Molecular Genetics — Flashcards

Flashcard 391: 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 392: A 2 y/o boy comes with easy bruising. -Parent stated he develops marked bruising & open wounds following minor trauma. -Skin is difficult to suture due to its extreme fragility. -Physical exam: Hyperextensible skin, multiple ecchymoses over the forearms. - Skin biopsy: defect in extracellular processing of collagen. -Which steps of collagen synthesis is most likely impaired in this patient?

Answer: N-terminal propeptide removal or N & C terminal propeptide removal. due to defect in procollagen peptidases (defect in collagen 3 & 5) that lead to Ehlers-Danlos syndrome. (hyperextensible skin, joint laxity, tissue fragility)

Flashcard 393: 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 394: 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 395: What are the two types of DNA mutation that occurs in duchenne muscular dystrophy?

Answer: Frameshift, nonsense mutation.

Flashcard 396: 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 397: In an experiment, a protein mixture obtained from a cell culture is separated by gel electrophoresis and subsequently transferred to a filter membrane. -Labeled: Double-stranded DNA probes are used to detect a specific protein of interest in the sample. -What protein is most likely to be detected by this method? a.) Ras b.) C-Jun c.) B1- adrenoreceptor d.) S-100 e.) Adenylate cyclase

Answer: C-jun Other possible answers: c-Fos, or c-Jun & c-Fos because Double stranded DNA probes were use, which means they are using Southwestern blotting technique, (DNA - binding protein).

Flashcard 398: 5 y/o boy comes with progressive muscle weakness that has resulted in numerous recent falls. - Physical exam: Bilateral calf enlargement. - He uses his hands and arms to help push himself to an upright position. - Genetic analysis reveals a point mutation within exon 48 of the gene encoding this muscle protein. - This patient's gene mutation has most likely resulted in which mRNA codon changes?

Answer: Creation of a premature stop codon (Nonsense mutation) Duchenne Muscular Dystrophy (DMD) is typically caused by frameshift deletions, but when a point mutation is specified, it is most often a nonsense mutation (e.g., UCA → UGA/UAG/UAA).

Flashcard 399: Describe these 2 genetics term? -Transition -Transversion

Answer: Transition: you replaced a purine by a purine, a pyrimidine by a pyrimidine. -Transversion: you replaced a purine by a pyrimidine. A pyrimidine by a purine.

Flashcard 400: 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.