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Search Results: 1 - 10 of 32504 matches for " John Novembre "
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forqs: Forward-in-time Simulation of Recombination, Quantitative Traits, and Selection
Darren Kessner,John Novembre
Quantitative Biology , 2013,
Abstract: forqs is a forward-in-time simulation of recombination, quantitative traits, and selection. It was designed to investigate haplotype patterns resulting from scenarios where substantial evolutionary change has taken place in a small number of generations due to recombination and/or selection on polygenic quantitative traits. forqs is implemented as a command- line C++ program. Source code and binary executables for Linux, OSX, and Windows are freely available under a permissive BSD license.
The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele
John Novembre,Alison P. Galvani,Montgomery Slatkin
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0030339
Abstract: The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.
The geographic spread of the CCR5 Delta32 HIV-resistance allele.
Novembre John,Galvani Alison P,Slatkin Montgomery
PLOS Biology , 2005,
Abstract: The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10%) for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.
The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele
John Novembre ,Alison P Galvani,Montgomery Slatkin
PLOS Biology , 2005, DOI: 10.1371/journal.pbio.0030339
Abstract: The Δ32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Δ32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Δ32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Δ32 allele, we implemented a spatially explicit model of the spread of Δ32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Δ32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Δ32 allele is consistent with previous reports of a strong selective advantage (>10%) for Δ32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Δ32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Δ32 allele and establish a general methodology for studying the geographic distribution of selected alleles.
Maximum Likelihood Estimation of Frequencies of Known Haplotypes from Pooled Sequence Data
Darren Kessner,Tom Turner,John Novembre
Quantitative Biology , 2012, DOI: 10.1093/molbev/mst016
Abstract: DNA samples are often pooled, either by experimental design, or because the sample itself is a mixture. For example, when population allele frequencies are of primary interest, individual samples may be pooled together to lower the cost of sequencing. Alternatively, the sample itself may be a mixture of multiple species or strains (e.g. bacterial species comprising a microbiome, or pathogen strains in a blood sample). We present an expectation-maximization (EM) algorithm for estimating haplotype frequencies in a pooled sample directly from mapped sequence reads, in the case where the possible haplotypes are known. This method is relevant to the analysis of pooled sequencing data from selection experiments, as well as the calculation of proportions of different strains within a metagenomics sample. Our method outperforms existing methods based on single- site allele frequencies, as well as simple approaches using sequence read data. We have implemented the method in a freely available open-source software tool.
Conflation of short identity-by-descent segments bias their inferred length distribution
Charleston W. K. Chiang,Peter Ralph,John Novembre
Quantitative Biology , 2014,
Abstract: Identity-by-descent (IBD) is a fundamental concept in genetics with many applications. In a common definition, two haplotypes are said to contain an IBD segment if they share a segment that is inherited from a recent shared common ancestor without intervening recombination. Long IBD segments (> 1cM) can be efficiently detected by a number of algorithms using high-density SNP array data from a population sample. However, these approaches detect IBD based on contiguous segments of identity-by-state, and such segments may exist due to the conflation of smaller, nearby IBD segments. We quantified this effect using coalescent simulations, finding that nearly 40% of inferred segments 1-2cM long are results of conflations of two or more shorter segments, under demographic scenarios typical for modern humans. This biases the inferred IBD segment length distribution, and so can affect downstream inferences. We observed this conflation effect universally across different IBD detection programs and human demographic histories, and found inference of segments longer than 2cM to be much more reliable (less than 5% conflation rate). As an example of how this can negatively affect downstream analyses, we present and analyze a novel estimator of the de novo mutation rate using IBD segments, and demonstrate that the biased length distribution of the IBD segments due to conflation can lead to inflated estimates if the conflation is not modeled. Understanding the conflation effect in detail will make its correction in future methods more tractable.
