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

HUMAN reproduction; BIOLOGICAL models; GENETICS; SEQUENCE analysis; DISEASE vectors; ANIMAL experimentation; SINGLE nucleotide polymorphisms; GENOTYPES; MICE

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 nontraditional 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 accurate impute genotypes at 16 million single nucleotide polymorphisms. Conditional on observed genotypes simulations were conducted in which three different sized quantitative trait loci contribute to a complex trait under three different genetic models. Using a stringent significance threshold power was modest, largely a function of the percent variation attributable to the simulated quantitative trait loci, with the underlying genetic model having only a subtle impact. We additionally simulated 2,000 pseudo-individuals, whose genotypes were consistent with those observed in the genotyped cohort and carried out additional power simulations. In experiments employing more than 1,000 mice power is high to detect quantitative trait loci contributing greater than 2.5% to a complex trait, with a localization ability of -100 kb. We finally carried out a Genome-Wide Association Study 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. [ABSTRACT FROM AUTHOR]

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