Chromosome abnormality

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A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. [1] [2] These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene. [3] Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individual's karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing.

Contents

Sometimes chromosomal abnormalities arise in the early stages of an embryo, sperm, or infant. [4] A mother's age is one of the many environmental factors that might lead to genetic abnormalities. The implications of chromosomal abnormalities depend on the specific problem, they may have quite different ramifications. Some examples are Down syndrome and Turner syndrome.


Numerical abnormality

A karyotype of an individual with trisomy 21, showing three copies of chromosome 21. Down Syndrome Karyotype.png
A karyotype of an individual with trisomy 21, showing three copies of chromosome 21.

An abnormal number of chromosomes is known as aneuploidy, and occurs when an individual is either missing a chromosome from a pair (resulting in monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.). [5] [6] Aneuploidy can be full, involving a whole chromosome missing or added, or partial, where only part of a chromosome is missing or added. [5] Aneuploidy can occur with sex chromosomes or autosomes.[ citation needed ]

Rather than having monosomy, or only one copy, the majority of aneuploid people have trisomy, or three copies of one chromosome.[ citation needed ] An example of trisomy in humans is Down syndrome, which is a developmental disorder caused by an extra copy of chromosome 21; the disorder is therefore also called trisomy 21. [7]

An example of monosomy in humans is Turner syndrome, where the individual is born with only one sex chromosome, an X. [8]

Sperm aneuploidy

Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa. [9] In particular, risk of aneuploidy is increased by tobacco smoking, [10] [11] and occupational exposure to benzene, [12] insecticides, [13] [14] and perfluorinated compounds. [15] Increased aneuploidy is often associated with increased DNA damage in spermatozoa.

Structural abnormalities

The three major single-chromosome mutations: deletion (1), duplication (2) and inversion (3). Single Chromosome Mutations.svg
The three major single-chromosome mutations: deletion (1), duplication (2) and inversion (3).
The two major two-chromosome mutations: insertion (1) and translocation (2). Two Chromosome Mutations.png
The two major two-chromosome mutations: insertion (1) and translocation (2).

When the chromosome's structure is altered, this can take several forms: [16]

Chromosome instability syndromes are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.

Inheritance

Most chromosome abnormalities occur as an accident in the egg cell or sperm, and therefore the anomaly is present in every cell of the body. Some anomalies, however, can happen after conception, resulting in Mosaicism (where some cells have the anomaly and some do not). Chromosome anomalies can be inherited from a parent or be "de novo". This is why chromosome studies are often performed on parents when a child is found to have an anomaly. If the parents do not possess the abnormality it was not initially inherited; however, it may be transmitted to subsequent generations.[ citation needed ]

Acquired chromosome abnormalities

Most cancers, if not all, could cause chromosome abnormalities, [17] with either the formation of hybrid genes and fusion proteins, deregulation of genes and overexpression of proteins, or loss of tumor suppressor genes (see the "Mitelman Database" [18] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology, [19] ). Furthermore, certain consistent chromosomal abnormalities can turn normal cells into a leukemic cell such as the translocation of a gene, resulting in its inappropriate expression. [20]

DNA damage during spermatogenesis

During the mitotic and meiotic cell divisions of mammalian gametogenesis, DNA repair is effective at removing DNA damages. [21] However, in spermatogenesis the ability to repair DNA damages decreases substantially in the latter part of the process as haploid spermatids undergo major nuclear chromatin remodeling into highly compacted sperm nuclei. As reviewed by Marchetti et al., [22] the last few weeks of sperm development before fertilization are highly susceptible to the accumulation of sperm DNA damage. Such sperm DNA damage can be transmitted unrepaired into the egg where it is subject to removal by the maternal repair machinery. However, errors in maternal DNA repair of sperm DNA damage can result in zygotes with chromosomal structural aberrations.[ citation needed ]

Melphalan is a bifunctional alkylating agent frequently used in chemotherapy. Meiotic inter-strand DNA damages caused by melphalan can escape paternal repair and cause chromosomal aberrations in the zygote by maternal misrepair. [22] Thus both pre- and post-fertilization DNA repair appear to be important in avoiding chromosome abnormalities and assuring the genome integrity of the conceptus.[ citation needed ]

Detection

Depending on the information one wants to obtain, different techniques and samples are needed.[ citation needed ]

Nomenclature

The International System for Human Cytogenomic Nomenclature (ISCN) is an international standard for human chromosome nomenclature, which includes band names, symbols and abbreviated terms used in the description of human chromosome and chromosome abnormalities. Abbreviations include a minus sign (-) for chromosome deletions, and del for deletions of parts of a chromosome. [24]

See also

Related Research Articles

<span class="mw-page-title-main">Autosome</span> Any chromosome other than a sex chromosome

An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal pairs, which may have different structures. The DNA in autosomes is collectively known as atDNA or auDNA.

