Comprehensive Study Notes: DNA, Chromatin, Replication, Transcription/Translation, Cell Cycle, ANS, Embryology, Cytogenetics, Metabolic Disorders, Pharmacology
DNA Structure and Nuclear Organization
Nucleolus: inside the nucleoplasm, the site of rRNA synthesis; rRNA combines with proteins to form ribosomes.
Ribosomal proteins are first synthesized in the cytoplasm by existing ribosomes.
Proteins imported into the nucleolus, where they join with newly made rRNA to form ribosomal subunits: 40S (small) and 60S (large).
Subunits are exported to the cytoplasm and remain free until they bind to mRNA to form a functional ribosome.
Fates of ribosomes after assembly in cytoplasm:
Free ribosomes: stay in cytoplasm and synthesize proteins used inside the cell.
Bound ribosomes: attach to rough ER (including outer nuclear membrane) and synthesize proteins destined for secretion, insertion into membranes, or to lysosomes.
Chromatin: DNA + histone proteins; two forms:
Heterochromatin: tightly packed; transcriptionally inactive.
Euchromatin: loosely packed; histone-DNA interaction weak enough to allow RNA polymerase transcription.
During cell replication, chromatin condenses into chromosomes to ensure accurate DNA transmission to daughter cells.
DNA (deoxyribonucleic acid): structure and building blocks
Repeating units: nucleotides (phosphate, sugar, nitrogenous base).
Nitrogenous bases: Purines (Adenine A, Guanine G) with two rings; Pyrimidines (Cytosine C, Thymine T) with one ring.
When base attaches only to sugar, it’s a nucleoside; when phosphate is added, it becomes a nucleotide.
DNA double helix: two antiparallel strands; complementary base pairing (A with T via 2 hydrogen bonds; C with G via 3 hydrogen bonds).
Nucleotide connectivity: phosphodiester bonds link the 5' carbon of one nucleotide to the 3' carbon of the next.
Phosphodiester bonds in DNA
Definition: Bonds that connect nucleotides together.
Bond formation: links the 5' carbon of one nucleotide to the 3' carbon of the next.
Result: continuous chain of nucleotides (a DNA strand).
Directionality: each strand has a 5' end and a 3' end; orientation is essential for polynucleotide synthesis.
Base pairing details
Phosphodiester bonds create the sugar-phosphate backbone (negatively charged).
A-T pairs via 2 hydrogen bonds; C-G pairs via 3 hydrogen bonds.
Double-stranded DNA structure and topology
Two strands paired together; antiparallel orientation: one 5'→3', the other 3'→5'.
Helical structure with bases packed inside and phosphate backbone outside.
Major and minor grooves serve as binding sites for proteins involved in transcription and replication.
Packaging of DNA: histones and nucleosomes
Histones are rich in positively charged amino acids (lysine, arginine) and bind the negatively charged DNA backbone.
DNA wraps twice around a histone core (octamer) composed of 2× each of H2A, H2B, H3, H4.
H1 histone secures DNA around the core, forming a nucleosome bead (~146 bp DNA).
Euchromatin vs heterochromatin in the nucleosome context; epigenetic regulation controls condensation and gene activity.
Epigenetic regulation: acetylation and methylation
Histone acetylation reduces positive charge on histones, loosening DNA and promoting transcription (euchromatin).
DNA methylation adds methyl groups to bases, often repressing gene expression; histone methylation has variable effects.
Epigenetics governs euchromatin vs heterochromatin states and gene expression without changing DNA sequence.
Telomeres and telomerase
Telomeres: protective repeats at chromosome ends; human telomeres consist of ~2500 TTAGGG repeats.
Function: telomeres protect coding DNA from loss during replication; they are sacrificed gradually as a buffer.
Telomerase: extends telomeres; active in stem cells and some gametes and cancer cells; limited activity in most somatic cells.
Shortening of telomeres links to aging; overactivity of telomerase is associated with cancer.
Progeria (clinical correlation)
Rare disease caused by LMNA gene mutation; defective lamin A disrupts nuclear envelope structure and chromatin organization, affecting euchromatin/heterochromatin regulation and epigenetic control.
