Genomics in drug discovery Flashcards
Define the genome and define genomics
The genome is defined as an organism’s complete set of genes and chromosomes. Genomics is defined as the process of mapping, sequencing and analysing genomes.
Define pharmacogenomics
Pharmacogenomics is usually regarded as the broader, whole
genome, application of genomic and analytical technologies to search for a patient’s individual genetic profile for disease and genetic interaction.
Which enzymes are needed to go from DNA to RNA?
Helicase and DNA polymerase
Which enzyme is needed to go from RNA to DNA?
Reverse transcriptase
Define pharmacogenetics
Pharmacogenetics is usually regarded as the study or clinical
testing of genetic variation (single-nucleotide polymorphisms;
SNPs) giving rise to differing responses to drugs usually through
varying drug metabolism. This can affect both efficacy and side
effect profiles.
Define splicing
Removal of introns (useless genes) and the rearrangement of exons (useful genes) are joined together, which is also how different varieties of antibodies can be made.
What is RTPCR?
Reverse transcriptase polymerase chain reaction is used to produce several copies of cDNA from a single piece of mRNA
Describe the process of RTPCR and how a probe can be used
1) A colour marker/fluorescent marker is attached to the mRNA
2) RT is used to form cDNA
This cDNA has a fluorescent marker that can be placed in a DNA microarray that can light up via UV light. The more light, the more cDNA. = more mRNA at the start
How can DNA microarrays be used?
The microarrays can be used based on by comparing healthy mRNA and faulty mRNA. Different coloured markers can be used to distinguish healthy and faulty mRNA, eg: green for healthy, red for faulty., yellow = found in both and this can be used to identify which genes are expressed in conditions
Describe 3 ways to identify the significant genes using statistics
1) Ranking - highest to lowest expression and take top 1%,but may miss out crucial genes.
2) Threshold - a threshold can be used to identify the right number of genes by using t-tests, every gene must be below <0.05. Correction may be added for false positives.
3) From 2), RTPCR is conducted from each significant gene to ensure that this gene is expressed and Western Blotting can be used to confirm the presence of the gene
What are the advantages of genomics based drug discovery?
It is fast and looks at the expression levels of >10,000 genes an experiment. It is comprehensive and can fit the entire human genome on two chips. It could be used to identify patient groups drugs work in and don’t work in and may even be used to revive dead drugs.
What are the disadvantages of genomics based drug discovery?
It is very expensive. The expression levels of mRNA may not truely represent what occurs at the protein level. It can also only be used for genetic diseases.
