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History of human cannibalism eats away at researchers |
| TheallIneed.com/NC&T/CSHL |
Prof. Jaume Bertranpetit, a scientist at the Universitat Pompeu Fabra, and his colleagues used a fresh set of genetic data to show that balancing selection associated with cannibalism has not been a major selective driving force on the prion protein gene, as has recently been proposed. Their work also has important scientific implications for researchers using a specific class of DNA markers called SNPs (single nucleotide polymorphisms) to examine genetic associations with diseases or to evaluate historical patterns of human migration.
The prion protein gene (PRNP) encodes a protein that can abnormally fold and amass in brain tissues to cause fatal neurodegenerative diseases such as mad cow disease. These diseases are cumulatively known as transmissible spongiform encephalopathies (TSEs) and in humans, include CJD (Creutzfeldt-Jakob disease) and kuru. Kuru is confined to a human population in Papua-New Guinea and is transmitted by cannibalism at ritualistic mortuary feasts.
A high-profile study published nearly three years ago suggested that individuals who were heterozygous for a common polymorphism in the PRNP gene were relatively resistant to the disease. Over time, homozygotes who participated in the cannibalistic rituals purportedly diminished in numbers due to their increased susceptibility to kuru. This indicated that cannibalism conferred an effect of balancing selection on the PRNP gene throughout human history.
Bertranpetit and his colleagues sequenced 2,378 base pairs of the PRNP gene in 174 individuals; in addition, they genotyped two SNPs (or single nucleotide polymorphisms) from the PRNP gene in 1000 individuals from populations worldwide. They identified 28 different haplotypes – or combinations of DNA variants – in the PRNP gene and used this data to assess the ages of the mutations, to identify geographic patterns of variation, and to evaluate selective forces that have potentially influenced these patterns.
"In contrast to the previous study, which concluded that variation in the PRNP gene was strongly skewed toward intermediate frequency variants, our results showed that there was, in fact, a deficit of intermediate frequency variants," says Bertranpetit. "Our results are consistent with a complex history of episodic or fluctuating selection, including positive selection, purifying selection, and possibly even short periods of balancing selection."
On a more technical note, the study cautions researchers involved in SNP-based population genetics studies. The work is one of the first to empirically demonstrate how SNP ascertainment can introduce a strong bias in population genetics studies and severely affect the conclusions. Bertranpetit and his colleagues point out that at a time when a flood of ascertained SNP data is being generated, it is essential that SNP ascertainment be taken into consideration in data analyses.
The first author on the study is Dr. Marta Soldevila, who completed her Ph.D. at the Universitat Pompeu Fabra and performed a substantial part of the sequencing work at DeCODE Genetics (Reykjavik, Iceland).
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Nepal's human rights commission has made great strides, says UN official