Gene Rearrangement. The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
What is an organism containing a new gene?
Genes from different organisms that have been cut and pasted together are called transgenes. An organism whose genome contains a transgene is considered to be transgenic. In the news, transgenic organisms are often referred to as genetically modified organisms or GMOs. Transgenic animals have uses in research, the medical field, and agriculture.
What is recessive gene and dominant gene?
Individuals receive two versions of each gene, known as alleles, from each parent. If the alleles of a gene are different, one allele will be expressed; it is the dominant gene. The effect of the other allele, called recessive, is masked. Dominant refers to a relationship between two versions of a gene.
What is gene mutation and cancer?
The mutations may affect different genes that control cell growth and division. Some of these genes are called tumor suppressor genes. Mutations may also cause some normal genes to become cancer-causing genes known as oncogenes (oncogenes and tumor suppressor genes are discussed in more detail later).
What is recombination in genetics?
recombination, in genetics, primary mechanism through which variation is introduced into populations. Recombination takes place during meiosis, when maternal and paternal genes are regrouped in the formation of gametes (sex cells).
What is the purpose of gene rearrangement?
Rearrangements in these genes are a normal part of T-cell development. The purpose of the rearrangements is to produce a wide variety of receptors within the T-cell population to recognize and address the vast number of antigens that a person may encounter.
Where Does gene rearrangement occur?
The T-cell receptor gene segments rearrange during T-cell development to form complete V-domain exons (Fig. 4.12). T-cell receptor gene rearrangement takes place in the thymus; the order and regulation of the rearrangements will be dealt with in detail in Chapter 7.
Is gene Rearrangement a mutation?
In genetics, a chromosomal rearrangement is a mutation that is a type of chromosome abnormality involving a change in the structure of the native chromosome. Such changes may involve several different classes of events, like deletions, duplications, inversions, and translocations.
What are the four types of chromosomal rearrangements?
Errors during the repair of multiple double strand breaks or incorrect meiotic crossovers can cause four types of chromosome rearrangements: deletion, inversion, duplication or translocation.
What is VDJ gene rearrangement?
V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively.
What are the two major causes of chromosomal rearrangements?
Chromosome rearrangements can be caused by exposure to radiation, and/or TEs have also been implicated in chromosome rearrangements (Fig. 3.10). Many of these rearrangements can be detected by chromosome painting, FISH, or Giemsa staining.
Why are chromosomal rearrangements important?
Chromosomal rearrangements (CRs) are an important source of genetic variation, whose involvement in speciation has been long suspected. A recent body of theory has focused on how they may facilitate speciation by suppressing recombination between loci involved in reproductive isolation.
What are single gene disorders?
Single-gene disorder is a disease caused by a known alteration or mutation in one of more than 20.000 genes in nearly every cell in the body. Single-gene disorder may be inherited from both members of a couple carry the same condition.
What is the rearrangement of alleles in DNA known as?
DNA Rearrangement: Genetic Recombination The mechanisms of genetic recombination allow large sections of DNA helix to move from one chromosome to another. There are two classes of genetic recombination: general, or homologous, and site-specific.
Is rearrangement the same as translocation?
The most common structural chromosome rearrangements are translocations and inversions. Translocations are structural chromosome abnormalities that occur after a double break in two different chromosomes and exchange of fragments between these chromosomes.
What is rearrangement sequence?
We say that a sequence {yn} is a rearrangement of a sequence {xn} if there is a 1-1 correspondence f:N→N such that ∀ n∈N, yn=xf(n).
What is the movement of part of one chromosome to another chromosome called?
Translocations. A translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome. This type of rearrangement is described as balanced if no genetic material is gained or lost in the cell.
What is the role of gene rearrangement?from sciencedirect.com
Gene rearrangement plays a role in determining the sequences in which the genes are joined as the DNA of the immunoglobulin producing cell matures.
