Molecular Genetics — Flashcards

Flashcard 401: A researcher develops 2 functional mRNA sequences composed of CUC & CUU trinucleotide repeats. - He subsequently incubates them. - After a few hours, it is found that both mRNA sequences produce polypeptide chains containing leucine repeats. - This observed finding is due to what genetic principles?

Answer: Degeneracy and the Wobble hypothesis - Degeneracy: Multiple codons code for the same amino acid. - Wobble hypothesis: The 3rd position of the codon can undergo non-traditional base pairing with the anticodon, allowing a single tRNA to recognize multiple codons.

Flashcard 402: Describe the characteristics or mutations associated with the following Hemoglobins: - Hemoglobin C - Hemoglobin F - Hemoglobin H - Hemoglobin S

Answer: - **HbC**: Glutamate → **Lysine** mutation at position 6 of the β-globin chain. - **HbF**: Fetal hemoglobin (α2γ2); has higher O2 affinity than HbA. - **HbH**: β4 tetramers; occurs in **3-gene deletion** α-thalassemia. - **HbS**: Glutamate → **Valine** mutation at position 6 of the β-globin chain.

Extra: Note: **Hb Barts** (γ4) occurs in **4-gene deletion** α-thalassemia (Hydrops fetalis). Both HbH and Hb Barts have very high oxygen affinity and are poor at oxygen delivery. Mnemonic for β6 mutations: - Hb**S**: **V**aline (**S**ickle) - Hb**C**: **L**ysine (Ly-**C**-ine)

Flashcard 403: A 6-year-old African American boy presents with easy fatigability and splenomegaly. CBC shows mild anemia. Hemoglobin electrophoresis shows a hemoglobin variant that migrates more slowly toward the anode than both HbA and HbS. What mutation is the most likely cause of this patient's condition?

Answer: Missense mutation (Glutamic acid to Lysine substitution at position 6 of the β-globin chain) **Diagnosis:** Hemoglobin C (HbC) disease **Electrophoresis migration (toward anode):** HbA > HbS > HbC (A Fat Slow Crawl)

Extra: - **HbC disease** is caused by a missense mutation where a negatively charged glutamic acid is replaced by a positively charged lysine. - **Clinical features:** Mild hemolytic anemia, splenomegaly, and HbC crystals (rod-shaped) in red blood cells. - **Electrophoresis:** Since lysine is more positive than valine (HbS) or glutamic acid (HbA), HbC migrates the slowest toward the positive anode.

Flashcard 404: 15 y/o boy comes with unexplained erythrocytosis on lab analysis. -Father & sister also have high red cell levels. -Further analysis shows that this mutation impairs the ionic interaction between B-subunit & 2,3-bisphosphoglycerate. -As a result of this mutation, the patient's hemoglobin will be most similar to what hemoglobin types?

Answer: Hemoglobin F because the mutation causes low affinity of HbA to 2,3-BPG, which inhibit 2,3-BPG to bind to HbA, but will increase HbA affinity to oxygen. Thus will resemble HbF due to high affinity to oxygen. Normally, HbA has high affinity to 2,3 BPG. HbF has high affinity to oxygen.

Flashcard 405: Lab animals deprived of folic acid experience a marked increase in marrow erythroid precursor cell production. -Many of these erythroid cells undergo apoptosis without further maturation. -Provision of what supplements would reduce erythroid precursor cell apoptosis in these animals?

Answer: Thymidine Folate deficiency leads to decreased dTMP synthesis (by thymidylate synthase), causing megaloblastic anemia and apoptosis of erythroid precursors. Thymidine supplementation bypasses this deficiency via the salvage pathway (thymidine kinase).

Flashcard 406: What is the mode of inheritance of Hartnup disease? _____

Answer: Autosomal recessive

Flashcard 407: Why is the dystrophin (DMD) gene prone to spontaneous mutations? _____

Answer: Largest protein-coding human gene

Flashcard 408: What is the most common cause (95%) of Down syndrome? _____

Answer: Meiotic nondisjunction

Flashcard 409: If a disease has an X-linked dominant inheritance pattern, there is NO _____ transmission

Answer: male-to-male

Flashcard 410: What is the penetrance of neurofibromatosis I? _____

Answer: 100%