Haploinsufficiency

Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene (with the other copy inactivated by mutation) and the single functional copy of the gene does not produce enough of a gene product (typically a protein) to bring about a wild-type condition, leading to an abnormal or diseased state.

Haploinsufficiency is therefore an example of incomplete or partial dominance, as a heterozygote (with one mutant and one normal allele) displays a phenotypic effect.

A Haploinsufficient gene is therefore described as needing both alleles to be functional in order to express the wild type. A mutation is not haploinsufficient, but dominant loss of function mutations are the result of mutations in haploinsufficient genes.

Human diseases caused by haploinsufficiency include:
* Some cancers
* Cleidocranial dysostosis
* Marfan syndrome
* Polydactyly
* 5q- syndrome in myelodysplastic syndrome (MDS)

References

* Griffiths, Anthony J. et al. (2005). "Introduction to Genetic Analysis (8th Ed.)". W.H. Freeman. ISBN 0-7167-4939-4
* Robinson PN, Arteaga-Solis E, Baldock C, Collod-Béroud G, Booms P, De Paepe A, Dietz HC, Guo G, Handford PA, Judge DP, et al. (2006). "The molecular genetics of Marfan syndrome and related disorders". "Journal of Medical Genetics" 43:769-787.
* Ebert BL, et al. (2008). "Identification of RPS14 as a 5q- syndrome gene by RNA interference screen". Nature 451:335-340.