Exploratory analysis of L1 retrotransposons expression in autism.
Giovanni Spirito, Michele Filosi, Enrico Domenici and 3 others
PMID 37381037WHAT IT FOUND
Young L1 gene elements were strongly increased in only a small subset of postmortem autism brain samples, mainly in anterior cingulate cortex and in ATRX knockout cells.
Blood samples showed no such increase, so this is not a general autism marker.
Key findings
01Only a subset of ASD postmortem brain samples showed strong upregulation of young L1 elements, mainly in anterior cingulate cortex rather than prefrontal cortex.
02In knockout cell lines, loss of ATRX produced the largest increase in L1 expression, with an average net number of about 60 compared with no value above 30 for other knockouts.
03Blood samples from ASD participants and unaffected siblings showed no strong L1 increase and similar total young L1 expression.
STILL TO COME
How it was doneWhat they found
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What it does not show
The postmortem brain analysis used a small number of donors and no replicates for each brain sample, so the findings are exploratory and need validation in larger cohorts. Transposable element expression is hard to measure because repetitive sequences can map to many places, and fragments may be part of host transcripts. The blood dataset had lower sequencing coverage than the brain and cell line datasets, so the absence of a blood signal may partly reflect measurement limits. The upregulated L1s were found in only some ASD brain and knockout samples, and it remains unclear whether this phenotype causes symptoms or reflects broader chromatin changes.
Declared interests
The paper reports funding from the Italian Institute of Technology and the International School for Advanced Studies.
The easy way to misread this
Do not conclude that measuring L1 expression in blood or brain can diagnose autism or guide therapy. The increase was seen in only a few postmortem brain samples and ATRX knockout cells, not in blood, and the authors call the work exploratory.