Implications of human evolution andadmixture for mitochondrial replacementtherapy人類進(jìn)化的意義 線粒體替代療法的外加劑

Implications of human evolution andadmixture for mitochondrial replacementtherapy人類進(jìn)化的意義 線粒體替代療法的外加劑

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時(shí)間:2019-08-08

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1、RishishwarandJordanBMCGenomics(2017)18:140DOI10.1186/s12864-017-3539-3RESEARCHARTICLEOpenAccessImplicationsofhumanevolutionandadmixtureformitochondrialreplacementtherapy1,2,31,2,3*LavanyaRishishwarandI.KingJordanAbstractBackground:Mitochondrialreplacement(MR)therapyisanewassisted

2、reproductivetechnologythatallowswomenwithmitochondrialdisorderstogivebirthtohealthychildrenbycombiningtheirnucleiwithmitochondriafromunaffectedeggdonors.EvolutionarybiologistshaveraisedconcernsaboutthesafetyofMRtherapybasedontheextenttowhichnuclearandmitochondrialgenomesareobserv

3、edtoco-evolvewithinnaturalpopulations,i.e.thenuclear-mitochondrialmismatchhypothesis.Insupportofthishypothesis,anumberofpreviousstudiesonmodelorganismshaveprovidedevidenceforincompatibilitybetweennuclearandmitochondrialgenomesfromdivergentpopulationsofthesamespecies.Results:Wetes

4、tedthenuclear-mitochondrialmismatchhypothesisforhumansbyobservingtheextentofnaturallyoccurringnuclear-mitochondrialmismatchseenfor2,504individualsacross26populations,from5continentalpopulationsgroups,characterizedaspartofthe1000GenomesProject(1KGP).Wealsoperformedareplicationanal

5、ysisonmitochondrialDNA(mtDNA)haplotypesfor1,043individualsfrom58populations,characterizedaspartoftheHumanGenomeDiversityProject(HGDP).NuclearDNA(nDNA)andmtDNAsequencesfromthe1KGPweredirectlycomparedwithinandbetweenpopulations,andthepopulationdistributionsofmtDNAhaplotypesderivedf

6、rombothsequence(1KGP)andgenotype(HGDP)datawereevaluated.LevelsofnDNAandmtDNApairwisesequencedivergencearehighlycorrelated,consistentwiththeirco-evolutionamonghumanpopulations.However,therearenumerouscasesofco-occurrenceofnuclearandmitochondrialgenomesfromdivergentpopulationswithi

7、nindividualhumans.Furthermore,pairsofindividualswithcloselyrelatednucleargenomescanhavehighlydivergentmtDNAhaplotypes.Supposedlymismatchednuclear-mitochondrialgenomecombinationsarefoundnotonlywithinindividualsfrompopulationsknowntobeadmixed,wheretheymaybeexpected,butalsofrompopul

8、ationswithlowoveralllevelsofobservedadmi

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