DNA Structure Deep Dive: Key Concepts and Terminology
DNA nucleotide components: phosphate, deoxyribose sugar, nitrogenous base (A, G, C, T).
Purines vs pyrimidines: A/G are purines; C/T are pyrimidines.
Nucleoside vs nucleotide: nucleoside lacks phosphate; nucleotide includes phosphate.
Base pairing rules: A pairs with T (2 H-bonds); G pairs with C (3 H-bonds).
Directionality and antiparallel strands: 5'→3' vs 3'→5' orientation.
Phosphodiester bond: linkage between 5' phosphate and 3' sugar of adjacent nucleotides; backbone is negatively charged.
Telomere biology: TTAGGG repeats; role in genomic stability; telomerase in stem/cancer cells.
Epigenetic marks: DNA methylation (usually represses expression); histone acetylation (generally activates expression); histone methylation can activate or repress depending on context.
Fates and Function of Ribosomes
Ribosome assembly occurs in the nucleolus with rRNA and ribosomal proteins.
Ribosomal proteins synthesized in cytoplasm, imported into nucleolus, assemble with rRNA into 40S and 60S subunits.
Ribosome export to cytoplasm; final assembly occurs upon binding to mRNA to form complete ribosome.
Free ribosomes: synthesize intracellular proteins.
Bound ribosomes: synthesize proteins for secretion, insertion into membranes, or lysosomes.
Epigenetics and Chromatin Regulation
Euchromatin vs heterochromatin: transcriptionally active vs silent.
Epigenetic modifications:
Histone acetylation: promotes decondensation and gene expression.
DNA methylation: generally represses gene expression; histone methylation has context-dependent effects.
Clinical corollary: epigenetic regulation can influence disease, development, and aging processes (e.g., progeria links to chromatin structure).
Key Equations and Formulas (LaTeX)
Loading dose (accounting for bioavailability):
ext{Loading dose} = rac{C{ ext{desired}} imes Vd}{F}Maintenance dose (accounting for bioavailability and interval):
ext{Maintenance dose} = rac{C_{ ext{desired}} imes CL imes au}{F}Telomere repeat unit: TTAGGG
Base-pairing summary: A-T with 2 H-bonds; C-G with 3 H-bonds.
DNA backbone charge: phosphate groups are negatively charged.
DNA Replication: Core Concepts
Semiconservative replication: each daughter DNA contains one old and one new strand.
Origins of replication: multiple origins in eukaryotes to speed up copying of long genomes; A-T rich regions facilitate opening.
Replication fork: Y-shaped structure where DNA unwinds; helicase unzips; SSBPs keep strands apart; nucleases monitor exposed DNA.
Topoisomerases address supercoiling ahead of the fork by cutting and rejoining DNA strands; Top1 (no ATP, mainly eukaryotes), Top2 (ATP-dependent, both eukaryotes and prokaryotes), Top4 (prokaryotes only, separates linked circular DNA).
DNA replication enzymes (prokaryotes):
Primer synthesis: RNA primase; main DNA synthesis: DNA Polymerase III; primer removal and replacement: DNA polymerase I; ligation: DNA ligase; SSBPs stabilize single strands; helicase unwinds; nucleases remove damaged ssDNA.
DNA replication enzymes (eukaryotes):
Primer synthesis: DNA polymerase α with primase; main synthesis: DNA polymerase δ (lagging) and ε (leading); primer removal/replacement: DNA polymerase I (in combination with RNase H in places); ligation: DNA ligase; SSBPs stabilize; Topoisomerases relieve supercoiling.
Leading vs lagging strand synthesis:
Leading strand: continuous synthesis toward the replication fork; primer laid by primase; DNA Pol III (or δ); proofreading occurs 5'→3' polynomial activity.
Lagging strand: discontinuous Synthesis in short Okazaki fragments; RNA primers laid repeatedly; DNA Pol I removes primers and replaces with DNA; ligase seals gaps.
Primers and proofreading:
RNA primers provide 3' OH for DNA polymerase extension.
DNA polymerase III proofreading via exonuclease activity; can backtrack and correct mistakes.
