Public Health + Genetics + Photocarcinogenesis Flashcards
Define illness behaviour
Illness behaviour = “the ways in which given symptoms may be differentially perceived, evaluated, acted upon (or not acted upon) by different kinds of person.”
What is the difference between illness and disease?
Disease is a pathological condition of the body:
- Objective & demonstrable
- Fits with the “body as machine” model
- Can be measured and quantified
Illness is the experience of discomfort and suffering:
- Subjective
- Depends on the individual concerned, their psychological & social situation, culture & belief
- Hard to measure and quantify
What is the difference between sensation and perception?
Sensation refers to the ‘raw data’ that impacts on the sense organs
Perception provides meaning from this raw data
What is Gestalt psychology?
Gestalt psychology - the human eye sees objects in their entirety before perceiving their individual parts; the whole is greater than the sum of its parts.
Infantile seizures _ ash leaf macule = ?
Tuberous sclerosis
Tuberous sclerosis
- Common clinical features?
- Type of inheritance
- Investigation for skin?
- Infantile seizures
- Ash-leaf macule (depigmented macule)
- Periungual fibromas
- Facial angiofibromas
- Hamartomas (angiomyolipomas) - heart, lung, kidneys
- Bone cysts
- Shagreen patches
- Enamel pitting
Autosomal dominant
Woods lamp
Give some genetic features of tuberous sclerosis
Autosomal dominant
Disease seen in all generations
50% risk of affected child if parent is affected
Disease severity can be variable (Variable expressivity)
Individuals with mutation may not show disease (Variable penetrance)
May be a multi-systemic disease (depends on what gene does)
Males and females equally likely to be affected
Tuberous sclerosis shows genetic heterogeneity.
What does this mean?
The phenotype can be produced by different genetic mutations - in this case it can be in two different genes which are even on different chromosomes- TSC1, TSC2
Widespread blistering and loss of skin 24h after birth = ?
Epidermolysis bullosa
Epidermolysis bullosa
- What pattern of inheritance?
- Severity?
Very diverse genetic route - dominant, recessive, new mutation or acquired
Variable severity – blistering at birth doesn’t determine prognosis
What are the three main types of epidermolysis bullosa?
What is the difference between them?
Different mutations lead to cleavage in different areas of skin:
- Simplex - epidermis
- Junctional - DEJ
- Dystrophic - dermis
Which condition can mimic epidermolysis bullosa?
EB aquisita is a rare autoimmune condition – autoantibodies attack collagen 17 -> mimicks mutation
Different mutations in genes cause disease in different ways. Define the following: - Haploinsufficiency - Dominant negative - Gain of function - Complete loss of protein
Haploinsufficiency = only one copy of working - reduced protein production
Dominant negative = expression of abnormal protein interferes with normal protein
Gain of function = mutant protein gains a new function, affecting cell processes
Complete loss of protein = autosomal recessive - 2 faulty copies of gene produce no protein
14 year old boy presents with multiple asymptomatic coffee coloured flat marks which have been appearing over the last few years
Clinical sign?
Diagnosis?
Café au lait macules
>5 suggests genetic disease
Neurofibromatosis type I
What are the two main clinical features in neurofibromatosis type I?
What are some other features?
Cafe-au lait macules Neurofibromas (soft neural tumours) - Plexiform neuroma - diffuse - Axillary or inguinal freckling - Optic glioma - 2 or more Lisch nodules - A distinctive bony lesion
What are Lisch nodules and which disease are they characteristic of?
Nodules on the retina which usually develop in the 2nd or 3rd decade
Neurofibromatosis type I
Baby develops red, roughened patches of skin at 2 weeks of age
At 9 months of age, the child’s skin is itchy & broken; sleep is disturbed because of scratching
Diagnosis = ?
Atopic eczema
What is the function of Filaggrin?
Name two associated diseases
Filaggrin is a skni barrier gene
FILament AGGregating proteIN
1. Ichthyosis vulgaris
2. Atopic eczema
What is clonal evolution?
What happens when a cell population becomes genetically unstable?
When a series of mutations accumulate in successive generations
Multiple parallel clonal expansions occur
Give some hallmarks of cancer cells
- Sustaining proliferative signalling
- Evading growth suppressors
- Activating invasion and metastases
- Enabling replicative immortality
- Resisting cell death
- Inducing angiogenesis – to provide nutrients and growth factors to sustain the tumour population
- Deregulating cellular genetics – cell has to be able to reprogramme metabolism of cell in order for it to have increased metabolism
- Avoid immune destruction
What is an oncogene?
An over-active form of a gene that positively regulates cell division. Drives tumour formation when activity or copy number is increased (accelerator) e.g. Ras, Raf, growth factor receptors.
What is a proto-oncogene?
The normal, not yet mutated, form of an oncogene.
What is a tumour suppressor gene?
Inactive or non-functional form of a gene that negatively regulates cell division, i.e. preventing a tumour from developing. In tumours there genes are faulty. Prevents the formation of a tumour when functioning normally (brake) e.g. Rb, TP53.
When is p53 activated?
What does it then do?
What does this allow?
P53 is normally activated in response to DNA damage – becomes activated, binds to DNA, activates cell cycle inhibitors which halt the cell cycle.
It buys time for the cell to repair the DNA and also triggers cell death by apoptosis.
If mutated, p53 is no longer able to bind to DNA and so cell cycle progresses even in the presence of damaged DNA.
