Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes.
Abstract: The polymorphism of major histocompatibility complex (MHC) class II DQ and DR genes in five common equine leukocyte antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine bacterial artificial chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next generation sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse.
Publication Date: 2016-11-26 PubMed ID: 27889800PubMed Central: PMC5316504DOI: 10.1007/s00251-016-0964-4Google Scholar: Lookup
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- Journal Article
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Summary
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This study explored the variability of major histocompatibility complex (MHC) class II DQ and DR genes in five common equine leukocyte antigen (ELA) haplotypes. This was achieved by sequencing mRNA transcripts from lymphocytes of ELA homozygous horses and identifying locus-specific residues. The results revealed a high degree of conservation across different haplotypes, offering potential insights into MHC conservation and evolution and disease association.
Examination of MHC Class II DQ and DR Genes
- The research investigated the polymorphism of Major Histocompatibility Complex (MHC) class II DQ and DR genes in five common equine leukocyte antigen (ELA) haplotypes. Polymorphism in this context refers to the occurrence of different forms, or alleles, of a particular gene in a population.
- The investigation involved isolating mRNA transcripts from the lymphocytes of eight ELA homozygous horses. Homozygous refers to a genetic condition where an individual contains two identical forms of a particular gene.
Findings on Expressed MHC Class II Genes
- In horses of the ELA-A3 haplotype, ten expressed MHC class II genes were identified, comprising four DR genes and six DQ genes. This haplotype was carried by the donor horses of the equine bacterial artificial chromosome (BAC) library and the reference genome sequence.
- The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. A locus is the specific location or place of a gene on a chromosome.
Use of Next Generation Sequencing
- Next generation sequencing (NGS) techniques were used to further examine the genomic DNA of the four MHC haplotypes. This technique allows for the rapid sequencing of large amounts of DNA.
- The NGS of genomic DNA revealed the presence of stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. A stop codon is a nucleotide in messenger RNA that signals the end of translation.
Insights into Mammalian MHC Conservation and Evolution
- Phylogenetic analysis of the amino acid sequences across haplotypes revealed that they contained locus-specific residues, and the locus clusters formed from this analysis were well supported.
- The identification of allelic series of equine MHC class II loci may aid in understanding MHC conservation and evolution in mammals and potentially provide insights into associations between the equine MHC class II region and diseases of the horse.
Cite This Article
APA
Miller D, Tallmadge RL, Binns M, Zhu B, Mohamoud YA, Ahmed A, Brooks SA, Antczak DF.
(2016).
Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes.
Immunogenetics, 69(3), 145-156.
https://doi.org/10.1007/s00251-016-0964-4 Publication
Researcher Affiliations
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Equine Analysis Systems, 5472 Leestown Road, Lexington, KY, 40511, USA.
- Children's Hospital of Oakland Research Institute, Oakland, CA, 94609, USA.
- Weill Cornell Medicine-Qatar, Doha, Qatar.
- Weill Cornell Medicine-Qatar, Doha, Qatar.
- University of Florida, Gainesville, FL, 32611, USA.
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. dfa1@cornell.edu.
MeSH Terms
- Alleles
- Amino Acid Sequence
- Animals
- Chromosomes, Artificial, Bacterial
- Female
- Gene Conversion
- Gene Library
- HLA-DQ Antigens / genetics
- HLA-DR Antigens / genetics
- Haplotypes / genetics
- High-Throughput Nucleotide Sequencing
- Homozygote
- Horses / genetics
- Major Histocompatibility Complex / genetics
- Male
- Phylogeny
- Polymerase Chain Reaction / veterinary
- Polymorphism, Genetic / genetics
- Sequence Homology, Amino Acid
Grant Funding
- R01 HD049545 / NICHD NIH HHS
References
This article includes 47 references
- Albright-Fraser DG, Reid R, Gerber V, Bailey E. Polymorphism of DRA among equids.. Immunogenetics 1996;43(5):315-7.
- Andersson LS, Swinburne JE, Meadows JR, Broström H, Eriksson S, Fikse WF, Frey R, Sundquist M, Tseng CT, Mikko S, Lindgren G. The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.. Immunogenetics 2012 Mar;64(3):201-8.
