Table 1.
Genetic Approaches to Identification of QTL in Mice
Figure 1.
A Neighbor-Joining Tree of Wild-Caught House Mice Based on Allele-Sharing at 4158 SNP Loci
The individuals include ten M. m. domesticus from Western Europe, seven M. m. musculus from Eastern Europe, nine M. m. castaneus from India, and 94 mice from Tucson, Arizona. The Arizona mice appear closely related to domesticus from Western Europe, as expected from the history of North American colonization and other evidence [1]. The small terminal branch lengths of musculus and castaneus may be due to an ascertainment bias in the SNPs, which were discovered in laboratory strains in which the nuclear genome seems to be predominantly of domesticus origin [4,56].
Figure 2.
LD between Pairs of ∼2,900 Autosomal SNPs in Humans and Mice
The r2 variable is the composite (genotypic) measure of LD, which is very similar to the usual gametic measure (see Materials and Methods). The jagged red line is the 95th percentile of the r2 values within a 25 kb sliding window. The horizontal red line is the genome-wide threshold for significance of r2 at α = 0.05 (calculated as the 95th percentile of permuted data). The jagged black line is the mean of the r2 values within a 25 kb sliding window. HS is an outbred laboratory strain.
Figure 3.
LD between SNPs Discovered by Resequencing in Selected Regions of the Genome, Measured as the Genotypic r2
The top panel shows LD in 77 Arizona mice for pairs of SNPs within each of four regions (points) and summary statistics for all four regions combined (lines). The total number is 163 common SNPs (nine Alox15, 53 Apoa2, 70 C3ar1, 31 Nr1h3). The lines connect the midpoint of each distance bin and give either the mean or the 95th percentile of r2 for that bin. The lower panel compares LD in 60 unrelated individuals each of Arizona mice and humans of European ancestry from the CEU sample of the HapMap project. The mouse SNPs are the same as in the top panel, except that the total number is 141 (removing those with MAF < 0.05 in the sample of 60 individuals). The human SNPs are a subset from 10 ENCODE regions, selected to have the same allelic frequency distribution as the mouse SNPs. The human SNP numbers range from 131 to 803 per region, with a total of 3891 over all ten regions. The ranges of r2 statistics (mean or 95th percentile) for the ten ENCODE regions are given by the vertical bars.
Figure 4.
Mean LD in 94 Arizona Mice and 90 Asian Humans, Evaluated in a Sliding Window of 0.025 cM
The data are the same as in Figure 2, but physical distance has been converted to genetic distance using genome-wide averages of cM/Mb. The expected value of r2 for a sample size of n diploids is calculated as E (r2) = (1 / (1 + 4Nec)) + (1 / n), where Ne is effective population size and c is recombination rate (converted to cM for plotting by the Kosambi mapping function). In this case, n = 92 and Ne = 1,000, 3,000, or 10,000 (from top to bottom).