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41 Cards in this Set
- Front
- Back
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Pt w/rapid loss of vision in he central visual field as a result of optic nerve death. Vision loss is in the 3rd decade of life and is irreversible. This runs in the family. The mutation is a missense mutation in the mtDNA.
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Leber hereditary optic neuropathy (LHON)
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Pt w/epilepsy , dementia, ataxia, and myopathy. Caused by a single base mutation in a mtDNA tRNA gene.
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Myoclonic epilepsy with ragged red fibers
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What disease is caused by a single-base mutation in tRNA mitochondria?
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Mitochondrial encephalomyopathy and stroke like episodes (MELAS)
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What are the mitocondrial disorders
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1. Leber hereditary optic neuropathy (LHON), 2. myoclonic epilepsy with ragged red fibers (MERRF), 3. mitochondrial encephalomyopathy and stroke-like episodes (MELAS), 4. kearns-sayre disease, 5. pearson syndome, 6. chronic progressive external opthalmoplegia
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What is leber hereditary optic neuropathy(LHON)
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Optic nerve death in 3rd decade, heteroplasmy uncommon, MISSENSE mutation in protein coding genese
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What is myoclonic epilepsy with ragged red fibers (MERRF)
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Single base changes in tRNA, epilepsy, ataxia, dementia, myopathy, heteroplasmic, highly variable expression
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What is mitochondrial encephalomyopathy and stroke-like episodes(MELAS)
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Single-base mutation in tRNA, heteroplasmic w/variable expression
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What are the mitochondrial disorders due to duplications and deletions in the mitochondrial chromosome
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1. Kearns-sayre disease, 2. pearson syndrome, 3. chronic progressive external opthalmoplegia
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Define:anticipation
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Some dominant disorders are more severe in later generations (ie myotonic dysrophy or huntingtons chorea)
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What is the MOA of huntingtons?
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Repeated codon sequence expansion (CAG) glutamine -> occurs during meiosis(greater number can cause earlier and/or more severe disorder)
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Inheritance pattern of myotonic dystrophy
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Anticepation -> every generation gets the disease earlier and earlier age
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Fragile X-syndrome
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Most common inherited form of mental retardation (down syndrome is more common but not inherited)
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Cells that are in culture but end of long arm of X-breaks in low folic aicd
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Fragile-x-syndrome
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The sherman paradox
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Normal transmitting males occur -> not affected, but have affected descendants
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Pt w/ long face, prominent jaw, large ear
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Fragile-x
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Genomic imprinting
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Certain genes are only expressed (inherited from mom or dad)
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Which disease sees a deletion from dad?
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Prader willie
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Which disease sees a maternal deletion?
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Angelman
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Fragile X-inheritance pattern
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Transmitting numbered copied repeats -> greater than 230 is abnormal
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Dosage compensation
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Dosage compensation is a genetic regulatory mechanism which operates to equalize the phenotypic expression of characteristics determined by genes on the X chromosome so that they are equally expressed in the human XY male and the XX female
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What is the lyon hypothesis?
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One X chromosome in each XX cell is inactivated -> barr body is seen in nucleus
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What are the rules of X-inactivation
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1. Inactivation is random, fixed, and incomplete
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X-inactivation center
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XIST gene on the X-chromosome -> transcribes 17kb RNA from inactivated X-chromosome -> coats inactive X (maintains inactivation) -> methylation = high + histone = deacetylation
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What are the X-linked disorders we need to know?
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1. Hemophilia A, 2. duchenne's muscular dystrophy, 3. red-green color blindness
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What is the hardy-weinberg expression of males in x-linked recessive? Females?
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Males = q, females = q^2
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What is unique about x-linked recessive pedigrees
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No father -> son transmission or passage thru females is a skipped generation; affect father + normal mother = no affected children
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What are the characterisitcs of hemophilia A?
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Factor VIII deficiency (X-chromosome) -> results in prolonged bleeding from wounds, hemorrhages in joints and muscles(hemearthrosis) -> intracranial bleeding -> death
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What type of mutations occur in the Factor VIII gene?
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Non-sense, deletion, inversion = severe; missence = mild
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5 yo Pt w/severe muscular arophy, clumsy, weak-> heart/respiratory muscles impaired, Creatinine kinase released by msucle -> cardiac/respiratory failure by 25 yo
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Duchenne muscular dysrophy
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What does the DMD protein do?
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On cytoplasmic side of membrane -> involved in cytoskeltal integrity -> binds F-actin and dystroglycan (in membrane)
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What disease is the altered function of dystrophin?
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Beckers muscular dystrophy
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What is the MOA for color blindness?
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Opsin proteins absorb colors -> red + green opsins are adjacent on X-chromosome thus can affect both at same time (caused by unequal crossing over)
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Define: deuteranopia
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No green vision
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Define:protanopia
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No red vision
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What is the mode of transmission for x-linked dominant inheritance
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Males get from mother, females get from either parent
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What are the x-linked dominant disorders
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1. Hypophosphatemic rickets, 2. incontinetia pegmenti, 3. rett syndrome
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Hypophosphatemic rickets
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Kidnesy cant reabsorb phosphate, abnormal ossification -> bones bend and distort (x-linked dominant)
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Incontinentia pigmenti
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Abnormal skin pigmentation + teeth, neurological and ocular abnormalities, males losst in utero(x-linked dominant)
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Rett syndrome
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Autism, ataxia, mental retardation, some males survive to term (x-linked dominant)
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Holandric inheritance
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Y-chromosome inheritance-> father to son transmission; most genes involved w/sex determination, spermatogenesis, testicular function; X-Y crossing -over occur in this region
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What is unique about mitochondrial inheritance
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Circular chromosome, produces its own ribosomes and tRNAs, Inheritance = maternal(from the mom only), mutation rate = high -> lacks repair systems
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