Massive single-cell study by Kanai et al (www.medrxiv.org/content/10.1...): - Once statistical power is high, constrained genes have more (though weaker) eQTLs. - Chromatin-QTLs near constrained genes have "normal" effect sizes, colocalize more with disease, but exhibit attenuated peak-gene effects.

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”

New study of 800K+ genomes from gnomAD reveals most “pathogenic” variants in healthy people aren’t truly disease-tolerant. They are explained by annotation errors, mosaicism, or compensatory variants. 🧬 A big step for precision medicine! www.nature.com/articles/s41...

📃 We’re excited to share our latest work, now published in Nature Communications — a major update to the Genome Aggregation Database (gnomAD) that improves allele frequency resolution for two gnomAD-defined genetic ancestry groups using local ancestry inference (LAI).

Now published! Our paper on: (1) Accurate sequencing of sperm at scale (2) Positive selection of spermatogenesis driver mutations across the exome (3) Offspring disease risks from male reproductive aging [1/n] www.nature.com/articles/s41...

📣 We are recruiting! Please share!! Are you a bioinformatician / computational scientist who wants to apply your skills to understanding regulatory biology and improving rare disease diagnosis and treatment? 🧠 💻 🧬 🩺 We have two roles available 👇 🧵 1/4

Isn't genetics cool??? Within only 145 nucleotides(!) of a non-coding RNA (RNU4-2) - different variants in distinct regions / structures cause three distinct disorders!!! (all discovered within the last 18 months) 🤯🤓🧬❤️

🗣️ Quote of #ESHG2025 (so far) "Who licks bone !?!" 🦴 - Johannes Krause Anyone have that on your bingo card? Well apparently archeologists do, to distinguish bone from stones and it causes problems in DNA sequencing. 🤔

We are just wrapping up day 1 at #ESGH2025 in beautiful Milan. For those who want some extra fun while listening to the great science, you can play bingo.👇 I know multiple of these have already occurred.

Buongiorno Milano! Ready for a great day 1 of #eshg2025? Packed program of excellent science 8.30am-8.00pm - plus networking event till 9.30pm to meet many friends, colleagues and collaborators! …andiamo @eshg.bsky.social @eshgyoung.bsky.social

🤗 Hugely excited to share our work on automating iterative reanalysis in #raredisease, preprint out: www.medrxiv.org/content/10.1... 🤖🧬 github.com/populationge... A superb collaboration with @dgmacarthur.bsky.social @cassimons.bsky.social @heidirehm.bsky.social @ksamocha.bsky.social and many more!

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

A few weeks ago, I had an incredibly emotional call with James Coney, a writer for the Sunday Times whose son Charlie was in the @genomicsengland.bsky.social 100k project and was recently diagnosed with ReNU syndrome. This beautiful article tells their story ❤️ www.thetimes.com/article/0bcc...

Join leading experts working in #RareDisease research at our #GRD25 conference. 📅 Dates: 9-11 April 2025 💭 Share insights in person Explore the latest #genomics advances accelerating improvements in clinical care for rare disorders, globally. ⏰Secure your place by 11 March: bit.ly/3BpAe44

Recently out on #bioRxiv: our updated approach to identify regional variability in missense mutation intolerance (“constraint”) in protein-coding genes using the gnomAD database. www.biorxiv.org/content/10.1... 1/10

Some updated guidance on our gnomAD v4 constraint scores: gnomad.broadinstitute.org/news/2024-03... The @gnomad-project.bsky.social team is hard at work on v4.1 and improvements across the board, so expect more updates. Thanks to Katherine Chao for spearheading this blogpost.

Our paper describing a way to infer the phase of rare variant pairs using gnomAD v2 is out now in Nature Genetics. We hope that the resource we generated will be useful when interpreting rare co-occurring variants in the context of recessive disease. www.nature.com/articles/s41...

It’s the final day of giving thanks for the teams that make gnomAD possible. Today is focused on the participants in studies, data contributors (>300!), the Scientific Advisory Board, and our steering committee. 1/6

Day four of giving thanks to the teams that make gnomAD happen is focused on the CNV and SV teams! v4 is the first time we released structural variants at the same time as SNVs/indels, specifically: - CNVs from 464,297 exomes - SVs from 63,046 genomes 1/4

Continuing the week of thanking the teams that make gnomAD possible, today I’m thanking the data generation and operations teams! As a reminder, I'm only highlighting a few individuals of the many that contribute. You can see more on our team page: gnomad.broadinstitute.org/team 1/5

Next up in my week of thanks to the teams that make gnomAD: the gnomAD browser team! With 150k+ views a week, the browser is a crucial part of making gnomAD accessible. Quickly loading data from >800k samples + presenting it in a user-friendly format is no small feat. 1/6

Now that the dust has settled on the gnomAD v4 release, which hopefully many of you have already checked out, I wanted to take this week to thank many of the members of the team who made this possible. First up this week is the amazing production team. 1/7

Helpful description of the choices of population designators in gnomAD: gnomad.broadinstitute.org/news/2023-11...

Constraint scores are now up for v4!

To learn more about the impact of diversity on variant discovery and gene constraint please attend Katherine Chao’s #ASHG23 talk tomorrow (11/4) at 11am in rm 202A

As part of #gnomAD v4, in collaboration with the Talkowski Lab, we have released 1,199,117 genome SVs and 66,903 rare exome CNVs. These data represent the first gnomAD SV dataset released native to the GRCh38 reference genome. (1/2)

First of our gnomAD talks at #ASHG2023 is Jack Fu on copy number variants (CNVs) in >630k individuals. Starts by discussing major challenges of calling CNVs from exome data. False positives are an issue -- using the newly described GATK-gCNV (nature.com/articles/s41...)

So, so hyped to have gnomAD v4 out for #ASHG23. We'll be discussing it at a few talks this meeting. Please see: - Jack Fu, Nov 2, 1:45pm - Julia Goodrich, Nov 4, 10:30am - Katherine Chao, Nov 4, 11am cc: @gnomad-project.bsky.social

The #gnomAD team is proud to announce the release of gnomAD v4! The v4 dataset includes 730,947 exomes & 76,215 genomes, which is ~5x larger than the v2 & v3 releases combined, & includes nearly 120K indivs of non-European genetic ancestry broad.io/gnomad #ASHG23 (1/11)

🧬 🖥️ For our genetics/genomics friends visiting #ASHG23, you can follow the conference's conversation on this feed: bsky.app/profile/did:... Just use #ASHG23 (or #ASHG2023) to post to the feed.

You know exciting things are afoot when Slack threads are >150 messages long within a few hours and no one can open them.

The resolution to this (from that other site) and a warning to anyone using these data: The bgen and plink files for the 200k genome release in UK Biobank are missing all multi-allelic sites, meaning there are a large proportion of variants missing from these files! 😮 The pVCF files look OK 🧬🖥️

Big welcome to @gnomad-project.bsky.social! Keep an eye on this space in the coming weeks for updates. #AcademicSky #Genomics

I'm delighted to release the first half of my new textbook in human genetics: web.stanford.edu/group/pritch... "An Owner's Guide to the Human Genome: an introduction to human population genetics, variation and disease"