Family-based Analysis of Allele-Specific Expression Reveals Mostly Simple, Intermediate-type of Inheritance

Background The phenomenon of allele-specific expression (ASE) is widespread in diploids and can be used to infer the activities of variants in cis-regulatory elements. ASE can be detected by counting RNA-seq reads, but this requires variants to be present in the transcribed region. Another method is RNA and genome sequencing of many individuals, which is not cost effective. Here, we introduce a family-based experimental approach for identifying ASE and possible cis-acting elements that avoids these limitations. Results Using a rabbit family with eight offspring, we identified 913 genes that exhibit ASE. All of these examples show intermediate inheritance of the gene expression level trait. As expected, not all genes presented variants in their RNA transcripts. Therefore, we inferred the ASE by counting the RNA-seq reads across the family. We identified seven categories of expression patterns by assuming three possible expression levels (high, medium, and low). For example, H_L means that the expression level of a gene is high in the mother, low in the father, and medium in the offspring. Using the same logic, we identified nearby conserved transcription factor binding sites where a sequence variant had the same genotype pattern (e.g., AAxBB) as the identified potential cis-acting element. We also performed a differential gene expression (DEG) analysis between the parents to identify genes with potential roles in meat quantity and quality. Conclusions We demonstrated that RNA and whole-genome sequencing of only two parents and eight offspring was sufficient to detect ASE and possible corresponding cis-acting elements in large numbers.