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Pascarella G, Hon CC, Hashimoto K, Busch A, Luginbühl J, Parr C, Hin Yip W, Abe K, Kratz A, Bonetti A, Agostini F, Severin J, Murayama S, Suzuki Y, Gustincich S, Frith M, Carninci P
Cell 185 (16) 3025-3040.e6 [2022-08-04; online 2022-07-25]
Non-allelic recombination between homologous repetitive elements contributes to evolution and human genetic disorders. Here, we combine short- and long-DNA read sequencing of repeat elements with a new bioinformatics pipeline to show that somatic recombination of Alu and L1 elements is widespread in the human genome. Our analysis uncovers tissue-specific non-allelic homologous recombination hallmarks; moreover, we find that centromeres and cancer-associated genes are enriched for retroelements that may act as recombination hotspots. We compare recombination profiles in human-induced pluripotent stem cells and differentiated neurons and find that the neuron-specific recombination of repeat elements accompanies chromatin changes during cell-fate determination. Finally, we report that somatic recombination profiles are altered in Parkinson's and Alzheimer's disease, suggesting a link between retroelement recombination and genomic instability in neurodegeneration. This work highlights a significant contribution of the somatic recombination of repeat elements to genomic diversity in health and disease.
PubMed 35882231
DOI 10.1016/j.cell.2022.06.032
Crossref 10.1016/j.cell.2022.06.032
pii: S0092-8674(22)00784-X