, Volume 62, Issue 7, pp 465–477

Haplotype variation, recombination, and gene conversion within the turkey MHC-B locus

  • Lee D. Chaves
  • Gretchen M. Faile
  • Stacy B. Krueth
  • Julie A. Hendrickson
  • Kent M. Reed
Original Paper


The major histocompatibility complex (MHC) is a gene dense region with profound effects on the disease phenotype. In many species, characterizations of MHC polymorphisms have focused on identifying allelic haplotypes of the highly polymorphic class I and class II loci through direct immunological approaches such as monoclonal antibodies specific for the major antigens or indirectly through DNA sequence-based approaches. Invariably, these studies fail to assess the broader range of variation at the other loci within the MHC. This study examines variation in the turkey MHC by resequencing 15 interspersed amplicons (∼14 kb) spaced across the MHC-B locus in a representative sampling of 52 commercial birds. Over 200 single nucleotide polymorphisms (SNPs) were identified with high levels of polymorphism (1 SNP/70 bp) and heterozygosity (average minor allele frequency of 0.15). SNP genotypes were used to identify the major haplotypes segregating in the commercial lines. Sequencing of the peptide binding region (PBR, exon 2) of the class IIB loci of select individuals identified 10 PBR alleles/isotypes among the major MHC haplotypes. Examination of pedigreed families provides direct evidence of gene conversion and recombination within the B locus. Results of this study demonstrate the MHC diversity available in commercial flocks and provide genomic resources for studying the effect of this diversity (alleles and/or haplotypes) on disease susceptibility and resistance.


Turkey MHC SNP Haplotype Recombination 

Supplementary material

251_2010_451_MOESM1_ESM.doc (262 kb)
Supplemental Table 1FastPHASE MHC haplotypes reconstructed from 49 SNP loci. Reference SNP positions are based on Genbank # DQ993255. Individuals marked in bold were homozygous at all SNPs. (DOC 262 kb)


