Comparative genomic studies between Caenorhabditis species as well as within C. elegans strains have proved useful for unveiling the genetic basis of differences in biological processes and phenotypical variation. An important step for such studies is the accurate detection and characterization of genomic conservation and divergence. Using newly developed tools OrthoCluster and OrthoClusterDB, perfect and imperfect conserved synteny between the two chromosomal assemblies of C. elegans and its sister species C. briggsae is estimated, showing that syntenic information can be used for improving hundreds of gene models and for detecting new ones. Additionally, a large segmental duplication within the C. elegans genome involving 216 kb is detected using OrthoCluster. Genotyping of 76 N2 strains reveals that this duplication is polymorphic and occurred very recently in the C. elegans genome. In particular, this large segmental duplication was found to be absent in a wild isolate from Hawaii (CB4856) which has a high degree of polymorphism and a number of trait differences with N2, some of which have an explained genetic basis. This study provides the first genome-wide detection of breakpoint-resolution single nucleotide variants, small InDels and large genomic variations (GVs) between the genomes of N2 and CB4856 based on complementary next-generation sequencing technologies. Assessment of the co-occurring GVs on the protein-coding genes with a newly developed tool, Variant-Analyzer, shows that hundreds of single-copy genes with lethal and sterile phenotypes are impacted by GVs, many of them homologs to human genes with associated diseases. This study confirms most of the known GVs associated with trait differences and serves as a source of candidates that could explain the genetic basis for others. Overall, this thesis provides a deeper understanding of the conservation and divergence between Caenorhabditis species as well as within C. elegans strains.
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Thesis advisor: Chen, Nansheng
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