File Heteroplasmy present in Tsar Nicholas II.jpg thumb Heteroplasmy 16169 C T of Nicholas II of Russia . From Coble et al., 2009. ref name pmid19277206 cite journal author Coble MD, Loreille OM, Wadhams MJ, Edson SM, Maynard K, Meyer CE, Niederst tter H, Berger C, Berger B, Falsetti AB, Gill P, Parson W, Finelli LN title Mystery solved the identification of the two missing Romanov children using DNA analysis journal PLoS ONE volume 4 issue 3 pages e4838 year 2009 pmid 19277206 pmc 2652717 doi 10.1371 journal.pone.0004838 url http dx.plos.org 10.1371 journal.pone.0004838 ref Heteroplasmy is the presence of a mixture of more than one type of an organelle organellar genome mitochondrial DNA mtDNA or plastid DNA within a cell or individual. It is a factor for the severity of mitochondrial disease s, since most eukaryotic cells contain many hundreds of mitochondria with hundreds of copies of mtDNA, it is possible and indeed very frequent for mutation s to affect only some of the copies, while the remaining ones are unaffected. Symptoms of severe heteroplasmic mitochondrial disorders frequently do not appear until adulthood because many cell divisions and a lot of time is required for a cell to receive enough mitochondria containing the mutant alleles to cause symptoms. An example of this phenomenon is Leber s hereditary optic neuropathy Leber optic atrophy . Individuals with this condition often do not experience vision difficulties until they have reached adulthood. Another example is MERRF syndrome or Myoclonic Epilepsy with Ragged Red Fibers . In mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes MELAS , heteroplasmy explains the variation in severity of the disease among siblings. Notable cases One notable example of an otherwise healthy individual whose heteroplasmy was discovered incidentally is Nicholas II of Russia , whose heteroplasmy and that of his ... title Mitochondrial DNA sequence heteroplasmy in the Grand Duke of Russia Georgij Romanov establishes ... more details
Unreferenced stub auto yes date December 2009 Homoplasmy is the presence of a mutation affecting all of the mitochondrial DNA mtDNA copies in a mammalian cell or chloroplast DNA in a plant cell. However, when a mutation occurs, it only affects some of the mitochondria, but not all of them known as heteroplasmy. Since there are hundreds or even thousands of mtDNA copies in every eukaryotic cell, mutations may either be present in all copies homoplasmy or affect only a fraction of them heteroplasmy . Homoplasmy may also refer to the presence of mutation, or insertion of a foreign gene, into all of the plant plastid organelles DNA e.g. all chloroplasts . Homoplasmy, more generally, is the state whereby all non nuclear genomes are the same, whether wild type or mutated. A mutation load needs to be present before disease occurs, which is called the Threshold effect. This load is generally 80 or above mutated mitochondria in a given cell. Mitotic segregation may affect the mutant mtDNA among the daughter cells. Bottom line, in order to get mitochondrial disease you need to have certain usually above 80 of mutant mtDNA to show the phenotype. See also Heteroplasmy Microheteroplasmy Category Mutation Molecular cell biology stub Genetics stub ... more details
In biology, microheteroplasmy is a form of heteroplasmy , a type of mutation al damage to mitochondrial DNA . While heteroplasmy in general includes mutations present in any fraction of mtDNA from fractions of a percent to almost a hundred percent , microheteroplasmy is the presence of mutations levels of up to about 2 5 . This distinction is dictated by technical considerations classical DNA sequencing of mtDNA by the use of PCR is capable only of detecting mutations at levels of 10 or more, as a result of which mutations at lower levels were never systematically observed until the work of Lin et al. ref Hum Mol Genet. 2002 Jan 15 11 2 133 45. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer s disease brain. Lin MT, Simon DK, Ahn CH, Kim LM, Beal MF. PMID 11809722 ref . As it became apparent after the use of Lin s cloning and sequencing strategy, capable of detecting mutations at levels of 1 or less, such low level heteroplasmy , or microheteroplasmy, is exceedingly common, and is in fact the most common form of mutational damage to human DNA found to date. In aged adults, each mtDNA copy has on average 3.3 mutations changing protein structure. This exceeds previous estimates by more than three orders of magnitude. The discovery of microheteroplasmy lends support to the mitochondrial theory of aging, and has already been linked to the causation of Parkinson s disease ref Biochem Biophys Res Commun. 2005 Jan 21 326 3 667 9. Mitochondrial ND5 mutations in idiopathic Parkinson s disease. Parker WD Jr, Parks JK. PMID 15596151 ref . References references Further reading Rejuvenation Res. 2005 Fall 8 3 172 98. Mitochondrial microheteroplasmy and a theory of aging and age related disease. Smigrodzki RM, Khan SM. PMID 16144471 Category Mutation ... more details
