94
Predicting Swine MHC Haplotypes from High-Density SNP Genotypes
The major histocompatibility complex (MHC) region in swine, the swine leukocyte antigen (SLA) complex, is rich in genes associated with disease resistance. Many of these genes have haplotype-specific expression. There are various ways to determine MHC haplotypes, including wet lab assays such as using PCR-sequence-specific primers (PCRSSP) for low-resolution (Lr) SLA haplotyping, which can be time intensive and costly. Alternatively, high-density single nucleotide polymorphism (SNP) panels can be used to infer haplotypes in a genomic region. The objective of this study was to determine whether SNP genotypes from a commercial high-density SNP chip can be used to predict haplotypes within the MHC region of the swine genome.
A total of 140 pigs from four PRRS Host Genetics Consortium trials, were haplotyped using the PCRSSP method. Pigs were selected, in roughly equal numbers per trial, based on extreme (high/low) viremia and growth after inoculation with the NVSL 97-7985 PRRS strain.
All pigs were genotyped using the Illumina SNP60 BeadChip. Seventy-five SNPs located within the 23-27 Mb SLA I region and 64 SNPs within the 29-31 Mb SLA II region of chromosome 7 were used to analyze MHC class I and II, respectively. SNP genotypes in each region were phased into haplotypes using BEAGLE software. Resulting haplotypes in the 23-27 Mb window (the entire window used for phasing) or the 24 Mb window were analyzed for SLA class I. Similarly, SNP haplotypes in either the 29-31 Mb window or 29 Mb window were analyzed for SLA class II. Identical SNP haplotypes for a given window were grouped to determine which Lr SLA haplotype they shared. Accuracy of prediction was calculated as the percentage of SNP haplotypes that could be assigned to a Lr SLA haplotype.
When analyzing SNP haplotypes using the entire window used for phasing to group haplotypes, accuracy of prediction was 85% for class I and 88% for class II. Greater haplotype prediction accuracy was obtained when grouping SNP haplotypes using the 1 Mb approach (91% and 95%, for class I and II, respectively).
In conclusion, BEAGLE software can be used to predict MHC haplotypes from high-density SNP genotype data with fairly high accuracy. These results indicate that the Illumina SNP60 BeadChip can be used to predict SLA haplotypes as an alternative to wet lab methods. This will enable us to investigate the role of SLA class I and II genes in PRRS resistance/susceptibility.
Keywords: swine leukocyte antigen