What is Chromosomal Translocation?- Definition, Mechanism and Types

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When a part of chromosome breaks or is deleted and reinserted at another location on a chromosome is known as a chromosome translocation. Conventional karyotyping is a technique commonly employed to study translocations. 

Any sudden change, alteration or undesirable alteration in a gene or chromosome might be harmful to our health. “Mutation” is a common term used for them. 

PCR and sequencing for gene mutations and karyotyping and FISH for chromosomal mutations are common techniques used. Chromosomal mutations are either structural – change in shape or size or numerical- change in the number

Alteration in chromosome number or structure may cause serious problems like mental retardation, cancer, less cognitive skills, infertility, aneuploidy and other congenital problems. 

Trisomies like Down Syndrome or Edward’s syndrome are associated with mental problems, translocations are majorly associated with various types of cancer. 

In the present piece of the article, I will explain to you the concept of translocation, its mechanism and various type of translocation. Along with that, I will also enlist various translocation syndromes and how karyotyping is used to detect chromosomal translocations. 

  • What is chromosome translocation? 
    • Definition 
    • History
    • Mechanism 
    • Types 
    • Nomenclature
  • Role in development of disease 
  • List of translocations 
  • Role of karyotyping in studying translocations
  • Conclusion

Read more: Preparing a Karyotype (Karyogram) in 5 Steps.

What is chromosome translocation? 

Mutation or mutations is known to us since the time Darwin, chromosome aberrations or mutations were first reported by Karl Sax using X-rays. Janet Rowley was the first person to identify Philadelphia translocation in 1972. 

From many chromosomal alterations, the translocations are most common, larger, visible in the microscope and can be identified using karyotyping. However, only experts can do it. FISH is another molecular cytogenetic technique employed to do the same. 

The phenomenon of translocation can also be reported in a gene or DNA, but the larger chromosomal translocations are more responsible for causing various carcinoma. 

Definition: 

To define the process of translocation three things are very significant, the break, translocation to another chromosome (on which chromosome it translocates) and its health consequences. 

Let us define it, 

“The chromosome translocation is a random process in which a part of a chromosome breaks and binds to another chromosome which inversely affects a person and can be studied by the karyotyping.”

Mechanism of chromosomal translocation: 

The mechanism of how the phenomenon occurs helps scientists to learn more about the disease, how it occurs and what to do with it. 

The chromosomal translocation causes carcinoma in common cases and happens in two steps: DNA double-strand break and joining to another chromosome. 

As we said due to the random events on the chromosome, a double-strand break occurs. Generally, the double-strand break occurs at two different loci. 

Once the double-strand break happens the portion of the chromosome attaches to another loci or chromosome. 

The present process usually inversely influences the activity of oncogenes and protooncogenes present on the various chromosomes. That commonly causes cancer. 

The results of translocation generate a new chromosome, a portion of the chromosome usually possesses so many genes transfer to another non homologous chromosome or another arm of the same chromosome. 

Read further: GTG-Banding (G-bands by Trypsin using Giemsa) for karyotyping.

Types of chromosome translocation: 

Based on the incident at where the chromosomal portion translocate and what it makes, the translocations are divided into;

  1.  Reciprocal translocations 
  2. Non-reciprocal translocations 
  3. Robertsonian translocations 
  4. Balanced translocations 
  5. Imbalanced translocations
  6. Reciprocal translocations: 

When translocation of genetic material occurs between two unrelated or non-homologous chromosomes are referred to as reciprocal translocations. 

The types of reciprocal translocations are a common event in nature and usually harmless, however, not all. 

The consequences of translocations are the transfer of genes and establishing new linkage relations between chromosomes. It also results in a change in the size of the chromosome and position of the centromere. 

In laymen, the event of translocation may cause shortening or enlarging chromosomes. 

For instance, if a metacentric and acrocentric chromosome reciprocally translocates, it causes shortening of the metacentric one and enlarging of the acrocentric one. 

Graphical representation of reciprocal translocation.

The reciprocal translocation occurs in 1 in 491 live births. 

Non-reciprocal translocations: 

When only a portion of a single chromosome translocates to another unrelated chromosome, it is categorized into a non-reciprocal type of translocation.  

Translocation nonreciprocal results in the shortening of one chromosome and enlarging another chromosome at the same time. 

