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Record W2152079029 · doi:10.1016/j.ajhg.2010.10.004

Deletion 17q12 Is a Recurrent Copy Number Variant that Confers High Risk of Autism and Schizophrenia

2010· article· en· W2152079029 on OpenAlexaff
Daniel Moreno‐De‐Luca, Jennifer G. Mullé, Erin B. Kaminsky, Stephan Sanders, Scott M. Myers, Margaret P Adam, Amy T. Pakula, Nancy Eisenhauer, Kim Uhas, LuAnn Weik, Lisa Guy, Melanie Care, Chantal F. Morel, Charlotte Boni, Bonnie Anne Salbert, Ashadeep Chandrareddy, Laurie Demmer, Eva W. C. Chow, Urvashi Surti, Swaroop Aradhya, Diane L. Pickering, Denae M. Golden, Warren G. Sanger, Emily Aston, Arthur R. Brothman, Troy J. Gliem, Erik C. Thorland, Todd Ackley, Ram Iyer, Shuwen Huang, John Barber, John A. Crolla, Stephen T. Warren, David H. Ledbetter

Bibliographic record

VenueThe American Journal of Human Genetics · 2010
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsUniversity of TorontoUniversity Health NetworkCentre for Addiction and Mental HealthMount Sinai Hospital
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Mental HealthSimons Foundation Autism Research Initiative
KeywordsAutismCopy-number variationSchizophrenia (object-oriented programming)NeurocognitiveNeurodevelopmental disorderHNF1BAutism spectrum disorderMicrodeletion syndromeMedicineBioinformaticsGeneticsPhenotypeBiologyPsychiatryGeneCognitionGenome

Abstract

fetched live from OpenAlex

Autism spectrum disorders (ASD) and schizophrenia are neurodevelopmental disorders for which recent evidence indicates an important etiologic role for rare copy number variants (CNVs) and suggests common genetic mechanisms. We performed cytogenomic array analysis in a discovery sample of patients with neurodevelopmental disorders referred for clinical testing. We detected a recurrent 1.4 Mb deletion at 17q12, which harbors HNF1B, the gene responsible for renal cysts and diabetes syndrome (RCAD), in 18/15,749 patients, including several with ASD, but 0/4,519 controls. We identified additional shared phenotypic features among nine patients available for clinical assessment, including macrocephaly, characteristic facial features, renal anomalies, and neurocognitive impairments. In a large follow-up sample, the same deletion was identified in 2/1,182 ASD/neurocognitive impairment and in 4/6,340 schizophrenia patients, but in 0/47,929 controls (corrected p = 7.37 × 10⁻⁵). These data demonstrate that deletion 17q12 is a recurrent, pathogenic CNV that confers a very high risk for ASD and schizophrenia and show that one or more of the 15 genes in the deleted interval is dosage sensitive and essential for normal brain development and function. In addition, the phenotypic features of patients with this CNV are consistent with a contiguous gene syndrome that extends beyond RCAD, which is caused by HNF1B mutations only.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.237
Teacher spread0.230 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations332
Published2010
Admission routes1
Has abstractyes

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