@article{Parkinson01022015, author = {Parkinson, Nicholas J. and Roddis, Matthew and Ferneyhough, Ben and Zhang, Gang and Marsden, Adam J. and Maslau, Siarhei and Sanchez-Pearson, Yasmin and Barthlott, Thomas and Humphreys, Ian R. and Ladell, Kristin and Price, David A. and Ponting, Chris P. and Hollander, Georg and Fischer, Michael D.}, title = {Violation of the 12/23 rule of genomic V(D)J recombination is common in lymphocytes}, volume = {25}, number = {2}, pages = {226-234}, year = {2015}, doi = {10.1101/gr.179770.114}, abstract ={V(D)J genomic recombination joins single gene segments to encode an extensive repertoire of antigen receptor specificities in T and B lymphocytes. This process initiates with double-stranded breaks adjacent to conserved recombination signal sequences that contain either 12- or 23-nucleotide spacer regions. Only recombination between signal sequences with unequal spacers results in productive coding genes, a phenomenon known as the “12/23 rule.” Here we present two novel genomic tools that allow the capture and analysis of immune locus rearrangements from whole thymic and splenic tissues using second-generation sequencing. Further, we provide strong evidence that the 12/23 rule of genomic recombination is frequently violated under physiological conditions, resulting in unanticipated hybrid recombinations in ∼10% of Tcra excision circles. Hence, we demonstrate that strict adherence to the 12/23 rule is intrinsic neither to recombination signal sequences nor to the catalytic process of recombination and propose that nonclassical excision circles are liberated during the formation of antigen receptor diversity.}, URL = {http://genome.cshlp.org/content/25/2/226.abstract}, eprint = {http://genome.cshlp.org/content/25/2/226.full.pdf+html}, journal = {Genome Research} }