Allelic exclusion

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Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. For most genes, the individual inherits one copy of each gene from each parent.

At least two distinct selection events can lead to allelic exclusion. On one hand, one allele of the gene can be transcriptionally silent, which would result in the expression of only the second allele. On the other hand, both alleles can be transcribed, in which case posttrancriptional and posttranslational mechanisms will lead to the elimination of the protein product of one allele.

Though the mechanism by which allelic exclusion occurs is not fully understood.[1]

Allelic exclusion in B-Lymphocytes[edit]

Allelic exclusion has been observed most often in genes for cell surface receptors and has been extensively studied in immune cells such as B lymphocytes.[2] In B lymphocytes, successful heavy chain gene rearrangement of the genetic material from one chromosome results in the shutting down of rearrangement of genetic material from the second chromosome. If no successful rearrangement occurs, rearrangement of genetic material on the second chromosome takes place. If no successful rearrangement occurs on either chromosome, the cell dies.

As a result of allelic exclusion, all the antigen receptors on an individual lymphocyte will have the same amino acid sequence in the variable domain of the heavy chain protein. As the specificity of the antigen receptor is modulated by the variable domain of the light chain encoded by one of the immunoglobulin light chain loci, the specificities of B cells containing the same heavy chain recombination event can differ according to their light chain recombination event.

Allelic exclusion in sensory neurons[edit]

A recent study showed that CpA-methylation helps for allelic exclusion in sensory neurons.[3]

References[edit]

  1. ^ Mostoslavsky R, Alt FW, Rajewsky K (2004). "The lingering enigma of the allelic exclusion mechanism". Cell 118 (5): 539–44. doi:10.1016/j.cell.2004.08.023. PMID 15339659. 
  2. ^ Chess A (1998). "Expansion of the allelic exclusion principle?". Science 279 (5359): 2067–8. doi:10.1126/science.279.5359.2067. PMID 9537917. 
  3. ^ S. Lomvardas, G. Barnea, D.J. Pisapia, M. Mendelsohn, J. Kirkland and R. Axel (2006). "Interchromosomal interactions and olfactory receptor choice". Cell 126: 403–413. doi:10.1016/j.cell.2006.06.035. PMID 16873069. 

Further reading[edit]

  • Cellular and Molecular Immunology (5th Ed.) Abbas AK, and Lichtman AH., Editor: Saunders, Philadelphia, 2003.