ArticleProceedings of the National Academy of Sciences of the United States of America2009
The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 2 of them syntheses that pooled it.
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Who cites it
212 citing papers in PubMed, 2 syntheses or guidelines pooled it, 396 citations in OpenAlex.
- Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.Human molecular genetics · 2016Pooled it
- Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes.BMC genomics · 2011Pooled it
- A collagen VI-dependent pathogenic mechanism for Hirschsprung's disease.The Journal of clinical investigation · 2015Trial
- Duplication-based genetic dissection of the Down syndrome critical region reveals its complex functional organization.G3 (Bethesda, Md.) · 2026Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.eLife · 2026Article
- Amyloid precursor protein dosage normalization rescues neurogenesis and Alzheimer's Disease phenotypes associated with Down Syndrome.Medical research archives · 2026Article
- Discrepant findings of prenatal diagnostics in a case of fetal partial trisomy 21 and fetoplacental mosaicism.Molecular cytogenetics · 2026Article
- Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Inducible chromosomal rearrangement reveals nonlinear polygenic dosage effects in driving aneuploid yeast traits.Nature communications · 2025Article
- Future Directions for Studying the Potential of Mammalian Dscam in Autism Spectrum Disorder and Alzheimer's Disease: Insights from Dose Sensitivity.Molecular neurobiology · 2025Review
- Development of Molecular Neuropathology in Down Syndrome across the Lifespan.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Article
- Ripply3 overdosage induces mid-face shortening through Tbx1 downregulation in Down syndrome models.PLoS genetics · 2025Article
- Neurons maintain sequential order during radial migration by DSCAM-facilitated antagonism of N-Cadherin.bioRxiv : the preprint server for biology · 2025Article
- PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Understanding Keratoconus in Down Syndrome: From Etiology to Management - A Narrative Review.Clinical ophthalmology (Auckland, N.Z.) · 2025Review
- ZBTB21 suppresses CRE-mediated transcription to impair synaptic function in Down syndrome.Science advances · 2024Article
- MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A.World journal of gastrointestinal oncology · 2024Article
152 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 19 institutions in 7 countries.
Funding
Abstract
Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes. Although several hypotheses have been put forward, it is unclear as to whether particular gene loci on chromosome 21 (HSA21) are sufficient to cause DS and its associated features. Here we present a high-resolution genetic map of DS phenotypes based on an analysis of 30 subjects carrying rare segmental trisomies of various regions of HSA21. By using state-of-the-art genomics technologies we mapped segmental trisomies at exon-level resolution and identified discrete regions of 1.8-16.3 Mb likely to be involved in the development of 8 DS phenotypes, 4 of which are congenital malformations, including acute megakaryocytic leukemia, transient myeloproliferative disorder, Hirschsprung disease, duodenal stenosis, imperforate anus, severe mental retardation, DS-Alzheimer Disease, and DS-specific congenital heart disease (DSCHD). Our DS-phenotypic maps located DSCHD to a <2-Mb interval. Furthermore, the map enabled us to present evidence against the necessary involvement of other loci as well as specific hypotheses that have been put forward in relation to the etiology of DS-i.e., the presence of a single DS consensus region and the sufficiency of DSCR1 and DYRK1A, or APP, in causing several severe DS phenotypes. Our study demonstrates the value of combining advanced genomics with cohorts of rare patients for studying DS, a prototype for the role of copy-number variation in complex disease.
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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.