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Laney Graduate School

Emory College

Emory Libraries

Genetic variation caused by active retrotransposons in the human genome


Bennett, E. Andrew (2008)
Dissertation (217 pages)
Committee Chair / Thesis Adviser: Devine, Scott
Committee Members: Warren, Stephen ; Matsumura, Ichiro ; Thomas, James ; Vertino, Paula M
Research Fields: Biology, Genetics; Biology, Microbiology; Biology, Bioinformatics
Keywords: transposons; genetic variation; Alu
Program: Laney Graduate School, Biological and Biomedical Sciences (Genetics and Molecular Biology)
Permanent url: http://pid.emory.edu/ark:/25593/17jbj

Abstract


Abstract
Genetic variation caused by active retrotransposons in the human genome
By E. Andrew Bennett
Nearly one third of our genome belongs to three families of active retrotransposons: L1,
Alu, and SVA, that continue to create genetic variation and cause disease in humans. We
developed several novel methods to detect the contribution transposable elements have
made to human genetic diversity, and identified 25-35% of transposon insertion
polymorphisms commonly found in human populations. Our method improved on
previous assays by identifying different families of recently mobile elements equally.
Using this same approach, we identified nearly 11,000 species-specific transposon
insertions that have mobilized in the past 6 million years in humans and chimps. We
found that humans possess a more diverse and active collection of retrotransposon
subfamilies, and have sustained almost twice as many new insertion events since our last
common ancestor. The majority of recent insertions in both humans and chimps were
caused by Alu elements. There are over 1 million Alus in humans and they collectively
occupy 10% of our genome. It was unclear however, how many of these remained active,
and what constituted an active Alu sequence. In order to define the requirements for Alu
activity, we performed a comprehensive analysis using conservation data and
retrotransposition assays. We show that active Alu elements display a high degree of
sequence variation, but must conserve nucleotides that enable them to bind to SRP9/14
proteins. Furthermore, we show the affinity for SRP9/14 binding has decreased since the
earliest Alus evolved from 7SL RNA. We estimate that at least 10,000 of the Alus in our
genome are capable of causing new genetic variation through future retrotransposition.

Table of Contents


Table of Contents



Chapter 1. Introduction
1


Introduction to retrotransposons
2


Impact of retrotransposons in humans
12


Scope of the dissertation
19


Chapter 2. Single nucleotide polymorphisms (SNPs) that map to gaps in the
22
human SNP map


Introduction
23


Materials and methods
26


Results
32


Discussion
35


Chapter 3. Natural genetic variation caused by transposable elements in humans
42


Introduction
43


Materials and methods
48


Results
54


Discussion
80


Chapter 4. Recently mobilized transposons in the human and chimpanzee
89
genomes


Introduction
90


Results
92


Materials and methods
109


Chapter 5. Active Alu retrotransposons in the human genome
112


Introduction
113


Files

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