title: Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat.
abstract: Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, along with their respective control strains. Altogether, we identified more than 13 million single-nucleotide variants, indels, and structural variants across these rat strains. Analysis of strain-specific selective sweeps and gene clusters implicated genes and pathways involved in cation transport, angiotensin production, and regulators of oxidative stress in the development of cardiovascular disease phenotypes in rats. Many of the rat loci that we identified overlap with previously mapped loci for related traits in humans, indicating the presence of shared pathways underlying these phenotypes in rats and humans. These data represent a step change in resources available for evolutionary analysis of complex traits in disease models.
authors.affiliation: Physiological Genomic and Medicine Group, MRC Clinical Sciences Centre, Imperial College London, London W12 0NN, UK.
authors.forename: Santosh S
authors.initials: SS
authors.lastname: Atanur
authors.forename: Ana Garcia
authors.initials: AG
authors.lastname: Diaz
authors.forename: Klio
authors.initials: K
authors.lastname: Maratou
authors.forename: Allison
authors.initials: A
authors.lastname: Sarkis
authors.forename: Maxime
authors.initials: M
authors.lastname: Rotival
authors.forename: Laurence
authors.initials: L
authors.lastname: Game
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tschannen
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Kaisaki
authors.forename: Georg W
authors.initials: GW
authors.lastname: Otto
authors.forename: Man Chun John
authors.initials: MC
authors.lastname: Ma
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Keane
authors.forename: Oliver
authors.initials: O
authors.lastname: Hummel
authors.forename: Kathrin
authors.initials: K
authors.lastname: Saar
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.forename: Kathirvel
authors.initials: K
authors.lastname: Gopalakrishnan
authors.forename: Michael R
authors.initials: MR
authors.lastname: Garrett
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.forename: Lorena
authors.initials: L
authors.lastname: Citterio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Martin
authors.initials: M
authors.lastname: McBride
authors.forename: Anna
authors.initials: A
authors.lastname: Dominiczak
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Anne
authors.initials: A
authors.lastname: Kwitek
authors.forename: Howard
authors.initials: H
authors.lastname: Jacob
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016678:Genome; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D051381:Rats / Q000145:classification* / Q000235:genetics*; D011919:Rats, Inbred Strains
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