Lecture 5 Genetics - Annika (molecular stuff) Flashcards
Are DNA methylation patterns are passed onto daughter cells - explain this
DNA methylation patterns are passed onto daughter cells, yes
This allows any type of cell to have its own methylation pattern so that a unique set of proteins are expressed to perform the functions specific for that cell type
What actually happens is that the parental strand in the DNA replication will have the methyl groups but when the correction enxyme comes around, it will see the new strand doesnt have methyl group then the it will add one to the new strand.
DNA methylation is a chemical modification and they are relatively easily influenced by lifestyle factors (hence modfify gene expression).
Are DNA methylations and other chemical modifications erased in the germ line? Explain
Yes, they usually are erased in germ line, allowing the embryo to reset gene expression to the normal original ‘start’ state buttttttttt, they can be stable and might not always be erased so they might get passed on and change gene expression pattern in child.
With DNA mutations though, you’ll have those passed on
Looking at the DNA methylation graph - what does it look like during the zygote stage?
So DNA methylation goes down during the zygote to implantation stage but then goes back up after
Give a summary of DNA methylation
So methylation decreases transcription because the methyl groups physically block access to the promotor or recruit enzymes that deacetylate the histone proteins to produce tightly packed heterogeneity chromatin.
DNA methylation regulates gene expression in response to day-to-day cellular needs buuuuuut normal gene expression can be inappropriately modulated by environmental factors and lifestyle choices that inappropriately affect the DNA methylation pattern
How can DNA methylation lead to DNA mutations?
Since it’s the cytosine bases that are methylated - they are somewhat more likely to become reanimated and this turn into a thymine base. Sooooo, if you increase methylation due to environmental stimuli/lifestyle factor then you may increase cytosine to thymine changes and produce point mutations
So epigenetic (histone modifications + DNA meth) and DNA sequence make up the set of signals that guide the genes to express themselves at the right time, right place and in right amount. But what must you also take into account?
So almost all genes are part of gene networks and a single gene can enhance or decrease the activity of multiple other genes. And these gene networks are influenced by environmental and lifestyle factors via the epigenetics thing.
Gene networks make the regulation of gene expression very complex.
Genes usually never work alone. One gene is affected by another gene etc
These gene networks makes it almost impossible to predict what changes to gene expression happen.
So the gene expression profile of any particular cell or cell type in a given individual at a given time and under a given set of circumstances is this the integrated sum of what different effects?
- Primary DNA sequence
- Regulatory sequences
- Gene networks
- Chromatin architecture
- Epigenetics
For some genes, the changes made by epigenetic are of little importance but for some, that varied gene expression can have severe clinical consequences (might have a phenotypic change if change importatn gene)
Environmental and lifestyle factors may influence epigenetic mechanisms such as (3)
What have the changes in epigenetic marks been associated with?
- Histone modifications
- DNA methylation
- miRNA expression
miRNA inhibit translation and therefore prevent gene from being expressed. The seuqences of miRNA is complementary to mRNA so get this double stranded mRNA molecule so ribsome cant move along mRNA and it signals for other proteins to destroy that mRNA and that’s how miRNA repvent the gene expression of a gene.
Cancer can be too much miRNA (by demethylating the promotor of the miRNA so increase its expression).
What are examples of lifestyle factors that that affect the histones, DNA methylation and miRNA?
Physical activity:
- It will methylate DNA and inactivate TEs in blood lymphocytes so the chromosomes are more stable
- It will acetylate histone proteins and activate gene regions in muscles cells
- It will alter the miRNA profiles in neutrophils
Or if you are smoking in pregnant mother than it will affect growing fetes:
- will get hypomethylation of TEs
- Abnormal CpG methylation of several genes
- Differently expressed miRNA (involved in regulating growth and development)
What is the importance of epigenetic in non-random mono allelic gene expression?
Go read slides 92, 93 and 94
Basically, some genes are monoallelic - one is inactivated and other activated. X-chromosome inactivation is random so monoalleic. Sometimes there is non-random inactivation of materanl/parental alleles caused by deletions or like environmental lifestyle factors of mother. So if parental specific inactivated then Prader Willi syndrome and if maternal specific genes inactivated then Angel syndrome
How can gene expression of one gene be regulated to give rise to several different protein products?
Alternative splicing and post transitional modifications like polypeptide processing or chemical modifications
Go read slide 105
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What is the difference between single gene disorders and complex diseases?
Singe only involve one gene - very little environmental effect and follow typical inheritance pattern (autosomal dominant etc). Complex diseases are caused by many contributing factors like multiple genes in combo or with environ + lifestyle factors - mutation will have a weak effect on gene expression and these don’t follow typical inheritance pattern
What is personalised medicine and what does it provide?
Why would you want it?
It can provide person-specific treatment: info about one’s genome sequence and (bio)chemical individuality provides the basis for the practise of ()
Would want it bc one dose/drug doesn’t fit all so personalised medicine means everyone only benefits. So info about a person’s genes and genome determines pharmacogenetics and pharmacodynamic responses that’s used to develop personalised medicine.
Advantages: no ADR and you can maximise therpeutic effects
Bad: Identification of genes that may infleucen drug response is v difficult esp as most genes are part of a gene network. Also, the interaction with environmental factors needs to be determined before any conclusions can be made about the genetic influence on how the drug is working
