Mutations, gain-of-function

Mutation is typically a gain of function Mutation is typicaUy a loss of function... 

Unlike tumor suppressors, in which loss-of-function mutations are required in both copies of the gene in a specific cell, a single gain-of-function mutation in a proto-oncogene is usually sufficient to give rise to cancer. 

For gain-of-function mutations gene-blocking therapy, using antisense oligonucleotides or ribozymes to block gene expression... 

Gene-blocking therapy for gain of function mutations... 

Families affected by ADH, autosomal dominant hypoparathyroidism, and hypocal-cemic hypercalcinria have each been defined by gain-of-function mutations in the CASR gene (44). ADH is associated with the expression of constitutively activated CASR, which serves to suppress PTH secretion from the parathyroid gland. In the kidney it induces hypercalciuria, which further contributes to the hypocalcemia. 

Dominant, gain-of-function mutations that activate oncogenes confer a rapid-growth phenotype on cells. 

Chen YH et al KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003 299 251. [PMID 12522251]... 

A form of epilepsy (Table 27-4) appears to be a result of repeats of a (G + C)-rich sequence that may be a dodecamer.405 Dinucleotide repeats and other "minisatellite" DNA sequences are also associated with instability of DNA and may undergo expansion.419 21 A pentanucleotide repeat (CCTTT) is associated with increased expression of the nitric oxide synthase gene NOS2A. Persons with n = 14 were found to have enhanced resistance to development of diabetic retinopathy. This seems to be a case of a beneficial "gain of function" mutation.422... 

Tirichine L, Sandal N, Madsen LH, Radutoiu S, Albrektsen AS, Sato S, Asamizu E, Tabata S, Stougaard J. 2007 A gain-of-function mutation in a cytokinin receptor triggers spontaneous root nodule organogenesis. Science 315 104-107. 

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