MHC class IIa haplotypes derived by high-throughput SNP screening in an isolated sheep population.

Kara L Dicks,Susan E Johnston,Keith T Ballingall,Josephine M Pemberton

doi:10.1093/g3journal/jkab200

Kara L Dicks, Susan E Johnston + Show 2 more

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https://doi.org/10.1093/g3journal/jkab200

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Abstract

Investigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within the DQA1 gene enabled detection of a recombinant haplotype affecting only the SNPs downstream of the expressed genes. The panel of 13 SNPs was genotyped in 5951 Soay sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of the recombinant SNP haplotype. This SNP-based method has enabled the rapid generation of locus-specific MHC genotypes for large numbers of Soay sheep. This volume of high-quality genotypes in a well-characterized population of free-living sheep will be valuable for investigating the mechanisms maintaining diversity at the MHC.

Highlights

The most highly polymorphic region of the vertebrate genome is the major histocompatibility complex (MHC), and yet the evolutionary processes driving this diversity remain much debated (Bernatchez and Landry 2003; Spurgin and Richardson 2010)
We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip
Identification of SNPs linked to MHC class IIa haplotypes

Summary

Introduction

The most highly polymorphic region of the vertebrate genome is the major histocompatibility complex (MHC), and yet the evolutionary processes driving this diversity remain much debated (Bernatchez and Landry 2003; Spurgin and Richardson 2010). The key PMS mechanisms involved, which are not necessarily mutually exclusive, are heterozygote advantage (Doherty and Zinkernagel 1975; Slade and McCallum 1992) and variation in selection pressure through either negative frequency-dependent selection (Apanius et al 1997) or fluctuating selection (Hill 1991; Hedrick 2002) Disentangling these mechanisms is challenging in experimental systems which may be incapable of replicating the wide array of pathogens and parasites that occur within a wild host ( see Kalbe et al 2009 and Eizaguirre et al 2012), and within wild systems which may be swamped with variation in individual ontogeny, environment, genetic background, and pathogen diversity.

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