ArticlePLoS computational biology2026
Combinatorial multiomic analysis from a pedigree of Sox10Dom Hirschsprung mice identifies multiple high confidence candidate modifiers of Enteric Nervous System development.
Article in PLoS computational biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
- Update of
Authors and funding
4 authors.
Funding
Abstract
Hirschsprung disease (HSCR) is characterized by absence of enteric ganglia (aganglionosis) along variable lengths of the distal intestine. This disorder results from deficient colonization of fetal intestine by enteric neural crest-derived cells (ENCDCs). HSCR exhibits complex, multifactorial inheritance with penetrance and severity varying widely even within families. SOX10 is among causal genes that predispose to aganglionosis. Yet, how gene interactions influence severity of HSCR aganglionosis is not understood. Prior mapping of aganglionosis modifiers was achieved in a standard F1-intercross utilizing the Sox10Dom HSCR mouse model. Here we deploy a novel strategy of genotyping an extended pedigree pedigree of Sox10Dom mice on a mixed genetic background. GWAS in this pedigree points to novel aganglionosis modifier intervals with replication and refinement of prior modifier regions. Complementary omics analysis of the developing Enteric Nervous System (ENS) enabled identification of multiple high-priority candidate genes within these modifier intervals based on gene expression, chromatin accessibility, and presence of conserved SOX10 binding motifs. We implemented a prioritization pipeline for ranking potential modifiers that generated candidate lists including several well-known for effects on ENS development as well as multiple novel genes. Among the novel genes, Dach1 ranked as a top priority candidate gene for modifying migration of ENCDCs and thus influencing aganglionosis severity. The results identify genome intervals with intrinsic genes that are logical candidates for modifying Sox10Dom aganglionosis severity. We also note that several human orthologs to aganglionosis modifier candidate genes are within linkage disequilibrium blocks containing genetic variants associated with human gut motility disorders, which offers opportunity for gaining biological insight into human HSCR severity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.