Genomic landscape of rat strain and substrain variation
Open accessAbstract
BACKGROUND: Since the completion of the rat reference genome in 2003, whole-genome sequencing data from more than 40 rat strains have become available. These data represent the broad range of strains that are used in rat research including commonly used substrains. Currently, this wealth of information cannot be used to its full extent, because the variety of different variant calling algorithms employed by different groups impairs comparison between strains. In addition, all rat whole genome sequencing studies to date used an outdated reference genome for analysis (RGSC3.4 released in 2004). RESULTS: Here we present a comprehensive, multi-sample and uniformly called set of genetic variants in 40 rat strains, including 19 substrains. We reanalyzed all primary data using a recent version of the rat reference assembly (RGSC5.0 released in 2012) and identified over 12 million genomic variants (SNVs, indels and structural variants) among the 40 strains. 28,318 SNVs are specific to individual substrains, which may be explained by introgression from other unsequenced strains and ongoing evolution by genetic drift. Substrain SNVs may have a larger predicted functional impact compared to older shared SNVs. CONCLUSIONS: In summary we present a comprehensive catalog of uniformly analyzed genetic variants among 40 widely used rat inbred strains based on the RGSC5.0 assembly. This represents a valuable resource, which will facilitate rat functional genomic research. In line with previous observations, our genome-wide analyses do not show evidence for contribution of multiple ancestral founder rat subspecies to the currently used rat inbred strains, as is the case for mouse. In addition, we find that the degree of substrain variation is highly variable between strains, which is of importance for the correct interpretation of experimental data from different labs.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
With advancements in rat genetic modification technologies, it is now possible to create rat models of senescent cell clearance.
“With advancements in genetic modification technologies in the rat [47–51], it is now possible to create rat models of senescent cell clearance.”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 4,408 · cited 2× · see citing works
“Conservation scores for alignments of 8 vertebrate genomes with Rat (PhastCons9way scores [34], rn4 assembly (Nov.”
Large-scale gene function analysis with the PANTHER classification system
Mi, H., Muruganujan, A., Casagrande, J. T., & Thomas, P. D. (2013) · Nature Protocols · doi:10.1038/nprot.2013.092 · Cited by 2,422 · see citing works
DELLY: structural variant discovery by integrated paired-end and split-read analysis
Rausch, T., Zichner, T., Schlattl, A., Stütz, A. M., Beneš, V., & Korbel, J. O. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts378 · Cited by 2,384 · see citing works
Genome sequence of the Brown Norway rat yields insights into mammalian evolution
Gibbs, R. A., Weinstock, G. M., Metzker, M. L., Muzny, D. M., Sodergren, E. J., Scherer, S. E., Scott, G., Steffen, D. L., Worley, K. C., Burch, P. E., et al. (2004) · Nature · doi:10.1038/nature02426 · Cited by 2,147 · see citing works
fastSTRUCTURE: Variational Inference of Population Structure in Large SNP Data Sets
Raj, A., Stephens, M., & Pritchard, J. K. (2014) · Genetics · doi:10.1534/genetics.114.164350 · Cited by 1,666 · see citing works
Abyzov, A., Urban, A. E., Snyder, M., & Gerstein, M. (2011) · Genome Research · doi:10.1101/gr.114876.110 · Cited by 1,658 · see citing works
The genomic signature of dog domestication reveals adaptation to a starch-rich diet
Axelsson, E., Ratnakumar, A., Arendt, M.-L., Maqbool, K., Webster, M. T., Perloski, M., Liberg, O., Arnemo, J. M., Hedhammar, Å., & Lindblad-Toh, K. (2013) · Nature · doi:10.1038/nature11837 · Cited by 963 · see citing works
Whole-genome sequencing of multiple Arabidopsis thaliana populations
Cao, J., Schneeberger, K., Ossowski, S., Günther, T., Bender, S., Fitz, J., Koenig, D., Lanz, C., Stegle, O., Lippert, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.911 · Cited by 934 · see citing works
Flicek, P., Amode, M., Barrell, D., Beal, K., Billis, K., Brent, S., Carvalho-Silva, D., Clapham, P., Coates, G., Fitzgerald, S., et al. (2013) · Nucleic Acids Res. · doi:10.1093/nar/gkt1196 · Cited by 926 · see citing works
Subspecific origin and haplotype diversity in the laboratory mouse
