Diseases Unit 1 Flashcards
What is Patau Syndrome?
Trisomy 13
What is Cystic Fibrosis?
1) Autosomal Recessive
2) 3 base deletion in CFTR results in F508 mutation that prevents normal folding of channel, leading to protein degradation
3) Can detect 3 base pair deletion using PCR
What is OTCase deficiency?
1) X-linked recessive
2) Ornithine carbamoyltransferase (OTCase) catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle and is located in the mitochondrial matrix
What is Rett syndrome?
1) X-linked dominant; lethal in males
2) Mutation in MeCP2 (CpG island binding protein)
3) scoliosis; mental problems
What is MERRF (Myoclonic Epilepsy with Ragged Red Fibers)?
1) Point mutation in mtDNA A8344G (MTTK)
What is MELAS (Mitochondrial Encephalopathy with Lactic Acid and Stroke)?
1) Point mutation in mtDNA A3243G (MTTL) or in mtDNA G4332A (MTTQ)
2) Mutations in ND genes and tRNA
What is LHON (Leber Hereditary Optic Neuropathy)?
1) Point mutation in mtDNA G11778A
2) Mutations in ND genes
What is KSS (Kearns-Sayre Syndrome)?
1) Deletion in mtDNA
2) Mutant mitochondria are localized to muscle and CNS
What is Pearson Syndrome?
1) Deletion in mtDNA
2) Mutant mitochondria found in high amounts in tissues, especially in blood
What is CPEO (Chronic Progressive Opthalmoplegia)?
1) Deletion in mtDNA
2) Mutant mitochondria is more localized
What is Alpers/Ataxia?
1) Mutation in nuclear encoded mt DNA causes mutations in Pol G
What is Lupus?
1) Autoimmune disease with CNV involvement
What is CYP2C9 deficiency?
1) Polymorphic alleles result in “poor metabolizers” (16%)
2) Cannot metabolize Warfarin as well
What is CYP2D6 deficiency?
1) Polymorphic alleles result in “poor metabolizers” (20%)
What is OI (Osteogenesis Imperfecta)?
1) Autosomal Dominant
2) Type 2>3>4>1 (severity)
3) Type 1 reduces production of collagen; Types 2-4 result in Glycine (Every third amino acid in collagen) to be substituted for a bulky amino acid
What is common between Bovine Spongiform Encephalopathy (Mad cow disease), kuru, Scrapie, Creutzfeldt–Jakob disease (CJD), Fatal Familial Insomnia, & Gerstmann-Straussler-Scheinker (GSS) ?
1) Transmissible Spongiform Encephalopathy (TSE)
2) Presence of abnormal prion protein causing an increase of beta sheet formation (Constitutive –> Scrapie)
What is HIV?
1) HIV provirus uses Rev protein to prevent mRNAs from getting spliced. Allows them to leave nucleus unspliced
What are indicators of Liver Damage?
Elevated levels of:
1) Alanine Aminotransferase (ALT)
2) Aspartate Aminotransferase (AST)
What are indicators of Pancreatitis?
Elevated levels of:
1) Amylase
2) Lipase
What are indicators of Myocardial infarction?
Elevated levels of:
1) CK-MB (Creatine Kinase MB)
2) cTnI (Cardiac Tropnin I; Gold Standard)
What is ATR-X Syndrome?
1) X-linked recessive
2) Chromatin disease affecting DNA helicase
3) mental retardation, facial & skeletal abnormalities, alpha thalassemia
What is Rubinstein-Taybi Syndrome?
1) Autosomal Dominant
2) Affects histone acetyltransferase in CBP (CREB Binding protein)
3) Broad thumbs, big toes, & mental retardation
What is Dyskeratosis Congenita?
1) X-linked recessive
2) Decreased telomerase; shortened telomeres
3) Causes loss of keratin, resulting in many skin, nail, & hair defects
What is Adenosine Deaminase Deficiency?
1) Autosomal recessive
2) Immune deficiency; affects lymphocytes
3) Very susceptible to infection
How is tuberculosis treated?
1) Rifampin binds to bacterial RNA Pol changing its comformation and preventing mRNA synthesis
What is alpha-amantin?
1) Poisonous mushroom
2) Blocks elongation by RNA Pol 2
What is Hemophilia B Leyden?
