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Record W2949471222 · doi:10.1002/humu.23842

The spectrum of <i>BRCA1</i> and <i>BRCA2</i> pathogenic sequence variants in Middle Eastern, North African, and South European countries

2019· article· en· W2949471222 on OpenAlexafffund
Yael Laitman, Tara M. Friebel, Drakoulis Yannoukakos, Florentia Fostira, Irene Konstantopoulou, Gisella Figlioli, Bernardo Bonanni, Siranoush Manoukian, Monica Zuradelli, Carlo Tondini, Barbara Pasini, Paolo Peterlongo, Dijana Plaseska‐Karanfilska, Milena Jakimovska, Keivan Majidzadeh‐A, Shiva Zarinfam, Maria A. Loizidou, Andreas Hadjisavvas, Kyriaki Michailidou, Kyriacos Kyriacou, Doron M. Behar, Rinat Bernstein‐Molho, Patricia A. Ganz, Paul A. James, Michael T. Parsons, Aminah Sallam, Olufunmilayo I. Olopade, Arun Seth, Georgia Chenevix‐Trench, Goska Leslie, Lesley McGuffog, Makia J. Marafie, André Mégarbané, Fahd Al‐Mulla, Timothy R. Rebbeck, Eitan Friedman

Bibliographic record

VenueHuman Mutation · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversity of Toronto
FundersEuropean Social FundNational Cancer InstituteMedical Research CouncilMinistero dello Sviluppo EconomicoNational Health and Medical Research CouncilDr. Ralph and Marian Falk Medical Research TrustCancer Research UKDipartimenti di EccellenzaNational Institutes of HealthOvarian Cancer Research FundUniversity of ChicagoNational Breast Cancer FoundationMinistère du Développement Économique, de l’Innovation et de l’ExportationJonsson Comprehensive Cancer CenterCanadian Institutes of Health ResearchAssociazione Italiana per la Ricerca sul CancroEuropean CommissionBreast Cancer Research Foundation
KeywordsBiologyGenotypingDemographyPopulationInbreedingGeneticsConsanguinityFounder effectAlleleHaplotypeGeneGenotype

Abstract

fetched live from OpenAlex

BRCA1 BRCA2 mutational spectrum in the Middle East, North Africa, and Southern Europe is not well characterized. The unique history and cultural practices characterizing these regions, often involving consanguinity and inbreeding, plausibly led to the accumulation of population-specific founder pathogenic sequence variants (PSVs). To determine recurring BRCA PSVs in these locales, a search in PUBMED, EMBASE, BIC, and CIMBA was carried out combined with outreach to researchers from the relevant countries for unpublished data. We identified 232 PSVs in BRCA1 and 239 in BRCA2 in 25 of 33 countries surveyed. Common PSVs that were detected in four or more countries were c.5266dup (p.Gln1756Profs), c.181T>G (p.Cys61Gly), c.68_69del (p.Glu23Valfs), c.5030_5033del (p.Thr1677Ilefs), c.4327C>T (p.Arg1443Ter), c.5251C>T (p.Arg1751Ter), c.1016dup (p.Val340Glyfs), c.3700_3704del (p.Val1234Glnfs), c.4065_4068del (p.Asn1355Lysfs), c.1504_1508del (p.Leu502Alafs), c.843_846del (p.Ser282Tyrfs), c.798_799del (p.Ser267Lysfs), and c.3607C>T (p.Arg1203Ter) in BRCA1 and c.2808_2811del (p.Ala938Profs), c.5722_5723del (p.Leu1908Argfs), c.9097dup (p.Thr3033Asnfs), c.1310_1313del (p. p.Lys437Ilefs), and c.5946del (p.Ser1982Argfs) for BRCA2. Notably, some mutations (e.g., p.Asn257Lysfs (c.771_775del)) were observed in unrelated populations. Thus, seemingly genotyping recurring BRCA PSVs in specific populations may provide first pass BRCA genotyping platform.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.716
Threshold uncertainty score0.254

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 head0.011
GPT teacher head0.240
Teacher spread0.229 · 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 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

Citations48
Published2019
Admission routes2
Has abstractyes

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