User:Agnihotrin123/Transposable element

Unedited version (03/09/2020)

In disease

TEs are mutagens and their movements are often the causes of genetic disease. They can damage the genome of their host cell in different ways:

• a transposon or a retrotransposon that inserts itself into a functional gene will most likely disable that gene;
• after a DNA transposon leaves a gene, the resulting gap will probably not be repaired correctly;
• multiple copies of the same sequence, such as Alu sequences, can hinder precise chromosomal pairing during mitosis and meiosis, resulting in unequal crossovers, one of the main reasons for chromosome duplication.

Diseases often caused by TEs include hemophilia A and B, severe combined immunodeficiency, porphyria, predisposition to cancer, and Duchenne muscular dystrophy. LINE1 (L1) TEs that land on the human Factor VIII have been shown to cause haemophilia and insertion of L1 into the APC gene causes colon cancer, confirming that TEs play an important role in disease development. Transposable element dysregulation can cause neuronal death in Alzheimer's disease and similar tauopathies.

Additionally, many TEs contain promoters which drive transcription of their own transposase. These promoters can cause aberrant expression of linked genes, causing disease or mutant phenotypes.

Applications

Main article: Transposons as a genetic tool

The first TE was discovered in maize (Zea mays) and is named dissociator (Ds). Likewise, the first TE to be molecularly isolated was from a plant (snapdragon). Appropriately, TEs have been an especially useful tool in plant molecular biology. Researchers use them as a means of mutagenesis. In this context, a TE jumps into a gene and produces a mutation. The presence of such a TE provides a straightforward means of identifying the mutant allele relative to chemical mutagenesis methods.

Sometimes the insertion of a TE into a gene can disrupt that gene's function in a reversible manner, in a process called insertional mutagenesis; transposase-mediated excision of the DNA transposon restores gene function. This produces plants in which neighboring cells have different genotypes. This feature allows researchers to distinguish between genes that must be present inside of a cell in order to function (cell-autonomous) and genes that produce observable effects in cells other than those where the gene is expressed.

TEs are also a widely used tool for mutagenesis of most experimentally tractable organisms. The Sleeping Beauty transposon system has been used extensively as an insertional tag for identifying cancer genes.

The Tc1/mariner-class of TEs Sleeping Beauty transposon system, awarded Molecule of the Year in 2009, is active in mammalian cells and is being investigated for use in human gene therapy.

TEs are used for the reconstruction of phylogenies by the means of presence/absence analyses. transposons can act as biological mutagen in bacteria

Edited (03/02/2020)

Negative Effects of Transposons

Transposons have coexisted with eukaryotes for thousands of years and through their coexistence have become integrated in many organisms' genomes. Colloquially known as 'jumping genes', transposons can move within and between genomes allowing for this integration. While there are many positive effects of transposons in their host eukaryotic genomes, there are some instances of mutagenic effects that TEs have on genomes leading to disease and malignant genetic alterations. [31]

Mechanisms of Mutagenesis

TEs are mutagens and their movements are often the causes of genetic disease. They can damage the genome of their host cell in different ways: [31]

• A transposon or a retrotransposon that inserts itself into a functional gene can disable that gene.
• After a DNA transposon leaves a gene, the resulting gap may not be repaired correctly
• Multiple copies of the same sequence, such as Alu sequences, can hinder precise chromosomal pairing during mitosis and meiosis, resulting in unequal crossovers, one of the main reasons for chromosome duplication.

TEs use a number of different mechanisms to cause genetic instability and disease in their host genomes.

• Expression of disease causing, damaging proteins that inhibit normal cellular function.
  • Many TEs contain promoters which drive transcription of their own transposase. These promoters can cause aberrant expression of linked genes, causing disease or mutant phenotypes.

Diseases

Diseases often caused by TEs include

• Hemophilia A and B
  • LINE1 (L1) TEs that land on the human Factor VIII have been shown to cause haemophilia [34]
• Severe combined immunodeficiency
  • Insertion of L1 into the APC gene causes colon cancer, confirming that TEs play an important role in disease development. [35]
• Porphyria
• Predisposition to cancer
• Duchenne muscular dystrophy. [32][33]
• Alzheimer’s Disease and other Tauopathies
  • Transposable element dysregulation can cause neuronal death, leading to neurodegenerative disorders [36]

Neha edit notes: I changed the language and format of most of the section and cleaned it up. I referenced the sources and am compiling updated information throughout the process. I also added in a few mechanisms and organized the entire subsection so it is less vague.

Applications

There have been various uses of Transposons such as a genetic tool used for analysis of gene expression and protein functioning in signature-tagging mutagenesis or in genetic engineering with insertional mutagenesis. Common organisms which the use of Transposons has been well developed are Drosophila, Arabidopsis thaliana and Escherichia coli.

The analytical function of using a TE uses a technique called signature-tagging mutagenesis. This analytical tool allows researchers the ability to determine phenotypic expression of gene sequences. The technique mutates the desired locus of interest so that the phenotypes of the original and the mutated gene can be compared.

Insertional mutagenesis uses the features of a TE to insert a sequence. In most cases this is used to remove a DNA sequence or cause a frameshift mutation. In some cases the insertion of a TE into a gene can disrupt that gene's function in a reversible manner where transposase-mediated excision of the DNA transposon restores gene function. This produces plants in which neighboring cells have different genotypes. This feature allows researchers to distinguish between genes that must be present inside of a cell in order to function (cell-autonomous) and genes that produce observable effects in cells other than those where the gene is expressed.

Specific applications are listed below:

TEs are also a widely used tool for mutagenesis of most experimentally tractable organisms. The Sleeping Beauty transposon system has been used extensively as an insertional tag for identifying cancer genes.[50]

The Tc1/mariner-class of TEs Sleeping Beauty transposon system, awarded Molecule of the Year in 2009,is active in mammalian cells and is being investigated for use in human gene therapy.[51][52][53][54]

TEs are used for the reconstruction of phylogenies by the means of presence/absence analyses.[55] transposons can act as biological mutagen in bacteria.