Pharmacogenomics 1 Flashcards
cost of sequencing is ______
dropping
what is the human genome project
10 year international collaborative research programme
to complete mapping and understanding of all the genes of human beings
TF we have more geans than other mammals?
false, found only 20,000 genes which was lower than initial estimates
how many nucleotides?
3.2 billion
individuals are ____% identical
99.9
what is the NHS 100000 genomes project? who participates
set up in 2012 has 100,000 genomes from 85,000 people from tumour and normal cells
NHS patients with rare diseases and their families
what is the UK biobank?
private investment
cohort study with deep genetic and phenotypic data on 500,000 people in the UK aged 40-69
followed up overtime to see if theres changes with diagnoses
what is genetics? how does this differ to genomics
study of DNA
studies the genes not the junk, genomics covers everything
genotype codes for ____
phenotype
___ pairs of chromosomes +2____
22 pairs
2 sex chromosomes
= 23 pairs and 46 chromosomes
how are chromosomes ordered
by size normally
process of DNA to protein? simple
DNA replication, transcription, RNA replication, translation to amino acids
RNA is ____ compared to DNA. (stability)
unstable
what can reverse transcription?
viruses
retrotransponsons
telomere extension
_ons code for proteins
exons
where are introns spliced?
from RNA- are coded into RNA first them removed
____% of DNA is junk
95
a key role of junk DNA?
can bend to get different elements closer to where the gene is
can cause activatio of promotors, TF
why do we have mutations if theyre linked to risk?
need mutation for protection from environment e.g. antigenic shift in viruses
whats copy number variation?
large chunks of DNA inserted, repeated or deleted
what does synonymous mean
no change to AA sequence
what is pharmacogenetics?
effects of genetic variation on drug response which can lead to altered therapeutic effect or an adverse effect
common gene variant for AEDs
CYP450
what can you sample to get dna
saliva, blood, cheek
what can pharmacogenetics effect
PK- absorption, distribution, metabolism, excretion
PD- modified targets, sensitivity
toxicity
4 types of metaboliser?
poor
intermediate
extensive
ultra rapid (29% of ethiopians)
what is gene therapy
treating or curing disease by altering gene expresison
correct genetic defects in inherited diseases
how can you replace defective genes?
transgenes transferred into body cells
NOT GERM LINE- ILLEGAL passes to offspring
can be from just one injection
issues with replacing defrective genes
insufficient delivery to target cells
adverse effects
autoimmune response
off targets
what is delivery using vectors
retroviruses used to intergrate into the host genome- transfers gene into genome
size of genes which can be integrated using vectors
small, some diseases have large mutations so wouldnt work here
effect of adenoviral vectors? long lasting? used in which diseases?
dont intergrate into the genome or replication- temporary effects
cancer
what is an adeno associated virus? why do we use?
human DNA containing viruses that wont trigger an immune response
what does PG commonly need to help treatment outcomes
needs knowledge of the geneome before prescribing
what is a KRAS mutation? common in what?
EGFR antibody wont work against them
30% of patients with colon cancer
HER2 overexpression in ___% of BC
20
what can PG be used to do in relation to older discontinued drugs
re-trial compounds where testing can aid
TF its always a single variant causing the effect?
false can be lots of little ones
what role may pharmacists have in PG in the future?
interpreting genetic tests to determine appropriate treatment
difference betwen monogenic and polygenic effects
monogenic: mendelian, one gene, easy to identify
polygenic: lots of variants in more than one gene, harder to pinpoint
what does 312 G>A mean
guanine at nucleotide position 312 in a particular sequence is changed to an A
what does p mean what does q mean
p: short arm of the chromosome (petite)
q: long arm
what does 6p12.2 mean
chromosome 6, at area 12.2 million base pares on the short arm
what does G312A mean
glycine at position 312 has been changed to alanine
what level is CYP2D6*4
the phenotype level
what does homozygous for risk allele mean? heterozygous for risk alleles?
2 copies
1 copy- carrier can pass to children
what does compound heterozygous mean
2 risk alleles from different places in the DNA
