Immunogenetics

, Volume 70, Issue 5, pp 305–315 | Cite as

MHC haplotype diversity in Persian Arabian horses determined using polymorphic microsatellites

Original Article

Abstract

Previous research on the equine major histocompatibility complex (MHC) demonstrated strong correlations between haplotypes defined by polymorphic intra-MHC microsatellites and haplotypes defined using classical serology. Here, we estimated MHC diversity in a sample of 124 Arabian horses from an endangered strain native to Iran (Persian Asil Arabians), using a validated 10-marker microsatellite panel. In a group of 66 horses related as parent-offspring pairs or half-sibling groups, we defined 51 MHC haplotypes, 49 of which were new. In 47 of the remaining 58 unrelated horses, we could assign one previously identified MHC haplotype, and by default, we gave provisional haplotype status to the remaining constellation of microsatellite alleles. In these horses, we found 21 haplotypes that we had previously defined and 31 provisional haplotypes, two of which had been identified in an earlier study. This gave a total of 78 new MHC haplotypes. The final 11 horses were MHC heterozygotes that we could not phase using information from any of the previously validated or provisional haplotypes. However, we could determine that these horses carried a total of 22 different undefined haplotypes. In the overall population sample, we detected three homozygous horses and one maternally inherited recombinant from 21 informative segregations. Virtually all of the horses tested were MHC heterozygotes, and most unrelated horses (98%) were heterozygous for rare microsatellite-defined haplotypes found less than three times in the sampled horses. This is evidence for a very high level of MHC haplotype variation in the Persian Asil Arabian horse.

Keywords

MHC Microsatellite Haplotype diversity Horse Recombination rate 

Abbreviations

MHC

Major histocompatibility complex

ELA

Equine leukocyte antigen

FAO

Food and Agriculture Organization

Notes

Acknowledgments

We gratefully acknowledge horse owners who permitted us to obtain samples for DNA analysis. This work was supported in part by the Harry M. Zweig Memorial Fund for New York State and the Morris Animal Foundation. DFA is an Investigator of the Dorothy Russell Havemeyer Foundation, Inc.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal welfare