Robertsonian translocations: 

When translocations occur between two acrocentric chromosomes and result in one large metacentric chromosome and one smaller gene less chromosome, it is referred to as Robertsonian translocation. See the image below, 

The graphical representation of Robertsonion translocation.

Usually, as another chromosome can’t be identified using karyotyping, it shows only 45 chromosomes in this case. 

The Robertsonian translocations have very few phenotypic adverse effects as the small arm of the acrocentrics have few genes in variable copy numbers. 

Still, some are notable and may cause serious effects. 

The most common Down syndrome also occurs due to Robertsonian translocation between acrocentric chromosomes 21. The type is known as translocation down syndrome, is inherited and very rare. 

Balance translocations: 

When translocation occurs between two same-sized fragments is known as a balanced translocation. The total number of chromosomes remains the same. 

Graphical representation of balanced translocation.

Imbalance translocations: 

When translocations occur between two different sized fragments, is known as imbalance translocation. The number of chromosomes in a genome may change. 

Graphical representation of imbalanced translocation.

Read more: Explaining the whole karyotyping technique and procedure.

Role of translocation in the development of diseases: 

Mapping translocation on chromosomes is very important to study its adverse effects. In nature, mutations occur to favor us, to help us survive and most of the chromosomes originate due to translocations. 

Translocation is also a type of chromosomal alteration that occurs to help us from the adverse effect of the agent (non-biological or biological) due to which it happens. 

Observing the translocation in a specific condition or type of cancer isn’t actually enough to study the condition, indeed. Scientists have to know what consequences the event causes, for example which gene or group of genes is affected. 

Other molecular genetic techniques are also performed to study the DNA sequences or genes around the translocation point. The common translocations activate oncogenes but it may cause other problems as well. 

Unfortunately not all the translocations are helpful, some are yet not characterized indeed. What is actually the cause? 

  • It alters copy number variation of genes 
  • Genes may duplicate
  • Genes may retard
  • Fashion gene products produce 
  • Influence the activity of normal genes

Those are the possible outcomes of translocations. For instance, the BCR-ABL gene fusion originates due to the translocation between chromosome 9 and 22 causing chronic myeloid leukemia. 

Several adverse effects of it are enlisted here: 

Down syndrome: location Down syndrome occurs by the acrocentric chromosomal translocation of 21. It is a type of inherited Down syndrome that may pass down in progeny. 

Cancer- cancer is the most common cause of translocations, in fact of many chromosome alterations.  We already have discussed chronic myeloid leukemia. 

As we discussed the phenomenon actually alters the activity of oncogenes and proto-oncogenes present on different chromosomes. Proto Oncogenes promote cell division whilst oncogenes prevent cell division. 

Their activity regulates the entire cell cycle. The above reason we have listed may change the activities or cancer causing genes. 

Sex reversal- XX male syndrome and XY female syndrome are the types of sex reversal that happens due to the translocation of portions of sex chromosomes 

In the XX male, a portion from the X translocates to the Y while in the XY female the TDF or SRY region of the Y chromosome translocates to one of the X chromosomes. 

This event results in an alteration in the phenotypic profile of male and female. 

Infertility- Sex reversal causes infertility. However, other balanced translocation also results in serious infertility problems.

List of translocations 

Nomenclature of translocation: 

t(A;B)(p1;q2). 

t(21;21)(p1.1;q2.0)

International systems for Human cytogenetics Nomenclature- ISCN have postulated a specific indication technique to denote the translocation as you can see above. 

Here the t denotes the translocation, 

(A;B) denotes the event occurs between the chromosomes A and B 

(p1;q2) denotes that it occurs between arm p of one chromosome to arm q or another chromosome. 

If you want to learn more about the cytogenetic nomenclature technique you can read our previous article here: Cytogenetic nomenclature.

