Chromosomal translocation
 | This articleneeds morereliable medical referencesforverificationor relies too heavily onprimary sources.(December 2011) |  |
Ingenetics,chromosome translocationis a phenomenon that results in unusual rearrangement of chromosomes. This includesbalancedandunbalancedtranslocation, with two main types:reciprocal,andRobertsoniantranslocation. Reciprocal translocation is achromosome abnormalitycaused by exchange of parts between non-homologouschromosomes.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.[1]
Agene fusionmay be created when the translocation joins two otherwise-separated genes. It is detected oncytogeneticsor akaryotypeof affectedcells.Translocations can bebalanced(in an even exchange of material with no genetic information extra or missing, and ideally full functionality) orunbalanced(where the exchange ofchromosomematerial is unequal resulting in extra or missinggenes).[1][2]
Reciprocal translocations
[edit]Reciprocal translocations are usually anexchangeof material between non-homologous chromosomes and occur in about 1 in 491 live births.[3]Such translocations are usually harmless, as they do not result in a gain or loss of genetic material, though they may be detected inprenatal diagnosis.However, carriers of balanced reciprocal translocations may creategameteswithunbalancedchromosome translocations duringmeioticchromosomal segregation.This can lead to infertility,miscarriagesorchildrenwith abnormalities.Genetic counselingandgenetic testingare 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 ingerm cells,due to errors inmeiosis(i.e. duringgametogenesis), and those that occur insomatic cells,due to errors inmitosis.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 inchronic myelogenous leukemiawith thePhiladelphia chromosometranslocation.
Nonreciprocal translocation
[edit]Nonreciprocal translocation involves the one-way transfer ofgenesfrom onechromosometo another nonhomologous chromosome.[4]
Robertsonian translocations
[edit]Robertsonian translocationis a type of translocation caused by breaks at or near the centromeres of twoacrocentricchromosomes. The reciprocal exchange of parts gives rise to one largemetacentricchromosome and one extremely small chromosome that may be lost from the organism with little effect because it contains few genes. The resultingkaryotypein 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 chromosomes13and14and is seen in about 0.97 / 1000 newborns.[6]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 involvingchromosome 21have a higher risk of having a child withDown 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 ofuniparental disomy14 due totrisomy rescue.
Role in disease
[edit]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 inleukemia(acute myelogenous leukemiaandchronic myelogenous leukemia). Translocations have also been described in solid malignancies such asEwing's sarcoma.
- Infertility:One of the would-be parents carries abalanced translocation,where the parent is asymptomatic but conceived fetuses are not viable.
- Down syndromeis caused in a minority (5% or less) of cases by a Robertsonian translocation of thechromosome 21long arm onto the long arm ofchromosome 14.[7]
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 theSRYgene from the Y to the X chromosome
By chromosome
[edit]
ALL –Acute lymphoblastic leukemia
AML –Acute myeloid leukemia
CML –Chronic myelogenous leukemia
DFSP –Dermatofibrosarcoma protuberans
Denotation
[edit]The International System for Human Cytogenetic Nomenclature (ISCN) is used to denote a translocation betweenchromosomes.[9]The designationt(A;B)(p1;q2)is used to denote a translocation betweenchromosomeA 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—withpindicating the short arm of the chromosome,qindicating the long arm, and the numbers after p or q refers to regions, bands and sub-bands seen when staining the chromosome with astaining dye.[10]See also the definition of agenetic 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
[edit]| Translocation | Associated diseases | Fused genes/proteins | |
|---|---|---|---|
| First | Second | ||
| t(8;14)(q24;q32) | Burkitt's lymphoma | c-mycon chromosome 8, gives thefusion proteinlymphocyte-proliferative ability |
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-2on 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[13](peroxisome proliferator-activated receptor γ1) on chromosome 3 |
| t(8;21)(q22;q22)[12] | Acute myeloblastic leukemia with maturation | ETOon chromosome 8 | AML1on chromosome 21 found in ~7% of new cases of AML, carries a favorable prognosis and predicts good response tocytosine arabinosidetherapy[12] |
| t(9;22)(q34;q11)Philadelphia chromosome | Chronic myelogenous leukemia(CML),acute lymphoblastic leukemia(ALL) | Abl1geneon chromosome 9[14] | BCR( "breakpoint cluster region" onchromosome 22[14] |
| t(15;17)(q22;q21)[12] | Acute promyelocytic leukemia | PML proteinon chromosome 15 | RAR-αon 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 | TELon chromosome 12 | TrkC receptoron chromosome 15 |
| t(9;12)(p24;p13) | CML,ALL | JAKon chromosome 9 | TELon chromosome 12 |
| t(12;16)(q13;p11) | Myxoid liposarcoma | DDIT3(formerly CHOP) on chromosome 12 | FUSgene on chromosome 16 |
| t(12;21)(p12;q22) | ALL | TEL on chromosome 12 | AML1on 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 Ion chromosome 17 | Platelet derived growth factor Bon chromosome 22 |
| t(1;12)(q21;p13) | Acute myelogenous leukemia | ||
| t(X;18)(p11.2;q11.2) | Synovial sarcoma | ||
| t(1;19)(q10;p10) | Oligodendrogliomaandoligoastrocytoma | ||
| t(17;19)(q22;p13) | ALL | ||
| t(7,16) (q32-34;p11) or t(11,16) (p11;p11) | Low-grade fibromyxoid sarcoma | FUS | CREB3L2orCREB3L1 |
History
[edit]In 1938,Karl Sax,at theHarvard UniversityBiological Laboratories, published a paper entitled "Chromosome Aberrations Induced by X-rays", which demonstrated thatradiationcould induce majorgeneticchanges 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
[edit]The initiating event in the formation of a translocation is generally adouble-strand break in chromosomal DNA.[16]A type of DNA repair that has a major role in generating chromosomal translocations is thenon-homologous end joiningpathway.[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 3Dgenome.[18]
See also
[edit]References
[edit]- ^ab"EuroGentest: Chromosome Translocations".www.eurogentest.org.Archived fromthe originalon January 24, 2018.RetrievedMarch 29,2019.