1) Reduces HNF4 (Hepatocyte nuclear factor 4) binding
2) Factor IX levels increase during puberty
What is HPV caused by?
1) E6AP catalyzes degradation of p53 tumor suppressor protein and contributes to cervical carcinoma
What is HbC?
1) Beta chain Glu 6 Lys
2) Oxygenated HbC crystallizes
3) Mild hemolysis
What is Hb-Hammersmith?
1) Beta chain His 92 Tyr
2) Unstable hemoglobin causes precipitation and hemolysis
What is Hb Kempey?
1) Beta chain Asp 99 Asn
2) Hb has high oxygen affinity, so less oxygen is released to tissues
What is alpha thalassemia?
1) Deficiency in alpha subunits most commonly caused by uneven crossing over events (deletion from chromosome 16)
2) Mild microcytic anemia
What is beta thalassemia?
1) Deficiency in beta subunits caused by alpha chain inclusion body formation in hematopoetic stem cells
2) Splenic enlargement, gall stones, microcytic anemia
What is hereditary persistence of fetal hemoglobin?
1) Big deletion in beta and delta hemoglobin chain genes, resulting in persistence of HbF (gamma chain genes still present)
What is Muscular Dystrophy?
1) X-linked recessive
What is Huntington’s disease?
1) Autosomal Dominant
2) Increased Beta sheet creating amyloid fibers
What is Neurofibromatosis?
1) Autosomal Dominant
What is true in Autism?
1) 10-20% of patients with autism have CNVs
What is thrombophilia?
1) Hypercoagulation
2) Mutations in factor 5 (A to T) or prothrombin
What is Bart’s hemoglobin?
1) Gamma tetramer
2) Extremely high affinity for oxygen
What is Immunodeficiency, Centromere Instability and Facial anomalies syndrome (ICF)?
1) Problem with DNA Methyltransferase
What is Meier Gorlyn Syndrome?
1) Mutation in ORC genes
2) Underdeveloped/missing kneecaps, small ears, microcephaly, but normal intellect
What is Seckel Syndrome?
1) Mutation in ATR (checkpoint kinase used in cell cycle)
2) Narrow, birdlike faces & mental retardation
Topoisomerase inhibitors are used widely as ______ drugs
1) Anticancer
What is idiopathic pulmonary fibrosis?
1) Mutation in telomerase
2) Lung scarring
3) Undetectable
What is aplastic anemia?
1) Mutation in telomerase
2) Hematopoietic stem cells cannot proliferate in absence of telomerase
What is Junctional Epidermolysis Bullosa?
1) Homozygous defecy in LAMB3 gene
2) Can undergo intragenic second site suppression t o create somatic mosaicism
What is hereditary non polyposis colon cancer (Lynch syndrome)?
1) Autosomal Dominant
2) Defective mismatch repair
What is Hemophilia B Brandenburg?
1) Reduces HNF4 binding and Androgen Receptor Binding
2) Factor IX levels remain low throughout life
What is Aniridia?
1) Defect in Pax6 gene, resulting in defective Pax6 protein
2) Lack of irises
What is Spinal Muscle Atrophy?
1) Two genes: SMN1 and SMN2.
2) Silent mutation in SMN2 interferes with spliceosome binding, leads to exon skipping
3) Results from homozygous mutations that inactivate SMN1
What is Diptheria?
1) Symptoms: swollen neck, thick gray membranous coating in throat
2) Cause: toxin ADP ribosylates eEF2, preventing elongation of translation
What is Hereditary Hyperferritinemia Cataract Syndrome?
1) IRE is mutated so it cannot bind IRE-Binding Protein, resulting in excess ferritin synthesis
2) Symptom: cataract formation
What is Vanishing White Matter?
1) Autosomal Recessive
2) Cause: mutation in eIF2B which inhibits translation initiation by decreasing supply of Met-tRNA
3) Symptoms: neurological deterioration, ataxia, ovarian failure
What is Prader Willi Syndrome?
1) Autosomal Dominant
2) Symptoms: Mental retardation, large appetite
3) Cause: large deletion on chromosome 15 inherited from father or uniparental disomy
What is Angelman Syndrome?
