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The mutations produced an inadvertent stop signal in the gene, causing the cell to make a cut-down version of the gene's normal protein, the researchers report in Nature Genetics.
The new deletion and missense mutations produced an amino acid substitution at positions that are well conserved among several species.
In the first class, the two mutations produced an additive effect.
Furthermore, combining the T157C and L189C mutations produced an ∼500-fold reduction in TPenA sensitivity.
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The trouble, they report in the current issue of Nature, was that each separate cluster of mutations produced a dead receptor, no matter which one was chosen first.
A series of experiments eventually showed that four mutations produced a virus that transmitted well among the animals, he said.
Combining these with field resistance mutations produced a set of 36 non-synonymous polymorphisms associated with drug resistance.
However, on the BKS background, both mutations produced a life-shortening diabetes, whereas mice on the B6 background were normoglycemic (24– 24).
Nonsense mutations segregated at appreciable frequencies in TLR09B in L. montandoni, the more common of these mutations produced a stop codon in position 48, indicating that the respective allele does not encode a functional protein.
However, the technique can only identify genes for which mutations produce an easily recognizable mutant phenotype, and so genes with subtle effects are often missed.
"If it were not the case, then every time a mutation produced an improvement in body plan — a large significant change in anatomy — the animal would die and the beneficial mutation would be lost".
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com