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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 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 ar ...
. 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. A gene fusion may be created when the translocation joins two otherwise-separated genes. It is detected on cytogenetics or a karyotype of affected
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
. Translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of
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 ar ...
material is unequal resulting in extra or missing
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 ...
s).


Reciprocal translocations

Reciprocal translocations are usually an ''exchange'' of material between non-homologous chromosomes and occur in about 1 in 491 live births. Such translocations are usually harmless, as they do not result in a gain or loss of genetic material, though they may be detected in prenatal diagnosis. However, carriers of balanced reciprocal translocations may create gametes with ''unbalanced'' chromosome translocations during
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 ...
chromosomal segregation. This can lead to infertility, miscarriages or children with abnormalities. Genetic counseling and genetic testing are often offered to families that may carry a translocation. Most balanced translocation carriers are healthy and do not have any symptoms. It is important to distinguish between chromosomal translocations that occur in
germ cell Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embr ...
s, due to errors in
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 ...
(i.e. during gametogenesis), and those that occur in somatic cells, due to errors in mitosis. The former results in a chromosomal abnormality featured in all cells of the offspring, as in translocation carriers. Somatic translocations, on the other hand, result in abnormalities featured only in the affected cell and its progenitors, as in chronic myelogenous leukemia with the
Philadelphia chromosome The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). This chromosome is defective and unusually short becaus ...
translocation.


Nonreciprocal translocation

Nonreciprocal translocation involves the one-way transfer of genes from one
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 ar ...
to another nonhomologous chromosome.


Robertsonian translocations

Robertsonian translocation is a type of translocation caused by breaks at or near the centromeres of two acrocentric chromosomes. The reciprocal exchange of parts gives rise to one large
metacentric Metacentric may refer to: * Metacentric height, the distance between the center of gravity of a ship and its metacenter * Metacentric centromere, the position of a centromere on a chromatid {{disambiguation ...
chromosome and one extremely small chromosome that may be lost from the organism with little effect because it contains few genes. The resulting karyotype in humans leaves only 45 chromosomes, since two chromosomes have fused together. This has no direct effect on the phenotype, since the only genes on the short arms of acrocentrics are common to all of them and are present in variable copy number (nucleolar organiser genes). Robertsonian translocations have been seen involving all combinations of acrocentric chromosomes. The most common translocation in humans involves chromosomes 13 and 14 and is seen in about 0.97 / 1000 newborns. Carriers of Robertsonian translocations are not associated with any phenotypic abnormalities, but there is a risk of unbalanced gametes that lead to miscarriages or abnormal offspring. For example, carriers of Robertsonian translocations involving chromosome 21 have a higher risk of having a child with
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 d ...
. This is known as a 'translocation Downs'. This is due to a mis-segregation ( nondisjunction) during gametogenesis. The mother has a higher (10%) risk of transmission than the father (1%). Robertsonian translocations involving chromosome 14 also carry a slight risk of uniparental disomy 14 due to
trisomy rescue Trisomic rescue (also known as trisomy rescue or trisomy zygote rescue) is a genetic phenomenon in which a fertilized ovum containing three copies of a chromosome loses one of these chromosomes (anaphase lag) to form a diploid chromosome complement. ...
.


Role in disease

Some human diseases caused by translocations are: *
Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
: Several forms of cancer are caused by acquired translocations (as opposed to those present from conception); this has been described mainly in
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
(
acute myelogenous leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
and chronic myelogenous leukemia). Translocations have also been described in solid malignancies such as Ewing's sarcoma. * Infertility: One of the would-be parents carries a ''balanced translocation'', where the parent is asymptomatic but conceived fetuses are not viable. *
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 d ...
is caused in a minority (5% or less) of cases by a Robertsonian translocation of the chromosome 21 long arm onto the long arm of chromosome 14. Chromosomal translocations between the sex chromosomes can also result in a number of genetic conditions, such as *
XX male syndrome XX male syndrome, also known as de la Chapelle syndrome, is a rare congenital intersex condition in which an individual with a 46, XX karyotype (otherwise associated with females) has phenotypically male characteristics that can vary among cases ...
: caused by a translocation of the SRY gene from the Y to the X chromosome


By chromosome


Denotation

The International System for Human Cytogenetic Nomenclature (ISCN) is used to denote a translocation between
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 ar ...
s. The designation t(A;B)(p1;q2) is used to denote a translocation between
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 ar ...
A and chromosome B. The information in the second set of parentheses, when given, gives the precise location within the chromosome for chromosomes A and B respectively—with ''p'' indicating the short arm of the chromosome, ''q'' indicating the long arm, and the numbers after p or q refers to regions, bands and sub-bands seen when staining the chromosome with a
staining dye Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in the ...
. See also the definition of a genetic locus. The translocation is the mechanism that can cause a gene to move from one linkage group to another.


Examples of translocations on human chromosomes


History

In 1938,
Karl Sax Karl Sax (November 2, 1892 – October 8, 1973) was an American botanist and geneticist, noted for his research in cytogenetics and the effect of radiation on chromosomes. Early life and education Sax was born in Spokane, Washington in 1892. His ...
, at the
Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of highe ...
Biological Laboratories, published a paper entitled "Chromosome Aberrations Induced by X-rays", which demonstrated that radiation could induce major genetic changes by affecting chromosomal translocations. The paper is thought to mark the beginning of the field of radiation cytology, and led him to be called "the father of radiation cytology".


DNA double-strand break repair

The initiating event in the formation of a translocation is generally a double-strand break in chromosomal DNA.Agarwal S, Tafel AA, Kanaar R. DNA double-strand break repair and chromosome translocations. DNA Repair (Amst). 2006 Sep 8;5(9-10):1075-81. doi: 10.1016/j.dnarep.2006.05.029. Epub 2006 Jun 23. PMID: 16798112 A type of DNA repair that has a major role in generating chromosomal translocations is the non-homologous end joining pathway. When this pathway functions appropriately it restores a DNA double-strand break by reconnecting the originally broken ends, but when it acts inappropriately it may join ends incorrectly resulting in genomic rearrangements including translocations. In order for the illegitimate joining of broken ends to occur, the exchange partners DNAs need to be physically close to each other in the 3D
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 ...
.Rocha PP, Chaumeil J, Skok JA. Molecular biology. Finding the right partner in a 3D genome. Science. 2013 Dec 13;342(6164):1333-4. doi: 10.1126/science.1246106. PMID: 24337287; PMCID: PMC3961821


See also

* Accipitridae * Aneuploidy * Chromosome abnormalities * DbCRID * Fusion gene * Pseudodiploid * '' Takifugu rubripes''


References


External links

* {{DEFAULTSORT:Chromosomal Translocation Chromosomal abnormalities Cytogenetics Modification of genetic information