Two-dimensional site frequency spectrum for detecting, classifying and dating incomplete selective sweeps

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  • Satta Yoko
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies)
  • Zheng Wanjing
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies)
  • Nishiyama Kumiko V.
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies)
  • Iwasaki Risa L.
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies)
  • Hayakawa Toshiyuki
    Graduate School of Systems Life Sciences and Faculty of Arts and Science, Kyushu University
  • Fujito Naoko T.
    Institute for Human Genetics and Department of Epidemiology and Biostatistics, University of California
  • Takahata Naoyuki
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies)

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<p>The two-dimensional site frequency spectrum (2D SFS) was investigated to describe the intra-allelic variability (IAV) maintained within a derived allele (D) group that has undergone an incomplete selective sweep against an ancestral allele group. We observed that recombination certainly muddles the ancestral relationships of allelic lineages between the two allele groups; however, the 2D SFS reveals intriguing signatures of recombination as well as the genealogical structure of the D group, particularly the size of a mutation and the time to the most recent common ancestor (TMRCA). Coalescent simulations were performed to achieve powerful and robust 2D SFS-based statistics with special reference to accurate evaluation of IAV, significance of recombination effects, and distinction between hard and soft selective sweeps. These studies were extended to a case wherein an incomplete selective sweep is no longer in progress and ceased in the recent past. The 2D SFS-based method was applied to 100 intronic linkage disequilibrium regions randomly chosen from the East Asian population of modern humans to examine the P value distributions of the summary statistics under the null hypothesis of neutrality in a nonequilibrium demographic model. We argue that about 96% of intronic variants are non-adaptive with a 10% false discovery rate. Furthermore, this method was applied to six genomic regions in Eurasian populations that were claimed to have experienced recent selective sweeps. We found that two of these genomic regions did not have significant signals of selective sweeps, but the remaining four had undergone hard and soft sweeps and were dated, in terms of TMRCA, after the major out-of-Africa dispersal of modern humans.</p>

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