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Genetics of familial amyotrophic lateral sclerosis

2008· review· en· W2027416732 on OpenAlexaff
Paul N. Valdmanis, Guy A. Rouleau

Bibliographic record

VenueNeurology · 2008
Typereview
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsHôpital Notre-Dame
Fundersnot available
KeywordsAmyotrophic lateral sclerosisSOD1GeneticsC9orf72DiseaseBiologyIdentification (biology)Genetic epidemiologyGeneMutationMedicineTrinucleotide repeat expansionAllelePathology

Abstract

fetched live from OpenAlex

The completion of the Human Genome Project, together with a better understanding of some of the emerging genetic patterns of human disease, has enabled a thorough examination of the most appropriate genetic models for amyotrophic lateral sclerosis (ALS). The pathology and epidemiology of ALS have been intensively studied since Adar, Charcot, and Duchenne first described the disease in the 1860s. Results of genetic studies that have emerged over the past two decades have led to the identification of <i>SOD1</i> as a well-established causative gene for ALS. However, the identification of <i>SOD1</i> has not been followed up by the identification of other genes responsible for classic ALS. This leads to the speculation that more complex genetic mechanisms are involved than initially assumed. While mutations in single genes are still likely to constitute a small proportion of ALS cases, the genes responsible for ALS in families with clusters of two or three affected individuals, and more particularly in sporadic cases, are far from being determined. Multigenic, somatic mutation, and gene–environment models may all contribute to the genetic etiology of ALS. The challenge now lies in determining which models are the most appropriate to dissect out the genetic components involved. This research will ultimately aid in identifying the cumulative risk of developing ALS. <b>GLOSSARY: </b><b>ALS</b> = amyotrophic lateral sclerosis; <b>FALS</b> = familial ALS; <b>FTD</b> = frontotemporal dementia; <b>HSP</b> = hereditary spastic paraplegia; <b>PDC</b> = Parkinson-dementia complex; <b>PLS</b> = primary lateral sclerosis; <b>PON</b> = paraoxonase; <b>SALS</b> = sporadic ALS; <b>SBMA</b> = spinal and bulbar muscular atrophy; <b>SMA</b> = spinal muscular atrophy; <b>SNP</b> = single nucleotide polymorphism.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.988
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.115
GPT teacher head0.347
Teacher spread0.233 · 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.

Study designOther design
Domainnot available
GenreReview

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

Citations277
Published2008
Admission routes1
Has abstractyes

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