E3: Jenney Flashcards
Which neuropsychiatric disorders have the highest annual cost?
- Addictions
- Alzheimer and dementias
- Pain (with migraine)
- Head and spinal cord injuries
- Anxiety disorders
What is the overall heritability of head/SC injuries vs. Hungtington’s?
0.05 vs. 1.00
overall heritability of all neuropsych disorders is 0.39
What is dystonia?
Neurological movement disorder, sustained/repetitive twitching, muscle contraction, posture
T/F: Mutations have to be in protein-coding regions of genome to exert effects.
False
What are some examples of genetic mutations?
Single base changes, deletions, or insertions
Instability (expansion/shrinkage of long repeat regions)
Deletions, duplications, inversions, exchanges of large regions of chromosomes
What is Mendelian inheritance?
Monogenic traits (phenotypes) which obey the laws of segregation and independent assortment
How can Mendelian inheritance patterns be modified?
Newly arising mutations
Mosaicism
Somatic mutations
Epigenetic effects
What is non-Mendelian inheritance?
Changes in DNA methylation patterns regulating gene expression with ‘parent-of-origin’ effects
Changes in covalent modifications of histones
Mitochondrial inheritance
Uniparental disomy
What are some ways to determine the role of genetics in neuropsych disorders?
Family history Twin studies Case-control studies / candidate gene association studies Sibling pair analyses Complex segregation analyses Molecular techniques Neuroimaging
How can family history help determine the role of genetics?
Used for simple Mendelian (single gene) traits
What are complex segregation analyses used for?
To study familial aggregation of disease looking for linkage (essentially family history with clinical and/or molecular aspects)
What are some problems in measuring how the genotype maps to a phenotype?
Incomplete penetrance Multi-gene phenotypes Epistasis Epigenetic effects Spontaneous mutations
What are motor neuron diseases?
Progressive degenerative diseases in which death of the cell bodies of motor neurons is the primary process
What are spinal muscular atrophies?
A group of autosomal-recessive disorders characterized by progressive degeneration of the lower motor neurons and muscle weakness
What causes SMAs?
Progressive loss of anterior horn cells
What is the most common disease of motor neurons in newborns?
Spinal muscular atrophies
What is the most frequent genetic cause of death in infants and toddlers?
Gene SMN mutations
Gene SMN: Siblings of an affected _____ have the same risks as any autosomal recessive disorder.
proband
Wtf is a proband?
A person serving as the starting point for the genetic study of a family (used especially in medicine and psychiatry).
What is a potential treatment for SMN mutations?
It has been shown that inhibitors of histone deacetylases such as phenylbutyrate and valproic acid promote acetylation of histones, increasing expression levels of full-length SMN protein.
What is a key point in SMN diseases?
While disease first manifests as death of anterior horn neurons, it affects many other cell types.
Recent data shows what drug is effective for treating SMA?
Nusinersen
Yes, you will be injecting patients with ______.
siRNAs
Which disease is strongly correlated with oxidative stress?
Parkinson’s
Which Parkinson’s genes are autosomal dominant?
PARK1/PARK 4 –> synuclein protein
PARK 8
Which Parkinson’s genes are autosomal recessive?
PARK 2
PARK 6
PARK 7
PARK 9
What is SNCA?
alpha-Synuclein: protein in cytoplasm. Binds lipids, thought to help in maturation of presynaptic vesicles, negative co-regulator of neurotransmitter release
What can Lewy bodies contain?
Truncated, oxidized, phosphorylated, insoluble forms of SNCA
What is the most common cause of familial and sporadic Parkinsonism?
LRRK2 – Leucine-rich repeat kinase 2
What is involved in proteosomal degradation of proteins in Parkinson’s?
Park gene – Parkin: E3 type ubiquitin ligase
DJ-1 regulator/chaperone/sensor of oxidative stress
What is PINK1?
PETN-induced kinase / serine-threonine protein
Which enzyme in Parkinson’s is associated with lysosomes?
ATP13A2 neuronal ATPase
Which bacterial infection has been linked more and more to Parkinson’s?
H. pylori
What is ALD?
Adrenoleukodystrophy – rare X-linked disorder, build-up of cholesterol esters and saturated VLCFs in adrenal cells
What is Lorenzo’s oil?
A derivative of olive and rapeseed oils and the first agent to have demonstrated a therapeutic effect by halting the destruction, by the disease, of the myelin sheathing of the nervous system.
Which dietary oils should be limited to help treat ALD?
C26:0
What is 5MTHF deficiency?
Inborn error of metabolism. Leads to irreversible brain damage early in childhood.
Children with 5MTHF deficiency are being treated with excess _____ in diet.
Betaine
Which diseases are polyglutamine expanded CGG triplet repeat diseases?
HUNTINGTON’s
Spinal and bulbar muscular atrophy
SCA ataxias
_____ has potential to treat ‘gain of function’ mutations by removing the toxic protein at the level of mRNA
RNAi
What is the basis of a continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice with advancing age.
CYP genetics
