Hand, Normal Variants

Uchida A, Moffa P, Perez-Riera A et al., 2006). On the other hand in patients without heart disease the presence of prominent R wave inVl, especially if the voltage of R is low, is much probably due to a normal variant (see Table 5.5). 

Intolerance. Here, a patient shows a qualitatively normal response to the drug, but at an abnormally low dose. This may simply be a resp9nse at the extreme of the normal range of variation. The Gaussian distribution of response to a drug includes individuals who are unusually sensitive as well as those who are resistant. On the other hand, the response to some drugs shows two or more genetically determined populations, e.g. the response to suxamethonium in normal persons and in those with abnormal variants of cholinesterase. 

Individual A will produce only normal hemoglobin chains. Individual C, will produce only variant hemoglobin chains. Individual B, with genes for both types, will produce both. If the mutation is deleterious, A will be unaffected, but C will be in serious trouble. B, on the other hand, may do fairly well, because he or she will make normal protein chains along with the variant ones. 

Animal Models Early experimental hints for protein immunogenicity may arise from animal models, especially from experiments with transgenic animals that are tolerant to the human protein [65], hut might develop anti-protein variant anti-hodies. On the other hand, if the drug fails to stimulate an immune response in normal (nonengineered) animals, preferably in non-human primates, even when administered with some adjuvant, then there is a good probability of low immunogenicity in humans [66, 67]. 

On the other hand, a plastome mutant (thm-u-i) has been found in Chlamydomonas reinhardtli, which has a variant thylakoid protein (polypeptide 5 is about 1000 dalton larger than its wild type counterpart 5) and nevertheless a normal photosynthetic capacity (34). Mutations in the plaetid gene rbcL, coding for the LS of rubisco, lead to mlseenee and nonsense codons, as referred to in the preceeding paragraphs. They result in the synthesis of unstable or truncated polypeptides, which arte nonfunctional and thus block the dark reactions of photosynthesis. 

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