Thank you to all our members and collaborators for an inspiring and productive @gregor-research.bsky.social meeting last week in San Diego! ☀️🧬

#RareDisease #Research

This work was done as part of a collaboration between Stanford and the Broad and facilitated through the UDN and
@gregor-research.bsky.social consortia. A special thanks to my co-first author Rodrigo Mendez, who identified the RNU6ATAC variants, and @vijayganesh.bsky.social, who led this project!

The spliceosome is large, with many components related to disease, leaving the question… how many more patients can we diagnose (and diseases can we uncover!) by examining the transcriptome for global outlier patterns?

These results demonstrate that examining RNA-sequencing data for transcriptome-wide signatures can increase the diagnostic yield of individuals with rare diseases, provide variant-to-function interpretation of spliceopathies, and uncover novel disease-gene associations.

We also identified an individual with excess minor intron retention events who had rare, highly conserved, compound heterozygous variants in RNU6ATAC that may disrupt the formation of the catalytic spliceosome, suggesting a novel gene-disease candidate!

By examining the RNA-seq data of 390 individuals in a rare disease cohort for patterns of minor intron retention events, we were able to identify four individuals with RNU4atac-opathies, a difficult-to-diagnose disease, caused by biallelic variants in RNU4ATAC (as well as reclassify four variants!).

Spliceopathies are a group of rare diseases that interfere with the function of the spliceosome. Variants in the minor spliceosome snRNA RNU4ATAC have been associated with the retention of a special type of intron called “minor introns”.

What if one variant can cause splicing outliers transcriptome-wide? In our preprint, we show how examining transcriptome-wide patterns of splicing outliers can both diagnose individuals with rare spliceopathies and uncover novel disease-gene relationships! (www.medrxiv.org/content/10.1...)

We've created a Starter Pack with GREGoR Cosortium Members: go.bsky.app/KW4m3zR

Let us know if you're a part of GREGoR and would like to be added!

Aww thank you! I couldn't have done it without you!

Congratulations to my mentee Maggie Maurer, an ASHG Trainee Research Excellence Pre-Doctoral Winner. She
discovered a new disease gene in her rotation project last year! The critical method for this project was shared with us by collaborator Vijay Ganesh and clinical work was done by Rodrigo Mendez.

🚨 Excited to announce the Marker paper for the GREGoR Consortium! arxiv.org/abs/2412.14338

Accelerating #RareDisease diagnostics with cutting-edge #Genomics and global data sharing of omics and deep phenotyping from ~7500 individuals on NHGRI AnVIL and much more to come! 🧬