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dc.contributor.authorStammnitz, Maximillian
dc.date.accessioned2022-01-21T02:20:50Z
dc.date.available2022-01-21T02:20:50Z
dc.date.submitted2020-05-31
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332838
dc.description.abstractTransmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Such epidemics have only ever been observed to affect two mammals in nature, yet two distinct clones known as devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2) have arisen within populations of the same marsupial carnivores: Tasmanian devils. As a consequence of these aggressive infectious cancers and their rapid spread, the species has been undergoing a substantial decline since the mid-1990s. In my here presented PhD dissertation research, conducted between 2015 and 2020, I provide the first genetic and functional comparisons of these two transmissible Tasmanian devil cancer lineages. My results suggest that both DFT1 and DFT2 emerged recently and independently in different devil subpopulations, yet from similar Schwann cell-related progenitor cells with comparable molecular properties. Through deep sequencing of whole genomes from tumour cohorts of 65 DFT1 and 41 DFT2 cases as well as a normal panel of 80 animals, I reconstruct the mutational trajectories of both clones in space and time. These somatic phylogenies allow for a detailed longitudinal analysis of lineage-specific cell heterogeneity, mutation rates, Darwinian selection and immunological adaptation events. A parallel line of my research was dedicated to the production of data resources for the wider genetics and animal conservation community. Primarily, this comprises ultra-long nanopore DNA sequencing for the assembly of a high-quality Tasmanian devil reference genome, together with a devil tissue-specific gene expression atlas. In this thesis, I show how these can be integrated to deliver valuable new insights into the genetics of the Tasmanian devil population and their transmissible cancers.
dc.description.sponsorshipGates Cambridge Trust; Wellcome Trust
dc.rightsAll Rights Reserved
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.subjectTransmissible cancer
dc.subjectTasmanian devil
dc.subjectDevil facial tumour disease
dc.subjectCancer genomics
dc.subjectComputational biology
dc.subjectBioinformatics
dc.subjectPhylogenetics
dc.subjectAnimal conservation
dc.subjectMarsupial genetics
dc.subjectNanopore sequencing
dc.titleGenetics of transmissible cancers in the Tasmanian devil (Sarcophilus harrisii)
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.date.updated2022-01-19T18:28:28Z
dc.identifier.doi10.17863/CAM.80272
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.contributor.orcidStammnitz, Maximillian [0000-0002-1704-9199]
rioxxterms.typeThesis
dc.publisher.collegePembroke
cam.supervisorMurchison, Elizabeth
cam.supervisor.orcidMurchison, Elizabeth [0000-0001-7462-8907]
cam.depositDate2022-01-19
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2023-01-21


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