Transposable Element Structural Variants in Parkinson’s Disease: Focusing on Genotyping Alu Transposable Element Insertions with TypeTE

Abstract

AbstractGenetic variation contributes significantly to Parkinson’s disease (PD) risk, onset, and progression. However, most of the common genetic variation that contributes to PD is still unknown. This is in part since many previous genetic studies have focused solely on the contribution of single nucleotide variants (SNVs). Structural variants (SVs), such as transposable element (TE) insertion variants, represent a major source of genetic variation in the human genome. Yet TE insertion variants have not been characterized in a large-scale and genome-wide manner, and their contribution to the risk of PD remains unexplored due to a lack of tooling to accurately detect and genotype TE insertion varia nts. In this chapter, we describe the importance of including accurately called TE insertion variants in routine genetic analyses. We give a brief overview of current TE detection methods, focusing on describing the analysis of TE insertion variants in whole genome sequencing data. Specifically, we describe a detailed protocol for genotyping Alu TE insertion variants with the TypeTE pipeline (https://github.com/clemgoub/TypeTE), an open-source software. Finally, we outline future developments for the pipeline , including incorporating other TE classes such as SVAs and LINE-1s.Key wordsTransposable elementsHuman reference genomeDeletionWhole genome sequencing Alu SVALINE1