A High-Resolution Genetic Map for the Laboratory Rat.

ABSTRACT

An accurate and high-resolution genetic map is critical for mapping complex traits, yet the resolution of the current rat genetic map is far lower than human and mouse, and has not been updated since the original Jensen-Seaman map in 2004. For the first time, we have refined the rat genetic map to sub-centimorgan (cM) resolution (<0.02 cM) by using 95,769 genetic markers and 870 informative meioses from a cohort of 528 heterogeneous stock (HS) rats. Global recombination rates in the revised sex-averaged map (0.66 cM/Mb) did not differ compared to the historical map (0.65 cM/Mb); however, substantial refinement was made to the localization of highly recombinant regions within the revised map. Also for the first time, sex-specific rat genetic maps were generated, which revealed both genomewide and fine-scale variation in recombination rates between male and female rats. Reanalysis of multiple quantitative trait loci (QTL) using the historical and refined rat genetic maps demonstrated marked changes to QTL localization, shape, and effect size. As a resource to the rat research community, we have provided revised centimorgan positions for all physical positions within the rat genome and commonly used genetic markers for trait mapping, including 44,828 SSLP markers and the RATDIV genotyping array. Collectively, this study provides a substantial improvement to the rat genetic map and an unprecedented resource for analysis of complex traits and recombination in the rat.