Epigenetics Flashcards
Epigenetics
It refers to stable heritable traits not explained by changes in the DNA sequence
Chromosome modifications
-Histones, DNA methylation
-Essential for normal development
-Can be modified by the environment
-Can be disrupted in disease
DNA methylation
-Human genome contains 30,000, 000 CpGs (1%)
-CpGs are not evenly spaced across the genome
-tend to be present in clusters called CpG islands
-CpG methylation is spatially correlated
-Prevents promoters and enhancers from binding to DNA to reduce expression
Methylation differeneces uses
-Determine cell type ( regulatory T cell vs Naive T Cell)
-Disrupted by disease (Cancer vs Normal)
-Affected by environment (smokers vs Non-smokers)
EWAS
Epigenome-wide associated studies
-Compare lots of cases to lots of controls (often looking for small effects, eg. complex disease or environmental effects)
-Need lots of samples
-100s or 1000s of cases and controls
How to measure methylation
-Bisulphite conversion
-Enrichment of methylated DNA
-Single nucleotide resolution
-Regional resolution
Bisulphite conversion
A methylated site treated with bisulphite does not change (Cs protected) while an unmethylated site will cause Cs to be converted to Ts
-Creates SNP
-Chemical process
-Comparing intensity of C/T gives the proportion of methylation at single CpG
Enrichment of methylated DNA
restriction enzymes
affinity
Single necleotuide resolution
Array
Sequencing
regional resolution
Array
sequencing