rescuing alu recovery of new inserts shows line-1 preserves alu activity through a-tail expansion拯救alu复苏新插入显示1号线保留alu活动通过尾巴扩张.pdfVIP

Rescuing Alu: Recovery of New Inserts Shows LINE-1 Preserves Alu Activity through A-Tail Expansion 1 2 1 3 Bradley J. Wagstaff , Dale J. Hedges , Rebecca S. Derbes , Rebeca Campos Sanchez , 3 3 1 Francesca Chiaromonte , Kateryna D. Makova , Astrid M. Roy-Engel * 1Tulane Cancer Center, Department of Epidemiology, Tulane University, New Orleans, Louisiana, United States of America, 2 Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America, 3 Department of Biology, Center for Medical Genomics, Pennsylvania State University, University Park, Pennsylvania, United States of America Abstract Alu elements are trans-mobilized by the autonomous non-LTR retroelement, LINE-1 (L1). Alu-induced insertion mutagenesis contributes to about 0.1% human genetic disease and is responsible for the majority of the documented instances of human retroelement insertion-induced disease. Here we introduce a SINE recovery method that provides a complementary approach for comprehensive analysis of the impact and biological mechanisms of Alu retrotransposition. Using this approach, we recovered 226 de novo tagged Alu inserts in HeLa cells. Our analysis reveals that in human cells marked Alu inserts driven by either exogenously supplied full length L1 or ORF2 protein are indistinguishable. Four percent of de novo Alu inserts were associated with genomic deletions and rearrangements and lacked the hallmarks of retrotransposition. In contrast to L1 inserts, 59 truncations of Alu inserts are rare, as most of the rec