Clinical Lab Testing
Patterns of Inheritance
Cytogenetics
Genetic Testing
Neoplasia 1
Neoplasia 2
Proteins & Enzymes 1
Proteins & Enzymes 2
Receptors
Membrane Transport
CBL #2
CBL #3
100
What does the "SNOUT" mnemonic stand for, and what type of test does it apply to?
Sensitive test Negative rule OUT disease — applies to a sensitive test.
100
What is the difference between locus heterogeneity and allelic heterogeneity?
Locus heterogeneity = same disease caused by mutations in different genes
Allelic heterogeneity = same disease caused by different mutations at the same locus/gene
100
What is the difference between euploidy and aneuploidy?
Euploidy = exact multiples of the haploid set (23+23+23...)
Aneuploidy = gain or loss of individual chromosomes.
100
What are the 3 steps of PCR?
Denature, Anneal, Elongate.
100
Is a tumor that is well-differentiated and grows slowly more likely benign or malignant?
Benign
100
What effect explains increased glucose uptake by cancer cells, and what imaging technique is based on this?
The Warburg effect; PET scans (FDG-PET/CT).
100
What are the four levels of protein structure?
Primary - linear sequence of Amino Acids - peptide bonds
Secondary - local folding (alpha helices / beta sheets) - hydrogen bonds
Tertiary - 3D shape of one protein chain
Quaternary - Assembly of multiple protein subunits
100
Name the four catalytic strategies enzymes use.
Covalent catalysis,
General acid-base catalysis
Metal ion catalysis
Catalysis by approximation.
100
Name the four major types of cell-cell signaling.
Direct cell-cell signaling
Endocrine
Paracrine
Autocrine
100
Is the cell membrane hydrophobic or hydrophilic?
Both
Hydrophobic Tail Region
Hydrophilic Heads
100
Which gender is at higher risk for skin cancer, and which race is at highest risk?
Males
White individuals
100
This blood test measures how quickly red blood cells settle and is considered good for detecting chronic inflammation, as opposed to the test better suited for acute inflammation.
Erythrocyte sedimentation rate (ESR) / Sed rate
200
A CBC uses which type of blood specimen, while SPEP uses which type?
CBC uses whole blood; SPEP uses serum.
200
Define penetrance and variable expressivity. How are they different from each other?
Penetrance = how many people with a mutation show the phenotype
Variable expressivity = people with the same mutation can have different phenotypes
200
Name the three viable trisomies along with their associated chromosome numbers and syndrome names.
Chromosome 13 = Patau syndrome
Chromosome 18 = Edward's syndrome
Chromosome 21 = Down syndrome
200
Which type of blot measures DNA, and what mnemonic helps remember Southern/Northern/Western blots?
Southern blot measures DNA. Mnemonic: SNoW DRoP — Southern=DNA, Northern=RNA, Western=Protein.
200
What do tumor names ending in "-sarcoma" or "-carcinoma" indicate?
Malignant
200
What immune checkpoint protein-ligand relationship allows tumors to evade the immune system?
PD-L1 on tumor cells binds PD-1 on T cells, blunting cytotoxic T cell activity
200
What vitamin deficiency destabilizes collagen, and what disease results?
Vitamin C; scurvy.
200
Kinases add or remove a phosphate group? Phosphatases?
Kinases — add
Phosphatases — remove
200
In GPCR signaling, what do GEF and GAP stand for?
GEF — Guanine Exchange Factor
GAP — GTPase Activating Protein.
200
Does passive diffusion require proteins? Does facilitated diffusion?
Passive — no
Facilitated — Generally yes (Ionophore no)
200
Name one environmental factor and one hereditary factor that increase risk of skin tumorigenesis.
Environmental — higher altitude UV exposure (less atmosphere to travel through) or chemical exposure (e.g., fracking, coal/tar chemicals).
Hereditary — family history of skin cancer, or EGFR mutations (heritable prooncogenic gene mutations).
