Molecular Genetics — Flashcards

Flashcard 391: 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 392: An experiment was conducted using DNA polymerase III extracted from E. coli. Given that this enzyme possesses 3' to 5' exonuclease activity, which enzymatic action would be observed during DNA replication?

Answer: Proofreading (removal of mismatched base pairs)

Flashcard 393: 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 394: What kind of mutation exists in the following base changes? - CUU (Leucine) → AUU (Isoleucine) - UUU (Phenylalanine) → UUC (Phenylalanine) - CAG CCC ACT → CAG TCC CAC T - CAG CAG UAA → CAG CAG CAA - UCA → UGA (Silent, Missense, Nonsense, Nonstop, Frameshift)

Answer: - **CUU (Leucine) → AUU (Isoleucine)**: Missense mutation - **UUU (Phenylalanine) → UUC (Phenylalanine)**: Silent mutation - **CAG CCC ACT → CAG TCC CAC T**: Frameshift mutation - **CAG CAG UAA → CAG CAG CAA**: Nonstop mutation (Stop codon → Amino acid) - **UCA → UGA**: Nonsense mutation (Amino acid → Stop codon)

Extra: - **Silent**: Same amino acid (often 3rd position/wobble). - **Missense**: Different amino acid. - **Nonsense**: Changes to a Stop codon (UAA, UAG, UGA). - **Nonstop**: Stop codon changes to an amino acid. - **Frameshift**: Insertion or deletion not in a multiple of 3, shifting the reading frame.

Flashcard 395: 24 y/o woman is diagnosed with gestational diabetes mellitus during her 1st pregnancy. -Mother & younger sister had high blood surgars during pregnancy. -If this patient's gestational hyperglycemia is genetically predisposed, she is most likely to have decreased activity in what enzyme?

Answer: Glucokinase Glucokinase need to phosphorylate glucose to breakdown in glycolysis in order to release ATP to close down the K channel, which lead to influx of Ca that causes release of insulin. due to Maturity Onset Diabetes of the Young (MODY) (hereditary mutation of glucokinase gene) Key: Her mother & her younger sister had diabetes too during their pregnancy, very young.

Flashcard 396: 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 397: How do the following mutations affect protein speed in gel electrophoresis compared to normal Hemoglobin (HbA)? - Frameshift mutation - Missense mutation - Nonsense mutation - Silent mutation - Trinucleotide expansion

Answer: - **Frameshift mutation:** Can result in shorter or longer proteins. In α-thalassemia, loss of α-chains leads to formation of **HbH (β4)**, which moves **faster** than HbA toward the anode. - **Missense mutation:** Single amino acid substitution (e.g., HbS, HbC). These lose negative charge compared to HbA and thus move **slower** toward the anode (HbA > HbS > HbC). - **Nonsense mutation:** Results in a truncated (shorter) protein, which moves **faster** due to reduced size/mass. - **Silent mutation:** No change in amino acid sequence; mobility remains the **same** as HbA. - **Trinucleotide expansion:** Results in a larger protein (e.g., Huntington disease), which moves **slower** due to increased size.

Flashcard 398: True or False in relation to sickle cell anemia? a.) HbS decreases Beta -globin interaction with 2,3-diphosphoglycerate b.) HbS impairs oxygen binding to the heme moiety c.) HbS allows hydrophobic interaction among hemoglobin molecules.

Answer: a.) **False**: The mutation (Glu → Val) is on the surface of the $\beta$-globin chain and does not significantly alter the 2,3-BPG binding site. b.) **False**: HbS molecules bind oxygen normally; the pathology is the polymerization of *deoxygenated* HbS. c.) **True**: Replacing polar Glutamate with non-polar Valine creates a hydrophobic "patch" on the surface, allowing interaction with other hemoglobin molecules.

Extra: In **Sickle Cell Anemia**, a point mutation in the $\beta$-globin gene (GAG $\to$ GTG) results in the substitution of **Glutamate (polar)** with **Valine (non-polar)** at the 6th position. This hydrophobic Valine residue fits into a hydrophobic pocket on an adjacent hemoglobin molecule (specifically the $\beta$ chain of another deoxy-HbS tetramer), leading to **polymerization** and the characteristic "sickling" of the RBC.

Flashcard 399: In a research study, small circular DNA molecules that resemble a bacterial chromosome are isolated from exocrine pancreatic cells. Further analysis shows that these molecules code for proteins, transfer RNA, and ribosomal RNA. From which of the following cellular structures did these DNA molecules most likely originate?

Answer: Mitochondria Mitochondria contain circular DNA chromosomes that resemble bacterial (prokaryotic) chromosomes. They are inherited maternally and encode their own proteins, transfer RNA (tRNA), and ribosomal RNA (rRNA).

Flashcard 400: 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)