title: A high-density SNP panel reveals extensive diversity, frequent recombination and multiple recombination hotspots within the chicken major histocompatibility complex B region between BG2 and CD1A1.
abstract: BACKGROUND
  The major histocompatibility complex (MHC) is present within the genomes of all jawed vertebrates. MHC genes are especially important in regulating immune responses, but even after over 80 years of research on the MHC, much remains to be learned about how it influences adaptive and innate immune responses. In most species, the MHC is highly polymorphic and polygenic. Strong and highly reproducible associations are established for chicken MHC-B haplotypes in a number of infectious diseases. Here, we report (1) the development of a high-density SNP (single nucleotide polymorphism) panel for MHC-B typing that encompasses a 209,296 bp region in which 45 MHC-B genes are located, (2) how this panel was used to define chicken MHC-B haplotypes within a large number of lines/breeds and (3) the detection of recombinants which contributes to the observed diversity.
  
  
  METHODS
  A SNP panel was developed for the MHC-B region between the BG2 and CD1A1 genes. To construct this panel, each SNP was tested in end-point read assays on more than 7500 DNA samples obtained from inbred and commercially used egg-layer lines that carry known and novel MHC-B haplotypes. One hundred and one SNPs were selected for the panel. Additional breeds and experimentally-derived lines, including lines that carry MHC-B recombinant haplotypes, were then genotyped.
  
  
  RESULTS
  MHC-B haplotypes based on SNP genotyping were consistent with the MHC-B haplotypes that were assigned previously in experimental lines that carry B2, B5, B12, B13, B15, B19, B21, and B24 haplotypes. SNP genotyping resulted in the identification of 122 MHC-B haplotypes including a number of recombinant haplotypes, which indicate that crossing-over events at multiple locations within the region lead to the production of new MHC-B haplotypes. Furthermore, evidence of gene duplication and deletion was found.
  
  
  CONCLUSIONS
  The chicken MHC-B region is highly polymorphic across the surveyed 209-kb region that contains 45 genes. Our results expand the number of identified haplotypes and provide insights into the contribution of recombination events to MHC-B diversity including the identification of recombination hotspots and an estimation of recombination frequency.
authors.affiliation: Hy-Line International, Dallas Center, IA, USA. jfulton@hyline.com.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Fulton
authors.affiliation: Hy-Line International, Dallas Center, IA, USA. amccarron@hyline.com.
authors.forename: Amy M
authors.initials: AM
authors.lastname: McCarron
authors.affiliation: Hy-Line International, Dallas Center, IA, USA. alund@hyline.com.
authors.forename: Ashlee R
authors.initials: AR
authors.lastname: Lund
authors.affiliation: Hy-Line International, Dallas Center, IA, USA. kpinegar@hyline.com.
authors.forename: Kara N
authors.initials: KN
authors.lastname: Pinegar
authors.affiliation: Hy-Line International, Dallas Center, IA, USA. awolc@iastate.edu.|Iowa State University, 239C Kildee, Ames, IA, 50011, USA. awolc@iastate.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolc
authors.affiliation: Department of Pathology and Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. oc248@cam.ac.uk.|Génétique Animale et Biologie Intégrative, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France. oc248@cam.ac.uk.
authors.forename: Olympe
authors.initials: O
authors.lastname: Chazara
authors.affiliation: Génétique Animale et Biologie Intégrative, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France. bertrand.bedhom@jouy.inra.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bed'Hom
authors.affiliation: Department of Animal Sciences, University of Wisconsin, Madison, USA. meberres@wisc.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Berres
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA. mamiller@coh.org.
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Miller
mesh_terms: D000818:Animals; D002645:Chickens / Q000235:genetics*; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D012641:Selection, Genetic