Figure 1.

Strategy and analysis pipeline exploiting human insulin-receptoropathy-associated polymorphisms and linking them to emerging C. elegans genetic tools. Among the components of the insulin signaling pathway, the human insulin receptor was chosen for its high degree of sequence similarity with C. elegans DAF-2. A combination of existing dauer mutants (Daf-defective and Daf-constitutive), MMP alleles and CRISPR-Cas9 generated alleles were coupled with a recursive verification of a high-temperature induction of dauer (Hid) phenotype to provide a detailed look at conserved regions of the human insulin receptor and the functional consequences of conservative and nonconservative replacements of critical residues in the tyrosine kinase domain.