Chromosome abnormality
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.
Almost every single cell in our body is made up of two of the 46 chromosomal pairs that make up our whole body.
Sometimes chromosomal abnormalities arise in the early stages of an
The kind of chromosomal aberration is
Numerical abnormality
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.).[7][8] Aneuploidy can be full, involving a whole chromosome missing or added, or partial, where only part of a chromosome is missing or added.[7] Aneuploidy can occur with sex chromosomes or autosomes.[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.[9]
An example of monosomy in humans is Turner syndrome, where the individual is born with only one sex chromosome, an X.[10]
Sperm aneuploidy
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa.[11] In particular, risk of aneuploidy is increased by tobacco smoking,[12][13] and occupational exposure to benzene,[14] insecticides,[15][16] and perfluorinated compounds.[17] Increased aneuploidy is often associated with increased DNA damage in spermatozoa.
Structural abnormalities
When the chromosome's structure is altered, this can take several forms:[18]
- Deletions: A portion of the chromosome is missing or has been deleted. Known disorders in humans include Wolf–Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.
- Charcot–Marie–Tooth disease type 1A, which may be caused by duplication of the gene encoding peripheral myelin protein 22(PMP22) on chromosome 17.
- Inversions: A portion of the chromosome has broken off, turned upside down, and reattached, therefore the genetic material is inverted.
- Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.
- Translocations: A portion of one chromosome has been transferred to another chromosome. There are two main types of translocations:
- Reciprocal translocation: Segments from two different chromosomes have been exchanged.
- Robertsonian translocation: An entire chromosome has attached to another at the centromere - in humans, these only occur with chromosomes 13, 14, 15, 21, and 22.
- Rings: A portion of a chromosome has broken off and formed a circle or ring. This happens with or without the loss of genetic material.
- Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.
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
Acquired chromosome abnormalities
Most cancers, if not all, could cause chromosome abnormalities,[19] 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" [20] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[21]). 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.[22]
DNA damage during spermatogenesis
During the
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.[24] 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]
- For the prenatal diagnosis of a foetus, amniocentesis, chorionic villus samplingor circulating foetal cells would be collected and analysed in order to detect possible chromosomal abnormalities.
- For the blastocyst biopsywould be performed.
- For a lymphoma or leukemia screening the technique used would be a bone marrow biopsy.
Nomenclature
-
Three chromosomal abnormalities with ISCN nomenclature, with increasing complexity: (A) A tumour karyotype in a male with loss of the Y chromosome, (B) Prader–Willi Syndrome i.e. deletion in the 15q11-q12 region and (C) an arbitrary karyotype that involves a variety of autosomal and allosomal abnormalities.[25]
-
Humanautosomal chromosome pairs, both the female (XX) and male (XY) versions of the two sex chromosomes, as well as the mitochondrial genome(at bottom left).
The
See also
- Aneuploidy
- Chromosome segregation
- Genetic disorder
- Gene therapy
- Nondisjunction
- Obstetrical complications
References
- ^ "Chromosomal Abnormalities", Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals, Genetic Alliance, 2009-07-08, retrieved 2023-09-27
- ^ NHGRI. 2006. Chromosome Abnormalities Archived 2006-09-25 at the Wayback Machine
- ISBN 978-0-387-07668-3.
- )
- ISBN 978-1-58829-681-8.
- PMID 9797104.
- ^ OCLC 769344040.
- ^ "Numerical Abnormalities: Overview of Trisomies and Monosomies - Health Encyclopedia - University of Rochester Medical Center". www.urmc.rochester.edu. Retrieved 2020-11-17.[failed verification]
- S2CID 10403507.
- ^ "Turner Syndrome". National Institute of Child Health and Human Development. Retrieved 2020-11-17.
- PMID 23720770.
- S2CID 35230655.
- PMID 9797104.
- PMID 20418200.
- S2CID 36073841.
- PMID 15615886.
- S2CID 13484513.
- ^ "Chromosome Abnormalities". atlasgeneticsoncology.org. Archived from the original on 14 August 2006. Retrieved 9 May 2018.
- ^ "Chromosomes, Leukemias, Solid Tumors, Hereditary Cancers". atlasgeneticsoncology.org. Archived from the original on 28 January 2015. Retrieved 9 May 2018.
- ^ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-29.
- ^ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org. Archived from the original on 2011-02-23.
- PMID 11071361.
- PMID 11226027.
- ^ PMID 25567288.
- PMID 31228194.)"
- "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ - ^ "ISCN Symbols and Abbreviated Terms". Coriell Institute for Medical Research. Retrieved 2022-10-27.
External links
- Chromosome+disorders at the U.S. National Library of Medicine Medical Subject Headings (MeSH)