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

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References

  1. Aguilar A, Roemer G, Debenham S, Binns M, Garcelon D, Wayne RK (2004) High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. Proc Natl Acad Sci U S A 101:3490–3494CrossRefPubMedPubMedCentralGoogle Scholar
  2. Albright-Fraser DG, Reid R, Gerber V, Bailey E (1996) Polymorphism of DRA among equids. Immunogenetics 43:315–317PubMedGoogle Scholar
  3. Almarzook S, Reissmann M, Brockmann GA (2017) Diversity of mitochondrial DNA in three Arabian horse strains. J Appl Genet 58:273–276CrossRefPubMedGoogle Scholar
  4. Andersson LS, Swinburne JE, Meadows JR, Brostrom H, Eriksson S, Fikse WF, Frey R, Sundquist M, Tseng CT, Mikko S, Lindgren G (2012) The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations. Immunogenetics 64:201–208CrossRefPubMedGoogle Scholar
  5. Antczak DF, Bailey E, Barger B, Guerin G, Lazary S, McClure J, Mottironi VD, Symons R, Templeton J, Varewyck H (1986) Joint report of the Third International Workshop on Lymphocyte Alloantigens of the Horse, Kennett Square, Pennsylvania, 25-27 April 1984. Anim Genet 17:363–373CrossRefPubMedGoogle Scholar
  6. Azab W, Harman R, Miller D, Tallmadge R, Frampton AR Jr, Antczak DF, Osterrieder N (2014) Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors. J Gen Virol 95:1554–1563CrossRefPubMedGoogle Scholar
  7. Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331PubMedPubMedCentralGoogle Scholar
  8. Bowling AT, Del Valle A, Bowling M (2000) A pedigree-based study of mitochondrial D-loop DNA sequence variation among Arabian horses. Anim Genet 31:1–7CrossRefPubMedGoogle Scholar
  9. Brinkmeyer-Langford CL, Cai JJ, Gill CA, Skow LC (2013) Microsatellite variation in the equine MHC. Anim Genet 44:267–275CrossRefPubMedGoogle Scholar
  10. Burger D, Meuwly C, Marti E, Sieme H, Oberthur M, Janda J, Meinecke-Tillmann S, Wedekind C (2017) MHC-correlated preferences in diestrous female horses (Equus caballus). Theriogenology 89:318–323 e1CrossRefPubMedGoogle Scholar
  11. de Groot N, Doxiadis GG, Otting N, de Vos-Rouweler AJ, Bontrop RE (2014) Differential recombination dynamics within the MHC of macaque species. Immunogenetics 66:535–544CrossRefPubMedPubMedCentralGoogle Scholar
  12. Doxiadis GG, de Groot N, Otting N, de Vos-Rouweler AJ, Bolijn MJ, Heijmans CM, de Groot NG, van der Wiel MK, Remarque EJ, Vangenot C, Nunes JM, Sanchez-Mazas A, Bontrop RE (2013) Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques. Immunogenetics 65:569–584CrossRefPubMedPubMedCentralGoogle Scholar
  13. Ellegren H (2004) Microsatellites: simple sequences with complex evolution. Nat Rev Genet 5:435–445CrossRefPubMedGoogle Scholar
  14. Frampton AR Jr, Goins WF, Cohen JB, von Einem J, Osterrieder N, O’Callaghan DJ, Glorioso JC (2005) Equine herpesvirus 1 utilizes a novel herpesvirus entry receptor. J Virol 79:3169–3173CrossRefPubMedPubMedCentralGoogle Scholar
  15. Fraser DG, Bailey E (1998) Polymorphism and multiple loci for the horse DQA gene. Immunogenetics 47:487–490CrossRefPubMedGoogle Scholar
  16. Fritz KL, Kaese HJ, Valberg SJ, Hendrickson JA, Rendahl AK, Bellone RR, Dynes KM, Wagner ML, Lucio MA, Cuomo FM, Brinkmeyer-Langford CL, Skow LC, Mickelson JR, Rutherford MS, McCue ME (2014) Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses. Anim Genet 45:392–399CrossRefPubMedGoogle Scholar
  17. Gharahveysi S, Irani M (2011) Inbreeding study on the Iranian Arab horse population. World J Zool 6:1–6Google Scholar
  18. Głażewska I (2010) Speculations on the origin of the Arabian horse breed. Livest Sci 129:49–55CrossRefGoogle Scholar
  19. Głażewska I, Gralak B (2006) Balancing selection in Polish Arabian horses. Livest Prod Sci 105:272–276CrossRefGoogle Scholar
  20. Głażewska I, Jezierski T (2004) Pedigree analysis of Polish Arabian horses based on founder contributions. Livest Prod Sci 90:293–298CrossRefGoogle Scholar
  21. Glazewska I, Wysocka A, Gralak B, Sell J (2007) A new view on dam lines in Polish Arabian horses based on mtDNA analysis. Genet Sel Evol 39:609–619CrossRefPubMedPubMedCentralGoogle Scholar