DNA replication inhibitors (cancer context): drugs can trap topoisomerases in cleaved state, leading to double-stranded breaks and cell death.
Transcription and RNA Processing
Central dogma: DNA → RNA (transcription) → Protein (translation).
Transcription overview (eukaryotes):
Initiation: RNA polymerase II binds promoter elements (TATA box, CAAT box); activators/enhancers can upregulate transcription.
Elongation: RNA polymerase moves 5'→3' adding nucleotides to the 3' end of RNA.
Termination: polyadenylation signals (AAUAAA) direct cleavage and release of mature RNA; in prokaryotes, Rho-dependent/independent termination mechanisms exist.
Prokaryotic vs eukaryotic termination:
Prokaryotes: Rho-dependent and Rho-independent termination mechanisms.
Eukaryotes: RNA polymerase II continues beyond the gene; mRNA processing signals mark cleavage and polyadenylation; no Rho factor.
Post-transcriptional processing (eukaryotes):
5' cap (methylguanosine cap) added to 5' end; protects RNA and aids ribosome recognition.
3' poly-A tail added to 3' end after polyadenylation signal; stabilizes mRNA.
Splicing: introns removed; exons joined to form mature mRNA.
mRNA fate in cytosol:
Translation into protein by ribosomes.
Degradation: some mRNAs marked for destruction; processing bodies (P-bodies) involved.
Translation: key steps
Initiation:
Prokaryotes: small subunit binds to Shine-Dalgarno sequence on mRNA; start codon AUG; formyl-methionine tRNA; large subunit joins.
Eukaryotes: small subunit binds 5' cap; scans to start codon AUG; methionine tRNA; large subunit joins.
Elongation: codon-by-codon tRNA delivery; peptide bonds form; chain elongated.
Termination: stop codon reached; release factor binds; protein released.
Transcription inhibition: RNA Polymerase II is highly sensitive to alpha-amanitin (mushroom toxin) which inhibits mRNA synthesis.
Protein Synthesis and Cellular Machinery (Overview)
Role of ribosomes in translation; basic steps and fidelity.
Post-translational considerations (not deeply covered in the slides but often implied in integrated notes).
The Cell Cycle and its Regulation
Phases: Interphase (G1, S, G2) and M phase (mitosis + cytokinesis). Some cells enter G0 (quiescent).
Checkpoints and regulators:
G1/S checkpoint: ensures readiness for DNA replication; key players include Cyclin D, CDK4/6; p53 and Rb help monitor DNA integrity.
S-phase: DNA replication occurs; S-CDK ensures replication happens once and only once.
G2/M checkpoint: ensures DNA replicated correctly before mitosis; genes and kinases regulate entry into mitosis.
Metaphase checkpoint: ensures all chromosomes are properly attached to spindle before anaphase.
Cyclins and CDKs:
Cyclins: D (G1), E (G1-S), A (S), B (M).
CDKs: always present; activity controlled by cyclins and other regulators.
Activation and inactivation controls: CAK (CDK-activating kinase) fully activates; Wee1 adds inhibitory phosphates; Cdc25 removes the inhibitory phosphate; CKIs can block activation.
The “Must-Knows”:
Cyclin D + CDK4/6 phosphorylates Rb, releasing E2F to initiate S phase.
p53 halts the cycle when DNA is damaged; can promote apoptosis if damage is irreparable.
S-CDK initiates DNA replication and prevents re-replication.
M-CDK drives mitosis; Wee1 inhibition and Cdc25 activation are necessary to proceed.
APC/C (anaphase-promoting complex) drives destruction of cyclin B and securin to finish mitosis.
Mitosis stages and cytokinesis (high level): Prophase, Metaphase, Anaphase, Telophase, Cytokinesis.
Nervous System and Autonomic Nervous System (ANS)
ANS overview:
Two-neuron chain in both sympathetic and parasympathetic divisions (preganglionic and postganglionic neurons).
Preganglionic neurons release ACh onto nicotinic receptors; postganglionic neurons usually release norepinephrine onto adrenergic receptors (exception: sweat glands use ACh).
