(Week 3) [T5] Precision Medicine Genetics and Epigenetics Flashcards
What is exposomics? Refer its types.
Comprehensive measure of a person’s exposures events (from conception to death), and determination of how those exposures relate to health and disease.
- Internal (microbiome: unbalances in microbial communities can pave the way for infections, can affect our ability to digest or breathe)
- External (physical environment: water and air quality, climate, altitude, exposure to virus and bacteria; lifestyle and behaviour: diet, physical activity, substance abuse; social factors: socioeconomic status, social relationships, access to services).
Explain the concept of development.
Egg and sperm combine into the zygote, which leads to 200-300 specialized cells types (some cells don’t have nucleus like the hemoglobin).
Some cells reproduce more easily than others. Degradation of cells lead to disorders.
Cells differ from which genes are active and which proteins are present. Genes are hard-coded through epigenetics.
We cannot revert specializations from cells. We want to allow the creation of pluripotent cells; this would allow to create every cell that we want.
Explain the concept of evolution.
Only 10% of genes are coded into proteins. Genes that do not code proteins have a regulatory role.
RNA believed to have been the genetical material of the first live on earth (can easily self-replicate, catalyse basic reactions and store heritable information).
Epigenetics modifications play a key role in regulating gene expression. They hard-code cellular differentiation during development. They are “soft inheritance” systems.
We evolve from other species, by changing regulatory genes, not protein coded genes.
What is cancer? Explain the difference between driver and passenger mutations. What is the current approach for cancer?
Cancer is the accumulation of mutations that could be either driver (that cause the disease) or passenger (that cause noise to the disease).
As cancer progresses, mutations tend to accumulate, and the cancer may become more aggressive.
Before, the approach for cancer was with coded genes; now the approach is the use of non-coded genes and epigenetics.
Talk a little bit about chemotherapy, radiotherapy, immunotherapy and neoantigen therapy.
- Chemotherapy. Does not distinguish between normal and cancerous cells.
Precision medicine can be used to estimate dosage and number of treatments. - Radiotherapy. Localized, but aggressive.
- Immunotherapy. Use the immune system to attack cancer.
- Neoantigen therapy. With the immune system, targeting proteins with passenger mutations. Not sufficient to look at genome.
What is epigenetics and how many types there are?
Epigenetics is the set of modifications to our genetic material that regulate gene transcription, determining our molecular phenotype.
- Histone modification (more than 30 modifications to histone known for changing gene expression).
- DNA methylation.
Epigenetic mechanisms are our main mechanism for adaptation to the environment.
What is DNA methylation?
Chemic, addiction of small methyl or hydroxymethyl group to cytosine (carried by DNMT enzymes), with preference for cytosines in C-G pair (CpG).
Does not alter the sequence, but affects the gene expression.
Methylation causes less transcription and with that genes are switched off.
What is histone modification?
DNA is coiled around histones (proteins). 2 groups of 4 histones come together to form octamer (it has a globular structure + tail of amino-acids).
Chemical changes to nucleosome affect transcription.
Acetylation, methylation, phosphorylation and ubiquitylation are the most well-understood types of histone modifications.
How do DNMT enzymes know which CpG pairs to methylate and which to ignore in methylation?
Triggered by binding long ncRNAs (that have complex regulatory networks).
Epigenetics is highly refered to a lot of healthcare topics. Refer some.
- Neurological disorders.
- Memory.
- Childhood neglect and abuse.
- Depression.
- Addiction.
- Aging.
- Inheritance.
- Nutrition.
