title: Efficient analysis of mouse genome sequences reveal many nonsense variants.
abstract: Genetic polymorphisms in coding genes play an important role when using mouse inbred strains as research models. They have been shown to influence research results, explain phenotypical differences between inbred strains, and increase the amount of interesting gene variants present in the many available inbred lines. SPRET/Ei is an inbred strain derived from Mus spretus that has ∼1% sequence difference with the C57BL/6J reference genome. We obtained a listing of all SNPs and insertions/deletions (indels) present in SPRET/Ei from the Mouse Genomes Project (Wellcome Trust Sanger Institute) and processed these data to obtain an overview of all transcripts having nonsynonymous coding sequence variants. We identified 8,883 unique variants affecting 10,096 different transcripts from 6,328 protein-coding genes, which is about 28% of all coding genes. Because only a subset of these variants results in drastic changes in proteins, we focused on variations that are nonsense mutations that ultimately resulted in a gain of a stop codon. These genes were identified by in silico changing the C57BL/6J coding sequences to the SPRET/Ei sequences, converting them to amino acid (AA) sequences, and comparing the AA sequences. All variants and transcripts affected were also stored in a database, which can be browsed using a SPRET/Ei M. spretus variants web tool (www.spretus.org), including a manual. We validated the tool by demonstrating the loss of function of three proteins predicted to be severely truncated, namely Fas, IRAK2, and IFNγR1.
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium;
authors.forename: Sophie
authors.initials: S
authors.lastname: Steeland
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium;
authors.forename: Steven
authors.initials: S
authors.lastname: Timmermans
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium;
authors.forename: Sara
authors.initials: S
authors.lastname: Van Ryckeghem
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium;
authors.forename: Paco
authors.initials: P
authors.lastname: Hulpiau
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Internal Medicine, Ghent University, 9052 Ghent, Belgium;
authors.forename: Yvan
authors.initials: Y
authors.lastname: Saeys
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Ghent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium; International Plant Biotechnology Outreach, VIB, Ghent, Belgium marc.vanmontagu@ugent.be claude.libert@irc.vib-ugent.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Van Montagu
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium;
authors.forename: Roosmarijn E
authors.initials: RE
authors.lastname: Vandenbroucke
authors.affiliation: Inflammation Research Center, Flanders Institute for Biotechnology (VIB), 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium; marc.vanmontagu@ugent.be claude.libert@irc.vib-ugent.be.
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
mesh_terms: D000818:Animals; D018389:Codon, Nonsense; D063990:Gene Ontology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017471:Receptors, Interferon / Q000502:physiology; D019014:fas Receptor / Q000502:physiology; D000096743:Interferon gamma Receptor
chemical_list: D018389:Codon, Nonsense; D053592:Interleukin-1 Receptor-Associated Kinases; D017471:Receptors, Interferon; D019014:fas Receptor; D000096743:Interferon gamma Receptor; C491899:Fas protein, mouse
keywords: bioinformatics; genomics; inflammation; mouse; mutations