The utility of a closed breeding colony of Peromyscus leucopus for dissecting complex traits.

Deermice of the genus Peromyscus are well suited for addressing several questions of biologist interest, including the genetic bases of longevity, behavior, physiology, adaptation, and their ability to serve as disease vectors. Here we explore a diversity outbred approach for dissecting complex traits in Peromyscus leucopus, a non-traditional genetic model system. We take advantage of a closed colony of deer-mice founded from 38 individuals and subsequently maintained for ∼40-60 generations. From 405 low-pass short-read sequenced deermice we accurately imputed genotypes at 16 million SNPs. Conditional on observed genotypes simulations were conducted in which three different sized QTL contribute to a complex trait under three different genetic models. Using a stringent significance threshold power was modest, largely a function of the % variation attributable to the simulated QTL, with the underlying genetic model having only a subtle impact. We additionally simulated 2000 pseudo-individuals, whose genotypes were consistent with those observed in the genotyped cohort and carried out additional power simulations. In experiments employing more than 1000 mice the power is high to detect QTL contributing greater than 2.5% to a complex trait, with a localization ability of ∼100kb. We finally carried out a GWAS on two demonstration traits, bleeding time and body weight, and uncovered one significant region. Our work suggests that complex traits can be dissected in founders-unknown P. leucopus colony mice and similar colonies in other systems using easily obtained genotypes from low-pass sequencing.