Multi-dimensional annotation of porcine variants using genomic and epigenomic features in pigs.

Abstract

Background: Investigating the functional impact of genomic variants is essential to uncover the molecular mechanisms behind complex traits. This study compiled a comprehensive dataset of 1,817 whole-genome sequences from diverse pig breeds and populations, capturing the global pig genetic diversity.

Results: Our analyses first revealed 27,167 loss-of-function variants (LoFs), the majority of which also influenced gene expression and splicing, and enriched in genomic regions associated with complex traits in pigs. We further genome-wide annotated non-coding variants, and then focused on these resided in 5' untranslated region (5'UTR). Although they had lower deleterious impact on protein sequence compared to coding variants, they enriched in promoters and exhibited functional consequences on gene expression and splicing and finally complex traits. We employed the Basenji deep learning model and ATAC-seq to predict the impact of these SNPs on chromatin accessibility in 13 pig tissues. SNPs with higher predicted scores demonstrated stronger effects on gene expression/splicing and complex traits-particularly average backfat thickness-compared to variants with lower scores.

Conclusions: In summary, our study provides a comprehensive catalog of genomic variants in both protein-coding and non-coding regions, and elucidated their functional consequences on epigenome, transcriptome, and complex traits in pigs.