Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

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buir.advisorÖzçelik, Tayfun
dc.contributor.authorDal, Gülşah Merve
dc.date.accessioned2016-01-08T20:02:19Z
dc.date.available2016-01-08T20:02:19Z
dc.date.issued2014
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.descriptionAnkara : Department of Molecular Biology and Genetics and the Graduate School Engineering and Science of Bilkent University, 2014.en_US
dc.descriptionThesis (Ph. D.) -- Bilkent University, 2014.en_US
dc.descriptionIncludes bibliographical references leaves 106-118.en_US
dc.description.abstractCharacterizing the patterns and rate of de novo mutations is crucial for our perception of evolution and genetic basis of human disease. Direct observation of de novo single nucleotide variation (SNV) rate in healthy individuals revealed a rate in a range of 0.82 – 1.70 ×10-8 base pair per generation. However, the developmental timing of the de novo mutations is unknown and thus, contribution of the early post-zygotic mutations to the human de novo SNV rate remained unknown. In an attempt to estimate the rate of de novo mutations regarding the developmental timing of mutagenesis, we sequenced the whole genomes of a healthy monozygotic twin pair and their parents with a total of 170 fold coverage. We identified the de novo SNVs through examination of the genotypes of each individual for each of the variants in a synchronous manner. Subsequent to the Sanger sequencing based validation, we conservatively characterized a total of 32 de novo SNVs. Of these 23 were shared by the twin pair, 8 were specific to twin I, and 1 was specific to twin II. We estimated the overall de novo SNV rate of 1.31 × 10-8 for twin I and 1.01 × 10-8 for twin II. The rate of the early post-zygotic de novo SNVs was calculated to be 0.34 × 10-8 and 0.04 × 10-8 for twin I and twin II, respectively. These data indicate the growing importance of genome mosaicism which might be resulted from de novo mutations of early post-zygotic origin in disease pathogenesis.en_US
dc.description.degreePh.D.en_US
dc.description.statementofresponsibilityDal, Gülşah Merveen_US
dc.format.extentxvvi, 199, [5] leaves, graphics, tablesen_US
dc.identifier.urihttp://hdl.handle.net/11693/16882
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMutation rateen_US
dc.subjectde novo SNVen_US
dc.subjectmonozygotic twinsen_US
dc.subjectsomatic mosaicismen_US
dc.subjectearly post-zygoticen_US
dc.subjectnext generation sequencingen_US
dc.subject.lccQZ50 .D35 2014en_US
dc.subject.lcshGenetic disorders.en_US
dc.subject.lcshHuman chromosome abnormalities.en_US
dc.subject.lcshGenomics.en_US
dc.subject.lcshGenetic disorders--Epidemiology.en_US
dc.subject.lcshSingle nucleotide polymorphisms.en_US
dc.subject.lcshGenetics--Research.en_US
dc.titleEarly postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pairen_US
dc.typeThesisen_US

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