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Related Concept Videos

Viral Recombination00:57

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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.
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Conservative Site-specific Recombination and Phase Variation02:53

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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.
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Overview of Transposition and Recombination02:13

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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...
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Homologous Recombination02:31

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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...
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Exon Recombination02:32

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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Diversity of Antigen Receptors01:28

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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.
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Individualized VDJ recombination predisposes the available Ig sequence space.

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Immunoglobulin (Ig) gene recombination rules vary between individuals, even identical twins. This suggests non-genetic factors influence VDJ recombination, impacting antigen recognition and personalized medicine.

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Area of Science:

  • Immunology
  • Genetics
  • Bioinformatics

Background:

  • Variable (V), Diversity (D), and Joining (J) immunoglobulin gene segment recombination shapes the naive Ig repertoire and antigen recognition.
  • VDJ recombination is understood to follow probabilistic rules, but inter-individual variability has not been established.
  • Individual-specific VDJ recombination rules could lead to unique Ig sequence repertoires and (auto)antigen recognition probabilities.

Purpose of the Study:

  • To determine if VDJ recombination rules differ between individuals.
  • To develop a method for comparing VDJ recombination models across individuals.
  • To investigate the implications of inter-individual VDJ recombination variability for (auto)antigen recognition.

Main Methods:

  • Development of a sensitivity-tested distance measure for inter-individual comparison of VDJ recombination models.
  • Statistical modeling of VDJ recombination processes.
  • Analysis of immunoglobulin sequencing data, accounting for noise and allelic variation.

Main Results:

  • Statistically distinguishable immunoglobulin recombination models were found not only between unrelated individuals but also between human monozygotic twins and inbred mice.
  • This inter-individual variability suggests the influence of non-genetic factors on VDJ recombination.
  • Individualized VDJ recombination models can lead to substantial differences in the probability of generating specific (auto)antigen-binding Ig sequences.

Conclusions:

  • VDJ recombination rules are not universal and exhibit significant inter-individual variation.
  • Non-genetic factors play a role in modulating VDJ recombination processes.
  • Understanding individualized VDJ recombination is crucial for developing effective immune receptor-based personalized medicine strategies for vaccination, infection, and autoimmunity.