A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

Tristan V. de Jong; Yanchao Pan; Pasi Rastas; Daniel Munro; Monika Tutaj; Huda Akil; Chris Benner; Denghui Chen; Apurva S. Chitre; William Chow; Vincenza Colonna; Clifton L. Dalgard; Wendy M. Demos; Peter A. Doris; Erik Garrison; Aron M. Geurts; Hakan M. Gunturkun; Victor Guryev; Thibaut Hourlier; Kerstin Howe; Jun Huang; Ted Kalbfleisch; Panjun Kim; Ling Li; Spencer Mahaffey; Fergal J. Martin; Pejman Mohammadi; Ayse Bilge Ozel; Oksana Polesskaya; Michal Pravenec; Pjotr Prins; Jonathan Sebat; Jennifer R. Smith; Leah C. Solberg Woods; Boris Tabakoff; Alan Tracey; Marcela Uliano-Silva; Flavia Villani; Hongyang Wang; Burt M. Sharp; Francesca Telese; Zhihua Jiang; Laura Saba; Xusheng Wang; Terence D. Murphy; Abraham A. Palmer; Anne E. Kwitek; Melinda R. Dwinell; Robert W. Williams; Jun Z. Li; Hao Chen

doi:10.1016/j.xgen.2024.100527

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

Tristan V. de Jong, Yanchao Pan, Pasi Rastas, Daniel Munro, Monika Tutaj, Huda Akil, Chris Benner, Denghui Chen, Apurva S. Chitre, William Chow, Vincenza Colonna, Clifton L. Dalgard, Wendy M. Demos, Peter A. Doris, Erik Garrison, Aron M. Geurts, Hakan M. Gunturkun, Victor Guryev, Thibaut Hourlier, Kerstin HoweJun Huang, Ted Kalbfleisch, Panjun Kim, Ling Li, Spencer Mahaffey, Fergal J. Martin, Pejman Mohammadi, Ayse Bilge Ozel, Oksana Polesskaya, Michal Pravenec, Pjotr Prins, Jonathan Sebat, Jennifer R. Smith, Leah C. Solberg Woods, Boris Tabakoff, Alan Tracey, Marcela Uliano-Silva, Flavia Villani, Hongyang Wang, Burt M. Sharp, Francesca Telese, Zhihua Jiang, Laura Saba, Xusheng Wang, Terence D. Murphy, Abraham A. Palmer, Anne E. Kwitek, Melinda R. Dwinell, Robert W. Williams, Jun Z. Li, Hao Chen

Research output: Contribution to journal › Article › peer-review

Abstract

The seventh iteration of the reference genome assembly for Rattus norvegicus—mRatBN7.2—corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

Original language	English
Article number	100527
Journal	Cell Genomics
Volume	4
Issue number	4
DOIs	https://doi.org/10.1016/j.xgen.2024.100527
State	Published - Apr 10 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

