PT  - JOURNAL ARTICLE
AU  - G. Pascarella
AU  - K. Hashimoto
AU  - A. Busch
AU  - J. Luginbühl
AU  - C. Parr
AU  - C. C. Hon
AU  - W. H. Yip
AU  - K. Abe
AU  - A. Kratz
AU  - A. Bonetti
AU  - F. Agostini
AU  - J. Severin
AU  - S. Murayama
AU  - Y. Suzuki
AU  - S. Gustincich
AU  - M. Frith
AU  - P. Carninci
TI  - Recombination of repeat elements generates somatic complexity in human genomes
AID  - 10.1101/2020.07.02.163816
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.07.02.163816
4099  - http://biorxiv.org/content/early/2021/09/24/2020.07.02.163816.short
4100  - http://biorxiv.org/content/early/2021/09/24/2020.07.02.163816.full
AB  - Millions of Alu and L1 copies in our genomes contribute to evolution and genetic disorders via non-allelic homologous recombination, but the somatic extent of these rearrangements has not been systematically investigated. Here we combine short and long DNA reads sequencing of repeat elements with a new bioinformatic pipeline to show that somatic recombination of Alu and L1 elements is common in human genomes. We report new tissue-specific recombination hallmarks, and show that retroelements acting as recombination hotspots are enriched in centromeres and cancer genes. We compare recombination profiles in human induced pluripotent stem cells and differentiated neurons and show that neuron-specific recombination of repeat elements accompanies chromatin changes during cell-fate determination. Finally, we find that somatic recombination profiles are altered in Parkinson’s and Alzheimer’s disease, indicating a link between retroelements recombination and genomic instability in neurodegeneration. This work shows that somatic recombination of repeat elements contributes massively to genomic diversity in health and disease.Competing Interest StatementThe authors have declared no competing interest.