<span class="mw-page-title-main">Chromosome</span> DNA molecule containing genetic material of a cell

A chromosome is a package of DNA with part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells the most important of these proteins are the histones. These proteins, aided by chaperone proteins, bind to and condense the DNA molecule to maintain its integrity. These chromosomes display a complex three-dimensional structure, which plays a significant role in transcriptional regulation.

<span class="mw-page-title-main">Spermatozoon</span> Motile sperm cell

A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.

<span class="mw-page-title-main">Karyotype</span> Photographic display of total chromosome complement in a cell

A karyotype is the general appearance of the complete set of chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is discerned by determining the chromosome complement of an individual, including the number of chromosomes and any abnormalities.

<span class="mw-page-title-main">Deletion (genetics)</span> Mutation that removes a part of a DNA sequence

In genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome. Some chromosomes have fragile spots where breaks occur, which result in the deletion of a part of the chromosome. The breaks can be induced by heat, viruses, radiation, or chemical reactions. When a chromosome breaks, if a part of it is deleted or lost, the missing piece of chromosome is referred to as a deletion or a deficiency.

<span class="mw-page-title-main">Aneuploidy</span> Presence of an abnormal number of chromosomes in a cell

Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any number of complete chromosome sets is called a euploid cell.

<span class="mw-page-title-main">Cytogenetics</span> Branch of genetics

Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology, that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis and meiosis. Techniques used include karyotyping, analysis of G-banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH).

<span class="mw-page-title-main">Trisomy 18</span> Chromosomal disorder in which there are three copies of chromosome 18

Trisomy 18, also known as Edwards syndrome, is a genetic disorder caused by the presence of a third copy of all or part of chromosome 18. Many parts of the body are affected. Babies are often born small and have heart defects. Other features include a small head, small jaw, clenched fists with overlapping fingers, and severe intellectual disability.

<span class="mw-page-title-main">Nondisjunction</span> Failure to separate properly during cell division

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

<span class="mw-page-title-main">Chromosomal translocation</span> Phenomenon that results in unusual rearrangement of chromosomes

In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal, and Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" and blends together homogeneously.

<span class="mw-page-title-main">Isochromosome</span>

An isochromosome is an unbalanced structural abnormality in which the arms of the chromosome are mirror images of each other. The chromosome consists of two copies of either the long (q) arm or the short (p) arm because isochromosome formation is equivalent to a simultaneous duplication and deletion of genetic material. Consequently, there is partial trisomy of the genes present in the isochromosome and partial monosomy of the genes in the lost arm.

Trisomy 8 causes Warkany syndrome 2, a human chromosomal disorder caused by having three copies (trisomy) of chromosome 8. It can appear with or without mosaicism.

<span class="mw-page-title-main">Polysomy</span> Abnormal multiples of one or more chromosomes

Polysomy is a condition found in many species, including fungi, plants, insects, and mammals, in which an organism has at least one more chromosome than normal, i.e., there may be three or more copies of the chromosome rather than the expected two copies. Most eukaryotic species are diploid, meaning they have two sets of chromosomes, whereas prokaryotes are haploid, containing a single chromosome in each cell. Aneuploids possess chromosome numbers that are not exact multiples of the haploid number and polysomy is a type of aneuploidy. A karyotype is the set of chromosomes in an organism and the suffix -somy is used to name aneuploid karyotypes. This is not to be confused with the suffix -ploidy, referring to the number of complete sets of chromosomes.

<span class="mw-page-title-main">Chromosome 13</span> Human chromosome

Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 113 million base pairs and represents between 3.5 and 4% of the total DNA in cells.

<span class="mw-page-title-main">Chromosome 22</span> Human chromosome

Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 51 million DNA base pairs and representing between 1.5 and 2% of the total DNA in cells.

A dicentric chromosome is an abnormal chromosome with two centromeres. It is formed through the fusion of two chromosome segments, each with a centromere, resulting in the loss of acentric fragments and the formation of dicentric fragments. The formation of dicentric chromosomes has been attributed to genetic processes, such as Robertsonian translocation and paracentric inversion. Dicentric chromosomes have important roles in the mitotic stability of chromosomes and the formation of pseudodicentric chromosomes. Their existence has been linked to certain natural phenomena such as irradiation and have been documented to underlie certain clinical syndromes, notably Kabuki syndrome. The formation of dicentric chromosomes and their implications on centromere function are studied in certain clinical cytogenetics laboratories.

<span class="mw-page-title-main">Genetics of Down syndrome</span>

Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on chromosome 21, either in whole or part. The effects of the extra copy varies greatly from individual to individual, depending on the extent of the extra copy, genetic background, environmental factors, and random chance. Down syndrome can occur in all human populations, and analogous effects have been found in other species, such as chimpanzees and mice. In 2005, researchers have been able to create transgenic mice with most of human chromosome 21.

Virtual karyotype is the digital information reflecting a karyotype, resulting from the analysis of short sequences of DNA from specific loci all over the genome, which are isolated and enumerated. It detects genomic copy number variations at a higher resolution for level than conventional karyotyping or chromosome-based comparative genomic hybridization (CGH). The main methods used for creating virtual karyotypes are array-comparative genomic hybridization and SNP arrays.

