RT Journal Article SR Electronic T1 Discovery and characterization of Alu repeat sequences via precise local read assembly JF bioRxiv FD Cold Spring Harbor Laboratory SP 014977 DO 10.1101/014977 A1 Julia H. Wildschutte A1 Alayna Baron A1 Nicolette M. Diroff A1 Jeffrey M. Kidd YR 2015 UL http://biorxiv.org/content/early/2015/05/21/014977.abstract AB Alu insertions have contributed to >11% of the human genome and ~30-35 Alu subfamilies remain actively mobile, yet the characterization of polymorphic Alu insertions from short-read data remains a challenge. We build on existing computational methods to combine Alu detection and de novo assembly of WGS data as a means to reconstruct the full sequence of insertion events from Illumina paired end reads. Comparison with published calls obtained using PacBio long-reads indicates a false discovery rate below 5%, at the cost of reduced sensitivity due to the colocation of reference and non-reference repeats. We generate a highly accurate call set of 1,614 completely assembled Alu variants from 53 samples from the Human Genome Diversity Project panel. We utilize the reconstructed alternative insertion haplotypes to genotype 1,010 fully assembled insertions, obtaining >99% accuracy. In our assembled sequences, we find evidence of non-classical insertion mechanisms and observe 5’ truncation in 16% of AluYa5 and AluYb8 insertions. The sites of truncation coincide with stem-loop structures and SRP9/14 binding sites in the Alu RNA, implicating L1 ORF2p pausing in the generation of 5’ truncations.