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.
Type
Journal articleSubject
AnimalsBase Sequence
Conserved Sequence
DNA
Gene Rearrangement
Genome
Genome, Human
Humans
Mice
Models, Genetic
Models, Statistical
Molecular Sequence Data
Recombination, Genetic
Sequence Homology, Nucleic Acid
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Show full item recordScholars@Duke
Lindsay Grey Cowell
Adjunct Assistant Professor in the Department of Biostatistics and Bioinformatics
Somatic Diversification of Lymphocyte Antigen Receptor Genes * V(D)J Recombination
* Somatic Hypermutation Biomedical Ontology * Ontological Representation of Cells
of Hematopoietic Lineage Biomedical Text Mining Logic-based Reasoning
Garnett H. Kelsoe
James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and
T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for
clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction
of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis.
4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies.
5. Mathematical modeling of immune responses,
Thomas B. Kepler
Adjunct Professor in the Department of Immunology
Computational and Systems Immunology, Theoretical and Evolutionary Medicine
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