Aneuploidy Classification and external resources ICD-10 Q90-Q98 ICD-9 758 MeSH D000782
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders (birth defects). Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate properly between the two cells. Chromosome abnormalities occur in 1 of 160 live births. The most common extra chromosomes among live births are 21, 18 and 13.
Different species have different numbers of normal chromosomes and thus the term "aneuploidy" refers to the chromosome number being different for that species.
Every cell in the human body, apart from enucleated red blood cells and the haploid gametes, has 23 pairs of chromosomes (for a total of 46). 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 (referred to as autosomes) are numbered from 1 to 22, and are arranged from largest to smallest in a karyotype (see figure). 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.
During meiosis, when germ cells divide to create sperm and egg (gametes), each half should have the same number of chromosomes. But 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 (numbered chromosome) and are spontaneously aborted. The most frequent aneuploidy in humans is trisomy 16, although fetuses affected with the full version of this chromosome abnormality do not survive to term (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, which is found in Down syndrome, affecting 1 in 800 births. Trisomy 18 (Edwards syndrome) affects 1 in 6,000 births, and 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. When aneuploidy is detected in a fraction of cells in an individual, it is called chromosomal mosaicism. In general, individuals who are mosaic 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. However, mitotic aneuploidy may be more common than previously recognized in somatic tissues, and aneuploidy is a characteristic of many types of tumorigenesis (see below).
In the strict sense, 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.
Number of chromosomes Name Description 1 Monosomy 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 (see deletion (genetics)). Monosomy of the sex chromosomes (45,X) causes Turner syndrome. 2 Disomy Disomy is the presence of two copies of a chromosome. For organisms such as 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 aneuploid chromosome complement. In uniparental disomy, both copies of a chromosome come from the same parent (with no contribution from the other parent). 3 Trisomy 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 and Patau Syndrome, respectively, are the two other autosomal trisomies recognized in live-born humans. Trisomy of the sex chromosomes is possible, such as in (47,XXX), (47,XXY), and (47,XYY). 4/5 tetrasomy/pentasomy 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, XXXXX, XXXXY and XYYYY.
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.
Completely inactive mitotic checkpoints may cause non-disjunction at multiple chromosomes, possibly all. Such a scenario could result in each daughter cell possessing a disjoint set of genetic material.
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.
Multipolar spindles: 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.
Monopolar spindle: only a single spindle pole forms. This produces a single daughter cell with its copy number doubled.
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.
Somatic mosaicism in the nervous system
Mosaicism for aneuploid chromosome content may be part of the constitutional make-up of the mammalian brain. In the normal human brain, brain samples from six individuals ranging from 2–86 years of age had mosaicism for chromosome 21 aneuploidy (average of 4% of neurons analyzed). This low-level aneuploidy appears to arise from chromosomal segregation defects during cell division in neuronal precursor cells, and neurons containing such aneuploid chromosome content reportedly integrate into normal circuits. These results suggest the possibility that somatic mosaicism in the brain (and perhaps, by extension, other tissues) may contribute to the diversity between individuals.
Somatic mosaicism in cancer
Somatic mosaicism also occurs in many cancer cells, including trisomy 12 in chronic lymphocytic leukemia (CLL) and trisomy 8 in acute myeloid leukemia (AML). However, these forms of mosaic aneuploidy occur through mechanisms distinct from those typically associated with genetic syndromes involving complete or mosaic aneuploidy.
Loss of p53 creates genomic instability that most often results in the aneuploidy phenotype.
In addition, genetic syndromes in which an individual is predisposed to breakage of chromosomes (chromosome instability syndromes) are frequently associated with increased risk for various types of cancer, thus highlighting the role of somatic aneuploidy in carcinogenesis. Studies indicate that aneuploidy directly contributes to carcinogenesis by disrupting the asymmetric division of adult stem cells.
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. In particular, 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 this situation, the individual would have 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.
Germline aneuploidy is typically detected through karyotyping, 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 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 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 diagnosis because the chance of chromosomal aneuploidy increases as the mother's age increases. For more information, see prenatal diagnosis.
