Abstract
The ovine MHC class IIa is known to consist of six to eight loci located in close proximity on chromosome 20, forming haplotypes that are typically inherited without recombination. Here, we characterise the class IIa haplotypes within the Soay sheep (Ovis aries) on St. Kilda to assess the diversity present within this unmanaged island population. We used a stepwise sequence-based genotyping strategy to identify alleles at seven polymorphic MHC class IIa loci in a sample of 118 Soay sheep from four cohorts spanning 15 years of the long-term study on St. Kilda. DRB1, the most polymorphic MHC class II locus, was characterised first in all 118 sheep and identified six alleles. Using DRB1 homozygous animals, the DQA (DQA1, DQA2 and DQA2-like) and DQB (DQB1, DQB2 and DQB2-like) loci were sequenced, revealing eight haplotypes. Both DQ1/DQ2 and DQ2/DQ2-like haplotype configurations were identified and a single haplotype carrying three DQB alleles. A test sample of 94 further individuals typed at the DRB1 and DQA loci found no exceptions to the eight identified haplotypes and a haplotype homozygosity of 21.3%. We found evidence of historic positive selection at DRB1, DQA and DQB. The limited variation at MHC class IIa loci in Soay sheep enabled haplotype characterisation but showed that no single locus could capture the full extent of the expressed variation in the region.
Highlights
The major histocompatibility complex (MHC) is a genomic region containing highly polymorphic genes which encode cell surface proteins involved in the presentation of pathogen-derived peptides to T cells, enabling an immune response (Klein 1986)
All six alleles were represented in the IPD-MHC database and each allele was assigned to an individual haplotype
Six DRB1 alleles in Soay sheep were identified, which matched sequences previously identified in commercial Scottish sheep breeds and held in the IPD-MHC database
Summary
The major histocompatibility complex (MHC) is a genomic region containing highly polymorphic genes which encode cell surface proteins involved in the presentation of pathogen-derived peptides to T cells, enabling an immune response (Klein 1986). The highly complex and polymorphic nature of the MHC region has made it a focus of many studies in immunology and evolution; these features make it difficult to develop locus-specific assays to genotype individual loci. Some are lost through decay, producing pseudogenes and gene fragments, which are characteristic of mammalian MHC regions. Genotyping the MHC region is often challenging, and locus-specific assays can difficult to develop, as multiple loci and pseudogenes may co-amplify with primers that are too generic, whilst allelic dropout may occur with primers that are too specific (Babik et al 2009)
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