RT Journal Article
T1 Characterisation of retrotransposon insertion polymorphisms in whole genome sequencing data from individuals with amyotrophic lateral sclerosis.
A1 Savage, Abigail L
A1 Iacoangeli, Alfredo
A1 Schumann, Gerald G
A1 Rubio-Roldan, Alejandro
A1 Garcia-Perez, Jose L
A1 Al Khleifat, Ahmad
A1 Koks, Sulev
A1 Bubb, Vivien J
A1 Al-Chalabi, Ammar
A1 Quinn, John P
K1 Alu
K1 Amyotrophic lateral sclerosis
K1 LINE-1
K1 Polymorphism
K1 Retrotransposon
K1 SVA
K1 Whole genome sequencing
AB The genetics of an individual is a crucial factor in understanding the risk of developing the neurodegenerative disease amyotrophic lateral sclerosis (ALS). There is still a large proportion of the heritability of ALS, particularly in sporadic cases, to be understood. Among others, active transposable elements drive inter-individual variability, and in humans long interspersed element 1 (LINE1, L1), Alu and SINE-VNTR-Alu (SVA) retrotransposons are a source of polymorphic insertions in the population. We undertook a pilot study to characterise the landscape of non-reference retrotransposon insertion polymorphisms (non-ref RIPs) in 15 control and 15 ALS individuals' whole genomes from Project MinE, an international project to identify potential genetic causes of ALS. The combination of two bioinformatics tools (mobile element locator tool (MELT) and TEBreak) identified on average 1250 Alu, 232 L1 and 77 SVA non-ref RIPs per genome across the 30 analysed. Further PCR validation of individual polymorphic retrotransposon insertions showed a similar level of accuracy for MELT and TEBreak. Our preliminary study did not identify a specific RIP or a significant difference in the total number of non-ref RIPs in ALS compared to control genomes. The use of multiple bioinformatic tools improved the accuracy of non-ref RIP detection and our study highlights the potential importance of studying these elements further in ALS.
YR 2022
FD 2022-08-10
LK http://hdl.handle.net/10668/22249
UL http://hdl.handle.net/10668/22249
LA en
DS RISalud
RD Mar 14, 2025