  22. Guerin G, Bailey E, Bernoco D, Anderson I, Antczak DF, Bell K, Biros I, Bjornstad G, Bowling AT, Brandon R, Caetano AR, Cholewinski G, Colling D, Eggleston M, Ellis N, Flynn J, Gralak B, Hasegawa T, Ketchum M, Lindgren G, Lyons LA, Millon LV, Mariat D, Murray J, Neau A, Roed K, Sandberg K, Skow LC, Tammen I, Tozaki T, Van Dyk E, Weiss B, Young A, Ziegle J (2003) The second generation of the International Equine Gene Mapping Workshop half-sibling linkage map. Anim Genet 34:161–168CrossRefPubMedGoogle Scholar
  23. Horin P, Matiasovic J (2002) A second locus and new alleles in the major histocompatibility complex class II (ELA-DQB) region in the horse. Anim Genet 33:196–200CrossRefPubMedGoogle Scholar
  24. Horin P, Cothran EG, Trtkova K, Marti E, Glasnak V, Henney P, Vyskocil M, Lazary S (1998) Polymorphism of Old Kladruber horses, a surviving but endangered baroque breed. Eur J Immunogenet 25:357–363CrossRefPubMedGoogle Scholar
  25. 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 60:1–18CrossRefPubMedPubMedCentralGoogle Scholar
  26. Janova E, Matiasovic J, Vahala J, Vodicka R, Van Dyk E, Horin P (2009) Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae. Immunogenetics 61:513–527CrossRefPubMedGoogle Scholar
  27. Kashi Y, King DG (2006) Simple sequence repeats as advantageous mutators in evolution. Trends Genet 22:253–259CrossRefPubMedGoogle Scholar
  28. Kelenka P (2009) The horse in human history. Cambridge University Press, CambridgeGoogle Scholar
  29. Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695CrossRefPubMedGoogle Scholar
  30. Khadka R (2010) Global horse population with respect to breeds and risk status. Master’s Degree, Swedish University of Agricultural SciencesGoogle Scholar
  31. Khanshour AM, Cothran EG (2013) Maternal phylogenetic relationships and genetic variation among Arabian horse populations using whole mitochondrial DNA D-loop sequencing. BMC Genet 14:83CrossRefPubMedPubMedCentralGoogle Scholar
  32. Khanshour A, Conant E, Juras R, Cothran EG (2013) Microsatellite analysis of genetic diversity and population structure of Arabian horse populations. J Hered 104:386–398CrossRefPubMedGoogle Scholar
  33. Kimura M, Crow JF (1964) The number of alleles that can be maintained in a finite population. Genetics 49:725–738PubMedPubMedCentralGoogle Scholar
  34. Klumplerova M, Vychodilova L, Bobrova O, Cvanova M, Futas J, Janova E, Vyskocil M, Vrtkova I, Putnova L, Dusek L, Marti E, Horin P (2013) Major histocompatibility complex and other allergy-related candidate genes associated with insect bite hypersensitivity in Icelandic horses. Mol Biol Rep 40:3333–3340CrossRefPubMedGoogle Scholar
  35. Kydd JH, Case R, Winton C, MacRae S, Sharp E, Ricketts SL, Rash N, Newton JR (2016) Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: preliminary evidence. Vet Microbiol 188:34–40CrossRefPubMedGoogle Scholar
  36. Lange C (2016) Purity, nobility, beauty, and performance—past and present construction of meaning for the Arabian horse. In: Davis DL, Maurstad A (eds) The meaning of horses - biosocial encounters. Routledge, OxfordGoogle Scholar
  37. Lazary S, Antczak DF, Bailey E, Bell TK, Bernoco D, Byrns G, McClure JJ (1988) Joint Report of the Fifth International Workshop on Lymphocyte Alloantigens of the Horse, Baton Rouge, Louisiana, 31 October-1 November 1987. Anim Genet 19:447–456CrossRefPubMedGoogle Scholar
  38. Lazary S, Marti E, Szalai G, Gaillard C, Gerber H (1994) Studies on the frequency and associations of equine leucocyte antigens in sarcoid and summer dermatitis. Anim Genet 25(Suppl 1):75–80CrossRefPubMedGoogle Scholar
  39. Librado P, Gamba C, Gaunitz C, Der Sarkissian C, Pruvost M, Albrechtsen A, Fages A, Khan N, Schubert M, Jagannathan V, Serres-Armero A, Kuderna LFK, Povolotskaya IS, Seguin-Orlando A, Lepetz S, Neuditschko M, Theves C, Alquraishi S, Alfarhan AH, Al-Rasheid K, Rieder S, Samashev Z, Francfort HP, Benecke N, Hofreiter M, Ludwig A, Keyser C, Marques-Bonet T, Ludes B, Crubezy E, Leeb T, Willerslev E, Orlando L (2017) Ancient genomic changes associated with domestication of the horse. Science 356:442–445CrossRefPubMedGoogle Scholar
  40. Luis C, Cothran EG, Oom MM, Bailey E (2005) Major histocompatibility complex locus DRA polymorphism in the endangered Sorraia horse and related breeds. J Anim Breed Genet 122:69–72CrossRefPubMedGoogle Scholar
