Chromosomal translocation

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

In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. 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]

Translocations can be reciprocal (balanced or unbalanced) or nonreciprocal (balanced or unbalanced).[3]

Reciprocal translocations

Reciprocal translocations are usually an exchange of material between nonhomologous chromosomes. Estimates of incidence range from about 1 in 500 [4] to 1 in 625 human newborns.[5] 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 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. But about 6% of them have a range of symptoms that may include autism, intellectual disability, or congenital anomalies. A gene disrupted or disregulated at the breakpoint of the translocation carrier is likely the cause of these 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.

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 so few genes. The resulting karyotype in humans leaves only 45 chromosomes, since two chromosomes have fused together.[6] 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.[7] 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 chance 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,[9] with chromosomes arranged in standard karyogram order. Abbreviations:
ALL - Acute lymphoblastic leukemia
AML - Acute myeloid leukemia
CML - Chronic myelogenous leukemia
DFSP - Dermatofibrosarcoma protuberans


The International System for Human Cytogenetic Nomenclature (ISCN) is used to denote a translocation between chromosomes.[10] 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 respectivelywith 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.[11] 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.


For an explanation of the symbols and abbreviations used in these examples, see Cytogenetic notation.
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[12] cyclin D1[12] on chromosome 11,
gives fusion protein cell-proliferative ability
IGH@[12] (immunoglobulin heavy locus) on chromosome 14,
induces massive transcription of fusion protein
t(14;18)(q32;q21) Follicular lymphoma (~90% of cases)[13] IGH@[12] (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 [14] RET proto-oncogene[14] on chromosome 10 PTC (Papillary Thyroid Cancer) - Placeholder for any of several other genes/proteins [14]
t(2;3)(q13;p25) Follicular thyroid cancer[14] PAX8 - paired box gene 8[14] on chromosome 2 PPARγ1[14] (peroxisome proliferator-activated receptor γ 1) on chromosome 3
t(8;21)(q22;q22)[13] 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[13]
t(9;22)(q34;q11) Philadelphia chromosome Chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) Abl1 gene on chromosome 9[15] BCR ("breakpoint cluster region" on chromosome 22 [15]
t(15;17)(q22;q21)[13] 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[13]
t(12;15)(p13;q25) Acute myeloid leukemia, congenital fibrosarcoma, secretory breast carcinoma, mammary analogue secretory carcinoma of salivary glands 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;21)(p12;q22) ALL TEL on chromosome 12 AML1 on chromosome 21
t(11;18)(q21;q21) MALT lymphoma[16] API-2 MLT[16]
t(1;11)(q42.1;q14.3) Schizophrenia [9]
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".

See also


  1. "EuroGenTest Chromosome Translocations". Retrieved March 5, 2016.
  2. "Balanced translocation". Retrieved March 4, 2016.
  3. "Chromosomal Translocations". Retrieved March 5, 2016.
  4. Caroline Mackie Ogilvie; Paul N Scriven (December 2002). "Meiotic outcomes in reciprocal translocation carriers ascertained in 3-day human embryos". European Journal of Human Genetics. European Society of Human Genetics. 10 (12): 801–806. doi:10.1038/sj.ejhg.5200895. PMID 12461686. Retrieved December 26, 2008.
  5. M. Oliver-Bonet; J. Navarro1; M. Carrera; J. Egozcue; J. Benet (October 2002). "Aneuploid and unbalanced sperm in two translocation carriers: evaluation of the genetic risk". Molecular Human Reproduction. Oxford University Press for the European Society for Human Reproduction and Embryology. 8 (10): 958–963. doi:10.1093/molehr/8.10.958. ISSN 1460-2407. PMID 12356948. Retrieved December 26, 2008.
  6. Hartwell, Leland H. (2011). Genetics: From Genes to Genomes. New York: McGraw-Hill. p. 443. ISBN 978-0-07-352526-6.
  7. 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. Oxford University Press. 19 (6): 1345–1351. doi:10.1093/humrep/deh232. ISSN 1460-2350. PMID 15117905. Retrieved December 25, 2008.
  9. 1 2 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.
  10. Schaffer, Lisa. (2005) International System for Human Cytogenetic Nomenclature S. Karger AG ISBN 978-3-8055-8019-9
  11. "Characteristics of chromosome groups: Karyotyping". Radiation Effects Research Foundation. Retrieved June 30, 2014.
  12. 1 2 3 4 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 1866594Freely accessible. PMID 10329598.
  13. 1 2 3 4 5 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.
  14. 1 2 3 4 5 6 Chapter 20 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
  15. 1 2 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.
  16. 1 2 Page 626 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
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