Lecture 1 - Intro Flashcards
Actionable Signature
Information used to make treatment decision
Genetic markers that can distinguish patients
Who are most likely to respond to a drug
Who develops side effects
Who should NOT take the drug
The best dose to be taken
Which 3 polymorphisms determine ~50% of dose variance in pts taking Warfarin?
VKOCR1, CYP2C9 and CYP24F2
PK
What the body does to the drug
ADME
PD
What the drug does to the body
Receptor
Target
Enzyme
Signaling
FDA has approved _ pharmacogenomic drug labels as of 2018, 2020, and 2023
150
385
317
DNA
Thin (2nm diameter)
Linear polymer fiber
Double-stranded helix
DNA ant-parallel
A=T (2 hydrogen bonds)
G=-C (3 hydrogen bonds)
Genome definition
A genome is an organism’s complete set of DNA including all of its genes. Each genome contains all of the information needed to build and maintain that organism
In humans, a copy of the entire genome - more than _ is contained in all cells that have a nucleus
3 billion DNA base pairs
Gene definition
A sequence of DNA or RNA which codes for a molecule that has a function
Protein coding genes
Genes that are expressed to be proteins
-only 1-3% of the human genome are protein-coding sequences
How many genes in humans
21,000
Noncoding genes
Final product is an RNA, not a protein
Types of noncoding genes
Transfer RNAs (tRNA): transfer amino acids to the RNA template to make protein
Ribosomal RNAs (rRNAs): the RNA component of ribosome
MicroRNAs (mRNA): play very important role in regulating protein-coding gene expression
Others: Long noncoding RNA (LncRNA), antisense RNA, Pseudogenes
CYP3A4 meaning
Cytochrome P450 gene family 3 subfamily A gene #4
Structure of a gene
Protein coding gene
Promoter/5’-flanking
Exon
Intron
3’UTR
3’-flanking
(on average: 8.8 exons/gene, 7.8 introns/gene)
Sequence Position
Locating each gene - coordinates
Each nucleotide has its unique position in the reference genome
The position is often called a “locus” (pl. loci)
Central Dogma
DNA - RNA - Protein
RNA can reverse transcribe to DNA (coronavirus)
Protein can reverse translate
Prions
Transcription: mRNA maturation process
Matured RNA = missing introns
Cytoplasm
Matured RNA: Translation
RNA to protein
Starts with AUG (making amino acid “Methionine”)
Stops at one of the three stop codons (UAG, UAA, UGA)
Genetic coding system
64 Codons
-3 stop codons: UAA, UAG, UGA
-1 initiation codon (ATG)
20 amino acids
Sequence variations
Present in any given human genome
Present between individuals
Present In a population
Sequence variation (polymorphism)
Largely influences diversity and adaptability of humans to a changing environment
Whether a variation has a functional consequence depends on its
Location and Nature
Nature of a polymorphism
A sequence variation at the Same position of homologous chromosomes (diploid genome)
There are NO polymorphisms in the genome of a single germ cell (haploid genome)