  1. Afanassieff M, Goto RM, Ha J, Sherman MA, Zhong L, Auffray C, Coudert F, Zoorob R, Miller MM (2001) At least one class I gene in restriction fragment pattern-Y (Rfp-Y), the second MHC gene cluster in the chicken, is transcribed, polymorphic, and shows divergent specialization in antigen binding region. J Immunol 166:3324–3333PubMedGoogle Scholar
  2. Ahmed KA, Saxena VK, Saxena M, Ara A, Pramod AB, Rajaram ML, Dorman KS, Majumdar S, Rasool TJ (2007) Molecular cloning and sequencing of MHC class II beta 1 domain of turkey reveals high sequence identity with chicken. Int J Immunogenet 34:97–105CrossRefPubMedGoogle Scholar
  3. Belov K, Deakin JE, Papenfuss AT, Baker ML, Melman SD, Siddle HV, Gouin N, Goode DL, Sargeant TJ, Robinson MD, Wakefield MJ, Mahony S, Cross JG, Benos PV, Samollow PB, Speed TP, Graves JA, Miller RD (2006) Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex. PLoS Biol 4:e46CrossRefPubMedGoogle Scholar
  4. Bloom SE, Bacon LD (1985) Linkage of the major histocompatibility (B) complex and the nucleolar organizer in the chicken. Assignment to a microchromosome. J Hered 76:146–154PubMedGoogle Scholar
  5. Briles WE, Briles RW, Taffs RE, Stone HA (1983) Resistance to a malignant lymphoma in chickens is mapped to subregion of major histocompatibility (B) complex. Science 219:977–979CrossRefPubMedGoogle Scholar
  6. Briles WE, Goto RM, Auffray C, Miller MM (1993) A polymorphic system related to but genetically independent of the chicken major histocompatibility complex. Immunogenetics 37:408–414CrossRefPubMedGoogle Scholar
  7. Chaves LD, Rowe JA, Reed KM (2005) Survey of a cDNA library from the turkey (Meleagris gallopavo). Genome 48:12–17CrossRefPubMedGoogle Scholar
  8. Chaves LD, Krueth SB, Reed KM (2007) Characterization of the turkey MHC chromosome through genetic and physical mapping. Cytogenet Genome Res 117:213–220CrossRefPubMedGoogle Scholar
  9. Chaves LD, Harry DE, Reed KM (2009a) Genome-wide genetic diversity of ‘Nici’, the DNA source for the CHORI-260 turkey BAC library and candidate for whole genome sequencing. Anim Genet 40:348–352CrossRefPubMedGoogle Scholar
  10. Chaves LD, Krueth SB, Reed KM (2009b) Defining the turkey MHC: sequence and genes of the B Locus. J Immunol 183:6530–6537CrossRefPubMedGoogle Scholar
  11. Delany ME, Robinson CM, Goto RM, Miller MM (2009) Architecture and organization of chicken microchromosome 16: order of the NOR, MHC-Y, and MHC-B subregions. J Hered 100:507–514CrossRefPubMedGoogle Scholar
  12. Fillon V, Zoorob R, Yerle M, Auffray C, Vignal A (1996) Mapping of the genetically independent chicken major histocompatibility complexes B@ and RFP-Y@ to the same microchromosome by two-color fluorescent in situ hybridization. Cytogenet Cell Genet 75:7–9CrossRefPubMedGoogle Scholar
  13. Fulton J, Juul-Madsen H, Ashwell C, McCarron A, Arthur J, O'Sullivan N, Taylor R (2006) Molecular genotype identification of the Gallus gallus major histocompatibility complex. Immunogenetics 58:407–421CrossRefPubMedGoogle Scholar
  14. Goto RM, Afanassieff M, Ha J, Iglesias GM, Ewald SJ, Briles WE, Miller MM (2002) Single-strand conformation polymorphism (SSCP) assays for major histocompatibility complex B genotyping in chickens. Poult Sci 81:1832–1841PubMedGoogle Scholar
  15. Green P, Falls K, Crooks S (1990) Documentation for CRIMAP, version 2.4. Washington University School of Medicine, St. Louis. Ref Type: Computer ProgramGoogle Scholar
  16. Guillemot F, Billault A, Pourquié O, Béhar G, Chaussé AM, Zoorob R, Kreibich G, Auffray C (1988) A molecular map of the chicken major histocompatibility complex: the class II beta genes are closely linked to the class I genes and the nucleolar organizer. EMBO J 7:2775–2785PubMedGoogle Scholar
  17. Hala K, Vilhelmova M, Schulmannova J, Plachy J (1979) A new recombinant allele in the B complex of the chicken [proceedings]. Folia Biol (Praha) 25:323–324Google Scholar
  18. Hala K, Chausse AM, Bourlet Y, Lassila O, Hasler V, Auffray C (1988) Attempt to detect recombination between B-F and B-L genes within the chicken B complex by serological typing, in vitro MLR, and RFLP analyses. Immunogenetics 28:433–438CrossRefPubMedGoogle Scholar
  19. Harry DE, Zaitlin D, Marini PJ, Reed KM (2003) A first-generation map of the turkey genome. Genome 46:914–924CrossRefPubMedGoogle Scholar
