Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences
Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8...
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| Published in | Genome biology Vol. 15; no. 6; p. R88 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BioMed Central Ltd
30.06.2014
BioMed Central |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes.
We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively.
We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research. |
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| AbstractList | BACKGROUND: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. RESULTS: We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. CONCLUSIONS: We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research. Background: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. Results: We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. Conclusions: We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research. This work was supported by The Wellcome Trust (098051), an Italian National Research Council (CNR) short-term mobility fellowship from the 2013 program to VC, and an EMBO Short Term Fellowship ASTF 324–2010 to VC Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research. Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes.BACKGROUNDPopulation differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes.We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively.RESULTSWe demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively.We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.CONCLUSIONSWe identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research. |
| ArticleNumber | R88 |
| Author | Pagani, Luca Pybus, Marc Garrison, Erik Xue, Yali Chen, Yuan Tyler-Smith, Chris Luisi, Pierre Ayub, Qasim Colonna, Vincenza |
| AuthorAffiliation | 2 Institute of Genetics and Biophysics ‘A. Buzzati-Traverso’, National Research Council (CNR), Naples 80131, Italy 4 Department of Biology, Boston College, Chestnut Hill, MA 02467, USA 3 Institute of Evolutionary Biology (Universitat Pompeu Fabra-CSIC), CEXS-UPF-PRBB, Barcelona, Catalonia 08003, Spain 1 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs CB10 1SA, UK |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24980144$$D View this record in MEDLINE/PubMed |
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| Snippet | Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify... Background: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential... BACKGROUND: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential... |
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| SubjectTerms | calcium data collection Gene Frequency genes Genetic Drift genetic variation Genome, Human Genètica de poblacions humanes Genètica humana human population Humans INDEL Mutation loci metabolism Polymorphism, Single Nucleotide Selecció natural Selection, Genetic Sequence Analysis, DNA single nucleotide polymorphism surveys Variació |
| Title | Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences |
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