200
Unlike osteoarthritis, where pain worsens with movement, this is what happens to RA pain as a patient increases movement throughout the day.
It gets better (improves) with increased movement
300
What is the DeRitis ratio, and what does a value greater than 1 suggest?
DeRitis ratio = AST:ALT. It's usually <1, but a ratio >1 suggests alcohol use or cirrhosis.
300
In Prader-Willi syndrome, which parental allele is imprinted/silenced, and which allele is typically deleted? How does this compare to Angelman syndrome?
In Prader-Willi, the maternal allele is imprinted/silenced and the paternal allele is deleted. In Angelman, it's reversed — the paternal allele is imprinted/silenced and the maternal allele is deleted.
300
What is nondisjunction, and during what process does it occur?
Nondisjunction is the failure of a chromosome to disjoin (separate) during one of the two meiotic divisions.
300
What enzymes are used to fragment DNA in gel electrophoresis and RFLP analysis?
Restriction enzymes.
300
What is the difference between grade and stage of a cancer?
Grade = how "bad"/differentiated the tumor looks morphologically
Stage = how big the tumor is and how far it has spread
300
At what tumor size does a tumor typically require angiogenesis to continue growing?
About 1–2 mm.
300
Name the type of collagen associated with Osteogenesis Imperfecta, and the type associated with Ehlers-Danlos and Alport syndrome.
Type I — Osteogenesis Imperfecta
Type III and V - Ehlers-Danlos
Type IV — and Alport syndrome.
300
What are inactive forms of proteolytic enzymes called?
Zymogens (proenzymes)
300
Name four second messengers used in GPCR signaling.
cAMP, DAG, IP3, Ca2+ (or NO)
300
What is the difference between antiport, symport, and uniport?
Antiport — two molecules, opposite directions;
Symport — two molecules, same direction;
Uniport — one molecule, independent.
300
What is the key histologic difference between in situ squamous cell carcinoma (Bowen's disease) and invasive squamous cell carcinoma?
In situ SCC — chaotic squamous cell layer, but the basal cell layer is still clearly visible with no downward spread of squamous cells.
Invasive SCC — presence of keratin pearls (irregular layering of keratinocytes), downward spread of squamous cells, and disintegration of the basal cell layer.
300
This gene mutation, found in about 80% of RA cases, normally helps the immune system tell the difference between self and nonself.
HLA-DRB1
400
According to the error distribution data presented, what percentage range of total testing errors occur at the preanalytical level, and name three examples of preanalytical errors.
46–68% of errors occur at the preanalytical level.
- incorrect test ordered,
- patient identification error
- patient preparation error
- mislabeling of the test tube
- sample collection error
- incorrect handling of samples
- transport error
400
A father is affected with an X-linked dominant condition and a mother is unaffected. What proportion of his sons will be affected, and what proportion of his daughters will be affected?
100% of daughters affected (obligate), 0% of sons affected (no male-to-male transmission).
400
What is the difference between a reciprocal translocation and a Robertsonian translocation?
Reciprocal translocation = one part of a chromosome is exchanged with another
Robertsonian translocation = translocation of the long arms of two acrocentric chromosomes with loss of the short arms
400
In real-time PCR, what are the roles of the reporter and the quencher?
Reporter = fluorescent label; Quencher = prevents fluorescence until the gene is polymerized (cleaved off during amplification).
400
Tumor suppressor genes cause cancer when they are activated or inactivated?
Proto-oncogenes cause cancer when they are activated or inactivated?
Tumor suppressor genes cause cancer when inactivated
Proto-oncogenes cause cancer when activated.
400
In the RB tumor suppressor pathway, what happens to RB when it is hyperphosphorylated, and what transcription factor becomes overactivated as a result?
RB becomes hyperphosphorylated, releasing/overactivating E2F.
400
Compare hemoglobin and myoglobin: quaternary structure and relative O2 binding affinity for each.
Hemoglobin — tetrameric, lower affinity
Myoglobin — monomeric, higher affinity
400
What three amino acids form the catalytic triad in serine protease digestive enzymes?
