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. 2005 Feb;169(2):1133-46.
doi: 10.1534/genetics.104.035212. Epub 2004 Nov 15.

The Genomes of Recombinant Inbred Lines

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Free PMC article

The Genomes of Recombinant Inbred Lines

Karl W Broman. Genetics. .
Free PMC article

Erratum in

  • Genetics. 2006 Aug;173(4):2419

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.

Figures

F<sc>igure</sc> 1.—
Figure 1.—
The production of recombinant inbred lines by selfing (A) and by sibling mating (B).
F<sc>igure</sc> 2.—
Figure 2.—
The production of an eight-way recombinant inbred line by selfing (A) and by sibling mating (B).
F<sc>igure</sc> 3.—
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.
F<sc>igure</sc> 4.—
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|AA) 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.
F<sc>igure</sc> 5.—
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.
F<sc>igure</sc> 6.—
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.

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