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The Jumping Genes and their Applications
#1
Every single gene possess a distinct and definite location in a particular chromosome. This is well established by the ability to reconstruct gene maps using various physical methods and gene techniques. Besides this, the suspicion on gene relocation triggered researches to find out that some of the genes can actually relocate (change its position) in a chromosome. The relocation of the genes were identified to be the occurrence of two phenomenon like mispairing or unequal recombination and the presence of commuting elements called as Transposons. Transposons are one among the other two mobile genetic elements like episomes and cassettes.

Transposons are the genes present as the segments of DNA, able to commute independently from one site to the other on a chromosome. The DNA with transposon genes are also called as the selfish DNA or mobilized DNA. Transposons are also classified as mutagens. They are called by different names like mobile genes, jumping genes, roving genes etc. The scientist Barbara Mc Clintock is the founder of Transposon, as she was the first person to discover the presence of such mobilizing elements in maize crop.

The Different Transposons: Transposons were classified into prokaryotic transposons and Eukaryote transposons based on their existence in the type of cell. Prokaryote transposons have sub classes like insertion transposon first identified in E. coli and Transposons. The latter possess the genes that not only encode for the enzyme transposase but also encode genes for antibiotic resistance and heavy metal resistance. The process of transposition was found to be not frequent. Also the insertion type of translocation occurring in bacteria can be transferred either vertically to bacteria of the same species or horizontally to the bacteria of the different species.

The Eukryotic transposons are divided into two major groups called as class I transposon and class II transposon. The class I transposons are retrotranposons which undergoes two phases before fixing themselves into a new location. Retrotranposon commutes to the new location on a chromosome by first transcribing into RNA and then reverse transcribing into DNA. The former step is induced by the action of the enzyme RNA polymerase II or RNA polymerase III and the reverse transcription is due to the action of the reverse transcriptase enzyme. The long terminal repeats (LTR), long interspersed elements (LINEs) and short interspersed elements (SINEs) forms the class I transposons.

The class II transposons are those elements which relocate as DNA itself from the origin site to the target site (not RNA mediated). Transposase is the enzyme involved in this activity which snaps the new location, creating glue ends enabling the cut DNA to paste into the new site. The family of transposon elements is composed of autonomous members and non autonomous members. The autonomous members are like earning members in a family who code for their own transposition and non autonomous members are like non earning members in a family who always depend on the autonomous member for their movement into new location. Few examples of the identified class II transposable elements are Ac – Ds element in maize, Tam element in Antirrhinum, p element in Drosophila, Ty element in yeast, Tc1 element in the worm species Caenhorabditis elegans and Alu in humans.

Transposable elements are known mutagens and considered as rich source of mutation. The type of mutation caused by the transposable elements is the insertion mutation. Some of the diseases associated with the mutagenic property of transposons are cancer, muscular dystrophy, hemophilia A & B, porphyria and immunodeficiency.

The definite frequency at which the transposons relocate to a new site is considered as the unique property of transposons. The mutation causing property of transposons has derived ways for multiple applications in the field of medicine, genetics, gene therapy and biotechnology. Characterization of various strains of the species Plasmodium falciparum, the major source responsible for malaria in humans is made possible by the use of transposons as markers in clinical studies. Identification of carriers of genes responsible for diseases like sickle cell trait and Down’s syndrome is made possible by using transposon as a genetic tool. Also transposons are identified as suitable vectors in Transformation mode of gene transfer. Transposons are applied in molecular genetics which involves gene isolation and they are also used to construct gene maps. The research on transposons as tools for genetics and gene therapy are underway in the labs of Zsuzsanna Izsvak and Zoltan Ivics at Max Delbruck center for molecular medicine.
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#2
Jumping genes also called as transposable elements are the sequences of DNA that shift from one location to another in the genome. These transposable elements were first discovered by Barbara McClintock (geneticist of Cold Spring Harbor Laboratory) about fifty years ago. Following several decades of research found that the TEs not only jump but are also found in all eukaryotes and prokaryotes. Transposable elements make up to around 90% of the maize genome and about 50% of the genome of humans.

Transposable elements are comparable to integrating viruses as natural transfer vehicles of DNA and also in efficient capability of genomic insertion. The mobility of DNA transposons (class II transposable elements) can be controlled by providing conditionally, the transposase constituent of the transposition reaction. Therefore, desired DNA (such as a therapeutic gene construct, a fluorescent marker or a small hairpin RNA expression cassette) that is cloned in between the inverted repeat sequences (IR sequences) of a transposon based vector can be utilized for efficient genomic insertion in a highly stable and regulated manner. This technique has created many opportunities for genetic manipulation in vertebrates such as transgenesis (to produce transgenic cells in tissue culture), in the creation of germline transgenic animals for fundamental and applied research and also to treat genetic disorders in human beings. The first transposon that was capable of transferring gene in vertebrate cells was Sleeping Beauty (SB). And the current data supports a whole spectrum of genetic engineering with SB including, insertional mutagenesis, transgenesis and therapeutic gene transfer both in vivo and ex vivo.

Genetic engineering mediated by transposons is also useful in studying physiology and pathogenesis of bacteria in living hosts. As randomly inserted transposons are important tools in various applications such as STM (signature-tagged mutagenesis), genetic footprinting, cDNA or DNA sequencing, SLM (scanning linker mutagenesis) and transposon site hybridization or TraSH.



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