How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller? Excited to share our latest work in @science.org on a new small polymerase. 1/n

A small polymerase ribozyme that can synthesize itself and its complementary strand

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

science.org

Vanderbilt's division of Genetic Medicine has an open faculty position: apply.interfolio.com/177945

Additionally, the functional evidence for 275 SCN5A variants from our recent SCN5A automated patch-clamp study is now accessible in ClinVar.

Andrew Glazer@amglazer.bsky.social · 7mo ago

A nice editorial about our recent SCN5A automated patch clamp paper. @chaiannng.bsky.social academic.oup.com/eurheartj/ad...

A nice editorial about our recent SCN5A automated patch clamp paper. @chaiannng.bsky.social academic.oup.com/eurheartj/ad...

Reducing the variant of uncertain significance burden in inherited cardiac disorders: from variant to function to action?

This editorial refers to ‘Automated patch clamp data improve variant classification and penetrance stratification for SCN5A–Brugada syndrome’, by M.J. O’Ne

academic.oup.com

Whoa--Gemini Nano Banana is amazing at turning a "napkin sketch" of a molecular pathway into a nice-looking figure! 🤯

Excited to share our preprint: “Mapping the Functional Landscape of KCNQ1 to Define Ion Channel Mechanisms and Arrhythmia Risk!” We performed ~50,000 experimental measurements of KCNQ1 variants. www.medrxiv.org/content/10.64898/2025.12.15.25341924v1

The effects of genetic variants primarily occur in differentiated cells meaning we need to access these cell types to measure variant effects for most disease genes. We developed saturation genome editing in stem cells (iPSC-SGE) to enable phenotyping in diverse genetic and cell contexts at scale!

Editing stem cell genomes at scale to measure variant effects in diverse cell and genetic contexts

Multiplexed assays of variant effect (MAVEs) systematically measure variant function but have been limited to cancer cell lines rather than disease-relevant cell types. We developed saturation genome ...

medrxiv.org

The Mosley lab is seeking creative postdoctoral fellows interested in applying innovative population-based genomic and informatics approaches to translate genetics into clinical settings. labs.utsouthwestern.edu/mosley-lab/p... www.utsouthwestern.edu/research/pos... 🧪🧬🖥️

Thank you @amglazer.bsky.social for the exciting opportunity to collaborate! Since then, we've provided functional evidence supporting the VUS reclassification in children with abnormal sodium #ionchannel function at Sydney Children’s Hospital.

Andrew Glazer@amglazer.bsky.social · 9mo ago

📝 Excited to share our latest work, now out at European Heart Journal! We studied 252 SCN5A variants previously found in patients with Brugada Syndrome, an inherited arrhythmia disorder linked to sudden cardiac death. [1/4]

📝 Excited to share our latest work, now out at European Heart Journal! We studied 252 SCN5A variants previously found in patients with Brugada Syndrome, an inherited arrhythmia disorder linked to sudden cardiac death. [1/4]

Congrats to Matthew O'Neill for winning an American Heart Association Early Career award for our work on functional studies of SCN5A variants from patients with Brugada syndrome!

So excited about this new work from our CardioVar consortium out this week in Science led by the amazing Daniel Tabet and @fritzroth.bsky.social. www.science.org/doi/10.1126/

I gave my daughter C, A, and T cards to spell "cat." She grabbed a G and added it to the mix. Is she hinting at a future career in genetics? 🧬 🐾

🧬 Out this month in Nature Reviews Cardiology: A powerful look at how multiplexed assays of variant effects (MAVEs) are reshaping our understanding of cardiovascular disease genetics. Contributors include members of the AVE Alliance. 📑 www.nature.com/articles/s41... #Cardiology #FunctionalGenomics

Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine - Nature Reviews Cardiology

In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to impr...

nature.com

The 9th Annual Mutational Scanning Symposium will be held in Melbourne, Australia March 25-27, 2026 🌟 #VariantEffect26 www.mss2026.org Registration will open soon!!!!

