Recombination of repeat elements generates somatic complexity in human genomes
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Abstract
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.
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A recent study identified an increase in mosaicism due to recombination between Alu and L1 elements in Parkinson's and Alzheimer's disease.
“Recently, a study identified an increase in mosaicism due to recombination between Alu and L1 elements in Parkinson’s and Alzheimer’s disease120.”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [120]
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References 71 · Cited by 77
- Authors
- Pascarella, G., Hon, C. C., 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.
- Affiliations
- RIKEN Center for Integrative Medical Sciences (JP)
- The University of Tokyo (JP)
- University of California San Diego (US)
- Stockholm University (SE)
- Science for Life Laboratory (SE)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Italian Institute of Technology (IT)
- Artificial Intelligence Research Center (JP)
- Human Technopole (IT)
- Corresponding author
- Pascarella, Giovanni
- Carninci, Piero
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 185
- Issue
- 16
- Pages
- 3025-3040.e6
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4287448803
- Cited by
- 77
- References
- 71
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 25 · 2023: 16 · 2022: 2 · 2021: 1
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- RIKEN
- Japan Agency for Medical Research and Development (JP19dm0107106)
- Japan Society for the Promotion of Science (JP16H06277)
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- V(D)J recombination, non-allelic homologous recombination, repetitive elements, Alu elements, LINE-1 retrotransposons, retrotransposons, centromere, cancer genes, induced pluripotent stem cells, neurons, cell fate determination, chromatin, Parkinson's disease, Alzheimer's disease, genomic instability, neurodegeneration
- MeSH terms
- Humans, Repetitive Sequences, Nucleic Acid, Genome, Human, Retroelements, Long Interspersed Nucleotide Elements, Alu Elements, Homologous Recombination
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