We have also identified a transcriptional signature of aneuploidy that is associated with cellular stress and slow proliferation, and is found
in aneuploid primary and cancer cells across a host of organisms.
Having an irregular number of chromosomes, almost by definition, leads to imbalances in the numbers of proteins expressed
in aneuploid cells.
By analyzing gene expression and measured traits
in aneuploids and polyploids, and in their hybrids, he derived the Gene Balance Hypothesis, an encompassing concept that can explain hybrid vigor (heterosis), as well as evolutionary selection in polyploids and in duplicated genes.
Not exact matches
Miscarriage occurs
in about a fourth of pregnancies — most of these are
aneuploid.
In the embryology lab, at the earliest days of embryo development, most of these
aneuploid embryos don't develop, and are never seen clinically.
Half or more (sometimes all) embryos
in a particular IVF treatment cycle are
aneuploid, and while we can't prove this, we suspect that the majority of natural conceptions are affected by aneuploidy as well.
A few
aneuploid embryos continue development and result
in clinical problems.
In a woman under age 30, half of embryos are
aneuploid.
The rate of
aneuploid embryos resulting
in miscarriage increases dramatically with maternal age such that 50 % or more of pregnancies after age 40 will miscarry.
In a retrospective analysis of clinical trial data, they found that melanoma patients with highly
aneuploid tumors were less likely to benefit from immune checkpoint blockade therapy than patients whose tumors showed fewer chromosomal disruptions.
In short, the suddenly awakened cells displayed massive genomic instability, quite beyond their simple
aneuploid condition at the start of the experiments.
«We think this rapid evolution could allow the
aneuploid cells to acquire some of the pro-cancer characteristics that might promote cancer development or cause a cancer
in a person to proliferate,» Sheltzer says.
Cells isolated from lungs of infected animals exhibited relatively stable
aneuploid phenotypes and were found to retain their
aneuploid chromosome
in 70 — 80 % of isolates based on multiplex PCR [20 isolates were analyzed from each strain, 15 were
aneuploid for MN35 (75 %), 16 for MN55 (80 %), 14 for MN77 (70 %), and 15 for MN89 (75 %)(Figure S9)-RSB-.
In S. cerevisiae, strains
aneuploid for different chromosomes all share several common phenotypes, including temperature sensitivity [8].
In contrast to the view that aneuploidy is deleterious, the aneuploid unisexually generated isolates MN35 (n +113) and MN55 (n +19) were as virulent as the euploid wild - type parent, despite their modest TS growth at 37 °C on YPD rich media in vitro (Figure 7
In contrast to the view that aneuploidy is deleterious, the
aneuploid unisexually generated isolates MN35 (n +113) and MN55 (n +19) were as virulent as the euploid wild - type parent, despite their modest TS growth at 37 °C on YPD rich media
in vitro (Figure 7
in vitro (Figure 7).
Consistent with the observed consequences of aneuploidy
in S. cerevisiae, all
aneuploid C. neoformans strains
in our study exhibited a TS phenotype (Figure 3A).
Among 11 strains that had the most overt phenotypic changes, four were
aneuploid and no other
aneuploids were detected
in the larger progeny set (Figure 9A).
Although this chromosomal assortment process is imprecise, it may be retained due to a selective pressure that favors
aneuploid strains under certain environmental conditions, such as
in patients receiving fluconazole, a situation
in which an isochromosome 5 derivative that confers drug resistance often arises [15].
Mutations
in a deubiquitinating enzyme of S. cerevisiae, which arose during the evolution of an
aneuploid isolate, leads to improved proliferation of many
aneuploid strains, likely by promoting degradation of aberrant proteins produced
in perturbed stoichiometric ratios [11].
Drugs that target these pathways may have broad utility against a wide range of
aneuploid cancers, while exhibiting minimal toxicity
in euploid tissue.
We're working to understand how aneuploidy impacts cancer progression,
in hopes of developing therapies that can specifically eliminate
aneuploid cancers while leaving normal cells unharmed.
Moreover, many human tumors have highly abnormal numbers of chromosomes (that is, they are
aneuploid), with initial chromosomal loss participating
in the early steps of the transformation cascade
in inherited cancers caused by heterozygous mutation
in tumor suppressor genes and the more widespread aneuploidy characteristic of advance tumors thought to drive acquisition of malignant growth properties.??
Thus, differences between
aneuploid and euploid cells may represent crucial therapeutic vulnerabilities
in cancer.
Cole Laboratory publishes new paper
in Cell (10/19/2017)- Chromosome mis - segregation creates cells with the wrong number of chromosomes (
aneuploid cells).
Leishmania, a major protozoan parasite, is emerging as a new model for aneuploidy, since
in vitro - cultivated strains are highly
aneuploid, with interstrain diversity and intrastrain mosaicism.
We are particularly interested
in the mechanism of chromosome pairing and the quality control of the crossover formation process, and we aim to understand how the formation of gametes with abnormal /
aneuploid genome is minimized
in mammals.