SNP and haplotype mapping for genetic analysis in the rat

Abstract

The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies.

Figure 1

Phylogenetic neighbor-net network constructed from 20,283 polymorphic positions genotyped in 167 laboratory rats. Reticulation in the center of the network likely reflects genetic heterogeneity of ancestral rat population. The group of WKY-related strains exhibits complex pattern of relationships probably due to incomplete inbreeding of stocks before they were disseminated to various laboratories and subsequently inbred to completion. The network also shows presence of residual inter-isolate variation within SHR, LEW, BB, WKY, LE, GK and BN inbred strains.

Figure 2

Identified discrepancies between rat genome assembly and genetic maps. Rearrangement of the physical map according to genetic mapping information. Data from each cohort are color coded (red: FXLE-LEXF, green: HXB-BXH, blue: GKxBN). Black lines: all crosses support this rearrangement; lime green: HXB-BXH and F2 cross support this rearrangement. Orange lines indicate unresolved genomic conflicts. The outer circle marks positions of informative SNPs for each cohort. Arrows indicate the relocation of SNP markers that had extreme genetic distances compared to their physical distance from adjacent markers. Markers were relocated according to minimal recombination fraction. Conflicts in the genetic map are marked by bars in the inner circle.