Parkinson, Nicholas J., Roddis, Matthew, Ferneyhough, Ben, Zhang, Gang, Marsden, Adam J., Maslau, Siarhei, Sanchez-Pearson, Yasmin, Barthlott, Thomas, Humphreys, Isla, Ladell, Kristin Ingrid  ORCID: https://orcid.org/0000-0002-9856-2938, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Ponting, Chris P., Hollander, Georg and Fischer, Michael D.
2015.
Violation of the 12/23 rule of genomic V(D)J recombination is common in lymphocytes.
Genome Research
25
(2)
, pp. 226-234.
10.1101/gr.179770.114
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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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) |
| Subjects: | R Medicine > R Medicine (General) |
| Publisher: | Cold Spring Harbor Laboratory Press |
| ISSN: | 1088-9051 |
| Date of First Compliant Deposit: | 5 September 2017 |
| Date of Acceptance: | 31 October 2014 |
| Last Modified: | 06 May 2023 16:43 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/74815 |
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