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Variation in somatic mutation accumulation and its underlying causes? -…
Variation in somatic mutation accumulation and its underlying causes?
Keywords
Accumulation
Variation
Underlying causes
Somatic Mutation
Mitochondrial??
Nuclear
Passed onto progeny of mutated cell
Not in germ cells/reproductive
Change to DNA
Mutagens
Detection methods
Variation
Tissues
And mutation rates in tissues
Tolerances for mutations
Countries/Regions
Societal/cultural
Generally a geographical factor
Sun
Pollution levels
Degree of mutation
Type of mutations
In different diseases
Over time
But maybe need to be critical of previous techniques/accuracy with them?
Also rate element
Time of life?
More variation at different stages?
Is there a confounding variable
Gender
Underlying physiological differences??
In different species
Any organisms with mechanisms resulting in significantly lower mutation levels
Mouse
Elephant
P53
Naked mole rat
Also difference in causes?
And therefore targets?
Modifiers
Tissues
General mutation rate variability
And the cause of this?
Part of the genome
Does the cause of the mutation affect where the somatic mutation is targeted to or where it accumulates?
Are Certain types easier to fix or less of an issue?
Underlying causes
In mitosis/cell cycle processes??
CIP2A??
Environmental
Food
Drugs..?
Stress
Inc. cortisol lv
Stress induced mutagenesis
Trauma
E.g. transplanted tissues??
Carcinogens?
Age
And factors/causes related
Diseases
Viruses
Immune system
Common causes also underlying/present in disease
On a more technical level???
E.G.
ROS
Crossing over?
Double stranded breaks
Then link to environmental??
Link them to the different variations-> are some methods/mechanisms more commonly associated with different variation patterns
e.g. mechanisms
Born with or develop?
Random
Broader scope/context
Evolution
Phylogenetics
Disease
Cancer
Implications
Why is this question even important
How can this/answers to this question be used to solve other problem
Types of somatic mutation
To epigenetic mechanisms
Can this affect the rate of accumulation
Can this result in more widespread accumulation or just consequences?
Relating to cancer mechanisms
Location (e.g in genome)
Introns
Exons
Regulatory sequences
RNA
mRNA??
DO THESE COUNT AS SOMATIC MUTATIONS?
Deletions
Insertions
Translocations
Inversions
Point mutations
Missense
Non-sense
Silent
Frame shifts
Duplication
Evolution roots as well??
Of chromosomes
Somatic
In cells that cannot be inherited
Genome stability
Vs, chromosomal stability
Substitution
Accumulation
In one place?
In one tissue
Overall in an organism
Does the type affect toxicity or tolerability
Over a time frame
Part of the genome
Are there fragile sites?
Are some regions less tolerable
In relation to immune system?
Patterns in disease
Do different cancers show different accumulation patterns?
Is there a threshold for disease?
Are there weightings of the accumulation
If in certain places then lower threshold before disease etc.?
Tissue
Introns vs exons
Regulators/regulatory regions vs genes coding proteins
RATE
Can somatic mutation accumulation still lead to evolution or only accumulation in the germ line?
Of beneficial mutations vs no change/deleterious/harmful
Evolution states of humans? Are we still able to have advantageous mutations or less so vs. animals
Can this play a factor on the tolerable mutation rates of species?
Also conditions of society, less natural selection
Can also comment on ethics of eugenics?
Time in life, e.g. before born in development vs later and if e.g. before born is this more likely to be a miscarriage ? vs develop into issues after birth??