CoChat
Sign Up
Cited by 249Down syndrome and intellectual disability researchGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesGenomic variations and chromosomal abnormalities

Transcript level alterations reflect gene dosage effects across multiple tissues in a mouse model of down syndrome

Open access
Kahlem, Pascal, Sultan, Marc, Herwig, Ralf, Steinfath, Matthias, Balzereit, Daniela, Eppens, Barbara, Saran, Nidhi G., Pletcher, Mathew T. +5 more·2004·Genome Research
DOI 10.1101/gr.1951304PMC PMC442140
Open this paper in CoChat — free accountOpen PDF

Abstract

Human trisomy 21, which results in Down syndrome (DS), is one of the most complicated congenital genetic anomalies compatible with life, yet little is known about the molecular basis of DS. It is generally accepted that chromosome 21 (Chr21) transcripts are overexpressed by about 50% in cells with an extra copy of this chromosome. However, this assumption is difficult to test in humans due to limited access to tissues, and direct support for this idea is available for only a few Chr21 genes or in a limited number of tissues. The Ts65Dn mouse is widely used as a model for studies of DS because it is at dosage imbalance for the orthologs of about half of the 284 Chr21 genes. Ts65Dn mice have several features that directly parallel developmental anomalies of DS. Here we compared the expression of 136 mouse orthologs of Chr21 genes in nine tissues of the trisomic and euploid mice. Nearly all of the 77 genes which are at dosage imbalance in Ts65Dn showed increased transcript levels in the tested tissues, providing direct support for a simple model of increased transcription proportional to the gene copy number. However, several genes escaped this rule, suggesting that they may be controlled by additional tissue-specific regulatory mechanisms revealed in the trisomic situation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/gr.1951304

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A frequent assumption regarding gene dosage effects in trisomy is that expression of all trisomic genes is upregulated according to the gene copy number (1.5-fold) in every cell in the body throughout the lifespan.

    “A frequent assumption regarding gene dosage effects in trisomy is that expression of all trisomic genes is upregulated according to the gene copy number (1.5-fold) in every cell in the body throughout the lifespan of the individual, though some have reported dosage compensation for some genes (Ait Yahya-Graison et al., 2007; Hwang et al., 2021; Kahlem et al., 2004; Lyle et al., 2004).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Kahlem et al., 2004

    The Abstract (page unavailable) says it is widely assumed that trisomic Chr21 genes have transcript levels about 50% above normal. But the Gene Dosage Effects section reports that several genes escape the 1.5-fold pattern, and the Discussion says whole-tissue measurements cannot establish expression in every cell or at every developmental stage. The source therefore supports the description of a frequent assumption, but not its extension to all genes in every cell throughout life. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Some have reported dosage compensation for some genes.

    “A frequent assumption regarding gene dosage effects in trisomy is that expression of all trisomic genes is upregulated according to the gene copy number (1.5-fold) in every cell in the body throughout the lifespan of the individual, though some have reported dosage compensation for some genes (Ait Yahya-Graison et al., 2007; Hwang et al., 2021; Kahlem et al., 2004; Lyle et al., 2004).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Kahlem et al., 2004

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Epstein, C.J. 1986. The consequences of chromosomal imbalance. Cambridge University Press, Cambridge, UK.

Cited by

Sorted by citations

Related

Authors
Kahlem, P., Sultan, M., Herwig, R., Steinfath, M., Balzereit, D., Eppens, B., Saran, N. G., Pletcher, M. T., South, S. T., Stetten, G., Lehrach, H., Reeves, R. H., & Yaspo, M.-L.
Affiliations
  • Max Planck Society (DE)
  • Johns Hopkins University (US)
  • Scripps Research Institute (US)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2004-07
Volume
14
Issue
7
Pages
1258-1267
ISSN
1088-9051 (ISSN-L)
DOI
10.1101/gr.1951304
PMC
PMC442140
OpenAlex
W2100192472
Cited by
249
References
37
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 11 · 2017: 4 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 18 · 2012: 20
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
Funders
  • Bundesministerium für Bildung und Forschung
  • Max-Planck-Gesellschaft
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-24605, P01HD024605, R01HD038384, HD 38384)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
Down syndrome, Ts65Dn mouse model, gene dosage imbalance, tissue-specific gene regulation
MeSH terms
Animals, Chromosome Mapping, Chromosomes, Chromosomes, Human, Pair 21, Disease Models, Animal, Down Syndrome, Gene Expression Regulation, Genes, Humans, Male, Mice, Mutant Strains, Organ Specificity, Transcription, Genetic, Translocation, Genetic, Trisomy, Gene Dosage, Chromosome Breakage, Gene Expression Profiling, Databases, Genetic, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review