The Role of Geography in Human Adaptation
Graham Coop equal contributor ,Joseph K. Pickrell equal contributor ,John Novembre,Sridhar Kudaravalli,Jun Li,Devin Absher,Richard M. Myers,Luigi Luca Cavalli-Sforza,Marcus W. Feldman,Jonathan K. Pritchard
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000500
Abstract: Various observations argue for a role of adaptation in recent human evolution, including results from genome-wide studies and analyses of selection signals at candidate genes. Here, we use genome-wide SNP data from the HapMap and CEPH-Human Genome Diversity Panel samples to study the geographic distributions of putatively selected alleles at a range of geographic scales. We find that the average allele frequency divergence is highly predictive of the most extreme FST values across the whole genome. On a broad scale, the geographic distribution of putatively selected alleles almost invariably conforms to population clusters identified using randomly chosen genetic markers. Given this structure, there are surprisingly few fixed or nearly fixed differences between human populations. Among the nearly fixed differences that do exist, nearly all are due to fixation events that occurred outside of Africa, and most appear in East Asia. These patterns suggest that selection is often weak enough that neutral processes—especially population history, migration, and drift—exert powerful influences over the fate and geographic distribution of selected alleles.
Vaccination against Heterologous R5 Clade C SHIV: Prevention of Infection and Correlates of Protection
Samir K. Lakhashe, Wendy Wang, Nagadenahalli B. Siddappa, Girish Hemashettar, Patricia Polacino, Shiu-Lok Hu, Fran?ois Villinger, James G. Else, Francis J. Novembre, John K. Yoon, Sandra J. Lee, David C. Montefiori, Ruth M. Ruprecht, Robert A. Rasmussen
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022010
Abstract: A safe, efficacious vaccine is required to stop the AIDS pandemic. Disappointing results from the STEP trial implied a need to include humoral anti-HIV-1 responses, a notion supported by RV144 trial data even though correlates of protection are unknown. We vaccinated rhesus macaques with recombinant simian immunodeficiency virus (SIV) Gag-Pol particles, HIV-1 Tat and trimeric clade C (HIV-C) gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a simian-human immunodeficiency virus (SHIV) that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all controls became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p<0.001) and cross-nAb titers (p<0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time.
Population-genetic comparison of the Sorbian isolate population in Germany with the German KORA population using genome-wide SNP arrays
Arnd Gross, Anke T?njes, Peter Kovacs, Krishna R Veeramah, Peter Ahnert, Nab R Roshyara, Christian Gieger, Ina-Maria Rueckert, Markus Loeffler, Mark Stoneking, Heinz-Erich Wichmann, John Novembre, Michael Stumvoll, Markus Scholz
BMC Genetics , 2011, DOI: 10.1186/1471-2156-12-67
Abstract: The degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies.Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses.Sorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable.Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses.The Sorbs living in the Upper Lusatia region of Eastern Saxony are one of the few historic ethnic minorities in Germany. They are of Slavonic origin speaking a west Slavic language (Sorbian), and it is assumed that they have lived in ethnic isolation among the German majority during the past 1100 years [1]. Therefore, this population may be of special interest for genetic studies of complex traits.The value of isolated populations f
Condicionamento fisiológico de sementes de berinjela
Fanan, Sheila;Novembre, Ana Dionisia da Luz Coelho;
Bragantia , 2007, DOI: 10.1590/S0006-87052007000400018
Abstract: the objective of this research was to study priming methods of eggplant seeds. three seed lots of the napoli cultivar were conditioned between paper towels )with 30, 60 and 90 ml of water at 15, 20 and 25 °c), and with peg solutions (-0.5, -1.0, -1.5, and -2.5 mpa at 20 °c); following that, seeds were dried at 30 °c until water contents similar to original ones. the unconditioned (check) and conditioned seeds were evaluated in relation to water content, germination and vigor (speed of germination, accelerated aging, controlled deterioration and electrical conductivity). the most effective treatments (20 °c, with water or -0.5 mpa peg) were again applied to other samples of same seeds which, together with the those of the check, were stored and evaluated through the same tests at 0, 60 and 120 days. results showed that there is the possibility of conditioning eggplant seeds at 20 °c, between paper towels, with water or with solution of -0.5 mpa peg 6000, followed by drying.
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