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Immunogenetics2016; 69(3); 145-156; doi: 10.1007/s00251-016-0964-4

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.
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Publication Date: 2016-11-26 PubMed ID: 27889800PubMed Central: PMC5316504DOI: 10.1007/s00251-016-0964-4Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

Immunogenetics
ISSN: 1432-1211
NlmUniqueID: 0420404
Country: United States
Language: English
Volume: 69
Issue: 3
Pages: 145-156

Researcher Affiliations

Miller, Donald
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Tallmadge, Rebecca L
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Binns, Matthew
  • Equine Analysis Systems, 5472 Leestown Road, Lexington, KY, 40511, USA.
Zhu, Baoli
  • Children's Hospital of Oakland Research Institute, Oakland, CA, 94609, USA.
Mohamoud, Yasmin Ali
  • Weill Cornell Medicine-Qatar, Doha, Qatar.
Ahmed, Ayeda
  • Weill Cornell Medicine-Qatar, Doha, Qatar.
Brooks, Samantha A
  • University of Florida, Gainesville, FL, 32611, USA.
Antczak, Douglas F
  • 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

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