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Drugs and Genetics Definitions ~Drugs: chemical substances used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental wellbeing. ~Genome: a full set of chromosomes; all the inheritable traits of an organism. ~Gene: a linear sequence of nucleotides along a segment of DNA that provides the coded instructions for synthesis of RNA, which, when translated into protein, leads to the expression of hereditary character. ~Nucleotides: any of a group of molecules that, when linked together, form the building blocks of DNA or RNA. ~Mutation: a change or alteration in a cell. ~DNA: Deoxyribonucleic Acid. The nucleic acid that is the genetic material determines the makeup of all living cells and many viruses. ~ mRNA: synthesized from a DNA template during transcription, that mediates the transfer of genetic information from the cell nucleus to ribosomes in the cytoplasm, where it serves as a template for protein synthesis. ~Transcription: The process by which mRNA is synthesized from a DNA template resulting in the transfer of genetic information from the DNA molecule to mRNA. ~Splicing: to join (segments of DNA or RNA) together. ~Introns: a noncoding segment in a length of DNA that interrupts a genecoding sequence or non-translated sequence, the corresponding segment being removed from the RNA copy before transcription. ~Exon: A segment of a gene that contains information used in coding for protein synthesis. ~Translation: The process by which mRNA, tRNA, and ribosomes effect the production of a protein molecule from amino acids, the specificity of synthesis being controlled by the base sequences of the mRNA. ~Amino Acids: Building blocks for proteins. ~Codon: a triplet of adjacent nucleotides in the messenger RNA chains that code for a specific amino acid in the synthesis of a protein molecule. ~Non-coding DNA: noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences. ~SNP: genetic variation in a DNA sequence that occurs when a single nucleotide in a genome is altered; SNPs are usually considered to be point mutations that have been evolutionarily successful enough to recur in a significant proportion of the population of a species ~Alleles: any of several forms of a gene, usually arising through mutation, that are responsible for hereditary variation. ~Hydrophilic: Having an affinity for water. ~Hydrophobic: Repelling, tending not to combine with, or unable to dissolve in water. ~Signaling Pathways: ___________________________________________________ ___________________________________________________. ~Genetic Linkage: tendency of genes that are located proximal to each other on a chromosome to be inherited together during meiosis ~Pharmacogenomics: the study of human genetic variability in relation to drug action and its application to medical treatment. Drugs and Genetics Questions ~How does a gene become a protein? A gene becomes a protein through transcription and translation. ~In a given gene, what kind of DNA mutation would not change the protein that is made? A substitution wouldn’t change the protein that is made. ~Why is non-coding DNA important? Non-coding DNA is important because it was found that it controls embryos. ~What makes some amino acids hydrophobic and others hydrophilic? The specific amino acids in the mRNA strand makes them hydrophobic or hydrophilic. ~Why is it important for pharmaceutical companies to test new drugs on a large number of people? It’s important for pharmaceutical companies to test new drugs on a large number of people because it helps them see if it would work on different people. Drugs and Genetics Procedure questions Determining How Genetics Change Drug Responses: Clopidogrel - Prevents Blood Clots 2a. Clopidogrel is a antiplatelet agent similar to Ticlopidine. Patients who have had a recent stroke, IM, or have peripheral vascular disease would use Clopdiogrel. It is used to reduce atherosclerotic events. 2b1. Trade Names: Clopidogrel, Clopidogrel sulfate, Plavix. 2b2. What kind of chemical drug: Antiplatelet agent Related to: 2b3. Prevents Blood Clots 2b4. 4a. P2RY12 gene is located in the q25. 4b. They are all implicated as cytochrome P450 enzymes involved in the metabolism of clopidogrel. 4c. Drug-drug interactions of clopidogrel were reported with atorvastatin. 4e. Multidrug resistance protein 1. 5d1. Involved in the intestinal absorption. 5d2. The change of alleles can affect how the body responds to the drug by decreasing the risk for bleeding. Identifying the Mutations: 3c. Gene ABCB1: Protein coding, Homo sapiens (human). 5d4. A substitution wouldn't have changed the amino acid sequence because there are 20 amino acids and over 60? triplet codons. 5d5. A framshift would have changed the allele because it shifts the sequence however many spaces right or left changing it completely. How Amino Acid Changes Matter: 3b. It can make the protein hydrophilic or hydrophobic which could 3c. A Point Mutation would be least likely to change the proteins normal function. 4a. If the function of this protein changes, the drug wouldn’t function properly and wouldn't help reduce atherosclerotic events. 4b. No my hypothesis isn't similar to what is known about how this allele mutation changes a patient's response to the drug.