Genetics Syllabus - Topic Breakdown

1. Mendelian Genetics; Monohybrid, Dihybrid, and Trihybrid Cross | Complete, Incomplete, and Codominance

• Monohybrid cross: A cross between two individuals differing in ONE trait (e.g., Tt x Tt). Produces a 3:1 phenotypic ratio in F2.
• Dihybrid cross: A cross involving TWO traits (e.g., TtRr x TtRr). Produces a 9:3:3:1 ratio in F2.
• Trihybrid cross: THREE traits considered simultaneously.
• Complete dominance: One allele fully masks the other (e.g., T over t - tall over short).
• Incomplete dominance: The heterozygote shows an intermediate phenotype (e.g., red x white = pink).
• Codominance: Both alleles are expressed simultaneously (e.g., AB blood type - both A and B antigens present).

2. Nonallelic Gene Interaction and Its Inheritance Characteristics

• Epistasis: One gene masks or modifies the expression of another gene at a different locus.
• Types: Dominant epistasis, recessive epistasis, duplicate dominant, complementary, etc.
• Example: Coat color in Labrador dogs involves two genes - the E gene can suppress B gene expression entirely.
• These interactions produce modified Mendelian ratios (e.g., 9:7, 12:3:1, 15:1 instead of 9:3:3:1).

3. Linkage and Crossing Over. Main Genetical Basis of Recombination

• Linkage: Genes located on the same chromosome tend to be inherited together (violating Mendel's law of independent assortment). Named "linked genes."
• Crossing over (recombination): During meiosis I, homologous chromosomes exchange segments at points called chiasmata. This shuffles alleles and produces new combinations (recombinants).
• Genetic basis of recombination: The physical exchange of DNA segments between non-sister chromatids of homologous chromosomes.
• Recombination frequency is used to map genes - genes far apart recombine more frequently than genes close together.

4. Sex Genetics. Sex Linkage. X and Y Chromosome Linkage

• Sex determination: In humans, females are XX and males are XY. The Y chromosome carries the SRY gene which triggers male development.
• Sex-linked inheritance: Genes located on sex chromosomes follow different inheritance patterns.
• X-linked traits: Genes on the X chromosome. Since males have only one X, they express even recessive X-linked traits (e.g., hemophilia, color blindness).
• Y-linked (holandric) traits: Genes on the Y chromosome pass exclusively from father to all sons (e.g., some male fertility genes).
• X-linked dominant vs recessive patterns differ in carrier females vs affected males.

5. Changeability (Variability). Main Types of Variability. Inherited Variability - Mutation

• Non-hereditary (phenotypic/modification) variability: Changes due to environment; not passed to offspring.
• Hereditary (genotypic) variability: Changes in genetic material that ARE passed to offspring. Two types:
  • Combinative variability: New combinations of existing alleles through sexual reproduction (crossing over, independent assortment, fertilization).
  • Mutation: A sudden, heritable change in the DNA sequence.
    • Gene (point) mutations: Change in single nucleotide (substitution, insertion, deletion).
    • Chromosomal mutations: Structural changes - deletion, duplication, inversion, translocation.
    • Genomic mutations: Change in chromosome number - aneuploidy (e.g., trisomy 21 = Down syndrome), polyploidy.

Heart Anatomy

Overview

• An apex - formed by the inferolateral part of the left ventricle; lies deep to the left 5th intercostal space, 8-9 cm from the midsternal line
• A base (posterior surface) - directed posteriorly; formed mainly by the left atrium, receiving the pulmonary veins

Layers of the Heart Wall

The Pericardium

• Fibrous pericardium - tough outer layer
• Serous pericardium - has two sub-layers:
  • Parietal layer - lines the inner surface of the fibrous pericardium
  • Visceral layer (epicardium) - adheres to the heart surface

Four Chambers

Right Atrium

• Receives deoxygenated blood from the body via the superior vena cava (upper), inferior vena cava (lower), and coronary sinus (cardiac veins)
• Interior divided by the crista terminalis into:
  • Sinus of venae cavae (posterior - smooth wall)
  • Atrium proper + right auricle (anterior - rough walls with pectinate muscles)
• Blood exits through the tricuspid valve into the right ventricle

Right Ventricle

• Thin-walled (low pressure - pumps to lungs only)
• Receives blood from right atrium through the tricuspid (right AV) valve
• Pumps blood out through the pulmonary valve into the pulmonary trunk → lungs

Left Atrium

• Receives oxygenated blood from lungs via four pulmonary veins
• Smooth interior walls
• Blood exits through the mitral (bicuspid) valve into the left ventricle

Left Ventricle

• Thick, powerful walls (generates high pressure to pump blood to the entire body)
• Separated from right ventricle by the interventricular septum
• Pumps blood out through the aortic valve into the aorta

Valves

Conducting System

1. SA node (sinoatrial) - in the right atrium near the SVC; the pacemaker (~60-100 bpm)
2. AV node (atrioventricular) - at the junction of atria and ventricles; delays conduction
3. Bundle of His - transmits impulse to the ventricles via the interventricular septum
4. Left and right bundle branches - run down each side of the septum
5. Purkinje fibers - spread impulse through the ventricular myocardium from apex upward

Coronary Blood Supply

• Left coronary artery (LCA) - gives off the:
  • Anterior interventricular (LAD) branch - supplies anterior LV and septum
  • Circumflex branch - supplies left atrium and posterior LV
• Right coronary artery (RCA) - runs in the coronary sulcus; supplies the right atrium, RV, and (usually) the SA and AV nodes

