genes epigenetics nutrition injury-toxicity infection immune dysfunction neoplasia what can make you...
Post on 21-Dec-2015
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Genes
Epigenetics
Nutrition
Injury-toxicity
Infection
Immune dysfunction
Neoplasia
What can make you
ill ?
Scurvy
Hemophilia
Prostate cancer
Crohn’s diseaseFracture
Tuberculosis
Angelman Syndrome
However, most diseases are multifactorial
Tuberculosis
Infectious agent
Quality of immune response
Genetic susceptibility
Nutritional condition
Lung cancer
Neoplasia
Toxicity
Genetic susceptibility
Quality of immune response
Some useful terms:
Genome:
Gene:
Alelle:
Haplotype:
All genetic information of an organism (stored as DNA)
DNA segment that goes from the transcription start siteto the transcription end site
“Version” or variant of a gene. Frequently refers to variants involving a single nucleotide
Version of a gene comprising several pointdifferences.
Promoter:
Replication:
Transcription:
Translation:
Epigenetics:
DNA region close (usually upstream) of a gene, that regulates its expression
Synthesis of an identical copy of a DNA molecule
Synthesis of an RNA molecule using a DNA moleculeas template.
Synthesis of a protein following the code given bya RNA molecule.
The study of changes in DNA that do not change thenucleotide sequence, but alter function and are heritable.
GeneGene
FunctionFunction
ProteinProteinRNA
StructureStructure
Fold
ing
Reg
ula
tion
By John Quackenbush
…CACGGTACCATCACACATCGACGCGGCGATGCTACGATCGCACAGCAGCGATCAGCGAGCACGAGCATCTATTACTATCGGCAGCATCGTACTACGATCTACACTCGCGCACAGCCTCGTACGATCGTAGCATCGATGCTAGCATGCTAGCTAGCTGCTGCTGACTGCTGCTAGCTAGCTAGCTAGCTAGCTAGCTGCGATGCATCATCGATCTAGCTATCGATCGGGATCGATGCACGATGCTAGCACGATCAATTACGATCGATGCGGCTATATAGCATGCATTATCTTCCGGCGATATGCGCGCATGCTAGCGCATGCTAGCATCGAGCTAGCATCGAGCGCGCATATCGACGGAGAGCGGCAGAGCGGAGAGCTCTCTATATTCTATACTCCTCTATTATTATATATCCTCGGGCGGCGCTCCTTCTTCAATCGAGGCGCTACTTCTGCCGGATTCGATTATATAATACCGGAGAGAGCTCTATACGAGCGGCCGATACGAGCAGCGAGCGAGGCGGCAGCGAGCGTATACTATTATAGCGCGATATCGAGCGAGCGACGAGCGAGCAGCGGAGCGTATTCTAGCGACGGAGCGACGAGCAGCGAGCGACGCCGAGCTATTTATCGGCGAATTCGAGCGCCGCGTATAGCTAGCGCGCGCGTCTCTAGAGCTATTCTTATCGGCGCGAGAGGCGCGAGGCGAGGGAGAGACTATACATGCGGATTACTATTCTATCGAGCGCAGCAGCGTATTACTAGCAGCGAGCACTAGCGGCAGCTAGCATGCAGCGCGATCTACTTACGAGGCGGACGGACGGACGGGCGATATATCGAGCGGAGCTACGATGCTCGTAGCTGGTACGAGCTAGCTAGCTAGCGGCGCATATATTACGCGCGGCGGCATATGCTAGACTGACTAGCTAGCGCGATCGACTAGCGACGCGGATCGAGCGCGGACGAGCGGCGAGCGGACGGGAGGATTCATAGGGATCACGATCTTGGAGCATTATATGCGAGCGAGCGATCGCGCTACGGAGTCGAGCGACGATCGATCGAGCAGCGAGCGTTCTCTAGCGGAGCGGGAG…
…CACGGTACCATCACACATCGACGCGGCGATGCTACGATCGCACAGCAGCGATCAGCGAGCACGAGCATCTATTACTATCGGCAGCATCGTACTACGATCTACACTCGCGCACAGCCTCGTACGATCGTAGCATCGATGCTAGCATGCTAGCTAGCTGCTGCTGACTGCTGCTAGCTAGCTAGCTAGCTAGCTAGCTGCGATGCATCATCGATCTAGCTATCGATCGGGATCGATGCACGATGCTAGCACGATCAATTACGATCGATGCGGCTATATAGCATGCATTATCTTCCGGCGATATGCGCGCATGCTAGCGCATGCTAGCATCGAGCTAGCATCGAGCGCGCATATCGACGGAGAGCGGCAGAGCGGAGAGCTCTCTATATTCTATACTCCTCTATTATTATATATCCTCGGGCGGCGCTCCTTCTTCAATCGAGGCGCTACTTCTGCCGGATTCGATTATATAATACCGGAGAGAGCTCTATACGAGCGGCCGATACGAGCAGCGAGCGAGGCGGCAGCGAGCGTATACTATTATAGCGCGATATCGAGCGAGCGACGAGCGAGCAGCGGAGCGTATTCTAGCGACGGAGCGACGAGCAGCGAGCGACGCCGAGCTATTTATCGGCGAATTCGAGCGCCGCGTATAGCTAGCGCGCGCGTCTCTAGAGCTATTCTTATCGGCGCGAGAGGCGCGAGGCGAGGGAGAGACTATACATGCGGATTACTATTCTATCGAGCGCAGCAGCGTATTACTAGCAGCGAGCACTAGCGGCAGCTAGCATGCAGCGCGATCTACTTACGAGGCGGACGGACGGACGGGCGACATATCGAGCGGAGCTACGATGCTCGTAGCTGGTACGAGCTAGCTAGCTAGCGGCGCATATATTACGCGCGGCGGCATATGCTAGACTGACTAGCTAGCGCGATCGACTAGCGACGCGGATCGAGCGCGGACGAGCGGCGAGCGGACGGGAGGATTCATAGGGATCACGATCTTGGAGCATTATATGCGAGCGAGCGATCGCGCTACGGAGTCGAGCGACGATCGATCGAGCAGCGAGCGTTCTCTAGCGGAGCGGGAG…
