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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
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An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
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Sex differences in interindividual gene expression variability across human tissues.

Samuel Khodursky1, Caroline S Jiang2, Eric B Zheng1

  • 1Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA.

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|January 30, 2023
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Summary
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This study reveals that genes with sex-differentiated variability (SDV) are linked to crucial biological functions and may play a role in sex-biased diseases like Graves

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Phenotypic sex differences are crucial in medicine and evolution.
  • Focus has been on average differences, not variability.
  • Molecular basis of sex differences in variability is understudied.

Purpose of the Study:

  • Investigate sex differences in gene expression variability.
  • Identify genes with sex-differentially variable (SDV) expression.
  • Explore the biological and evolutionary implications of SDV genes.

Main Methods:

  • Analyzed RNA-sequencing data from 43 tissues (Genotype-Tissue Expression project).
  • Utilized single-cell RNA sequencing for breast tissue analysis.
  • Examined associations with Graves' disease and evolutionary constraints (eQTL data).

Main Results:

  • Identified numerous SDV genes linked to hormone response, immunity, and signaling.
  • SDV genes in breast tissue show cell-type-specific expression.
  • Found enrichment of Graves' associated genes among female-higher variability genes in thyroid tissue.
  • SDV genes show evidence of increased selective constraint and a potential genetic basis.

Conclusions:

  • SDV gene expression is widespread and linked to key biological processes.
  • SDV expression may contribute to sex-biased disease prevalence.
  • Evolutionary models suggest sex-specific constraints drive SDV emergence.