Subspecific origin and haplotype diversity in the laboratory mouse

The Jackson Laboratory, Bar Harbor, Maine, USA.
Nature Genetics (Impact Factor: 29.35). 05/2011; 43(7):648-55. DOI: 10.1038/ng.847
Source: PubMed


Here we provide a genome-wide, high-resolution map of the phylogenetic origin of the genome of most extant laboratory mouse inbred strains. Our analysis is based on the genotypes of wild-caught mice from three subspecies of Mus musculus. We show that classical laboratory strains are derived from a few fancy mice with limited haplotype diversity. Their genomes are overwhelmingly Mus musculus domesticus in origin, and the remainder is mostly of Japanese origin. We generated genome-wide haplotype maps based on identity by descent from fancy mice and show that classical inbred strains have limited and non-randomly distributed genetic diversity. In contrast, wild-derived laboratory strains represent a broad sampling of diversity within M. musculus. Intersubspecific introgression is pervasive in these strains, and contamination by laboratory stocks has played a role in this process. The subspecific origin, haplotype diversity and identity by descent maps can be visualized using the Mouse Phylogeny Viewer (see URLs).

Download full-text


Available from: Jaroslav Piálek, Oct 04, 2015
1 Follower
30 Reads
    • "Where more recent phylogeographical studies have used additional nonmtDNA markers, these have tended to be autosomal microsatellites that have been useful to examine population-level genetic parameters of the study populations but, so far, they are of less value for inferring colonization history (Hardouin et al., 2010; Jones et al., 2010a, b, 2011; Förster et al., 2013; Gabriel, Mathias & Searle, 2013). There is further potential for nuclear studies from large-scale house mouse single nucleotide polymorphism arrays (Yang et al., 2011); these could provide a reliable phylogeographical history for the autosomes, although the cost of the chips may be prohibitive for phylogeographical studies. Phylogeographical studies based on the nuclear genome (restriction fragment length polymophism or amplified fragment length polymorphism data from earlier studies; microsatellites from more recent ones) have been inconsistent with studies using mtDNA data, reflecting the different histories of the nuclear and mtDNA genomes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We used Y chromosome microsatellites to infer the phylogeography of the house mouse (Mus musculus; predominantly the domesticus subspecies) across western Europe, and compared this with mitochondrial (mt)DNA phylogeography for the same samples. Overall, the distributions of mtDNA and Y haplotype lineages within M. m. domesticus were discordant, probably as a result of behavioural differences between males and females. In island contexts, there is evidence for a greater number of Y chromosome introductions compared to mtDNA introductions, indicating that island populations are more resistant to incoming females than males. This contrasts with a subspecies hybrid zone, which acts as a nonpermeable barrier to the Y chromosome but is relatively porous to mtDNA. Interestingly, within Norway, where Mus musculus Y chromosomes are prevalent in the resident domesticus populations, the musculus Y is apparently of a single, recent origin, with a distribution that is likely the result of a positive selection allowing the subspecies barrier to be crossed. Overall, we confirm the utility of Y chromosome microsatellites for inferring global ancestry and phylogeography in the house mouse. © 2015 Crown copyright. Biological Journal of the Linnean Society © 2015 The Linnean Society of London, 2015, ●●, ●●–●●.
    Biological Journal of the Linnean Society 04/2015; 115(2). DOI:10.1111/bij.12522 · 2.26 Impact Factor
  • Source
    • "We called genotypes at 584,729 SNPs using apt-probeset-genotype (Affymetrix) and standard settings . We used the MouseDivGeno algorithm to identify variable intensity oligonucleotides (VINOs) (Yang et al., 2011); 53,148 VINOs were removed from the dataset. In addition, we removed 18,120 SNPs with heterozygosity >0.9 in any population because these SNPs likely represent additional VINOs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone. DOI:
    eLife Sciences 12/2014; 3. DOI:10.7554/eLife.02504 · 9.32 Impact Factor
  • Source
    • "Mb) from the Mus mus musculus progenitor ( (Yang et al. 2011). Cxcr4 has been shown to play a role in regulation of neutrophil release from the bone marrow (Eash et al. 2009), making it a strong functional candidate. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic mapping studies in the mouse and other model organisms are used to search for genes underlying complex phenotypes. Traditional genetic mapping studies that employ single-generation crosses have poor mapping resolution and limit discovery to loci that are polymorphic between the two parental strains. Multiparent outbreeding populations address these shortcomings by increasing the density of recombination events and introducing allelic variants from multiple founder strains. However, multiparent crosses present new analytical challenges and require specialized software to take full advantage of these benefits. Each animal in an outbreeding population is genetically unique and must be genotyped using a high-density marker set; regression models for mapping must accommodate multiple founder alleles, and complex breeding designs give rise to polygenic covariance among related animals that must be accounted for in mapping analysis. The Diversity Outbred (DO) mice combine the genetic diversity of eight founder strains in a multigenerational breeding design that has been maintained for >16 generations. The large population size and randomized mating ensure the long-term genetic stability of this population. We present a complete analytical pipeline for genetic mapping in DO mice, including algorithms for probabilistic reconstruction of founder haplotypes from genotyping array intensity data, and mapping methods that accommodate multiple founder haplotypes and account for relatedness among animals. Power analysis suggests that studies with as few as 200 DO mice can detect loci with large effects, but loci that account for <5% of trait variance may require a sample size of up to 1000 animals. The methods described here are implemented in the freely available R package DOQTL.
    G3-Genes Genomes Genetics 09/2014; 4(9):1623-33. DOI:10.1534/g3.114.013748 · 3.20 Impact Factor
Show more