Complete sequence data support lack of balancing selection on PRNP in a natural Chinese population.
The M129V mutation in the human prion protein gene (PRNP) is the primary site linked to susceptibility to prion diseases in humans. The heterozygous state of this allele has been proven to be more resistant to prion-related diseases such as Creutzfeldt-Jakob disease. Based on a study of the common genetic variations, it has been proposed that balancing selection has played a critical role in shaping the distribution of 129V in worldwide populations. Kreitman and Di-Rienzo [Kreitman and Di-Rienzo (2004)Trend Genet 20:300-304] challenged this hypothesis by pointing out that the exclusion of polymorphisms with low frequency may introduce an ascertainment bias and, in turn, lead to a wrong conclusion. By studying sequence variations in samples from the Human Genome Diversity Project, Soldevila et al. [Soldevila et al. (2005) Trends Genet 21:389-391] showed that this ascertainment bias does exist. We argue that the evidence presented by Soldevila et al. may be compromised by the samples tested since they were selected from a population that may be substructured. In this study, we re-evaluated the hypothesis of balancing selection in a natural Chinese population using a much longer segment encompassing the entire genomic region of the PRNP gene (15 kb). We showed that the pattern of genetic variation in PRNP is not consistent with the presence of balancing selection in this gene.
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Qin
Q
Zan
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Bo
B
Wen
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Yungang
Y
He
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Yi
Y
Wang
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Shuhua
S
Xu
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Ji
J
Qian
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China.
Daru
D
Lu
State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, People's Republic of China. ljin007@gmail.com.|CAS-MPG Partner Institute of Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China. ljin007@gmail.com.|Center for Genome Information, Department Environmental Health, University of Cincinnati, Cincinnati, OH, USA. ljin007@gmail.com.|Institute of Genetics, Fudan University, 220 Handan Rd., 200433, Shanghai, People's Republic of China. ljin007@gmail.com.
Li
L
Jin
D044466:Asian People / Q000235:genetics; D030541:Databases, Genetic; D005069:Evaluation Studies as Topic; D014644:Genetic Variation; D006801:Humans; D044382:Population Groups; D011328:Prions / Q000235:genetics*
D011328:Prions