Although the nature of these forces is hotly debated, there is evidence that the tendency for excess DNA to accumulate depends on the combined effects of the mutation rate and the effective genetic population size (Ne; Lynch and Conery 2003).
In muscle tissue with mutation I736T, only slightly more than 1/3 of total myosin was mutated and only small effects of the mutation on the contractile apparatus were observed [ 15, 36].
Now drug companies have started a race to develop a drug that mimics the effects of the mutation.
The DNA is then inserted into a cell or organism, and the effects of the mutation are studied.
It is a fevered race among three pharmaceutical companies, Amgen, Pfizer and Sanofi, to test and win approval for a drug that mimics the effects of the mutation, drives LDL levels to new lows and prevents heart attacks.
Moreover, these effects of the mutation could be complemented.
Functional studies on the first described case demonstrated gain-of-function effects of the mutation.
The 2.2 Å structure of Thr114Phe α1-antitrypsin demonstrates that the effects of the mutation are mediated entirely by well-defined partial cavity blockade and allows in silico screening of fragments capable of mimicking the effects of the mutation.
Next, we evaluated the effects of the mutation on protein structures at the molecular structural level using an in silico model [15].
Thus, interval mapping was used to locate the mutation by analyzing the quantitative effects of the mutation (MAPManager QTX; Meer et al. 2002).
We studied the functional effects of the mutation K239N, which shows incomplete penetrance at the age of 65 years and compared it with the more aggressive mutation E120G.
