Chromosomal translocation

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" and blends together homogeneously.[1]

Chromosomal reciprocal translocation of the 4th and 20th chromosome.

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).[1][2]

Reciprocal translocations


Reciprocal translocations are usually an exchange of 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 in prenatal diagnosis. However, carriers of balanced reciprocal translocations may create gametes with unbalanced chromosome translocations during meiotic 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 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 genes from one chromosome to another nonhomologous chromosome.[4]

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 13 and 14 and 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 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:

Chromosomal translocations between the sex chromosomes can also result in a number of genetic conditions, such as

By chromosome

Overview of some chromosomal translocations involved in different cancers, as well as implicated in some other conditions, e.g. schizophrenia,[8] with chromosomes arranged in standard karyogram order. Abbreviations:
ALL – Acute lymphoblastic leukemia
AML – Acute myeloid leukemia
CML – Chronic myelogenous leukemia
DFSP – Dermatofibrosarcoma protuberans
Human karyotype with annotated bands and sub-bands as used for the nomenclature of chromosomal abnormalities. It shows dark and white regions as seen on G banding. Each row is vertically aligned at centromere level. It shows 22 homologous autosomal chromosome pairs as well as both the female (XX) and male (XY) versions of the two sex chromosomes.



The International System for Human Cytogenetic Nomenclature (ISCN) is used to denote a translocation between chromosomes.[9] 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 sub-bands seen when staining the chromosome with a staining dye.[10] 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

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[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[13] (peroxisome proliferator-activated receptor γ 1) on chromosome 3
t(8;21)(q22;q22)[12] 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[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



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



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  2. ^ "Can changes in the structure of chromosomes affect health and development?". Genetics Home Reference. National Library of Medicine. Retrieved July 15, 2020.
  3. ^ Milunsky, Aubrey; Milunsky, Jeff M. (2015). Genetic Disorders and the Fetus: Diagnosis, Prevention, and Treatment (7th ed.). Hoboken: John Wiley & Sons. p. 179. ISBN 978-1-118-98152-8. Retrieved July 15, 2020.
  4. ^ "Translocation". Carmel Clay Schools. Archived from the original on December 1, 2017. Retrieved March 2, 2009.
  5. ^ Hartwell, Leland H. (2011). Genetics: From Genes to Genomes. New York: McGraw-Hill. p. 443. ISBN 978-0-07-352526-6.
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  7. ^ "Causes". Archived from the original on June 4, 2017. Retrieved September 16, 2023.
  8. ^ a b Semple 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. PMID 11352574.
  9. ^ Schaffer, Lisa. (2005) International System for Human Cytogenetic Nomenclature S. Karger AG ISBN 978-3-8055-8019-9
  10. ^ "Characteristics of chromosome groups: Karyotyping". Radiation Effects Research Foundation. Retrieved June 30, 2014.
  11. ^ a b c d Li 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. PMC 1866594. PMID 10329598.
  12. ^ a b c d e Burtis, 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. ISBN 978-1-4557-5942-2. Retrieved November 5, 2012.
  13. ^ a b c d e f Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Mitchell, Richard Sheppard (2007). "Chapter 20: The Endocrine System". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1.
  14. ^ a b Kurzrock 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. PMID 12755554. S2CID 25865321.
  15. ^ a b Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Mitchell, Richard Sheppard (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. p. 626. ISBN 978-1-4160-2973-1.
  16. ^ a b Agarwal, 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. PMID 16798112.
  17. ^ 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. ISBN 978-3-319-20290-7. PMID 26376870. {{cite book}}: |journal= ignored (help)
  18. ^ 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. PMC 3961821. PMID 24337287.