Structural Variation Discovery and Genotyping from Whole Genome Sequencing: Methodology and Applications: A Dissertation
Authors
Zhuang, JialiFaculty Advisor
Zhiping Weng, PhDAcademic Program
Bioinformatics and Computational BiologyUMass Chan Affiliations
Biochemistry and Molecular PharmacologyDocument Type
Doctoral DissertationPublication Date
2015-09-15Keywords
Dissertations, UMMSGenomic Structural Variation
DNA Transposable Elements
Genome-Wide Association Study
Genomic Structural Variation
DNA Transposable Elements
Genome-Wide Association Study
Bioinformatics
Computational Biology
Genomics
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Show full item recordAbstract
A comprehensive understanding about how genetic variants and mutations contribute to phenotypic variations and alterations entails experimental technologies and analytical methodologies that are able to detect genetic variants/mutations from various biological samples in a timely and accurate manner. High-throughput sequencing technology represents the latest achievement in a series of efforts to facilitate genetic variants discovery and genotyping and promises to transform the way we tackle healthcare and biomedical problems. The tremendous amount of data generated by this new technology, however, needs to be processed and analyzed in an accurate and efficient way in order to fully harness its potential. Structural variation (SV) encompasses a wide range of genetic variations with different sizes and generated by diverse mechanisms. Due to the technical difficulties of reliably detecting SVs, their characterization lags behind that of SNPs and indels. In this dissertation I presented two novel computational methods: one for detecting transposable element (TE) transpositions and the other for detecting SVs in general using a local assembly approach. Both methods are able to pinpoint breakpoint junctions at single-nucleotide resolution and estimate variant allele frequencies in the sample. I also applied those methods to study the impact of TE transpositions on the genomic stability, the inheritance patterns of TE insertions in the population and the molecular mechanisms and potential functional consequences of somatic SVs in cancer genomes.DOI
10.13028/M2Q30PPermanent Link to this Item
http://hdl.handle.net/20.500.14038/32251Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M2Q30P
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