title: Retrotransposon Capture Sequencing (RC-Seq): A Targeted, High-Throughput Approach to Resolve Somatic L1 Retrotransposition in Humans.
abstract: Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an individual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem; however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given sample can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an individual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states.
authors.affiliation: Mater Research Institute,University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.|Pfizer-University of Granada-Andalusian Goverment Centre for Genomics and Oncological Research, Av. de la Ilustracion 114, Granada, 18016, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Sanchez-Luque
authors.affiliation: Mater Research Institute,University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.|Department of Human Genetics, University of Michigan Medical School, 1241 E. Catherine St, Ann Arbor, MI, 48109, USA.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Richardson
authors.affiliation: Mater Research Institute,University of Queensland, 37 Kent Street, Woolloongabba, QLD, 4102, Australia. faulknergj@gmail.com.|Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia. faulknergj@gmail.com.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Faulkner
mesh_terms: D019295:Computational Biology / Q000379:methods; D015894:Genome, Human; D015698:Genomic Library; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D018626:Retroelements
chemical_list: D018626:Retroelements
keywords: Alu; LINE-1; Mobile genetic element; Neurogenesis; Oncogenesis; Retrotransposition; Somatic mosaicism; Whole genome sequencing (WGS)