RT Journal
A1 Parkinson, Nicholas J.
A1 Roddis, Matthew
A1 Ferneyhough, Ben
A1 Zhang, Gang
A1 Marsden, Adam J.
A1 Maslau, Siarhei
A1 Sanchez-Pearson, Yasmin
A1 Barthlott, Thomas
A1 Humphreys, Ian R.
A1 Ladell, Kristin
A1 Price, David A.
A1 Ponting, Chris P.
A1 Hollander, Georg
A1 Fischer, Michael D.
T1 Violation of the 12/23 rule of genomic V(D)J recombination is common in lymphocytes
JF Genome Research 
JO Genome Research 
YR 2015 
FD February 01 
VO 25 
IS 2 
SP 226 
OP 234 
DO 10.1101/gr.179770.114 
UL http://genome.cshlp.org/content/25/2/226.abstract 
AB 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.