Which gene family regulates the formation of cortical folds?from sciencedirect.com
In the neurosciences, specific UHGs have evolved from gene families such as Notch (i.e., Notch2NL) that mediate the formation of neurons, and others from the Ras GTPase superfamily (i.e., ARHGAP11b) that regulate the formation of cortical folds.
What genes are involved in ALK?from sciencedirect.com
The ALK gene rearrangements on chromosome 2p23 can involve a variety of fusion partners, including TPM3 , TPM4 , CLTC, RANBP2, and other genes (see Chapters 10 and 16 ). 194,211-215 Recently, a variety of non- ALK gene fusions have been discovered in ALK-negative IMTs and involve ROS1, PDGFRB, RET, and NTRK 3. 201-203,216,217 ALK and ROS1 immunohistochemistry are surrogates for molecular testing in some but not all cases, with the respective gene rearrangements. 201,216 Cases that are negative by ALK immunohistochemistry may require additional testing for the possibility of an ALK rearrangement or one of the other gene rearrangements. TP53 mutations are not found. 218
Does LC gene rearrangement always result in cessation of LC gene rearrangement?from sciencedirect.com
Productive LC gene rearrangement resulting in the expression of membrane Ig on the cell surface does not always result in cessation of LC gene rearrangement. Ongoing or reactivated LC gene rearrangement may occur, for example, when an antibody is autoreactive (Gay et al., 1993; Radie et al., 1993; Tiegs et al., 1993) or when it fails to promote positive selection ( Rolink et al., 1993 ). Newly generated B cells carrying an autoreactive BCR can undergo ongoing LC gene rearrangement in the bone marrow to replace the autoreactive LC with a nonautoreactive κ or A chain ( C. Chen et al., 1994; Prak et al., 1994 ). Replacement of an autoreactive κ LC could be accomplished either by sequential κ locus rearrangement events ( Levy et al., 1989) or by activation of A locus rearrangement. Autoreactive B cells unable to undergo receptor editing are deleted in the bone marrow ( Chen et al., 1995 ). In addition, Rag-1 and Rag-2 expression has been shown to be reactivated in mature germinal center B cells ( Han et al., 1996; Hikida et al., 1996 ), a possibility that is consistent with reactivation of LC gene rearrangement on exposure to antigen. Such processes could remove autoreactive B cells that arise as a result of somatic hypermutation, either by secondary LC gene rearrangements or by HC V H replacement events ( M. Reth et al., 1986 ).
What is the role of gene rearrangement?from sciencedirect.com
Gene rearrangement plays a role in determining the sequences in which the genes are joined as the DNA of the immunoglobulin producing cell matures.
Which gene family regulates the formation of cortical folds?from sciencedirect.com
In the neurosciences, specific UHGs have evolved from gene families such as Notch (i.e., Notch2NL) that mediate the formation of neurons, and others from the Ras GTPase superfamily (i.e., ARHGAP11b) that regulate the formation of cortical folds.
