Reading LINEs within the cocaine addicted brain

Brain and Behavior
Glenn A DoyleWade H Berrettini

Abstract

Long interspersed element (LINE)-1 (L1) is a type of retrotransposon capable of mobilizing into new genomic locations. Often studied in Mendelian diseases or cancer, L1s may also cause somatic mutation in the developing central nervous system. Recent reports showed L1 transcription was activated in brains of cocaine-treated mice, and L1 retrotransposition was increased in cocaine-treated neuronal cell cultures. We hypothesized that the predisposition to cocaine addiction may result from inherited L1s or somatic L1 mobilization in the brain. Postmortem medial prefrontal cortex (mPFC) tissue from 30 CA and 30 control individuals was studied. An Alexafluor488-labeled NeuN antibody and fluorescence activated nuclei sorting were used to separate neuronal from non-neuronal cell nuclei. L1s and their 3' flanking sequences were amplified from neuronal and non-neuronal genomic DNA (gDNA) using L1-seq. L1 DNA libraries from the neuronal gDNA were sequenced on an Illumina HiSeq2000. Sequences aligned to the hg19 human genome build were analyzed for L1 insertions using custom "L1-seq" bioinformatics programs. Previously uncataloged L1 insertions, some validated by PCR, were detected in neurons from both CA and control brain samples. Steady...Continue Reading

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Citations

Mar 8, 2020·Environmental and Molecular Mutagenesis·Brunella Del Re, Gianfranco Giorgi
Dec 14, 2018·Frontiers in Neuroscience·Robert J Oliver, Chitra D Mandyam
Jul 20, 2018·Open Biology·Gabriela O BodeaGeoffrey J Faulkner
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Methods Mentioned

BETA
pharmacotherapy
genotyping
PCR

Key Resources (RRID) Mentioned

SCR_00872
SCR_010624
AB_2149209
SCR_002105
SCR_003139
SCR_011919
SCR_001881
SCR_004869

Software Mentioned

Samtools
BLAT
QuantaSoft
Primer3
DAVID
bowtie2
PANTHER
Excel
JMP Pro
GraphPad Quickcalcs

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