Every human organ begins as just a few cells that gradually take on specialized roles. Understanding how this complex process unfolds — and how it can go wrong — is essential for uncovering the origins of rare genetic diseases. With new single-cell technologies, we can now follow thousands of individual cells during development, track how they change over time, and see how genetic alterations disrupt normal pathways.  In my talk, I will present applications of these methods to patient-derived samples and mouse models for rare congenital malformations, with a particular focus on non-coding mutations and structural variants that perturb 3D genome architecture. Integrating perturbation screens and new sequencing enables us to link regulatory variation to disrupted cell states and tissue morphogenesis. These insights not only illuminate the pathogenesis of Mendelian disorders but also establish a framework for systematically decoding the functional impact of genetic variation at single-cell resolution.

More information:

• https://research.uni-luebeck.de/en/persons/malte-spielmann