A comprehensive linkage map of the dog genome

Abstract

We have leveraged the reference sequence of a boxer to construct the first complete linkage map for the domestic dog. The new map improves access to the dog's unique biology, from human disease counterparts to fascinating evolutionary adaptations. The map was constructed with approximately 3000 microsatellite markers developed from the reference sequence. Familial resources afforded 450 mostly phase-known meioses for map assembly. The genotype data supported a framework map with approximately 1500 loci. An additional approximately 1500 markers served as map validators, contributing modestly to estimates of recombination rate but supporting the framework content. Data from approximately 22,000 SNPs informing on a subset of meioses supported map integrity. The sex-averaged map extended 21 M and revealed marked region- and sex-specific differences in recombination rate. The map will enable empiric coverage estimates and multipoint linkage analysis. Knowledge of the variation in recombination rate will also inform on genomewide patterns of linkage disequilibrium (LD), and thus benefit association, selective sweep, and phylogenetic mapping approaches. The computational and wet-bench strategies can be applied to the reference genome of any nonmodel organism to assemble a de novo linkage map.

Figure 1.—

Variation in recombination rate across the autosomal genome. Recombination rate along each of the 38 autosomes is shown from centromeric to telomeric end (left to right). x-axis, physical length, scaled to accommodate different chromosome sizes. y-axis, sex-averaged recombination rate. Sliding windows of 5 Mb were used to calculate cM/Mb along the chromosome. The pattern of recombination rate for two autosomes (CFA27 and CFA32) suggested their orientation may be incorrectly specified in the canFam2 build.

Figure 2.—

Correlation of recombination with physical chromosome size. (A) Genetic length of autosomes plotted against physical length. (B) Mean recombination rate across autosomes plotted against physical length. Results are shown for canine (black), human (blue), and mouse (red) autosomes. Data describing physical sizes and sex-averaged recombination rates were obtained from Kong et al. (2002) and Shifman et al. (2006) for human and mouse, respectively. Physical chromosome sizes in the dog were calculated from the canFam2 coordinates of the first and last markers for each autosome. The average recombination rate for canine chromosomes was calculated from the autosomal linkage maps.