External Sulci

• Coronary sulcus - horizontal groove separating atria from ventricles; contains the RCA, circumflex artery, coronary sinus
• Anterior interventricular sulcus - contains the LAD and great cardiac vein
• Posterior interventricular sulcus - contains the posterior interventricular artery and middle cardiac vein

Kidney Cross Section

Overview Diagram

1. Fibrous Capsule

2. Renal Cortex (Outer Region)

• Reddish-brown in the fresh specimen; the outermost parenchymal zone just beneath the capsule
• Contains the main filtration structures:
  • Renal corpuscles (glomerulus + Bowman's capsule) - easily identified in histology as spherical structures
  • Proximal convoluted tubules (PCT)
  • Distal convoluted tubules (DCT)
• Also contains cortical labyrinths (areas between medullary rays with corpuscles and convoluted tubules)
• Medullary rays - cone-shaped extensions of medullary tissue projecting into the cortex, containing straight tubules and collecting ducts
• Renal columns (of Bertin) - extensions of cortical tissue that dip down between the pyramids, separating them

3. Renal Medulla (Inner Region)

• Paler than the cortex; divided into 8-18 renal pyramids (typically 8-12 in humans)
• Each pyramid is a cone-shaped mass with:
  • Base - faces the cortex (at the corticomedullary junction)
  • Apex (papilla) - points toward the renal sinus and projects into a minor calyx

• Outer medulla - further divided into outer stripe and inner stripe; contains thick limbs of the loop of Henle and collecting ducts; straight vessels (vasa recta) are prominent here
• Inner medulla - lighter, more homogeneous; contains thin limbs of the loop of Henle and inner medullary collecting ducts

4. Renal Pyramids

5. Collecting System (Renal Sinus)

6. Hilum

• Renal vein (most anterior)
• Renal artery
• Ureter (most posterior)
• Lymphatics and autonomic nerves

7. Blood Supply (seen in cross section)

• Vasa recta - long straight capillaries that dip into the medulla alongside the loops of Henle; essential for the countercurrent exchange mechanism that concentrates urine

8. The Nephron - Functional Unit

• Cortical nephrons (85%) - short loops of Henle, stay in outer medulla
• Juxtamedullary nephrons (15%) - long loops reaching deep into the inner medulla; critical for urine concentration

How the Nephron Filters and Concentrates Urine

Urinary Excretion = Filtration - Reabsorption + Secretion

Step 1 - Glomerular Filtration (Renal Corpuscle)

GFR = Kf × [(P_GC - P_BS) - π_GC] (Kf = filtration coefficient; P_GC = glomerular capillary pressure; P_BS = Bowman's space pressure; π_GC = oncotic pressure)

Step 2 - Proximal Convoluted Tubule (PCT) — Bulk Reabsorption

• Na+ is actively pumped out by Na+/K+-ATPase on the basolateral side, creating a gradient that drives Na+ in from the lumen
• Glucose and amino acids: reabsorbed by secondary active transport via SGLT2 (90%) and SGLT1 (10%) co-transporters - virtually 100% of filtered glucose is recovered here (this is the target of SGLT2 inhibitors like dapagliflozin)
• HCO₃⁻: reabsorbed via Na+/H+ exchanger (NHE3)
• Water: follows osmotically through aquaporin-1 (AQP1) channels
• Urea, phosphate, uric acid, low-molecular-weight proteins: also reclaimed here

Step 3 - Loop of Henle — Building the Concentration Gradient

Descending Limb (thin)

• Freely permeable to water, relatively impermeable to solutes
• Water is drawn out into the hypertonic medullary interstitium → tubular fluid becomes progressively more concentrated as it descends to the papilla

Ascending Limb (thin then thick)

• Impermeable to water - this is the key
• The thick ascending limb (TAL) actively pumps Na+/K+/2Cl− out via the NKCC2 cotransporter (the target of loop diuretics like furosemide)
• Cl− and Na+ leave into the interstitium, but water cannot follow → tubular fluid becomes hypotonic (~100-200 mOsm/L) as it exits the loop

Step 4 - Distal Convoluted Tubule (DCT)

• Receives hypotonic fluid from the loop of Henle
• Tight junctions - relatively impermeable; maintains the gradient set up by the loop
• Reabsorbs ~5% of filtered Na+ via the NCC cotransporter (target of thiazide diuretics)
• Major site of PTH- and vitamin D-mediated Ca²+ reabsorption
• The macula densa cells (specialized DCT cells at the glomerulus) sense NaCl delivery and regulate GFR via tubuloglomerular feedback

Step 5 - Collecting Duct — Final Concentration (ADH-controlled)

With ADH (dehydration, low blood volume):

• ADH released from posterior pituitary
• Binds V2 receptors on collecting duct cells
• Triggers insertion of aquaporin-2 (AQP-2) water channels into the apical membrane
• Water flows out of the tubule down the osmotic gradient into the hypertonic interstitium → small volume of concentrated urine (up to ~1200 mOsm/L)

Without ADH (overhydration):

• AQP-2 channels absent from luminal membrane
• Water cannot leave the tubule
• Large volume of dilute urine produced (~50-100 mOsm/L)
• Absence of ADH response = diabetes insipidus

Step 6 - Vasa Recta — Countercurrent Exchange

• As blood descends into the hypertonic medulla, NaCl and urea diffuse in and water diffuses out
• As blood ascends, the process reverses
• Net result: solutes are recycled within the medulla and the osmotic gradient is preserved rather than washed away

Summary Table