I wrote about gene-gene interactions (epistasis) and the implications for heritability, trait definitions, natural selection, and therapeutic interventions. Biology is clearly full of causal interactions, so why don't we see them in the data? A 🧵:

The two key studies of the International Brain Laboratory @intlbrainlab.bsky.social are out today! A brain-wide map of neural activity during complex behaviour www.nature.com/articles/s41... Brain-wide representations of prior information in mouse decision-making www.nature.com/articles/s41...

Extraordinary resource! "Comprehensive recordings from 621,733 neurons in 297 brain areas of 139 mice (12 labs) performing a decision-making task with sensory, motor & cognitive components: a public dataset to understand how computations distributed across & within brain areas drive behaviour."👇🧪

FOXP genes regulate Purkinje cell diversity and cerebellar morphogenesis @nagham-farah.bsky.social www.nature.com/articles/s41...

Fresh preprint by @flavia-con.bsky.social from our lab uncovers how SMCHD1 finds & binds chromatin using live-cell single-molecule imaging🔬 She reveals how SMCHD1 dynamically engages chromatin, including the inactive X chromosome, to maintain gene silencing. www.biorxiv.org/content/10.1...

“Focus on single gene effects limits discovery and interpretation of complex trait-associated variants” Very interesting preprint by Kathryn Lawrence @tamigj.bsky.social @sbmontgom.bsky.social good arguments to move beyond single-gene-at-a-time approaches 🧪🧬 www.biorxiv.org/content/10.1...

Role of X chromosome and dosage-compensation mechanisms in complex trait genetics www.cell.com/ajhg/fulltex...

Delighted to have our work on Polygenic Modifiers of #TelomereBiologyDisorders, led by Michael Poeschla, @sashagusevposts.bsky.social, @mitchiela.bsky.social, @sharonsavage.bsky.social, @tummalalab.bsky.social, + co, published in @jclinical-invest.bsky.social today: www.jci.org/articles/vie...

One of the coolest papers in the field of sex determination! It is the first evidence that environmental aspects can affect mammalian sex determination!! www.nature.com/articles/s41...

This seems to argue against the notion that girls are under-diagnosed because they express autistic symptoms differently, favoring a real sex difference in prevalence instead

There is an ongoing debate about phenotypic differences in #autism spectrum disorder between girls and boys. In this study, Pierce et al found no significant sex differences in ASD toddlers across 17 of 18 measures. www.nature.com/articles/s41...

Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X www.nature.com/articles/s41... @natcomms.nature.com @derubeislab.bsky.social

New publication! We expand on our prior work demonstrating that pleiotropic effects of cognitive GWAS can provide biological insights into schizophrenia GWAS results. We differentiated "concordant" from "discordant" subsets of schizophrenia risk SNPs (1/3)

Parent-of-origin regulation by maternal auts2 shapes neurodevelopment and behavior in fish genomebiology.biomedcentral.com/articles/10....

Scalable co-sequencing of RNA and DNA from individual nuclei www.nature.com/articles/s41...

Delighted to share our latest work deciphering the landscape of chromatin accessibility and modeling the DNA sequence syntax rules underlying gene regulation during human fetal development! www.biorxiv.org/content/10.1... Read on for more: 🧵 1/16 #GeneReg 🧬🖥️

Out today in AJHG, this work from my (recently graduated) student Teng Heng on recessive effects in 44k British South Asians from the Genes & Health project @genesandhealth.bsky.social . She found 185 independent hits of which >40% were novel. Worth looking for these in your own cohorts!

Delighted to share the latest preprint from the lab led by Janith Seneviratne We reveal novel roles for #embryonic regulators DPPA2/4 in facilitating a H2AK119Ub primed #chromatin state when aberrantly up-regulated in non-small cell lung #cancers 🧬🔬 (1/6) www.biorxiv.org/content/10.1...

Autism-related traits in myotonic dystrophy type 1 model mice are due to MBNL sequestration and RNA mis-splicing of autism-risk genes www.nature.com/articles/s41...

Brain circuits that regulate social behavior www.nature.com/articles/s41...

Human de novo mutation rates from a four-generation pedigree reference www.nature.com/articles/s41...

Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning www.science.org/doi/10.1126/...

Low overlap of transcription factor DNA binding and regulatory targets www.nature.com/articles/s41...

Exonic enhancers are a widespread class of dual-function regulatory elements x.com/biorxiv_geno...

I am honored to receive this grant. I am hopeful that it will allow us to learn more about the mechanisms involved in the increased risk of autism among boys.

