TMC 4- The Human Genome Flashcards
where is mammalian DNA methylated?
Mammalian DNA can be methylated at the carbon 5 of cytosine
in mammals, cytosine can be methylated at carbon 5 to generate 5-methylcytosine (5-mC) at CG sequences (also called CpG).
how can Methylation patterns be altered
by DNA methyltransferases (DNMTs)
and by demethylation enzymes.
when are DNA methylation patterns laid down
In the early embryo
Demethylation event in zygotes
In mammals, a demethylation event demethylates the whole genome in zygote shortly after fertilisation and in
primordial germ cells.
New (de novo) methylation then
occurs generating a methylation pattern that persists throughout development and becomes modifed at genes that are expressed in a tissue specific manner.
what does Deamination of cytosine generate in DNA
uracil
what enzyme works in deamination of cytosine
UDG - uracil DNA glycoslase
** doesnt act on uracil in RNA
What happens once uracil is removed as a part of the deamination process
Once the uracil is removed,
– DNA repair enzymes of the base excision repair pathway (BER) – repair the area and – reinserts cytosine.
What does deamination of
5-methylcytosine (5-mC) in DNA generate
thymine
what enzyme works in deamination of
5-methylcytosine (5-mC)
TDG - Thymine DNA Glycosylase
deamination of 5-methylcytosine (5-mC)
- C is replaced w/ T
- repair by TDG and other DNA repair enzymes of BER replace T w/ cytosine
– thus CG when replicated gives GC - However TDG not as efficient as UDG
– thus usually replication without repair
– produces AC from TG instead of GC
This is an example of an SNP
What is the most common SNP in people
C to T changes at CG sequences
BER?
Base Excision Repair pathway
SNP
Single Nucleotide Polymorphism (SNP) – A single DNA base change found between humans or individuals of any species
deamination of cytosine
- Cytosine is replaced with Uracil
- UDG recognises uracil - and removes it
- UDG along with other DNA repair enzymes of the Base Excision Repair pathway (BER) come in and replace Uracil with Cytosine
- If replication without repair – U is not replaced with C
– Thus instead of G pairing with C – A is paired with a T (as U is replaced with a T in DNA)
how do DNA changes occur
- mistakes in copying DNA
- through damage to bases in DNA that change their base pairing properties
mutations vs polymorphisms
polymorphism - Harmless chnage in DNA
Mutation - chnage in DNA that causes a change in the phenotype of an organism
How many new mutations are present in each newborn
about 200 new DNA changes in a new born
why do mutations accumulate in humans and other organisms over successive generations?
- due to DNA replication errors and naturally occurring damage to the DNA over time – 200 new DNA changes found in a newborn
- These changes passed onto the offspring of the newborn along with 200 more new DNA chnages
- Thus more the generations - more the DNA chnages accumulating
CpG islands and where they occur
Regions rich in CGs occur in ~ 60-70% of human / mammalian promoters.
CpG and CpG island methylation
CpG islands in promoters in DNA – mostly not methylated
If CpG islands in promoters are methylated – silences the gene - thus silences/NO transcription
CpGs not in CpG islands – generally methylated
Genome instability
Term used when increased frequency of alterations
of the genome are seen in a cell
Typical alterations:
- change in chromosome number
- change in chromosome structure
What are the diff -omes
- genome
- transcriptome
- proteome
- methylome
- epigenome
(Go To Pick ME)
Genome
- DNA sequence of a species.
- same in all somatic cells
- doesnt change within the cell or when the cell divides into daughter cells
Transcriptome
- It is the RNA transcribed from genes in a cell or tissue
- also known as RNA profile
- differs between cells of different tissues
- Transcriptome changes in cells depending on various factors - the environment, age, signals etc.
