Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates

Area of Science:

• Genetics
• Animal Models
• Bioinformatics

Background:

• The laboratory rat (Rattus norvegicus) is a key model organism in biomedical research.
• Understanding genetic variation between rat strains is crucial for pharmacogenetics, genetic cloning, and association studies.

Purpose of the Study:

• To investigate the representation of Single Nucleotide Polymorphisms (SNPs) from commonly used laboratory rat strains within wild rat populations.
• To evaluate efficient strategies for SNP discovery in rats.

Main Methods:

• Shotgun sequencing of 814 Kbp from one wild rat.
• Identification of 485 SNPs compared to the Brown Norway genome sequence.
• Genotyping of 36 commonly used inbred rat strains to assess allele polymorphism.

Main Results:

• Single Nucleotide Polymorphisms (SNPs) found in laboratory rat strains are well-represented in wild rat isolates.
• 84% of identified SNPs were also polymorphic in a representative set of laboratory rat strains.
• Wild rat sequencing followed by laboratory strain genotyping proved efficient for SNP discovery.

Conclusions:

• Shotgun sequencing of a wild rat sample followed by genotyping multiple laboratory strains is proposed as an efficient SNP discovery approach.
• Laboratory rat strains retain a significant portion of haplotypes from wild isolates, suggesting a recent common origin.
• Rat inbred strains likely originate from a single species, Rattus norvegicus, unlike mouse strains.