User:Rachelv37/sandbox

Article Evaluation: The article did not go off topic and it seemed to cover a lot of different subjects about cancer. I also checked some of the article's sources and they seemed to be up to date and reliable. The article does need more detail though; many topics were covered, but they were broad. The article needs a little more detail about how cancer cells are produced and how they spread throughout the body. More statistics and facts would be helpful for a topic like cancer. It informs the audience how cancer can affect them and what the chances of survival are for different types and stages of cancer.

Article to Edit: Silent Mutations.

Sources: https://books.google.com/books?id=MUw0eHzuH2AC&pg=PA163&dq=%22silent+mutation%22&hl=en&sa=X&ved=0ahUKEwiQiO7b5ePdAhUR7FMKHXwjBI4Q6AEIKTAA#v=onepage&q=%22silent%20mutation%22&f=false NOTES:'

https://books.google.com/books?id=FlfPSpBvKLgC&pg=PA142&dq=%22silent+mutation%22&hl=en&sa=X&ved=0ahUKEwju_d-D6uPdAhVIuVMKHfBUBg0Q6AEINzAC#v=onepage&q=%22silent%20mutation%22&f=false NOTES: If the mutated codon still produces the same amino acid then it would be called a silent mutation because the product did not change. there are some diseases that are linked to "silent mutations" proving silent mutations to not be so silent. Hutchinson- Gilford progeria syndrome and the multi-drug resistance 1 gene.

https://books.google.com/books?id=crAnYWLB09QC&pg=PA348&dq=%22silent+mutation%22&hl=en&sa=X&ved=0ahUKEwjszdvH7OPdAhWLvFMKHWrsAqUQ6AEIMDAB#v=onepage&q=%22silent%20mutation%22&f=false NOTES: MDR1 has silent mutations that actually do have effects on a person and that their response to certain drugs have been changed. Same amino acid but different protein. Translation is different because when a silent mutation codon is being transferred it changes the amount of time it takes for the ribosome to produce its protein confirmation. and since the pace changes, the protein changes. mRNA is important in that it also tell the exonic splicing enhancers when to cut out introns. one codon could differ from its silent mutation codon in that the original splicing centers will be different than the silent mutations splicing center which can lead to introns being cut out that should have never been cut out. mRNA 2ndary structures: mRNA can fold which means different codons correspond to different folding's of the mRNA which then in response "changes the speed at which the mRNA is translated." An example of this is from the gene that is most associated with the level of pain we can tolerate. Catechol -O-Methyltransferase has enzymes that help us perceive pain but when silent mutations interrupt the sequence the mRNA gets folded differently which then gets translated into a different level of the enzyme. this then causes us to either be more, less, or averagely tolerant to pain. Summary. Silent mutations are not so silent because when the codons change, the introns tend to change leading to different phenotypes. BLUE

https://www.sciencemag.org/news/2006/12/sound-silent-mutation

NOTES: MDR1 gene has different proteins that help exile the drugs (used for chemo) from cancer cells. having a silent mutated gene tends to get rid of the drugs at a higher quality. This is explained through the process of the proteins being made at different speeds which tends to change the shape of the protein. PURPLE

https://books.google.com/books?id=dSwWBAAAQBAJ&printsec=frontcover&dq=what+are+silent+mutations&hl=en&sa=X&ved=0ahUKEwi_p_CY8OPdAhVM0VMKHbsMAdAQ6AEILjAB#v=onepage&q=silent%20mutations&f=false NOTES: Silent mutations can effect splice sites by inactivating the splicing site. For example on chromosome thirteen there is the SMN gene which has two copies of the gene. the codon TTT but this codon sometimes mutates to TTC. The two codon appear at different locations on the chromosome. One copy is highly expressed near the centromere while the other does not even produce a protein. The silent mutation vs the original codon splices at different intron leading to slightly different proteins. "spinal muscular atrophy" can result in one of the mutated copies of the gene while the other copy will result in a less extreme case of SMA. "TTC to TTT marks the difference between an active correctly spliced gene and an inactive incorrectly spliced gene". In MDR 1 the gene 3535C can mutate to 3535T (at exon 26) which then changes the tRNA into one that is not often as seen which means there is not a lot of it and therefore it changes the outcome during translation. ORANGE