<span class="mw-page-title-main">Trisomy X</span> Chromosome disorder in women

Trisomy X, also known as triple X syndrome and characterized by the karyotype 47,XXX, is a chromosome disorder in which a female has an extra copy of the X chromosome. It is relatively common and occurs in 1 in 1,000 females, but is rarely diagnosed; fewer than 10% of those with the condition know they have it.

<span class="mw-page-title-main">XXXYY syndrome</span> Chromosomal disorder

XXXYY syndrome, also known as 49,XXXYY, is a chromosomal disorder in which a male has three copies of the X chromosome and two copies of the Y chromosome. XXXYY syndrome is exceptionally rare, with only eight recorded cases. Little is known about its presentation, but associated characteristics include intellectual disability, anomalies of the external genitalia, and characteristic physical and facial features. It is not caused by characteristics of the parents, but rather occurs via nondisjunction, a random event in gamete development. The karyotype observed in the syndrome is formally known as 49,XXXYY, which represents the 49 chromosomes observed in the disorder as compared to the 46 in normal human development.

References

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  2. ↑ NHGRI. 2006. Chromosome Abnormalities Archived 2006-09-25 at the Wayback Machine
  3. ↑ Rieger, R., Michaelis, A., Green, M.M. (1968). "Mutation" . A glossary of genetics and cytogenetics: Classical and molecular. New York: Springer-Verlag. ISBN   978-0-387-07668-3.
  4. ↑ Chen H (2006). Atlas of genetic diagnosis and counseling. Totowa, N.J: Humana Press. ISBN   978-1-58829-681-8.
  5. 1 2 Gardner, R. J. M. (2012). Chromosome abnormalities and genetic counseling. Sutherland, Grant R., Shaffer, Lisa G. (4th ed.). Oxford: Oxford University Press. ISBN   978-0-19-974915-7. OCLC   769344040.
  6. ↑ "Numerical Abnormalities: Overview of Trisomies and Monosomies - Health Encyclopedia - University of Rochester Medical Center". www.urmc.rochester.edu. Retrieved 2020-11-17.[ failed verification ]
  7. ↑ Patterson D (2009-07-01). "Molecular genetic analysis of Down syndrome". Human Genetics. 126 (1): 195–214. doi:10.1007/s00439-009-0696-8. ISSN   1432-1203. PMID   19526251. S2CID   10403507.
  8. ↑ "Turner Syndrome". National Institute of Child Health and Human Development. Retrieved 2020-11-17.
  9. ↑ Templado C, Uroz L, Estop A (2013). "New insights on the origin and relevance of aneuploidy in human spermatozoa". Mol. Hum. Reprod. 19 (10): 634–43. doi:10.1093/molehr/gat039. PMID   23720770.
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  12. ↑ Xing C, Marchetti F, Li G, Weldon RH, Kurtovich E, Young S, Schmid TE, Zhang L, Rappaport S, Waidyanatha S, Wyrobek AJ, Eskenazi B (2010). "Benzene exposure near the U.S. permissible limit is associated with sperm aneuploidy". Environ. Health Perspect. 118 (6): 833–9. doi:10.1289/ehp.0901531. PMC   2898861 . PMID   20418200.
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  15. ↑ Governini L, Guerranti C, De Leo V, Boschi L, Luddi A, Gori M, Orvieto R, Piomboni P (2014). "Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds". Andrologia. 47 (9): 1012–9. doi: 10.1111/and.12371 . hdl:11365/982323. PMID   25382683. S2CID   13484513.
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  17. ↑ "Chromosomes, Leukemias, Solid Tumors, Hereditary Cancers". atlasgeneticsoncology.org. Archived from the original on 28 January 2015. Retrieved 9 May 2018.
  18. ↑ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-29.
  19. ↑ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org. Archived from the original on 2011-02-23.
  20. ↑ Chaganti RS, Nanjangud G, Schmidt H, Teruya-Feldstein J (October 2000). "Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance". Seminars in Hematology. 37 (4): 396–411. doi:10.1016/s0037-1963(00)90019-2. ISSN   0037-1963. PMID   11071361.
  21. ↑ Baarends WM, van der Laan R, Grootegoed JA (2001). "DNA repair mechanisms and gametogenesis". Reproduction. 121 (1): 31–9. doi: 10.1530/reprod/121.1.31 . hdl: 1765/9599 . PMID   11226027.
  22. 1 2 Marchetti F, Bishop J, Gingerich J, Wyrobek AJ (2015). "Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair". Sci Rep. 5: 7689. Bibcode:2015NatSR...5E7689M. doi:10.1038/srep07689. PMC   4286742 . PMID   25567288.
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    - "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)"
  24. ↑ "ISCN Symbols and Abbreviated Terms". Coriell Institute for Medical Research. Retrieved 2022-10-27.
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