nCATS to Sequence Mobile Element Insertions

Camille Mumm, a graduate student at the University of Michigan, presented at London Calling 2023 a five-minute session entitled “Exploring the impact of mobile elements on Alzheimer’s disease using targeted long-read sequencing. They explained that Alzheimer’s disease (AD) is a devastating neurodegenerative disease with not yet fully characterized genetic mechanisms. Somatic mutations in the brains of patients with AD have been thought to be responsible for the pathophysiology. Mumm was interested in characterizing the mosaicism from retrotransposons. To do this, Mumm used post-mortem brain samples and targeted long-read sequencing. For this, they used Cas9-targeted sequencing (nCATS) for mobile element insertions (MEIs) for elements active in the human genome. They have samples from control (5) and high likelihood AD (4), and Mumm will characterize MEI events between regions from the same patient and between patients and groups. Mumm shared preliminary data from regions from the cerebellum, frontal cortex, and hippocampus using IGB. Methylation patterns were compared between MEIs from different regions were compared. Future studies Mumm and colleagues will work on include exploration of methylation between reference and non-reference MEIs and evaluation of other repetitive element variation between regions and samples. The targeted approach using long-read sequencing will help Mumm obtain useful information about sequence and methylation variations both within and between patients. This is such an exciting graduate student project: whatever they find is novel and likely will generate future questions. I have to think about nCATS and adaptive sampling to better understand sequence variation and potential methylation patterns in bacteria.

brain image on digital tablet
How can targeted sequencing help researchers learn about active mobile genetic elements in the human brain? Photo by Tima Miroshnichenko on Pexels.com