Aneuploidy

From Wikipedia, the free encyclopedia

Aneuploidy
Classification and external resources
ICD-10 Q90.-Q98.
ICD-9 758
MeSH D000782

Aneuploidy is a change in the number of chromosomes that can lead to a chromosomal abnormality.

Every cell in the human body, apart from anuclear red blood cells and the haploid gametes, has 46 chromosomes. The 46 chromosomes can be arranged into 23 pairs. From each pair, humans will typically inherit one chromosome from our mother and one from our father. The first 22 pairs of chromosomes are referred to as autosomes, or body chromosomes. They are numbered from 1 through 22 from largest to smallest in a Karyogram. The last pair of chromosomes are the sex chromosomes. Females will typically have two X chromosomes, while males will typically have one X chromosome and one Y chromosome. The most common form of meiotic aneuploidy in humans is Down syndrome, which is caused by an extra copy of chromosome number 21. [1] However, mitotic aneuploidy is a characteristic of many types of tumorigenesis (in cancer).

Contents

[edit] Common forms

Name # Description
monosomy 1 Monosomy refers to lack of one chromosome of the normal complement. Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies (see deletion (genetics)). Monosomy in sex chromosome is 45, X
disomy 2 A disomy is the presence of two copies of a chromosome. For organisms, like humans, that have two copies of each chromosome (those that are diploid), it is the normal condition. For organisms that normally have three or more copies of each chromosome (those that are triploid or above), disomy is an aneuploidy. In uniparental disomy, both copies of the chromosome are from the same parent (with no contribution from the other parent).
trisomy 3 A trisomy is the presence of three copies, instead of the normal two, of a particular chromosome. The presence of an extra chromosome 21, which is found in Down syndrome, is called trisomy 21. In sex chromosomes it is called 47, XXX in woman and 47, XYY or 47, XXY (also called Klinefelter's syndrome).
tetrasomy/pentasomy 4/5 A tetrasomy and a pentasomy are the presence of a respectively four or five copies of a chromosome. Although very rare, reported examples of tetrasomy and pentasomy in humans include the karyotypes XXXX, XXXY, XXYY, XYYY, XXXXX, XXXXY, XXXYY, XXYYY and XYYYY.[2]

Changes in chromosome number may not necessarily be present in all cells in an individual. It may be detected in just a specific tissue or within different cells in a tissue. When the presence of chromosomal abnormalities occurs differentially within an individual, it is called chromosomal mosaicism. In general, as we would expect, individuals who are mosaic for a chromosome change tend to have a less severe form of the syndrome present than full trisomy individuals. Critical examples of mosaicism are found in leukemia cases, specifically; chronic lymphocytic leukemia (CLL) which is a trisomy of chromosome 12 and acute myeloid leukemia (AML) prognosis which is a trisomy of chromosome 8. Aneuploidy is common in cancerous cells.

[edit] Mechanisms

  1. Nondisjunction usually occurs as the result of a weakened mitotic checkpoint, as these checkpoints tend to arrest or delay cell division until all components of the cell are ready to enter the next phase. If a checkpoint is weakened, the cell may fail to 'notice' that a chromosome pair is not lined up on the mitotic plate, for example. In such a case, most chromosomes would separate normally (with one chromatid ending up in each cell), while others could fail to separate at all. This would generate a daughter cell lacking a copy and a daughter cell with an extra copy.
  2. Completely inactive mitotic checkpoints may cause non-disjunction at multiple chromosomes, possibly all. Such a scenario could result in each daughter cell possessing a disjunct set of genetic material.
  3. Merotelic attachment occurs when one kinetochore is attached to both mitotic spindle poles. One daughter cell would have a normal complement of chromosomes, the second would lack one. A third daughter cell may end up with the 'missing' chromosome.
  4. Multipolar spindle: more than two spindle poles form. Such a mitotic division would result in one daughter cell for each spindle pole; each cell may possess an unpredictable complement of chromosomes.
  5. Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled.
  6. A tetraploid intermediate may be produced as the end result of the monopolar spindle mechanism. In such a case, the cell has double the copy number of a normal cell, and produces double the number of spindle poles as well. This results in four daughter cells with an unpredictable complement of chromosomes, but in the normal copy number.

[edit] Detection

Example of Trisomy 21 detected via qPCR Short Tandem Repeat assay
Example of Trisomy 21 detected via qPCR Short Tandem Repeat assay

Aneuploidy is typically detected through karyotyping, a process where a picture of the chromosomes of an individual is analyzed. Other techniques include Fluorescence In Situ Hybridization (FISH), Quantitative Polymerase Chain Reaction (PCR) of Short Tandem Repeats, Quantitative Fluorescence PCR (QF-PCR), Quantitative Real-time PCR (RT-PCR) dosage analysis, Quantitative Mass Spectrometry of Single Nucleotide Polymorphisms, and Comparative Genomic Hybridization (CGH). These tests can also be done prenatally to detect aneuploidy in a pregnancy, either through amniocentesis or chorionic villus sampling.

Pregnant women over the age of 35 are typically offered various tests for aneuploidy in the fetus because the chance of these syndromes increases as the mother's age increases. For more information, see prenatal diagnosis.

[edit] See also

[edit] References

  1. ^ Aneuploidy. Retrieved on 2007-12-20.
  2. ^ Linden MG, Bender BG, Robinson A (1995). "Sex chromosome tetrasomy and pentasomy". Pediatrics 96 (4 Pt 1): 672–82. PMID 7567329. 

[edit] External links

v • d • e
Pathology: chromosome abnormalities (Q90-Q99, 758)
Autosomal trisomies
Autosomal monosomies/deletions
X/Y linked
Translocations
Other