Detection and annotation of transposable element insertions and deletions on the human genome using nanopore sequencing

Javier Cuenca-Guardiola; Belén de la Morena-Barrio; Esther Navarro-Manzano; Jonathan Stevens; Willem H Ouwehand; Nicholas S Gleadall; Javier Corral; Jesualdo Tomás Fernández-Breis

doi:10.1016/j.isci.2023.108214

Detection and annotation of transposable element insertions and deletions on the human genome using nanopore sequencing

iScience. 2023 Oct 14;26(11):108214. doi: 10.1016/j.isci.2023.108214. eCollection 2023 Nov 17.

Authors

Affiliations

¹ Departamento de Informática y Sistemas, Universidad de Murcia, CEIR Campus Mare Nostrum, IMIB-Pascual Parrilla, Facultad de Informática, Campus de Espinardo, Murcia 30100, Spain.
² Servicio de Hematología, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-III, Ronda de Garay S/N, Murcia 30003, Spain.
³ Department of Haematology, University of Cambridge, CB2 0PT, Cambridge Biomedical Campus, Cambridge, Cambridge, England, UK.
⁴ Blood and Transplant, National Health Service (NHS), CB2 0QQ, Cambridge Biomedical Campus, Cambridge, England, UK.
⁵ British Heart Foundation Cambridge Centre of Excellence, Division of Cardiovascular Medicine, Cambridge Heart and Lung Research Institute, Cambridge Biomedical Campus, Cambridge, England CB2 0AY, UK.
⁶ University College London Hospitals, NHS Foundation Trust, London, England, UK.

Abstract

Repetitive sequences represent about 45% of the human genome. Some are transposable elements (TEs) with the ability to change their position in the genome, creating genetic variability both as insertions or deletions, with potential pathogenic consequences. We used long-read nanopore sequencing to identify TE variants in the genomes of 24 patients with antithrombin deficiency. We identified 7 344 TE insertions and 3 056 TE deletions, 2 926 were not previously described in publicly available databases. The insertions affected 3 955 genes, with 6 insertions located in exons, 3 929 in introns, and 147 in promoters. Potential functional impact was evaluated with gene annotation and enrichment analysis, which suggested a strong relationship with neuron-related functions and autism. We conclude that this study encourages the generation of a complete map of TEs in the human genome, which will be useful for identifying new TEs involved in genetic disorders.

Keywords: Genomics; Human Genetics; Methodology in biological sciences; Sequence analysis.