This work is supported by the Academy of Finland (grant no. 343656) to P.R.; NIH NHLBI R01HL064541 and P01HL149620 and Office of the Director R24OD024617 to M.T.; NIH NIDA U01DA043098 to H.A.; NIH NIDA U01DA051972 to C.B.; NIH NHLBI R01HL064541 and Office of the Director R24OD024617 to W.M.D.; NIH NHLBI P01HL149620 and Office of the Director R24OD024617 to A.M.G.; Wellcome Trust WT222155/Z/20/Z to T.H.; NIH R01HG011252 to T.K.; Wellcome Trust WT222155/Z/20/Z to F.J.M.; NIH R01GM140287 to P.M.; a program from the National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID project no. LX22NPO5104) funded by the European Union \u2013 Next Generation EU to M.P.; National Institute of Food and Agriculture, United States Department of Agriculture (2016-67015-24470/2020-67015-31733/2022-51300-38058/2023-67015-39566/2023-67015-40080) to Z.J.; NIH NIDA U01DA051234 to J.S.; NIH NHLBI R01HL064541, NHGRI U24HG010859, and Office of the Director R24OD024617 to J.R.S.; NIH NIDA P50DA037844 to L.C.S.W. (HS rats); NIH NIAAA R24AA013162 to B.T.; NIH NIDA U01DA050239 and U01DA051972 to F.T.; NIH NIDA P30DA044223 to L.S.; the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health to T.D.M.; NIH NHLBI R01HL064541 and P01HL149620, NHGRI U24HG010859, and Office of the Director R24OD024617 to A.E.K.; NIH Office of the Director grant R24OD024617 to M.R.D. (HRDP); NIH NIDA U01DA047638 and P30DA044223 to R.W.W.; NIH NIDA U01DA043098 to J.Z.L.; and NIH NIDA U01DA047638, P50DA037844, and R01DA048017 to H.C. The majority of the computation for this work was performed on the University of Tennessee Infrastructure for Scientific Applications and Advanced Computing (ISAAC) computational resources. This work is dedicated to the memory of Dr. Mary Shimoyama. Conceptualization, A.A.P. R.W.W. J.Z.L. and H.C.; formal analysis, T.V.d.J. Y.P. P.R. D.M. M.T. X.W. T.D.M. J.Z.L. and H.C.; visualization, T.V.d.J. Y.P. P.R. D.M. F.T. Z.J. L.S. X.W. and J.Z.L.; investigation, H.A. C.B. D.C. A.S.C. W.C. V.C. W.M.D. P.A.D. E.G. A.M.G. H.M.G. V.G. T.H. K.H. J.H. T.K. P.K. L.L. S.M. F.J.M. P.M. A.B.O. O.P. P.P. J.S. J.R.S. L.C.S.W. B.T. A.T. M.U.-S. F.V. H.W. F.T. Z.J. and L.S.; resources, C.L.D. M.P. A.E.K. and M.R.D.; data curation, W.M.D. A.M.G. J.R.S. A.E.K. and M.R.D.; writing \u2013 original draft, T.V.d.J. Y.P. P.R. D.M. T.H. L.S. X.W. T.D.M. J.Z.L. and H.C.; writing \u2013 review & editing, A.M.G. B.M.S. L.S. X.W. T.D.M. A.A.P. A.E.K. M.R.D. R.W.W. J.Z.L. and H.C.; supervision, J.Z.L. and H.C. The authors declare no competing interests. This work is supported by the Academy of Finland (grant no. 343656 ) to P.R.; NIH NHLBI R01HL064541 and P01HL149620 and Office of the Director R24OD024617 to M.T.; NIH NIDA U01DA043098 to H.A.; NIH NIDA U01DA051972 to C.B.; NIH NHLBI R01HL064541 and Office of the Director R24OD024617 to W.M.D.; NIH NHLBI P01HL149620 and Office of the Director R24OD024617 to A.M.G.; Wellcome Trust WT222155/Z/20/Z to T.H.; NIH R01HG011252 to T.K.; Wellcome Trust WT222155/Z/20/Z to F.J.M.; NIH R01GM140287 to P.M.; a program from the National Institute for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, ID project no. LX22NPO5104 ) funded by the European Union \u2013 Next Generation EU to M.P.; NIH NIDA U01DA051234 to J.S.; NIH NHLBI R01HL064541 , NHGRI U24HG010859 , and Office of the Director R24OD024617 to J.R.S.; NIH NIDA P50DA037844 to L.C.S.W. (HS rats); NIH NIAAA R24AA013162 to B.T.; NIH NIDA U01DA050239 and U01DA051972 to F.T.; NIH NIDA P30DA044223 to L.S.; the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health to T.D.M.; NIH NHLBI R01HL064541 and P01HL149620 , NHGRI U24HG010859 , and Office of the Director R24OD024617 to A.E.K.; NIH Office of the Director grant R24OD024617 to M.R.D. (HRDP); NIH NIDA U01DA047638 and P30DA044223 to R.W.W.; NIH NIDA U01DA043098 to J.Z.L.; and NIH NIDA U01DA047638 , P50DA037844 , and R01DA048017 to H.C. The majority of the computation for this work was performed on the University of Tennessee Infrastructure for Scientific Applications and Advanced Computing (ISAAC) computational resources.

