Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro.

PURPOSE: Our aim was to compare the accuracy of family- or disease-specific targeted haplotyping and direct mutation-detection strategies with the accuracy of genome-wide mapping of the parental origin of each chromosome, or karyomapping, by single-nucleotide polymorphism genotyping of the parents, a close relative of known disease status, and the embryo cell(s) used for preimplantation genetic diagnosis of single-gene defects in a single cell or small numbers of cells biopsied from human embryos following in vitro fertilization. METHODS: Genomic DNA and whole-genome amplification products from embryo samples, which were previously diagnosed by targeted haplotyping, were genotyped for single-nucleotide polymorphisms genome-wide detection and retrospectively analyzed blind by karyomapping. RESULTS: Single-nucleotide polymorphism genotyping and karyomapping were successful in 213/218 (97.7%) samples from 44 preimplantation genetic diagnosis cycles for 25 single-gene defects with various modes of inheritance distributed widely across the genome. Karyomapping was concordant with targeted haplotyping in 208 (97.7%) samples, and the five nonconcordant samples were all in consanguineous regions with limited or inconsistent haplotyping results. CONCLUSION: Genome-wide karyomapping is highly accurate and facilitates analysis of the inheritance of almost any single-gene defect, or any combination of loci, at the single-cell level, greatly expanding the range of conditions for which preimplantation genetic diagnosis can be offered clinically without the need for customized test development.

Distribution patterns of segmental aneuploidies in human blastocysts identified by next-generation sequencing.

OBJECTIVE: To evaluate the ability of next-generation sequencing (NGS) to detect pure and mosaic segmental aneuploidies in trophectoderm biopsies and to identify distribution patterns in whole blastocysts. DESIGN: Validation study. SETTING: Reference laboratory. PATIENT(S): Seventy couples with known karyotypes who had undergone preimplantation genetic screening with diagnoses at the blastocyst stage using array comparative genomic hybridization (aCGH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Concordance rates for segmental and whole-chromosome aneuploidies determined between aCGH and NGS, and estimates of mosaicism levels of segmental aneuploidies in fixed blastocysts. RESULT(S): We used NGS with amplified DNA from trophectoderm biopsies in which segmental aneuploidies had been previously detected by array comparative genomic hybridization (aCGH). Single-cell fluorescent in situ hybridization (FISH) was then used as an independent form of analysis. The concordance rate between NGS and aCGH was 124 (98.4%) of 126 for the detection of segmental aneuploidies, and 48 (96.0%) of 50 for whole-chromosome aneuploidies. The overall concordance rate was 99.8% (2,276 of 2,280 chromosomes assessed). After FISH analyses with 41.4 ± 24.3 cells per blastocyst, 26 (92.9%) of 28 segmentals detected by aCGH and NGS were confirmed. The FISH analysis did not detect the segmentals in two blastocysts, in which all cells analyzed were euploid. CONCLUSION(S): This is the first report analyzing distribution patterns of segmental aneuploidies in trophectoderm biopsy by NGS. We have demonstrated that NGS allows the detection of pure and mosaic segmental aneuploidies with the same efficiency as aCGH. The FISH analysis confirmed the existence of these events in the trophectoderm and the inner cell mass.

Agent-specific impact of single trades in financial markets.

We present an analysis of the price impact associated with single trades effected by different financial firms. Using data from the Spanish Stock Market, we find a high degree of heterogeneity across different market members, both in the instantaneous impact functions and in the time-dependent market response to trades by individual members. This heterogeneity is statistically incompatible with the existence of market-wide universal impact dynamics that apply uniformly to all trades and suggest that, rather, market dynamics emerge from the complex interaction of different behaviors of market participants. Several possible reasons for this are discussed, along with potential extensions one may consider to increase the range of applicability of existing models of market impact.

Learning dynamics in public goods games.

We extend recent analyses of stochastic effects in game dynamical learning to cases of multiplayer games and to games defined on networked structures. By means of an expansion in the noise strength we consider the weak-noise limit and present an analytical computation of spectral properties of fluctuations in multiplayer public goods games. This extends existing work on two-player games. In particular we show that coherent cycles may emerge driven by noise in the adaptation dynamics. These phenomena are not too dissimilar from cyclic strategy switching observed in experiments of behavioral game theory.

Evolutionary dynamics, intrinsic noise, and cycles of cooperation.

We use analytical techniques based on an expansion in the inverse system size to study the stochastic evolutionary dynamics of finite populations of players interacting in a repeated prisoner's dilemma game. We show that a mechanism of amplification of demographic noise can give rise to coherent oscillations in parameter regimes where deterministic descriptions converge to fixed points with complex eigenvalues. These quasicycles between cooperation and defection have previously been observed in computer simulations; here we provide a systematic and comprehensive analytical characterization of their properties. We are able to predict their power spectra as a function of the mutation rate and other model parameters and to compare the relative magnitude of the cycles induced by different types of underlying microscopic dynamics. We also extend our analysis to the iterated prisoner's dilemma game with a win-stay lose-shift strategy, appropriate in situations where players are subject to errors of the trembling-hand type.