In addition to the co-segregation observed, the rarity of these variants in publically available controls databases, the predicted effect of the variants on translation or protein structure and the functional evidence confirming the effect on enzymatic activity all help support the pathogenic role of these variants.
To examine effects of rs563649 allelic variants on translation efficiency, we transiently transfected human neuroblastoma BE2C cells with reporter constructs that carried allelic variants of MOR-1K IRES inserted between transcription and translation start sites (Fig. 3B).
In the VDRff variant initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein comprised of 427 amino acids.
In the VDRff variant, initiation of translation occurs at the first ATG site, giving rise to a full length VDR protein of 427 amino acids.
In the ff variant, initiation of translation occurs at the first ATG site, giving a long version of VDR protein comprised 427 amino acids.
The corresponding human variant of the protein (translation from M143) was not enriched in mitochondrial fractions and was shown to be non-mitochondrial by immunofluorescence ([11], Fig. 4 and not shown).
Provided that the minor allele of the studied CD40 variant decreases the efficiency of translation, this lower amount of CD40 would then result in a reduced induction of Treg, which would lead to a disruption of immune tolerance.
We discuss in turn (i) Some ODE models (ii) Simulation algorithms and variants for stochastic simulation of translation (iii Formulation of Boolean rules to describe different events in translation.
There are multiple ways in which genetic variation can modulate the nature, abundance and function of proteins, including effects of non-coding variants on transcription, regulation of translation and RNA editing, and alternative splicing.
Many slight variants have been discovered since then, including various alternative mitochondrial codes, and small variants such as translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than a leucine in yeasts of the "CTG clade" (Candida albicans is member of this group).
Finally, when the uORF start codon was mutated in the context of the c.−95T > G variant, translation of the dORF was increased to a level significantly higher than for the wt sequence, suggesting that the uORF is a physiologically acting negative regulator of EFNB1 translation and that abolition of the stop codon by the c.−95T > G mutation accentuates this negative effect.
