Answers to Your Genetics/Biochemistry Notes

Q1. tRNA functions as...

• Has a characteristic cloverleaf secondary structure with 4 stem-loop arms
• The 3' end (CCA-OH) is where the specific amino acid is covalently attached
• The anticodon loop base-pairs with the complementary mRNA codon
• Each tRNA is "charged" (loaded with its amino acid) by a specific enzyme called aminoacyl-tRNA synthetase
• There is at least one tRNA for each of the 20 amino acids

Q2. Point (Pt.) Mutation is...

Q3. Sickle Cell Anemia is...

• Mutation: GAG → GTG at codon 6, causing Glutamic acid (Glu) → Valine (Val) substitution
• This is an autosomal recessive disorder (both alleles affected = homozygous HbSS)
• The abnormal hemoglobin is called HbS
• Under low oxygen conditions, HbS polymerizes → sickling of red blood cells
• This causes vaso-occlusion, hemolytic anemia, and organ damage
• Sickle cell trait (HbAS) = one abnormal allele; generally asymptomatic but can sickle under extreme conditions

Q4. Down Syndrome is caused by...

• Most common chromosomal disorder (1 in 700 live births)
• Karyotype: 47, XX/XY, +21
• Cause: usually non-disjunction during meiosis (most commonly in maternal meiosis I), strongly correlated with advanced maternal age
• Less commonly: Robertsonian translocation (14;21) or mosaicism
• Features include: intellectual disability, flat facial profile, upward-slanting eyes (epicanthal folds), single palmar crease, cardiac defects (especially AV canal defect), increased risk of acute leukemia and early-onset Alzheimer's disease

Q5. P__ Syndrome → XXY

• Affects males (most common sex chromosome disorder in males; ~1 in 600 males)
• Extra X chromosome due to non-disjunction
• Clinical features:
  • Small, firm testes (hypogonadism)
  • Azoospermia (infertility) - almost universal in 47,XXY
  • Gynecomastia (enlarged breast tissue)
  • Tall stature, long limbs
  • Decreased testosterone → increased LH/FSH (hypergonadotropic hypogonadism)
  • May have mild learning difficulties
• Variants: 48,XXXY; 48,XXYY; 49,XXXXY (more severe)

Q6. Turner Syndrome → XO (45,X0)

• Affects females (1 in 5000 female births)
• Loss of one X chromosome (usually paternal X is lost)
• Clinical features:
  • Short stature
  • Streak gonads → primary amenorrhea, infertility
  • Webbed neck (pterygium colli)
  • Shield chest, widely spaced nipples
  • Cubitus valgus (wide carrying angle)
  • Coarctation of aorta (most common cardiac defect)
  • Bicuspid aortic valve
  • Normal intelligence (may have visuospatial difficulties)
  • No Barr body (only 1 X chromosome)

Q7. Hepatomegaly + Splenomegaly + Fever + Weight loss + Pancytopenia → Diagnosis: Visceral Leishmaniasis (also called Kala-azar)

• Causative organism: Leishmania donovani complex
• Vector: Female sandfly (Phlebotomus sp. in Old World)
• Pathology: Parasites infect macrophages in the reticuloendothelial system (liver, spleen, bone marrow, lymph nodes)
• The classic symptom complex is:
  • Hepatomegaly + massive splenomegaly (spleen often most prominent finding)
  • Prolonged fever (often with double daily spike)
  • Weight loss / cachexia
  • Pancytopenia (anemia, leukopenia, thrombocytopenia - due to bone marrow infiltration + hypersplenism)
  • Hypergammaglobulinemia
  • Skin darkening ("kala-azar" = black fever in Hindi)
• Common in tropical/subtropical regions (Indian subcontinent, East Africa, South America, Mediterranean)
• Diagnosis: splenic aspirate / bone marrow aspirate showing amastigotes (Leishman-Donovan bodies), rK39 antigen test, PCR
• Treatment: liposomal amphotericin B (first line in most regions), miltefosine