Diverse Patterns of Allele-Specific Expression in Healthy Human Tissues
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Differences in gene sequence and gene expression underlie variation in traits. However, even monozygotic twins do not express their genes in the same way, develop divergence in traits, and succumb to distinct chronic diseases. During development, epigenetic silencing programs cause diversity in allele expression, resulting in differences in traits and chronic disease risk. To quantify human autosomal allele expression between individuals, we analyzed human allele-specific expression data from the GTEx project. For hundreds of genes, some individuals will express the gene biallelically, while many others may only express one allele or extreme bias towards one allele. We found gene-specific patterns of interindividual variation in allele bias. We found that some individuals have more genome-wide monoallelic/biased expression than others. Individuals also had distinct combinations of allele expression bias. These differences can underlie variation in traits, idiopathic or incompletely penetrant traits/diseases, and chronic diseases.
Significance/Impact
Allele-specific expression can affect cancer, immune response, and genetic disease. This work reveals 1) gene-specific multimodal patterns of interindividual variation in allele bias, 2) that individuals can maintain bias across tissues, and 3) that different individuals have distinct combinations of silenced alleles. These different patterns and the weighted classifications demonstrate how allele bias manifests between individuals; there are individuals and tissues with more biased/non-Mendelian expression and some tissues have more age-related changes in which alleles are silenced.