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dc.contributor.authorWalker, Conor
dc.date.accessioned2022-02-20T14:21:30Z
dc.date.available2022-02-20T14:21:30Z
dc.date.submitted2021-10-01
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334246
dc.description.abstractMany complex rearrangements arise in human genomes through template switch mutations, which occur during DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. These variants are routinely captured at kilobase-to-megabase scales in studies of genetic variation by using methods for structural variant calling. However, the genomic and evolutionary consequences of replication-based rearrangements remain poorly characterised at smaller scales, where they are usually interpreted as complex clusters of independent substitutions, insertions and deletions. In this thesis, I describe statistical methods for the detection and interpretation of short template switch mutations within DNA sequence data. I then use my methods to explore small-scale template switch mutagenesis within human genome evolution, population variation, and cancer. I show that small-scale, replication- based rearrangements are a ubiquitous feature of the germline and somatic mutational landscape of human genomes.
dc.description.sponsorshipEuropean Molecular Biology Laboratory National Institute for Health Research
dc.rightsAll Rights Reserved
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/
dc.subjecthuman genetic variation
dc.subjecthominid evolution
dc.subjectstatistical alignment
dc.subjectpair hidden Markov models
dc.subjectDNA replication
dc.subjecttemplate switching
dc.titleStatistical analysis of short template switch mutations in human genomes
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.date.updated2022-02-17T21:10:34Z
dc.identifier.doi10.17863/CAM.81659
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved/
rioxxterms.typeThesis
dc.publisher.collegeHughes Hall
cam.supervisorGoldman, Nick
cam.supervisorScally, Aylwyn
cam.supervisor.orcidScally, Aylwyn [0000-0002-0807-1167]
cam.depositDate2022-02-17
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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