Rat Genome Mapping and Genomics

Szpirer, Claude; Levan, Göran

doi:10.1007/978-3-642-31316-5_9

Cited by 5 publications

(4 citation statements)

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“…I am retired (from the “Université Libre de Bruxelles”); with my coworkers, I contributed, amongst other things, to the development of the rat gene map and the understanding of the genetic basis of susceptibility to rat mammary and uterine cancers [ 18 ].…”

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confidence: 99%

“…Just as the traits that were selected for, most of these phenotypes are polygenic. All these phenotypes can be used as models of human traits or diseases [18], implying that the genes underlying these traits or diseases should be identified. Information on rat strains and rat disease models, can be found at the Rat Genome Database (RGD, https://rgd.mcw.edu/) [19].…”

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Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Szpirer

2020

J Biomed Sci

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The laboratory rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering causal disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout mutations]. Furthermore, even when the human gene causing a disease had been identified without resorting to a rat model, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, over 350 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases, thereby providing a rich resource of disease models. This article is an update of the progress made in this research and provides the reader with an inventory of these disease genes, a significant number of which have similar effects in rat and humans.

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confidence: 99%

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Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Szpirer

2020

J Biomed Sci

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“…Rat has facilitated many studies on physiology, pharmacology and metabolism, and over the last 100 years, more than 200 inbred rat strains representing various human diseases like diabetes, hypertension, cardiovascular disorders, immunological disorders, neurological disorders and behavioural disorders have been identified (Aitman et al 2008;Mashimo and Serikawa 2009;Dwinell et al 2011;Szpirer and Levan 2012). All these strains are known to have their origin from less than a dozen original outbred stocks, among which Wistar stock (maintained at Wistar Institute, Philadelphia) was known to be widely distributed and contributed to major animal models in biomedical research (Lindesy and Baker 2006).…”

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confidence: 99%

Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research

et al. 2015

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WNIN (Wistar/NIN) is an inbred rat strain maintained at National Institute of Nutrition (NIN) for more than 90 years, and WNIN/Ob is an obese mutant originated from it. To determine their genetic relatedness with major rat strains in biomedical research, they were genotyped at various marker loci. The recently identified markers for albino and hooded mutations which clustered all the known albino rats into a single lineage also included WNIN and WNIN/Ob rats. Genotyping using microsatellite DNA markers and phylogenetic analysis with 49 different rat strains suggested that WNIN shares a common ancestor with many Wistar originated strains. Fst estimates and Fischer's exact test suggest that WNIN rats differed significantly from all other strains tested. WNIN/Ob though shows hyper-leptinemia, like Zucker fatty rat, did not share the Zucker fatty rat mutation. The above analyses suggest WNIN as a highly differentiated rat strain and WNIN/Ob a novel obese mutant evolved from it.

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“…Just as the traits that were selected for, most of these phenotypes are polygenic. All these phenotypes can be used as models of human traits or diseases [10], implying that the genes underlying these traits or diseases should be identified. Information on rat strains and rat disease models, can be found at the Rat Genome Database (RGD, https://rgd.mcw.edu/) [11].…”

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confidence: 99%

Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Szpirer

2020

Preprint

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The rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout (KO) mutations]. Furthermore, even when the human gene causing a disease is identified, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, about 300 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases. This article provides the reader with an inventory of these genes.

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Rat Genome Mapping and Genomics

Cited by 5 publications

References 409 publications

Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

Genetic Relatedness of WNIN and WNIN/Ob with Major Rat Strains in Biomedical Research

Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes

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