What genes are involved in ALK?from sciencedirect.com
The ALK gene rearrangements on chromosome 2p23 can involve a variety of fusion partners, including TPM3 , TPM4 , CLTC, RANBP2, and other genes (see Chapters 10 and 16 ). 194,211-215 Recently, a variety of non- ALK gene fusions have been discovered in ALK-negative IMTs and involve ROS1, PDGFRB, RET, and NTRK 3. 201-203,216,217 ALK and ROS1 immunohistochemistry are surrogates for molecular testing in some but not all cases, with the respective gene rearrangements. 201,216 Cases that are negative by ALK immunohistochemistry may require additional testing for the possibility of an ALK rearrangement or one of the other gene rearrangements. TP53 mutations are not found. 218
Does LC gene rearrangement always result in cessation of LC gene rearrangement?from sciencedirect.com
Productive LC gene rearrangement resulting in the expression of membrane Ig on the cell surface does not always result in cessation of LC gene rearrangement. Ongoing or reactivated LC gene rearrangement may occur, for example, when an antibody is autoreactive (Gay et al., 1993; Radie et al., 1993; Tiegs et al., 1993) or when it fails to promote positive selection ( Rolink et al., 1993 ). Newly generated B cells carrying an autoreactive BCR can undergo ongoing LC gene rearrangement in the bone marrow to replace the autoreactive LC with a nonautoreactive κ or A chain ( C. Chen et al., 1994; Prak et al., 1994 ). Replacement of an autoreactive κ LC could be accomplished either by sequential κ locus rearrangement events ( Levy et al., 1989) or by activation of A locus rearrangement. Autoreactive B cells unable to undergo receptor editing are deleted in the bone marrow ( Chen et al., 1995 ). In addition, Rag-1 and Rag-2 expression has been shown to be reactivated in mature germinal center B cells ( Han et al., 1996; Hikida et al., 1996 ), a possibility that is consistent with reactivation of LC gene rearrangement on exposure to antigen. Such processes could remove autoreactive B cells that arise as a result of somatic hypermutation, either by secondary LC gene rearrangements or by HC V H replacement events ( M. Reth et al., 1986 ).
What is a T cell gene rearrangement test?from labcorp.com
A T-cell receptor gene rearrangement test evaluates the T-cells in a person's sample to determine whether the majority of T-cell rearrangement profiles are diverse or identical. This information, along with clinical signs and symptoms and results of other laboratory tests, can help clarify a person's diagnosis, or evaluate for persistent, residual, or recurrent lymphoma.
What is the somatic assembly of TCR genes?from ncbi.nlm.nih.gov
The somatic assembly of T cell receptor (TCR) genes (Tcra, Tcrb, Tcrg, Tcrd) generates a diverse T cell repertoire and is an essential component of thymocyte development that instructs numerous cell lineage and cell fate decisions. TCR genes are assembled through V(D)J recombination, a site specific recombination process directed by the lymphoid-specific recombinase (RAG, composed of RAG1 and RAG2) and ubiquitously expressed DNA repair proteins [1]. RAG proteins create double-strand breaks at recombination signal sequences (RSSs) that flank TCR variable (V), diversity (D) and joining (J) gene segments, and these breaks are subsequently resolved by nonhomologous end joining. The four TCR genes are assembled according to distinct developmental programs. Recombination of Tcrd, Tcrgand Tcrball occur during the CD4−CD8−double-negative (DN) 2 (CD44+CD25−) and DN3 (CD44−CD25+) stages of thymocyte development, during an initial period of recombinase expression. Thymocytes commit to the αβ or γδ lineages concurrent with, and likely as an outcome of, these TCR gene recombination events [2]. Successful recombination of Tcrdand Tcrgpromotes assembly of a γδ TCR, whereas successful recombination of Tcrbpromotes assembly of TCRβ with pre-Tα to form a pre-TCR. Pre-TCR signals then provoke downregulation of recombinase expression, several rounds of proliferation, and differentiation of thymocytes to the CD4+CD8+double positive (DP) compartment, within which Raggenes are re-expressed and Tcrarecombination initiated. The specificity of assembled αβ TCR for intrathymic ligands then dictates cell survival and differentiation into the CD4, CD8 or other αβ T cell lineages.
What is the function of T-cell receptor genes?from labcorp.com
The T-cell receptor genes control the development of these receptor subunits. Rearrangements in these genes are a normal part of T-cell development. The purpose of the rearrangements is to produce a wide variety of receptors within the T-cell population to recognize and address the vast number of antigens that a person may encounter.
When does DNA need to be repeated?from labcorp.com
Testing may need to be repeated when the sample does not contain enough DNA to test or if the sample is not suitable for testing.
