Diverse Patterns of Allele-Specific Expression in Healthy Human Tissues.

Area of Science:

• Genetics
• Epigenetics
• Human Biology

Background:

• Gene sequence and expression drive trait variation.
• Even identical twins exhibit differences in gene expression, trait development, and disease susceptibility.
• Epigenetic silencing during development creates diverse allele expression patterns, impacting traits and disease risk.

Purpose of the Study:

• To quantify interindividual differences in human autosomal allele-specific expression.
• To investigate gene-specific patterns of allele bias variation among individuals.
• To explore how allele expression bias contributes to human trait and disease variability.

Main Methods:

• Analysis of human allele-specific expression data from the Genotype-Tissue Expression (GTEx) project.
• Quantification of gene expression patterns, including biallelic, monoallelic, and biased expression.
• Identification of gene-specific patterns and individual-level variations in allele bias.

Main Results:

• Significant interindividual variation exists in allele-specific gene expression.
• Some individuals exhibit more genome-wide monoallelic or biased expression than others.
• Distinct combinations of allele expression bias were observed across individuals and maintained across tissues.
• Age-related changes in allele silencing were noted in certain tissues.

Conclusions:

• Allele-specific expression patterns vary significantly between individuals and can be tissue-specific.
• These variations, including non-Mendelian expression, contribute to human trait diversity and susceptibility to diseases.
• Understanding allele bias is crucial for comprehending genetic disease, immune response, and cancer development.