Random Flashcards
You are evaluating a 4 year-old girl referred from a nutritionist for severe obesity. The past medical history is notable for decreased fetal movements, severe hypotonia for the first year of life, strabismus, and mild intellectual disability. At age three-years she began to rapidly gain weight and is now obsessed with food to the point that her parents have to carefully control food in the home. Which of the following tests has the best chance of confirming the likely diagnosis?
A. Growth hormone levels B. Methylation studies of chromosome 15q11-q13
C. High resolution chromosome analysis in her father
D. Sequencing of the UBE3A gene E. FISH deletion testing for PRader Willi/Angelman Syndrome
B. Methylation studies of chromosome 15q11-q13
A 5-year-old girl presents with classic Duchenne Muscular Dystrophy, an X-linked recessive disorder. Which of the following explanations could best explain this unsual occurrence?
A. An Xp chromosomal deletion that includes the DYSTROPHIN gene (the gene mutated in Duchenne Muscular Dystrophy)
B. An unbalanced X-autosomal chromosomal translocation that transects the DYSTROPHIN gene.
C. X linked testicular feminization
D. Autosomal translocation of SRY
C. X linked testicular feminization
A pregnant woman and her husband are referred for genetic counseling regarding their risk of having a second child with Duchenne Muscular Dystrophy. There is no history of his DMD disease in her family. What is the best estimate of their risk
that this fetus will have DMD?
A. 50% B. 33% C. 25% D. 17%
D. 17%
Which of the following best describes the frequency of occurrence of a medical problem in Down Syndrome?
A. Seizures in 25%
B. Thyroid disease in 25% C. Webbed neck in 25%
D. Autism in 50%
E. Horseshoe kidneys in 50% F. Structural GI tract defects in 50%
B. Thyroid disease in 25%
Which of the following approaches have been highly successful when applied to discovery of genes involved in susceptibility to common “complex” diseases such as type 1 diabetes, asthma, coronary artery disease, and many others?
A. Candidate gene DNA sequencing analysis
B. Candidate gene association studies
C. Genomewide genetic linkage studies
D. Genomewide association studies
E. All of the above
Genomewide association studies
A man is affected with an X linked dominant disorder which has a penetrance of 60%. His wife is homozygous normal at this locus. What is the probability that his first daughter will be affected?
A. 25% B. 40% C. 50% D. 60% E. 100%
D
An African American couple comes to the clinic for counseling because the husband’s brother is affected with sickle cell anemia. Neither the husband nor wife is are anemic. The population carrier rate for heterozygotes in the African American community is approximately 1 in 12. What is the risk that this couple will have a child with sickle cell anemia
1/72
Common methylation on DNA
5- methylcytosine
if 5 methylcytosine is deaminated….
Thymine
deamination of cytosine….
uracil
Origin of replication usually rich in
A-T repeats
Origin binding proteins in eukaryotes and prokaryotes
E- ORC
P- DNAA
Helicases in P and E
E- MCM
P- DnaB
SSBPs in P and E
E- RPA
P- SSB
Common alkylation of DNA
0-6 methylguanine
O6 methylguanin->
A
Enzymes that fix 06 methylguanine
methyltransferase
CTD of Pol ___ is phosphorylated by ____ subunit of ____
II
CDK7
TFIIH
How far is the TATA box from start site?
