First Aid 54-77 Flashcards
Promoter mutation results in
dramatically lower level of gene transcription
alpha-amanitin
toxin in death cap mushrooms
inhibits RNA Pol II
severe hepatotoxicity
MOA Rifampin
inhibits RNA Pol in prokaryotes
MOA Actinomycin D
inhibits RNA Pol in both prokaryotes and eukaryotes
What is the function of P bodies
in cytoplasm
for quality control
exonucleases, microRNAs, decapping enzymes
can store mRNA there for future use
Smith and U1 RNP, whose antibodies are associated with SLE and MCTD, respectively, function normally as
part of the spliceosome
An example of a condition thought to be due to an abnormal splicing variant
beta-thalassemia
What end of tRNA binds the aa?
3’ CCA
Can Carry Amino acids
Function of aminoacyl-tRNA snythetase
“matchmaker”
makes sure the right aa is being chosen
1 per aa
uses ATP to charge tRNA
A site
aminoacyl -tRNA binds to A site
rRNA ribozyme catalyzes peptide bond formation to add polypeptide to aa in A site
P site
ribosome advances 3 nucleotides toward 3’ end of mRNA, moving peptidyl tRNA to P site (translocation
P site accomodates growing peptide
E site
holds empty tRNA as it exits
Regulatory proteins that control cell cycle events, activate CDKs
cyclins
become cyclin-CDK complexes which phosphorylate other proteins to coordinate cell cycle progression
function of p21
induced by p53
inhibits CDKs –> hypophosphorylation (activation) of Rb
Active Rb binds and inactivated TF EF2 –> inhibition of G1–>S
Give two examples of stable cell lines, that can enter G1 from G0 if stimulated
Hepatocytes
Lymphocytes
Where does N-linked oligosaccharide addition to proteins occur?
RER
The golgi complex modifies N-oligosaccharides on:
asparagiNe
The golgi comples modifies O-oligosaccharides on
serine and threOnine
What does the mannose-6-phosphate tag mean?
Trafficking from golgi to lysosomes
Defect in I cell disease (aka mucolipidosis type II)
defect in N-acetylglucosaminyl-1-phosphotransferase
–> failure of golgi to phosphorylate mannose residues
–> proteins that should be degraded are instead secreted
coarse facial features, restriced joint movement, high plasma levels of lysosomal enzymes
COPI
vesicular trafficking protein
golgi–golgi
cis-golgi–RER
retrograde
COPI II
vesicular trafficking protein
ER–cis golgi
anterograde
Defects in the ubiquitin-proteasome pathway have been implicated in some cases of
Parkinson disease
Function of peroxisome
catabolism of very long chain FA (through beta-oxidation), branched chain FA, amino acids, ethanol
Actin and microvilli are made of
microfilaments
vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAPs), neurofilaments
all made of
intermediate filaments
Immunohistochemical stain for vimentin (IF) identifies
mesenchymal tissue
ie fibroblasts, endothelial cells, macrophages
sarcomas, RCC, endometrial carcinoma, meningioma
Desmin (IF) stains for
muscle
Immunohistochemical stain for epithelium
cytokeratin (IF)
“Microtubules Get Constructed Very Poorly”
Drugs that act on Microtubules Mebendazole (antihelminth) Griseofulvin (antifungal) Colchicine (antigout) Vincristine/Vinblastine (anticancer) Paclitaxel (anticancer)
Defect in primary ciliary dyskinesia
aka Kartagener syndrome
dynein arm defect –> immotile cilia
bronchiectasis, recurrent sinusitis, ectopic pregnancy, infertility
Where does ouabain bind?
K+ site (extracellular)
inhibits Na/K ATPase
Digoxin directly inhibits
Na/K ATPase –> indirect inhibition of the Na/Ca exchange –> Ca increased –> cardiac contractility increased
Type I collagen, where is it found besides bone?
skin tendon dentin fascia cornea late wound repair
The vitreous body contains what kind of collagen?
type II
Collagen type found in:
reticulin
skin, blood vessels, uterus, fetal tissue, granulation tissue
type III
defective in vascular type of Ehlers-Danlos (3-ED)
type IV collagen found where?
