Numericaal Chromosomal

Páginas: 29 (7205 palabras) Publicado: 21 de agosto de 2011
Numerical Chromosomal Aberrations in Human Diseases
Zuzana Storchova, Max-Planck Institute of Biochemistry, Martinsried, Germany

Advanced article
Article Contents
. Causes of Chromosomal Numerical Aberrations . Congenital Aneuploidy . Age Dependency . Aneuploidy in Spontaneous Abortion and at Birth . Sex Chromosome Aneuploidies: XXX, XYY, XXY, X . Autosomal Aneuploidies . Polyploidy .Mosaicism . Aneuploidy . Conclusions

Online posting date: 17th January 2011

Numerical aberrations (whole chromosomal aneuploidy) represent a significant proportion of chromosomal changes found in humans. These aberrations can occur as a consequence of chromosome segregation defects during cell division. Segregation errors arising during reductive cell division, or meiosis, are upon fertilisationand subsequent embryo development constitutively present in all cells, resulting in whole organismal aneuploidy. Missegregation in mitosis leads to a mosaic distribution of aneuploidy. Aneuploidy is associated with pathological states in most organisms. Numerical aberrations represent a significant cause of pregnancy loss as well as abnormalities found in live births. Moreover, numericalaberrations are frequently found in ageing tissues or in tumour cells. Although the association of aneuploidy and cancer is known for almost a century, the dispute is still ongoing whether this is a cause or a consequence of cell transformation. Recently, new evidence is emerging that numerical aberrations significantly alter the physiology of eukaryotic cells and might indeed directly contribute totumorigenesis.

will be used throughout the rest of the article), occur due to a defect in chromosome segregation (Thompson et al., 2010). After chromosome replication, the two sets of chromosomes have to segregate equally into the newly arising daughter cells. Three major mechanisms are required for chromosome segregation to be successful (Figure 1). First, the newly replicated sister chromatids haveto be kept together through protein links called cohesins; this sister chromatid cohesion facilitates both keeping the two chromosome copies together and establishing stable attachment to the microtubules. Second, mitotic spindle has to be properly assembled. Mitotic spindle consists of microtubule organising centres (called centrosomes) arranging among others the microtubules that attach to thekinetochores – large protein complexes formed on each sister chromatid. Third, the

A

B

Causes of Chromosomal Numerical Aberrations
C

Vast majority of numerical chromosomal aberrations, also called whole chromosomal aneuploidy (aneuploidy for short
D
Figure 1 Sources of segregation errors during cell division. A – Bipolar attachment of the sister chromatids to the opposite spindlepoles yields equal segregation of genetic information. B – A defect in spindle or kinetochores disables correct attachment. C – Lack of sister chromatid cohesion is incompatible with proper chromosome segregation. D – Failure to sense defects during cell division and to arrest the cells until the defects are corrected also results in chromosome missegregation.

ELS subject area: Genetics andMolecular Biology How to cite: Storchova, Zuzana (January 2011) Numerical Chromosomal Aberrations in Human Diseases. In: Encyclopedia of Life Sciences (ELS). John Wiley & Sons, Ltd: Chichester. DOI: 10.1002/9780470015902.a0001451.pub2

ENCYCLOPEDIA OF LIFE SCIENCES & 2011, John Wiley & Sons, Ltd. www.els.net

1

Numerical Chromosomal Aberrations in Human Diseases

correct attachment of thenewly replicated sister chromatids to the microtubules is monitored by the spindle assembly checkpoint (SAC): the presence of an unoccupied kinetochore that lacks stable associated microtubules emanates so-called wait signal that keeps the cell from cell cycle progression. A failure in each of these three building blocks of chromosome segregation results in unequal distribution of sister chromatids...
Leer documento completo

Regístrate para leer el documento completo.

Estos documentos también te pueden resultar útiles

  • Chromosomal Disorders

Conviértase en miembro formal de Buenas Tareas

INSCRÍBETE - ES GRATIS