Pathology L08 Intro to Genetic Pathology 2 Flashcards
What is a gene?
DNA segment that contributes to phenotype/function. In the absence of a demonstrated function a gene may be characterised by a sequence, transcription or homology OR entire nucleic sequence that is necessary for the synthesis of a functional polypeptide or RNA
How big is the human genome?
~3000Mb
What percentage of the human genome is thought to be protein-encoding?
1-2%
What is the central dogma of genetics?
DNA is transcribed into RNA which is translated into protein
What are some examples of coded and non-coded regulation of expression?
Pseudogenes, Alternate transcriptional events, Alternate splicing events, RNA editing
Describe the concept of gene expression.
Every cell contains the complete genome, but in any given cell only some of the genes are producing mRNA. Some are always silent. Others produce mRNA at certain points in the life of a the cell or in response to particular conditions.
After mutation, what does the future cell function depend on?
Role of protein, level of redundancy, when and where it is expressed, whether some or no abnormal protein can be tolerated
What is recombination? Disjunction?
Recombination - due to crossing over during tetrad formation and is unique to meiosis and contributes to normal variation
Disjunction - separation of homologue pairs and chromatids during anaphase
What are 3 things that may occur when disjunction or recombination fail?
Nondisjunction at meiosis -> monosomy or trisomy
Unequal crossing over at meiosis -> large deletions or duplications
Abnormal chromosome structure in parent -> segregation at meiosis resulting in gains and losses of chromosomes
Why is knowing about the recombination/disjunction important for clinical use?
Knowing underlying mechanism of disease will aid in understanding why things occurred and if they will happen again
What is epigenetics? What mechanisms does it use to work? How is it influenced?
The study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence (change in phenotype without a change in genotype)
Mechanisms: DNA methylation, histone modification, Non-coding RNA (ncRNA)
Influenced by age, environment/lifestyle and disease state
Explain the process and impact of DNA methylation?
A cytosine in a CpG site can be methylated -> methyl group (-CH3) added - methyl groups added by methyltransferases and removed by hydroxylases
Associated with repressed gene expression -> methylation of promoters associated with no or low gene expression
Exact mechanism of action unknown
How does acetylation of histones work as an epigenetic mechanism?
Histone acetylation upregulates gene expression as it keeps the DNA in an open conformation, allowing TF to bind.
Histone hypoacetylation decreases gene expression
At which 2 points does non-coding RNA regulate gene expression?
Promotes mRNA degradation and inhibit translation AND alters chromatin configuration
What are the three main mechanisms of epigenetics?
DNA methylation, histone modification and non-coding RNA
