Mapping Modifiers of Protein Aggregation

Polyglutamine expansions that go beyond 35 CAG repeats in disease causing genes such as the Huntington gene, cause misfolding of proteins and can lead to aggregation and disease. Disruption of proteostasis and aggregation it thought to play a significant role in conformational diseases. In addition, there are other aspects that influence onset, progression and severity of disease. In this study, we look at how natural variants can contribute to increased protein aggregation as well as suppress aggregation. Specifically, we try to map a single recessive locus that contributes to increased aggregation in head muscle cells in Caenorhabditis elegans, as well as a network of modifiers contributing to suppression of aggregation. Here we describe how these strains were created, the process of determining whether these phenotypes are a result of a single modifier, or network of genes as well as mapping the modifier responsible to high aggregation of head muscle cells.