Sympathetic division:
Preganglionic cell bodies in T1–L2 lateral horn; postganglionic cell bodies in paravertebral or prevertebral ganglia.
Parasympathetic division:
Preganglionic neurons originate in the brainstem (CN III, VII, IX, X) and sacral spinal cord (S2–S4); postganglionic neurons often release ACh on muscarinic receptors.
Key clinical entities:
Horner’s syndrome: ptosis, miosis, anhidrosis due to sympathetic pathway disruption.
Hirschsprung disease: congenital absence of enteric ganglion cells; failure to relax, proximal dilation; associated with Down syndrome; rectal suction biopsy shows absence of ganglion cells.
CNS integration of ANS:
Hypothalamus as primary regulator; receives input from solitary nucleus (visceral sensory input via Vagus) and higher brain regions (limbic system and cortex).
Synaptic transmission and receptors:
Postganglionic sympathetic neurons typically release norepinephrine acting on adrenergic receptors; sweat glands use ACh on muscarinic receptors.
Parasympathetic preganglionic neurons release ACh on nicotinic receptors; postganglionic release ACh on muscarinic receptors.
Practical pharmacology notes:
Atropine is a muscarinic antagonist; blocks rest-and-digest effects; increases heart rate by removing vagal tone; used to treat bradycardia and organophosphate poisoning.
Dale’s phenomenon: vasomotor reversal—after irreversible α-blockade, epinephrine can cause a drop in BP due to unopposed β2 vasodilation; clinical relevance in pheochromocytoma management.
Embryology and Development: Weeks, Germ Layers, and Morphogenesis
Fertilization and early development:
Fertilization occurs in the fallopian tube within 24 hours of ovulation; zygote forms, followed by morula, then blastocyst.
Trophoblast forms placenta; inner cell mass forms embryo.
Week-by-week development overview:
Weeks 1–2: fertilization, implantation, bilaminar disc; no teratogenic effects if exposure occurs during this “all-or-none” window (conceptus either dies or is unaffected).
Week 3 (gastrulation): formation of trilaminar disc—ectoderm, mesoderm, endoderm; neurulation begins later; somites form.
Week 4: folding of trilaminar disc; formation of trunk and organ primordia; neural tube forms.
Weeks 5–8: organogenesis; formation of organ systems; severe teratogenic effects if exposure occurs during this sensitive window.
Weeks 9–38: fetal period; organ maturation and growth; mostly physiologic/minor anomalies if teratogens present.
Germ layers and derivatives (summary):
Ectoderm: nervous system, skin, neural crest derivatives (peripheral nervous system, adrenal medulla, etc.).
Mesoderm: musculoskeletal system, cardiovascular system, kidneys, gonads, dermis; notochord remnants form nucleus pulposus.
Endoderm: GI and respiratory tract linings and glands (liver, pancreas, thyroid parafollicular cells, etc.).
Neural crest derivatives (extensive list): peripheral nervous system components, sensory ganglia, adrenal medulla, Schwann cells, melanocytes, odontoblasts, facial bones, etc.
Organogenesis gene families: Homeobox (HOX), Hox, Sox, Pax, Wnt, Hedgehog (SHH), TGF-β (including BMPs), FGF.
Teratogens and morphogenesis:
Teratogen timing matters: Weeks 1–2 all-or-none; Weeks 3–8 major malformations; Weeks 9–38 physiologic/minor anomalies.
Infections (TORCH), chemical agents (lithium, valproic acid, retinoic acid, thalidomide), substances of abuse (smoking, alcohol, cocaine).
Maternal diseases (diabetes, PKU) affect fetal development.
Types of morphologic anomalies
Malformation: intrinsic developmental defect (e.g., cleft lip, neural tube defects).
Disruption: extrinsic damage to a normally developing structure (trauma, amniotic bands).
Deformation: external mechanical forces alter development (uterine constraint, oligohydramnios).
Dysplasia: abnormal organization of cells within a tissue (e.g., skeletal dysplasias).
Sequences and syndromes:
Sequence: cascade of anomalies due to a single initiating event (e.g., Potter sequence from oligohydramnios).
