Kaitlin Samocha

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. nature.com/articles/s4158…

📣Big news! Our tag-team effort on common variants in rare neurodevelopmental conditions is now out in @Nature! 📣 Co-first authoring with the brilliant @qinqin_huang🌟—proof that teamwork does make the dream work. 💪 nature.com/articles/s4158…

What about the genes which aren’t currently associated with disease? We find that 4 of them have excess loss-of-function variants in healthy populations, suggesting that they are over transmitted to offspring but are at least partially tolerated [13/15]

The novel genes are mostly known cancer and developmental disorder genes, but unlike previously known genes, most are enriched for loss-of-function (LOF) mutations rather than missense hotspots and they are linked to diverse pathways [10/15]

We detected >35k coding mutations in sperm, equivalent to yields from sequencing >20k trios (!). Using dN/dS tests, we replicate 9 of 13 previously known genes and identify 31 novel genes under positive selection in sperm [9/15]

Excited to share our new preprint in which we address: (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 [1/15] medrxiv.org/content/10.110…

Excited to report our study in @NEJM on the discovery of deletions in a long noncoding RNA gene 🧬 (𝘊𝘏𝘈𝘚𝘌𝘙𝘙) as the cause of a newly defined human neurodevelopmental disorder 🧠. 🧵1/10 nejm.org/doi/full/10.10…

Excited to share our @Nature paper introducing constraint metrics for #mtDNA! Constraint models are powerful tools that were missing for mtDNA—until now. By applying our model to #gnomAD, we reveal which sites in mtDNA are most crucial for health & disease nature.com/articles/s4158…

Interestingly, and perhaps most importantly, this residual burden was almost completely in non-monoallelic DDG2P genes. This implies that this residual burden is in de novo variants in genes we would not normally consider for monoallelic developmental disorders.

Next, we looked at multi- gene diagnoses. We did not find any residual burden for recessive variants in those already diagnosed. However, to our surprise, there was a substantial residual burden of de novo variants for those diagnosed with either de novo or non-de novo variants!

I'm very excited to have our work on recessive developmental disorders published at @NatureGenet! See here for the tweetorial (x.com/kartikchundru/…). There were some exciting updates during the reviews which I'll highlight here... (1/n) sanger.ac.uk/news_item/most…