Serine, histidine, aspartate
400
In receptor tyrosine kinase signaling, what happens to the receptor upon ligand binding, and on what residue does autophosphorylation occur?
Dimerization
Tyrosine residues.
400
What ion pump establishes and maintains the resting membrane potential, and how many Na+/K+ ions does it move (and in which directions)?
Na+/K+ ATPase; moves 3 Na+ out, 2 K+ in.
400
What is Mohs surgery?
Mohs surgery removes tissue by periphery, a little at a time, testing each layer to check for remaining cancerous tissue
400
This term describes the extra growth of inflamed tissue in the joint — made of proliferating synovial cells — that causes pain, swelling, and damage to bone and cartilage, and defines Stage 2 of RA progression.
Pannus
500
A blood sample sits too long before analysis. Explain what happens to glucose and lactate levels in the sample and why this occurs physiologically.
Glucose falls and lactate rises because RBCs continue metabolism (glycolysis) within the collection tube even after the sample is drawn.
500
Identify the inheritance pattern
X-linked Dominant.
Key distinguishing features: affected fathers pass to 100% of daughters but NOT sons, and there is no male-to-male transmission (this is what distinguishes it from Autosomal Dominant, since AD is transmitted through both M & F equally).
500
A patient has isodisomy of a chromosome. Explain what this means in terms of parental origin, and how it differs from heterodisomy.
Isodisomy = two copies of a chromosome from the SAME parent (uniparental disomy)
Heterodisomy = two different copies of a chromosome, which can be from the same parent (uniparental heterodisomy) or different parents (biparental heterodisomy)
500
A researcher wants to detect thousands of gene expression levels simultaneously using DNA hybridization with cDNA. What technique is this?
Microarray
500
Explain the 2-hit hypothesis for tumor suppressor genes, and name the inherited condition (and the DNA repair defect involved) associated with increased cancer risk mentioned on the slides.
The 2-hit hypothesis states that both alleles of a tumor suppressor gene must be inactivated (via two separate mutations/hits) for cancer to develop — the first hit may be inherited (susceptible carrier), the second is acquired.
Lynch syndrome (HNPCC) is an inherited defect in mismatch repair, causing increased cancer risk.
500
A cell deprived of nutrients enters an apoptosis pathway. Name this pathway and the initiator caspase activated.
The intrinsic pathway, activated via caspase 9 (triggered by stress signals like radiation, hypoxia, ER/metabolic stress, leading to BAX/BAK activation and cytochrome c release).
500
2,3-BPG stabilizes which hemoglobin state (T or R)? Does fetal hemoglobin have higher or lower affinity for 2,3-BPG compared to maternal, and how does this affect its O2 affinity?
T state.
Fetal Hb — lower affinity for 2,3-BPG → higher O2 affinity.
500
Name the enzyme that converts fibrinogen to fibrin,
the enzyme that resolves clots,
and the activator that converts plasminogen to plasmin.
Thrombin — fibrinogen→fibrin
Plasmin — resolves clots
tPA — activates plasminogen→plasmin.
500
In the Wnt pathway, what happens to beta-catenin when Wnt ligand is ABSENT vs. PRESENT? What does beta-catenin do once it enters the nucleus?
Absent — APC/destruction complex destroys beta-catenin.
Present — APC inhibited, beta-catenin survives.
In nucleus — acts as a transcription factor.
500
Name the disease associated with mutated CFTR?
What type of transporter, and how many ATP do they use?
CFTR — cystic fibrosis
ABC cassettes (primary active transporters); use 2 ATP.
500
UV radiation causes thymine dimers. What repair mechanism uses nuclease cleavage and helicase excision of the damaged oligonucleotide to fix this damage?
Nucleotide excision repair.
500
This drug class, which includes the medication infliximab, works by blocking a specific pro-inflammatory cytokine so that the inflammation cascade cannot be activated.
TNF inhibitor