BM, basal lamina, lens
defective in Alport syndrome
targeted by autoantibodies in Goodpasture syndrome
Collagen is 1/3 made of
glycine
Gly-X-Y-Gly-X-Y…
Problems forming the triple helix in collagen synthesis (glycosylation step)
Osteogenesis imperfecta
Diseases with problems collagen cross-linking
Menkes disease
Ehlers-Danlos
Gene defects in COL1A1 and COL1A2
Osteogenesis imperfecta
most common type is AD with reduced production of normal type I collagen
X-linked recessive disease
impaired Copper absorption and transport
defective ATP7A gene
Menkes disease
reduced activity of lysyl oxidase
kinky, brittle hair, growth retardation, hypotonia
Complications seen in Ehlers-Danlos
organ rupture
berry and aortic aneurysms
joint dislocation
connections between vertebrae are called
ligamenta flava
Why use a Northern blot?
Useful for studying mRNA levels which reflect gene expression
Test that identifies DNA-binding proteins ie TFs using labeled oligonucleotide probes
Southwestern blot
How is a CD4 count performed?
Flow cytometry
Immunologic test to detect either specific antigen or antibody in a patient’s blood sample
ELISA
Test used for specific localization of genes and direct visualization of chromosomal anomalies at the molecular level, ie microdeletions, duplications, translocations
FISH
Phenotype varies among individuals with the same genotype
Variable expressivity
Not all individuals with a mutant genotype show the mutant phenotype
Incomplete penetrance
One gene contributes to multiple phenotypic effects
Pleiotropy ie PKU (light skin, intellectual disability, musty body odor)
A heterozygote produced a nonfunctional protein that inhibits the normal gene product from functioning
Dominant negative mutation
An example of mosaicism
McCune-Albright syndrome
defective G-protein signaling
unilateral cafe-au-lait spots, precocious puberty, polyostotic fibrous dysplasia, multiple endocrine abnormalities
Mutations at different loci can produce a similar phenotype
Locus heterogeneity
ie albinism
Different mutations at the same locus produce a similar phenotype
Allelic heterogeneity
ie beta-thalassemia
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
Heteroplasmy
An individual can inherit an AR disorder from one parent through
Uniparental disomy
Explain p^2 + 2pq + q^2 = 1
p^2 = frequency of homozygosity for allele p q^2 = frequency of homozygosity for allele q 2pq = frequency of heterozygotes p+q = 1
Using Hardy-Weinberg, the frequency of an X linked recessive disease in males and females is:
q = males q^2 = females
How does imprinting work in Prader-Willi syndrome?
Gene from mom silent, gene from dad is mutated or deleted
or
No genes from dad, both from mom maternally imprinted (uniparental disomy)
**opposite for Angelman syndrome, but both on chrom 15
In AD diseases, with one heterozygous parent, about how many children affected?
1/2
X-linked recessive means
Sons of heterozygous mothers have a 50% chance of being affected;
skips generations;
no male–>male inheritance possible
X-linked dominant means
transmitted through both parents
dad transmits to all daughters but no sons
mom transmits to half of her children
Alport syndrome fragile X syndrome Rett syndrome hypophosphatemic rickets all what inheritance?
X-linked (dominant)
X-linked
increased phosphate wasting in PCT
rickets-like presentation
hypophosphatemic rickets
Muscl biopsy showing ragged red fibers
MELAS syndrome - Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes
failure in oxidative phosphorylation
mitochondrial inheritance
Mutation in fibroblast growth factor receptor 3
Achondroplasia
Inhibits chondrocyte proliferation
most common cause of dwarfism
AD
PKD2
chromosome 4
second most common mutation in Autosomal dominant polycystic kidney disease
AD
5 letters on polyp, think
FAP
chrom 5
progresses to colon cancer if colon not resected
AD
Autosomal dominant disorder to blood vessels
Heredity hemorrhagic telangectasia aka Osler-Weber-Rendu recurrent episxtaxis skin discolorations AV malformations GI bleeds Hematuria
severe atherosclerotic disease early in life
corneal arcus
tendon xanthomas
mutation in or absence of:
LDL receptor
Familial hypercholesterolemia
AD
Inheritance of hereditary spherocytosis
AD
Caudate atrophy in HD (chrom 4) results in what changes to these chemicals:
dopamine
GABA
ACh
dopamine up
GABA down
ACh down
AD
SBLA cancer syndrome aka
Li Fraumeni syndrome
TP53 abnormalities
sarcoma, breast, leukemia, adrenal gland
AD
Fibrillin is the scaffold for
Elastin
chrom 15
Marfan syndrome
AD
MEN 2A and 2B are associated with the RET proto-oncogene whereas MEN 1 is associated with
MEN1 gene
AD
juvenile cataracts
meningiomas
ependymomas
what syndrome?