- Antczak DF, Bailey E, Barger B, Guerin G, Lazary S, McClure J, Mottironi VD, Symons R, Templeton J, Varewyck H. Joint report of the Third International Workshop on Lymphocyte Alloantigens of the Horse, Kennett Square, Pennsylvania, 25-27 April 1984.. Anim Genet 1986;17(4):363-73.
- Antczak DF, Bright SM, Remick LH, Bauman BE. Lymphocyte alloantigens of the horse. I. Serologic and genetic studies.. Tissue Antigens 1982 Sep;20(3):172-87.
- Antczak DF, Miller JM, Remick LH. Lymphocyte alloantigens of the horse. II. Antibodies to ELA antigens produced during equine pregnancy.. J Reprod Immunol 1984 Aug;6(5):283-97.
- Barbis DP, Maher JK, Stanek J, Klaunberg BA, Antczak DF. Horse cDNA clones encoding two MHC class I genes.. Immunogenetics 1994;40(2):163.
- Brinkmeyer-Langford CL, Cai JJ, Gill CA, Skow LC. Microsatellite variation in the equine MHC.. Anim Genet 2013 Jun;44(3):267-75.
- Brown JJ, Thomson W, Clegg P, Eyre S, Kennedy LJ, Matthews J, Carter S, Ollier WE. Polymorphisms of the equine major histocompatibility complex class II DRA locus.. Tissue Antigens 2004 Aug;64(2):173-9.
- Brunsberg U, Edfors-Lilja I, Andersson L, Gustafsson K. Structure and organization of pig MHC class II DRB genes: evidence for genetic exchange between loci.. Immunogenetics 1996;44(1):1-8.
- Carpenter S, Baker JM, Bacon SJ, Hopman T, Maher J, Ellis SA, Antczak DF. Molecular and functional characterization of genes encoding horse MHC class I antigens.. Immunogenetics 2001 Dec;53(9):802-9.
- Crepaldi T, Crump A, Newman M, Ferrone S, Antczak DF. Equine T lymphocytes express MHC class II antigens.. J Immunogenet 1986 Aug;13(4):349-60.
- Díaz S, Giovambattista G, Peral-García P. Polymorphisms of the upstream regulatory region of the major histocompatibility complex DRB genes in domestic horses.. Int J Immunogenet 2005 Apr;32(2):91-8.
- Ellis SA, Bontrop RE, Antczak DF, Ballingall K, Davies CJ, Kaufman J, Kennedy LJ, Robinson J, Smith DM, Stear MJ, Stet RJ, Waller MJ, Walter L, Marsh SG. ISAG/IUIS-VIC Comparative MHC Nomenclature Committee report, 2005.. Immunogenetics 2006 Jan;57(12):953-8.
- Fraser DG, Bailey E. Demonstration of three DRB loci in a domestic horse family.. Immunogenetics 1996;44(6):441-5.
- Fraser DG, Bailey E. Polymorphism and multiple loci for the horse DQA gene.. Immunogenetics 1998 May;47(6):487-90.
- 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. Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses.. Anim Genet 2014 Jun;45(3):392-9.
- Gustafson AL, Tallmadge RL, Ramlachan N, Miller D, Bird H, Antczak DF, Raudsepp T, Chowdhary BP, Skow LC. An ordered BAC contig map of the equine major histocompatibility complex.. Cytogenet Genome Res 2003;102(1-4):189-95.
- Hickford JG, Zhou H, Slow S, Fang Q. Diversity of the ovine DQA2 gene.. J Anim Sci 2004 Jun;82(6):1553-63.
- Högstrand K, Böhme J. Gene conversion can create new MHC alleles.. Immunol Rev 1999 Feb;167:305-17.
- Horín P, Matiasovic J. A second locus and new alleles in the major histocompatibility complex class II (ELA-DQB) region in the horse.. Anim Genet 2002 Jun;33(3):196-200.
- Janova E, Matiasovic J, Vahala J, Vodicka R, Van Dyk E, Horin P. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.. Immunogenetics 2009 Jul;61(7):513-27.
- Kamath PL, Getz WM. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus.. BMC Evol Biol 2011 May 18;11:128.
