Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling

Lindsay G. Cowell, Marco Davila, Kaiyong Yang, Thomas B. Kepler, Garnett Kelsoe

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-220
Number of pages14
JournalJournal of Experimental Medicine
Volume197
Issue number2
DOIs
StatePublished - Jan 20 2003

Fingerprint

Genetic Recombination
Genome
V(D)J Recombination
Statistical Models
Human Genome
Nucleotides
DNA

Keywords

  • Cryptic recombination signal
  • Illegitimate V(D)J recombination
  • Recombination efficiency
  • Recombination signal models
  • Recombination signal sequence

ASJC Scopus subject areas

  • Immunology

Cite this

Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling. / Cowell, Lindsay G.; Davila, Marco; Yang, Kaiyong; Kepler, Thomas B.; Kelsoe, Garnett.

In: Journal of Experimental Medicine, Vol. 197, No. 2, 20.01.2003, p. 207-220.

Research output: Contribution to journalArticle

@article{c5a479071dbc4ed8b652eb953807c902,
title = "Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling",
abstract = "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.",
keywords = "Cryptic recombination signal, Illegitimate V(D)J recombination, Recombination efficiency, Recombination signal models, Recombination signal sequence",
author = "Cowell, {Lindsay G.} and Marco Davila and Kaiyong Yang and Kepler, {Thomas B.} and Garnett Kelsoe",
year = "2003",
month = "1",
day = "20",
doi = "10.1084/jem.20020250",
language = "English (US)",
volume = "197",
pages = "207--220",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

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

UR - http://www.scopus.com/inward/record.url?scp=0037454957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037454957&partnerID=8YFLogxK

U2 - 10.1084/jem.20020250

DO - 10.1084/jem.20020250

M3 - Article

VL - 197

SP - 207

EP - 220

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 2

ER -