Epigenetics Flashcards
Definition of epigenetics
Study of heritable changes in gene function that occur without a change in DNA base sequence
Definition of imprinted genes
Genes that are only expressed from either the maternal/paternal allele
Definition of parthenogenote
Both sets of nuclear material in an egg cell is from females
Definitions of androgenote
Both sets of nuclear material in an egg cell is from males
Definition of uniparental disomy
2 copies of a chromosome come from the same parent
Definition of continuous gene syndromes
Clinical phenotype caused by a deletion/duplication of many genes in close proximity
Describe the functions and properties of epigenetics
- Stable in cell division in somatic cells
- Markers reset in germ cells and early embryos
- Pluripotent cells <=epigenetics=> differentiated cells
- Imprinting
- X inactivation
- Control of transposons
What are the pros and cons of transposons
Needed for variation
If inserted into genes => can be harmful
What are the 3 genetic factors that contribute to disease
Genetics
Phenotypes
Epigenetics
Describe the epigenetic mechanism
Interact with transcription factors to regulate gene expression patterns
Underly embryonic development, differentiation and identity
Describe the properties and function of CpG dinucleotides
- what is a CpG dinucleotide
- how does it contribute to epigenetics
- where are they found
5’ Cytosine + phosphodiester bond + Guanine 3’
Methylation of cytosine => repression of gene expression
Often found in CpG dinucleotides
- unmethylated at promotors => allow for transcription
- methylated promoters in germline somatic cells => differentiation
CpG is methylated in the rest of the genome and not common compared to other nucleotides
In development, move between unmethylated <=> methylated in gene bodies
Can be found within gene sequences (iGpG)
Describe how histone proteins are modified
Chemical tags bind to histone proteins (arginine, lysine)
tags indicate whether gene is expressed/not expressed
Describe the 3 outcomes of genomic imprinting in reproduction
- biparental
- parthenogenote
- androgenote
Each gamete has the genes but different genes are expressed
Fertilised biparental
- viable embryo
- normal sized placenta
Parthogenote
-large embryo
-small placenta
=>ovarian teratoma as a result of hyperdifferentiation
Androgenote
- small embryo
- huge placenta
- hydatidiform mole forms as a result of trophoblastic hyperplasia
Describe uniparental disomies in imprinting disorders
-what are the associated symptoms generally
2 copies of a chromosome come from the same parent
generally associated with
- growth failure
- dwarfism
- neonatal diabetes
Describe Angelman syndrome
- who and what is inherited
- cause
- symptoms
Deletion/mutation (imprinting/genetic) transmitted from mother but received from father which is silent
Results from deleted/mutated maternally expressed genes
Cheerful, mental retardation
UPD more common due to higher rates of maternal non disjunction
Describe Prader Willi syndrome
- who and what is inherited
- cause
- symptoms
Deletion/mutation (imprinting) transmitted from father but received from mother which is silent
Results from deletion/imprinting mutated paternally expressed genes
Central obesity, always hungry
What is a potential treatment for Angelman Syndrome
No cure but activating the silenced allele => ameliorated associated symptoms
Describe the cause of Beckwith-Weidmann
-what can lead to an increased incidence
Deregulation of inherited genes from epimutations
Increased incidence in IVF
Describe the cause of Silver Russell
Maternal UPD instead of 1 chromosome from each parent
Describe the cause of Transient Neonatal Diabetes Mellitus
Genetic mutation=> epimutation
-Affects maintenance of imprinted DNA methylation in development
Describe the 3 epigenetic gene players and examples
- writers
- readers
- erasers
Where are the genes that code for these players
What happens when mutations occur in these regions
Writers
- introduce chemical modifications onto DNA and histone
- histone methyl and acetyltransferase
readers
- identify and interpret modifications
- bromo and chromodomains
Erasers
- remove chemical tags
- histone demethyl and deacetylases
All coded for by genes in DNA
Any mutations in these regions => different pathologies, can be Mendelian
Describe the relationship between twins and epigenetics
How does this arise
Increased MZ disconcordance for common diseases due to environmental/epigenetics
- Identical DNA sequences
- Differences in intrauterine and postnatal environments
What is the ENCODE project
-what does it aim to do
Aims to catalogue regulatory elements that affect epigenomes
-study epigenomic signatures of cells grown in culture
Linked epigenomic data to corresponding genetic info => reference epigenome
-representation of how epigenomic elements regulate gene expression in human body
Describe the outcomes of ENCODE
identify
- non traditional disease causing mutations
- long range enhancer mutations and mutations in gene deserts from GWAS
- inform on disease mechanisms => potential treatment modalities
Describe the link between cancer and epigenetics
Hypomethylation/loss of imprinting => tumour formation
Epigenetic mechanisms change accessibility of chromatin to transcriptional regulation locally/globally via DNA/nucleosome arrangement modifications
Epigenetic gene regulation collaborates with genetic alterations => cancer
What are the 3 classifications of epigenetic modifiers and their effects
DNA modifications
Histone modification
Chromatin modelling
Contributes to all stages of cancer
+50% of cancers involve chromatin organisation
Melanoma = 92% affected have 1+ EM mutation
What are the potential targets in cancer therapy
What are examples of drugs
Methylation is the only flexible genomic parameter that can alter genome function under environmental influence
Genomes of many cancers are hypermethylated => silence regulatory genes (tumour suppressors)
-demethylating drugs (azacytidine, decitabine)
Histone deacetylase inhibitors (HDAC)
-combination of 5AzaC + HDAC as epigenetic factors work together
Histone methyltransferases (EH22) have antitumour effects
