Alterations in a cell's chromosomal content from normal is known as polyploidy or aneuploidy. Polyploidy is a change that is a multiple of the haploid chromosome content while aneuploidy is a change in the chromosome content that is not a multiple of the haploid number. There are many instances demonstrating that polyploidy is reasonably well tolerated at the organismal level, and whole genome duplications likely have served to promote the evolution of species (1). However, this is not the case for aneuploidy where the gain or loss of individual chromosomes has been demonstrated to result in lethality and the development of disease (1). Mitosis is a highly regulated process with various surveillance mechanisms in place to coordinate the proper segregation of genetic material between the daughter cells. Nevertheless, even in the presence of these checkpoints aneuploidy can occur, as chromosome mis-segregation has been estimated to happen at a rate of once in every 104 to 105 cell divisions in mammalian cells (2).
Aneuploidy has long been known to be a characteristic of cancer cells (3), and changes in chromosome number have been proposed to be a mechanism by which cancer cells acquire additional copies of oncogenes or lose the expression of tumor suppressor genes, thereby driving the tumorigenic process. Interestingly, individuals with Down syndrome (DS) are at an increased risk to develop leukemia, retinoblastoma, and germ cell tumors, but are less likely to develop other solid tumors (4, 5). As I develop my own research group, I am seeking to further define how the presence of an extra chromosome influences the fitness of mammalian cells, and how these differences might lend insight into the role of aneuploidy in cancer...
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One chromosome has been donated from each parent cell in order to create a homologous chromosome pair. These chromosomes have identical lengths and gene placement but can contain different alleles. When homologous chromosomes attach at the centromere they create a tetrad, which is defined as a pair of sister chromatids. Once the sister chromatids are attached, the non-sister chromatids participate in crossing over. Crossing over is the transfer of genetic information in order to create greater genetic variability. In metaphase I, the centromere of each tetrad attaches to spindle fibers. These spindle fibers slowly shift the tetrads position to the center of the cell until they are side by side. Immediately after they line up, homologous chromosomes are separated by microtubules called kinetochore fibers that are used to pull sister chromatids to opposite poles of the cell. Once the sister chromatids are on opposite poles of the cell, anaphase I is complete and the cytoplasm of the cell begins to separate. This is known as cytokinesis and occurs during telophase. Once meiosis I is complete, meiosis II begins and repeats each step, however, instead of two haploid cells there will be a total of
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In Meiosis 1, chromosomes in a diploid cell resegregate, producing four haploid daughter cells. It is this step in Meiosis that generates genetic diversity.Meiosis 2 is similar to mitosis. However, there is no "S" phase. The chromatids of each chromosome are no longer identical because of recombination. Meiosis II separates the chromatids producing two daughter cells each with 23 chromosomes (haploid), and each chromosome has only one chromatid.
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