Pharmacogenomics Midterm
eSNP
expressed SNP
Exon
A region of DNA that resides with a gene that remains in mature mRNA
Phase 1 enzymes
CYP450 (18 families and 43 subfamilies)
Name 3 technologies that are considered NGS
Rosche/454 (pyrosequencing), Illumina Sequencing (Illumina Dye Sequencing), Ion Torrent (proton sequencing)
RNA
complex compound of high molecular weight that functions in cellular protein synthesis and replaces DNA as a carrier of genetic codes in some viruses
Gene
a DNA fragment encoding an RNA or protein
Single nucleotide variant (SNV)
a DNA sequence variation that occurs when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered
Pharmacokinetics
a branch of science that determines the movement of drug through the body including the absorption, distribution, metabolism, and excretion (ADME)
Pharmacodynamics
a branch of science that studies the biochemical and physiological impact of medication
Microarray technology
a collection of microscopic DNA spots attached to a solid surface used to detect variations in a gene sequence and to measure the expression levels of large numbers of genes simultaneously
Organic cationic transporter
a family of multi-specific, bidirectional, carrier-type permeases that transport organic cations (OCT1, OCT2, and OCT3)
Pharmacogenomics
a field of research that studies how a person's genome affects how they respond to medications
Microsomes
a fragment of endoplasmic reticulum and attached ribosomes obtained by the centrifugation of homogenized cells.
Drug target
a molecule in the body, usually a protein, that is intrinsically associated with a particular disease process and that could be addressed by a drug to produce a desired therapeutic effect
Base pair
a pair of complementary bases in a double-stranded nucleic acid molecule, consisting of a purine in one strand linked by hydrogen bonds to a pyrimidine in the other. Cytosine always pairs with guanine, and adenine with thymine (in DNA) or uracil (in RNA).
Haplotype
a physical grouping of genomic variants that tend to be inherited together; subset of all alleles on specific chromosomes in the population
Intron
a region of DNA that resides within a gene but does not remain in the mature mRNA
Endoplasmic reticulum
a sac like subcellular structure in eukaryotic cells that are involved in lipid synthesis and serving as the site of drug metabolism
Duplication variant
a sequence change between the translation initiation (start) and termination (stop) codon where, compared to a reference sequence, a copy of one or more amino acids are inserted directly C-terminal of the original copy of that sequence
Promotor
a specific DNA sequence responsible for initiation of a transcription
Diplotype
a subset of all genotypes on homologous chromosome pairs in the population
Duplication alleles
a type of mutation in which one or more copies of a DNA segment (which can be as small as a few bases or as large as a major chromosomal region) is produced
Indel
an insertion or deletion of bases in the genome of an organism
Frequency of alleles
calculated by dividing the number of times the allele of interest is observed in a population by the total number of copies of all the alleles at that particular genetic locus in the population
Sanger method of gene sequencing
chain termination method; sequencing with fluorescent chain-termination ddNTP, size separation by capillary gel electrophoresis, laser excitation and detection by sequencing machine
Nuclear receptor
class of proteins responsible for sensing steroids, thyroid hormones, cholesterol, and vitamins
Variation in drug response
different profiles of drug elimination must be caused by the activity of proteins involved in the drug metabolism. As each protein and its amount in the body are directly determined by one's genes, the variability in drug response must have its roots in one's genome.
Noncoding region
does not encode for proteins; made up of regulatory elements, noncoding RNA genes, introns, pseudogenes, repeating sequences, and telomeres
P-gp
drug transporter that determines the uptake and efflux of a range of drugs
Pharmacogenomic therapy
genome-based drug therapy that combines pharmacology (the science of drug) and genomics (the study of genes and their functions) to achieve effective and safe medication that can be prescribed based on a person's genetic makeup
Phase 2 enzymes
glucoronyl transferase (glucuronidation), sulfotransferase (sulfation), glutathione-S-transferase (glutathione), acetyl transferase (acetylation), acyl transferase (amino acid conjugation), methyl transferase (methylation)
Star alleles
haplotype patterns at the gene level associated with protein activity levels
Drug absorption
how the drug moves from the site of administration to the site of action
Frameshift SNV
insertion and deletion in a DNA sequence that shifts the way the sequence is read
Promoter polymorphism
may modify the transcription factor binding sites, thus affecting gene expression.
Alleles
one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome
Next generation sequencing
parallel sequencing technology that offers ultra high throughput, scalability, and speed; used to determine the order od nucleotides in entire genomes or targeted regions of DNA or RNA
Negative strand of DNA
reverse complementary to both the positive-sense strand and the RNA transcript
Nonsense substitution
single base change that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product
Missense substitution
single base change that results in an amino acid substitution in a protein
Single nucleotide polymorphism (SNP)
single nucleotide substitution in a DNA sequence with prevalence of greater than 1% of the population
Mutation
single nucleotide variation in a population at the frequency of less than 1%
Transporters
specialized membrane-spanning proteins that assist in the movement of ions, peptides, small molecules, lipids and macromolecules across a biological membrane.
Membrane receptor
specialized protein molecules attached to or integrated into the cell membrane. Through interaction with specific ligands (e.g., hormones and neurotransmitters), the receptors facilitate communication between the cell and the extracellular environment
Genome wide association study
study design for identifying associations between occurring variations in DNA sequence and drug response; often conducted using thousands of participants capturing genetic variation in the form of SNPs across the human genome
Synonymous SNP
substitutions do not result in change of amino acid sequence in the protein
Non-synonymous SNP
substitutions result in change of amino acid in the protein
Major difference between Sanger method and NGS
the Sanger method only sequences a single DNA fragment at a time, NGS is massively parallel, sequencing millions of fragments simultaneously per run
Drug concentration
the amount of drug in a given volume, such as mg/L
Genome
the complete set of DNA (genetic material) in an organism
Pharmacogene
the genes which decide the fate of drugs pharmacology in biological system
Genotype
the genetic constitution of an individual organism
Human genome project
the international research project deciphering the entire DNA sequence of human genome
Drug distribution
the journey of the drug through the bloodstream to various tissues of the body
Copy number variant
the number of copies of a specific segment of DNA varies among different individuals' genomes
Phenotype
the observable traits of an individual organism
Drug metabolism
the process that breaks down the drug
Coding region
the protein-coding genes, which encode for proteins; made up of exons
Regulatory region
the region of a gene where RNA Polymerase and other accessory transcription modulator Proteins bind and interact to control RNA synthesis
Drug elimination
the removal of the drug from the body
Randomized clinical trial
the researchers decide randomly as to which participants in the trial receive the new treatment and which receive a placebo
Organic anionic transporter
the secondary/tertiary active transporter proteins that regulate anion balance in the body. They are primarily expressed in the kidney and liver
Pharmacogenetics
the study of genes that influence the outcome of a drug treatment
Chromosome
threadlike structures made of proteins and a single molecule of DNA
Pharmacogene-based therapy
treatment of disease guided by one's genetic make-up