https://books.google.com/books?id=g-d--DOdnQAC&pg=PA106&dq=silent+mutations&hl=en&sa=X&ved=0ahUKEwie-oyP5-XdAhXJct8KHZJyB6YQ6AEIMjAC#v=onepage&q=silent%20mutations&f=false NOTES: Also called single-nucleotide polymorphisms. Silent mutations don't have to just be in the third space of a codon, they can also be in spacer DNA and introns. The reason behind this is because no matter which origin the mutations comes from, it does not alter the amino acid which then does not change the protein, leaving the gene to function as it would have if there was no mutation.

https://books.google.com/books?id=xWpnDAAAQBAJ&pg=PA359&dq=why+is+the+MDR1+gene+not+silent&hl=en&sa=X&ved=0ahUKEwiR5_bZ4bHeAhWJ3VMKHTqiDfIQ6AEIKjAA#v=snippet&q=%20MDR1&f=false  MDR1 codes for the P-glycoprotein which helps get rid of drugs in our body. It is located in parts of our body including the intestines, liver, pancreas, brain etc. MDR 1 is located in the same places that CYP3A4 is located which is an enzyme that helps get rid of toxins or drugs from the liver and intestines. After texting mice a creating a shortage of the gene MDR1 they experienced" Neurotoxicity to the drug ivermectin " and their bodies had a harder time recognizing the cyclosporine drug (organ transplants and rejected them sometimes). MRD1 has "more than 50 single nucleotide polymorphisms" these are changes in the nucleotides base sequence. C3435T which is exon 26, 21 G2677T/A, and 12 C1236T have been studied to have SNP's that occur at the same time, therefore making the phenotypic "function "change. This suggests that there may be a haplotype dependency between exon 26 and other exon that have polymorphisms. For example, efavirenz and nelfinavir are two types of drugs that help decrease the HIV infection in a person's body. These drugs appear in MDR 1. When the SNP from exon 26 is coupled with other SNP exons, the drugs had a lower chance of helping maintain the HIV infection (TT TC and CC). Although, when the TT nucleotides were expressed the patient had a lower concentration of the virus but when the genotype morphed into CC or CT the infection was able to spread like normal leaving the MDR 1 gene almost defenseless. These changes in bases of the DNA for MDR 1 shows a correlation between the MDR 1 gene mutations and the ability of the antiretroviral drugs to suppress the HIV infection. The presence of the SNP of exon 26 changes phenotypic functions when it is paired with the presence of mutations from eons 12 and 21. But when acting alone, it does not effect the phenotypic outcome as strongly. Since MDR 1 removes drugs from our cells, Inhibitors have been used to block MRD 1's ability to remove drugs, thus letting beneficial drugs like chemotherapy and immunosuppressants aid our body in recovery more efficiently. Verapamil and cyclosporine A are common inhibitors for MDR 1. Unfortunately, when C3435T is mutated with a mutation from either exon 12 or exon 21 ( or if all three mutations occur at the same time (haplotype)), the inhibitors are less likely to weaken the function of MDR 1. This further shows that a "silent mutation" is not always silent. Around 99.8% of our genes that undergo mutations are deemed silent because the nucleotide change does not change the amino acid being translated. Some silent mutations like MDR 1 do express a change in phenotypic response. Looking at the molecular level, the reason why C3435T in exon 26 of MDR 1 gene is not silent is because of the pace at which the amino acids are making the proteins. For example, when exon 26 changes ATC to ATT both codons produce the same amino acid but ATC is seen more often then the mutation which means there is less mutated codon to synthesize. As a consequence, the protein has time to change its structural shape which can vary from the usual shape of the protein when the original codon is used. ( Proves that "silent mutations could have a greater impact on our lives than we expect.) RED