A wild derived quantitative trait locus on mouse chromosome 2 prevents obesity

Mollah, Md. Bazlur R.; Ishikawa, Akira

doi:10.1186/1471-2156-11-84

Cited by 12 publications

(24 citation statements)

References 44 publications

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“…These facts thus reinforce the mouse Ly75 gene as a putative QTG for the Pbwg1 . 5 QTL with a preventive effect on obesity when mice are fed both low-fat standard and high-fat diets [17]. …”

Section: Discussionmentioning

confidence: 99%

“…In contrast, at Pbwg1 . 5 , the wild-derived allele decreases WAT weight [16] and shows resistance to obesity in mice fed both standard and high-fat diets [17]. In addition, exome sequencing and bioinformatics analysis revealed three nonsynonymous single-nucleotide polymorphisms (nsSNPs) of two putative candidate genes, Gcg (glucagon) and Grb14 (growth factor receptor-bound protein 14), for Pbwg1 .…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Putative Quantitative Trait Gene for Resistance to Obesity in Mice Using Transcriptome Analysis and Causal Inference Tests

Ishikawa

2017

PLoS ONE

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It is still challenging to identify causal genes governing obesity. Pbwg1.5, a quantitative trait locus (QTL) for resistance to obesity, was previously discovered from wild Mus musculus castaneus mice and was fine-mapped to a 2.1-Mb genomic region of mouse chromosome 2, where no known gene with an effect on white adipose tissue (WAT) has been reported. The aim of this study was to identify a strong candidate gene for Pbwg1.5 by an integration approach of transcriptome analysis (RNA-sequencing followed by real-time PCR analysis) and the causal inference test (CIT), a statistical method to infer causal relationships between diplotypes, gene expression and trait values. Body weight, body composition and biochemical traits were measured in F2 mice obtained from an intercross between the C57BL/6JJcl strain and a congenic strain carrying Pbwg1.5 on the C57BL/6JJcl background. The F2 mice showed significant diplotype differences in 12 traits including body weight, WAT weight and serum cholesterol/triglyceride levels. The transcriptome analysis revealed that Ly75, Pla2r1, Fap and Gca genes were differentially expressed in the liver and that Fap, Ifih1 and Grb14 were differentially expressed in WAT. However, CITs indicated statistical evidence that only the liver Ly75 gene mediated between genotype and WAT. Ly75 expression was negatively associated with WAT weight. The results suggested that Ly75 is a putative quantitative trait gene for the obesity-resistant Pbwg1.5 QTL discovered from the wild M. m. castaneus mouse. The finding provides a novel insight into a better understanding of the genetic basis for prevention of obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a Putative Quantitative Trait Gene for Resistance to Obesity in Mice Using Transcriptome Analysis and Causal Inference Tests

Ishikawa

2017

PLoS ONE

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“…A series of genetic mapping studies identified a large number of loci that contribute to weight differences between M. m. castaneus from the Philippines (a smaller form) and the C57BL/6 laboratory strain (primarily M. m. domesticus in origin) (Ishikawa et al 2000;Ishikawa and Namikawa 2004;Mollah and Ishikawa 2010), including one in the region of the QTL we identified in the distal part of chromosome 10. Although the considerable divergence time between the two subspecies M. m. castaneus and M. m. domesticus makes it difficult to associate QTL with island evolution in this case, the resemblance between these results and ours is encouraging.…”