Syndrome: multiple anomalies with a common etiology (e.g., Down syndrome).
Common congenital syndromes and chromosomal abnormalities (high-yield overview):
Down syndrome (Trisomy 21)
Edwards syndrome (Trisomy 18)
Patau syndrome (Trisomy 13)
Turner syndrome (45,X)
Klinefelter syndrome (47,XXY)
Other sex chromosome variations (46,XX,Y; 46,XY,del X; etc.)
Fertilization basics and ploidy
Gametes are haploid (1N); zygote is diploid (2N).
Meiosis I and II yield 23 chromosomes per gamete.
Mosaicism vs chimerism definitions and examples.
Practical clinical correlations
Folate (B9) deficiency linked to neural tube defects; importance of folic acid supplementation in pregnancy.
Cytogenetics and Chromosomal Abnormalities
Chromosome structure and organization
Centromere position classes: metacentric, submetacentric, acrocentric.
Banding techniques to detect structural abnormalities: G-banding is standard; Q-banding first; R-banding, C-banding, NOR staining provide additional details.
High-resolution banding in prophase/prometaphase for microdeletions.
Fluorescent in situ hybridization (FISH)
Uses fluorescent DNA probes to detect deletions, duplications, and rearrangements.
Numerical vs structural abnormalities
Numerical: gains or losses of chromosomes (aneuploidy); euploidy is normal multiples of 23; polyploidy is extra complete sets.
Structural: deletions, duplications, translocations (reciprocal or Robertsonian), rings, isochromosomes, etc.
Robertsonian translocations
Fusion of two acrocentric chromosomes at the centromere; long arms fuse; short arms lost.
Common genetic disorders and chromosomal etiologies (high-yield highlights)
Down syndrome: Trisomy 21; features include facial characteristics and risk for congenital heart disease.
Edwards syndrome: Trisomy 18; severe congenital anomalies; poor prognosis.
Patau syndrome: Trisomy 13; CNS and facial defects; poor prognosis.
Turner syndrome: 45,X; short stature, webbed neck, streak ovaries, cardiovascular anomalies.
Klinefelter syndrome: 47,XXY; hypogonadism, infertility, tall stature.
Other mosaicisms and sex chromosome abnormalities.
DNA Damage, Repair, and Genomic Integrity
DNA damage and sources
Free radicals and ROS, UV light causing pyrimidine dimers (thymine-thymine), spontaneous deamination (e.g., cytosine to uracil).
Chemotherapy agents deliberately damage DNA to trigger apoptosis.
Telomeres and telomerase (recap)
Telomeres protect coding DNA ends; telomerase extends telomeres in stem/germ/cancer cells; limited activity in most somatic cells.
Telomere shortening is associated with cellular aging; overactivity of telomerase can support cancer cell immortality.
DNA repair pathways (overview)
Nucleotide Excision Repair (NER): removes bulky lesions like pyrimidine dimers; active in G1; critical genes include endonucleases; XP (Xeroderma pigmentosum) is a defect.
Base Excision Repair (BER): fixes oxidative deamination and spontaneous base modifications; uses DNA glycosylase, AP endonuclease, lyase, DNA polymerase β, ligase.
Mismatch Repair (MMR): fixes mispaired bases post-replication; MutS/MutL detect; defects cause Lynch syndrome (HNPCC).
Double-strand break repair: Homologous recombination (HR) uses sister chromatid; nonhomologous end-joining (NHEJ) ligates ends, error-prone.
Clinical correlations and NBME-style associations
XP: defect in NER leading to extreme UV sensitivity and skin cancers.
Lynch syndrome: autosomal dominant MMR defects; high risk for colorectal and other cancers.
BRCA1/BRCA2 and HR defects elevate breast/ovarian cancer risk.
Key question patterns (high-yield themes)
Endonuclease cuts in NER during removal of pyrimidine dimers.
Telomerase activity and cancer relation: inhibition reduces replicative potential of tumor cells.
SSBPs prevent reannealing after DNA separation; their absence leads to fork collapse.
