*A new pre-print on increasing gene expression!* 🧬📈 doi.org/10.64898/202...

Our new study defines a distinct #neurogenetic condition arising from recurrent structural variants at 16p13.3 palindrome. Individuals show progressive ataxia, cognitive decline, and a characteristic MRI pattern with caudate & cerebellar atrophy. #Genomics #RareDisease 🧵1/3

Early Christmas present! Thank you Father Quistmas!🎅

Domain-wide Mapping of Peer-reviewed Literature for Genetic Developmental Disorders using Machine Learning and Gene2Phenotype https://www.medrxiv.org/content/10.1101/2025.11.24.25340871v1

It was a privilege to be part of this important international effort. How should we determine the value of genomics in healthcare?

Please forward this to any you know who could be interested! The incredible @drghawkes.bsky.social will be leading a course on analysis of genome sequence data, functional annotation of the genome, and using the very, very exciting AlphaGenome tool

Rarely in the entire history of science, has QC been a topic of such passion, importance and impact. If only the French and Americans had adopted such rigor when they messed up the design of that multi billion $ telescope because one was using the metric system, the other the imperial system.

hell yes! (another quote for you kartik)

Genomic superstar @chundru.bsky.social taking on fake-news genotypes in >900k individuals. He shows allele-level filtering is rarely suffifient, and makes the brave choice to properly tackle chrX! We’ll be providing our filtered AoU WGS plink pgens for all registered users: watch this space

New paper on everyone’s favourite topic, QC! We show why you should do genotype-level QC on your WGS data www.biorxiv.org/content/10.1... Very real quotes about this paper - “The most exciting, mind-blowing paper of the year!” “On a par with Fisher 1918” “I read it every night. Just so beautiful”

Really cool work from @jacquesml.bsky.social and @kash-a-patel.bsky.social 🥳 24% common variant heritability for a rare disease (MODY)! This very elegantly shows the overlap between MODY and T2D, and hints at some potential MODY phenocopies

New preprint out now! We show polygenic background shapes GCK-MODY clinical presentation. In >1,000 cases, higher polygenic risk increased the chance of exceeding diagnostic diabetes thresholds, highlighting how monogenic & polygenic factors jointly shape disease. #Genetics

Super excited to share our new review paper - The role of untranslated region variants in Mendelian disease! www.nature.com/articles/s41...

⌛Just over a week left! Submit your abstract for the Cardiac Precision Medicine in the 21st Century Conference 🫀 📅 Oct 29–31, 2025 | Toronto Showcase your research + compete for Best Abstract Award! 🔗 cardiacprecisionmedicine.com #CardiacPrecision #Genomics #callforabstracts

Excited to launch our AlphaGenome API goo.gle/3ZPUeFX along with the preprint goo.gle/45AkUyc describing and evaluating our latest DNA sequence model powering the API. Looking forward to seeing how scientists use it! @googledeepmind

Excited to share the preprint of our paper (my first paper!) looking at limited evidence MODY genes. We use rare variant burden testing and one of the largest MODY cohorts to evaluate the pathogenicity of these genes. This evidence can help inform clinical guidelines in MODY genetic testing!

Last day of #ESHG25 #ESHG2025, make sure to catch two fantastic back-to-back talks from @hls.exeter.ac.uk @drghawkes.bsky.social describing whole genome association analysis and meta-analysis across >500,000 people (Tuesday 11:15 & 11:30, C32)

Come along today and see me and Harry begin to tackle the exponentially increasing population scale WGS data! #ESHG2025 #ESHG25

The team have all done their job beautifully #proudPI - now it is my turn. Join us in the late breaking session to hear about collaborative work with @gregfindlay.bsky.social on saturation genome editing of RNU4-2 (at 11:30). You will also get to hear the awesome @chundru.bsky.social! #eshg2025

At #ESHG25, make sure to hear the fantastic @chundru.bsky.social speak about characterizing genome-wide de novo mutations in control populations versus rare disease cases (Monday 11:15, C29), part of the work we're doing in paradigmgenomics.org

I will be talking today in Space 3. The session starts at 10:30, my talk will be at 11:15 Come join if you are interested in de novo mutations, non-coding genome, rare disease, or just up for seeing @nickywhiffin.bsky.social talk about RNU4-2 saturation mutagenesis after me 😂 #ESHG2025

Thanks Gareth! I'm speaking at Workshops W10 and W19. Also please do see Leigh's poster that has some our data on low penetrance of TS in biobank - keen for feedback! #ESHG2025

Do come see some of these talks and posters! These are all incredible scientists (and @drghawkes.bsky.social), I can’t recommend them and their research enough #ESHG2025

I’m really looking forward to #ESHG2025! Hopefully it goes better than my start, I dropped my laptop bag first thing this morning 😅 luckily no damage

Human Developmental Cell Atlas (HDCA) expression data is now displayed. Expression is displayed in 12 sections of a 6-7 post-conception week human embryo, alongside a sagittal view which displays the region of the embryo represented by each section @mhaniffa.bsky.social

It's finally out people ✅🗞️! Check out the final version of our work exploring factors influencing the germline mutation rate and spectra on ~10,000 WGS family trios 🧬👨‍👩‍👦! www.nature.com/articles/s41...

