Abstract
Mutations are changes to the DNA sequence that can occur either in the germline or somatic cellular lineages. These mutations are parts of the genetic code for cellular function but can also act as a molecular marker to identify distinct cellular lineages within or between individuals. With decreasing costs and the maturing of technology, there are increasingly more families with whole-genome sequencing data available. In this dissertation, I have used mutations to study DNA sequence of families in the context of DNA contamination within family members and monozygotic twinning. In Chapter 2, I used germline mutations to investigate how deviation from the Mendelian inheritance pattern could be used to accurately quantify intrafamilial DNA contaminations. Intrafamilial DNA contamination produces an expected pattern of variant allele frequency changes which can be measured from next generation sequencing data. Read count information from single nucleotide polymorphisms scattered throughout the genome was used to build a maximum likelihood estimation to quantify the familial contamination levels. This method also allowed the detection of biological phenomena, including chimerism and uniparental disomy. In Chapter3, I used somatic mutations, specifically those arising as early embryonic mutations, to trace the embryonic lineages of monozygotic twins. I conducted whole-genome sequencing and targeted sequencing of the twin families to detect and validate early embryonic mutations in twins. Using these early embryonic mutations, I reconstructed the clonal history of the twins and inferred the timing of their twinning events. In the final chapter, I will summarize the future directions of family sequencing studies.
Committee Chair
Obi Griffith
Committee Members
Malachi Griffith
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Molecular Genetics & Genomics)
Document Type
Dissertation
Date of Award
5-8-2024
Language
English (en)
DOI
https://doi.org/10.7936/844a-f916
Author's ORCID
0000-0001-5714-7087
Recommended Citation
Yoon, Christopher Jongsoo, "Lineage tracing of twins and families using massively parallel sequencing" (2024). Arts & Sciences Theses and Dissertations. 3077.
The definitive version is available at https://doi.org/10.7936/844a-f916