Refers to the presence of an abnormal number of chromomes from the normal number of 46 in human cells.
Associated with significant morbidity and mortality, especially in infancy and childhood.
People with sex chromosome aneuploidy area characterized by an atypical number of X or Y chromosomes and has a prevalence estimate ranging from one in 1400 births to one and 650 births.
Sex, chromosome, aneuploidies are associated with anthropometric differences.
Tall stature is seen with supernumerary sex chromosomes, that is more than 26 chromosomes, or short stature in those with loss of sex chromosomes, addition to biochemical imbalances that can affect long-term health.
Adults with supernumerary, sex, chromosome aneuploidy compared to sex chromosomes have a small but statistically significant increase risk of venothromboembolism.
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, instead of the usual 46.
A cell with any number of complete chromosome sets is called a euploid cell.
Down syndrome, one of the most common human conditions due to aneuploidy: There are three chromosomes 21.
An extra or missing chromosome is a common cause of some genetic disorders.
Some cancer cells also have abnormal numbers of chromosomes.
About 68% of human solid tumors are aneuploid.
Aneuploidy originates during cell division when the chromosomes do not separate properly between the two cells (nondisjunction).
Most cases of aneuploidy in the autosomes result in miscarriage.
The most common extra autosomal chromosomes among live births are 21, 18 and 13.
Chromosome abnormalities are detected in 1 of 160 live human births.
Autosomal aneuploidy is more dangerous than sex chromosome aneuploidy.
Autosomal aneuploidy is almost always lethal to embryos that cease developing because of it.
Most cells in the human body have 23 pairs of chromosomes, or a total of 46 chromosomes.
The sperm and egg, or gametes, each have 23 unpaired chromosomes.
One copy of each pair is inherited from the mother and the other copy is inherited from the father.
The first 22 pairs of chromosomes, called autosomes,are numbered from 1 to 22, from largest to smallest.
The 23rd pair of chromosomes are the sex chromosomes.
Normal females have two X chromosomes, while normal males have one X chromosome and one Y chromosome.
The characteristics of the chromosomes in a cell as they are seen under a light microscope are called the karyotype.
During meiosis, when germ cells divide to create sperm and egg (gametes), each half should have the same number of chromosomes.
Sometimes, the whole pair of chromosomes will end up in one gamete, and the other gamete will not get that chromosome at all.
Most embryos cannot survive with a missing or extra autosome and are spontaneously aborted.
The most frequent aneuploidy in humans is trisomy 16 and fetuses affected with this chromosome abnormality do not survive to term, although it is possible for surviving individuals to have the mosaic form, where trisomy 16 exists in some cells but not all.
The most common aneuploidy that infants can survive with is trisomy 21: Down syndrome, affecting 1 in 800 births.
Trisomy 18 (Edwards syndrome) affects 1 in 6,000 births.
Trisomy 13 (Patau syndrome) affects 1 in 10,000 births.
10% of infants with trisomy 18 or 13 reach 1 year of age.
Changes in chromosome number may not necessarily be present in all cells in an individual.
Aneuploidy is detected in a fraction of cells in an individual, it is called chromosomal mosaicism.
In general, mosaicism for a chromosomal aneuploidy tend to have a less severe form of the syndrome compared to those with full trisomy.
For many of the autosomal trisomies, only mosaic cases survive to term.
Aneuploidy arises from errors in chromosome segregation:
Nondisjunction-a weakened mitotic checkpoint, which tends to arrest cell division until all components of the cell are ready to enter the next phase.
Merotelic attachment occurs when one kinetochore is attached to both mitotic spindle poles, resulting in one daughter cell with a normal complement of chromosomes, while the second would lack one.
Multipolar spindles: more than two spindle poles form, resulting in one daughter cell for each spindle pole; each cell may possess an unpredictable complement of chromosomes.
Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled.
Mosaicism for aneuploid chromosome content may be part of the constitutional make-up of the brain.
In the normal human brain, mosaicism for chromosome 21 aneuploidy occurs at an average of 4% of neurons analyzed.
A low-level aneuploidy arises from chromosomal segregation defects during cell division in neuronal precursor cells, and neurons containing such aneuploid chromosome content reportedly integrate into normal circuits.
Aneuploidy is observed in virtually all cancers.
Somatic mosaicism occurs in virtually all cancer cells: trisomy 12 in chronic lymphocytic leukemia (CLL) and trisomy 8 in acute myeloid leukemia (AML).
Alteration of normal mitotic checkpoints are important tumorigenic events, and these may directly lead to aneuploidy.
Loss of tumor suppressor p53 gene often results in genomic instability, which could lead to the aneuploidy genotype.
Genetic syndromes that predispose to breakage of chromosomes, the chromosome instability syndromes, are frequently associated with increased risk for various types of cancer.
Aneuploidy can occur due to loss of a whole chromosome, gain of a whole chromosome or rearrangement of partial chromosomes known as gross chromosomal rearrangements (GCR).
Most cancer cells are aneuploid, meaning that they have an abnormal number of chromosomes which often have significant structural abnormalities such as chromosomal translocations, where sections of one chromosome are exchanged or attached onto another.
Changes in ploidy can alter expression of proto-oncogenes or tumor suppressor genes.
Segmental aneuploidy can occur due to deletions, amplifications or translocations, which arise from breaks in DNA, while loss and gain of whole chromosomes is often due to errors during mitosis.
This process points to the role of somatic aneuploidy in carcinogenesis.
The ability to evade the immune system appears to be enhanced in tumoral cells with strong aneuploidy.
