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36 Cards in this Set
- Front
- Back
What is polyplasm?
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cells have multiple mitochondria which contain multiple copies of genomes
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what is heteroplasm?
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not all mtDNA is the same
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What is the threshold effect?
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the phenotypic expression of a pathogenic mtDNA based on the proportion of wild type vs. mutant mtDNA in diffferent tissue… thus the minimum critical number necessary to impair energy metabolism.
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What is Mtiototic segregation?
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if there is a mutation in mtDNA it may be distributed unequally and a mutant phenotype may be expressed.
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What is the mutation rate of mtDNA compared to nuclear DNA?
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5-10 times greater
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What is a Gomori trichromehistochemical stain and what color is a positive test result for abnormal mtDNA? What does the red indicate?
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allows detection of abnormal deposits of mtDNA… red: RRF (ragged red fibers)… red indicated an excess of mtDNA, which is an compensatory measure
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What does a ragged-blue-fibers result indicate?
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succinate dehydrogenase excess
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What type of inheritance accounts for 4/5 of the mitochondrial metaboism disorders? Why?
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mendelian… the defects are caused by nuclear DNA, for stubstrate transport and utililization, krebs cycle and oxidative-phosphorylation coupling)
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What is the effected mechanism that is affected by mtDNA?
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ETC complexes…
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What are 3 major modes of genetic defects affecting mtDNA
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mtDNA point mutations, mtDNA rearrangements, and defects of intergenomic signalling.
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What is genererally affected by mtDNA point mutations?
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mitochondrial tRNA
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How can point muations of mtDNA be determined?
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PCR and RFLP
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What are the 3 most common point mutation diseases? And which symptoms are associated with them
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MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), MERRF (myoclonus epilepsy with ragged-red fibers), and NARP (Neuropathy, ataxia, and retinitis pigmentosa)/MILS (maternally-inherited Leigh syndrome)
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What is the cause of Kearns-Sayres syndrome?
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mtDNA rearrangements
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What types of inheritance is shown with mtDNA rearrangements?
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It's not… it's sporadic… but deletions show up early in development such that cell population widely affected
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What test is used to determine mtDNA rearrangements?
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southern blot
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what are defects of intergenomic signaling?
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mtDNA defected that are caused because nDNA factors that affect replication, transcription and translation
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Why is it believed that nDNA plays a role in defects of intergenomic signalling?
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mendelian inheritance
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What are the two most seen clinical manifestation of mitochondrial diseases?
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CNS and skeletal and heart muscle… usually multi-systems in tissues with high ATP requirements
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What are the pedigree characteristics of mitochondrial inheritance,.
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passed on from the mother only to both males and females
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what is homoplasmy?
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where all mtDNA is the same
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What are the symptoms associated with MERF?
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myoclonus, seizures, myopathy, cerbellar ataxia
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What are VER (visual evoked responses) associated with?
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MERRF
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what is anaerobic threshold?
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it's a measure of muscle capcity to perfomr oxidative phophorylation before lactic acid begins to accumulate in the body
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Which mitochondrial disease is associated with sensory neuropathy, ataxia, retinitis pigmentosa, dementia, reduced fetal movemnts developmental delay, and abnormal EEG?
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NARP/MILS
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Which has the worse mutation load, NARP or MILS?
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Moderate: NARF is 70%, High: MILS is 80-90%
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What explains differences in mitochondrial disease expression?
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mutation load
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T/F MILS and NARP coexist in the same family.
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TRUE
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How is aminoglycoside induced deafness (AID) caused?
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a mutation in some mitochondria causes it to (like some bacteria) interact with aminoglycosidease, by interfering with mitochondrial translation
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Which disease causes large-scale deletions?
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Kearns-Sayre Syndrom
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What are disease associated with the nuclear genome?
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carnitine cycle enzymes, Krebes cycle enzymes, and coenzyme Q deficiencies
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What are 5 sites of carnitine cycle defects?
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transporter, CPT I deficiency, carnitine-acy carnitine translocase, and CPT II deficiency
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What are the 4 clinical manifestations of transporter deficiencies associated with the transporter? (which is the hallmark symptom)
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cardiomyopathy (hallmark), hyptonia (weakness), failure to thrive, and hypoketotic hypoglycemia
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What is the genetic cause of carnitine transporter (OCTN2) deficiencies?
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stop codons on chr 5
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Which enzymes have been implicated in Kreb's cycle deficiencies?
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∂-ketoglate dehydrogenase, fumarase, and succinate dehydrogenase deficiency
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What are the clinical manifestation of CoQ deficiencies?
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Myopathy, ataxia, and encephalomyopathy with renal failure
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