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Record W4408956707 · doi:10.1111/vde.13341

Intragenic <i>PNPLA1</i> duplication in Labrador retrievers with nonepidermolytic ichthyosis

2025· article· en· W4408956707 on OpenAlexaboutno aff
Stefan J. Rietmann, Jennifer Loraine Clegg, Vidhya Jagannathan, Dominique J. Wiener, Angelica Kallenberg, Robert A. Grahn, Clarissa P. Souza, Tosso Leeb

Bibliographic record

VenueVeterinary Dermatology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSkin and Cellular Biology Research
Canadian institutionsnot available
FundersSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
KeywordsGene duplicationIchthyosisMedicineDermatologyBiologyGeneticsGene

Abstract

fetched live from OpenAlex

BACKGROUND: Ichthyoses represent a heterogeneous group of cornification disorders characterised by epidermal scaling. OBJECTIVES: To describe the clinical, histopathological and genetic analysis of a Labrador retriever with nonepidermolytic ichthyosis, and the results of a population screening for a newly detected PNPLA1 genomic duplication. ANIMALS: Two 7-year-old male littermates, 531 population samples. MATERIALS AND METHODS: Clinical and histopathological analysis, whole genome sequencing and digital PCR-based genotyping were performed. RESULTS: Generalised scaling and histological laminar orthokeratotic hyperkeratosis confirmed the ichthyosis diagnosis on Dog 1. Dog 2 showed mild clinical signs possibly associated with allergies and not ichthyosis. The genome of Dog 1 was sequenced and compared to 1469 genetically diverse control genomes. The analysis identified a 6099-bp duplication spanning three internal exons of the PNPLA1 gene, which is predicted to result in an altered C-terminal tail of the protein, NP_001277038.2:p.(E558Lfs*17). Dog 2 had a heterozygous genotype and carried one copy of the duplicated PNPLA1 allele. Of the screened 531 additional Labrador retrievers, 491 were homozygous wild-type, 36 were heterozygous carriers and four carried the duplication in a homozygous state. CONCLUSIONS AND CLINICAL RELEVANCE: Previously identified PNPLA1 variants cause autosomal recessive ichthyosis in golden retrievers and humans. Given the well-established function of PNPLA1, the identified genomic duplication represents a likely candidate causal variant for the observed ichthyosis in the examined Labrador retriever. This is the first report of a new form of autosomal recessive ichthyosis in Labrador retrievers, which provides the basis for genetic testing.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.205
Threshold uncertainty score0.618

Codex and Gemma teacher scores by category

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

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 head0.010
GPT teacher head0.270
Teacher spread0.260 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations1
Published2025
Admission routes1
Has abstractyes

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