Single Gene Disorders Flashcards
<p>Factor V Leiden</p>
<p>Discovered in 1994, the Leiden mutation (1961 A->G, R506Q) in the coagulation factor V gene F5 (1q23) causes a hypercoagulable (thrombophilic) phenotype. Present in heterozygous form in 4-7% of general population, .06-.25% homozygous. Treated with anticoagulants. Contraceptive use increases risk for women. PCR-RFLP, SSP-PCR and Invader used. A mutation in the 3' untranslateed region of the gene that codes for prothrombin or coagulation factor II, F2 (11p11-q12), results in an autosomal-dominant increased risk of thrombosis.</p>
<p class=”large” style=”text-align:center”;>Hemachromatosis</p>
<p class=”large” style=”text-align:center”;>Autosomal-recessive condition that causes overabsorption fo iron from food.Iron acumulation causes pancreas, liver, and skin damage, heart disease, and diabetes. Tested by blood levels. Treated by phlebotomy. Caused by a dysfunction of the hemachromatosis type I gene, HFE or HLA-H (6p21.3). HFE codes for a membrane-bound protein that binds with beta2 microgloblin and transferrin on the membrane of cells in the small intestine and also on the placenta. The protein directs iron absorption based on cellular iron loads. In the absense of HFE function, intestinal cells do not sense iron stores, and iron absorption continues into overload. Most frequent mutation is C282Y (PCR-RFLP), present in approximately 10% of white population. Others in HFE are H63D and S65C.</p>
<p>Cystic Fibrosis</p>
<p>Autosomal-recessive life-threatening disorder causes severe lung damage and nutritional deficiencies. Affects the cells that produce mucus, sweat, saliva, and digestive juices causing them to become thick and sticky. No cure but gene therapy theorizied. Caused by a loss of function of the CF transmembrane conductance regulator, CFTR gene (7q31.2) wich codes for a Cl channel membrane probtein. 3-bp deletion that removes phenylalanine residue fro position 508 of the protein (F508del). More that 1300 other mutations and variations have been reported in and around the CFTR gene in diverse populations. RFLP, PCR-RFLP, heteroduplex analysis, temporal temperature gradient gel electrophoresis, single-strand conforemation polymorphism (SSCP), SSP-PCR, Invader, bead array technolog (Tag-It, TM Bioscience), and direct sequencing.</p>
<p>Cytochrome P-450</p>
<p>Cytochrome P-450 comprises a group of enzymes localized to the endoplasmic reticulum which are mono-oxygenases (participate in enzymatic hydroxylation reactions and also transfer electrons to oxygen) and influemnce steroid, AA, and drug metabolism using NADH or NADPH as H donors. Present in high concentrations in the liver and small intestine. Hormones, caffeine, chemotherpeutic drugs, antidepressants, and oral contraceptives all affected. Over 30 reported variations, classified according to families and subfamilies. ie CP2A6 = cytochrome P-450, subfamily IIA, polypeptide 6. CYP1A2, CYP2 and Cyp3 most important for drug metabolism. Allele-specific PCR, microarray or bead array technology.</p>
