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Record W2990639324 · doi:10.1101/851089

Balancing Selection at <i>HLA-G</i> Modulates Fetal Survival, Preeclampsia and Human Birth Sex Ratio

2019· preprint· en· W2990639324 on OpenAlexaff
Satu Wedenoja, Masahito Yoshihara, Hindrek Teder, Hannu Sariola, Mika Gissler, Shintaro Katayama, Juho Wedenoja, Inka M K Häkkinen, Sini Ezer, Nina Linder, Johan Lundin, Tiina Skoog, Ellika Sahlin, Erik Iwarsson, Karin Pettersson, Eero Kajantie, Mikael Mökkönen, Seppo Heinonen, Hannele Laivuori, Kaarel Krjutškov, Juha Kere

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicReproductive System and Pregnancy
Canadian institutionsKwantlen Polytechnic UniversitySimon Fraser University
FundersAstellas Foundation for Research on Metabolic DisordersPäivikki ja Sakari Sohlbergin SäätiöKarolinska InstitutetAstellas PharmaGreat Britain Sasakawa FoundationSuomen Lääketieteen SäätiöJapan Eye Bank AssociationJapan Society for the Promotion of ScienceHelsingin YliopistoEye Bank Association of America
KeywordsHuman leukocyte antigenOffspringFetusHLA-GBiologyPreeclampsiaPopulationBalancing selectionPregnancyImmunologySex ratioAntigenGeneticsMedicineMajor histocompatibility complex

Abstract

fetched live from OpenAlex

Abstract The population sex ratio is thought to be maintained through balancing selection on rare phenotypes. However, empirical evidence for genetic influence has thus far proven elusive. We combined 1000 Genomes data and large cohorts to study human sex ratios. We found underrepresentation of male offspring in preeclampsia, a serious pregnancy disorder with uncertain pathogenesis. Genetic variation of fetal human leukocyte antigen G ( HLA-G ), regulating maternal anti-fetal immune responses, was found to be under balancing selection. Sex-linked downregulation of HLA-G and upregulation of interferon alpha-1 ( IFNA1 ) expression contribute to loss of fetal immunotolerance in preeclampsia and suggest hydroxychloroquine as a treatment option. Our findings indicate that an evolutionary trade-off between fetal immunotolerance and protection against infections promotes genetic diversity in HLA-G , thereby maintaining human sex ratios. One Sentence Summary Fetal HLA-G modulates human sex ratio.

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)0.001
metaresearch head score (Gemma)0.002
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 score0.008
Threshold uncertainty score0.025

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0080.001

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 head0.212
Teacher spread0.201 · 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

Citations1
Published2019
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicReproductive System and PregnancyFrench-language works237,207