RNA interference based Screen to Identify Genetic Modifiers of dVAPB

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neuro-degenerative disease affecting motor neurons. VAPB- VAMP (vesicle associated membrane protein-associated protein) –associated protein B has been identified as gene involved in type 8 ALS. However, the exact mechanism by which mutation in VAPB causes neuro-degeneration is unknown. Here we present an RNAi based genetic screen to dissect out an integrated genetic network of VAPB function modifiers. We have screened 10% of Drosophila melanogaster genome and have identified 78 modifiers (27 enhancer and 51 suppressors). Modifiers detected in our screen include known ALS causing genes such as SOD1, Alsin2 and TDP-43. Modifiers also include genes that have been implicated in other neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. We have also identified proteins such as SNAMA, with a known role in apoptosis, and Derlin-1, a component of ER associated degrading machinery as VAPB modifiers.