- Kambayashi T, Laufer TM. Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?. Nat Rev Immunol 2014 Nov;14(11):719-30.
- Kelley J, Walter L, Trowsdale J. Comparative genomics of major histocompatibility complexes.. Immunogenetics 2005 Jan;56(10):683-95.
- Klumplerova M, Vychodilova L, Bobrova O, Cvanova M, Futas J, Janova E, Vyskocil M, Vrtkova I, Putnova L, Dusek L, Marti E, Horin P. Major histocompatibility complex and other allergy-related candidate genes associated with insect bite hypersensitivity in Icelandic horses.. Mol Biol Rep 2013 Apr;40(4):3333-40.
- Lazary S, Antczak DF, Bailey E, Bell TK, Bernoco D, Byrns G, McClure JJ. Joint Report of the Fifth International Workshop on Lymphocyte Alloantigens of the Horse, Baton Rouge, Louisiana, 31 October-1 November 1987.. Anim Genet 1988;19(4):447-56.
- Lazary S, Bullen S, Müller J, Kovacs G, Bodo I, Hockenjos P, De Weck AL. Equine leukocyte antigen system. II. Serological and mixed lymphocyte reactivity studies in families.. Transplantation 1980 Sep;30(3):210-5.
- Lazary S, Dubath ML, Luder C, Gerber H. Equine leucocyte antigen system. IV. Recombination within the major histocompatibility complex (MHC).. J Immunogenet 1986 Aug;13(4):315-25.
- Lazary S, Marti E, Szalai G, Gaillard C, Gerber H. Studies on the frequency and associations of equine leucocyte antigens in sarcoid and summer dermatitis.. Anim Genet 1994 Jun;25 Suppl 1:75-80.
- Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform.. Bioinformatics 2010 Mar 1;26(5):589-95.
- Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. The Sequence Alignment/Map format and SAMtools.. Bioinformatics 2009 Aug 15;25(16):2078-9.
- Minias P, Bateson ZW, Whittingham LA, Johnson JA, Oyler-McCance S, Dunn PO. Contrasting evolutionary histories of MHC class I and class II loci in grouse--effects of selection and gene conversion.. Heredity (Edinb) 2016 May;116(5):466-76.
- Nasir L, Ndiaye M, Seely C, Stear MJ. Sequence polymorphism in the bovine major histocompatibility complex DQB loci.. Anim Genet 1997 Dec;28(6):441-5.
- Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees.. Mol Biol Evol 1987 Jul;4(4):406-25.
- Staiger EA, Tseng CT, Miller D, Cassano JM, Nasir L, Garrick D, Brooks SA, Antczak DF. Host genetic influence on papillomavirus-induced tumors in the horse.. Int J Cancer 2016 Aug 15;139(4):784-92.
- Szalai G, Antczak DF, Gerber H, Lazary S. Molecular cloning and characterization of horse DQA cDNA.. Immunogenetics 1994;40(6):457.
- Szalai G, Antczak DF, Gerber H, Lazary S. Molecular cloning and characterization of horse DQB cDNA.. Immunogenetics 1994;40(6):458.
- Tallmadge RL, Campbell JA, Miller DC, Antczak DF. Analysis of MHC class I genes across horse MHC haplotypes.. Immunogenetics 2010 Mar;62(3):159-72.
- Tallmadge RL, Lear TL, Antczak DF. Genomic characterization of MHC class I genes of the horse.. Immunogenetics 2005 Nov;57(10):763-74.
- Tamura K, Dudley J, Nei M, Kumar S. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0.. Mol Biol Evol 2007 Aug;24(8):1596-9.
- Trowsdale J. The MHC, disease and selection.. Immunol Lett 2011 Jun 30;137(1-2):1-8.
- Tseng CT, Miller D, Cassano J, Bailey E, Antczak DF. Identification of equine major histocompatibility complex haplotypes using polymorphic microsatellites.. Anim Genet 2010 Dec;41 Suppl 2(Suppl 2):150-3.
- Villegas-Castagnasso EE, Díaz S, Giovambattista G, Dulout FN, Peral-García P. Analysis of ELA-DQB exon 2 polymorphism in Argentine Creole horses by PCR-RFLP and PCR-SSCP.. J Vet Med A Physiol Pathol Clin Med 2003 Aug;50(6):280-5.
- Vranova M, Alloggio I, Qablan M, Vyskocil M, Baumeisterova A, Sloboda M, Putnova L, Vrtkova I, Modry D, Horin P. Genetic diversity of the class II major histocompatibility DRA locus in European, Asiatic and African domestic donkeys.. Infect Genet Evol 2011 Jul;11(5):1136-41.
- Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker 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, Guérin 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, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
- Yuhki N, Beck T, Stephens R, Neelam B, O'Brien SJ. Comparative genomic structure of human, dog, and cat MHC: HLA, DLA, and FLA.. J Hered 2007;98(5):390-9.
- Yuhki N, Beck T, Stephens RM, Nishigaki Y, Newmann K, O'Brien SJ. Comparative genome organization of human, murine, and feline MHC class II region.. Genome Res 2003 Jun;13(6A):1169-79.
Citations
This article has been cited 13 times.- Li W, Huang Q, Peng Y, Pan S, Hu M, Wang P, He Y. A deep learning approach based on multi-omics data integration to construct a risk stratification prediction model for skin cutaneous melanoma. J Cancer Res Clin Oncol 2023 Sep 7;.
- Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure. Genes (Basel) 2023 Jul 10;14(7).
- Tozaki T, Ohnuma A, Kikuchi M, Ishige T, Kakoi H, Hirota KI, Takahashi Y, Nagata SI. Short Insertion and Deletion Discoveries via Whole-Genome Sequencing of 101 Thoroughbred Racehorses. Genes (Basel) 2023 Mar 3;14(3).
- Kamm JL, Riley CB, Parlane N, Gee EK, McIlwraith CW. Interactions Between Allogeneic Mesenchymal Stromal Cells and the Recipient Immune System: A Comparative Review With Relevance to Equine Outcomes. Front Vet Sci 2020;7:617647.
- Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE. Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting. Stem Cells Transl Med 2021 May;10(5):694-710.
- Liu C, Lei H, Ran X, Wang J. Genetic variation and selection in the major histocompatibility complex Class II gene in the Guizhou pony. PeerJ 2020;8:e9889.
- Klumplerova M, Splichalova P, Oppelt J, Futas J, Kohutova A, Musilova P, Kubickova S, Vodicka R, Orlando L, Horin P. Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae. BMC Genomics 2020 Sep 30;21(1):677.
- Jaworska J, Tobolski D, Janowski T. Is similarity in Major Histocompatibility Complex (MHC) associated with the incidence of retained fetal membranes in draft mares? A cross-sectional study. PLoS One 2020;15(8):e0237765.
- Jaworska J, Ropka-Molik K, Wocławek-Potocka I, Siemieniuch M. Inter- and intrabreed diversity of the major histocompatibility complex (MHC) in primitive and draft horse breeds. PLoS One 2020;15(2):e0228658.
- Jeannerat E, Marti E, Thomas S, Herrera C, Sieme H, Wedekind C, Burger D. Embryo survival in the oviduct not significantly influenced by major histocompatibility complex social signaling in the horse. Sci Rep 2020 Jan 23;10(1):1056.
- Ballingall KT, Bontrop RE, Ellis SA, Grimholt U, Hammond JA, Ho CS, Kaufman J, Kennedy LJ, Maccari G, Miller D, Robinson J, Marsh SGE. Comparative MHC nomenclature: report from the ISAG/IUIS-VIC committee 2018. Immunogenetics 2018 Nov;70(10):625-632.
- Sadeghi R, Moradi-Shahrbabak M, Miraei Ashtiani SR, Miller DC, Antczak DF. MHC haplotype diversity in Persian Arabian horses determined using polymorphic microsatellites. Immunogenetics 2018 May;70(5):305-315.
- Banico EC, Sira EMJS, Fajardo LE, Dulay ANG, Odchimar NMO, Simbulan AM, Orosco FL. Advancing one health vaccination: In silico design and evaluation of a multi-epitope subunit vaccine against Nipah virus for cross-species immunization using immunoinformatics and molecular modeling. PLoS One 2024;19(9):e0310703.
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