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dc.contributor.authorErnst, Christinaen
dc.contributor.authorPike, Jen
dc.contributor.authorAitken, Sarahen
dc.contributor.authorLong, HKen
dc.contributor.authorEling, Nen
dc.contributor.authorStojic, Lovorkaen
dc.contributor.authorWard, MCen
dc.contributor.authorConnor, Fen
dc.contributor.authorRayner, TFen
dc.contributor.authorLukk, Men
dc.contributor.authorKlose, RJen
dc.contributor.authorKutter, Cen
dc.contributor.authorOdom, Duncanen
dc.date.accessioned2017-04-24T10:49:57Z
dc.date.available2017-04-24T10:49:57Z
dc.date.issued2016-11-18en
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263761
dc.description.abstractMost human aneuploidies originate maternally, due in part to the presence of highly stringent checkpoints during male meiosis. Indeed, male sterility is common among aneuploid mice used to study chromosomal abnormalities, and male germline transmission of exogenous DNA has been rarely reported. Here we show that, despite aberrant testis architecture, males of the aneuploid Tc1 mouse strain produce viable sperm and transmit human chromosome 21 to create aneuploid offspring. In these offspring, we mapped transcription, transcriptional initiation, enhancer activity, non-methylated DNA, and transcription factor binding in adult tissues. Remarkably, when compared with mice derived from female passage of human chromosome 21, the chromatin condensation during spermatogenesis and the extensive epigenetic reprogramming specific to male germline transmission resulted in almost indistinguishable patterns of transcriptional deployment. Our results reveal an unexpected tolerance of aneuploidy during mammalian spermatogenesis, and the surprisingly robust ability of mouse developmental machinery to accurately deploy an exogenous chromosome, regardless of germline transmission.
dc.description.sponsorshipThis research was supported by Cancer Research UK (CE, CK, FC, TFR, ML, DTO), the European Molecular Biology Laboratory (NE), the Wellcome Trust (106563/Z/14/A: SJA and 098024/Z/11/Z: RJK) and the European Research Council (DTO).
dc.languageengen
dc.language.isoenen
dc.publishereLife
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectaneuploidyen
dc.subjectchromosomesen
dc.subjectepigenetic reprogrammingen
dc.subjectgenesen
dc.subjecthumanen
dc.subjectmale germlineen
dc.subjectmeiosisen
dc.subjectmouseen
dc.titleSuccessful transmission and transcriptional deployment of a human chromosome via mouse male meiosisen
dc.typeArticle
prism.numbere20235en
prism.publicationDate2016en
prism.publicationNameeLifeen
prism.volume5en
dc.identifier.doi10.17863/CAM.9133
dcterms.dateAccepted2016-11-14en
rioxxterms.versionofrecord10.7554/eLife.20235en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-11-18en
dc.contributor.orcidErnst, Christina [0000-0002-3569-2209]
dc.contributor.orcidAitken, Sarah [0000-0002-1897-4140]
dc.contributor.orcidOdom, Duncan [0000-0001-6201-5599]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idEuropean Research Council (615584)
pubs.funder-project-idWELLCOME TRUST (106563/Z/14/Z)
pubs.funder-project-idNational Institute for Health Research (NIHR) (unknown)
cam.orpheus.successThu Jan 30 12:53:58 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International