  20. Högstrand K, Böhme J (1999) Gene conversion can create new MHC alleles. Immunol Rev 167:305–317CrossRefPubMedGoogle Scholar
  21. Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, Khodiyar VK, Lush MJ, Povey S, Talbot CC Jr, Wright MW, Wain HM, Trowsdale J, Ziegler A, Beck S (2004) Gene map of the extended human MHC. Nat Rev Genet 5:889–899CrossRefPubMedGoogle Scholar
  22. Horton R, Gibson R, Coggill P, Miretti M, Allcock RJ, Almeida J, Forbes S, Gilbert JG, Halls K, Harrow JL, Hart E, Howe K, Jackson DK, Palmer S, Roberts AN, Sims S, Stewart CA, Traherne JA, Trevanion S, Wilming L, Rogers J, de Jong PJ, Elliott JF, Sawcer S, Todd JA, Trowsdale J, Beck S (2008) Variation analysis and gene annotation of eight MHC haplotypes: the MHC haplotype project. Immunogenetics 60:1–18CrossRefPubMedGoogle Scholar
  23. Hosomichi K, Miller MM, Goto RM, Wang Y, Suzuki S, Kulski JK, Nishibori M, Inoko H, Hanzawa K, Shiina T (2008) Contribution of mutation, recombination, and gene conversion to chicken MHC-B haplotype diversity. J Immunol 181:3393–3399PubMedGoogle Scholar
  24. Jacob JP, Milne S, Beck S, Kaufman J (2000) The major and a minor class II beta-chain (B-LB) gene flank the Tapasin gene in the B-F/B-L region of the chicken major histocompatibility complex. Immunogenetics 51:138–147CrossRefPubMedGoogle Scholar
  25. Kaufman J, Völk H, Wallny HJ (1995) A “minimal essential Mhc” and an “unrecognized Mhc”: two extremes in selection for polymorphism. Immunol Rev 143:63–88CrossRefPubMedGoogle Scholar
  26. Kaufman J, Jacob J, Shaw I, Walker B, Milne S, Beck S, Salomonsen J (1999a) Gene organisation determines evolution of function in the chicken MHC. Immunol Rev 167:101–117CrossRefPubMedGoogle Scholar
  27. Kaufman J, Milne S, Gobel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999b) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401:923–925CrossRefPubMedGoogle Scholar
  28. Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695CrossRefPubMedGoogle Scholar
  29. Kim DK, Lillehoj HS, Hong YH, Park DW, Lamont SJ, Han JY, Lillehoj EP (2008) Immune-related gene expression in two B-complex disparate genetically inbred Fayoumi chicken lines following Eimeria maxima infection. Poult Sci 87:433–443CrossRefPubMedGoogle Scholar
  30. Koch C, Skjodt K, Toivanen A, Toivanen P (1983) New recombinants within the MHC (B-complex) of the chicken. Tissue Antigens 21:129–137PubMedGoogle Scholar
  31. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948CrossRefPubMedGoogle Scholar
  32. Li L, Johnson LW, Livant EJ, Ewald SJ (1999) The MHC of a broiler chicken line: serology, B–G genotypes, and B-F/B-LB sequences. Immunogenetics 49:215–224CrossRefPubMedGoogle Scholar
  33. Livant EJ, Brigati JR, Ewald SJ (2004) Diversity and locus specificity of chicken MHC B class I sequences. Anim Genet 35:18–27CrossRefPubMedGoogle Scholar
  34. Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Geraghty DE, Hansen JA, Hurley CK, Mach B, Mayr WR, Parham P, Petersdorf EW, Sasazuki T, Schreuder GM, Strominger JL, Svejgaard A, Terasaki PI, Trowsdale J (2005) Nomenclature for factors of the HLA system, 2004. Int J Immunogenet 32:107–159CrossRefPubMedGoogle Scholar
  35. Miller HC, Lambert DM (2004) Gene duplication and gene conversion in class II MHC genes of New Zealand robins (Petroicidae). Immunogenetics 56:178–191PubMedGoogle Scholar
  36. Miller MM, Goto RM, Taylor RL Jr, Zoorob R, Auffray C, Briles RW, Briles WE, Bloom SE (1996) Assignment of Rfp-Y to the chicken major histocompatibility complex/NOR microchromosome and evidence for high-frequency recombination associated with the nucleolar organizer region. Proc Natl Acad Sci U S A 93:3958–3962CrossRefPubMedGoogle Scholar
  37. Miller MM, Bacon LD, Hala K, Hunt HD, Ewald SJ, Kaufman J, Zoorob R, Briles WE (2004) Nomenclature for the chicken major histocompatibility (B and Y) complex. Immunogenetics 56:261–279PubMedGoogle Scholar
  38. O'Neill AM, Livant EJ, Ewald SJ (2009) The chicken BF1 (classical MHC class I) gene shows evidence of selection for diversity in expression and in promoter and signal peptide regions. Immunogenetics 61:289–302CrossRefPubMedGoogle Scholar
