Final Flashcards
Euchromatin
Loosely coiled, genes expressed
Heterochromatin
tightly coiled, genes not expressed
Prader Willi Syndrome and Symptoms
- rare neuro developmental disorder
- symptoms; rapid weight gain, obesity, delayed developmental motor skills; reduced muscle tone, infertility due to underdeveloped sex organs
- early death by age 30 from obesity and related complications
Prader Willi Syndrome genetic bases
- loss of genes located at 15q11-q13
- loss of functional paternal SNORD116
- SNORD116 paternally expressed, maternally imprinted
Angelman Syndrome Symptoms
-neurodegenerative mental retardation, awkward gait, tremors, seizures, frequent uncontrolled outbursts or laughter and happy disposition
Angelman Syndrome genetic basis
- Mutation; loss of genes located at 15q11-q13
- loss of UBE3A and ATP10A expression
- paternally imprinted, maternally expressed
UBE3A codes for…
ubiquitin-protein ligase E3A
XIST gene is responsible for…
The silencing of one X chromosome
Characteristics of Inactivated X Chromosome
- highly condensed chromatin(Barr Body)
- nuclear envelope association
- XSIT RNA production
Multiple Sclerosis and Symptoms
- autoimmune disease targeting myelin sheath of CNS
- Symptoms; depend on location of affected nerves; numbness or weakness in one or more limbs, partial or complete loss of vision, fatigue, dizziness
True or False; multiple sclerosis is 2/3 times more likely in women than in men?
True
Multiple Sclerosis Treatments
- Interferon Beta(cytokine); leads to reduction in disease activity, does not reverse damage
- Glatiramer; random tetramer of 4 amino acids in myelin basic protein, act as decoy, diverting autoimmune response away from myelin
- Cortico Steroids; reduce inflammation
Alzheimer’s Disease(AD) and Symptoms
- Severe impairment or loss of intellectual capacity and personality integration, due to loss of or damage to neurons in the brain
- Symptoms; inability to create new memories and loss of short term memory, no accurate sense of time, lack of speech
- death a result of respiratory failure
Genomic Imprinting
DNA methylation of Cytosine at CpG island is principle means of imprinting
Features of AD
- loss of synapses and neurons within certain areas of brain
- senile plaques accumulate outside of neurons in brain
- aggregations of NFTs within cell body and dendrites in the brain
Synaptic Pruning happens in what disease?
AD, decreased synapses
amyloid beta protein derived from what protein?
Amyloid precursor protein(APP)
What two enzymes cut APP and what two proteins are generated?
Enzymes; beta-secretase and y-secretase
Proteins generated; Amyloid-beta40 and Amyloid-beta42
MAPT gene encodes what protein?
Tau protein
Function of Tau protein?
helps to maintain stability of microtubules which are important for vesicle transport up and down axons
What 3 gene mutations represent 50% of familial EOAD?
APP, PS1, and PS2
Presenilin Mutations
- leads to the increase in the ration of amyloid beta42 produced compared to amyloid beta40
- amyloid beta42 more likely to aggregate to form plaques in the brain than amyloid beta 40
Genetic risk factors of LOAD
-ApoE4; accounts for 10-20% of LOAD risk
Amyloid Hyposthesis
-amyloid beta proteotoxic stress triggers hyperphosphorlation and aggregation of microtubule associated protein tau, leading to neurofibrillary tangles(NFTs) in AD
Ligand for DR6 signaling that promotes cell death?
N-APP binds to DR6 to trigger degeneration through caspase 6 in axons and caspase 3 in cell bodies
-AD
Parkinsons Disease(PD) and Symptoms
- 2nd most common neurodegenerative disease
- PD symptoms; tremors, rigidity, difficulty walking, talking
Changes in the PD brain
- diminished Substantia Nigra
- dopaminergic neurons in nigro-striatial pathway degenerate for unknown reasons
What do striatal neurons release?
Dopamine to the striatum
Causes of PD
-present in sporadic fashion
-PARK 1 and PARK 8; alpha-synuclein is inherently prone to misfold and to aggregate, which is major component of Lewy body
PARK 2; Parkin, impaired protein degradation
PARK 6; PINK 1, a deficiency in this protein leads to shortening, swelling, and fragmentation of mitochondria
PD Treatment
-Levadopa; precursor of dopamine
Carbidopa; inhibitor of dopamine decarboxylase; important for producing dopamine from Levadopa; Carbidopa delays conversion of levadopa into dopamine until it reaches brain
Huntington Disease(HD)
- localized in 4p16.3
- huntington gene has uninterrupted stretch of CAG/GTC repeats in the first exon
- HD patients have 40 or more repeats
- CAG repeats in DNA are inherently unstable
How does CAG repeat expansion lead to neurodengeneration
- misfolding of expanded polyglutamine tracts
- aggregation of nuclear inclusions
HD symptoms
-lose function of body
Transmissible Spongiform Encephalopathies(TSE)
- progessive neurodegenerative diorders that affect humans and animals; caused by Prions
- produces spongiform changes in the brain
Spongiform changes in brain due to Prions
-brain vaculolation, astrogliosis, neuornal apoptosis, accumulation of misfolded plaques
What is it that CAG/GTC repeats greater than 40 are inherently unstable?
1) unequal recombination
2) replication slippage
