Genetic and epigenetic medicine Flashcards
what does genomic medicine discovery reseach assess?
genotype phenotype association
human genome has how many bases?
3 million
___% of the human genome is the same in all people
99.9
what are the differences in DNA called between different people (the 0.1%)
polymorphisms
what is the most common polymorphism?
single nucleotide polymorphism- involves only one base
TF: single nucleotide polymorphisms have no effect on health
false
sometimes they have no effect but others they can lead to a change in function which increases your predisposition to a disease
how can we assess which nucleotide polymorphisms cause disease?
by comparing the single nucleotide polymorphisms in health people with patients diagnosed with certain diseases
what are the studies investigating the associations between disease and healthy polymorphisms?
genome wide association studies
what happens in genome wide association studies?
compare DNA of 2 groups of similar people with and without the disease
single nucleoptide polymorphism arrays read their DNA, if one variant is more frequent in people with the disease that polymorphism is said to be associated with the disease
what is functional genomics
investigation of large datasets produced by the genome aiming to determine the function of genes, RNA and proteins
tries to make sense iof the results of genomic association studies
want to find out the FUNCTIONS of the genes
how does genomics differ from functional genomics?
functional genomics focuses on the dynamic aspects such as:
gene transcription
translation
protein protein interactions
as oppose to just genomic information such as sequence and structure
what is comparative genomics?
what can this help us understand
aims to compare the genome sequence of different species
how genes are conserved through evolution and how they function
what is the biobank
a collection of biological samples for referencing purposes
BRCA1 and BRCA2 are what?
tumour suppressor genes which if mutated can lead to cancer
what is pharmacogenomics?
how the cell responds to drug treatment
what is pharmacogenetics
how variations in one gene can effect drug responsiveness
effect of CYP2D6 mutation on tamoxifen therapy?
mutates can either be: ultra rapid or poor metabolizers.
CYP2D6 metabolises tamoxifen
can lead to sub therapeutic levels or overdose.
what do histones organise?
genetic material
what are histones made of
protein
charge of histones?
positive as they have a high percentage of basic amino acids
why do these histones associate with DNA
as the positive amino acids interact with the negatively charged DNA
How can histones influence gene expression
the tighter the association, the more wound it is and therefore less transcription
what is the most compact shape called of dna and hhistone association. the dna here is ______
heterochromatin
inactive
what is euchromatin
nucleosome structure made of four histones ‘core histones’
contains a single copy of genetically active DNA
what does the epigenome influence?
which genes are active and which are turned off
TF the epigenome cannot change in your life
false
TF lifestyle and environment can change the epigenome
yes
where do epigenetic changes mostly occur?
on histone proteins
epigenetic changes on histone proteins include?
methylation, acetylation, phosphorylation, ubiquitination
_____ and ______ resides can be methylated
lysine
arginine
what is acetylation?
addition of acetyl groups on lysine resides
what is acetylation of lysine resides on histones catalysed by?
histone acetyltransferase enzymes
what catalyses deacetylation?
histone deacetylases
acetylation is associated with _______ of transcrption
deacetylation is associated with _______ of transcription
induction
repression
TF
cancers are caused only by changes to the genome not the epigenome
false
a combination
what were histone deacetylase 1 and 2 both correlated with?
increased proliferating capacity
what can DNA hypermethylation cause? where is this often seen?
transcriptional inactivation of genes
observed in tumours
a decrease in DNA methylation ______ genes
activates
how can we use a therapy to result in the re-expression of transcriptional incompeted chromatin
inhibit certain active histone methyltransferases
can lead to repression of genes
decitabine and azacitidine mechanisms of action?
blocks DNA methyltransferase causing hypomethylation of DNA
may reverse inactivation of suppressor genes
decitabine and azacitidine side effects
bone marrow suppression
cytotoxicity
in carcinogenesis how can TSGs be silenced. how can we target this
by DNA methylation
so can use a drug to inhibit DNA methyltransferases to re express the TSGs
MOA of temozolomide
kills cancer cells by adding methyl groups to DNA
decitabine is a _______ ______. what does it inhibit
nucleoside analoge
inhibits DNA methyltransferases by trapping them in a covalent complex on DNA thus resulting in enzyme degradatoin
