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• W2010969191 abstract "Ample evidence has accumulated showing that different coding variants of the PRNP gene confer differential susceptibility for prion diseases. Here we evaluate the patterns of nucleotide variation in PRNP exon 2, which includes all the protein-coding sequence, by resequencing a worldwide sample of 174 humans for 2378 bp. In line with previous studies, we found two main haplotypes differentiated by nonsynonymous substitution in codon 129. Our analyses reveal the worldwide pattern of variation at the PRNP gene to be inconsistent with neutral expectations, indicating instead an excess of low-frequency variants, a footprint of the action of either positive or purifying selection. A comparison of neutrality test statistics for PRNP with other human genes indicates that the signal of positive selection on PRNP is stronger than expected from a possible confounding genome-wide background signal of population expansion. Two main conclusions arise from our analysis. First, the existence of an ancient, stable, balanced polymorphism that has been claimed in a previous study and related to cannibalism can be rejected and is shown to be due to ascertainment bias. Second, our results are consistent with a complex history of selection including mainly positive selection, even if short local periods of balancing selection (Kuru-like episodes), or even a weak purifying selection model, are consistent with our data." @default.
• W2010969191 created "2016-06-24" @default.
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• W2010969191 date "2005-12-20" @default.
• W2010969191 modified "2023-10-17" @default.
• W2010969191 title "The prion protein gene in humans revisited: Lessons from a worldwide resequencing study" @default.
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• W2010969191 doi "https://doi.org/10.1101/gr.4345506" @default.
• W2010969191 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1361719" @default.
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