Genome-wide allele-specific expression in multi-tissue samples from healthy male baboons reveals the transcriptional complexity of mammals

Abstract

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could quantify ASE across 72% of the total annotated protein-coding gene set. We identified genes that exhibit ASE and affect specific tissues and genotypes. We discovered ASE SNVs that also exist in human populations with identical alleles and that are designated as pathogenic by both the PrimateAI-3D and AlphaMissense models.

Keywords: allele switching; allele-specific-expression; baboon; haplotype phasing; haplotype switching; heterozygosity; imprinting; pathogenic SNVs; primates; sequencing.