Joint Analysis of Strain and Parent-of-Origin Effects for Recombinant Inbred Intercrosses Generated from Multiparent Populations with the Collaborative Cross as an Example

Abstract

Multiparent populations (MPP) have become popular resources for complex trait mapping because of their wider allelic diversity and larger population size compared with traditional two-way recombinant inbred (RI) strains. In mice, the collaborative cross (CC) is one of the most popular MPP and is derived from eight genetically diverse inbred founder strains. The strategy of generating RI intercrosses (RIX) from MPP in general and from the CC in particular can produce a large number of completely reproducible heterozygote genomes that better represent the (outbred) human population. Since both maternal and paternal haplotypes of each RIX are readily available, RIX is a powerful resource for studying both standing genetic and epigenetic variations of complex traits, in particular, the parent-of-origin (PoO) effects, which are important contributors to many complex traits. Furthermore, most complex traits are affected by >1 genes, where multiple quantitative trait locus mapping could be more advantageous. In this paper, for MPP-RIX data but taking CC-RIX as a working example, we propose a general Bayesian variable selection procedure to simultaneously search for multiple genes with founder allelic effects and PoO effects. The proposed model respects the complex relationship among RIX samples, and the performance of the proposed method is examined by extensive simulations.

Mouse Genetic Reference Populations: Cellular Platforms for Integrative Systems Genetics

“…Model organism GRPs have been precisely designed to offer increased statistical power (e.g., mouse [24][25][26], Drosophila [27], yeast, see following text) and an opportunity for systems genetics discovery with in vivo correlation and validation capabilities. One of the pillars of model organism genetic mapping studies has been the analysis of pairwise crosses between two genetically divergent founder strains ( Figure 1A).…”

Antipsychotic Behavioral Phenotypes in the Mouse Collaborative Cross Recombinant Inbred Inter-Crosses (RIX)

“…By mating different CC strains, we can generate recombinant inbred inter-crosses (CC-RIX) (Zou et al 2005;Schoenrock et al 2018). CC-RIX are outbred but their genomes are completely reproducible (by mating their parental CC strains) and thus are an intriguing model of the genetic diversity akin to that in human populations (Zou et al 2005;Liu et al 2018). The genetic diversity of CC-RIX enables the study of parent-of-origin effects and their phenotypic characterization has demonstrated that there are strong strain effects in some measures (Crowley et al 2015;Schoenrock et al 2018).…”

Antipsychotic behavioral phenotypes in the mouse Collaborative Cross recombinant inbred inter-crosses (RIX)

“…CC-RIX are outbred but their genomes are completely reproducible (by mating their parental CC strains) and thus are an intriguing model of the genetic diversity akin to that in human populations (Z ou et al . 2005; L iu et al . 2018).…”