Premium
Investigation of long interspersed element‐1 retrotransposons as potential risk factors for idiopathic temporal lobe epilepsy
Author(s) -
Doyle Glenn A.,
Reiner Benjamin C.,
Crist Richard C.,
Rao Aditya M.,
Ojeah Nkechi S.,
AraucoShapiro Gabriella,
Levinson Rachel N.,
Shah Lokesh D.,
Sperling Michael R.,
Ferraro Thomas N.,
Buono Russell J.,
Berrettini Wade H.
Publication year - 2021
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16897
Subject(s) - retrotransposon , epilepsy , temporal lobe , biology , genetics , genome wide association study , temporal cortex , gene , neuroscience , genome , single nucleotide polymorphism , genotype , transposable element
Objective To determine if long interspersed element‐1 (L1) retrotransposons convey risk for idiopathic temporal lobe epilepsy (TLE). Methods Surgically resected temporal cortex from individuals with TLE ( N = 33) and postmortem temporal cortex from individuals with no known neurological disease ( N = 33) were analyzed for L1 content by Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq). Expression of three KCNIP4 splice variants was assessed by droplet digital PCR (ddPCR). Protein ANalysis THrough Evolutionary Relationships (PANTHER) was used to determine ontologies and pathways for lists of genes harboring L1 insertions. Results We identified novel L1 insertions specific to individuals with TLE, and others specific to controls. Although there were no statistically significant differences between cases and controls in the numbers of known and novel L1 insertions, PANTHER analyses of intragenic L1 insertions showed statistically significant enrichments for epilepsy‐relevant gene ontologies in both cases and controls. Gene ontologies “neuron projection development” and “calcium ion transmembrane transport” were among those found only in individuals with TLE. We confirmed novel L1 insertions in several genes associated with seizures/epilepsy, including a de novo somatic L1 retrotransposition in KCNIP4 that occurred after neural crest formation in one patient. However, ddPCR results suggest this de novo L1 did not alter KCNIP4 mRNA expression. Significance Given current data from this small cohort, we conclude that L1 elements, either rare heritable germline insertions or de novo somatic retrotranspositions, may contribute only minimally to overall genetic risk for idiopathic TLE. We suggest that further studies in additional patients and additional brain regions are warranted.