Subspecific origin and haplotype diversity in the laboratory mouse.

Area of Science:

• Genomics
• Evolutionary Biology
• Animal Genetics

Background:

• Laboratory mouse strains are crucial models in biological research.
• Understanding their genetic origins is vital for interpreting experimental results.
• Previous studies suggested limited diversity in classical inbred strains.

Purpose of the Study:

• To create a high-resolution, genome-wide map of the phylogenetic origins of laboratory mouse inbred strains.
• To assess the genetic diversity and haplotype structure of classical and wild-derived mouse strains.
• To investigate the impact of intersubspecific introgression and contamination in laboratory mouse genomes.

Main Methods:

• Genotyping of wild-caught mice from three Mus musculus subspecies.
• Generation of genome-wide haplotype maps utilizing identity by descent (IBD) analysis.
• Comparative analysis of genetic diversity between classical inbred strains and wild-derived strains.

Main Results:

• Classical laboratory mouse strains predominantly originate from Mus musculus domesticus, with a smaller contribution from Japanese origins.
• These strains exhibit limited and non-randomly distributed genetic diversity due to their ancestry from a few fancy mice.
• Wild-derived strains demonstrate a broader representation of genetic diversity within Mus musculus.
• Intersubspecific introgression is widespread in laboratory strains, with evidence of contamination from other laboratory stocks.

Conclusions:

• The genetic makeup of most laboratory mice is heavily skewed towards specific subspecies and limited ancestral founders.
• Wild-derived strains provide a more comprehensive resource for studying Mus musculus genetic diversity.
• The findings highlight the importance of considering the phylogenetic origins and genetic diversity when using mouse models in research.