Common chromosome translocations: 

Sr No Cytological indicationCondition note
1t(9;22)(q34.1;q11.21)Chronic myelogenous leukemia 
2t(6;9)(p22.2;q34)Acute nonlymphocytic leukemiaM1 and M2
3t(8;21)(q22.1;q22.3)Acute nonlymphocytic leukemiaM2
4t(9;11)(p22;q23)Acute nonlymphocytic leukemiaM2, M4, M5a
5t(9;22)(q34.1;q11.21)Acute nonlymphocytic leukemiaM1, M2
6t(15;17)(q22;q11.2)Acute nonlymphocytic leukemiaM2, M4, M5b
7t(1;3)(q36;q21)Mylodysplasia-preleukemiaRA, RAEB-CMML
8t(2;11)(q11;q23)Mylodysplasia-preleukemiaRA, RA-S, RAEB
9t(11;14)(q13;q32.3)Chronic lymphocytic leukemiaB-cell
10t(1;19)(q21-23;p13)Acute lymphocytic leukemiaL1, L2 and pre-B-cells
11t(4;11)(q21;q23)Acute lymphocytic leukemiaL1 and L2
12t(8;14)(qq24.1;q32.3)Acute lymphocytic leukemiaL3, B cells
13t(9;22)(q34.1;11.21)Acute lymphocytic leukemiaL1 and L2
14t(11;14)(p13-14.1;q11.2-13)Acute lymphocytic leukemiaL1, L2 and T cell
15t(8;14)(q24.1;q32.3)Burkitt’s lymphoma
16t(12;14)(q13;q32.3)Small lymphocytic B cells
17t(3;8)(p14.2-q24.1)Familial Renal cell carcinoma
18t(14;14)(q11.2;q32.3)Sezary syndrome, mycosis fungoides
19t(5;14)(q13;q22)Renal cell carcenoma
20t(6;14)(q21-q24)Ovarian pallilary crustadenocracinoma
21t(11;22)(q23;q11.23)Ewing’s sarcoma, neuroepithelioma, Askin’s tumor
22t(3;8)(p21;q22)Mixed parotid gland tumor
23t(1;3)(p36;q21)Mylodesplasia
24t(4;11)(q21;q23)Acute lymphocytic leukemia, M4
25t(6;9)(p21.2;q34)Acute nonlymphocytic leukemia, M1 and M2
26t(14;18)(q32;q21)Follicular lymphoma
27t(6;14)(q21;q24)Ovarian tumor
28t(3;8)(p21;q12)Mixed tumor of salivary gland
29t(9;12)(p13-22;q13-15)Mixed tumor of salivary gland
30t(X;18)(p11;q11)Synovial carcinoma
31t(3;8)(p21;q12)Pleomorphic adenoma
32t(9;12)(p13-22;q13-15)Pleomorphic adenoma
33t(12)(q13-15)Pleomorphic adenoma
34t(12-16)(q13;p11)liposarcoma
35t(12;14)(q13-15;q23-24)Leiomoma (uterus)
36t(19)(q13)Glioma
37t(1)(q21;23)Breast adenocarcinoma

Common chromosomal translocations: 

Chronic myeloid Leukemia: 

The present genetic condition is a type of cancer, abbreviated as CML occurs due to the translocation of genetic material between chromosome 9 and 22. Often known as the Philadelphia chromosome, the present condition can either be inherited or non-inherited.

The cytological location of the present condition is t(9;22)(q32;q11) and is occurred by the gene fusion of BCR and ABL gene due to the translocation of fragments. 

Myelogenous leukemia occurs due to slower progression of cancer cells. 

Translocation between chromosome 9 and 22.

Ewing’s sarcoma: 

Ewing’s sarcoma is categorized into bone sarcoma or soft-tissue sarcoma in which translocation of genetic material between chromosome 11 and 22 is one of the reasons. 

Swelling, pain at the size of cancer and bone fracture are common symptoms of the present condition. 

Here the translocation causes fusion of EWSR1 gene and FL1 gene of chromosome 22 and 11, respectively. Cytological indication of present condition is t(22;11)(q23;q11.23). 

Burkitt’s lymphoma: 

Burkitt’s lymphoma is a cancer of B lymphocytes and the lymphatic system. The condition was first reported by Irish surgeon Denis Parsons Burkitt in 1958. 

It’s condition occurs by translocation of chromosome 8, 14 and 22 and 2. Cytological indications of all translocations are; 

t(8;14)(q24.1-32.3)

t(8;22)(q24.1;q11.2)

t(2;8)(p11.1-q24.1)

Follicular lymphomas: 

The follicular lymphoma is a cancer of B- cell lymphocytes that affects white blood cells. 

