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Polytene Chromosomes02:04

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Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in salivary glands, intestine, muscles, malpighian tubules, and hypoderm of larvae Chironomus plumosus. Hence, these are also called "Salivary gland chromosomes." These are found in insects of the order Diptera and Collembola; in certain organs of mammals; and synergids, antipodes of flowering plants. Polytene chromosomes are also...
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In 1866, Gregor Mendel published the results of his pea plant breeding experiments, providing evidence for predictable patterns in the inheritance of physical characteristics. The significance of his findings was not immediately recognized. In fact, the existence of genes was unknown at the time. Mendel referred to hereditary units as “factors.”
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Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers.  Nondisjunction is common during anaphase I or anaphase II of meiosis.  Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
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During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
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Meiosis is a carefully orchestrated set of cell divisions, the goal of which—in humans—is to produce haploid sperm or eggs, each containing half the number of chromosomes present in somatic cells elsewhere in the body. Meiosis I is the first such division, and involves several key steps, among them: condensation of replicated chromosomes in diploid cells; the pairing of homologous chromosomes and their exchange of information; and finally, the separation of homologous chromosomes by...
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Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of meiosis, where the genetic recombination of homologous chromosomes and the reduction of the ploidy level by half occurs.
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Chromosome Preparation From Cultured Cells
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A cell-based model system links chromothripsis with hyperploidy.

Balca R Mardin1, Alexandros P Drainas1, Sebastian M Waszak1

  • 1European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.

Molecular Systems Biology
|September 30, 2015
PubMed
Summary
This summary is machine-generated.

Chromothripsis, a genomic catastrophe causing massive DNA rearrangements, can now be studied in vitro. This new method reveals chromothripsis occurs in cells with damaged telomeres and hyperploidy, a finding confirmed in medulloblastoma cancer genomes.

Keywords:
DNA rearrangementschromothripsishyperploidytelomere damagetransformation

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Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Genetics

Background:

  • Chromothripsis is a catastrophic genomic event causing extensive structural rearrangements (SRs) in cancer.
  • The mechanistic basis of chromothripsis has been poorly understood due to a lack of suitable experimental models.

Purpose of the Study:

  • To develop an efficient in vitro system for generating and studying chromothripsis.
  • To investigate the mechanistic basis, temporal sequence, and cellular impact of catastrophic SR formation.

Main Methods:

  • Developed an integrative method termed "complex alterations after selection and transformation (CAST)" for in vitro generation of complex DNA rearrangements.
  • Employed cell perturbations, a strong selection barrier, and massively parallel sequencing.
  • Analyzed the impact on gene expression and cell division.

Main Results:

  • Successfully generated complex DNA rearrangements, including chromothripsis, in vitro.
  • Identified a propensity for chromothripsis in cells with damaged telomeres and hyperploidy.
  • Validated the association between hyperploidy and chromothripsis in primary medulloblastoma cancer genomes.

Conclusions:

  • The CAST system provides a robust platform for mechanistic dissection of chromothripsis and other complex DNA rearrangement processes.
  • Hyperploidy is a significant factor promoting chromothripsis in both in vitro models and human cancers.
  • This research advances our understanding of the origins of genomic instability in cancer.