  39. Reed KM, Chaves LD, Garbe JR, Da Y, Harry DE (2003) Allelic variation and genetic linkage of avian microsatellites in a new turkey population for genetic mapping. Cytogenet Genome Res 102:331–339CrossRefPubMedGoogle Scholar
  40. Reed KM, Hall MK, Chaves LD, Knutson TP (2006) Single nucleotide polymorphisms for integrative mapping in the Turkey (Meleagris gallopavo). Anim Biotechnol 17:73–80CrossRefPubMedGoogle Scholar
  41. Reed KM, Chaves LD, Mendoza KM (2007) An integrated and comparative genetic map of the turkey genome. Cytogenet Genome Res 119:113–126CrossRefPubMedGoogle Scholar
  42. Rogers SL, Kaufman J (2008) High allelic polymorphism, moderate sequence diversity and diversifying selection for B-NK but not B-lec, the pair of lectin-like receptor genes in the chicken MHC. Immunogenetics 60:461–475CrossRefPubMedGoogle Scholar
  43. Rogers S, Shaw I, Ross N, Nair V, Rothwell L, Kaufman J, Kaiser P (2003) Analysis of part of the chicken Rfp-Y region reveals two novel lectin genes, the first complete genomic sequence of a class I alpha-chain gene, a truncated class II beta-chain gene, and a large CR1 repeat. Immunogenetics 55:100–108PubMedGoogle Scholar
  44. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425PubMedGoogle Scholar
  45. Shaw I, Powell TJ, Marston DA, Baker K, van Hateren A, Riegert P, Wiles MV, Milne S, Beck S, Kaufman J (2007) Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens. J Immunol 178:5744–5752PubMedGoogle Scholar
  46. Shiina T, Shimizu S, Hosomichi K, Kohara S, Watanabe S, Hanzawa K, Beck S, Kulski JK, Inoko H (2004) Comparative genomic analysis of two avian (quail and chicken) MHC regions. J Immunol 172:6751–6763PubMedGoogle Scholar
  47. Simonsen M, Crone M, Koch C, Hala K (1982) The MHC haplotypes of the chicken. Immunogenetics 16:513–532CrossRefPubMedGoogle Scholar
  48. Sironi L, Lazzari B, Ramelli P, Gorni C, Mariani P (2006) Single nucleotide polymorphism discovery in the avian Tapasin gene. Poult Sci 85:606–612PubMedGoogle Scholar
  49. Sironi L, Lazzari B, Ramelli P, Stella A, Mariani P (2008) Avian TAP genes: detection of nucleotide polymorphisms and comparative analysis across species. Genet Mol Res 7:1267–1281CrossRefPubMedGoogle Scholar
  50. Skjodt K, Koch C, Crone M, Simonsen M (1985) Analysis of chickens for recombination within the MHC (B-complex). Tissue Antigens 25:278–282PubMedCrossRefGoogle Scholar
  51. Stephens M, Donnelly P (2003) A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162–1169CrossRefPubMedGoogle Scholar
  52. Takagi Y, Kuramoto T, Voigt B, Tsurumi T, Nakanishi S, Mashimo T, Masui N, Serikawa T (2009) An informative set of SSLP markers and genomic profiles in the rat MHC, the RT1 complex. Immunogenetics 61:189–197CrossRefPubMedGoogle Scholar
  53. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599CrossRefPubMedGoogle Scholar
  54. Taylor RL Jr (2004) Major histocompatibility (B) complex control of responses against Rous sarcomas. Poult Sci 83:638–649PubMedGoogle Scholar
  55. Wallny HJ, Avila D, Hunt LG, Powell TJ, Riegert P, Salomonsen J, Skjødt K, Vainio O, Vilbois F, Wiles MV, Kaufman J (2006) Peptide motifs of the single dominantly expressed class I molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens. Proc Natl Acad Sci U S A 103:1434–1439CrossRefPubMedGoogle Scholar
  56. Wittzell H, Bernot A, Auffray C, Zoorob R (1999) Concerted evolution of two MHC class II B loci in pheasants and domestic chickens. Mol Biol Evol 16:479–490PubMedGoogle Scholar
  57. Zhu J, Nestor KE, Tang Y (1996) Frequencies and genetic diversity of major histocompatibility complex class II haplotypes in commercial turkey lines. Poult Sci 75:954–958PubMedGoogle Scholar
  58. Zuckerkandl E, Pauling L (1965) Evolutionary divergence and onvergence in proteins. In: Bryson V, Vogel HJ (eds) Evolving genes and proteins. Academic, New York, pp 97–166Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Lee D. Chaves
    • 2
  • Gretchen M. Faile
    • 1
  • Stacy B. Krueth
    • 1
  • Julie A. Hendrickson
    • 1
  • Kent M. Reed
    • 1
  1. 1.Department of Veterinary and Biomedical Sciences, College of Veterinary MedicineUniversity of MinnesotaSt PaulUSA
  2. 2.Division of Allergy & Clinical Immunology, Department of MedicineNational Jewish HealthDenverUSA

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