Complete and accurate burned area data are needed to document patterns of fires, to quantify relationships between the patterns and drivers of fire occurrence, and to assess the impacts of fires on ...human and natural systems. Unfortunately, in many areas existing fire occurrence datasets are known to be incomplete. Consequently, the need to systematically collect burned area information has been recognized by the United Nations Framework Convention on Climate Change and the Intergovernmental Panel on Climate Change, which have both called for the production of essential climate variables (ECVs), including information about burned area. In this paper, we present an algorithm that identifies burned areas in dense time-series of Landsat data to produce the Landsat Burned Area Essential Climate Variable (BAECV) products. The algorithm uses gradient boosted regression models to generate burn probability surfaces using band values and spectral indices from individual Landsat scenes, lagged reference conditions, and change metrics between the scene and reference predictors. Burn classifications are generated from the burn probability surfaces using pixel-level thresholding in combination with a region growing process. The algorithm can be applied anywhere Landsat and training data are available. For this study, BAECV products were generated for the conterminous United States from 1984 through 2015. These products consist of pixel-level burn probabilities for each Landsat scene, in addition to, annual composites including: the maximum burn probability and a burn classification. We compared the BAECV burn classification products to the existing Global Fire Emissions Database (GFED; 1997–2015) and Monitoring Trends in Burn Severity (MTBS; 1984–2013) data. We found that the BAECV products mapped 36% more burned area than the GFED and 116% more burned area than MTBS. Differences between the BAECV products and the GFED were especially high in the West and East where the BAECV products mapped 32% and 88% more burned area, respectively. However, the BAECV products found less burned area than the GFED in regions with frequent agricultural fires. Compared to the MTBS data, the BAECV products identified 31% more burned area in the West, 312% more in the Great Plains, and 233% more in the East. Most pixels in the MTBS data were detected by the BAECV, regardless of burn severity. The BAECV products document patterns of fire similar to those in the GFED but also showed patterns of fire that are not well characterized by the existing MTBS data. We anticipate the BAECV products will be useful to studies that seek to understand past patterns of fire occurrence, the drivers that created them, and the impacts fires have on natural and human systems.
•We developed an automated approach to map burned areas in Landsat data.•The algorithm was applied to Landsat data for the conterminous U.S.•The results showed patterns of burned area that are unique from existing fire data.•Fire histories can be constructed from Landsat data for a range of ecosystem types.
In western Cambodia, malaria parasites clear slowly from the blood after treatment with artemisinin derivatives, but it is unclear whether this results from parasite, host, or other factors specific ...to this population. We measured heritability of clearance rate by evaluating patients infected with identical or nonidentical parasite genotypes, using methods analogous to human twin studies. A substantial proportion (56%–58%) of the variation in clearance rate is explained by parasite genetics. This has 2 important implications: (1) selection with artemisinin derivatives will tend to drive resistance spread and (2) because heritability is high, the genes underlying parasite clearance rate may be identified by genome-wide association. Trial Registration. ClinicalTrials.gov identifier: NCT00493363; Current Controlled Trials identifier: ISRCTN15351875.
Sarcoidosis is characterized by noncaseating granulomas with an unknown cause that present primarily in the lung. Propionibacterium acnes, an immunogenic commensal skin bacterium involved in acne ...vulgaris, has been implicated as a possible causative agent of sarcoidosis. Here, we demonstrate that a viable strain of P. acnes isolated from a patient with sarcoidosis and instilled intratracheally into wild-type mice can generate pulmonary granulomas similar to those observed in patients with sarcoidosis. The formation of these granulomas is dependent on the administration of viable P. acnes. We also found that mice deficient in the innate immunity adapter protein MyD88 had a greater number and a larger area of granuloma lesions compared with wild-type mice administered P. acnes. Early after P. acnes administration, wild-type mice produced proinflammatory mediators and recruited neutrophils into the lung, a response that is dependent on MyD88. In addition, there was an increase in granuloma number and size after instillation with P. acnes in mice deficient in CybB, a critical component of nicotinamide adenine dinucleotide phosphate oxidase required for the production of reactive oxygen species in the phagosome. Myd88
or Cybb
mice both had increased persistence of P. acnes in the lung, together with enhanced granuloma formation. In conclusion, we have generated a mouse model of early granuloma formation induced by a clinically relevant strain of P. acnes isolated from a patient with sarcoidosis, and, using this model, we have shown that a deficiency in MyD88 or CybB is associated with impaired bacterial clearance and increased granuloma formation in the lung.
