The transposon work was not even McClintock's only major contribution to genetics. She also discovered chromosomal crossover in the 1930s and the breakage-fusion-bridge cycle that underlies aneuploidy in the 1940s

Most people fail to appreciate just how groundbreaking McClintock's work truly was. Her transposon work was first presented in 1950 - before we knew, for example, "DNA is the genetic material." Long before most discoveries that we consider fundamental to the question of: "What is a gene?"

🧬🌽 Happy Transposon Day! 🌽🧬

Today we celebrate the birthday of Barbara McClintock - scientist extraordinaire and discoverer of jumping genes. Still the only woman to have an unshared Nobel Prize in the biomedical sciences #TransposonDay2025

For example, each ALS subtype has its own flavor of dominant glial states. ALS-Glia samples show interferon genes (as we expected), while ALS-Ox microglia are largely expressing phagocytic or metabolic stress genes

There's so much more in the paper! We used single-cell data to show that subtypes are not just about shifts in cell composition. They're actually about subtype-specific changes happening in each cell type - especially motor neurons, astrocytes, and microglia

What about clinical features? Would subtypes correlate with anything? Turns out they're correlated with disease duration. In cortex, the more TEs & TDP-43 pathology you have, the shorter the disease duration. In spinal cord, it's ALS-Glia that's most correlated with shortened survival times

What about spinal cord? Would we see the same subtypes? And would spinal cord match cortex? For 267 pALS cases, the answer is no! Spinal cord is dominated by the glial inflammatory subtype (ALS-Glia) while cortex is dominated by stress pathways (ALS-Ox) - even in the same patient!

First of all, we tripled the number of pALS cases, adding a bunch of new clinical cohorts. What did we find? The same 3 molecular subtypes (ALS-Ox, ALSGlia, ALS-TE) showed up in about the same proportions

I'm excited to be taking part in the ALS Expert Talk Series happening next week: Jan 22 at 7pm ET.

I'll be presenting my lab's latest research into ALS molecular subtypes - what are subtypes and what can they tell us about ALS?

#EndALS #EverythingALS #ALS

🔔Register: everythingals.org/events

Tracking transposable element (TE) activity in genomics data can be a pain, but there are solutions! Our lab built TEtranscripts -- which we've updated to work for small RNAs (TEsmall), bulk RNA at the locus level (TElocal), and in single-cell data (TEsingle). Check it out!

www.mghlab.org/software