How tiny changes in DNA shape the developing brain

Diogo Castro

i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Portugal

Autism spectrum disorder (ASD) affects approximately one in every 44 children and is known to have a strong genetic basis . However, most of the genetic changes linked to ASD are not found in genes themselves, but in the non-coding regions of DNA that control how genes are turned on and off. Understanding how these changes influence brain development could help explain why ASD occurs and improve how we assess the risk of developing it.

This project aims to uncover how these non-coding genetic changes affect brain development, particularly in the early stages when the brain’s structure is being formed. The team will use advanced tools to test thousands of genetic variants to see how they influence gene activity in human brain cells grown in the lab. They will also use machine learning to identify which of these changes are most strongly linked to ASD, creating a model that could help predict who is at risk.

To understand how these changes affect brain development, the researchers will edit specific genetic variants into stem cells and grow them into mini-brains, or organoids. This will allow them to observe how these changes impact the formation and function of brain tissue. The project brings together experts in brain development, genetics, and data science, making it well positioned to tackle this complex challenge.

• Gaia Novarino, Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria

• Justin O'Sullivan, The Liggins Institute, University of Auckland, New Zeland

Deciphering the contribution of common non-coding genetic variation to Autism Spectrum Disorders

€731,631.00