Populations of Plasmodium falciparum show striking differences in linkage disequilibrium, population differentiation and diversity, but only fragmentary data exists on the genetic structure of ...Plasmodium vivax. We genotyped nine tandem repeat loci bearing 2–8bp motifs from 345 P. vivax infections collected from three Asian countries and from five locations in Colombia. We observed 9–37 alleles per locus and high diversity (He=0.72–0.79, mean=0.75) in all countries. Numbers of multiple clone infections varied considerably: these were rare in Colombia and India, but > 60% of isolates carried multiple alleles in at least one locus in Thailand and Laos. However, only one or two of the nine loci show >1 allele in many samples, suggesting that mutation within infections may result in overestimation of true multiple carriage rates. Identical nine-locus genotypes were frequently found in Colombian populations, contributing to strong linkage disequilibrium. These identical genotypes were strongly clustered in time, consistent with epidemic transmission of clones and subsequent breakdown of allelic associations, suggesting high rates of inbreeding and low effective recombination rates in this country. In contrast, identical genotypes were rare and loci were randomly associated in all three Asian populations, consistent with higher rates of outcrossing and recombination. We observed low but significant differentiation between different Asian countries (standardized FST=0.13–0.45). In comparison, we see greater differentiation between collection locations within Colombia (standardized FST=0.4–0.7), and strong differentiation between continents (standardized FST=0.48–0.79). The observed heterogeneity in multiple clone carriage rates, linkage disequilibrium and population differentiation are similar in some, but not all, respects to those observed in P. falciparum, and have important implications for the design of association mapping studies, and interpretation of P. vivax epidemiology.
Malaria parasites (Plasmodium falciparum) provide an excellent system in which to study the genomic effects of strong selection in a recombining eukaryote because the rapid spread of resistance to ...multiple drugs during the last the past 50 years has been well documented, the full genome sequence and a microsatellite map are now available, and haplotype data can be easily generated. We examined microsatellite variation around the dihydrofolate reductase (dhfr) gene on chromosome 4 of P. falciparum. Point mutations in dhfr are known to be responsible for resistance to the antimalarial drug pyrimethamine, and resistance to this drug has spread rapidly in Southeast (SE) Asia after its introduction in 1970s. We genotyped 33 microsatellite markers distributed across chromosome 4 in 61 parasites from a location on the Thailand/Myanmar border. We observed minimal microsatellite length variation in a 12-kb (0.7-cM) region flanking the dhfr gene and diminished variation for approximately 100 kb (6 cM), indicative of a single origin of resistant alleles. Furthermore, we found the same or similar microsatellite haplotypes flanked resistant dhfr alleles sampled from 11 parasite populations in five SE Asian countries indicating recent invasion of a single lineage of resistant dhfr alleles in locations 2000 km apart. Three features of these data are of especially interest. (1). Pyrimethamine resistance is generally assumed to have evolved multiple times because the genetic basis is simple and resistance can be selected easily in the laboratory. Yet our data clearly indicate a single origin of resistant dhfr alleles sampled over a large region of SE Asia. (2). The wide valley ( approximately 6 cM) of reduced variation around dhfr provides "proof-of-principle" that genome-wide association may be an effective way to locate genes under strong recent selection. (3). The width of the selective valley is consistent with predictions based on independent measures of recombination, mutation, and selection intensity, suggesting that we have reasonable estimates of these parameters. We conclude that scanning the malaria parasite genome for evidence of recent selection may prove an extremely effective way to locate genes underlying recently evolved traits such as drug resistance, as well as providing an opportunity to study the dynamics of selective events that have occurred recently or are currently in progress.
Abstract Background Although case-control approaches are beginning to disentangle schizophrenia’s complex polygenic burden, other methods will likely be necessary to fully identify and characterize ...risk genes. Endophenotypes, traits genetically correlated with an illness, can help characterize the impact of risk genes by providing genetically relevant traits that are more tractable than the behavioral symptoms that classify mental illness. Here, we present an analytic approach for discovering and empirically validating endophenotypes in extended pedigrees with very few affected individuals. Our approach indexes each family member’s risk as a function of shared genetic kinship with an affected individual, often referred to as the coefficient of relatedness. To demonstrate the utility of this approach, we search for neurocognitive and neuroanatomic endophenotypes for schizophrenia in large unselected multigenerational pedigrees. Methods A fixed-effects test within the variance component framework was performed on neurocognitive and cortical surface area traits in 1606 Mexican-American individuals from large, randomly ascertained extended pedigrees who participated in the Genetics of Brain Structure and Function study. As affecteds were excluded from analyses, results were not influenced by disease state or medication usage. Results Despite having sampled just 6 individuals with schizophrenia, our sample provided 233 individuals at various levels of genetic risk for the disorder. We identified three neurocognitive measures (digit-symbol substitution, facial memory, and emotion recognition) and six medial temporal and prefrontal cortical surfaces associated with liability for schizophrenia. Conclusions With our novel analytic approach, one can discover and rank endophenotypes for schizophrenia, or any heritable disease, in randomly ascertained pedigrees.
Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The ...population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.
Highlights ► Scalp-EEG study of a large baboon pedigree containing epileptic animals. ► Prevalence of interictal discharges in baboons with seizures was 62%. ► Photosensitivity provides a specific ...marker for seizure risk.
Inferred relatedness and heritability in malaria parasites Anderson, Tim J. C.; Williams, Jeff T.; Nair, Shalini ...
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
08/2010, Letnik:
277, Številka:
1693
Journal Article
Recenzirano
Odprti dostop
Malaria parasites vary in phenotypic traits of biomedical or biological interest such as growth rate, virulence, sex ratio and drug resistance, and there is considerable interest in identifying the ...genes that underlie this variation. An important first step is to determine trait heritability (H2). We evaluate two approaches to measuring H2 in natural parasite populations using relatedness inferred from genetic marker data. We collected single-clone Plasmodium falciparum infections from 185 patients from the Thailand–Burma border, monitored parasite clearance following treatment with artemisinin combination therapy (ACT), measured resistance to six antimalarial drugs and genotyped parasites using 335 microsatellites. We found strong relatedness structure. There were 27 groups of two to eight clonally identical (CI) parasites, and 74 per cent of parasites showed significant relatedness to one or more other parasites. Initially, we used matrices of allele sharing and variance components (VC) methods to estimate H2. Inhibitory concentrations (IC50) for six drugs showed significant H2 (0.24 to 0.79, p = 0.06 to 2.85 × 10−9), demonstrating that this study design has adequate power. However, a phenotype of current interest—parasite clearance following ACT—showed no detectable heritability (H2 = 0–0.09, ns) in this population. The existence of CI parasites allows the use of a simple ANOVA approach for quantifying H2, analogous to that used in human twin studies. This gave similar results to the VC method and requires considerably less genotyping information. We conclude (i) that H2 can be effectively measured in malaria parasite populations using minimal genotype data, allowing rational design of genome-wide association studies; and (ii) while drug response (IC50) shows significant H2, parasite clearance following ACT was not heritable in the population studied.
Statistical genetic analysis of quantitative traits in large pedigrees is a formidable computational task due to the necessity of taking the nonindependence among relatives into account. With the ...growing awareness that rare sequence variants may be important in human quantitative variation, heritability and association study designs involving large pedigrees will increase in frequency due to the greater chance of observing multiple copies of rare variants among related individuals. Therefore, it is important to have statistical genetic test procedures that utilize all available information for extracting evidence regarding genetic association. Optimal testing for marker/phenotype association involves the exact calculation of the likelihood ratio statistic which requires the repeated inversion of potentially large matrices. In a whole genome sequence association context, such computation may be prohibitive. Toward this end, we have developed a rapid and efficient eigen simplification of the likelihood that makes analysis of family data commensurate with the analysis of a comparable sample of unrelated individuals. Our theoretical results which are based on a spectral representation of the likelihood yield simple exact expressions for the expected likelihood ratio test statistic (ELRT) for pedigrees of arbitrary size and complexity. For heritability, the ELRT is where h2 and λgi are, respectively, the heritability and eigenvalues of the pedigree-derived genetic relationship kernel (GRK). For association analysis of sequence variants, the ELRT is given by where ht2, hq2, and hr2 are the total, quantitative trait nucleotide, and residual heritabilities, respectively. Using these results, fast and accurate analytical power analyses are possible, eliminating the need for computer simulation. Additional benefits of eigen simplification include a simple method for calculation of the exact distribution of the ELRT under the null hypothesis which turns out to differ from that expected under the usual asymptotic theory. Further, when combined with the use of empirical GRKs-estimated over a large number of genetic markers-our theory reveals potential problems associated with nonpositive semidefinite kernels. These procedures are being added to our general statistical genetic computer package, SOLAR.
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