Single-cell analyses reveal increased gene expression variability in human neurodevelopmental conditions www.cell.com/ajhg/fulltex...

What an amazing discovery from Scott Kennedy's lab! A new splicing system that recognizes transposons and removes them from mRNAs! t.co/3p3wyxkYXX

Constrained roads to complex brains Neural development and brain circuit evolution converged in birds and mammals www.science.org/doi/10.1126/...

Our new #preprint has: ✅ A KRAB Zinc Finger (the SCAN domain-containing kind) ✅ #transposon sequences (the SINE kind) ✅ #epigenetic regulation (the #enhancer kind) ✅ lineage specification (the neural kind) ❌ and NO heterochromatin! All by PhD student Daniel Moore 🚀 www.biorxiv.org/content/10.1...

G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability www.cell.com/molecular-ce...

I am excited to share our latest paper @Nature where we construct a hi-res spatial map of the human hypothalamus, the brain region central in appetite control. It is a collaboration between @IMS_MRL @Cambridge_Uni & @MPI_Metabolism www.nature.com/articles/s41...

📢 CUT&Tag version 3 Sometimes the preprint to paper route can be quite the odyssey. And so in that vein, we are delighted to give you version 3 of our CUT&Tag optimization and benchmarking manuscript: www.biorxiv.org/content/10.1...

The X chromosome’s influences on the human brain www.science.org/doi/10.1126/...

Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders www.cell.com/cell/abstrac...

Over 20% of cancers have mutations in SWI/SNF (BAF) chromatin remodelers, linking them to oncogenesis & neurodevelopmental disorders. #CancerResearch PMID:39014081, Nat Rev Drug Discov 2024, @NatRevDrugDisc

We often speak about chromatin as being accessible or inaccessible, but what does it mean? We wrote a short review on this, 🔬 focused: sciencedirect.com/science/arti... A big thank you to Tom Fillot for his efforts on this and to @hansen_lab @marcelonollmann for their help as editors.

Specification of claustro-amygdalar and palaeocortical neurons and circuits rdcu.be/d6qUO - nice! (in mice... mostly)

Sex Differences in Human Brain Structure at Birth rdcu.be/d5Cpt (as detected at the gross level of neuroimaging)

NSF makes you say who you got conflicts (coauthored) with. We (really just Jordan Matelsky) just built you a tool for that. Literally one click: bib.experiments.kordinglab.com/nsf-coa

How to do differential expression with scRNAseq data? State of the art is "pseudo-bulk" analysis with RNA-seq methods like edgeR or DESeq2, where "cell type" is encoded as discrete categories. Biologically, discrete categories are not always the most appropriate concept.(1/3) doi.org/10.1038/s415...

The structural basis for de novo DNA methylation in chromatin www.biorxiv.org/content/10.1... ▶️DNMT3A2/3B3 preferentially binds di-nucleosomes separated by short DNA linkers ▶️Linker length and position of cytosines control DNA methylation ▶️a large fraction of linkers is resistant to DNMT3A2/3B3

Human cortical pyramidal neurons are larger, with more elaborate branching, and distinct nonlinear biophysical properties compared to rat cortical pyramidal neurons. Are they more functionally complex? Could that boost the human brain’s computational power? and is that what makes us human? (1/11)

Yes, one of those "before Xmas" jobs, but here it is our WES study in children with dyslexia suggesting 5 candidates medrxiv.org/cgi/content/...

Chromosome X-wide common variant association study in autism spectrum disorder www.cell.com/ajhg/abstrac...

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis www.cell.com/neuron/fullt...

Deconstructing the neural circuit underlying social hierarchy in mice www.cell.com/neuron/abstr... - how your brain tells you if you're winning or losing (if you're a mouse)

Association of polygenic scores for neuropsychiatric traits with self-reported professions based on analysis of 420k individuals from UK Biobank and Million Veteran Program. Look at the 'arts & design' category. Artistic talent comes at a cost--a piece of your mind :)

I am looking for a PhD candidate interested in the genetics of language 🧬🧠🗨️ Get in touch if interested or please share with others who might be www.findaphd.com/phds/project...

🧠🧠🧠Could the brain influence evolution? Check out our super hot preprint: A single pair of neurons that sense temperature controls genetic changes in the inheritable genome by triggering transposons that change the genome for generations to come www.biorxiv.org/content/10.1...

Parent-of-Origin inference and its role in the genetic architecture of complex traits: evidence from ~220,000 individuals www.medrxiv.org/content/10.1...