title: The IGF1 small dog haplotype is derived from Middle Eastern grey wolves.
abstract: BACKGROUND
  A selective sweep containing the insulin-like growth factor 1 (IGF1) gene is associated with size variation in domestic dogs. Intron 2 of IGF1 contains a SINE element and single nucleotide polymorphism (SNP) found in all small dog breeds that is almost entirely absent from large breeds. In this study, we surveyed a large sample of grey wolf populations to better understand the ancestral pattern of variation at IGF1 with a particular focus on the distribution of the small dog haplotype and its relationship to the origin of the dog.
  
  
  RESULTS
  We present DNA sequence data that confirms the absence of the derived small SNP allele in the intron 2 region of IGF1 in a large sample of grey wolves and further establishes the absence of a small dog associated SINE element in all wild canids and most large dog breeds. Grey wolf haplotypes from the Middle East have higher nucleotide diversity suggesting an origin there. Additionally, PCA and phylogenetic analyses suggests a closer kinship of the small domestic dog IGF1 haplotype with those from Middle Eastern grey wolves.
  
  
  CONCLUSIONS
  The absence of both the SINE element and SNP allele in grey wolves suggests that the mutation for small body size post-dates the domestication of dogs. However, because all small dogs possess these diagnostic mutations, the mutations likely arose early in the history of domestic dogs. Our results show that the small dog haplotype is closely related to those in Middle Eastern wolves and is consistent with an ancient origin of the small dog haplotype there. Thus, in concordance with past archeological studies, our molecular analysis is consistent with the early evolution of small size in dogs from the Middle East.See associated opinion by Driscoll and Macdonald: http://jbiol.com/content/9/2/10.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, USA. mgray9@ucla.edu
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Gray
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Sutter
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Robert K
authors.initials: RK
authors.lastname: Wayne
mesh_terms: D000818:Animals; D004285:Dogs / Q000145:classification / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008877:Middle East; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D011995:Recombination, Genetic / Q000235:genetics; D013002:Somatomedins / Q000145:classification / Q000235:genetics*; D019596:Wolves / Q000145:classification / Q000235:genetics*
chemical_list: D013002:Somatomedins