When:
Thursday, May 8, 2025
2:00 PM - 3:00 PM CT
Where: Ward Building, 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it
Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students
Contact:
Lena N.
Group: Center for Autism and Neurodevelopment
Category: Lectures & Meetings
Martin Breuss, Ph.D
Assistant Professor in the Department of Pediatrics | Section of Genetics and Metabolism
Genomic mosaicism—where some but not all cells within a tissue carry a unique mutation—is typically considered a somatic phenomenon with no impact on the collective human genome. However, if such mosaic mutations occur within the germ cell lineage they can transmit to the next generation and present as a ‘germline mutation’ in offspring; in rare cases, this can have a disastrous impact on a child and cause congenital disorders, such as intellectual disability, epilepsy, or congenital heart disease.
We previously reported that this phenomenon is critical in autism spectrum disorder (Breuss et al. 2020, PMID 31873310) and allows for risk stratification to understand recurrence in these families. We further demonstrated through deep whole-genome sequencing (WGS) that on average sperm harbors 30 detectable mosaic variants, the majority of which are absent from blood (Yang*, Breuss* et al. 2021, PMID 34388390). Analysis of these early developmental mutations revealed early developmental dynamics and mutational rate differences between germ cells and somatic tissues. The detectable mosaic variants available through WGS further transmit to the next generation as expected based on the abundance of mosaic variants in sperm (Breuss*, Yang* et al. 2022, PMID 35787314).
Our current efforts include 1) the extension of our sperm mosaicism detection framework to additional clinical cohorts to establish the clinical utility of sperm mosaicism testing; 2) the development of experimental and computational methods to aid mosaic variant analysis; and 3) the testing of targeted deep sequencing as a predictive test to reduce the burden of pathogenic variants in future offspring. Together, our work aims to establish sperm mosaicism testing as a clinical tool to aid in genetic counseling of affected families and males; in parallel, we leverage these data to gain a deeper understanding of developmental and mutational mechanisms.