Difference of only one nucleotide in the DNA sequence
…… TT AA GG CC ……
…… TT GG GG CC ……
Example: Some people have in a given site an A, while others have a G. Each option is called an allele.
By John Quackenbush
- The set of alleles beared by an organism is called his genotype.
- For this SNP, there are three possible genotypes: AA, AG, or GG.
…… TT AA GG CC ……
…… TT GG GG CC ……
There are about 11 million SNPs in human populations
By John Quackenbush
Thrifty genotype: Genetic variation + selection
Good energy storers survive
…even though they change
looks
Their genes are still the same
And now they get A
LOT of energy
Food is scarce and sporadic
Thrifty genotype: Epigenetic imprinting in utero
Poor nutrition during fetal life
Body systems get tweaked (by epigenetic mechanisms) to make the most of little energy
Adult organism good at saving and storing energy
And now gets A LOT of energy
Inflammation as a clinical phenomenon
1st century AD: Cornelius Celsus (“De Medicina”)
“ Rubor et Tumor cum Calore et Dolore “
Traditionally associated withwounds and infection
A strong inflammatory response to environmental challenges providedan evolutionary advantage
Redness and swelling with heat and pain
Inflammation gone awry causes/aggravates disease
Atherosclerosis
Obesity
Inflammatory bowel disease
Blunt head trauma
Inflammation in the wall of arteries causes heart attacks/strokes
Inflammatory mediators from adipose tissue cause insulin resistance/diabetes
Targeting of normal intestinal cells by the immune system leads to diarrhea/malnutrition
Inflammation of the brain parenchyma may cause brainstem herniation and death
The neurotransmitter :The neurotransmitter :1. Is released in the synaptic cleft.2. Binds to its receptor 3. Is degraded enzymatically
An actual synapse
“d” = dendrite
“R” = axon
Which one is the postsynaptic neuron here?faculty.washington.edu/chudler/java/em.html
Many neurological diseases are associated with excess/deficit of a given neurotransmitter at some
synapsesParkinson’s disease
Alzheimer’s disease
Major depression
Deficit of dopamine at basal ganglia
Deficit of acetylcholine at cerebral cortex
Deficit of serotonin and norepinephrin atseveral key locations (ie. limbic system)
Schizophrenia Excess dopamine at sensory cortex
Ischemic stroke Vs Hemorragic strokeAtherosclerosis in arteries that feed the
cerebral circulation
In situ formation of a blood clot on Top of the atherosclerotic plaque
Cerebral artery
Direct obstruction
Carotid artery
Embolizationto the brain
Lack of oxygen in an area of the brainNeuronal death
Neurological deficit
Rupture of a blood vessel within the CNS:
Aneurism in a cerebral artery
Arterial-venous malformation
Bleeding from the meninges
Sub-arachnoideal hemorrage
Epidural hematoma
Subdural hematoma/Intraparenchymal hemorrageInflammatory reaction to the presence of blood
Mechanical pressure from blood in closed space