Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits

Takada, Toyoyuki; Mita, Akihiko; Maeno, Akiteru; Sakai, Takahiro; Shitara, Hiroshi; Kikkawa, Yoshiaki; Moriwaki, Kazuo; Yonekawa, Hiromichi; Shiroishi, Toshihiko

doi:10.1101/gr.7175308

Cited by 86 publications

(103 citation statements)

References 35 publications

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“…It is important to bear in mind, however, that a large X effect has not yet been demonstrated in mice, and this calculation is thus very rough. Two recent studies constructed large sets of consomic lines substituting individual chromosomes from M. m. molossinus (MSM/Ms; Takada et al 2008) or M. musculus (PWK/Ph; Gregorová et al 2008) on the background of the classic laboratory strain C57BL/6J. Both experiments uncovered putative incompatibilities involving most autosomes, with deleterious effects on strain reproduction and viability.…”

Section: Discussionmentioning

confidence: 99%

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

Good¹,

2008

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The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

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Section: Discussionmentioning

confidence: 99%

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

Good¹,

2008

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“…These chromosomes are included as smaller, subchromosomal segments in several congenic strains (Gregorová et al 2008). A third panel with 29 strains was derived from MSM (donor) and C57BL/6J (host) that similarly used congenic strains to span Chromosomes 2, 6, 7, 12, 13, and X that were not substituted intact (Takada et al 2008). Other partial panels are based on the following strain combinations: (donor:host) C57BL/6ByJ:129P3/J, C57BL/6J:129S1/SvImJ, 129P3/J:C57BL/ 6ByJ, 129S1/SvImJ:C57BL/6J, MOLF/Ei:129S1/SvImJ, C57BL/6J: C3H/HeJ, and NZM2328/NOD among others.…”

Section: Chromosome Substitution Strains (Csss)mentioning

confidence: 99%

Contrasting genetic architectures in different mouse reference populations used for studying complex traits

Buchner

Nadeau

2015

Genome Res.

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Quantitative trait loci (QTLs) are being used to study genetic networks, protein functions, and systems properties that underlie phenotypic variation and disease risk in humans, model organisms, agricultural species, and natural populations. The challenges are many, beginning with the seemingly simple tasks of mapping QTLs and identifying their underlying genetic determinants. Various specialized resources have been developed to study complex traits in many model organisms. In the mouse, remarkably different pictures of genetic architectures are emerging. Chromosome Substitution Strains (CSSs) reveal many QTLs, large phenotypic effects, pervasive epistasis, and readily identified genetic variants. In contrast, other resources as well as genome-wide association studies (GWAS) in humans and other species reveal genetic architectures dominated with a relatively modest number of QTLs that have small individual and combined phenotypic effects. These contrasting architectures are the result of intrinsic differences in the study designs underlying different resources. The CSSs examine contextdependent phenotypic effects independently among individual genotypes, whereas with GWAS and other mouse resources, the average effect of each QTL is assessed among many individuals with heterogeneous genetic backgrounds. We argue that variation of genetic architectures among individuals is as important as population averages. Each of these important resources has particular merits and specific applications for these individual and population perspectives. Collectively, these resources together with high-throughput genotyping, sequencing and genetic engineering technologies, and information repositories highlight the power of the mouse for genetic, functional, and systems studies of complex traits and disease models.

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“…Recently, many attempts have been made to characterize genetic factors, quantitative trait loci (QTLs), for a variety of complex traits [13,19,28,30,31,33]. Although QTL mappings were successful for many traits, further attempts to identify responsible genes represent challenging work that remains to be done.…”

Section: Introductionmentioning

confidence: 99%

Genomic Mixing to Elucidate the Genetic System of Complex Traits

2012

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Abstract:Understanding the genetic basis of complex traits has become one of the major issues in genetics, but recent advances in this field are still faced with a difficulty, the so-called "missing heritability." It is speculated that missing heritability mainly stems from a large number of variants of small effect that are poorly detected by currently available methods. In order to overcome this problem, many recent genetic studies of complex traits have actively used outbred stocks of mice. However, most of the available outbred stocks have a limited amount of genetic variation, because many stocks originate from Swiss mouse colonies. We have repeatedly shown that wild-derived strains are a useful mouse resource since there is a large genetic diversity among these strains. Here, we give an overview of mouse resources produced by crossing different founder mice. Finally, we propose an advantage of new attempts to conduct selective breeding using heterogeneous stocks created by mixing genomes of wild-derived inbred strains of mice when studying complex traits.

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Mouse inter-subspecific consomic strains for genetic dissection of quantitative complex traits

Cited by 86 publications

References 35 publications

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

Contrasting genetic architectures in different mouse reference populations used for studying complex traits

Genomic Mixing to Elucidate the Genetic System of Complex Traits

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