IndexAbstractGene DrivesProposed Gene Drive MethodsCRISPR/Cas9 and Gene DriveDangers and Precautionary MeasuresConclusionAbstractThis article reviews the overall process of gene drive and its methods. First, the reader will be provided with a brief overview of the gene drive concept along with a description of how gene drive systems can be used to manipulate Mendelian inheritance patterns. The focus of this article will be on gene drive methods, the importance of CRISPR/Cas9, and the dangers of gene drive. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essayGene DrivesGene drive is a method by which geneticists attempt to change the normal patterns of Mendelian inheritance within a population. Gene drive works on Mendelian inheritance patterns through two different processes. In the first process, homing, a desired allele copies itself to its counterpart in place of the wild-type allele, which leads to a greater number of offspring with that allele (Champer, Buchman & Akbari., 2016). reducing the viability of gametes containing wild-type alleles compared to gene drive alleles, thus reducing the frequency of wild-type alleles in the population. The purpose of gene drives, in general, is to push a desired trait through a population (Modification) or to suppress/eliminate a population (Suppression) (Champer et al., 2016). Gene drives work to achieve desired results through a number of different methodologies. Proposed Gene Drive Methods One proposed gene drive method seeks to mimic a natural process in which specialized genes search for and target a gene on the opposite chromosome. The genes, homing endonuclease genes (HEGs), code for a protein that binds to a specific sequence of nucleotides and cleaves DNA at that site. Gene drive systems based on this process are collectively known as homing-based drives (Champer et al., 2016). Naturally occurring HEGs do not allow targeting of specific genes. The task of identifying all possible naturally occurring HEGs and tailoring them to the individual needs of geneticists would be colossal. Instead, geneticists have sought new technology that allows for the creation of recombinant HEGs that can be made to target any desired gene within a species' genome (Champer, et al., 2016). This proposed method, CRISPR/Cas9, will be discussed later in this article. Homing-based drives work by forcing DNA repair through natural processes. The filament can repair itself without the aid of a template filament by tying the broken ends of the filament together; this pathway is known as nonhomologous end joining or NHEJ (Gilles & Averof, 2015). If NHEJ occurs, the target gene will simply be excised and the strand will be repaired with removal of the gene. Repair can also occur using the template strand via direct homology repair or HDR. In HDR the HEG will serve as a template for target strand repair, this will result in the HEG being present in both homologous chromosomes (Champer et al., 2016). In either case the normal Mendelian inheritance patterns will have been altered, due to the fact that homing-based units function during meiotic cell division (Champer et al., 2016). If NHEJ occurs, the target DNA will have reduced viability compared to HEG-containing DNA. Overall this leads to a lower frequency of the wild-type allele, meaning that the HEG functions as a suppressor gene drive. HDR has the additional benefit of spreading the mutant allele and reducing expression of the wild-type allele. Homing based unitsthey are desirable as a gene drive method due to this unique nature. Among proposed gene drive methods, homing-based drive is the only method capable of both suppressing and modifying a population ( Champer et al., 2016 ). Another proposed method of gene drive, related to meiotic sex drive, aims to suppress a population by altering the number of male offspring in female offspring. Sex-linked meiotic units are similar to homing-based units in that they contain an endonuclease-carrying gene. This gene is linked to the sex of males of a species. In the presence of an X chromosome during meiotic division, the endonuclease produced by the gene targets and cleaves the X chromosome at multiple locations. Any sperm containing the X chromosome will therefore not be viable (Champer et al., 2016). Genes that act in this way are known as X-shredder genes (Champer et al., 2016). Any offspring of males carrying X-shredder genes will also be male. If the X-shredder genes are found on autosomal chromosomes, then there is a possibility that the offspring will inherit the X-shredder. However, if the X-shredder gene is carried on the Y chromosome, then all offspring of that male will carry the gene (Champer et al., 2016). Populations in which the X-shredder alleles spread will see a sharp reduction in the number of female offspring. Eventually the population will be unable to sustain itself, resulting in a successful suppression gene drive. Unfortunately, X-shredder genes do not exist for all species; geneticists hope to create recombinant X-shredder genes using the same method proposed for homing-based drives. The final proposed gene drive method discussed in this article is maternal dominant embryonic arrest (Medea). Medea occurs in females of a species during oogenesis (Champer et al., 2016). It was first identified in beetles. The mother insect carries a gene that expresses a toxin during oogenesis. Offspring that inherit the gene also inherit a gene that produces an antidote early in zygotic development. Zygotes that do not carry the gene for Medea are unable to produce an antidote and die during development (Champer et al., 2016). Medea-bearing females select Medea-bearing offspring. The gene drives proposed with Medea aim to exploit this process with recombinant DNA. By inserting the desired gene and creating a unique combination of toxin and antidote using CRISPR/Cas9 technology, geneticists will be able to quickly spread a gene through a population. Of all the methods listed, natural processes have created the structure that geneticists are trying to exploit. A logical improvement of any gene drive is the ability to target any gene and insert the desired gene into the genome of the target organism. The emergence of CRISPR/Cas9 technology promises to do just that. CRISPR/Cas9 and gene drives Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated protein 9 (Cas 9) are an endonuclease system that allows geneticists to target any desired gene through the use of specialized guide RNAs ( Gilles & Averof, 2015). An endonuclease is a protein that cleaves DNA. CRISPR is a system used by bacteria to fight phages. Bacteria are able to integrate viral DNA into their genome, the viral DNA is then expressed in the form of RNA and is coupled with an endonuclease (Wade, 2015). A team of researchers was able to modify CRISPR to allow targeting of any DNA sequence. CRISPR/Cas9 uses custom guide RNAs (gRNAs) that can target any desired sequence. The appeal of CRISPR is its ease of use, low cost, and potential applications (Gilles & Averof,.
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