Funders	Funder number
US Department of Agriculture National Institute of Food and Agriculture, Agriculture and Food Research Initiative
University of Tennessee Infrastructure for Scientific Applications and Advanced Computing
Fair Isaac Corporation
U.S. National Library of Medicine
Research Council of Finland	343656
Research Council of Finland
Office of the Director	R24OD024617
Office of the Director
National Institutes of Health (NIH)	R01HG011252, R01DA048017, U01DA047638, R01GM140287
National Institutes of Health (NIH)
Wellcome Trust	WT222155/Z/20/Z
Wellcome Trust
NIH/NIDA	U01DA043098, U01DA051972
DBR/NIAAA/NIH	R24AA013162, U01DA050239, P30DA044223
National Heart, Lung, and Blood Institute (NHLBI)	P01HL149620, R01HL064541
National Heart, Lung, and Blood Institute (NHLBI)
U.S. Department of Agriculture	U01DA051234, 2016-67015-24470/2020-67015-31733/2022-51300-38058/2023-67015-39566/2023-67015-40080
U.S. Department of Agriculture
European Commission	U01DA051234
European Commission
National Institute for Research of Metabolic and Cardiovascular Diseases	LX22NPO5104
National Human Genome Research Institute	P50DA037844, U24HG010859
National Human Genome Research Institute

Keywords

Rnor_6.0
genetic map
heterogeneous stock
hybrid rat diversity panel
inbred strains
mRatBN7.2
phylogenetic tree
rat
recombinant inbred
reference genome

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Genetics

Access to Document

10.1016/j.xgen.2024.100527

Cite this

de Jong, T. V., Pan, Y., Rastas, P., Munro, D., Tutaj, M., Akil, H., Benner, C., Chen, D., Chitre, A. S., Chow, W., Colonna, V., Dalgard, C. L., Demos, W. M., Doris, P. A., Garrison, E., Geurts, A. M., Gunturkun, H. M., Guryev, V., Hourlier, T., ... Chen, H. (2024). A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats. Cell Genomics, 4(4), Article 100527. https://doi.org/10.1016/j.xgen.2024.100527

@article{054a938dc6fa4cf9afb85c0a5f9f8b4d,

title = "A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats",

abstract = "The seventh iteration of the reference genome assembly for Rattus norvegicus—mRatBN7.2—corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.",

keywords = "Rnor_6.0, genetic map, heterogeneous stock, hybrid rat diversity panel, inbred strains, mRatBN7.2, phylogenetic tree, rat, recombinant inbred, reference genome",

author = "{de Jong}, {Tristan V.} and Yanchao Pan and Pasi Rastas and Daniel Munro and Monika Tutaj and Huda Akil and Chris Benner and Denghui Chen and Chitre, {Apurva S.} and William Chow and Vincenza Colonna and Dalgard, {Clifton L.} and Demos, {Wendy M.} and Doris, {Peter A.} and Erik Garrison and Geurts, {Aron M.} and Gunturkun, {Hakan M.} and Victor Guryev and Thibaut Hourlier and Kerstin Howe and Jun Huang and Ted Kalbfleisch and Panjun Kim and Ling Li and Spencer Mahaffey and Martin, {Fergal J.} and Pejman Mohammadi and Ozel, {Ayse Bilge} and Oksana Polesskaya and Michal Pravenec and Pjotr Prins and Jonathan Sebat and Smith, {Jennifer R.} and {Solberg Woods}, {Leah C.} and Boris Tabakoff and Alan Tracey and Marcela Uliano-Silva and Flavia Villani and Hongyang Wang and Sharp, {Burt M.} and Francesca Telese and Zhihua Jiang and Laura Saba and Xusheng Wang and Murphy, {Terence D.} and Palmer, {Abraham A.} and Kwitek, {Anne E.} and Dwinell, {Melinda R.} and Williams, {Robert W.} and Li, {Jun Z.} and Hao Chen",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = apr,

