Chromosomal translocation
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In
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Reciprocal translocations
Reciprocal translocations are usually an exchange of material between non-homologous chromosomes and occur in about 1 in 491 live births.
It is important to distinguish between chromosomal translocations that occur in germ cells, due to errors in meiosis (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 translocation.
Nonreciprocal translocation
Nonreciprocal translocation involves the one-way transfer of
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.[5] 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
Role in disease
Some human diseases caused by translocations are:
- 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.
- chromosome 14.[7]
Chromosomal translocations between the sex chromosomes can also result in a number of genetic conditions, such as
- SRYgene from the Y to the X chromosome
By chromosome
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
The translocation is the mechanism that can cause a gene to move from one linkage group to another.
Examples of translocations on human chromosomes
| Translocation | Associated diseases | Fused genes/proteins | |
|---|---|---|---|
| First | Second | ||
| t(8;14)(q24;q32) | Burkitt's lymphoma |
c-myc on chromosome 8, lymphocyte-proliferative abilitygives the fusion protein |
IGH@ (immunoglobulin heavy locus) on chromosome 14, induces massive transcription of fusion protein |
| t(11;14)(q13;q32) | Mantle cell lymphoma[11] | cyclin D1[11] on chromosome 11, gives fusion protein cell-proliferative ability |
IGH@[11] (immunoglobulin heavy locus) on chromosome 14, induces massive transcription of fusion protein |
| t(14;18)(q32;q21) | Follicular lymphoma (~90% of cases)[12] | IGH@[11] (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[13] | RET proto-oncogene[13] on chromosome 10 | PTC (Papillary Thyroid Cancer) – Placeholder for any of several other genes/proteins[13] |
| t(2;3)(q13;p25) | Follicular thyroid cancer[13] | PAX8 – paired box gene 8[13] on chromosome 2 |
PPARγ1 peroxisome proliferator-activated receptor γ 1) on chromosome 3
|
| t(8;21)(q22;q22)[12] | Acute myeloblastic leukemia with maturation | ETO on chromosome 8 | cytosine arabinoside therapy[12]
|
| t(9;22)(q34;q11) Philadelphia chromosome | Chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) | Abl1 gene on chromosome 9[14] |
BCR ("breakpoint cluster region" on chromosome 22[14]
|
| t(15;17)(q22;q21)[12] | 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[12] |
| 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[15] | BIRC3 (API-2) | MLT[15] |
| t(1;11)(q42.1;q14.3) | Schizophrenia[8] | ||
| 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".
DNA double-strand break repair
The initiating event in the formation of a translocation is generally a double-strand break in chromosomal DNA.[16] A type of DNA repair that has a major role in generating chromosomal translocations is the non-homologous end joining pathway.[16][17] 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.[18]
See also
- Accipitridae
- Aneuploidy
- Chromosome abnormalities
- DbCRID
- Fusion gene
- Pseudodiploid
- Takifugu rubripes
References
- ^ a b "EuroGentest: Chromosome Translocations". www.eurogentest.org. Archived from the original on January 24, 2018. Retrieved March 29, 2019.
- ^ "Can changes in the structure of chromosomes affect health and development?". Genetics Home Reference. National Library of Medicine. Retrieved July 15, 2020.
- ISBN 978-1-118-98152-8. Retrieved July 15, 2020.
- ^ "Translocation". Carmel Clay Schools. Archived from the original on December 1, 2017. Retrieved March 2, 2009.
- ISBN 978-0-07-352526-6.
- PMID 15117905.
- ^ "Causes". nhs.uk. Archived from the original on June 4, 2017. Retrieved September 16, 2023.
- ^ PMID 11352574.
- ISBN 978-3-8055-8019-9
- ^ "Characteristics of chromosome groups: Karyotyping". rerf.jp. Radiation Effects Research Foundation. Retrieved June 30, 2014.
- ^ PMID 10329598.
- ^ ISBN 978-1-4557-5942-2. Retrieved November 5, 2012.
- ^ ISBN 978-1-4160-2973-1.
- ^ S2CID 25865321.
- ^ ISBN 978-1-4160-2973-1.
- ^ PMID 16798112.
- )
- PMID 24337287.
External links
Media related to Chromosomal translocations at Wikimedia Commons
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