A comprehensive identification and annotation of mobile LINE-1 retrotransposons across human reference and personal genomes

Abstract

LINE-1 (L1) is a type of mobile genetic element (retrotransposon) that can self-copy into distinct parts of its host genome by dynamically shaping its content. In humans, misregulation of these elements have been associated as the potential cause of distinct types of pathologies and neurodevelopmental disorders, including cancer, Rett syndrome and Aicardi Goutierrez disease. However, the precise annotation of these 6 kb long nucleotide sequence is a challenging task due to the high similarity between their internal regions (coding and non-coding) for distinct L1 families. Current L1 reference annotations such as RepeatMasker still lack sequence details and also provide confounding annotated information, that includes thousands of incomplete L1 sequences annotated as representative full-length, and missing information on their regulatory and coding regions (5UTR, ORF1, intron, ORF2 and 3UTR). Additionally, current L1 resources also provide annotations based on consensus reference genomes and does not include individual genome information at allele-level and nucleotide-level resolution. Here, we present L1Farm as a complementary databank and annotation resource that contains a comprehensive analysis and annotation of L1 subfamilies identified in the current human reference genome (build Hg38) and in two individual Asian and Caucasian genomes at allele-level and nucleotide-level resolution. L1 elements sequences were also annotated with genomic loci and ranked according to their full-length content and similarity.