We are just getting started
The 9P-ARCH network is pursuing next steps to better understand these syndromes & their biology
Thanks to all the families, collaborators, team members, & current funders & future potential donors who are making this all possible. Appreciate all of you! 😀 TNTurner
We are just getting started
The 9P-ARCH network is pursuing next steps to better understand these syndromes & their biology
Thanks to all the families, collaborators, team members, & current funders & future potential donors who are making this all possible. Appreciate all of you! 😀 TNTurner
Conclusions
🌍 We introduced the 9P-ARCH network
This study is the largest & most comprehensive genomic analysis of 9p-related syndromes to date.
Conclusions
🌍 We introduced the 9P-ARCH network
This study is the largest & most comprehensive genomic analysis of 9p-related syndromes to date.
Unexpected finding:
🧬 Individuals with 9p deletion syndrome show excess mitochondrial genome copy number.
Raises new questions about mitochondrial involvement in these syndromes.
Unexpected finding:
🧬 Individuals with 9p deletion syndrome show excess mitochondrial genome copy number.
Raises new questions about mitochondrial involvement in these syndromes.
Gene prioritization
Using human variation + spatial transcriptomics, we identified 24 genes driving most cases of 9p deletion syndrome (83% of individuals).
Gene prioritization
Using human variation + spatial transcriptomics, we identified 24 genes driving most cases of 9p deletion syndrome (83% of individuals).
We found two late-replicating regions where most structural variant breakpoints occur.
➡️ Suggests replication-based issues are a major driver of structural variant formation in 9p deletion syndrome.
We found two late-replicating regions where most structural variant breakpoints occur.
➡️ Suggests replication-based issues are a major driver of structural variant formation in 9p deletion syndrome.
Results
🔍 First detailed look at the genomic architecture of 9p syndromes.
✅ Found shared features & differences across individuals.
💻 Built a machine learning model to predict 9p deletion syndrome from WGS gene copy number data.
Results
🔍 First detailed look at the genomic architecture of 9p syndromes.
✅ Found shared features & differences across individuals.
💻 Built a machine learning model to predict 9p deletion syndrome from WGS gene copy number data.
Using our computational tools HAT and acorn, we also generated high-quality de novos from 5,824 autism trios (SPARK + SSC) and examined noncoding de novo variants on 9p
Using our computational tools HAT and acorn, we also generated high-quality de novos from 5,824 autism trios (SPARK + SSC) and examined noncoding de novo variants on 9p
We also updated denovo-db to v1.8 and it now includes 1,131,762 de novo variants from 72,794 trios. We tested for enrichment protein-coding de novo variants in genes on 9p using data from denovo-db
We also updated denovo-db to v1.8 and it now includes 1,131,762 de novo variants from 72,794 trios. We tested for enrichment protein-coding de novo variants in genes on 9p using data from denovo-db
We also built a new open-source computational tool: DiamondsDenovo
👉 Detects enrichment of de novo variants in genomic regions.
We also built a new open-source computational tool: DiamondsDenovo
👉 Detects enrichment of de novo variants in genomic regions.
Methods
We formed the 9P-ARCH network (Advanced Research in Chromosomal Health)
📊 100 individuals from families with 9p syndromes
🔬 WGS for all, plus other genomic tech for subsets
🧮 Gene prioritization via human genetics data and statistical testing + mouse embryo spatial transcriptomics
Methods
We formed the 9P-ARCH network (Advanced Research in Chromosomal Health)
📊 100 individuals from families with 9p syndromes
🔬 WGS for all, plus other genomic tech for subsets
🧮 Gene prioritization via human genetics data and statistical testing + mouse embryo spatial transcriptomics
Background
Until now, most work on 9p deletion & duplication syndromes relied on low-resolution methods (karyotypes, microarrays). They gave important first insights, but left many questions unanswered.
Our study is the first large-scale whole-genome sequencing (WGS) of 9p syndromes.
Background
Until now, most work on 9p deletion & duplication syndromes relied on low-resolution methods (karyotypes, microarrays). They gave important first insights, but left many questions unanswered.
Our study is the first large-scale whole-genome sequencing (WGS) of 9p syndromes.