The Role of the Mitochondria in the 16p12.2 Deletion

open_access
Open Access
Author:
Prabhu, Anisha
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Santhosh Girirajan, Thesis Supervisor
Scott E. Lindner, Thesis Honors Advisor
Keywords:
16p12.2 Deletion
Neurodevelopmental Disorders
Autism
Reactive Oxygen Species
Oxidative Stress
Abstract:
Childhood neurodevelopmental disorders such as autism and intellectual disability have a strong genetic basis, but the cellular mechanisms remain largely unknown. One feature of complex genetic disorders is that individuals carrying the same genetic mutation manifest different clinical features. An individual with the 16p12.2 deletion has a significant risk of developing a range of neurodevelopmental disorders due to a combinatorial effect of the 16p12.2 deletion and other background mutations. The 16p12.2 deletion encompasses seven genes with a wide variety of possible phenotypes and a diagnosis of autism spectrum disorder (ASD) or intellectual disability usually follows. Several neurodevelopmental disorders including ASD and others are linked to developmental neurotoxicity which has been known to regulate a range of brain processes converging on the presence of oxidative stress and build-up of reactive oxygen species (ROS). In this thesis, cellular ROS levels were measured and compared between CRISPR 16p12.2 deletion mutants and control induced pluripotent stem cell lines. Results showed no significant changes in ROS levels; however, deletion mutant cell lines trended toward a lower percentage of dead cells and higher total cell numbers. This supports the conclusion that cell proliferation pathways may be altered due to the 16p12.2 deletion, which has been reported in other studies. This research allows us to understand the altered cellular mechanisms in the 16p12.2 deletion and serves as a starting point for future studies to further uncover the mechanisms leading to various phenotypes associated with complex genetic disorders.