Recent advances have allowed for less invasive testing methods based on the presence of fetal genetic material in maternal blood.
key color significance lethal normal female phenotype normal male phenotype Turner's syndrome (abnormal female) Klinefelter's syndrome (abnormal male) Non-autosomal 0 X XX XXX XXXX XXXXX 0 00 X0 XX XXX XXXX XXXXX Y Y0 XY XXY XXXY XXXXY XXXXXY YY YY XYY XXYY XXXYY XXXXYY XXXXXYY YYY YYY XYYY XXYYY XXXYYY XXXXYYY XXXXXYYY YYYY YYYY XYYYY XXYYYY XXXYYYY XXXXYYYY XXXXXYYYY YYYYY YYYYY XYYYYY XXYYYYY XXXYYYYY XXXXYYYYY XXXXXYYYYY key color significance case where complete non-mosaic trisomy can never survive to term case where complete non-mosaic trisomy can occasionally (barring other complications) survive to term case where complete non-mosaic trisomy can always (barring other complications) survive to term Autosomal # monosomy trisomy 1 Trisomy 1 2 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 Warkany syndrome 2 9 Trisomy 9 10 Trisomy 10 11 Jacobsen syndrome Trisomy 11 12 Trisomy 12 13 Patau syndrome 14 Trisomy 14 15 Angelman syndrome
Trisomy 15 16 Trisomy 16 17 Miller-Dieker syndrome
Trisomy 17 18 18q deletion syndrome Edwards syndrome 19 Trisomy 19 20 Trisomy 20 21 Down syndrome 22 DiGeorge syndrome Cat eye syndrome
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Pathology: chromosome abnormalities (Q90–Q99 · 758) Autosomal1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome (1) · Wolf-Hirschhorn syndrome (4) · Cri du chat/Chromosome 5q deletion syndrome (5) · Williams syndrome (7) · Jacobsen syndrome (11) · Miller–Dieker syndrome/Smith–Magenis syndrome (17) · DiGeorge syndrome (22) · 22q13 deletion syndrome (22)
genomic imprinting (Angelman syndrome/Prader–Willi syndrome (15))Distal 18q-/Proximal 18q-
X/Y linked TranslocationsLymphoidMyeloidOther Other
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aneuploidy — aneuploidy. См. анеуплоидия. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) … Молекулярная биология и генетика. Толковый словарь.
aneuploidy — (n.) abnormal number of chromosomes, 1934, from aneuploid (1931), Modern Latin, coined 1922 by G. Täckholm from AN (Cf. an ) (1) not + euploid, from Gk. eu well, good (see EU (Cf. eu )) + ploid (comb. form of ploos fold + OID (Cf … Etymology dictionary
Aneuploidy — One or a few chromosomes above or below the normal chromosome number. For example, three number 21 chromosomes or trisomy 21 (characteristic of Down syndrome) is a form of aneuploidy. * * * State of being aneuploid. partial a. a type of mosaicism … Medical dictionary
aneuploidy — nesubalansuotoji poliploidija statusas T sritis augalininkystė apibrėžtis Nekartotiniai chromosomų rinkinių arba pavienių chromosomų pakitimai pagrindinio (haploidinio) jų skaičiaus atžvilgiu. atitikmenys: angl. aneuploidy; heteroploidy rus.… … Žemės ūkio augalų selekcijos ir sėklininkystės terminų žodynas
aneuploidy — noun see aneuploid … New Collegiate Dictionary
aneuploidy — an·eu·ploi·dy (ănʹyə ploi dē) n. The state or condition of being aneuploid. * * * … Universalium
aneuploidy — noun The condition of being aneuploid; the state of possessing chromosome number than is not an exact multiple of the haploid number. See Also: aneuploid, aneuploidic … Wiktionary
aneuploidy — an·eu·ploidy … English syllables
aneuploidy — n. the condition in which the chromosome number of a cell is not an exact multiple of the normal basic (haploid) number. See: monosomy, trisomy Compare: euploidy Derivatives: aneuploid adj., n … The new mediacal dictionary
aneuploidy — /ˈænjuplɔɪdi/ (say anyoohploydee) noun abnormality in the number of chromosomes … Australian English dictionary