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Related Concept Videos

Crossing Over01:30

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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,...
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Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
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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 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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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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Ultra-long Read Sequencing for Whole Genomic DNA Analysis
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Insights into non-crossover recombination from long-read sperm sequencing.

Regev Schweiger1, Sangjin Lee2, Chenxi Zhou1

  • 1Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, United Kingdom.

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Summary

New sperm sequencing methods capture human recombination events, revealing variations in crossover and gene conversion rates between donors. Non-crossover gene conversions favor PRDM9 sites, while crossovers show a downstream bias.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Reproductive Biology

Background:

  • Meiotic recombination generates genetic diversity through crossovers and gene conversions.
  • Studying non-crossover gene conversion at the individual level is challenging.
  • PRDM9 is a key regulator of meiotic recombination initiation.

Purpose of the Study:

  • To develop a method for analyzing both crossover and non-crossover recombination events in human sperm.
  • To investigate inter- and intra-individual variation in recombination rates.
  • To explore the relationship between recombination types and PRDM9 binding sites.

Main Methods:

  • Utilizing single high-fidelity long sequencing reads from human sperm.
  • Analyzing fifteen sperm samples from thirteen donors.
  • Characterizing crossover and non-crossover events, including gene conversion tract lengths.

Main Results:

  • Demonstrated variation in recombination rates between and within donors.
  • Observed non-crossover gene conversions upstream of PRDM9 binding sites, with crossovers showing a downstream bias.
  • Identified two distinct non-crossover processes: a common short-tract type associated with PRDM9 and a rare long-tract type potentially independent of PRDM9.

Conclusions:

  • Single sperm sequencing is a powerful tool for studying human recombination.
  • Recombination patterns, including gene conversion, show donor-specific variation and are influenced by PRDM9.
  • Two distinct non-crossover pathways exist, one standard and one potentially related to complex genomic rearrangements.