Does B12/23 recombination require order?from ncbi.nlm.nih.gov
Although B12/23 restrictions enforce a two step recombination process, they do not impose order. Why Dβ-to-Jβrecombination invariably precedes Vβ-to-Dβrecombination has been uncertain. Notably, the 3′ Dβ1 and 3′ Dβ2 23 RSSs were shown to include a highly conserved binding site for the transcription factor AP-1, and the AP-1 component c-Fos was found to recruit RAG to the 3′ Dβ1 23 RSS [32]. Although stimulatory for plasmid Dβ1-to-Jβ1 recombination, this recruitment inhibited Vβ-to-Dβ1 recombination, presumably because it sterically interferes with RAG access to the nearby 5′ Dβ1 12 RSS. Notably, deletion of the Dβ1 23 RSS [33] or gene-targeted loss of c-Fos [32] made Tcrbpermissive for Vβ-to-Dβ1 recombination. This suggests that during T cell development, removal of the 3′ Dβ1 23 RSS through Dβ1-to-Jβ1 recombination may signal to initiate Vβ-to-DβJβrecombination.
What is the false negative rate for T-cell gene rearrangement studies?
The false-negative rate for T-cell gene rearrangement studies by PCR is lower (approximately 10%). This lower false-negative rate is explained by the decreased complexity of the commonly examined T-cell receptor gamma ( TRG) locus and the absence of somatic hypermutation.
What genes are involved in NGS?
Mutations in the genes SETD2, INO80, STAT5B, SMARCA2, TET3, and PIK3CD were frequent.
What is MRD in leukemia?
Recent studies have indicated that detection of ‘minimal residual disease ’ (MRD) in patients with acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia (APL), and chronic myelogeneous leukemia (CML) can give clinically relevant insight into the effectiveness of treatment. Furthermore, it was shown that quantitative sensitive MRD information can be used for risk group classification in ALL. Such quantitative and sensitive MRD data can now be obtained by RQ-PCR analysis of leukemia-specific chromosome aberrations as PCR targets (APL, CML, subset of ALL) as well as junctional regions of immunoglobulin (lg) and T cell receptor (TCR) gene rearrangements (ALL).
What is chromosome rearrangement?
A chromosomal rearrangement means that pieces of chromosomes are missing, duplicated (there are extra copies), or moved around. The effects vary. They depend on which chromosome pieces are involved and how they are rearranged. Some have no effect, some are incompatible with life, and others are somewhere between.
What are the two categories of rearrangements?
Rearrangements fall broadly into two categories: balanced and unbalanced.
How are chromosomal rearrangements diagnosed?
Chromosomal rearrangements are diagnosed through genetic testing. Most tests use DNA from a blood sample or a cheek swab. Some rearrangements happen more often than others, and some give rise to syndromes with signature characteristics. Based on a person's characteristics, a doctor may order a specific test on just one chromosome to a confirm a diagnosis. Other tests look more broadly at all of the chromosomes. Some rearrangements can be detected before birth, through prenatal genetic testing. These tests are done during pregnancy on a DNA sample from the developing baby. They measure the number and arrangement of all of the baby's chromosomes.
How many copies of each chromosome are recombinated?
This process of recombination and seperation happens with all of the chromosomes at once, so that each egg or sperm gets one recombined copy of each chromosome.
What happens to chromosomes during recombination?
During recombination, pairs of chromosomes duplicate, swap pieces, and separate.
How many chromosomes are in a complete set of genetic information?
A complete set of genetic information consists of 46 chromosomes. Each parent contributes 23 chromosomes.
How common are balanced rearrangements?
Balanced rearrangements are fairly common, affecting about 1 in 1,000 people. They make up a large proportion of couples seeking fertility treatment.
What is the false negative rate for T-cell gene rearrangement studies?from sciencedirect.com
The false-negative rate for T-cell gene rearrangement studies by PCR is lower (approximately 10%). This lower false-negative rate is explained by the decreased complexity of the commonly examined T-cell receptor gamma ( TRG) locus and the absence of somatic hypermutation.
