionary histories. Results reveal striking variations in strain relationships across the genome,” said Bret Payseur who worked with Michael White on this part of the study.
In creating this unique resource, the team found an astonishing 56.7 million unique sites of variation (known as SNPs) between the strains. Among these, they identified biological difference between sequences associated with over 700 strains, which includes markers for heart diseases and diabetes as well.
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 help in querying the fundamental functions of genes which may be helpful in tracking disease causing disorders or mutations for a particular disease.
Inbred strains of mice are invaluable sources of genetic information. Every animal within each inbred strain is essentially genetically identical, but at the same time each strain is different from the other and shows characteristic variations across a huge range of medically and biologically related issues.
Dr Adams, from the Wellcome Trust Sanger Institute, who led the project said, “Today, we are living in an era where we have thousands of human genomes at our finger tips. 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.”
This new genome sequence will help reduce the amount of mouse breeding and testing needed to identify genes and mutations. The extensive catalogue will be invaluable for associating variation in a trait with changes to DNA - the biologist's journey from phenotype to genotype.
Using the sequence of the 17 mouse genomes, the team looked for variants associated with quantitative trait loci (QTLs) implicating differences in the sequence between strains as being associated with the phenotypes that distinguish them.
“This study is a first step in a long path that moves from understanding what the genome is, to what it does,” says Professor Jonathan Flint, from the Wellcome Trust Centre for Human genetics, who co-led the study.
The blueprint, coupled with further speedier sequencing, enables researchers to probe deeper to find mutations affecting gene function at a much faster rate. It also opens the doorway to the possibility of sequencing much larger numbers of mice.