ex21q Flashcards
What are the major composition elements in the human nuclear genome?
Protein-coding genes (~1-2%), intronic sequences (~26%), regulatory regions (~5%), repeats and transposable elements (~50%, LINEs 21%, SINEs 13%), non-coding RNA genes (e.g., miRNAs, lncRNAs).
Describe the different classes of non-protein coding genes and their roles.
rRNA: Ribosome structure and function, tRNA: Translation by carrying amino acids, miRNA: Post-transcriptional regulation of gene expression, lncRNA: Chromatin remodeling and transcriptional regulation, piRNA: Transposon silencing, snRNA: Splicing, snoRNA: RNA modification.
What are the most common epigenetic modifications on histone tails, and which amino acids are modified?
Methylation: Lysine (K) and Arginine (R), Acetylation: Lysine (K), Phosphorylation: Serine (S), Threonine (T), Tyrosine (Y), PARylation, ubiquitination, and SUMOylation: Lysine (K).
What are the two main mechanisms by which histone modifications exert their effects?
1) Chromatin structure modulation: Controls accessibility of DNA. 2) Effector molecule recruitment: Modifications create binding sites for proteins (readers) to regulate gene expression.
Define epigenetic writers, readers, and erasers with examples.
Writers: Add modifications (e.g., methyltransferases, HATs), Readers: Bind modifications (e.g., chromodomain of HP1 to H3K9me3, bromodomains to acetylated lysines), Erasers: Remove modifications (e.g., HDACs, TET enzymes).
What are the potential modes of inheritance of the disease in the pedigree?
1) Not Y-linked: Females affected. 2) Not X-linked dominant: Father-to-son transmission observed. 3) Not mitochondrial: Fathers pass it. 4) Not X-linked recessive: Male II.1 unaffected despite a homozygous mother. 5) Not autosomal recessive: Requires unlikely carriers. 6) Most likely autosomal dominant: Vertical inheritance with affected males and females.
Why are nonsense mutations less common in human diseases?
1) Nonsense-mediated decay (NMD): Degrades mRNA with premature stop codons. 2) Lethality: Severe nonsense mutations often cause embryonic lethality, reducing observation in living individuals.
Why is FH dominant and CF recessive?
FH: Haploinsufficiency—one defective allele reduces LDL receptor function. CF: One functional CFTR allele is sufficient to prevent disease.
Would Trikafta work against the Gly542X mutation in CF?
No. Trikafta improves folding of Phe508del CFTR but cannot restore function for Gly542X, a nonsense mutation leading to truncated protein.
Mention three types of transmembrane receptors and one intracellular receptor.
Transmembrane: GPCRs, receptor tyrosine kinases, ion channels. Intracellular: Nuclear hormone receptors.
Describe the players in a signal transduction pathway involving a transmembrane receptor, RAS, and MAPK cascade.
Receptor activation → RAS (GTP-binding protein) → RAF → MEK → ERK (MAPK cascade).
What are two pathways activated by EGFR signaling?
1) RAS-RAF-MEK-ERK pathway. 2) PI3K-AKT pathway.
Describe four targeted ways to inhibit EGFR signaling.
1) Monoclonal antibodies. 2) Tyrosine kinase inhibitors. 3) RNA interference. 4) Ligand blockers.
What is the main concept and limitations of immune checkpoint inhibitors?
Concept: Block immune checkpoints (e.g., PD-1/PD-L1) to boost T-cell activity against tumors. Limitations: Immune-related adverse events, resistance, and high cost.
What is the difference between global and local alignments in bioinformatics?
Global: Aligns entire sequences end-to-end. Local: Aligns only regions of high similarity.