Yang, H., Wang, J., Didion, J. P., Buus, R. J., Bell, T. A., Welsh, C. E., Bonhomme, F., Yu, A. H.-T., Nachman, M. W., Piálek, J., et al. (2011) · Nature Genetics · doi:10.1038/ng.847 · Cited by 459 · see citing works
A genome-wide view of Caenorhabditis elegans base-substitution mutation processes
Denver, D. R., Dolan, P. C., Wilhelm, L., Sung, W., Lucas‐Lledó, J. I., Howe, D. K., Lewis, S. C., Okamoto, K., Thomas, W. K., Lynch, M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904895106 · Cited by 269 · see citing works
Evolution of Hemoglobin and Its Genes
Hardison, R. C. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011627 · Cited by 217 · see citing works
Functional genomics and rat models
Jacob, H. J. (1999) · Genome Research · doi:10.1101/gr.9.11.1013 · Cited by 190 · see citing works
SNP and haplotype mapping for genetic analysis in the rat
Saar, K., Heinig, M., Hummel, O., Lee, Y.-A., Patone, G., Schulz, H., Zimdahl, H., Hübner, N., Beck, A., Klages, S., et al. (2008) · Nature Genetics · doi:10.1038/ng.124 · Cited by 189 · see citing works
Self-citationKurtz, T. W., Montano, M. A., Chan, L., & Kabra, P. M. (1989) · Hypertension · doi:10.1161/01.hyp.13.2.188 · Cited by 180 · see citing works
Combined sequence-based and genetic mapping analysis of complex traits in outbred rats
Baud, A., López-Aumatell, R., Mott, R., Flint, J., Hermsen, R., Guryev, V., Lansu, N. R., Toonen, P. W., Ruzius, F. P., de Bruijn, E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2644 · Cited by 163 · see citing works
Self-citationAtanur, S. S., Diaz, A. I. G., Maratou, K., Sarkis, A. B., Rotival, M., Gamé, L., Tschannen, M., Kaisaki, P. J., Otto, G., Ma, M. C. J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.040 · Cited by 158 · see citing works
Self-citationNiimura, Y. (2009) · Human Genomics · doi:10.1186/1479-7364-4-2-107 · Cited by 139 · see citing works
Effects on Atrial Fibrillation in Aged Hypertensive Rats by Ca 2+ -Activated K + Channel Inhibition
Diness, J. G., Skibsbye, L., Jespersen, T., Bartels, E. D., Sørensen, U. S., Hansen, R. S., & Grunnet, M. (2011) · Hypertension · doi:10.1161/hypertensionaha.111.170613 · Cited by 106 · see citing works
The genome sequence of the spontaneously hypertensive rat: Analysis and functional significancePreprint
Atanur, S. S., Birol, İ., Guryev, V., Hirst, M., Hummel, O., Morrissey, C., Behmoaras, J. V., Fernández, X. M., Johnson, M. D., McLaren, W. M., et al. (2010) · Genome Research · doi:10.1101/gr.103499.109 · Cited by 94 · see citing works
Self-citationHigashino, A., Sakate, R., Kameoka, Y., Takahashi, I., Hirata, M., Tanuma, R., Masui, T., Yasutomi, Y., & Osada, N. (2012) · Genome biology · doi:10.1186/gb-2012-13-7-r58 · Cited by 88 · see citing works
Sagvolden, T., DasBanerjee, T., Zhang‐James, Y., Middleton, F. A., & Faraone, S. V. (2008) · Behavioral and Brain Functions · doi:10.1186/1744-9081-4-56 · Cited by 70 · see citing works
The Rat Genome Database 2013--data, tools and users
Laulederkind, S. J. F., Hayman, G. T., Wang, S.-J., Smith, J. R., Lowry, T. F., Nigam, R., Petri, V., Pons, J. D., Dwinell, M. R., Shimoyama, M. E., et al. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbt007 · Cited by 65 · see citing works
Genetic Mapping of Blood Pressure Quantitative Trait Loci in Milan Hypertensive Rats
Zagato, L., Modica, R., Florio, M., et al. (2000) · Hypertension · doi:10.1161/01.hyp.36.5.734 · Cited by 46 · see citing works
C57BLack/BOX? The importance of exact mouse strain nomenclature
Wotjak, C. T. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(02)00049-5 · Cited by 45 · see citing works
Tomita‐Mitchell, A., Kat, A. G., Marcelino, L. A., et al. (2000) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(00)00020-8 · Cited by 42 · see citing works
Improving mammalian genome scaffolding using large insert mate-pair next-generation sequencing
van Heesch, S., Kloosterman, W. P., Lansu, N. R., Ruzius, F.-P., Levandowsky, E., Lee, C. C., Zhou, S., Goldstein, S., Schwartz, D. C., Harkins, T. T., et al. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-257 · Cited by 39 · see citing works
Self-citationSimonis, M., Atanur, S. S., Linsen, S. E. V., Guryev, V., Ruzius, F.-P., Gamé, L., Lansu, N. R., de Bruijn, E., van Heesch, S., Jones, S. J. M., et al. (2012) · Genome biology · doi:10.1186/gb-2012-13-4-r31 · Cited by 37 · see citing works
Self-citationGenetics of the polydactyly-luxate syndrome in the Norway rat, Rattus norvegicus.
