China is currently the world's most populous country. The second model featured a constant population size of 100 for 4979 generations; the size of the population was then increased exponentially with a base of 2.4 for 10 generations, giving a final population size of 10,968.

Depending on recombination rate, each Ne estimate represented Ne change in a different period of time. Therefore, the rest, 1−2c/(2Nn−1), should be applied to the portion without recombination.

It is fast and is able to handle large number of variants from sequencing data.

The amount of reduction from the original population directly determined the extent of reduction of the Ne estimates. This expectation is applicable when the direct identification of haplotypes is available. For a sampled population, the probability that both genes descend from the same gene is not dependent on the original population size but rather on the sampled population size. In addition, the LD between aged SNPs at equilibrium should be used for Ne estimation. The haplotype frequencies were derived using the EM algorithm. No, Is the Subject Area "Human genomics" applicable to this article? Yes In this estimate of Ne, the current effective population size was not involved.

Starting from the complete LD (r2 = 1), only two initial haplotypes for each pair at the first generation were generated by a binomial draw based on allele frequencies of 0.5. In the current study, the theoretical expectation for change in effective population size was exactly matched with the simulation results. Another analysis, which used the Perlegen data, did not identify GPHN as a gene under strong selection pressure, but supplementary information indicated that this gene region fell within the significant selective sweep with a p-value of ∼0.0006 in the Chinese sample [4], [50]. Email: © The Author(s) 2018. Compared to the continuous increment, the exponential increment showed smoother Ne increments, as the recombination rate increased. Neither was the value for the generations until equilibrium equivalent to 1/(2c) nor did the estimates indicate the Ne at a certain number of generations in the past. Therefore, an additional departure of LD, c2/(2Nn−1), should be added for the portion of recombination. The uncorrected sampling bias inflated Ne estimates at small recombination rates, especially 10,000∼20,000 years ago in their timeframe. One study, which used HapMap data, listed this region as under strong selection pressure in supplementary information that provided a summary of the strongest regions of selection in Europeans [49]. For the accuracy of estimates, single nucleotide polymorphisms (SNPs) without missing data were used for analysis of the HapMap data. Here, as in the previous study [19], sampling with replacement was assumed. The LD was measured with distances in each chromosome for each population in the HapMap data, and only autosomes were examined. These results verify previous observations of human population growth [26], [27] and provide further detailed information regarding the individual population histories. Because the Ne estimates reflect the recent population history much more than the old population history, the recent population history was examined in priority. To examine the difference between the original r2 and the sampled r2, the mean squared errors were obtained from simulations for a population size of 1,000 and various sample sizes (Table S2). This approach resulted in the formula 1/(4Nc+1) for small values of c [16], [19], [20]. here. This study investigated the expectation of LD decay involving changes of effective population size under various circumstances, and the results were applied to the human genome using HapMap phase III data to infer the past population history of each human population. Over time, the population sizes had been changed, and the LD, which depends on recombination rate, can indicate past changes in effective population size. plot we obtain is the following and shows complete concordance of The LD in the human genome has been used to determine the association between variants and traits [1], and efforts to understand selection pressures have been based largely on the LD status of populations [2]–[5], The theoretical basis of expectations for LD was established by the pioneering efforts of theoretical geneticists [6]–[14]. One period included generations 4916 to 4925 starting at approximately AD 500 (Bottleneck 1 in Figure 3). If ideal Wright-Fisher population assumptions hold for a given population, variances due to genetic drift and recombination will be the main factors for the decay of linkage disequilibrium. Linkage disequilibrium declined quickly to the background level at an average distance of 17 kb, but the extent of LD varied markedly within the genome and was more than 10-fold higher in ‘genomic islands’ of differentiation than in the rest of the genome. (A) Various increments of population size; (B) Ne estimates based on (A); (C) A decrement and various bottlenecks in population size; (D) Ne estimates based on (C). It therefore follows that the time per generation was shorter in Africa than on other continents. Yes

When the individual presented haplotypes such that its recombinants were distinguishable from the original haplotypes, whether the gamete would be a recombinant was determined by binomial draw based on the recombination rate. Relying on Eq. Including this one, all the previous methods assumed a constant effective population size. However, in the method in which the estimation of Ne is based on chromosome segment homozygosity, the assumption of linear Ne with time did not work well with exponential growth or complicated population size changes [27].

here. Analyzed the data: LP. However, when the value of r2 at equilibrium is very high (Ne = 100 and c = 0.0001), the time required to reach equilibrium may be expected to decrease. For simulations, the sampling of ns individuals among Nec individuals with replacement was conducted after the population sampling procedure described above.

