Activities and Biological Implications of Mobile Elements in Canines

Mobile short and long interspersed elements (SINEs and LINEs) are fragments of DNA that continue to shape the genomes of many organisms through retrotransposition, leading to sporadic cases of disease and phenotypic variation and serving as substrates that seed the formation of subsequent structural variants. The dog has emerged as an important model system for mapping traits relevant to human disease. Studies have linked canine mobile element insertions (MEI) to disease-associated variants in human orthologs such as narcolepsy and centronuclear myopathy. Akin to the active Alu and L1Hs in humans, canine MEIs have undergone recent expansion with thousands of dimorphic copies, indicating that these elements remain active.

To investigate the genomic impact and biology of canine MEIs, we implemented an anchored-mapping approach from genome sequence data of ~90 globally sampled canids, having identified >32,000 non-reference SINEC_Cf and >1,400 L1-Y_Cf copies. Local assembly was used to recover >19,000 complete SINEC_Cf copies, and infer ~140 ‘full-length’ L1-Y_Cf. To assess for their potential of retrotransposition, we subcloned a non-reference full-length L1-Y_Cf from a fosmid library constructed from a Great Dane individual. We used cell-based retrotransposition assays to demonstrate that the isolated L1 is competent for retrotransposition in human cells. We also demonstrate the ability of the canine L1 to mobilize, in trans, several variants of the canine SINE, SINEC_Cf. We anticipate these data will provide a MEI variant resource for incorporation to future canine GWAS analysis and will be critical for understanding how MEIs contribute to the structural variation observed in canines.