- ^"Can changes in the structure of chromosomes affect health and development?".Genetics Home Reference.National Library of Medicine.RetrievedJuly 15,2020.
- ^Milunsky, Aubrey; Milunsky, Jeff M. (2015).Genetic Disorders and the Fetus: Diagnosis, Prevention, and Treatment(7th ed.). Hoboken: John Wiley & Sons. p. 179.ISBN978-1-118-98152-8.RetrievedJuly 15,2020.
- ^"Translocation".Carmel Clay Schools. Archived fromthe originalon December 1, 2017.RetrievedMarch 2,2009.
- ^Hartwell, Leland H. (2011).Genetics: From Genes to Genomes.New York: McGraw-Hill. p. 443.ISBN978-0-07-352526-6.
- ^E. Anton; J. Blanco; J. Egozcue; F. Vidal (April 29, 2004)."Sperm FISH studies in seven male carriers of Robertsonian translocation t(13;14)(q10;q10)".Human Reproduction.19(6): 1345–1351.doi:10.1093/humrep/deh232.ISSN1460-2350.PMID15117905.
- ^"Causes".nhs.uk.Archived fromthe originalon June 4, 2017.RetrievedSeptember 16,2023.
- ^abSemple CA, Devon RS, Le Hellard S, Porteous DJ (April 2001). "Identification of genes from a schizophrenia-linked translocation breakpoint region".Genomics.73(1): 123–6.doi:10.1006/geno.2001.6516.PMID11352574.
- ^Schaffer, Lisa. (2005)International System for Human Cytogenetic NomenclatureS. Karger AGISBN978-3-8055-8019-9
- ^"Characteristics of chromosome groups: Karyotyping".rerf.jp.Radiation Effects Research Foundation.RetrievedJune 30,2014.
- ^abcdLi JY, Gaillard F, Moreau A, et al. (May 1999)."Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridization".Am. J. Pathol.154(5): 1449–52.doi:10.1016/S0002-9440(10)65399-0.PMC1866594.PMID10329598.
- ^abcdeBurtis, Carl A.; Ashwood, Edward R.; Bruns, David E. (December 16, 2011)."44. Hematopoeitic malignancies".Tietz Textbook of Clinical Chemistry and Molecular Diagnostics.Elsevier Health Sciences. pp. 1371–1396.ISBN978-1-4557-5942-2.RetrievedNovember 5,2012.
- ^abcdefKumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Mitchell, Richard Sheppard (2007). "Chapter 20: The Endocrine System".Robbins Basic Pathology(8th ed.). Philadelphia: Saunders.ISBN978-1-4160-2973-1.
- ^abKurzrock R, Kantarjian HM, Druker BJ, Talpaz M (May 2003). "Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics".Ann. Intern. Med.138(10): 819–30.doi:10.7326/0003-4819-138-10-200305200-00010.PMID12755554.S2CID25865321.
- ^abKumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Mitchell, Richard Sheppard (2007).Robbins Basic Pathology(8th ed.). Philadelphia: Saunders. p. 626.ISBN978-1-4160-2973-1.
- ^abAgarwal, S.; Tafel, A. A.; Kanaar, R. (2006). "DNA double-strand break repair and chromosome translocations".DNA Repair.5(9–10): 1075–1081.doi:10.1016/j.dnarep.2006.05.029.PMID16798112.
- ^Bohlander, S. K.; Kakadia, P. M. (2015). "DNA Repair and Chromosomal Translocations".Chromosomal Instability in Cancer Cells.Recent Results in Cancer Research. Vol. 200. pp. 1–37.doi:10.1007/978-3-319-20291-4_1.ISBN978-3-319-20290-7.PMID26376870.
{{cite book}}:|journal=ignored (help) - ^Rocha, P. P.; Chaumeil, J.; Skok, J. A. (2013)."Molecular biology. Finding the right partner in a 3D genome".Science.342(6164): 1333–1334.doi:10.1126/science.1246106.PMC3961821.PMID24337287.
External links
[edit]
Media related toChromosomal translocationsat Wikimedia Commons
