Lu Wang Thesis Defense

Transposable Element Polymorphism and Human Genome Regulation Defense Date: Monday, November 6th, 2017 Thesis Advisor: Dr. King Jordan School of Biological Sciences Georgia Institute of Technology Committee Members: Dr. Greg Gibson School of Biological Sciences Georgia Institute of Technology Dr. Victoria Lunyak Aelan Cell Technology San Francisco, CA Dr. John McDonald School of Biological Sciences Georgia Institute of Technology Dr. Fredrik Vannberg School of Biological Sciences Georgia Institute of Technology Abstract A large proportion of the human genome is derived from transposable element (TE) sequences. TE sequences derived sequences have been shown to contribute to the regulation of the human genome in a variety of ways. Despite that many of the known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations, there are several active families of TEs, including the Alu, LINE-1, and SVA retrotransposons that can mobilize via reverse transcription of RNA intermediates. Germline transposition of the active retrotransposons generates polymorphisms between individuals, and somatic transposition generates cellular heterogeneity. Given the disruptive potential of TE insertions, along with the regulatory potential of TE-derived sequences, one may expect a complex interplay between TE insertion polymorphisms and inter-individual differences in the expression of human genes, as well as TE activities and the host regulatory mechanisms. My work has been focusing on the role of polymorphic TEs (polyTE) in the regulation of the genes and how the human genome regulates TE activities. Genome-wide association screens were also performed to evaluate the extent to which recent TE activity could lead to regulatory polymorphisms among populations. TE insertion polymorphisms were also related to common health and disease phenotypes that have been previously interrogated through genome-wide association studies (GWAS). Lastly, the genome-wide association screen approach has also been applied to search for potential modifiers of TE activities. Numerous human polyTE insertion sites were identified as cis and trans expression quantitative trait loci (eQTL). Their regulatory effects were shown to directly related to cell type-specific function in the immune system. Two polyTE loci that are co-located with cell type-specific enhancers were linked to common diseases phenotypes. Both known and putative modifiers of TE expression were identified through the joint analysis of L1 and gene eQTLs. In summary, the results showed that the human genome regulates TE activities through different pathways and that polyTE could impact human health and disease phenotypes by causing changes in gene expression.