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Dominance and gene dosage balance in health and disease: why levels matter!
Author(s) -
Veitia Reiner A.,
Birchler James A.
Publication year - 2010
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2623
Subject(s) - haploinsufficiency , dominance (genetics) , biology , phenotype , gene , gene dosage , genetics , allele , gene expression
The classical concept of genetic dominance is a simplification of a more quantitative reality. This is clearly exemplified by aneuploid syndromes, of which the best known case is trisomy 21. Moreover, there is an increasing number of clinical conditions due to reduced dosage (haploinsufficiency) of genes encoding transcription factors and other proteins involved in signal transduction and macromolecular complexes. In such genetic diseases, a high degree of phenotypic variability is observed, which calls for an explanation. The sources of dominance are heterogeneous and difficult to cover in a brief review. Here, we will focus on the molecular bases of dosage‐sensitive syndromes from the perspective of the gene dosage balance hypothesis, which postulates that stoichiometric alterations of macromolecular complexes or cellular networks are responsible for dominant phenotypes, because of the existing non‐linear relationships between the genotypic and phenotypic values with which they are associated. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.