TY - JOUR
T1 - Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling
AU - Cowell, Lindsay G.
AU - Davila, Marco
AU - Yang, Kaiyong
AU - Kepler, Thomas B.
AU - Kelsoe, Garnett
PY - 2003/1/20
Y1 - 2003/1/20
N2 - The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we computed the position-wise information, a measure correlated with sequence conservation, for each nucleotide position in an RS alignment and demonstrate that most position-wise information is present in the RS heptamers and nonamers. We have previously demonstrated significant correlations between RS positions and here show that statistical models of the correlation structure that underlies RS variability efficiently identify physiologic and cryptic RS and accurately predict the recombination efficiencies of natural and synthetic RS. In scans of mouse and human genomes, these models identify a highly conserved family of repetitive DNA as an unexpected source of frequent, cryptic RS that rearrange both in extrachromosomal substrates and in their genomic context.
AB - The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we computed the position-wise information, a measure correlated with sequence conservation, for each nucleotide position in an RS alignment and demonstrate that most position-wise information is present in the RS heptamers and nonamers. We have previously demonstrated significant correlations between RS positions and here show that statistical models of the correlation structure that underlies RS variability efficiently identify physiologic and cryptic RS and accurately predict the recombination efficiencies of natural and synthetic RS. In scans of mouse and human genomes, these models identify a highly conserved family of repetitive DNA as an unexpected source of frequent, cryptic RS that rearrange both in extrachromosomal substrates and in their genomic context.
KW - Cryptic recombination signal
KW - Illegitimate V(D)J recombination
KW - Recombination efficiency
KW - Recombination signal models
KW - Recombination signal sequence
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U2 - 10.1084/jem.20020250
DO - 10.1084/jem.20020250
M3 - Article
C2 - 12538660
AN - SCOPUS:0037454957
SN - 0022-1007
VL - 197
SP - 207
EP - 220
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
ER -