title: An improved canine genome and a comprehensive catalogue of coding genes and non-coding transcripts.
abstract: The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog ∼175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional ∼3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to ∼20,700 high-confidence protein coding loci, we found ∼4,600 antisense transcripts overlapping exons of protein coding genes, ∼7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and ∼11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.
authors.affiliation: Science for Life Laboratories, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hoeppner
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America; Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lundquist
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Mono
authors.initials: M
authors.lastname: Pirun
authors.affiliation: Science for Life Laboratories, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Jennifer R S
authors.initials: JR
authors.lastname: Meadows
authors.affiliation: Science for Life Laboratories, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Neda
authors.initials: N
authors.lastname: Zamani
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Science for Life Laboratories, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Görel
authors.initials: G
authors.lastname: Sundström
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: April
authors.initials: A
authors.lastname: Cook
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: FitzGerald
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Ross
authors.initials: R
authors.lastname: Swofford
authors.affiliation: Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Evan
authors.initials: E
authors.lastname: Mauceli
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Behrooz Torabi
authors.initials: BT
authors.lastname: Moghadam
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Greka
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Alföldi
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Amr
authors.initials: A
authors.lastname: Abouelleil
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Lynne
authors.initials: L
authors.lastname: Aftuck
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bessette
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Berlin
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Brown
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Gearin
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Annie
authors.initials: A
authors.lastname: Lui
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: J Pendexter
authors.initials: JP
authors.lastname: Macdonald
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Margaret
authors.initials: M
authors.lastname: Priest
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Terrance
authors.initials: T
authors.lastname: Shea
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Turner-Maier
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America; Vertebrate and Health Genomics, The Genome Analysis Centre, Norwich, United Kingdom.
authors.forename: Federica
authors.initials: F
authors.lastname: di Palma
authors.affiliation: Science for Life Laboratories, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.affiliation: Science for Life Laboratories, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Manfred G
authors.initials: MG
authors.lastname: Grabherr
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs / Q000235:genetics*; D005091:Exons; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D050199:Podocytes / Q000166:cytology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D022661:RNA, Untranslated; D017423:Sequence Analysis, RNA
chemical_list: C119539:BAIAP2 protein, human; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022661:RNA, Untranslated