30 bp upstream
alpha amantin is a ____ inhibitor of RNA pol
Non competitive
Aspirin inhibits ___
degradation of IKB
Strong helix formers
Alanine and leucine
Helix breakers
Proline and glycine
Prions are rich in ____
beta sheets
____ read sequencers are useful for linking contiguous polymorphisms on the same haplotype
Long-read sequencers
52 BP1 ->
NHEJ
BRCA 1 ->
HR
HR depends on the presence of
Sister chromatids
Misregulated HR can lead to
Loss of heterozygosity
Enzyme that clears out beta amyloid
APOE
variation of APOE that is not very good at clearing out beta amyloid
apo 4
Competitive inhibitor effect on lineweaver burke plot
changes slope
Noncompetitive inhibitor effect on lineweaver burke plot
Changes y intercept
Percentage of genes in human genome that are imprinted
PKU defects
-Phenylalanine Hydroxylase defect (98%)
Catalyzes conversion of Phe Tyr
-PAH cofactor BH4 defect (1-2%)
-Defect in BH4 synthesis and recycling
-BH4 important in monoamine neurotransmitter synthesis
Sickle cell anemia is autosomal ___
Recessive
Alpha thal trait common in Africa, Mediterranean and Asia
alpha thal 2
a-/a-
HbH
(a-/–)
alpha thal trait common in SE Asia
alpha thal 1
–
Achondroplasia mutation
FGFR3
gain of function
Inheritance of Achondroplasia
AD
Inheritance of tuberous sclerosis
AD
Inheritance of osteogenesis Imperfecta
AD
Inheritance of Marfan
AD
Mutation of Marfan
FBN1
Huntington inheritance
AD
Paternal transmission bias Huntington
maternal- later onset
paternal- early onset
Hemophilia A inheritance
XR
Duchene muscular dystrophy inheritance
XR
HNPP
Deletion of PMP22
Charcot-Marie Tooth
duplication of PMP22
Autosomal dominant
Fabry occurs with a deficiency of
alpha-galactosidase A
Limited insertion size of retroviral gene therapy
7-8 KB
Achondroplasia nucleotide mutation
Gly380Arg
Extraintestinal manifestation IBD
Erythema nodosum
Anal fistulas Crohn’s vs. Ulcerative Colitis
common in Crohn’s
rare in UC
Insulin release from beta cell
- glucose enters through GLUT2 transporter
- glycolysis, increasing intracellular atp/adp ratio
- close atp sensitive potassium channel
- opens voltage gated calcium channel
- exocytosis of insulin
H/K exchanger
nonexistent
3 ways Na/Cl absorption into blood
- Na, Cl, and water leak in on apical side
- Na, Cl, and water leak through shunt pathway
- Na/2Cl/K cotransporter on apical side
Role of Na/K pump in action potential
Restores concentrations of Na and K
First stage of MS
inflammation
Later stage of MS
Neurodegeneration
Consequences of MS (2)
- decreased speed of conduction in nerves
- harder to depolarize due to constant leak of K out of cell (hyperpolarization)
Na channel blockers used in treatment of MS
phenytoin, flecainidine
K channel blockers in treatment of MS
Dalfampridine
Specific transporter of RanGDP into nucleus
NFT2
Karyopherin for mRNA and rRNA
NXF1/NXT1
Size cut off for nuclear import/export
20-30 KD
ER resident sequence
KDEL
Lysosome signal sequence
KFERQ (chaperone mediated autophagy)
mannose 6 phosphate
Function of N linked glycosylation
- keep proteins from aggregating
- monitor unfolded
Enzymes used in ubiquination
E1, E2, and E3
Alpha subunit of proteosome
Regulate substrate entry into death chamber
Beta subunit of proteosome
Actual clipping of subunits
Autophagy is induced by
nutrient starvation
Vesicle nucleation macroautophagy
activate a PI3K complex
CytC-> ____ -> _____ -> ______
Apaf-1-> caspase 9 -> caspase 3
Structure of microtubule
alpha and beta heterodimer
Functions of bones
- ca homeostasis
- protect hematopoetic tissue
Function of hyaline cartilage (4)
- Allows metabolites to readily diffuse through tissue
- Promotes resiliency to compression forces during joint movement
- Allows growth of chondrocytes and matrix from within the matrix
- During growth can calcify and attract cells that initiate bone formation
Location of osteoprogenitor cells
periosteal and endosteal surfaces
location of osteoblast
line inner layers of peiosteal and endosteal surfaces
parathyroid hormone
calcium liberation
calcitonin
calcium uptake in bone
ALK fuses with
EML4
Diapedesis
leukocytes crossing vessel walls (post capillary venules)
Defect in one-way flap valves in veins
varicose veins
How blood flow is regulated in capillary beds
- Arterio-venous shunts and metaarterioles
2. one red blood cell can fit in its diameter
Majority of mutations in HCM are ____
Missense
Muscle cell phenotype HCM (4)
- Cardiomyocyte and cardiac hypertrophy
- Myocyte disarray
- Fibrosis
- Dysplastic intramyocardial arterioles
Treatment of MH
IV dantrolene
