Clinical variants in Caenorhabditis elegans expressing human STXBP1 reveal a novel class of pathogenic variants and classify variants of uncertain significance.

ABSTRACT:

Purpose

Modeling disease variants in animals is useful for drug discovery, understanding disease pathology, and classifying variants of uncertain significance (VUS) as pathogenic or benign.

Methods

Using Clustered Regularly Interspaced Short Palindromic Repeats, we performed a Whole-gene Humanized Animal Model procedure to replace the coding sequence of the animal model's unc-18 ortholog with the coding sequence for the human STXBP1 gene. Next, we used Clustered Regularly Interspaced Short Palindromic Repeats to introduce precise point variants in the Whole-gene Humanized Animal Model-humanized STXBP1 locus from 3 clinical categories (benign, pathogenic, and VUS). Twenty-six phenotypic features extracted from video recordings were used to train machine l

SUBMITTER: Hopkins CE 

PROVIDER: S-EPMC11141691 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature