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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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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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Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I, duplicated...
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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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Alu repeats increase local recombination rates.

David J Witherspoon1, W Scott Watkins, Yuhua Zhang

  • 1Dept. of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112, USA. david.witherspoon@utah.edu

BMC Genomics
|November 18, 2009
PubMed
Summary

Mobile DNA elements called Alu insertions significantly increase local recombination rates in the human genome. This finding impacts our understanding of genome evolution and linkage disequilibrium patterns.

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Detection of Homologous Recombination Intermediates via Proximity Ligation and Quantitative PCR in Saccharomyces cerevisiae
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05:22

Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome

Published on: September 13, 2024

Area of Science:

  • Genetics
  • Genomics
  • Molecular Biology

Background:

  • Recombination rates vary across the human genome, with limited correlation to DNA sequence features.
  • Over one million Alu mobile element insertions exist in the human genome, influencing various genetic processes.
  • The collective impact of Alu insertions on recombination rates could significantly affect linkage disequilibrium and genome evolution.

Purpose of the Study:

  • To investigate the correlation between AluY insertion loci and local recombination rates in the human genome.
  • To determine if Alu insertions are a significant predictor of elevated local recombination rates.
  • To assess the impact of Alu insertions on genome evolution and linkage disequilibrium.

Main Methods:

  • Sequencing, SNP identification, and genotyping around 19 AluY insertion loci in 347 individuals from diverse populations.
  • Estimation of local recombination rates using SNP genotypes around AluY loci, controlling for factors like SNP ascertainment bias and density.
  • Analysis of HapMap Phase II data to validate findings across a larger set of AluY insertions and populations (CEU and YRI).

Main Results:

  • A significant increase in recombination rate was detected within approximately 2 kb of AluY insertions in an African population sample.
  • Analysis of HapMap Phase II data confirmed a significantly increased recombination rate near AluY insertions in both CEU and YRI populations.
  • The presence of a fixed AluY insertion was found to be a significant predictor of elevated local recombination rates.

Conclusions:

  • Fixed AluY insertions significantly elevate local recombination rates within 2 kb, independent of other known predictors.
  • The observed approximately 6% increase in recombination rate is comparable to effects of known recombinogenic DNA sequence motifs.
  • AluY insertions play a notable role in shaping recombination patterns within the human genome.