Mobile element insertions (MEIs) represent ∼25% of all structural variants in human genomes. Moreover, when they disrupt genes, MEIs can influence human traits and diseases. Therefore, MEIs should be ...fully discovered along with other forms of genetic variation in whole genome sequencing (WGS) projects involving population genetics, human diseases, and clinical genomics. Here, we describe the Mobile Element Locator Tool (MELT), which was developed as part of the 1000 Genomes Project to perform MEI discovery on a population scale. Using both Illumina WGS data and simulations, we demonstrate that MELT outperforms existing MEI discovery tools in terms of speed, scalability, specificity, and sensitivity, while also detecting a broader spectrum of MEI-associated features. Several run modes were developed to perform MEI discovery on local and cloud systems. In addition to using MELT to discover MEIs in modern humans as part of the 1000 Genomes Project, we also used it to discover MEIs in chimpanzees and ancient (Neanderthal and Denisovan) hominids. We detected diverse patterns of MEI stratification across these populations that likely were caused by (1) diverse rates of MEI production from source elements, (2) diverse patterns of MEI inheritance, and (3) the introgression of ancient MEIs into modern human genomes. Overall, our study provides the most comprehensive map of MEIs to date spanning chimpanzees, ancient hominids, and modern humans and reveals new aspects of MEI biology in these lineages. We also demonstrate that MELT is a robust platform for MEI discovery and analysis in a variety of experimental settings.
We leverage innovative spatial modeling techniques and data on the
precise geo-locations of more than 32,000 Constituency Development
Fund (CDF) projects in Kenya to test whether Members of ...Parliament
(MPs) reward their supporters. We find only weak evidence that MPs
channel projects disproportionately to areas inhabited by their
political allies, once we control for other factors that affect
where projects are placed, such as population density, poverty
rates, ethnic demographics, and distance to paved roads.
Notwithstanding this result, we find evidence for cross-constituency
variation in political targeting, driven in large part by the
spatial segregation of the MP’s supporters and opponents. Our
findings challenge the conventional wisdom about the centrality of
clientelistic transfers in Africa and underscore how local
conditions generate particular incentives and opportunities for the
strategic allocation of political goods. We also highlight the
benefits and challenges of analyzing allocations at the project
level rather than aggregated to the administrative unit.
Opportunistic pathogens enriched in showerhead biofilms Feazel, Leah M; Baumgartner, Laura K; Peterson, Kristen L ...
Proceedings of the National Academy of Sciences - PNAS,
09/2009, Volume:
106, Issue:
38
Journal Article
Peer reviewed
Open access
The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology ...to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Studies of the human microbiome, and microbial community ecology in general, have blossomed of late and are now a burgeoning source of exciting research findings. Along with the advent of ...next-generation sequencing platforms, which have dramatically increased the scope of microbiome-related projects, several high-performance sequence analysis pipelines (e.g. QIIME, MOTHUR, VAMPS) are now available to investigators for microbiome analysis. The subject of our manuscript, the graphical user interface-based Explicet software package, fills a previously unmet need for a robust, yet intuitive means of integrating the outputs of the software pipelines with user-specified metadata and then visualizing the combined data.
Native Americans from the Amazon, Andes, and coastal geographic regions of South America have a rich cultural heritage but are genetically understudied, therefore leading to gaps in our knowledge of ...their genomic architecture and demographic history. In this study, we sequence 150 genomes to high coverage combined with an additional 130 genotype array samples from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date. Demographic modeling reveals that the peopling of Peru began ∼12,000 y ago, consistent with the hypothesis of the rapid peopling of the Americas and Peruvian archeological data. We find that the Native American populations possess distinct ancestral divisions, whereas the mestizo groups were admixtures of multiple Native American communities that occurred before and during the Inca Empire and Spanish rule. In addition, the mestizo communities also show Spanish introgression largely following Peruvian Independence, nearly 300 y after Spain conquered Peru. Further, we estimate migration events between Peruvian populations from all three geographic regions with the majority of between-region migration moving from the high Andes to the low-altitude Amazon and coast. As such, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern-day Peruvians and a Native American ancestry dataset that will serve as a beneficial resource to addressing the underrepresentation of Native American ancestry in sequencing studies.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
•The authors use a detailed spatial dataset of 32,000 development projects and data on the local distribution of poverty in Kenyan parliamentary constituencies to explore how Members of Parliament ...distribute resources. In particular, they examine whether or not MPs target projects to poorer constituents.•By and large, most MPs do not target the poor in their distribution of development projects.•When pro-poor targeting does occur, it usually occurs in rural settings where the poor and non-poor are spatially segregated from one another.
Decentralization is thought to facilitate poverty reduction by giving power over resource distribution to officials with local knowledge about where resources are most needed. However, decentralization also implies less oversight and greater opportunities for local officials to divert resources for political or personal ends. We investigate this tradeoff by exploring the degree to which Kenya’s premier decentralized development program—the Constituency Development Fund–targets the poor. Using a detailed spatial dataset of 32,000 CDF projects and data on the local distribution of poverty within Kenyan constituencies, we find that most MPs do not target the poor in their distribution of CDF projects. In places where they do, this tends to be in constituencies that are more rural, not too large, and, in keeping with the findings in Harris and Posner (2019), where the poor and non-poor are spatially segregated from one another. Our analyses suggest that the poor are underserved not just because politicians lack incentives to target them with development resources but because the poor are challenging to reach. In addition to these substantive findings, we also make a methodological contribution by underscoring how aggregation to the administrative unit may truncate important variation within geographic areas, and how a point-level analysis may avoid this pitfall.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
On average, Peruvian individuals are among the shortest in the world
. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian ...individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.
Full text
Available for:
FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT For decades a wide variety of observations spanning the radio through optical and on to the X-ray have attempted to uncover signs of type Ia supernovae (SNe Ia) interacting with a ...circumstellar medium (CSM). The goal of these studies is to constrain the nature of the hypothesized SN Ia mass-donor companion. A continuous CSM is typically assumed when interpreting observations of interaction. However, while such models have been successfully applied to core-collapse SNe, the assumption of continuity may not be accurate for SNe Ia, because shells of CSM could be formed by pre-supernova eruptions (novae). In this work, we model the interaction of SNe with a spherical, low-density, finite-extent CSM and create a suite of synthetic radio synchrotron light curves. We find that CSM shells produce sharply peaked light curves. We also identify a fiducial set of models that obey a common evolution and can be used to generate radio light curves for an interaction with an arbitrary shell. The relations obeyed by the fiducial models can be used to deduce CSM properties from radio observations; we demonstrate this by applying them to the nondetections of SN 2011fe and SN 2014J. Finally, we explore a multiple shell CSM configuration and describe its more complicated dynamics and the resultant radio light curves.
Airway infection and inflammation lead to the progression of obstructive lung disease in persons with cystic fibrosis (PWCF). However, cystic fibrosis (CF) fungal communities, known drivers of CF ...pathophysiology, remain poorly understood due to the shortcomings of traditional fungal culture. Our objective was to apply a novel small subunit rRNA gene (SSU-rRNA) sequencing approach to characterize the lower airway mycobiome in children with and without CF.
Bronchoalveolar lavage fluid (BALF) samples and relevant clinical data were collected from pediatric PWCF and disease control (DC) subjects. Total fungal load (TFL) was measured using quantitative PCR, and SSU-rRNA sequencing was used for mycobiome characterization. Results were compared across groups, and Morisita-Horn clustering was performed.
161 (84%) of the BALF samples collected had sufficient load for SSU-rRNA sequencing, with amplification being more common in PWCF. BALF from PWCF had increased TFL and increased neutrophilic inflammation compared to DC subjects. PWCF exhibited increased abundance of
and
, while
,
, and Pleosporales were prevalent in both groups. CF and DC samples showed no clear differences in clustering when compared to each other or to negative controls. SSU-rRNA sequencing was used to profile the mycobiome in pediatric PWCF and DC subjects. Notable differences were observed between the groups, including the abundance of
and
.
Fungal DNA detected in the airway could represent a combination of pathogenic fungi and environmental exposure (e.g., dust) to fungus indicative of a common background signature. Next steps will require comparisons to airway bacterial communities.
PDF
