A high-resolution single nucleotide polymorphism genetic map of the mouse genome

Abstract

High-resolution genetic maps are required for mapping complex traits and for the study of recombination. We report the highest density genetic map yet created for any organism, except humans. Using more than 10,000 single nucleotide polymorphisms evenly spaced across the mouse genome, we have constructed genetic maps for both outbred and inbred mice, and separately for males and females. Recombination rates are highly correlated in outbred and inbred mice, but show relatively low correlation between males and females. Differences between male and female recombination maps and the sequence features associated with recombination are strikingly similar to those observed in humans. Genetic maps are available from http://gscan.well.ox.ac.uk/#genetic_map and as supporting information to this publication.

Figure 1. Average Recombination Rates for All Chromosomes

Rates for RIs are shown as a black line and for HS as a blue line. The ratio between the genetic distance and physical distance was calculated using a sliding window of 5 Mb and a shift of 2 Mb between windows centers, assuming a constant rate of recombination between two adjacent markers.

Figure 2. Sex-Specific Recombination Rates in the HS

Average recombination rate for all chromosomes calculated similar to the HS sex-averaged map, for males (black line) and females (blue line).

Figure 3. Relation between LD Levels in Inbred Strains and Recombination Rates in HS and RIs on Chromosome 7

The top figure is the recombination rate (cM/Mb) for the HS and RIs in 1-Mb non-overlapping windows across a 25-Mb region in Chromosome 7. Below, the six boxes represent the location of four recombination jungles (in red) and two deserts (in blue) of 1 Mb each. The bottom figure is the LD structure of the same region based on the SNP genotypes of 55 inbred strains. Each dot represents the pairwise LD level between two different SNPs. Regions of high LD measured by r² are in blue, whereas regions of linkage equilibrium are in red. As can be seen in this example, deserts tend to overlap with large blocks of LD, and jungles are typically located on the border of the blocks. The overlap proportion of the four recombination jungles with haplotype blocks is 0.00, 0.58, 0.55, and 0.35 for regions 1, 2, 5, and 6. The two deserts (3 and 4) overlap completely with haplotype blocks.

Figure 4. Recombination Jungles and Deserts

Enrichment of CCTCCCT motif in recombination jungles (upper panel). The standard deviation (SD) from the mean number of CCTCCCT motifs is plotted against recombination rate. Red bars are 1-Mb regions included in the top 10% recombination rate in both HS and RIs (recombination jungles), and blue bars are regions in the bottom 10% (recombination deserts). Histograms of human recombination rates for the orthologous regions of the mouse recombination jungles and deserts (lower panel).