title: Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates.
abstract: BACKGROUND
  The laboratory rat (Rattus norvegicus) is an important model for studying many aspects of human health and disease. Detailed knowledge on genetic variation between strains is important from a biomedical, particularly pharmacogenetic point of view and useful for marker selection for genetic cloning and association studies.
  
  
  RESULTS
  We show that Single Nucleotide Polymorphisms (SNPs) in commonly used rat strains are surprisingly well represented in wild rat isolates. Shotgun sequencing of 814 Kbp in one wild rat resulted in the identification of 485 SNPs as compared with the Brown Norway genome sequence. Genotyping 36 commonly used inbred rat strains showed that 84% of these alleles are also polymorphic in a representative set of laboratory rat strains.
  
  
  CONCLUSIONS
  We postulate that shotgun sequencing in a wild rat sample and subsequent genotyping in multiple laboratory or domesticated strains rather than direct shotgun sequencing of multiple strains, could be the most efficient SNP discovery approach. For the rat, laboratory strains still harbor a large portion of the haplotypes present in wild isolates, suggesting a relatively recent common origin and supporting the idea that rat inbred strains, in contrast to mouse inbred strains, originate from a single species, R. norvegicus.
authors.affiliation: Hubrecht Laboratory, Functional Genomics Group, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. smits@niob.knaw.nl
authors.forename: Bart M G
authors.initials: BM
authors.lastname: Smits
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.forename: Dimphy
authors.initials: D
authors.lastname: Zeegers
authors.forename: Dirk
authors.initials: D
authors.lastname: Wedekind
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hedrich
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
mesh_terms: D000818:Animals; D001331:Automation; D004247:DNA / Q000378:metabolism; D015723:Gene Library; D005821:Genetic Techniques; D016678:Genome; D005838:Genotype; D006239:Haplotypes; D051379:Mice; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D004247:DNA