| Description |
Transposable elements, or mobile elements, are underappreciated DNA sequences that impact the evolution of the human genome. Transposable elements cause genomic rearrangements either through insertion events or by ectopic recombination of existing insertions. Some transposable elements can also mobilize cellular mRNAs and genomic regions to other places in the genome. These elements are so successful that almost half of the human genome is made of transposable elements, with retrotransposons composing ~ 1/3 of the genome. Retrotransposons are the only currently active class of transposable elements in humans, and mobilize via a copy and paste mechanism. While there has been extensive research in understanding existing retrotransposon insertions, it is unclear how frequently and when heritable retrotransposition occurs during human development. This dissertation aims to better understand the mechanisms and consequences of retrotransposition inheritance in humans. Chapter 1 reviews the active retrotransposon families in humans and ways of identifying them through next-generation sequencing techniques. The analyses presented in Chapter 2 identify novel, rare AluYb8/9 elements confirms that the capture-based method, ME-Scan, identifies population structure using these elements. ME-Scan also finds elements identified by short-read sequencing and Mobile Element Locator Tool (MELT). Next, Chapter 3 focuses on the first direct estimate of retrotransposition rates in humans using large, three-generation pedigrees. These results include determining any parental sex or age biases, the developmental iv timing of each retrotransposition event, and the subfamily and source element classification of each de novo mobile element insertion. The results of these studies help to push the understanding of polymorphic and de novo retrotransposition events in humans. |
