Transcriptional enhancers in human neuronal development and the brain

The human genome contains more than 100,000 enhancers, regulatory elements along the DNA that fine-tune gene expression.

We will now pioneer the identification of new enhancer elements regulating neuronal development, with focus on cilia formation and axonal growth.

After this first phase, we will study samples available at The Brain Bank at Karolinska Institutet to map enhancer activity in different brain regions.

This project has broad implications for research on neuronal disorders, but will also create a resource for any researchers interested in how genes are regulated in different brain regions and how different genes are involved in neuronal development.

As examples, genome-wide association studies (GWAS) have been broadly used in finding susceptibility genes for many neuronal disorders, and it is now widely understood that most such findings involve regulatory elements.

Developmental dyslexia (DD) is the most common learning disability, and unrecognized DD may cause substantial social harm from school age to adulthood.

Its biological basis and major genetic influence have been firmly established, and tens of candidate risk genes have been identified by us and other researchers.

As biological factors involved in DD, our group has pioneered the identification of the first, best-replicated DD-associated genes and their role in regulating brain structures and functions. Now we aim at understanding the regulatory network of genes and enhancers involved in these disorders.