Threshold expression is a phenomenon in which phenotypic expression of a mitochondrial disease within an organ system occurs when the severity of the mutation, relative number of mutant mtDNA , and reliance of the organ system on oxidative phosphorylation combine in such a way that ATP production of the tissue falls below the level required by the tissue. The phenotype may be expressed even if the percentage of mutant mtDNA is below 50 if the mutation is severe enough. See also heteroplasmy References Marks basic medical biochemistry a clinical approach By Michael A. Lieberman, Michael Lieberman, Allan D. Marks Page 392 DEFAULTSORT Threshold Expression Category DNA Category Mitochondrial diseases biochem stub ... more details
Infobox disease Name MERRF syndrome Image Ragged red fibers in MELAS.jpg thumb Caption Example of ragged red fibers in MELAS syndrome . DiseasesDB 30794 ICD10 ICD10 G 31 8 g 30 ICD9 ICD9 277.87 ICDO OMIM 545000 MedlinePlus eMedicineSubj eMedicineTopic MeshID D017243 MERRF syndrome or Myoclonic Epilepsy with Ragged Red Fibers is a mitochondrial disease . It is extremely rare, with an estimated prevalence of 1 400,000 in Europe , and has varying degrees of expressivity owing to heteroplasmy . ref http www.ncbi.nlm.nih.gov bookshelf br.fcgi?book gene&part merrf Gene Reviews MERRF ref Presentation It involves the following characteristics progressive myoclonus epilepsies progressive myoclonic epilepsy Ragged Red Fibers clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fiber and appear as Ragged Red Fibers when muscle is stained with modified G m ri trichrome stain short stature hearing loss lactic acidosis exercise intolerance poor night vision Causes The MERRF syndrome is caused by a maternally inherited mutation at position 8344 in the mitochondrial genome in over 80 of cases. This point mutation disrupts the mitochondrial gene for tRNA Lys and so disrupts synthesis of proteins essential for oxidative phosphorylation . Many genes are involved. ref name OMIM MERRF OMIM 545000 MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED RED FIBERS MERRF ref These include MT TK ref name pmid8069654 cite journal author Zeviani M, Muntoni F, Savarese N, et al. title A MERRF MELAS overlap syndrome associated with a new point mutation in the mitochondrial DNA tRNA Lys gene journal Eur. J. Hum. Genet. volume 1 issue 1 pages 80 7 year 1993 pmid 8069654 doi url ref MT TL1 MT TH ref name pmid14967777 cite journal author Melone MA, Tessa A, Petrini S, et al. title Revelation of a new mitochondrial DNA mutation G12147A in a MELAS MERFF phenotype journal Arch. Neurol. volume 61 issue 2 pages 269 72 year 2004 month February pmid 14967777 doi 10.1001 archneur.61.2.26 ... more details
, heteroplasmy was observed in human mtDNA. In a recent paper, Kraytsberg et al 2004 take ... 1735965 ref , heteroplasmy is a newly discovered form of inheritance for mtDNA. Heteroplasmy introduces ... ref Heteroplasmy may result from a mutation during development which is propagated to only a subset ... more details
oocyte is what the new life will have to begin with in terms of mtDNA , the heteroplasmy ... in the same cell can have different variations of the mtDNA . This condition is referred to as heteroplasmy ... more details
of heteroplasmy , the percentage of mitochondria which have mutant alleles , may play a role. ref name ... optic neuropathy Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial ... more details
name Hoeh cite journal author Hoeh WR, Blakley KH, Brown WM year 1991 title Heteroplasmy suggests .... Res. Commun. 15, 127 132. ref See also Col begin Col 3 CORR Hypothesis Haplogroup Heteroplasmy ... more details
rate because they are likely to be overlooked. ref name howell2003 Heteroplasmy Individuals affected by heteroplasmy have a mixture of mtDNA types, some with new mutations and some without. The new ... journal J Mol Evol. year 2008 volume 67 issue 2 pages 191 200 title Frequency and pattern of heteroplasmy ... more details
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