Chromosomal reciprocal translocation of the 4th and 20th chromosome.
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" together.
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. 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 material is unequal resulting in extra or missing genes).
Reciprocal translocations
Reciprocal
translocations are usually an exchange of material between
non-homologous chromosomes. Estimates of incidence range from about 1 in
500 to 1 in 625 human newborns. Such translocations are usually harmless and may be found through prenatal diagnosis. However, carriers of balanced reciprocal translocations have increased risks of creating gametes with unbalanced chromosome translocations, leading 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 occurring in gametogenesis, due to errors in meiosis, and translocations that occur in cellular division of 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 line, as in chronic myelogenous leukemia with the Philadelphia chromosome translocation.
Nonreciprocal translocation
Nonreciprocal translocation involves the one-way transfer of genes from one chromosome 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
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. 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.
Role in disease
Some human diseases caused by translocations are:
- Cancer: Several forms of cancer are caused by acquired translocations (as opposed to those present from conception); this has been described mainly in leukemia (acute myelogenous leukemia 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 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: caused by a translocation of the SRY gene from the Y to the X chromosome
By chromosome
Overview
of some chromosomal translocations involved in different cancers, as
well as implicated in some other conditions, e.g. schizophrenia, with chromosomes arranged in standard karyogram order. Abbreviations:
ALL – Acute lymphoblastic leukemia
AML – Acute myeloid leukemia
CML – Chronic myelogenous leukemia
DFSP – Dermatofibrosarcoma protuberans
ALL – Acute lymphoblastic leukemia
AML – Acute myeloid leukemia
CML – Chronic myelogenous leukemia
DFSP – Dermatofibrosarcoma protuberans
Denotation
The International System for Human Cytogenetic Nomenclature (ISCN) is used to denote a translocation between chromosomes. The designation t(A;B)(p1;q2) is used to denote a translocation between chromosome
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 subbands seen when staining the chromosome with a staining dye. 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
| Translocation | Associated diseases | Fused genes/proteins | |
|---|---|---|---|
| First | Second | ||
| t(8;14)(q24;q32) | Burkitt's lymphoma | c-myc on chromosome 8, gives the fusion protein lymphocyte-proliferative ability |
IGH@ (immunoglobulin heavy locus) on chromosome 14, induces massive transcription of fusion protein |
| t(11;14)(q13;q32) | Mantle cell lymphoma | cyclin D1 on chromosome 11, gives fusion protein cell-proliferative ability |
IGH@ (immunoglobulin heavy locus) on chromosome 14, induces massive transcription of fusion protein |
| t(14;18)(q32;q21) | Follicular lymphoma (~90% of cases) | IGH@ (immunoglobulin heavy locus) on chromosome 14, induces massive transcription of fusion protein |
Bcl-2 on chromosome 18, gives fusion protein anti-apoptotic abilities |
| t(10;(various))(q11;(various)) | Papillary thyroid cancer | RET proto-oncogene[15] on chromosome 10 | PTC (Papillary Thyroid Cancer) – Placeholder for any of several other genes/proteins |
| t(2;3)(q13;p25) | Follicular thyroid cancer | PAX8 – paired box gene 8 on chromosome 2 | PPARγ1 (peroxisome proliferator-activated receptor γ 1) on chromosome 3 |
| t(8;21)(q22;q22)[14] | Acute myeloblastic leukemia with maturation | ETO on chromosome 8 | AML1 on chromosome 21 found in ~7% of new cases of AML, carries a favorable prognosis and predicts good response to cytosine arabinoside therapy |
| t(9;22)(q34;q11) Philadelphia chromosome | Chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) | Abl1 gene on chromosome 9 | BCR ("breakpoint cluster region" on chromosome 22 |
| t(15;17)(q22;q21)[14] | Acute promyelocytic leukemia | PML protein on chromosome 15 | RAR-α on chromosome 17 persistent laboratory detection of the PML-RARA transcript is strong predictor of relapse |
| t(12;15)(p13;q25) | Acute myeloid leukemia, congenital fibrosarcoma, secretory breast carcinoma, mammary analogue secretory carcinoma of salivary glands, cellular variant of mesoblastic nephroma | TEL on chromosome 12 | TrkC receptor on chromosome 15 |
| t(9;12)(p24;p13) | CML, ALL | JAK on chromosome 9 | TEL on chromosome 12 |
| t(12;16)(q13;p11) | Myxoid liposarcoma | DDIT3 (formerly CHOP) on chromosome 12 | FUS gene on chromosome 16 |
| t(12;21)(p12;q22) | ALL | TEL on chromosome 12 | AML1 on chromosome 21 |
| t(11;18)(q21;q21) | MALT lymphoma | BIRC3 (API-2) | MLT |
| t(1;11)(q42.1;q14.3) | Schizophrenia |
| |
| t(2;5)(p23;q35) | Anaplastic large cell lymphoma | ALK | NPM1 |
| t(11;22)(q24;q11.2-12) | Ewing's sarcoma | FLI1 | EWS |
| t(17;22) | DFSP | Collagen I on chromosome 17 | Platelet derived growth factor B on chromosome 22 |
| t(1;12)(q21;p13) | Acute myelogenous leukemia |
| |
| t(X;18)(p11.2;q11.2) | Synovial sarcoma |
| |
| t(1;19)(q10;p10) | Oligodendroglioma and oligoastrocytoma |
| |
| t(17;19)(q22;p13) | ALL |
| |
| t(7,16) (q32-34;p11) or t(11,16) (p11;p11) | Low-grade fibromyxoid sarcoma | FUS | CREB3L2 or CREB3L1 |
History
In 1938, Karl Sax, at the Harvard University 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".
