eNews September 26, 2011

The genetic sequence variations of 17 common laboratory mouse strains revealed

Mouse-based genetic resources have taken a quantum leap forward. The Welcome Trust Sanger Institute's Mouse Genomes Project has reported and made publicly available the genome sequences of 17 genetically diverse laboratory mouse strains (15 of which are JAX® Mice strains) (Keane et al. 2011):

  • Ten common inbred strains – A/J (000646), AKR/J (000648), BALB/cJ (000651), C57BL/6NJ (005304), CBA/J (000656), C3H/HeJ (000659), DBA/2J (000671), LP/J (000676), NOD/ShiLtJ (001976), NZO/HILtJ (002105)
  • Four wild-derived inbred strains – CAST/EiJ (000928) (Mus musculus castaneus), PWK/PhJ (003715) (Mus musculus musculus), SPRET/EiJ (001146) (Mus spretus), and WSB/EiJ (001145) (Mus musculus domesticus) (001146)
  • Three related 129 strains, representing the genetic backgrounds of more than 5,000 knockout strains – 129S1/SvImJ (002448), 129S5SvEvBrd, and 129P2/OlaHsd

The publication by the Sanger researchers reports the sequence variation between each inbred strain and that of the reference strain, C57BL/6J (000664). The analysis reveals ten times more genetic variants among strains than were previously known and explores the evolutionary origins of the subspecies that gave rise to the laboratory mouse. In addition, using two examples, the researchers demonstrate how sequence data can be used to investigate the molecular origins of phenotypic variation.

The sequence data reported by the Sanger team builds on the extensive phenotypic data available in the Mouse Phenome Database (MPD) for many of the newly sequenced strains. Together with the MPD data, the sequence data will greatly improve researchers' abilities to examine quantitative trait differences and will provide new insights into the nature of functional variants.

Six of the 17 newly sequenced strains are maintained under the strict standards of The Jackson Laboratory’s patented Genetic Stability Program (GSP), which effectively prevents accumulation of mutations over time and significantly limits genetic drift. Therefore, the phenotypic and genetic sequence data and the mice from which data was derived will remain valid and stable for generations to come.

Finally, the Sanger team's work makes it possible for researchers to impute the missing data in the genomes of any strains – such as the Collaborative Cross (CC) strains and Diversity Outbred (DO, 009376) mice – derived from the newly sequenced strains. CC and DO mice enable high-resolution mapping of multiple complex phenotypes, behavioral toxicology testing, and the study of gene-gene and gene-environment interactions that lead to disease susceptibility, drug resistance, and secondary complications.

The Sanger Institute has set up a suite of querying and visualization tools for accessing the sequence data on its website. The SNP data set will soon be available from the Mouse Phenome database as Sanger1.