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.
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
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
When the chromosome's structure is altered, this can take several forms:[16]
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.
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
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]
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.[23]
The
International System for Human Cytogenomic Nomenclature (ISCN) is an international standard for
human chromosomenomenclature, 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]
^"Chromosomal Abnormalities", Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals, Genetic Alliance, 2009-07-08, retrieved 2023-09-27
^Rieger, R., Michaelis, A., Green, M.M. (1968). "Mutation". A glossary of genetics and cytogenetics: Classical and molecular. New York: Springer-Verlag.
ISBN978-0-387-07668-3.
^Chen H (2006). Atlas of genetic diagnosis and counseling. Totowa, N.J: Humana Press.
ISBN978-1-58829-681-8.
^
abGardner, R. J. M. (2012). Chromosome abnormalities and genetic counseling. Sutherland, Grant R., Shaffer, Lisa G. (4th ed.). Oxford: Oxford University Press.
ISBN978-0-19-974915-7.
OCLC769344040.
^"Turner Syndrome". National Institute of Child Health and Human Development. Retrieved 2020-11-17.
^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.
PMID23720770.
^Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R (2001). "Cigarette smoking and aneuploidy in human sperm". Mol. Reprod. Dev. 59 (4): 417–21.
doi:
10.1002/mrd.1048.
PMID11468778.
S2CID35230655.
^Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X (2004). "Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate". Toxicology. 203 (1–3): 49–60.
doi:
10.1016/j.tox.2004.05.018.
PMID15363581.
S2CID36073841.