Kren, V. (1975) · PubMed · Cited by 37 · see citing works
López, B., Ryan, R. P., Moreno, C., Sarkis, A., Lazar, J., Provoost, A. P., Jacob, H. J., & Roman, R. J. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00335.2005 · Cited by 36 · see citing works
Reactive Oxygen Species and their Cytotoxic Mechanisms
Evans, M. D., Griffiths, H. R., & Lunec, J. (1997) · Advances in molecular and cell biology · doi:10.1016/s1569-2558(08)60271-4 · Cited by 34 · see citing works
Linkage Analysis and Construction of a Congenic Strain for a Blood Pressure QTL on Rat Chromosome 9
Rapp, J. P., Garrett, M. R., Dene, H., et al. (1998) · Genomics · doi:10.1006/geno.1998.5394 · Cited by 28 · see citing works
Bosse, J. D., Lin, H., Sloan, C., Zhang, Q., Abel, E. D., Pereira, T. J., Dolinsky, V. W., Symons, J. D., & Jalili, T. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00631.2012 · Cited by 24 · see citing works
Smits, B. M. G., Guryev, V., Zeegers, D., Wedekind, D., Hedrich, H. J., & Cuppen, E. P. J. G. (2005) · BMC Genomics · doi:10.1186/1471-2164-6-170 · Cited by 22 · see citing works
Self-citationGuo, X., Brenner, M., Zhang, X., Laragione, T., Tai, S., Li, Y., Bu, J., Yin, Y., Shah, A. A., Kwan, K., et al. (2013) · Genetics · doi:10.1534/genetics.113.153049 · Cited by 18 · see citing works
Vanderlinden, L. A., Saba, L. M., Printz, M. P., et al. (2014) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12471 · Cited by 12 · see citing works
Genetical Genomic Analysis of Complex Phenotypes Using the PhenoGen Website
Bennett, B., Saba, L. M., Hornbaker, C. K., Kechris, K. J., Hoffman, P. L., & Tabakoff, B. (2010) · Behavior Genetics · doi:10.1007/s10519-010-9427-0 · Cited by 11 · see citing works
Self-citationYagil, Y., Hessner, M. J., Schulz, H., Gösele, C., Lebedev, L., Barkalifa, R., Sapojnikov, M., Hübner, N., & Yagil, C. (2010) · Physiological Genomics · doi:10.1152/physiolgenomics.00149.2010 · Cited by 10 · see citing works
Self-citationGenomic structure of nucleotide diversity among Lyon rat models of metabolic syndrome
Ma, M. C. J., Atanur, S. S., Aitman, T. J., et al. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-197 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Reducing Senescent Cell Burden in Aging and Disease
Pignolo, R. J., Passos, J. F., Khosla, S., Tchkonia, T., & Kirkland, J. L. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.03.005 · Cited by 177 · see citing works
Exploring human disease using the Rat Genome Database
Shimoyama, M., Laulederkind, S. J. F., De Pons, J., Nigam, R., Smith, J. R., Tutaj, M., Petri, V., Hayman, G. T., Wang, S.-J., Ghiasvand, O., et al. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.026021 · Cited by 37 · see citing works
- Authors
- Hermsen, R., de Ligt, J., Spee, W., Blokzijl, F., Schäfer, S., Adami, E., Boymans, S., Flink, S., van Boxtel, R., van der Weide, R. H., Aitman, T., Hübner, N., Simonis, M., Tabakoff, B., Guryev, V., & Cuppen, E.
- Affiliations
- University Medical Center Utrecht (NL)
- Max Delbrück Center (DE)
- University of Colorado Anschutz (US)
- University Medical Center Groningen (NL)
- Corresponding author
- Cuppen, Edwin
- ORCID
- Venue
- BMC Genomics
- Published
- 2015-05-06
- Volume
- 16
- Issue
- 1
- Pages
- 357-357
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC4422378
- OpenAlex
- W1518386349
- Cited by
- 93
- References
- 44
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 14 · 2020: 16 · 2019: 12 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 5
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Genomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (FP7 2007-2013, 863.10.007, 700.58.303)
- Norwegian Biodiversity Information Centre
- National Institutes of Health (FP7/2007-2013, 241504)
- National Institute on Alcohol Abuse and Alcoholism (R24AA013162, T32AA007464)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- inbred rat strains, genetic variation, single nucleotide variants, indels, structural variants, variant calling, introgression, genetic drift, functional impact of variants
- MeSH terms
- Animals, Dogs, Species Specificity, Evolution, Molecular, Polymorphism, Single Nucleotide, Genomics, Genetic Drift, Mice, Rats, INDEL Mutation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
