Molecular Genetics — Flashcards

Flashcard 401: 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 402: 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 403: 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 404: Identify the location or function of the following molecular markers: - CCA sequence - Poly-A tail - 7-methylguanosine cap - TATA box

Answer: - **CCA sequence**: Located at the 3' end of **tRNA**; the site where amino acids bind ("**C**an **C**arry **A**mino acids"). - **Poly-A tail**: Added to the 3' end of **mRNA** after transcription (post-transcriptional modification). - **7-methylguanosine cap**: Located at the 5' end of **mRNA** (post-transcriptional modification). - **TATA box**: An upstream eukaryotic **DNA promoter** sequence that binds TATA-binding protein (TBP) to initiate transcription.

Flashcard 405: What are the followings associated with? -Cleavage of DNA strands to remove supercoils -Excision of thymine dimers within DNA -Removal of mismatched base pairs during DNA replication -Removal of RNA primer nucleotides -Unwinding of the 2 strands of template DNA (DNA polymerase 1, DNA gyrase, UV-specific endonuclease, helicase)

Answer: Cleavage of DNA strands to remove supercoils: DNA gyrase (topoisomerase 2) -Excision of thymine dimers within DNA: UV-specific endonuclease. -Removal of mismatched base pairs during DNA replication: DNA polymerase 3 (most common), DNA pol 1, DNA pol 2. -Removal of RNA primer nucleotides: DNA polymerase 1 -Unwinding of the 2 strands of template DNA: Helicase

Flashcard 406: Which cell cycle phase is characterized by resting, non-dividing cells?_____

Answer: G0

Flashcard 407: What form of hemoglobin protects against sickling in sickle cell anemia? _____

Answer: HbF

Flashcard 408: What protein is defective in Marfan syndrome?_____

Answer: Fibrillin (scaffold for elastin)

Flashcard 409: What is the most common cause (95%) of Down syndrome? _____

Answer: Meiotic nondisjunction

Flashcard 410: What is the mode of inheritance of Familial Mediterranean fever? _____

Answer: Autosomal recessive