The detection of ancient gene flow between human populations is an important issue in population genetics. A common tool for detecting ancient admixture events is the D-statistic. The D-statistic is based on the hypothesis of a genetic relationship that involves four populations, whose correctness is assessed by evaluating specific coincidences of alleles between the groups. When working with high-throughput sequencing data, calling genotypes accurately is not always possible; therefore, the D-statistic currently samples a single base from the reads of one individual per population. This implies ignoring much of the information in the data, an issue especially striking in the case of ancient genomes. We provide a significant improvement to overcome the problems of the D-statistic by considering all reads from multiple individuals in each population. We also apply type-specific error correction to combat the problems of sequencing errors, and show a way to correct for introgression from an external population that is not part of the supposed genetic relationship, and how this leads to an estimate of the admixture rate. We prove that the D-statistic is approximated by a standard normal distribution. Furthermore, we show that our method outperforms the traditional D-statistic in detecting admixtures. The power gain is most pronounced for low and medium sequencing depth (1–10×), and performances are as good as with perfectly called genotypes at a sequencing depth of 2×. We show the reliability of error correction in scenarios with simulated errors and ancient data, and correct for introgression in known scenarios to estimate the admixture rates.
Klinefelter syndrome (KS; 47,XXY) is the most common sex chromosomal anomaly and causes a multitude of symptoms. Often the most noticeable symptom is infertility caused by azoospermia with testicular histology showing hyalinization of tubules, germ cells loss, and Leydig cell hyperplasia. The germ cell loss begins early in life leading to partial hyalinization of the testis at puberty, but the mechanistic drivers behind this remain poorly understood. In this systematic review, we summarize the current knowledge on developmental changes in the cellularity of KS gonads supplemented by a comparative analysis of the fetal and adult gonadal transcriptome, and blood transcriptome and methylome of men with KS. We identified a high fraction of upregulated genes that escape X‐chromosome inactivation, thus supporting previous hypotheses that these are the main drivers of the testicular phenotype in KS. Enrichment analysis showed overrepresentation of genes from the X‐ and Y‐chromosome and testicular transcription factors. Furthermore, by re‐evaluation of recent single cell RNA‐sequencing data originating from adult KS testis, we found novel evidence that the Sertoli cell is the most affected cell type. Our results are consistent with disturbed cross‐talk between somatic and germ cells in the KS testis, and with X‐escapee genes acting as mediators.
We provide a general mathematical framework based on the theory of graphical models to study admixture graphs. Admixture graphs are used to describe the ancestral relationships between past and present populations, allowing for population merges and migration events, by means of gene flow. We give various mathematical properties of admixture graphs with particular focus on properties of the so-called F -statistics. Also the Wright-Fisher model is studied and a general expression for the loss of heterozygosity is derived.
13The detection of ancient gene flow between human populations is an important issue in 14 population genetics. A common tool for detecting ancient admixture events is the the data, an issue especially striking in the case of ancient genomes.
22We provide a significant improvement to overcome the problems of the D-statistic by 23 considering all reads from multiple individuals in each population. We also apply 24 type-specific error correction to combat the problems of sequencing errors and show a 25 way to correct for introgression from an external population that is not part of the 26 supposed genetic relationship, and how this leads to an estimate of the admixture rate. 27
1/42. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/127852 doi: bioRxiv preprint first posted online Apr. 16, 2017; We prove that the D-statistic is approximated by a standard normal. Furthermore
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