M2M Diseases and Drugs Flashcards
Gout
purine precipitate accumulates in joints
Trichothiodystrophy
Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. Caused by defects in NER
Marfan syndrome
Splicing defect: caused by mutations that disrupt splicing of the fibrillin gene transcript (fibrillin is a connective tissue protein that is important for the integrity of the walls of the heart and blood vessels). They are tall and prone to aneurysms
Beta-thalassemia
TATA box binding defect:
mild inherited anemia (low hemoglobin count). Caused, here, by a mutation in the promoter of the b-globin gene, resulting in lowered rate of production of b-globin protein. (less promotion = less transcription)
Gamma-delta-beta thalassemia
more serious anemia caused by a deletion in the locus control region for the transcription of all globin genes, resulting in the loss of globin transcription
Diseases caused by mutations in DNA Control Elements
Beta-thalassemia
Gamma-delta-beta thalassemia
Hemophilia B Leyden
Fragile-X syndrome
Hemophilia B Leyden
X-linked disease (usually males) that affects clotting. Again, a problem in the promoter region of a clotting protein gene. Tends to get partially better at puberty.
Fragile-X syndrome
Again, usually a disease of men. Results in mental retardation and atypical development of the face with enlarged testicles (macroorchidism). Caused by an expansion in the CGG count upstream of a particular gene (the FMR1 gene), which results in an abnormally high rate of methylation in that region and transcriptional silencing of the gene.
Diseases with mutations in SSDBP’s
Craniosynostosis
Waardenburg Syndrome
Androgen insensitivity syndrome
Craniosynostosis
premature closure of the skull sutures in infants. Arises from a mutation in a homeodomain protein that causes the protein to bind more strongly, creating a “hypermorphic allele” that activates genes more strongly than it should. (upregulates proteins that close sutures via homeodomain mutation)
Waardenburg Syndrome
Type II – white streak of hair, wide face. 15% of cases result from mutation in MITF gene (encodes a bHLH (basic Helix-loop-helix) DNA binding protein), affects transcription of genes important for pigmentation and hearing
Waardenburg syndrome: deafness, pigmentation defects. Associated with mutations in the MITF (microphthalmia-associated transcription factor) gene (which codes for a bHLH binding protein that regulates melanocyte development).
Androgen insensitivity syndrome
Feminization or undermasculinization. Indifference of androgen receptors to androgen hormones. Caused by a mutation in the zinc-finger androgen receptor binding domain or ligand binding domain. This downregulates the transcription of genes controlled by male androgens.
Diseases associated with HAT’s and HDAC’s
Leukemia
Rubinstein-Taybi syndrome
Leukemia
haematopoietic (formation of blood cell components) disease involving chromosomal translocations over-activating fusion proteins that alter the activity of HATs or HDACs.
Rubinstein-Taybi syndrome
growth and mental retardation, broad thumbs and toes, craniofacial dysmorphism. Results from mutations in one copy of CREB binding protein gene (haploinsufficiency); CBP is a widespread HAT important in development and its insufficiency has particularly drastic effects.
What happens when certain viruses (rhinovirus, poliovirus, etc) prevent eIF-4E and eIF-4G from coming together and forming the initiator complex?
Instead of participating in cap-dependant translation, ribosomes are free to bind to areas of the viral 5’ UTR called Internal Ribosomal Entry Sites (IRESes) (as well as any host IRESes present). Thus predominantly the viral mRNA will be translated instead of the host mRNA.
Diseases associated with defects in Post-Translational Modification
Scurvy
Clotting Disorders
Congenital Disorder of Glycosylation
Scurvy
Hydroxylation of proline residues in collagen stabilizes the structures, mediated by vitamin C. Underhydroxylation of collagen proline residues results in weak connective tissue
Clotting Disorders
Carboxylation of glutamate residues on prothrombin important for proper clotting. This process is mediated by Vit. K, thus Vit K deficiency àclotting disorder. Warfarin is an anticlotting drug that targets carboxylation of prothrombin
Congenital Disorder of Glycosylation
cells need to glycosylate asparagine residues of proteins within cell membrane to increase their hydrophilicity. Dysfunction of glycosylation mechanism results in CDG
Diseases associated with protein folding defects
Prion disease
Alzheimers
Parkinsons
Amyloidosis
Prion disease
the same prion protein simply misfolded, which then causes other normal prion proteins to misfold. These are altered from alpha helices to beta sheets causing them to aggregate within amyloid plaques leading to neuron loss and gliosis
Alzheimers
the normal AB-40 folds correctly, however the slightly different AB-42 misfolds and aggregates into amyloid plaques. This leads to B-amyloid plaque and tau tangles.
Parkinsons
Beta-synuclein misfolds into Lewy Bodies
