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Trends Genet. 2006 Feb;22(2):96-100. Epub 2005 Dec 27.

Sex is a threshold dichotomy mimicking a single gene effect.

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Galton Laboratory, Department of Biology, University College London, Wolfson House, London NW1 2HE, UK.


The discovery of SRY ended the search for the male-determining gene, but the much sought after molecular pathway that connects the gene to its phenotype remains elusive. It is timely, therefore, to consider an alternative route of inheritance that can simulate mendelian segregation. The term "threshold dichotomy" is applied to contrasting phenotypes that have their origin in multiple genes with quantitative effects and are divided by a physiological threshold. I suggest that this mechanism provides a plausible basis for male development in mammals, which is known to depend on enhanced rates of cell proliferation in the developing embryo and can be expected to require increased levels of cellular energy. The system is affected by the genetic and environmental background. I also propose that the Y chromosome minimizes the effects of these variables on XY embryos so that, barring rare exceptions, the inheritance of sex resembles a single gene effect.

[Indexed for MEDLINE]

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