Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme

Area of Science:

• Genomics and Bioinformatics
• Quantitative Genetics
• Plant Breeding

Background:

• Current genetic variant screening for gene regulation often relies on allele-specific expression (ASE) detected in vivo.
• While ASE reveals cis-acting variation, it doesn't fully explore underlying regulatory mechanisms.
• Identifying specific nucleotide changes governing gene expression differences requires more advanced methods.

Purpose of the Study:

• To introduce a quantitative genetics approach for genome-wide analysis of allele-specific expression differences (GASED).
• To distinguish cis- and trans-regulatory changes and attribute expression imbalances to cis-regulatory variation.
• To facilitate systematic surveys of naturally occurring cis-regulatory variation in various species.

Main Methods:

• Developed the genome-wide analysis of allele-specific expression differences (GASED) approach.
• Utilized a diallel design, commonly used in plant breeding, to estimate general combining abilities (GCA) and specific combining abilities (SCA).
• Applied GASED to analyze gene expression in diploid Arabidopsis thaliana hybrids.

Main Results:

• Identified 715 genes likely carrying allelic polymorphisms causing at least a 1.5-fold allelic expression difference in 10 Arabidopsis thaliana hybrids.
• GASED is not limited to genes with detectable allelic transcript variants, a key advantage over other ASE methods.
• Observed a false-positive rate of 9/41, indicating its utility as a pre-screening tool.

Conclusions:

• GASED is a valuable pre-screening method for accelerating the discovery of cis-regulatory variation.
• The approach can be applied to laboratory model species (Arabidopsis, mouse, rat, fruitfly) and crop species (corn).
• GASED enhances the systematic survey of naturally occurring cis-regulatory variation among inbred lines.