Are There Rearrangement Hotspots in the Human Genome 英文参考文献.docVIP

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2017-05-11 发布于上海
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Are There Rearrangement Hotspots in the Human Genome 英文参考文献.doc

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Are There Rearrangement Hotspots in the Human Genome 英文参考文献

AreThereRearrangementHotspotsinthe HumanGenome? Max A.Alekseyev*,Pavel A.Pevzner DepartmentofComputerScienceandEngineering,UniversityofCaliforniaSanDiego,SanDiego,California,UnitedStatesofAmerica Inalandmarkpaper,NadeauandTaylor[18]formulatedtherandombreakagemodel(RBM)ofchromosomeevolution thatpostulatesthattherearenorearrangementhotspotsinthehumangenome.Inthenexttwodecades,numerous studies with progressively increasing levels of resolution made RBM the de facto theory of chromosome evolution. Despite the fact that RBM had prophetic prediction power, it was recently refuted by Pevzner and Tesler [4], who introducedthefragilebreakagemodel(FBM),postulatingthatthehumangenomeisamosaicofsolidregions(with low propensity for rearrangements) and fragile regions (rearrangement hotspots). However, the rebuttal of RBM causedacontroversyandledtoasplitamongresearchersstudyinggenomeevolution.Inparticular,itremainsunclear whethersomecomplexrearrangements(e.g.,transpositions)cancreateanappearanceofrearrangementhotspots.We contribute to the ongoing debate by analyzing multi-break rearrangements that break a genome into multiple fragmentsandfurthergluethemtogetherinaneworder.Inparticular,wedemonstratethat(1)eveniftranspositions wereadominantforceinmammalianevolution,theargumentsinfavorofFBMstillstand,and(2)the‘‘genedeletion’’ argumentagainstFBMisflawed. Citation:AlekseyevMA,PevznerPA(2007)Arethererearrangementhotspotsinthehumangenome?PLoSComputBiol3(11):e209.doi:10.1371/journal.pcbi.0030209 Consequently,PevznerandTesler[4]suggestedanalternative fragilebreakagemodel(FBM)ofchromosomeevolutionthat Introduction In 1970, Susumu Ohno came up with two fundamental modelsofchromosomeevolution thatweresubjecttomany controversiesinthelast35years[1].Oneofthem(thewhole genomeduplicationmodel)was?rstmetwithskepticismand only recently was proven to be correct [2,3]. The other, the random breakage model (RBM), had a very different fate. It wasembraced bybiologistsfrom theverybeginning (dueto its