day = "10",

doi = "10.1016/j.xgen.2024.100527",

language = "English",

volume = "4",

journal = "Cell Genomics",

issn = "2666-979X",

publisher = "Cell Press",

number = "4",

}

de Jong, TV, Pan, Y, Rastas, P, Munro, D, Tutaj, M, Akil, H, Benner, C, Chen, D, Chitre, AS, Chow, W, Colonna, V, Dalgard, CL, Demos, WM, Doris, PA, Garrison, E, Geurts, AM, Gunturkun, HM, Guryev, V, Hourlier, T, Howe, K, Huang, J, Kalbfleisch, T, Kim, P, Li, L, Mahaffey, S, Martin, FJ, Mohammadi, P, Ozel, AB, Polesskaya, O, Pravenec, M, Prins, P, Sebat, J, Smith, JR, Solberg Woods, LC, Tabakoff, B, Tracey, A, Uliano-Silva, M, Villani, F, Wang, H, Sharp, BM, Telese, F, Jiang, Z, Saba, L, Wang, X, Murphy, TD, Palmer, AA, Kwitek, AE, Dwinell, MR, Williams, RW, Li, JZ & Chen, H 2024, 'A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats', Cell Genomics, vol. 4, no. 4, 100527. https://doi.org/10.1016/j.xgen.2024.100527

TY - JOUR

T1 - A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

AU - de Jong, Tristan V.

AU - Pan, Yanchao

AU - Rastas, Pasi

AU - Munro, Daniel

AU - Tutaj, Monika

AU - Akil, Huda

AU - Benner, Chris

AU - Chen, Denghui

AU - Chitre, Apurva S.

AU - Chow, William

AU - Colonna, Vincenza

AU - Dalgard, Clifton L.

AU - Demos, Wendy M.

AU - Doris, Peter A.

AU - Garrison, Erik

AU - Geurts, Aron M.

AU - Gunturkun, Hakan M.

AU - Guryev, Victor

AU - Hourlier, Thibaut

AU - Howe, Kerstin

AU - Huang, Jun

AU - Kalbfleisch, Ted

AU - Kim, Panjun

AU - Li, Ling

AU - Mahaffey, Spencer

AU - Martin, Fergal J.

AU - Mohammadi, Pejman

AU - Ozel, Ayse Bilge

AU - Polesskaya, Oksana

AU - Pravenec, Michal

AU - Prins, Pjotr

AU - Sebat, Jonathan

AU - Smith, Jennifer R.

AU - Solberg Woods, Leah C.

AU - Tabakoff, Boris

AU - Tracey, Alan

AU - Uliano-Silva, Marcela

AU - Villani, Flavia

AU - Wang, Hongyang

AU - Sharp, Burt M.

AU - Telese, Francesca

AU - Jiang, Zhihua

AU - Saba, Laura

AU - Wang, Xusheng

AU - Murphy, Terence D.

AU - Palmer, Abraham A.

AU - Kwitek, Anne E.

AU - Dwinell, Melinda R.

AU - Williams, Robert W.

AU - Li, Jun Z.

AU - Chen, Hao

PY - 2024/4/10

Y1 - 2024/4/10

N2 - The seventh iteration of the reference genome assembly for Rattus norvegicus—mRatBN7.2—corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

AB - The seventh iteration of the reference genome assembly for Rattus norvegicus—mRatBN7.2—corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

KW - Rnor_6.0

KW - genetic map

KW - heterogeneous stock

KW - hybrid rat diversity panel

KW - inbred strains

KW - mRatBN7.2

KW - phylogenetic tree

KW - rat

KW - recombinant inbred

KW - reference genome

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UR - http://www.scopus.com/inward/citedby.url?scp=85189630510&partnerID=8YFLogxK

U2 - 10.1016/j.xgen.2024.100527

DO - 10.1016/j.xgen.2024.100527

M3 - Article

AN - SCOPUS:85189630510

SN - 2666-979X

VL - 4

JO - Cell Genomics

JF - Cell Genomics

IS - 4

M1 - 100527

ER -

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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