An updated Pig Haplotype Reference Panel (PHARP 4.0) comprising 13,298 haplotypes.

Area of Science:

• Animal Genomics
• Bioinformatics
• Quantitative Genetics

Background:

• High-throughput sequencing accelerates genetic research but WGS is costly for large studies.
• Genotype imputation offers a cost-effective alternative for inferring genetic variants.
• Existing pig reference panels have limitations in size and diversity.

Purpose of the Study:

• To present the updated Pig Haplotype Reference Panel (PHARP) 4.0, the largest and most diverse pig reference panel to date.
• To evaluate the imputation accuracy of PHARP 4.0 compared to existing panels.
• To optimize imputation pipelines and assess their utility in genome-wide association studies (GWAS).

Main Methods:

• Assembled PHARP 4.0 from 6449 pig genomes across 154 breeds, containing 50.3 million SNPs and 5.8 million indels.
• Compared imputation accuracy of PHARP 4.0 against SWIM, AHC, AGIDB, and PGRP panels using low-density SNP data.
• Optimized an RNA-seq-based imputation pipeline and evaluated the impact of reference panel size on rare variant imputation.

Main Results:

• PHARP 4.0 demonstrated superior imputation accuracy (CR > 0.99, R² > 0.98) in European breeds and improved accuracy (CR = 0.936, R² = 0.924) in Chinese Jinhua pigs.
• Optimized RNA-seq pipeline achieved high accuracy (CR > 0.95, R² > 0.90) in European breeds and (CR = 0.93, R² = 0.92) in Chinese Jinhua pigs.
• Increased reference panel size improved rare variant imputation; PHARP 4.0 facilitated successful GWAS by imputing causal variants.

Conclusions:

• PHARP 4.0 is a valuable resource for pig genetic research, offering enhanced imputation accuracy and diversity.
• Optimized imputation methods, including RNA-seq-based approaches, improve cost-effectiveness and accuracy in pig genomics.
• PHARP 4.0 supports large-scale genetic studies and breeding programs by enabling accurate genotype imputation.