Metabolic and Genetic Disorders (Amino Acids and Teratogens)
Phenylketonuria (PKU)
Normal pathway: phenylalanine → tyrosine via phenylalanine hydroxylase, requires BH4.
PKU: deficient phenylalanine hydroxylase or BH4; phenylalanine accumulates; tyrosine becomes essential; musty odor; intellectual disability if untreated.
Treatment: low phenylalanine diet; supplement tyrosine; BH4 in deficiency.
Maple Syrup Urine Disease (MSUD)
Defect in branched-chain α-ketoacid dehydrogenase complex; accumulation of leucine, isoleucine, valine; urine smells like maple syrup.
Treatment: restrict branched-chain amino acids; thiamine supplementation may help some patients.
Albinism
Tyrosinase deficiency or melanin synthesis defect; pale skin, light hair/eyes; vision problems; increased skin cancer risk; autosomal recessive common.
Homocystinuria
CBS deficiency (requires B6/pyridoxine as cofactor) disrupts methionine to cysteine metabolism; accumulation of homocysteine; lens subluxation (downward), marfanoid habitus, thrombosis risk.
Alkaptonuria
Homogentisate oxidase deficiency; homogentisic acid accumulates; dark urine on standing; ochronosis (bluish-black pigment in cartilage); arthritis later in life; usually treated supportively.
Pharmacology and Therapeutics (Key Concepts from the NBME-style content)
Enzyme kinetics: competitive vs non-competitive inhibition
Competitive: inhibitor competes with substrate at active site; increases Km; Vmax unchanged; can be overcome by adding more substrate.
Non-competitive: inhibitor binds elsewhere; reduces Vmax; Km unchanged; not overcome by more substrate.
Dosing concepts
Loading dose depends on volume of distribution (Vd) and bioavailability (F):
ext{Loading dose} = rac{C{ ext{desired}} imes Vd}{F}Maintenance dose depends on clearance (CL) and dosing interval (τ):
ext{Maintenance dose} = rac{C_{ ext{desired}} imes CL imes au}{F}
Bioavailability (F)
IV administration has F = 1 (100%); oral F < 1 due to first-pass metabolism.
When F decreases, both loading and maintenance doses must be adjusted to achieve the same plasma concentration.
Pharmacodynamic concepts: potency vs efficacy
Efficacy: maximum effect achievable by a drug; higher efficacy means taller dose-response curve.
Potency: amount of drug needed to reach a given effect; leftward shift indicates higher potency.
Cytochrome P450 (CYP450) inducers and inhibitors
Inducers: Rifampin, Carbamazepine, Barbiturates, St. John’s wort, chronic alcohol; increase metabolism, reduce drug levels.
Inhibitors: Cimetidine, Ciprofloxacin, Erythromycin, Ketoconazole, Amiodarone, Grapefruit juice; decrease metabolism, increase drug levels.
G-protein coupled receptor signaling (second messengers)
Gs: stimulates adenylyl cyclase → ↑ cAMP → PKA activation.
Gi: inhibits adenylyl cyclase → ↓ cAMP.
Gq: activates phospholipase C → IP3 + DAG → ↑ Ca2+ → PKC activation.
Common receptor-class mnemonic (QISS/QIQ): α1 (Gq), α2 (Gi), β1/β2 (Gs), M1 (Q), M2 (I), M3 (Q), V1 (Q), V2 (S).
Organophosphate poisoning
Irreversible AChE inhibitors leading to accumulation of ACh at muscarinic and nicotinic receptors; treatment with atropine (muscarinic antagonist) and pralidoxime (oxime) as antidote.
Adrenergic pharmacology and Dale’s reversal
After irreversible α-blockade (e.g., phenoxybenzamine), epinephrine can cause a paradoxical drop in BP due to unopposed β2-mediated vasodilation (Dale’s vasomotor reversal).
Other drug classes in the notes
PDE inhibitors: PDE-5 inhibitors (sildenafil, vardenafil, tadalafil) increase cGMP to promote vasodilation; PDE-3 inhibitors (milrinone) increase cAMP to enhance cardiac contractility and vasodilation; nonspecific PDE inhibitors (theophylline) for bronchodilation.