What genes are involved in NGS?from sciencedirect.com
Mutations in the genes SETD2, INO80, STAT5B, SMARCA2, TET3, and PIK3CD were frequent.
What is fluorescent gene scanning?from jcp.bmj.com
Fluorescent gene scanning involves the amplification of specific TCR genes using fluorescently labelled primers. Such analysis is used in routine clonality assessment of TCRG and TCRB genes, TCRBV family usage, and MRD studies. The resulting PCR products are run on a gene sequencer and analysed using GeneScan software (Applied Biosystems, Warrington, Cheshire, UK). Polyclonal populations with varying PCR fragment lengths demonstrate a normal Gaussian distribution visualised as a series of peaks. Clonal populations are seen as distinct peaks (fig 4).
What are the factors that influence the expression of TCR?from jcp.bmj.com
These include the human MHC (HLA) system 37–39 and TCR gene polymorphisms, 25,40–47 in addition to environmental factors, such as infection 48–52 and superantigens. 53–56 In normal individuals the TCR repertoire is stable and polyclonal. Whereas clonal populations are the hallmark of malignancy, clonal or oligoclonal populations of T and B cells may occur in non-malignant conditions including: human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infections with specificity for virus, 48,57–59 in the elderly, 60,61 in autoimmunity, 62–65 in common variable immunodeficiency (CVID), 66,67 and in severe combined immunodeficiency (SC1D), where RAG1 or RAG2 gene defects allow only a limited number of successful antigen receptor gene rearrangements, as occurs in patients with the Omenn’s SCID variant. 68
What is TCRB recombination?from jcp.bmj.com
T cell receptor β gene (TCRB) rearrangement. The RAG mediated recombination of the TCRB locus is a two step process in which a diversity (D) gene segment first recombines with a joining (J) segment , followed by the recombination of a variable (V) gene to the DJ block. The rearranged VDJ segment is then spliced post transcriptionally to the C transcript.
How many genes are in the TCRB locus?from jcp.bmj.com
The TCRB locus comprises approximately 67 V genes of which 47 are functional and 19 are pseudogenes. 21 The functional TCRBV families are grouped into 23 families based upon greater than 75% nucleotide sequence identity. 22 Two C genes are associated with upstream clusters of J genes and a single D gene (D1 or D2) and are known as the D–J–C clusters. There are 13 J genes, designated J1S1 to J1S6 and J2S1 to J2S7. 23
Why is PCR used in clonality studies?from jcp.bmj.com
The advent of the polymerase chain reaction (PCR) technique has largely replaced Southern blot analysis for clonality studies because PCR offers several advantages, with the principal being that it is quicker to perform and poor quality DNA can be used. The type of PCR approach will depend on whether DNA or RNA based methods are applicable. Paraffin wax embedded material is often the only material available in routine diagnostic pathology laboratories, so protocols are restricted to DNA based methods and the amplification of small (< 250 bp) PCR fragments. 71 Both DNA and RNA methods are suitable for fresh material.
Disease Relevance of Gene Rearrangement
Psychiatry Related Information on Gene Rearrangement
High Impact Information on Gene Rearrangement
Chemical Compound and Disease Context of Gene Rearrangement
Biological Context of Gene Rearrangement
- A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate .
- Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement .
- A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate .
- Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement .
- Telomeric antigen genes can be expressed without apparent DNA rearrangement, but they can also, like non-telomeric genes, have access to the telomeric expression site through a duplicative transpos...
- Run-on transcription experiments were used to demonstrate that transcription of T cell receptor beta chain V genes is activated by DNA rearrangement, in a manner similar to immu…
Anatomical Context of Gene Rearrangement
Associations of Gene Rearrangement with Chemical Compounds
Gene Context of Gene Rearrangement
Analytical, Diagnostic and Therapeutic Context of Gene Rearrangement