genes epigenetics nutrition injury-toxicity infection immune dysfunction neoplasia what can make you...

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Genes Epigenetics Nutrition Injury-toxicity Infection Immune dysfunction Neoplasia What can make you ill ? Scurvy Hemophilia Prostate cancer Crohn’s disease Fracture Tuberculosis Angelman Syndrome

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

Genes

Why do some tissues express certain proteins and not others?

Gene expression is regulated especially atthe level of transcription

DNA RNA

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

Two randomly selected persons differ on average in 0.09% of their

nucleotides.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

Regulation of gene expression

All somatic cells have the same 46 chromosomes

Why do some tissues produce some proteins while some others do not ?

The central dogma, again

Chromatin

The structure of chromatin

The acetylation of histones

LOOSENS chromatin

STIMULATES gene expression

DNA methylation

Happens at some “C” sites.

Methylation of DNA:

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

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 at the cellular level

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

Sequence of events during synaptic transmissionSequence of events during synaptic transmission

Sequence of events during synaptic transmissionSequence of events during synaptic transmission

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