TMC 4 Flashcards
Describe DNA methylation in mammalian cells.
Cytosine can be methylated at carbon 5 to generate 5-methylcytosine at CG sequences (CpG)
Can be altered by DNA methyltransferases and by demethylation enzymes
Where does DNA methylation occur in mammalian DNA?
Cytosine can be methylated at carbon 5 to generate 5-methylcytosine at CG sequences (CpG)
How many new mutations are present in each newborn?
Approx. 200
Why do mutations accumulate in humans and other organisms over successive generations?
A variety of mechanisms such as mistakes in copying DNA and through damage to bases in DNA that change their base pairing properties
Explain the relationship between DNA methylation at cytosines in human DNA and the frequency of single nucleotide polymorphisms in the genome.
Cytosine in the human genome tends to be methylated at the 5th carbon atom creating 5-methylcytosine.
This methyl group is liable and when it is broken off it generates thymine
Thymine DNA glycosylases that recognise the mutation within the DNA and remove the thymine and then the DNA is repaired by the base excision repair pathway
Thymine DNA glycosylase is not very efficient and misses mutations frequently allowing them to be replicated and become part of the genome.
TG is the most common single nucleotide polymorphism in the human genome.
Describe deamination of cytosine and its relationship to mutation.
Deamination of cytosine creates uracil. When this happens Uracil DNA glycosylase will remove the uracil in the DNA strand.
DNA is repaired by the base excision repair pathway.
Uracil DNA glycosylase does not remove uracil from RNA
UDG is very efficient making this an uncommon mutation
Describe deamination of 5-methylcytosine and its relationship to mutation.
Deamination of 5-methylcytosine creates thymine
When this happens thymine DNA glycosylase will remove the thymine in the DNA strand
DNA is repaired by the base excision repair pathway
TDG is not as efficient making T:G the most common single nucleotide polymorphism
Explain the relationship between DNA methylation and gene expression.
Methylated = silenced or muted
What is the genome?
DNA sequence, the same in all somatic cells besides low levels of mutation accumulation
What is the methylome?
Pattern of methylation on the DNA in the genome
Changes due to signalling factors, environment, age, etc
What is the epigenome?
Nucleosome
DNA
pattern of all methylated cytosines
pattern of all modifications to chromatin
transcription factors bound to the chromatin
remodelling complexes bound to the chromatin
What is the transcriptome?
RNA transcribed from genes in a cell or tissue - RNA profile
Changes due to signalling factors, environment, age etc.
What is the proteome?
Full complement of proteins expressed in a cell or tissue.
Closely related to transcriptome
Changes due to signalling factors, environment, age etc.
Are the different -omes the same in different tissues?
No for all but the Genome in all somatic cells
