Molecular Genetics — Flashcards

Flashcard 391: 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 392: 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 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: 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 396: What are the two types of DNA mutation that occurs in duchenne muscular dystrophy?

Answer: Frameshift, nonsense mutation.

Flashcard 397: 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 398: A group of investigators is studying the mechanisms involved in cancer pathogenesis. -They find that interaction of a certain growth factor with its receptor leads to the following sequence of event: 1. Binding of growth factor 2. Autophosphorylation of tyrosine residues 3. Activation of phosphoinositide 3-kinase 4. Activation of protein kinase B (Akt) 5. Activation of X What is the most likely direct effect of X upon activation?

Answer: Stimulation of protein synthesis The sequence describes the **PI3K/Akt/mTOR** signaling pathway. Step 5 (X) is the activation of **mTOR**. mTOR then phosphorylates targets such as 4E-BP1 and p70S6K to increase mRNA translation. **Note:** mTOR inhibitors like **sirolimus (rapamycin)** are used to treat certain cancers and as immunosuppressants.

Flashcard 399: 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 400: 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).