Translocation between chromosomes 14 and 18 is one of the most common genetic causes for the present condition. The cytological location of it is t(14;18)(q32;q21). 

The FL is a type of non-Hodgkin’s lymphoma. 

Derivative chromosome: 

Cytogenetic expert or karyotype expert sometimes uses the term derivative chromosome having an important role in denoting the translocations. 

The derivative chromosome constructs from the translocation phenomenon. Through balanced translocations sometimes a whole new chromosome manufacture known as the derivative chromosome. 

For instance, in case of translocation between chromosome 12 and 17, which is one of the most common, a derivative chromosome 12; der(12) and 17; der(17) forms. Cytologically the event is denoted as der12 t(12;17) and der17 t(17;12). 

Scientists name it after the centromere from where it is derived, to be precise, the der (12) is derived from the centromere of 12. 

Fair credit: The information of this portion of the article is new, amazing and very important and derived from nature’s article “Human chromosome translocation and cancer”. The link is given at the end of the article. 

The actual image karyotyping image of translocation.

Techniques to investigate the translocations : 

Conventional karyotyping, M-FISH and spectral karyotyping are some of the amazing techniques commonly employed to study the translocations in clinical samples. 

Karyotyping:

Chromosomal translocations are huge approximately 20kb to more than 200kb unlike the nucleotide translocations, the conventional karyotyping technique is powerful enough to study larger translocations which are visible in microscopes. 

The technique karyotyping is known to us, as you on this dedicated blog! It’s a cell culture-based technique that relies on cell culture, cell harvesting and microscopy. 

Using the culture media, cells are harvested from the sample, under strict aseptic conditions, obviously. Cells are washed and harvested soon after to prepare slides. 

Metaphase slides are prepared and G bands are performed. The slides are observed under the microscope to observe the visible chromosomal change.

A karyogram or ideogram of chromosomes is prepared in order to study the karyotype.  

To study chromosomal aberrations like translocations or deletion, expert eyesight is required. Nonetheless, karyotyping can’t identify some of the balance translocations, and therefore techniques like FISH are used to do so. 

The common applications of a conventional cytogenetic technique like karyotyping are in cancer cytogenetics and identification of alteration in various types of cancer. 

Karyotype using G bands have limited resolution and therefore can’t identify smaller or balanced translocations. 

Related article: What is Karyotyping?- Definition, Steps, Process, and Advantages.

FISH: 

An excellent molecular cytogenetic technique known as the FISH- fluorescent in situ hybridization or multicolor fluorescent in situ hybridization is used. 

Here different colored radiolabeled probes are used to hybridize at the location where the translocation happens and gives a different color signal when analyzed. 

The FISH also have limited resolution and analytic limitations therefore another technique known as spectral karyotyping is used for studying cancer cells. 

Spectral karyotyping: 

Spectral karyotyping is powerful enough to even identify smaller translocations and commonly used in leukemia cytogenetics. 

In the present technique, probes complementary to different translocations are labelled with different colored fluorescence dye to hybridize. 

The mixture of probes allows hybridization on the metaphase if translocation occurred. 

Normal chromosomes paint with the single color dye while translocated or derived chromosomes paint with different color fluorescence due to the probe hybridization. 

This is the general overview of the S- karyotyping, if you are very much interested to learn it, you can read our article: what is spectral karyotyping? 

Conclusion: 

Translocation plays an important role in the development of various types of carcinoma. However, not involved in all cancer types. Karyotyping and FISH are two cytogenetic techniques commonly employed to study translocation and to detect cancer in various cases. 

Two important aspects of chromosomal alterations we should know in order to study cytogenetics, first the theory of Theodor Boveri’s “Growth-stimulatory chromosome” theory and second the role of DNA break in a cell. 

Theodor Boveri was the first person to postulate that chromosomal alterations like translocations play a vital role in developing malignancy and activating oncogenes. 

It means, translocations induce uncontrolled cell growth- cancer. However, at the time of Boveri, cytogenetic techniques like karyotyping and FISH were not discovered. 

DSB- double strand break a type of DNA break plays an important role in various types of cancerous and non-cancerous conditions. Cells are sensitive to DNA break as it is not a natural process, and modify the system to repair it. 

DNA breaks arrest cells at one stage and induces cell death. 


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