Next-generation sequencing and single-cell-based technologies have shown that a person’s genome in the cells of our body over time.
External pressure and the need to grow and repair tissues places our individual cells at constant risk of acquiring mutations. As we age, tissues become a jigsaw of distinct sub-populations of cells carrying distinct hereditary information, a phenomenon known as somatic mosaicism. Specifically structural variants (SVs; e.g. deletions and inversions - large chunks of DNA differing between genomes of individual cells account for most varying bases in the human genome and are thought to be a key contributor to somatic mosaicisms.
The aim of this study was to uncover the extent and impact of SV mosaicism in two kinds of human tissue. In order to do so, we pursued single cell analyses using novel cutting-edge technologies, which offered the most direct way to detect somatic SVs and allowed us to functionally characterize these variations in individual cells.
Copy-neutral SV classes (e.g. inversions and translocations) are usually missed in conventional methods, including bulk DNA sequencing and single cell DNA sequencing approaches, which are limited to the identification of copy-number variants (CNVs).
We harnessed our newly developed experimental and computational tools based on the DNA template strand sequencing single cell technology (Strand-seq_ to construct a single cell catalog of a wide variety of relevant copy-neutral and copy-imbalanced SV classes in the blood compartment and the skin during human aging. Using this catalog, we aimed to study the functional impact of SV mosaicism on the cellular level, as a foundation for elucidating roles of somatic SVs in age-related phenotypes and diseases.
The understanding of the common role of SV mosaicism on aging and disease, had a significant impact in the field of human lifescience and research.
