RC-Seq

Retrotransposon Capture Sequencing

RC-seq is a high-throughput protocol to map and study retrotransposon insertions (Baillie et al., 2011). In this method, after gDNA is fractionated, retrotransposon binding sites on DNA hybridize to transposon binding sites on a microarray. Deep sequencing provides accurate information that can be aligned to a reference sequence to discover novel retrotransposition events. A single-cell version (scRC-seq) has also been described (Upton et al., 2015).

Advantages:

  • Ability to clearly identify and detect novel retrotransposition events
  • Can specifically study transposon binding sites of interest
  • High-throughput protocol
  • PCR validation rate estimated at 98.5%

Disadvantages:

  • Different types of mobile element insertions (MEIs) require separate PCR experiments with different primers (Xing et al., 2013)
  • Hybridization errors can lead to sequencing unwanted DNA fragments
  • PCR biases can underrepresent GC-rich templates
  • Similar transposition binding sites can lead to sequence ambiguity and detection for a transposition event


Reagents:

Illumina Library prep and Array Kit Selector



Reviews:

Xing J., Witherspoon D. J. and Jorde L. B. Mobile element biology: new possibilities with high-throughput sequencing. Trends Genet. 2013;29:280-289



References:

Klawitter S., Fuchs N. V., Upton K. R., et al. Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells. Nat Commun. 2016;7:10286

Upton K. R., Gerhardt D. J., Jesuadian J. S., et al. Ubiquitous L1 mosaicism in hippocampal neurons. Cell. 2015;161:228-239

Solyom S., Ewing A. D., Rahrmann E. P., et al. Extensive somatic L1 retrotransposition in colorectal tumors. Genome Res. 2012;22:2328-2338

Shukla R., Upton K. R., Munoz-Lopez M., et al. Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell. 2013;153:101-111