Section: Discussionmentioning

confidence: 99%

Genetics of Rapid and Extreme Size Evolution in Island Mice

et al. 2015

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Organisms on islands provide a revealing window into the process of adaptation. Populations that colonize islands often evolve substantial differences in body size from their mainland relatives. Although the ecological drivers of this phenomenon have received considerable attention, its genetic basis remains poorly understood. We use house mice (subspecies: Mus musculus domesticus) from remote Gough Island to provide a genetic portrait of rapid and extreme size evolution. In just a few hundred generations, Gough Island mice evolved the largest body size among wild house mice from around the world. Through comparisons with a smaller-bodied wild-derived strain from the same subspecies (WSB/EiJ), we demonstrate that Gough Island mice achieve their exceptional body weight primarily by growing faster during the 6 weeks after birth. We use genetic mapping in large F 2 intercrosses between Gough Island mice and WSB/EiJ to identify 19 quantitative trait loci (QTL) responsible for the evolution of 16-week weight trajectories: 8 QTL for body weight and 11 QTL for growth rate. QTL exhibit modest effects that are mostly additive. We conclude that body size evolution on islands can be genetically complex, even when substantial size changes occur rapidly. In comparisons to published studies of laboratory strains of mice that were artificially selected for divergent body sizes, we discover that the overall genetic profile of size evolution in nature and in the laboratory is similar, but many contributing loci are distinct. Our results underscore the power of genetically characterizing the entire growth trajectory in wild populations and lay the foundation necessary for identifying the mutations responsible for extreme body size evolution in nature.KEYWORDS island syndrome; island evolution; phenotypic extreme; body size; complex trait T HE question of how organisms adapt to new environments continues to captivate biologists. Because adaptation requires genetic change, discovering the mutations responsible for adaptive phenotypes is a key step toward understanding the mechanisms of this process. There is a growing list of traits for which adaptive differences in nature have been directly traced to specific genes. Examples include adaptive coloration in pocket mice (Nachman et al. 2003), deer mice (Hoekstra et al. 2006), Drosophila melanogaster (Rebeiz et al. 2009), and peppered moths (van't Hof et al. 2011); armor plate patterning and pelvic spine reduction in stickleback fish (Colosimo et al. 2005;Chan et al. 2010;Jones et al. 2012); and defense chemistry in Boechera stricta (Prasad et al. 2012). Despite these advances, the genetic architecture of adaptation in nature remains poorly understood. Most progress has focused on traits with simple genetic bases, where one or a few loci explain observed phenotypic variation (Rockman 2012). But the majority of trait differences between populations inhabiting contrasting environments are quantitative, suggesting that adaptation often involves more complex inheritance.While it ...

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“…To confirm the presence of Pbwg1 and to narrow down its chromosomal location, I developed a congenic strain, named B6.Cg- Pbwg1 , with an M. m. castaneus genome region of approximately 44 Mb on the C57BL/6J genetic background [14]. I also developed more than 20 subcongenic strains with overlapping and non-overlapping genome regions from an F2 intercross of the B6.Cg- Pbwg1 congenic strain and the C57BL/6J strain (all congenic and subcongenic strains deposited in RIKEN BioResource Center, Japan ()) [14, 15]. …”

Section: Example Of M M Castaneusmentioning

confidence: 99%

“…Both means were significantly lower than that of C57BL/6J males (1.043 ± 0.009 g). Similarly, when mice were fed a high-fat diet for 7 weeks from 6 to 13 weeks of age, total fat weights were 1.745 ± 0.081 g in B6.Cg- Pbwg1 and 1.221 ± 0.098 g in B6.Cg- Pbwg1 /SR8, and both were significantly lower than that of C57BL/6J (3.100 ± 0.083 g) [15]. In addition, the wild-derived QTL allele decreased body weight and serum levels of glucose and triglyceride in mice fed a standard diet.…”

Section: Example Of M M Castaneusmentioning

confidence: 99%

Wild Mice As Bountiful Resources of Novel Genetic Variants for Quantitative Traits

Ishikawa

2013

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Most traits of biological importance, including traits for human complex diseases (e.g., obesity and diabetes), are continuously distributed. These complex or quantitative traits are controlled by multiple genetic loci called QTLs (quantitative trait loci), environments and their interactions. The laboratory mouse has long been used as a pilot animal model for understanding the genetic architecture of quantitative traits. Next-generation sequencing analyses and genome-wide SNP (single nucleotide polymorphism) analyses of mouse genomes have revealed that classical inbred strains commonly used throughout the world are derived from a few fancy mice with limited and non-randomly distributed genetic diversity that occurs in nature and also indicated that their genomes are predominantly Mus musculus domesticus in origin. Many QTLs for a huge variety of traits have so far been discovered from a very limited gene pool of classical inbred strains. However, wild M. musculus mice consisting of five subspecies widely inhabit areas all over the world, and hence a number of novel QTLs may still lie undiscovered in gene pools of the wild mice. Some of the QTLs are expected to improve our understanding of human complex diseases. Using wild M. musculus subspecies in Asia as examples, this review illustrates that wild mice are untapped natural resources for valuable QTL discovery.

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A wild derived quantitative trait locus on mouse chromosome 2 prevents obesity

Cited by 12 publications

References 44 publications

Identification of a Putative Quantitative Trait Gene for Resistance to Obesity in Mice Using Transcriptome Analysis and Causal Inference Tests

Identification of a Putative Quantitative Trait Gene for Resistance to Obesity in Mice Using Transcriptome Analysis and Causal Inference Tests

Genetics of Rapid and Extreme Size Evolution in Island Mice

Wild Mice As Bountiful Resources of Novel Genetic Variants for Quantitative Traits

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