Only 3 days until the deadline! Please pass along to anyone you feel would be interested

I thought I’d check what was new on Bluesky 😳 this is seriously f***ed up! Sending love to my US colleagues ❤️

Greg immediately hypothesised that these might be recessive variants, evident only as we used a haploid cell line. This led us to identify a novel NDD associated with biallelic RNU4-2 variants, with a phenotype distinct from ReNU 🤯 (companion manuscript fully describing this coming soon!) 9/12

🚨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

✅ In this paper, I used the UK Biobank to define 18 reference worldwide populations, and provided a method to easily infer ancestry proportions of individuals from your study more accurately. Please have it a try! Paper: doi.org/10.1093/bioi... Tutorial: privefl.github.io/bigsnpr/arti...

There are fewer than 10 documented genetic causes of Transient Neonatal Diabetes (TNDM) and now PAX4 is one of them! Really proud of this collaborative work done between the Neonatal Diabetes Research Team at Exeter and the Translational Genomics of Diabetes Lab in Stanford.

Come join us! I cannot recommend Exeter enough as a place to live and work @exeter.ac.uk! You’ll be joining a very friendly, collaborative, supporting environment. With the added bonus of working on ground-breaking research

A really nice paper by @drghawkes.bsky.social et al. argues that rare and common genetic associations converge on the same genes. While this seems at odds with our recent work about how burden tests and GWAS prioritize different genes, our results agree (🧬🧪🧵 1/6) www.biorxiv.org/content/10.1...

The strchive.org paper is out!! The paper describes STRchive as a resource to improve the diagnosis of tandem repeat disorders, then goes beyond it to consider what can be learned about childhood onset and population prevalence of these diseases. 🖥️ 🧬 link.springer.com/article/10.1...

Fantastically useful clinically-curated resource of structured monogenic gene-disease associations, including inheritance and disease mechanisms.

#standards, #mechanisms, & #identifiers - oh my! Just in time for #RareDisease Day, the @gene2phenotype.bsky.social website has a fresh look & new features to improve access to gene-disease models. 🧬💻 👉 Updated website: www.ebi.ac.uk/gene2phenoty... 👉 Why it matters: www.ebi.ac.uk/about/news/u...

We have launched an updated Gene2Phenotype website with a fresh new look. We now support more detailed disease mechanism information in our expert-curated gene-disease models. Available at www.ebi.ac.uk/gene2phenotype.

We finally have some well-powered whole-genome heritability estimates, including a quasi-behavioral trait (BMI). For height, ~89% of the heritability estimated to reside in common variants. For BMI and WHR, ~100% estimated in common variants. www.biorxiv.org/content/10.1...

Very happy to have this preprint out 😀 It's a testament to the amazing collaboration ongoing at the @exeter.ac.uk! I really loved working with this fantastic team and I think we have some very interesting findings which will be of interest to the wider research community! More to come from us soon!

Lovely work from @drghawkes.bsky.social and @rnbeaumont.bsky.social, it was great to be involved in. Just to highlight this part which is new since the preprint. This will be important to consider for interpretation of rare variant burden test results!

Excited to finally share that our paper looking at the effect of rare non-coding variants using WGS on circulating protein levels in the UKB has been released in Nature Genetics @naturegenet.bsky.social! We now analyse the full 3,000 circulating proteins in all 50,000 individuals rdcu.be/ea16i

Super excited to introduce our new study, now available as a preprint: tinyurl.com/2hv97yb4 We profiled circulating cell-free DNA during sepsis to understand why it increases >40-fold during disease. We assess cfDNA methylomes, fragmentomes, and nucleosome footprints. (1/3)

So happy to see this published in NatComms! tinyurl.com/yc66amvu Rare variant assocs with birth weight identify 9 genes. Insights into links between earlygrowth & later metabolic health. Great collabs between teams Exe&Camb. Amazing resources of UKB & deCODE made it possible.

It’s a privilege to announce Solve-RD’s latest manuscript based on years of work: “Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses” www.nature.com/articles/s41... A thread (1/n)

Proud to have played a part in this amazing study. This is a big milestone in the genetics of mental health research! Big ups to @markjamesadams.bsky.social, @mcintosh2001.bsky.social, @cathrynlewis.bsky.social and co. for organising and coordinating such a massive study, and persevering!

New study from the @pgcgenetics.bsky.social: Multi-ancestry GWAS of MDD in over half a million cases and 4 million controls. www.cell.com/cell/fulltex...

A small miracle of a fairly painless train journey via London is a good start to the Christmas holidays 🎄😌

🚨 Our preprint on parent-of-origin effects (POEs) is out! With our novel method, we inferred the parental origin of alleles for >220,000 individuals, uncovering novel insights into genetics, evolution, and health. 👉 Read here: www.medrxiv.org/content/10.1... 👇 Highlights below!

New work on penetrance of incidentally identified pathogenic RET variants, led by Kash Patel. Key findings: (1) Moderate-risk mutations are predominant in this context; (2) the risk of thyroid cancer is lower for population versus clinical ascertainment. www.medrxiv.org/content/10.1...