title: The genome of the chicken DT40 bursal lymphoma cell line.
abstract: The chicken DT40 cell line is a widely used model system in the study of multiple cellular processes due to the efficiency of homologous gene targeting. The cell line was derived from a bursal lymphoma induced by avian leukosis virus infection. In this study we characterized the genome of the cell line using whole genome shotgun sequencing and single nucleotide polymorphism array hybridization. The results indicate that wild-type DT40 has a relatively normal karyotype, except for whole chromosome copy number gains, and no karyotype variability within stocks. In a comparison to two domestic chicken genomes and the Gallus gallus reference genome, we found no unique mutational processes shaping the DT40 genome except for a mild increase in insertion and deletion events, particularly deletions at tandem repeats. We mapped coding sequence mutations that are unique to the DT40 genome; mutations inactivating the PIK3R1 and ATRX genes likely contributed to the oncogenic transformation. In addition to a known avian leukosis virus integration in the MYC gene, we detected further integration sites that are likely to de-regulate gene expression. The new findings support the hypothesis that DT40 is a typical transformed cell line with a relatively intact genome; therefore, it is well-suited to the role of a model system for DNA repair and related processes. The sequence data generated by this study, including a searchable de novo genome assembly and annotated lists of mutated genes, will support future research using this cell line.
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Póti
authors.affiliation: Department of Physics of Complex Systems, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Pipek
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Marcin
authors.initials: M
authors.lastname: Krzystanek
authors.affiliation: Cancer Research UK London Research Institute, London, WCA2 3PX, United Kingdom.
authors.forename: Nnennaya
authors.initials: N
authors.lastname: Kanu
authors.affiliation: Cancer Research UK London Research Institute, London, WCA2 3PX, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary.
authors.forename: Gábor E
authors.initials: GE
authors.lastname: Tusnády
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark Children's Hospital Informatics Program at the Harvard-Massachusetts Institutes of Technology Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, MA 02115.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szallasi
authors.affiliation: Department of Physics of Complex Systems, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Csabai
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Budapest, Hungary szuts.david@ttk.mta.hu.
authors.forename: Dávid
authors.initials: D
authors.lastname: Szüts
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002645:Chickens; D004265:DNA Helicases / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D059785:Karyotype; D008223:Lymphoma / Q000235:genetics*; D016254:Mutagenesis, Insertional; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D019869:Phosphatidylinositol 3-Kinases; D004265:DNA Helicases
keywords: DT40; chicken genome; gene targeting; single nucleotide polymorphism; tumor suppressor gene