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Related Concept Videos

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An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
10:17

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Published on: November 3, 2010

Hypothesis: genes which function in a stochastic lineage commitment process are subject to monoallelic expression.

M J Shulman1, G E Wu

  • 1Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

Seminars in Immunology
|September 25, 1999
PubMed
Summary

Monoallelic gene expression, where only one gene copy is active, may arise from selective developmental mechanisms. This contrasts with instructive mechanisms and helps explain phenomena like genomic imprinting and X-chromosome inactivation.

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Monoallelic gene expression is observed in diverse mammalian genes, including those for receptors and imprinted genes.
  • The physiological purpose of monoallelic expression is unclear for many genes, particularly those not encoding receptors.
  • Imprinted genes, expressed only from the maternal or paternal allele, present a unique puzzle in gene regulation.

Purpose of the Study:

  • To explore the hypothesis that selective developmental mechanisms, rather than instructive ones, underlie some instances of monoallelic gene expression.
  • To differentiate between instructive (external signals) and selective (internal, cell-autonomous events) mechanisms of lineage commitment.
  • To connect selective mechanisms to observed patterns of monoallelic gene expression in development.

Main Methods:

  • Conceptual analysis of gene expression mechanisms in mammalian development.
  • Comparison of predictions from instructive versus selective lineage commitment models.
  • Review of existing literature on monoallelically expressed genes, including receptor genes, cytokine genes, transcription factor genes, X-linked genes, and imprinted genes.

Main Results:

  • Selective mechanisms predict monoallelic gene expression during lineage commitment, contrasting with the biallelic expression predicted by instructive mechanisms.
  • For lineage commitment via gene activation, selective mechanisms predict post-commitment monoallelic expression, consistent with some cytokine and transcription factor genes.
  • For lineage commitment via gene silencing, selective mechanisms predict pre-commitment monoallelic expression, aligning with X-linked and imprinted genes.

Conclusions:

  • Monoallelic gene expression in mammals may frequently result from selective, cell-autonomous developmental processes.
  • The selective mechanism provides a unifying framework for understanding diverse cases of monoallelic gene expression, including genomic imprinting.
  • Further research is needed to fully elucidate the role of selective mechanisms in developmental gene regulation and lineage commitment.