Related Experiment Video
Updated: Jul 7, 2026
15:07
VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Large-scale analysis of human heavy chain V(D)J recombination patterns
Joseph M Volpe1, Thomas B Kepler
1Center for Computational Immunology, Duke University, Durham, NC, USA. jmv2@duke.edu
Immunome Research
|February 29, 2008
Summary
Researchers analyzed human immunoglobulin heavy chain genes, revealing biases in gene segment usage and pairing preferences. This suggests sequential D-J rearrangements occur in B-cell development.
Area of Science:
- Immunology
- Genetics
- Bioinformatics
Background:
- Somatic assembly of antigen receptor genes involves random events with potential subtle biases.
- Understanding these biases offers insights into molecular mechanisms of gene assembly and selection.
- Advancements in genetic databases enable large-scale analysis of immunoglobulin (Ig) genes.
Purpose of the Study:
- To investigate biases in human Ig heavy chain gene assembly.
- To analyze n-nucleotide distributions and D-J segment pairing preferences.
- To test the hypothesis of multiple sequential D-to-J rearrangements.
Main Methods:
- Analysis of nearly 6,500 productive and 325 non-productive human Ig heavy chain genes.
- Statistical comparison of n-nucleotide tract length distributions.
- Development of a statistical model to explain D-J segment pairing biases.
Main Results:
- Identified differences in n-nucleotide tract length distributions.
- Found statistically significant evidence for D-J segment pairing preferences.
- Observed differences between productive and non-productive Ig genes suggest selection biases.
Conclusions:
- Provided precise estimates of Ig gene segment usage frequencies.
- Presented statistical evidence for sequential D-J recombinations in human heavy chain locus.
- Estimated the frequency of sequential D-J recombinations to be approximately 20% during B-cell ontogeny.
Related Concept Videos
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
01:28Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
02:13Overview of Transposition and Recombination
Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
00:57Viral Recombination
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.