📣New today! 📄Landscapes of missense variant impact for human superoxide dismutase 1 🧑‍🤝‍🧑 @axakova.bsky.social @fritzroth.bsky.social & co

Landscapes of missense variant impact for human superoxide dismutase 1

SOD1 variants cause the motor neuron disease amyotrophic lateral sclerosis. Axakova et al. functionally assay ∼86% of all possible SOD1 missense variants, producing a variant-effect map resource that ...

cell.com

And follow it up with @natrevcardiol.nature.com's review on the application of MAVEs in cardiology by @amglazer.bsky.social et al. Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine go.nature.com/3JOJYc3 rdcu.be/eFmoe

Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine - Nature Reviews Cardiology

In this Review, Roden and co-workers describe how multiplexed assays of variant effects can be used for high-throughput functional assessment of nearly all coding variants in a target sequence to impr...

go.nature.com

📝Check out our review “Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine”, out in @natrevcardiol.nature.com. We review the use of Multiplexed Assays of Variant Effect and variant effect predictors in cardiovascular disease.

Our study on HCM intermediate effect variants (IEVs) is out today in Circulation, led by Juan Pablo Ochoa, Soledad García Hernandez and Luis De la Higuera Romero. IEVs are low frequency/penetrance variants with moderate effects sizes (OR:5-10). www.ahajournals.org/doi/10.1161/... #ESCcongress 🧬🫀

Redefining the Genetic Architecture of Hypertrophic Cardiomyopathy: Role of Intermediate Effect Variants | Circulation

Background: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder primarily linked to rare variants in sarcomere genes, though recently certain non-sarcomeric genes have emerged as...

ahajournals.org

Having some summer fun...Glazer Lab Olympics! Our lab competed in 6 lab-themed events.

More smiles to share with you; this time, Andrew Glazer and Richard Dolder from the Glazer Lab at Vanderbilt University Medical Center. New blog: timothysyndrome.org/research/det... #CACNA1C #RareDisease #Research @amglazer.bsky.social @vanderbilt.edu

My wife and I had a lovely time in Spain, including the excellent #VariantEffect25 meeting!

Our "Atlas of Variant Effects 2030 Roadmap" is live: zenodo.org/records/1542... 1/n

Congratulations, John Shelley. news.vumc.org/2025/04/25/p... #VUMCMSTP #VUMCDBMI #PopGen #Bioinformatics #Genomics 🧬🖥️🧪

Polygenic score for height could improve diagnosis for children with short stature: study

About 30% of children with short stature do not have a definitive diagnosis, leading to extra testing and anxiety.

news.vumc.org

New paper out in Genome Biology! 🎉 We lay out best-practice guidelines for releasing variant effect predictors, developed through the Atlas of Variant Effects Alliance @varianteffect.bsky.social Open, interpretable, and clinically useful VEPs are the goal. 📄 doi.org/10.1186/s130...

Guidelines for releasing a variant effect predictor - Genome Biology

Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well...

doi.org

📣New from Bastarache & co 📄Characterizing trends in clinical genetic testing: A single-center analysis of EHR data from 1.8 million patients over two decades

Characterizing trends in clinical genetic testing: A single-center analysis of EHR data from 1.8 million patients over two decades

A study of electronic health records (EHRs) from 1.8 million patients at Vanderbilt University Medical Center highlights the growing role of genetic testing in clinical medicine. The study demonstrate...

cell.com

🚨I could not be more excited to share our new preprint on saturation genome editing of the small nuclear RNA (snRNA) RNU4-2: www.medrxiv.org/content/10.1... A super fun collaboration with incredible duo @gregfindlay.bsky.social @joachimdejonghe.bsky.social from @crick.ac.uk 🧬🖥️🩺 🧵1/12

Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders

Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thous...

medrxiv.org

I am pleased to share this @ahajournals.bsky.social CircGen paper. It is a team effort. I hope we have provided valuable insights on how KCNH2 variant that alters splicing and causes a large in-frame deletion can lead to a dominant negative effect of Kv11.1 K+ #ionchannel function.

Combined RNA Splicing and Patch-Clamp Analysis Reveal Pathogenicity of Splice-Altering Variants in KCNH2-Related LQTS | Circulation: Genomic and Precision Medicine

ahajournals.org

It was great to attend the ACMG clinical genetics meeting for the first time, including a fun session on advances in cardiovascular genomics.

🧵 I’m excited to share our latest preprint! We studied 252 SCN5A variants found in patients with Brugada Syndrome by automated patch clamp. [1/7]