Investigation of repetitive sequences in the human genome

Abstract

Repetitive sequences and genomic variations mediated by repetitive sequences remain a barrier to our understanding of the function and dynamics of the human genome.Only recently have high throughput short and long reads sequencing provided an opportunity to overcome these challenges. In this thesis, I investigate the distribution, evolution and polymorphism of two types of repeats: subtelomeric and inverted repeats. I also investigate two distinct aspects of genomic mutations related to these repetitive sequences: inversion polymorphisms, and structural variation in chromosome subtelomeric regions.In the first chapter, I provide an overview of our current knowledge, as well as gaps in our understanding of the structure of the human genome. I also provide an overview of the sequencing technologies I will use in this thesis.In the second chapter, I show the performance of inversion detection by short read sequencing. Next, I develop and apply an approach for using long read nanopore sequencing data to detect inversion polymorphism. I show that using long reads it is possible to detect inversions mediated by long inverted repeats which are invisible to paired-end short read sequencing.