The genomes of recombinant inbred lines

Abstract

Recombinant inbred lines (RILs) can serve as powerful tools for genetic mapping. Recently, members of the Complex Trait Consortium proposed the development of a large panel of eight-way RILs in the mouse, derived from eight genetically diverse parental strains. Such a panel would be a valuable community resource. The use of such eight-way RILs will require a detailed understanding of the relationship between alleles at linked loci on an RI chromosome. We extend the work of Haldane and Waddington on two-way RILs and describe the map expansion, clustering of breakpoints, and other features of the genomes of multiple-strain RILs as a function of the level of crossover interference in meiosis.

Figure 1.—

The production of recombinant inbred lines by selfing (A) and by sibling mating (B).

Figure 2.—

The production of an eight-way recombinant inbred line by selfing (A) and by sibling mating (B).

Figure 3.—

Three-point coincidence in meiosis (A), RILs by selfing (B), the X chromosome for RILs by sibling mating (C), and autosomes for RILs by sibling mating (D). Solid curves are for the case of no interference; dashed curves correspond to strong positive crossover interference (according to the gamma model with ν = 11.3, as estimated for the mouse genome). (B–D) Black, blue, and red curves correspond to two-way, four-way, and eight-way RILs, respectively. Note that coincidence on the RIL chromosome is displayed as a function of the recombination fraction at meiosis.

Figure 4.—

Assessment of symmetry in the three-point probabilities on the autosomes of eight-way RILs by sibling mating. The conditional probabilities Pr(AxA|A–A) are displayed as a function of the recombination fraction between adjacent loci, with the solid curves corresponding to no interference and the dashed curves corresponding to strong positive interference.

Figure 5.—

Assessment of the Markov property in the three-point probabilities on autosomes of eight-way RILs by sibling mating. Log₂{Pr(xyA|xy–)/Pr(–yA|–y–)} is displayed for each distinct case of x, y, with the solid and dashed curves corresponding to no interference and strong positive crossover interference, respectively.

Figure 6.—

Results of 10,000 simulations of two-way RILs by selfing (black), two-way RILs by sibling mating (blue), and eight-way RILs by sibling mating (red), with a mouse-like genome of length 1665 cM and exhibiting strong crossover interference. (A) Distribution of the number of generations of breeding to achieve 99% fixation. (B) Distribution of the number of generations of breeding to achieve complete, genome-wide fixation. (C) Distribution of the total number of segments, genome-wide. (D) Distribution of the lengths of segments. (E) Distribution of the length of the smallest segment, genome-wide. (F) Distribution of the number of segments <1 cM in length.