The presence of an abnormal number of chromosomes might be an effective predictive biomarker for response to specific immunotherapy: melanoma patients, high somatic copy number alterations are associated with less effective response to immune checkpoint blockade anti–CTLA4 therapy.
Epigenetic inheritance is defined as cellular information other than the DNA sequence itself, that is still heritable during cell division.
DNA methylation and histone modifications comprise two of the main epigenetic modifications important for many physiological and pathological conditions, including cancer.
Aberrant DNA methylation is the most common molecular lesion in cancer-cells, even more frequent than gene mutations.
Tumor suppressor gene silencing by CpG island promoter hypermethylation is supposed to be the most frequent epigenetic modification in cancer cells.
Epigenetic characteristics of cells may be modified by several factors: environmental exposure, deficiencies of certain nutrients, and radiation.
It is suggested on a growing basis of evidence, that not only genetics but also epigenetics, contribute to aneuploid cell formation.
The terms partial monosomy and partial trisomy are used to describe an imbalance of genetic material caused by loss or gain of part of a chromosome:
these terms would be used in the situation of an unbalanced translocation, where an individual carries a derivative chromosome formed through the breakage and fusion of two different chromosomes.
In such an imbalance there would be three copies of part of one chromosome (two normal copies and the portion that exists on the derivative chromosome) and only one copy of part of the other chromosome involved in the derivative chromosome.
Robertsonian translocations account for a very small minority of Down syndrome cases (<5%): The formation of one isochromosome results in partial trisomy of the genes present in the isochromosome and partial monosomy of the genes in the lost arm.
Agents capable of causing aneuploidy are called aneugens.
X-rays may cause aneuploidy by fragmenting the chromosome, and may also target the spindle apparatus.
Colchicine can also produce aneuploidy by affecting microtubule polymerization.
Exposure of males to lifestyle, environmental and/or occupational hazards may increase the risk of the development pd aneuploidy in sperm.
Smoking also can induce aneuploidy: smoking increases chromosome 13 disomy in spermatozoa by 3-fold, and YY disomy by 2-fold.
Occupational exposure to benzene is associated with a 2.8-fold increase of XX disomy and a 2.6-fold increase of YY disomy in spermatozoa.
Insecticide exposure has been reported to increase spermatozoa aneuploidy.
Men contaminated with perfluorinated compounds (PFCs) in whole blood or seminal plasma have spermatozoa with increased levels of DNA fragmentation and chromosomal aneuploidies.
Germline aneuploidy is typically detected through karyotyping.
Karyotyping is a process in which a sample of cells is fixed and stained to create the typical light and dark chromosomal banding pattern and a picture of the chromosomes is analyzed.
Other techniques of chromosome analysis include fluorescence in situ hybridization (FISH), quantitative PCR of short tandem repeats, quantitative fluorescence PCR (QF-PCR), quantitative PCR dosage analysis, Quantitative Mass Spectrometry of Single Nucleotide Polymorphisms, and comparative genomic hybridization.
These tests can also be performed prenatally to detect aneuploidy in a pregnancy, through either amniocentesis or chorionic villus sampling.
Pregnant women of 35 years or older are offered prenatal testing because the chance of chromosomal aneuploidy increases as the mother’s age increases.
Less invasive testing methods based on the presence of fetal genetic material in maternal blood can be done (Triple test and Cell-free fetal DNA).
Autosomal
# monosomy trisomy
1 1p36 deletion syndrome
1q21.1 deletion syndrome Trisomy 1
2 2q37 deletion syndrome Trisomy 2
3 Trisomy 3
4 Wolf–Hirschhorn syndrome Trisomy 4
5 Cri du chat
5q deletion syndrome Trisomy 5
6 Trisomy 6
7 Williams syndrome Trisomy 7
8 Monosomy 8p
Monosomy 8q Trisomy 8
9 Alfi’s syndrome
Kleefstra syndrome Trisomy 9
10 Monosomy 10p
Monosomy 10q Trisomy 10
11 Jacobsen syndrome Trisomy 11
12 Trisomy 12
13 Patau syndrome
14 Trisomy 14
15 Angelman syndrome
Prader–Willi syndrome Trisomy 15
16 Trisomy 16
17 Miller–Dieker syndrome
Smith–Magenis syndrome Trisomy 17
18 Distal 18q-
Proximal 18q- Edwards syndrome
19 Trisomy 19
20 Trisomy 20
21 Down syndrome
22 DiGeorge syndrome
Phelan–McDermid syndrome
22q11.2 distal deletion syndrome Cat eye syndrome
Trisomy 22
A chromosome complement having a number of chromosomes other than 46 (in humans) is considered heteroploid while an exact multiple of the haploid chromosome complement is considered euploid.
Monosomy refers to lack of one chromosome of the normal complement.
Partial monosomy can occur in unbalanced translocations or deletions, in which only a portion of the chromosome is present in a single copy.
Monosomy of the sex chromosomes (45,X) causes Turner syndrome.
Disomy is the presence of two copies of a chromosome.
Humans that have two copies of each chromosome it is the normal condition.
Trisomy refers to 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.
Trisomy 18 and Trisomy 13, known as Edwards syndrome and Patau syndrome, respectively, are the two other autosomal trisomies recognized in live-born humans.
Trisomy of the sex chromosomes is also possible, for example (47,XXX), (47,XXY), and (47,XYY).
Tetrasomy and pentasomy are the presence of four or five copies of a chromosome, respectively.
Although rarely seen with autosomes, sex chromosome tetrasomy and pentasomy have been reported in humans, including XXXX, XXXY, XXYY, XXXXX, XXXXY, and XYYYY.