Allele Specific Expression in Human – Genomic Makeup and Phenotypic Implications

Abstract

The allele-specific expression phenomenon refers to unbalanced expression from the two parental alleles in a tissue of a diploid organism. AlleleDB is a high-quality resource that reports on about 30,000 ASE variants (ASE-V) from hundreds of human samples. In this study, we present the genomic characteristics and phenotypic implications of ASE. We identified tens of segments with extreme density of ASE-V, many of them are located at the major histocompatibility complex (MHC) locus. Notably, at a resolution of 100 nucleotides, the likelihood of ASE-V increases with the density of polymorphic sites. Another dominant trend of ASE is a strong bias of the expression to the major allele. This observation relies on the known allele frequencies in the healthy human population. Overlap of ASE-V and GWAS associations was calculated for 48 phenotypes from the UK-Biobank. ASE-V were significantly associated with a risk for inflammation (e.g. asthma), autoimmunity (e.g., rheumatoid arthritis, multiple sclerosis, and type 1 diabetes) and several blood cell traits (e.g., red cell distribution width). At the level of the ASE-genes, we seek association with all traits and conditions reported in the GWAS catalog. The statistical significance of ASE-genes to GWAS catalog reveals association with the susceptibility to virus infection, autoimmunity, inflammation, allergies, blood cancer and more. We postulate that ASE determines phenotype diversity between individuals and the risk for a variety of immune-related conditions.

Gene age shapes the transcriptional landscape of sexual morphogenesis in mushroom-forming fungi (Agaricomycetes)

“…At the same time, young genes are known to be under weaker evolutionary constraint than conserved ones, raising the possibility that ASE might arise neutrally in the transcriptome. This would be consistent with the neutral model of expression evolution ( Fay and Wittkopp, 2008 ) and nonadaptive explanations, such as leaky regulation or transcriptional noise ( Cheng et al, 2017 ; Khan et al, 2012 ; Shih and Fay, 2021 ; Wainer-Katsir and Linial, 2019 ). Under this interpretation, ASE may be a tolerated, rather than an adaptive phenomenon in agaricomycete fungi.…”

Gene age predicts the transcriptional landscape of sexual morphogenesis in multicellular fungi

“…This would be consistent with the neutral model of expression evolution (Fay and Wittkopp, 2008) and non-adaptive explanations, such as leaky regulation or transcriptional noise (Cheng et al, 2017;Khan et al, 2012;Shih and Fay, 2021;Wainer-Katsir and Linial, 2019). Under this interpretation, ASE may be a tolerated, rather than an adaptive phenomenon in CM fungi.…”