An Integrative Genetic Strategy for Identifying Causal Genes at Quantitative Trait Loci in Chickens

Identifying causal genes underlying quantitative trait loci (QTLs) remains challenging due to small effect sizes and the prevalence of non-coding variants. Although multi-omics integration frameworks such as eQTL- and epigenomic-based approaches and TWAS have advanced gene prioritization, their application in poultry and livestock is often constrained by limited reference panels and tissue resources. This review introduces a cost-effective F₂-based integrative framework and compares it with existing multi-omics strategies.

The proposed framework combines QTL remapping, transcriptome analysis, haplotype frequency comparison, association analysis, and conditional correlation analysis within a single workflow. Causal analysis and quantitative complementation tests using knockout birds are incorporated to identify causal genes.

By reusing the original F₂ population employed for QTL mapping, this approach enables hypothesis-independent gene prioritization without requiring additional fine-mapping crosses. Its effectiveness is demonstrated through comparison with conventional multi-omics methods, and the integration of causal analysis and quantitative complementation testing provides robust genetic evidence for pinpointing causal genes.

This F₂-based framework efficiently prioritizes and verifies causal gene candidates directly within the mapping population, offering a cost-effective alternative to multi-omics approaches that require large-scale resources. It is broadly applicable to diverse chicken crosses and readily transferable to other small livestock species and model organisms.