Atropine: muscarinic antagonist; used for bradycardia and ocular procedures; antidote in organophosphate poisoning.
Alpha blockers: prazosin, doxazosin (reversible), phentolamine (reversible nonselective), phenoxybenzamine (irreversible); used for hypertension, BPH, pheochromocytoma; Dale reversal relevance.
Neuromodulation and autonomic control: hypothalamic integration; parasympathetic/sympathetic balance; autonomic reflex pathways.
Imaging Modalities (Clinical Tools)
Computed Tomography (CT)
Uses X-ray photons; cross-sectional imaging via rotating X-ray tubes and detectors; assesses density differences; quick and widely available.
Magnetic Resonance Imaging (MRI)
Uses magnetic fields and radiofrequency waves; superior soft-tissue contrast; T1-weighted images highlight fat; T2-weighted images highlight fluids.
Ultrasound
Uses high-frequency sound waves; real-time imaging; safe; visualizes organs, soft tissues, and blood flow.
Practice Questions and Clinical Correlations (Representative Examples)
LMNA mutation in progeria-like syndrome reflects defective lamin proteins affecting nuclear envelope integrity and chromatin organization; this impacts euchromatin/heterochromatin balance and epigenetic regulation (Question 1 in the set).
Euchromatin vs. heterochromatin states are best described as: euchromatin = acetylated/histone modifications enabling transcription; heterochromatin = methylated and transcriptionally silent (Question 2).
Blocking ribosomal protein import into the nucleus halts ribosome assembly in the nucleolus (Question 3).
DNA melting temperature correlates with GC content: higher GC content (more H-bonds) yields higher Tm (Question 4).
Telomerase inhibition in dividing tumor cells leads to telomere shortening and reduced replication potential (Question 5).
Embryology and Teratology: Key Windows and Concepts
Teratogen windows of sensitivity
Weeks 1–2: all-or-none effect (death or no effect).
Weeks 3–8: major morphologic anomalies (organogenesis).
Weeks 9–38: physiologic or minor anomalies.
TORCH infections and congenital defects: Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, Herpes; each has characteristic fetal effects.
Critical gene families in development (transcription factors and signaling): Homeobox, Hox, Sox, Pax, Wnt, Hedgehog (SHH), TGF-β (BMPs), FGF.
Morphogenesis errors and congenital anomalies
Malformation, disruption, deformation, and dysplasia definitions with examples.
Sequences and syndromes: Potter sequence; Down syndrome; other common associations.
Cytogenetics in clinical practice
Karyotyping and chromosomal analysis; use of FISH and various banding methods; Robertsonian translocations and translocation carriers.
Quick References and High-Yield Takeaways
Base pairing rules and the chemistry of DNA structure are foundational for replication and transcription.
The cell cycle is tightly controlled by cyclins and CDKs; checkpoints ensure genome integrity.
The ANS relies on a two-neuron chain; neurotransmitter identity drives the response in target tissues; pharmacology heavily leverages receptor pharmacodynamics.
Teratogens exert stage-specific effects; folate supplementation is crucial during weeks 3–8 to mitigate neural tube defects.
Genetic diseases often arise from enzymatic defects (PKU, MSUD, albinism, homocystinuria, alkaptonuria) or chromosomal abnormalities (Down, Edwards, Patau, Turner, Klinefelter).
NBME-style pharmacology patterns emphasize: loading dose depends on Vd; maintenance dose depends on clearance; changes in bioavailability alter both doses accordingly.
Notes on Notation and LaTeX Usage
Equations are presented in LaTeX format for clarity:
Loading dose: ext{Loading dose} = rac{C{ ext{desired}} imes Vd}{F}
Maintenance dose: ext{Maintenance dose} = rac{C_{ ext{desired}} imes CL imes au}{F}
Telomere repeats: ext{TTAGGG}
All chemical and genetic notation is kept in standard scientific format for consistency with exam content.
If you’d like, I can tailor these notes further into a shorter study guide focused on specific topics you’ll be tested on, or extract a subset of high-yield questions with concise explanations for quick review.