title: 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.
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Tallmadge
authors.affiliation: Equine Analysis Systems, 5472 Leestown Road, Lexington, KY, 40511, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Binns
authors.affiliation: Children's Hospital of Oakland Research Institute, Oakland, CA, 94609, USA.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Weill Cornell Medicine-Qatar, Doha, Qatar.
authors.forename: Yasmin Ali
authors.initials: YA
authors.lastname: Mohamoud
authors.affiliation: Weill Cornell Medicine-Qatar, Doha, Qatar.
authors.forename: Ayeda
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: University of Florida, Gainesville, FL, 32611, USA.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Brooks
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. dfa1@cornell.edu.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Antczak
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D022202:Chromosomes, Artificial, Bacterial; D005260:Female; D005785:Gene Conversion; D015723:Gene Library; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006736:Horses / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011110:Polymorphism, Genetic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens
keywords: Genetics; Horse; Immunity; Major histocompatibility complex; Polymorphism