Neurofibromatosis type 2
also acoustic schwannomas
NF2 gene on chrom 22
AD
syndrome with optic gliomas and pheochromocytomas
Neurofibromatosis type 1 Lisch nodules cafe-au-lait spots cutaneous neurofibromas NF1 gene on chrom 17
What test screens newborns for CF?
Trypsinogen screening
What CF pattern is seen on CXR?
Reticulonodular pattern
How is infertility in men conferred in CF?
Absence of vas deferens
“Oblivious Females Will Often Give Her Boys Her x-Linked Disorders”
Ornithine transcarbamylase deficiency Fabry disease Wiskott-Aldrich syndrome Ocular albinism G6PD deficiency Hunter syndrome Bruton agammaglobulinemia Hemophilia A and B Lesch-Nyhan sndrome Duchenne (and Becker) MD
Pseudohypertrophy of calf muscles in MD due to
fibrofatty replacement of muscle
Function of dystrophin
Anchoring or muscle fibers
frameshift mutation most common
***non-frameshift –> Becker
AD
CTG trinucleotide repeat expansion in DMPK gene
symptoms?
Myotonic type 1 MD
cataracts, muscle wasting, frontal balding, testicular atrophy, arrhthmia
“My Tonia, My testicles, My Toupee, My Ticker”
Trinucleotide repeat results in hypermethylation of FMR1 gene –> gene inactivation
symptoms?
Fragile X syndrome
2nd most common genetic intellectual disability after Down syndrome
macroorchidism, long face, large jaw, large ears, MVP, autism
Trinucleotide expansion of CAG
Huntington disease
Trinucleotide expansion of CTG
Myotonic dystrophy
Trinucleotide expansion of GAA
Friederich ataxia (chrom 9)
gap between 1st two toes
duodenal atresia
Brushfield spots
Down syndrome
chrom 21 codes for APP
increased risk for ALL and AML
meiotic I nondisjunction most common cause
Ist trimester ultrasound shows increased nuchal translucency, hypoplastic nasal bone
Down syndrome
PAPP-A down
free beta HCG up
Second trimester quad screen shows increased inhibin A, decreased estriol
Down syndrome
First trimester shows low PAPP-A and beta-HCG
Both Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13)
cleft lip/palate rocker bottom feet holoprosenecephaly congenital HD cutis aplasia micropthalmia microcephaly
Patau syndrome
trisomy 13
rocker bottom feet prominent occiput clenched hands and overlapping fingers congenital heart disease rocker bottom feet small jaw (micrognathia)
Edwards syndrome
trisomy 18
Mineral oil intake can cause
fat soluble vitamin deficiencies
Pantothenic Acid, used in the body as
comes from
Vitamin B5
CoA
Biotin, aka
Vitamin B7
Folate, aka
Vitamin B9
stored in liver for 3-4 months
Pseudotumor cerebri - vitamin cause
Vitamin A excess
Bitot spots on conjunctiva (white plaques)
Immunosuppression
Vitamin A deficiency
How to diagnose Beriberi
increase in RBC transketolase (HMP Shunt) activity following B1 administration
Pyruvate dehydrogenase (link between glycolysis and TCA); alpha-ketoglutarate dehydrogenase (TCA); Transketolase (HMP Shunt); Branched chain ketoacid dehydrogenase All require:
TPP Cofactor From thiamine (B1)
Confusion
Ophthalmoplegia
Ataxia
damage to what part of the brain?
Common triad of Wernicke-Korsakoff
mamillary bodies, medial dorsal nucleus of thalamus
