Genetic modifiers in neurodevelopmental diseases: a C. elegans high-throughput forward genetic screen to identify suppressors of alg-1/AGO1

Rare diseases, despite being individually rare, cumulatively affect millions of people around the world. Over the last decades, high throughput sequencing elevated diagnostic success in rare diseases from ~10% to ~45% but have stalled at ~45% since. One reason for that may be that clinical presentation of the disease-causing alteration(s) could be highly variable. Some individuals may be severely affected while others may not be affected at all. Variants in disease-associated genes rarely act alone and play in concert with other variants in the genome, some of which enhance while some suppress disease presentations. These other variants that modulate the disease outcomes are called genetic modifiers and despite technological advances are extremely difficult to study using human genomes alone. One of the diseases where genetic modifiers are expected to play a role in documented phenotypic variability is Argonaute syndrome that is due to deficiency in the AGO1. To facilitate identification of genetic modifiers in patients with the Argonaute syndrome, we will utilize high throughput genetic modifier screens in a multicellular model organism Caenorhabditis elegans at the University of Calgary which could help identify targets and narrow the search space for modifier detection in patients with variable phenotypes at Strasbourg University.

Faculty Supervisor:

Maja Tarailo-Graovac

Student:

Partner:

Université de Strasbourg

Discipline:

Life Sciences

Sector:

Education

University:

University of Calgary

Program: