124 research outputs found
Detecting Polygenic Adaptation in Admixture Graphs
No full textAbstract
Polygenic adaptation occurs when natural selection changes the average value of a complex trait in a population, via small shifts in allele frequencies at many loci. Here, Racimo, Berg, and Pickrell present a method...
An open question in human evolution is the importance of polygenic adaptation: adaptive changes in the mean of a multifactorial trait due to shifts in allele frequencies across many loci. In recent years, several methods have been developed to detect polygenic adaptation using loci identified in genome-wide association studies (GWAS). Though powerful, these methods suffer from limited interpretability: they can detect which sets of populations have evidence for polygenic adaptation, but are unable to reveal where in the history of multiple populations these processes occurred. To address this, we created a method to detect polygenic adaptation in an admixture graph, which is a representation of the historical divergences and admixture events relating different populations through time. We developed a Markov chain Monte Carlo (MCMC) algorithm to infer branch-specific parameters reflecting the strength of selection in each branch of a graph. Additionally, we developed a set of summary statistics that are fast to compute and can indicate which branches are most likely to have experienced polygenic adaptation. We show via simulations that this method—which we call PolyGraph—has good power to detect polygenic adaptation, and applied it to human population genomic data from around the world. We also provide evidence that variants associated with several traits, including height, educational attainment, and self-reported unibrow, have been influenced by polygenic adaptation in different populations during human evolution.</jats:p
Ancient DNA reveals key stages in the formation of Central European mitochondrial genetic diversity
No full textThe processes that shaped modern European mitochondrial DNA (mtDNA) variation remain unclear. The initial peopling by Palaeolithic hunter-gatherers ~42,000 years ago and the immigration of Neolithic farmers into Europe ~8000 years ago appear to have played important roles but do not explain present-day mtDNA diversity. We generated mtDNA profiles of 364 individuals from prehistoric cultures in Central Europe to perform a chronological study, spanning the Early Neolithic to the Early Bronze Age (5500 to 1550 calibrated years before the common era). We used this transect through time to identify four marked shifts in genetic composition during the Neolithic period, revealing a key role for Late Neolithic cultures in shaping modern Central European genetic diversity.Guido Brandt, Wolfgang Haak, Christina J. Adler, Christina Roth, Anna Szécsényi-Nagy, Sarah Karimnia, Sabine Möller-Rieker, Harald Meller, Robert Ganslmeier, Susanne Friederich, Veit Dresely, Nicole Nicklisch, Joseph K. Pickrell, Frank Sirocko, David Reich, Alan Cooper, Kurt W. Alt, The Genographic Consortiu
False positive peaks in ChIP-seq and other sequencing-based functional assays caused by unannotated high copy number regions
No full textAbstract
Motivation: Sequencing-based assays such as ChIP-seq, DNase-seq and MNase-seq have become important tools for genome annotation. In these assays, short sequence reads enriched for loci of interest are mapped to a reference genome to determine their origin. Here, we consider whether false positive peak calls can be caused by particular type of error in the reference genome: multicopy sequences which have been incorrectly assembled and collapsed into a single copy.
Results: Using sequencing data from the 1000 Genomes Project, we systematically scanned the human genome for regions of high sequencing depth. These regions are highly enriched for erroneously inferred transcription factor binding sites, positions of nucleosomes and regions of open chromatin. We suggest a simple masking procedure to remove these regions and reduce false positive calls.
Availability: Files for masking out these regions are available at eqtl.uchicago.edu
Contact: [email protected]; [email protected]; [email protected]; [email protected]
Supplementary information: Supplementary data are available at Bioinformatics online.</jats:p
Joint Analysis of Functional Genomic Data and Genome-wide Association Studies of 18 Human Traits
No full textAnnotations of gene structures and regulatory elements can inform genome-wide association studies (GWASs). However, choosing the relevant annotations for interpreting an association study of a given trait remains challenging. I describe a statistical model that uses association statistics computed across the genome to identify classes of genomic elements that are enriched with or depleted of loci influencing a trait. The model naturally incorporates multiple types of annotations. I applied the model to GWASs of 18 human traits, including red blood cell traits, platelet traits, glucose levels, lipid levels, height, body mass index, and Crohn disease. For each trait, I used the model to evaluate the relevance of 450 different genomic annotations, including protein-coding genes, enhancers, and DNase-I hypersensitive sites in over 100 tissues and cell lines. The fraction of phenotype-associated SNPs influencing protein sequence ranged from around 2% (for platelet volume) up to around 20% (for low-density lipoprotein cholesterol), repressed chromatin was significantly depleted for SNPs associated with several traits, and cell-type-specific DNase-I hypersensitive sites were enriched with SNPs associated with several traits (for example, the spleen in platelet volume). Finally, reweighting each GWAS by using information from functional genomics increased the number of loci with high-confidence associations by around 5%
Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium
No full textAuthor Manuscript date February 9, 2013Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Institutes of Health (U.S.). (Training Grant 5T32HG004947-04)Simons Foundatio
The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation
No full textThere has long been interest in understanding the genetic basis of human adaptation. To what extent are phenotypic differences among human populations driven by natural selection? With the recent arrival of large genome-wide data sets on human variation, there is now unprecedented opportunity for progress on this type of question. Several lines of evidence argue for an important role of positive selection in shaping human variation and differences among populations. These include studies of comparative morphology and physiology, as well as population genetic studies of candidate loci and genome-wide data. However, the data also suggest that it is unusual for strong selection to drive new mutations rapidly to fixation in particular populations (the ‘hard sweep’ model). We argue, instead, for alternatives to the hard sweep model: in particular, polygenic adaptation could allow rapid adaptation while not producing classical signatures of selective sweeps. We close by discussing some of the likely opportunities for progress in the field
Inference of population splits and mixtures from genome-wide allele frequency data.
No full textMany aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com
Measurement Drift in 3-Hole Yaw Pressure Probes From 5 Micron Sand Fouling at 1050° C
No full text3-hole pressure probes are capable of accurately measuring flow angles in the yaw plane. These probes can be utilized inside a jet engine hot section for diagnostics and flow characterization. Sand and other particulate pose a significant risk to hot section components and measurement devices in gas turbine engines. The objective of this experiment was to develop a better understanding of the sensitivity of experimental 3-hole pressure probe designs to engine realistic sand fouling. In this study, Wedge, Cylindrical, and Trapezoidal probes were exposed to realistic hot section turbine environments of 1050 C at 65-70 m/s. 0-5 micron Arizona Road Dust(ARD) is heated under these conditions and used to foul the yaw probes. The sand deposited on the probe was observed to peel off the probe in thin sheets during ambient cool down.
Sand fouling was assessed using a stereoscope and digital camera. Probe calibrations were performed in an ambient temperature, open air, calibration jet to mimic engine cold start conditions at Mach numbers of 0.3 and 0.5. Yaw coefficients were calculated for each probe using probe pressure and jet dynamic pressure readings. These coefficients were used to develop calibration curves for each probe initially, and again for every fouling test. Each probe performed differently, but the trends showed that the sand fouling had little impact on the probe error at Mach 0.3, and a slightly increased effect on the probe error at Mach 0.5. The experiment showed that when flow direction was determined using a true dynamic pressure reading from the jet, the probes were able to accurately measure flow direction even after being significantly sanded, some probes holes being over 50% blocked by sand accumulation.
Accelerated erosion testing showed that the trapezoidal yaw probe was by far the most sensitive to sand accumulation, followed by the cylindrical probes, and the least sensitive was the wedge probe. A yaw angle range of interest was chosen to ±10 deg of yaw. The least errors from the Yaw Coefficient, as defined in this report, were found to be in the Trapezoidal and Perpendicular probe configurations. The least error found in the wedge probe.MS3-hole pressure probes are used to measure the speed and direction of air and other fluid flows. These probes can be used inside an active jet engine to measure aspects of the airflow inside the engine during flight. One risk to aircraft engines is sand being ingested into the engine. This can cause significant damage to the engine as well as the hardware inside the engine. The objective of this experiment will be to determine how sand accumulation affects the performance of these probes. The experiment involved sanding the probes in a hot jet, then placing them in front of a room temperature air jet to take measurements. A microscope was used to determine how much sand was on the holes of the probe. Sand was observed to peel off naturally, as the probe cooled from the hot jet. Sand was also noticed to break off during the room temperature jet.
The experiment showed that when the Jet pressures was measured from inside the jet, the probes were able to accurately measure flow direction even after being significantly sanded, <50% of the holes being blocked by sand. Of all the probes tested, the Wedge probe performed the best, though a close second was the Trapezoidal probe
Recommended from our members
Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data
No full textMany aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and “ancient” Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com.</p
Anchoring effects in the development of false childhood memories
No full textWhen people receive descriptions or doctored photos of events that never happened, they often come to remember those events. But if people receive both a description and a doctored photo, does the order in which they receive the information matter? We asked people to consider a description and a doctored photograph of a childhood hot air balloon ride, and we varied which medium they saw first. People who saw a description first reported more false images and memories than people who saw a photo first, a result that fits with an anchoring account of false childhood memories
- …
