The effects of genetic variation on gene expression dynamics during development

Area of Science:

• Genomics
• Developmental Biology
• Systems Biology

Background:

• Multicellular development and physiology rely on coordinated gene expression changes.
• Expression quantitative trait loci (eQTLs) map genetic variations influencing gene expression, but their dynamic effects are poorly understood.
• Previous studies identified cell-, tissue-, and age-dependent eQTLs, but lacked comprehensive dynamic characterization.

Purpose of the Study:

• To develop an efficient method for inferring gene expression dynamics from static profiles.
• To characterize the impact of cis and trans genetic variation on gene expression dynamics during development.
• To provide the first comprehensive analysis of genetic variation's effect on gene expression dynamics over an extended period.

Main Methods:

• Developed an experimental design to infer gene expression dynamics from single expression profiles across different genotypes.
• Applied this method to study gene expression over a 12-hour period in Caenorhabditis elegans development.
• Analyzed the effects of local (cis) and distant (trans) genetic variation on gene expression timing, rate, magnitude, and shape.

Main Results:

• >50% more cis-eQTLs were identified when considering dynamic variation, including over 900 affecting expression dynamics.
• Local sequence polymorphisms significantly altered the timing, rate, magnitude, and shape of gene expression changes.
• Distal (trans) loci extensively influenced expression dynamics, often acting as modifiers during specific developmental intervals.

Conclusions:

• Genetic variation profoundly impacts the dynamic patterns of gene expression during development.
• The developed approach enables the genetic dissection of dynamic biological processes.
• This study lays the groundwork for understanding genetic influences on development, physiology, and disease progression in humans.