  41. Marshall TC, Slate J, Kruuk LE, Pemberton JM (1998) Statistical confidence for likelihood-based paternity inference in natural populations. Mol Ecol 7:639–655CrossRefPubMedGoogle Scholar
  42. Martin M, Mann D, Carrington M (1995) Recombination rates across the HLA complex: use of microsatellites as a rapid screen for recombinant chromosomes. Hum Mol Genet 4:423–428CrossRefPubMedGoogle Scholar
  43. Meyer D, C Aguiar VR, Bitarello BD, C Brandt DY, Nunes K (2017) A genomic perspective on HLA evolution. Immunogenetics.  https://doi.org/10.1007/s00251-017-1017-3
  44. Miller D, Tallmadge RL, Binns M, Zhu B, Mohamoud YA, Ahmed A, Brooks SA, Antczak DF (2017) Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes. Immunogenetics 69:145–156CrossRefPubMedGoogle Scholar
  45. Morris KM, Kirby K, Beatty JA, Barrs VR, Cattley S, David V, O'Brien SJ, Menotti-Raymond M, Belov K (2014) Development of MHC-linked microsatellite markers in the domestic cat and their use to evaluate MHC diversity in domestic cats, cheetahs, and Gir lions. J Hered 105:493–505CrossRefPubMedPubMedCentralGoogle Scholar
  46. Mottironi VD, Perryman LE, Pollara B, Mickey MR, Swift R, McGrath P (1981) Major histocompatibility locus in the Arabian horse. Transplantation 31:290–294CrossRefPubMedGoogle Scholar
  47. Ramsay JD, Leib SR, Orfe L, Call DR, Tallmadge RL, Fraser DG, Mealey RH (2010) Development of a DNA microarray for detection of expressed equine classical MHC class I sequences in a defined population. Immunogenetics 62:633–639CrossRefPubMedPubMedCentralGoogle Scholar
  48. Santucci F, Ibrahim KM, Bruzzone A, Hewit GM (2007) Selection on MHC-linked microsatellite loci in sheep populations. Heredity (Edinb) 99:340–348CrossRefGoogle Scholar
  49. Schurink A, Wolc A, Ducro BJ, Frankena K, Garrick DJ, Dekkers JC, van Arendonk JA (2012) Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands. Genet Sel Evol 44:31CrossRefPubMedPubMedCentralGoogle Scholar
  50. Sommer S (2005) The importance of immune gene variability (MHC) in evolutionary ecology and conservation. Front Zool 2:16CrossRefPubMedPubMedCentralGoogle Scholar
  51. Staiger EA, Tseng CT, Miller D, Cassano JM, Nasir L, Garrick D, Brooks SA, Antczak DF (2016) Host genetic influence on papillomavirus-induced tumors in the horse. Int J Cancer 139:784–792CrossRefPubMedGoogle Scholar
  52. Tallmadge RL, Campbell JA, Miller DC, Antczak DF (2010) Analysis of MHC class I genes across horse MHC haplotypes. Immunogenetics 62:159–172CrossRefPubMedPubMedCentralGoogle Scholar
  53. Traherne JA, Horton R, Roberts AN, Miretti MM, Hurles ME, Stewart CA, Ashurst JL, Atrazhev AM, Coggill P, Palmer S, Almeida J, Sims S, Wilming LG, Rogers J, de Jong PJ, Carrington M, Elliott JF, Sawcer S, Todd JA, Trowsdale J, Beck S (2006) Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history. PLoS Genet 2:e9CrossRefPubMedPubMedCentralGoogle Scholar
  54. Tseng CT, Miller D, Cassano J, Bailey E, Antczak DF (2010) Identification of equine major histocompatibility complex haplotypes using polymorphic microsatellites. Anim Genet 41(Suppl 2):150–153CrossRefPubMedPubMedCentralGoogle Scholar
  55. Vranova M, Alloggio I, Qablan M, Vyskocil M, Baumeisterova A, Sloboda M, Putnova L, Vrtkova I, Modry D, Horin P (2011) Genetic diversity of the class II major histocompatibility DRA locus in European, Asiatic and African domestic donkeys. Infect Genet Evol 11:1136–1141CrossRefPubMedGoogle Scholar
  56. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blocker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guerin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Roed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvanen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Broad Institute Genome Sequencing P, Broad Institute Whole Genome Assembly T, Lander ES, Lindblad-Toh K (2009) Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 326:865–867CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • R. Sadeghi
    • 1
    • 2
  • Mohammad Moradi-Shahrbabak
    • 2
  • S. R. Miraei Ashtiani
    • 2
  • D. C. Miller
    • 1
  • Douglas F. Antczak
    • 1
  1. 1.Baker Institute for Animal Health, College of Veterinary MedicineCornell UniversityIthacaUSA
  2. 2.Department of Animal ScienceUniversity of TehranKarajIran

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