nature.com

Novel mRNA isoforms in human microglia refine genetic associations with neurodegeneration

Long-read RNA sequencing of human microglia expands the catalog of mRNA isoforms in this important cell type and assists with the interpretation of genetic associations with Alzheimer’s disease and Parkinson’s disease.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Change institution

Buy or subscribe

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

$29.99 / 30 days

cancel any time

Learn more

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Learn more

Buy this article

Purchase on SpringerLink

Instant access to full article PDF

Buy now

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Log in

Learn about institutional subscriptions

Read our FAQs

Contact customer support

Fig. 1: Complex regulation of PLCG2 in Alzheimer’s disease.

References

Romero-Molina, C., Garretti, F., Andrews, S. J., Marcora, E. & Goate, A. M. Microglial efferocytosis: Diving into the Alzheimer’s disease gene pool. Neuron 110, 3513–3533 (2022). A review article summarizing the recent advances in understanding the genetic links between microglia and Alzheimer’s disease.

ArticleCASPubMedGoogle Scholar

de Paiva Lopes, K. et al. Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies. Nat. Genet. 54, 4–17 (2022). This paper reports our previous analysis of the genetics of microglia gene expression and mRNA splicing in disease.

ArticlePubMed CentralGoogle Scholar

Kosoy, R. et al. Genetics of the human microglia regulome refines Alzheimer’s disease risk loci. Nat. Genet. 54, 1145–1154 (2022). This paper reports our previous analysis of the genetics of microglia chromatin accessibility in disease.

ArticleCASPubMedPubMed CentralGoogle Scholar

Castaldi, P. J., Abood, A., Farber, C. R. & Sheynkman, G. M. Bridging the splicing gap in human genetics with long-read RNA sequencing: finding the protein isoform drivers of disease. Hum. Mol. Genet. 31, R123–R136 (2022). A review article on the potential for long-read RNA-seq to better understand the genetics of human disease.

ArticlePubMedPubMed CentralGoogle Scholar

Pardo-Palacios, F. J. et al. Systematic assessment of long-read RNA-seq methods for transcript identification and quantification. Nat. Methods 21, 1349–1363 (2024). This paper from the LRGASP consortium reports benchmarking of a set of long-read RNA-seq methods and analysis tools.

ArticleCASPubMedPubMed CentralGoogle Scholar

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Humphrey, J. et al. Long-read RNA sequencing atlas of human microglia isoforms elucidates disease-associated genetic regulation of splicing. Nat. Genet. https://doi.org/10.1038/s41588-025-02099-0 (2025).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novel mRNA isoforms in human microglia refine genetic associations with neurodegeneration. Nat Genet (2025). https://doi.org/10.1038/s41588-025-02112-6

Download citation

Published:07 March 2025

DOI:https://doi.org/10.1038/s41588-025-02112-6

Share this article

Anyone you share the following link with will be able to read this content:

Get shareable link

Sorry, a shareable link is not currently available for this article.

Copy to clipboard

Provided by the Springer Nature SharedIt content-sharing initiative

Read full news in source page