{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/332838"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/332838","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Genetics of transmissible cancers in the Tasmanian devil (Sarcophilus harrisii)","abstract":"Transmissible 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.","abstract_html":"Transmissible 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.","abstract_has_math":false,"creators":["Stammnitz, Maximilian Ruprecht"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Murchison, Elizabeth"],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-05-31","date_published":"2020-05-31","updated_at":"2026-07-22T22:24:01Z","subjects":["Transmissible cancer","Tasmanian devil","Devil facial tumour disease","Cancer genomics","Computational biology","Bioinformatics","Phylogenetics","Animal conservation","Marsupial genetics","Nanopore sequencing"],"languages":["eng"],"rights":[],"rights_urls":["https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000174628907"],"render_values":[{"text":"0000-0001-7462-8907","href":"https://orcid.org/0000-0001-7462-8907","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.80272","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Murchison, Elizabeth"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Gates Cambridge Trust; Wellcome Trust"]},{"key":"dc:creator","label":"Author","values":["Stammnitz, Maximilian Ruprecht"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000174628907"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2020-05-31"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/332838"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Transmissible cancer","Tasmanian devil","Devil facial tumour disease","Cancer genomics","Computational biology","Bioinformatics","Phylogenetics","Animal conservation","Marsupial genetics","Nanopore sequencing"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.80272"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8c3d06f0-e305-45b9-939d-da272d10dd17/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Transmissible 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."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["4f4849a77f3fb6b04b83ebbea6522b6c"]},{"key":"dc:title","label":"Title","values":["Genetics of transmissible cancers in the Tasmanian devil (Sarcophilus harrisii)"]}]}],"canonical_facts":{"dc:contributor.advisor":["Murchison, Elizabeth"],"dc:contributor.sponsor":["Gates Cambridge Trust; Wellcome Trust"],"dc:creator":["Stammnitz, Maximilian Ruprecht"],"dc:creator.authoridentifier":["0000000174628907"],"dc:date.issued":["2020-05-31"],"dc:description.abstract":["Transmissible 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. 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