Mutations constitutive

Izutani, K., Nakata, A., Shinagawa, H. Kawamata, J. (1980) Forward mutation assay for screening carcinogens by alkaline phosphatase constitutive mutations in Escherichia coli K-12. BikenJ.,13,69-75... 

We find that the first periodic selection happens at about 100 hr, with 100-200 hr between subsequent ones. It can range from as early as 50 hr, if there is a common mutation which is strongly selected such as lactose constitutive mutations in lactose-limited chemostats,17 to as late as about 120 hr. We sample for about 100 hr and then eliminate deviant final points (those that significantly increase the variance) to eliminate frequency changes caused by periodic selection. It is this limitation of the time over which selection can be measured that limits the resolution of the measurement of the selection coefficient to about 0.002/hr. 

Sevenet N, Sheridan E, Amram D, et al. Constitutional mutations of the hSNF5/INIl gene predispose to a variety of cancers. Am J Hum Genet. 1999 65 1342-1348. 

In patients from Li-Fraumeni families with an inherited p53 mutation, normal cells are heterozygous (p53 wt/mt), whereas in cancer cells, the wild-type allele is lost or otherwise inactivated by a somatic mechanism. Experimental studies have shown that the wild-type allele retained the capacity to suppress cell proliferation even in the presence of the mutant allele (Frebourg et al., 1992). The penetrance of the mutated gene is close to 100%, suggesting a causal link between the constitutive mutation and the somatic inactivation of the wild-type allele. In keeping with these observations, normal cells from individuals with germline p53 mutations show altered genomic stability (Boyle et al., 1998). 

Some of the known constitutive mutations of the lactose operon occur in the operator sequence rather than the regulator gene. 

H. V. Rickenberg, G. N. Cohen, B. Buttin, and J. Monod [5]. Constitutive mutations expressed as the ability to synthesize large amounts of galactosidase and acetylase in the absence of inducer. Permease observed. 

There is another type of constitutive mutation in which the activity levels of all the enzymes in the system are increased in the absence of an inducer this mutation results from the deletion of a gene (I-mutant). 

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