Allelic value in gene regulation—implications for gene editing

The effectiveness of gene editing relies significantly on the roles of alleles generated in regulating specific genetic pathways. It is essential to conduct functional validation of the targeted allele across multiple distinct genetic backgrounds to ascertain its utility. The influence an allele exerts on a given trait is contingent upon factors like the nature of the trait, the position of the gene within a given pathway, and the genetic background in which it has been/will be tested. This perspective highlights how editing has led to a range of phenotypic variations influenced by the genetic background, with certain lines achieving the desired phenotype alongside pleiotropic effects, whereas others do not manifest the expected phenotype. This challenge may be addressed by prioritizing the identification of the right candidate and specific motifs in the regulatory regions as potential targets rather than directly intervening in coding sequences.