A new standard genetic map for the laboratory mouse

Abstract

Genetic maps provide a means to estimate the probability of the co-inheritance of linked loci as they are transmitted across generations in both experimental and natural populations. However, in the age of whole-genome sequences, physical distances measured in base pairs of DNA provide the standard coordinates for navigating the myriad features of genomes. Although genetic and physical maps are colinear, there are well-characterized and sometimes dramatic heterogeneities in the average frequency of meiotic recombination events that occur along the physical extent of chromosomes. There also are documented differences in the recombination landscape between the two sexes. We have revisited high-resolution genetic map data from a large heterogeneous mouse population and have constructed a revised genetic map of the mouse genome, incorporating 10,195 single nucleotide polymorphisms using a set of 47 families comprising 3546 meioses. The revised map provides a different picture of recombination in the mouse from that reported previously. We have further integrated the genetic and physical maps of the genome and incorporated SSLP markers from other genetic maps into this new framework. We demonstrate that utilization of the revised genetic map improves QTL mapping, partially due to the resolution of previously undetected errors in marker ordering along the chromosome.

Figure 1.—

Comparison of the original and revised genetics maps. Sex-averaged recombination rates (A) and sex-specific recombination rates (B) for the original and revised genetic maps of chromosome 1. Maps are based on data from Shifman et al. (2006) as described in materials and methods. Figures showing all chromosomes can be found in Figure S1.

Figure 2.—

Cumulative genetic maps of chromosome 1. Dotted lines show the original Shifman map; solid lines are from the revised Shifman map. Female, male, and sex-averaged maps are shown in red, blue, and black, respectively. See Figure S2 for the cumulative maps for each chromosome.

Figure 3.—

Physical and genetic positions of markers. Genetic marker positions (in centimorgans) are plotted against their physical positions (in megabases) for the MGI genetic map (red) and the revised Shifman map (black). Marker-ordering errors in the MGI map are indicated by non-monotone fluctuations. In contrast, the curves for the revised map are smooth and monotone.

Figure 4.—

QTL With changes in peak shape. Seven QTL were found where the peak shape was altered due to subtle differences between the original and the revised Shifman maps. (A) The QTL for femoral BMD on chromosome 12 in the NZBxRF cross appears as a double peak when analyzed using the Mouse Genome Database (MGD)/traditional genetic map (dashed line), suggesting the presence of two closely linked QTL. When reanalyzed using the new genetic map, this double peak is collapsed into a single peak (solid line). (B) This double peak is the result of two flipped neighboring markers. Seven markers were typed in this cross for chromosome 12. The markers are placed on the centimorgan scale (center line) in relation to the MGD/traditional map (left) and the new genetic map (right). Note the difference in spacing of the markers when comparing the two maps. The other QTL with a change in peak shape were found for: (C) B6xCAST on chromosome 2, (D) B6xC3H on chromosome 2 for vBMD, (E) NZBxRF on chromosome 4 for vBMD, (F) B6xCAST on chromosome 14, (G) B6xCAST on chromosome 18, and (H) NZBxSM on chromosome 19.