Restriction Enzyme Based Enriched L1Hs Sequencing (REBELseq): A Scalable Technique for Detection of Ta Subfamily L1Hs in the Human Genome.

TitleRestriction Enzyme Based Enriched L1Hs Sequencing (REBELseq): A Scalable Technique for Detection of Ta Subfamily L1Hs in the Human Genome.
Publication TypeJournal Article
Year of Publication2020
AuthorsReiner BC, Doyle GA, Weller AE, Levinson RN, Namoglu E, Pigeon A, Perea EDávila, Weickert CShannon, Turecki G, Mash DC, Crist RC, Berrettini WH
JournalG3 (Bethesda)
Volume10
Issue5
Pagination1647-1655
Date Published2020 05 04
ISSN2160-1836
Abstract

Long interspersed element-1 retrotransposons (LINE-1 or L1) are ∼6 kb mobile DNA elements implicated in the origins of many Mendelian and complex diseases. The actively retrotransposing L1s are mostly limited to the L1 human specific (L1Hs) transcriptional active (Ta) subfamily. In this manuscript, we present REBELseq as a method for the construction of Ta subfamily L1Hs-enriched next-generation sequencing libraries and bioinformatic identification. REBELseq was performed on DNA isolated from NeuN+ neuronal nuclei from postmortem brain samples of 177 individuals and empirically-driven bioinformatic and experimental cutoffs were established. Putative L1Hs insertions passing bioinformatics cutoffs were experimentally validated. REBELseq reliably identified both known and novel Ta subfamily L1Hs insertions distributed throughout the genome. Differences in the proportion of individuals possessing a given reference or non-reference retrotransposon insertion were identified. We conclude that REBELseq is an unbiased, whole genome approach to the amplification and detection of Ta subfamily L1Hs retrotransposons.

DOI10.1534/g3.119.400613
Alternate JournalG3 (Bethesda)
PubMed ID32132168
PubMed Central IDPMC7202019
Grant ListR21 NS095756 / NS / NINDS NIH HHS / United States
R01 DA040972 / DA / NIDA NIH HHS / United States
R01 MH109260 / MH / NIMH NIH HHS / United States
K01 DA036751 / DA / NIDA NIH HHS / United States