A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of
chromosomal
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
DNA. 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
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. Chromosome anomalies usually occur when there is an error in
cell division
Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...
following
meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...
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
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
via
genetic testing.
Numerical abnormality
![Down Syndrome Karyotype](https://upload.wikimedia.org/wikipedia/commons/1/11/Down_Syndrome_Karyotype.png)
An abnormal number of chromosomes is called
aneuploidy
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 ...
, and occurs when an individual is either missing a chromosome from a pair (resulting in
monosomy
Monosomy is a form of aneuploidy with the presence of only one chromosome from a pair. Partial monosomy occurs when a portion of one chromosome in a pair is missing.
Human monosomy
Human conditions due to monosomy:
* Turner syndrome – People wit ...
) or has more than two chromosomes of a pair (
trisomy
A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes).
Description and causes
Most organisms that reprodu ...
,
tetrasomy
A tetrasomy is a form of aneuploidy with the presence of four copies, instead of the normal two, of a particular chromosome.
Causes Full
Full tetrasomy of an individual occurs due to non-disjunction when the cells are dividing (meiosis I or II) ...
, etc.).
Aneuploidy can be full, involving a whole chromosome missing or added, or partial, where only part of a chromosome is missing or added.
Aneuploidy can occur with
sex chromosome
A sex chromosome (also referred to as an allosome, heterotypical chromosome, gonosome, heterochromosome, or idiochromosome) is a chromosome that differs from an ordinary autosome in form, size, and behavior. The human sex chromosomes, a typical ...
s or
autosomes.
An example of trisomy in humans is
Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
, which is a developmental disorder caused by an extra copy of chromosome 21; the disorder is therefore also called trisomy 21.
An example of monosomy in humans is
Turner syndrome
Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...
, where the individual is born with only one sex chromosome, an X.
Sperm aneuploidy
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of
aneuploid
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 ...
spermatozoa.
In particular, risk of aneuploidy is increased by
tobacco smoking
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
,
and occupational exposure to
benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
,
insecticides,
and
perfluorinated compound
A perfluorinated compound (PFC) or perfluoro compound is an organofluorine compound containing only carbon-fluorines and C−C bonds, as well as potentially heteroatoms. Perfluorinated compounds have properties that result from the presence of flu ...
s.
Increased aneuploidy is often associated with increased DNA damage in spermatozoa.
Structural abnormalities
![Two Chromosome Mutations](https://upload.wikimedia.org/wikipedia/commons/2/28/Two_Chromosome_Mutations.png)
When the chromosome's structure is altered, this can take several forms:
*
Deletions: A portion of the chromosome is missing or has been deleted. Known disorders in humans include
Wolf–Hirschhorn syndrome
Wolf–Hirschhorn syndrome (WHS) is a chromosomal deletion syndrome resulting from a partial deletion on the short arm of chromosome 4 (del(4p16.3)). Features include a distinct craniofacial phenotype and intellectual disability.
Signs and sympt ...
, which is caused by partial deletion of the short arm of chromosome 4; and
Jacobsen syndrome
Jacobsen syndrome is a rare Chromosome abnormality, chromosomal disorder resulting from Deletion (genetics), deletion of genes from chromosome 11 that includes band 11q24.1. It is a congenital disorder. Since the deletion takes place on the q arm ...
, also called the terminal 11q deletion disorder.
*
Duplications: A portion of the chromosome has been duplicated, resulting in extra genetic material. Known human disorders include
Charcot–Marie–Tooth disease type 1A, which may be caused by duplication of the gene encoding
peripheral myelin protein 22
Growth arrest-specific protein 3 (GAS-3), also called peripheral myelin protein 22 (PMP22), is a protein which in humans is encoded by the ''PMP22'' gene.
PMP22 is a 22 kDa transmembrane glycoprotein made up of 160 amino acids, and is mainly e ...
(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
The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers ...
- in humans, these only occur with chromosomes 13, 14, 15, 21, and 22.
*
Rings
Ring may refer to:
* Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry
* To make a sound with a bell, and the sound made by a bell
:(hence) to initiate a telephone connection
Arts, entertainment and media Film and ...
: A portion of a chromosome has broken off and formed a circle or ring. This can happen 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
Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized ...
(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.
Acquired chromosome abnormalities
Most cancers, if not all, could cause chromosome abnormalities, 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" and the
Atlas of Genetics and Cytogenetics in Oncology and Haematology
The Atlas of Genetics and Cytogenetics in Oncology and Haematology, created in 1997 by Jean-Loup Huret (with bioinformatics by Philippe Dessen) is a collection of resources on genes, Chromosome abnormality, chromosomes anomalies, leukemias, solid ...
,). 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.
DNA damage during spermatogenesis
During the
mitotic
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...
and
meiotic
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately res ...
cell divisions of mammalian
gametogenesis
Gametogenesis is a biological process by which diploid or haploid precursor cells undergo cell division and differentiation to form mature haploid gametes. Depending on the biological life cycle of the organism, gametogenesis occurs by meiotic di ...
,
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
is effective at removing
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
s.
However, in
spermatogenesis the ability to repair DNA damages decreases substantially in the latter part of the process as haploid
spermatid
The spermatid is the haploid male gametid that results from division of secondary spermatocytes. As a result of meiosis, each spermatid contains only half of the genetic material present in the original primary spermatocyte.
Spermatids are co ...
s undergo major nuclear
chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
remodeling into highly compacted
sperm nuclei. As reviewed by Marchetti et al.,
the last few weeks of sperm development before
fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
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
zygote
A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism.
In multicell ...
s with chromosomal structural aberrations.
Melphalan
Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and AL amyloidosis. It is taken by mouth or by injection into a vein.
Common side effects incl ...
is a bifunctional
alkylating agent
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
frequently used in
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
. Meiotic inter-strand DNA damages caused by melphalan can escape paternal repair and cause chromosomal aberrations in the zygote by maternal misrepair.
Thus both pre- and post-fertilization DNA repair appear to be important in avoiding chromosome abnormalities and assuring the
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
integrity of the
conceptus
A conceptus (from Latin: ''concipere'' to conceive) is an embryo and its appendages (adnexa), the associated membranes, placenta, and umbilical cord; the products of conception or, more broadly, "the product of conception at any point between fert ...
.
Detection
Depending on the information one wants to obtain, different techniques and samples are needed.
* For the
prenatal diagnosis
Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...
of a foetus,
amniocentesis
Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is n ...
,
chorionic villus sampling or circulating foetal cells would be collected and analysed in order to detect possible chromosomal abnormalities.
* For the
preimplantational diagnosis of an embryo, a
blastocyst biopsy
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
would be performed.
* For a lymphoma or leukemia screening the technique used would be a
bone marrow biopsy
Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditio ...
.
Nomenclature
![Three chromosomal abnormalities with ISCN nomenclature](https://upload.wikimedia.org/wikipedia/commons/6/6b/Three_chromosomal_abnormalities_with_ISCN_nomenclature.png)
The
International System for Human Cytogenomic Nomenclature The International System for Human Cytogenomic Nomenclature (previously International System for Human Cytogenetic Nomenclature), ISCN in short, is an international standard for human chromosome nomenclature, which includes band names, symbols and a ...
(ISCN) is an international standard for
human chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
nomenclature
Nomenclature (, ) is a system of names or terms, or the rules for forming these terms in a particular field of arts or sciences. The principles of naming vary from the relatively informal conventions of everyday speech to the internationally ag ...
, 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.
See also
*
Aneuploidy
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 ...
*
Chromosome segregation
Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregati ...
*
Genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
**
List of genetic disorders
The following is a list of genetic disorders and if known, type of mutation and for the chromosome involved. Although the parlance "disease-causing gene" is common, it is the occurrence of an abnormality in the parents that causes the impairment ...
*
Gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
*
Nondisjunction
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 ...
*
Obstetrical complications
References
External links
*
{{Authority control
Chromosomal abnormalities
Cytogenetics
Genetics concepts