SNPdbe conservation score (PKU)

<figure id="fig:pssm_wt">

Distribution of PSSM scores of SNP positions in the wildtype of the PAH gene

</figure> <figure id="fig:perc_wt">

Distribution of precentage of conservation of SNP positions in the wildtype of the PAH gene

</figure> <figure id="fig:pssm_mt">

Distribution of PSSM scores of SNP positions in mutants of the PAH gene

</figure> <figure id="fig:perc_mt">

Distribution of precentage of conservation of SNP positions in mutants of the PAH gene

</figure>

To find a quick-and-dirty way do decide whether a SNP in SNPdbe is disease-causing without looking at the predictions, we looked at the conservation scores, specificially the pssm score. We find low percentage scores and low PSSM scores of the wildtype and higher scores of the wildtype even if there is no known effect associated or predicted, so these scores are probably not a good indicator. Nonetheless we try to find a sensible cut-off of conservation values, below which we say a SNP has 'no effect'. The distribution of precentage of conservation in wildtype and mutant can be found in <xr id="fig:perc_wt"/> and <xr id="fig:perc_mt"/>, the PSSM scores in <xr id="fig:pssm_wt"/> and <xr id="fig:pssm_mt"/>. Almost all mutants have a percentage of conservation below 12, whereas the percentage of the wildtype is roughly equally distributed from 0 to 50 and declines linearly from 50 to 100. In addition, most mutants and only few wildtypes have a PSSM score below 0. From these observations and for simplicity, we decided to call SNPs in SNPdbe with a percentage of conservation of 12 or less and with a PSSM score of 0 or less 'not disease-causing'.