Main aim WP1: To generate isogenic iPSC cell lines to create an in-depth cell model landscape analysis that will include both morphological and molecular biological changes due to CAG-repeat length only: wild-type, intermediate, adult-onset and early-onset repeats for HD, SCA1 and SCA3 with identical genetic background but differing in CAG length only.

WP leader: Willeke van Roon-Mom (LUMC)

Specific Objectives: Determine disease landscapes for SCA1, SCA3 and HD that are due to increased pathological CAG-repeat length using isogenic iPSC cell lines. Since CAG repeat length in patients typically explains about 50% of variance in onset of disease symptoms, we will first capture disease landscapes that are due to CAG-repeat length only use isogenic iPSC cell lines from two well characterized control cell lines.