1) Autosomal Dominant
2) Symptoms: severe mental retardation, ataxia
3) Cause: defect in ubiquitin ligase (E3) due to large deletion on chromosome 15 inherited from mother or uniparental disomy
What is I cell disease?
1) Cause: genetic defect in adding mannose-6-phosphate resulting in enzyme failure to target proteins to lysosome and accumulation of inclusion bodies
What is Zellweger Syndrome?
1) Cause: mutation in genes required for peroxisome targeting or function
What is Multiple Sulftase Deficiency?
1) Symptoms: progressive paralysis, skeletal deformities, neurological defects
2) Cause: defect in Sulfatase Modifying Factor 1 (SMF1) required to modify an essential cysteine in the active site of sulfatases
What is Keshan Disease?
1) Symptoms: dilated cardiomyopathy, congestive heart failure, striated muscle degeneration, flabby heart
2) Cause: Selenium deficiency prevents selenoproteins from catalyzing oxido-reduction reactions such as reduction of peroxides.
What is Familial Hyperproinsulinemia?
1) Autosomal Dominant
2) Cause: defective proinsulin cleavage resulting in equal amounts of insulin and proinsulin
3) Note: no diabetes in the heterozygote
What is polio virus?
1) Mechanism: polio protease 2A cleaves eIF4G which makes it incompatible with CAP dependent initiation but still compatible with IRES mediated initiation favored by the polio virus.
What is sepsis?
1) Hypercatabolic state where protein turnover rate is elevated especially in skeletal muscle due to cortisol induction of ubiquitin-mediated proteolysis.
What is Xeroderma Pigmentosum (XP)
null mutation in early process of nucleotide excision repair, characterized by UV radiation sensitivity, skin malignancies, neurological/ocular abnormalities
What is Cockayne Syndrome?
loss/defect in CS-A/CS-B/XP-B/XP-D/XP-G causes RNA polymerase to stall at damage site (problem with transcription coupled repair), characterized by photosensitivity, growth/mental retardation, but little skin cancer
What is Trichothiodystrophy?
defective XPB or XPD (helicase components of TF2H) creates problems with repair and transcription, characterized by brittle hair and nails, UV sensitivity, but no cancer predisposition
What is Bloom Syndrome?
defective BLM gene that codes for RecQ-like helicase causes defect in double strand break repair, characterized by growth defects, sun sensitivity, cancer predisposition
What is Werner Syndrome?
defect in WRN coding for RecQ-family helicase (has helicase and nuclease activity) causes defect in double strand break repair, characterized as “premature aging disease” and other age related diseases (osteoporosis, atherosclerosis, diabetes, etc)
What is Li-Fraumeni Syndrome?
one p53 allele is mutated and increases risk of developing cancer 25x, defective DNA damage response (cancer predisposition syndrome)
What is Xeroderma Pigmentosum Variant?
lack DNA polymerase eta and cannot pair thymine dimers with adenine dimers, characterized by hypermutagenesis compared to XP (permanent mutator phenotype: mutator phenotype is permanent due to a first mutation in a repair gene, examples include HNPCC, XP, XPV)
What is mupirocin?
antibiotic that inhibits Isoleucine-tRNA synthase
What is streptomycin?
targets 30S subunit to cause misreading and inhibit initiation
What is Tetracycline?
targets 30S subunit to inhibit binding of AA-tRNA to A site
What is Chloramphenicol?
targets 50S subunit, inhibits peptidyl transferase
What is erythromycin?
targets 50S subunit, inhibits translocation
What is puromycin?
targets 50S and 60S subunits, causes premature release of nascent polypeptide, contains an alpha amino group that is very similar to tyrosine
What is Diphtheria Toxin?
targets eEF2 to inhibit translocation -fragment B allows internalization into cell, fragment A causes ADP ribosylation of eEF2
What is Ricin?
targets 60S subunit to inhibit binding of AA-tRNA to A site -fragment B allows internalization into cell, fragment A causes depurination of 28S rRNA at A residue
What is Multiple Sulfatase Deficiency (MSD)?
defect in sulfatase-modifying factor 1 gene (SMF-1) that normally modifies an essential cysteine residue in the active site of sulfatases, characterized by progressive paralysis/skeletal deformities)