The example can be found in decay_of_LD.py. Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China, BGI Genomics, BGI-Shenzhen, Shenzhen, China. CHB and CHD were prominent among samples with extreme exponential growth. It is also storage saving by avoiding exporting pair-wise results of LD measurements. SNPs with high minor allele frequencies would be a reasonable choice for aged SNPs. The center of the LD block was located within intron 2 of this gene.

In Eq. This article is also available for rental through DeepDyve. Second, one transmitting gamete was generated from each of the 2Nec individuals. Wrote the paper: LP. The random sampling from the generated gamete pool consisted of 2Nn gametes produced the formula described in the Introduction. 連鎖不平衡（れんさふへいこう、英: Linkage disequilibrium 、略称LD）とは生物の集団において、複数の遺伝子座の対立遺伝子または遺伝的マーカー（多型）の間にランダムでない相関が見られる、すなわちそれらの特定の組合せ（的な If the allele ages could be estimated accurately and the inaccuracies due to extreme frequencies and selection pressures were appropriately adjusted, a serial estimation of the effective population size from current to ancient generations might be possible. In India, colonial invasion began in the late 18th century; however the colonization of India was much more cautious and very different from that of Africa and America [46]. This result indicates that the earlier bottleneck might not be detectable in these Ne estimates and thus we need a detailed examination of Ne estimates in extremely small recombination rates.

Since the errors were relatively minor and influenced the data equally, the results of the current estimation might not differ greatly. (1), Eq. However, for Africans, the increment might have occurred over four to five generations, and this should be considered in the interpretations of relevant samples. However, for Ne estimates at very small recombination rates, the allele ages might not be sufficient.

In the estimation of Ne based on LD, the method was only applicable to small recombination rates due to approximation [26], [28]. When applied to human genome data, the detailed recent history of human populations was obtained. In reality, these simulation results did not show a distinguishable difference from simulation results with allele frequencies maintained between 0 and 1. Polygamy reduces the effective population size [43]; this may partly explain the results with LWK and MKKp, in which the culture persisted up to date. Thus, extreme exponential growth could be expected in the population samples originally from China. As the influence of recent population history on the Ne estimates is larger than old population history, recent changes in population size can be inferred more accurately than old changes. In European-American and African-American samples, the p-values of ∼0.10 and ∼0.83, respectively, associated with this region were not significant [50]. A total of 1198 samples were analyzed.

1, in which r2n−1 is the LD of the previous generation, and Nn−1 and Nn represent the effective sizes of the previous and current generations, respectively. To examine the effects of a greater reduction in population, the second bottleneck was repeated with an 80% reduction (Bottleneck 2b in Figure 3). The effective population size was estimated depending on the recombination rates. (A) Ne constant: for constant Ne = 100 and 1000, the r2 values at equilibrium decayed from the complete LD are plotted. To examine LD as the population size changed, the three situations that were most likely, i.e., increment, decrement, and bottleneck of population size, were selected. In that case, a more accurate picture of past population histories could be presented. Increasing the sample size reduced the mean squared error. The selection pressure on chromosome 14 found in this study was unexpected.

Changes in actual human population size showed a steep increment in Ne estimates depending on recombination rates. When the allele frequency is extreme for a given population size, only several limited r2 values are available, which deviates from the expectation of r2. The LD in the human genome has been used to determine the association between variants and traits [1] , and efforts to understand selection pressures have been based largely on the LD status of populations [2] – [5] , The theoretical basis of expectations for LD was established by the pioneering efforts of theoretical …

However, detailed simulation studies indicated that there was a more complicated relationship between the population LD, ro2, and the sampling variances than suggested by Eq. LINKAGE disequilibrium (LD), which refers to nonrandom association of alleles at different loci, has received increasing attention in recent years and has gained unprecedented momentum as a result of the availability of genome In recombining populations, genetic linkage decays with time.