@rmschu.bsky.social
Postdoc in the Zoghbi Lab at Baylor College of Medicine | Interested in gene regulation, neurogenetics, variant interpretation, and disease mechanism | Opinions are my own
@xshawncai.bsky.socialReposted by @rmschu.bsky.socialHave you ever looked at a gene in IGV or a genome browser and wondered “What are all those (ATAC-seq/H3K27ac/CTCF ChIP-seq/…) peaks doing?” 🤔 I’m thrilled to share that we developed a new technology called Swap-seq to answer that exact question.
Swap-seq: www.biorxiv.org/content/10.6...
@rmschu.bsky.socialThe Zoghbi lab previously showed that 30% less Mecp2 expression causes autism-like behaviors (but not Rett syndrome) in male mice, supporting our new data. Put together, this suggests that noncoding variants in X chromosome NDD genes contribute to autism's missing heritability and male bias
@rmschu.bsky.socialWe also identified and tested MECP2 noncoding variants that were passed from unaffected mothers to their autistic sons. We found two that overlapped the key TFBS regions and impacted regulation. One of these variants disrupts NFY binding and decreases MECP2 expression by 30%!
@rmschu.bsky.socialWe thought that understanding the disease relevance of MECP2 regulatory regions might illuminate the missing heritability of autism and its male bias. We used a MPRA in neurons to manipulate these regions, mapping key regions (TFBSs) where pathogenic variants are most likely to be found.
@rmschu.bsky.socialWe hypothesized that some of the missing heritability of autism is in the noncoding regulatory regions for dosage-sensitive neurodevelopmental disease (NDD) genes like MECP2. Because MECP2 is on the X chromosome, pathogenic variants cause more severe symptoms in boys than girls.
@rmschu.bsky.socialI'm excited to finally publish my postdoctoral work in
@ajhgnews.bsky.social! This work was motivated by two big mysteries in autism research: 1) where and what are the undiscovered genetic components of autism, and 2) why are males diagnosed with autism more frequently than females?
@bcmfromthelabs.bsky.socialReposted by @rmschu.bsky.socialNew genetic candidates help explain why #autism affects males more often than females. H. Zoghbi,
@rmschu.bsky.social explain in this interview. eurekalert.org/news-release... @ajhgnews.bsky.social @bcmhouston.bsky.social #TexasChildrens @bcmgenetics.bsky.social @eurekalert.bsky.social
@rmschu.bsky.socialThe Zoghbi lab previously showed that 30% less Mecp2 expression causes autism-like behaviors (but not Rett syndrome) in male mice, supporting our new data. Put together, this suggests that noncoding variants in X chrom. NDD genes contribute to both the missing heritability and male bias in autism.
@rmschu.bsky.socialWe also identified and tested MECP2 noncoding variants that were passed from unaffected mothers to their autistic sons. We found two that overlapped the key TFBS regions and impacted regulation. One of these variants, in the promoter, disrupts NFY binding and decreases MECP2 expression by 30%!
@rmschu.bsky.socialWe thought that understanding the disease relevance of MECP2 regulatory regions might illuminate both the missing heritability of autism and its male bias. We used a MPRA in neurons to manipulate these regions, mapping key regions (TFBSs) where pathogenic human variants are most likely to be found.
@rmschu.bsky.socialWe hypothesized that some of the missing heritability of autism lies in the noncoding regulatory regions for known dosage-sensitive neurodevelopmental disease (NDD) genes like MECP2. Because MECP2 is on the X chromosome, pathogenic variants tend to cause more severe symptoms in boys than girls.
@calliao.bsky.socialReposted by @rmschu.bsky.socialReally excited to share the latest results from the Bipolar Exome (BipEx) consortium! We analyzed rare coding variation in 64,435 people with bipolar disorder and 168,101 controls across 22 countries, identifying 13 genes at exome-wide significance. 🧵 1/n
www.medrxiv.org/content/10.6...
@kailifan.bsky.socialReposted by @rmschu.bsky.social1/13
The human body runs on one genome—but every cell reads it differently. How?
To find out, we need to measure both gene expression and chromatin accessibility in the same nucleus.
So we did, across 21 adult tissues and nearly half a million nuclei. 🧵
🔗 www.biorxiv.org/content/10.6...
@rmschu.bsky.socialAmazing opportunity to join a great genetics department at the University of Michigan!
@philippebatut.bsky.socialReposted by @rmschu.bsky.social🧬🔬 Why are enhancers transcribed and how does that impact gene regulation? I’m really excited to share our new paper in @science.org showing that noncoding RNAs control the timing of gene activation in embryos. With Mike Levine #ScienceResearch @columbiamed.bsky.social
A few highlights below... 🧵👇