ORCID
https://orcid.org/0000-0001-8183-213X
Date of Award
12-14-2023
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Structural variants (SVs) significantly contribute to genetic diversity among individuals and impact gene regulation, disease, and evolution. The predominant approach to profiling these genetic variants in large-scale population studies is through short-read whole-genome sequencing (WGS). This approach involves sequencing millions of short reads, aligning them to a linear reference genome, and subsequently identifying variants relative to this reference. However, its capability to detect SVs, especially long insertions and complex rearrangements, is limited. The primary limitation arises from the insufficient representation of structural diversity across human populations in the linear reference genome. As a result, short reads derived from non-reference SVs may either remain unaligned or be erroneously aligned to the reference genome. The advent of long-read sequencing technologies has enabled the creation of haplotype-resolved assemblies, revealing a vast number of previously unknown SVs. Nevertheless, the prohibitive cost of these technologies constrains their broad application in research. In response to this constraint, we collaborated with the Human Pangenome Reference Consortium (HPRC) to construct a first draft of the human pangenome reference by integrating haplotype-resolved assemblies from 44 genetically diverse individuals. Using this comprehensive reference, we developed a tool that leverages read depth from short-read WGS data to improve the detection of copy number variants across individuals.
Language
English (en)
Chair and Committee
Ira Hall
Recommended Citation
Liao, Wen-Wei, "Construction of a Human Pangenome Reference to Improve Structural Variation Detection" (2023). Arts & Sciences Electronic Theses and Dissertations. 3201.
https://openscholarship.wustl.edu/art_sci_etds/3201