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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (2015)
Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory--for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.
    Cover page: Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2019)
    Neanderthals and modern humans both occupied the Levant for tens of thousands of years prior to the spread of modern humans into the rest of Eurasia and their replacement of the Neanderthals. That the inter-species boundary remained geographically localized for so long is a puzzle, particularly in light of the rapidity of its subsequent movement. Here, we propose that infectious-disease dynamics can explain the localization and persistence of the inter-species boundary. We further propose, and support with dynamical-systems models, that introgression-based transmission of alleles related to the immune system would have gradually diminished this barrier to pervasive inter-species interaction, leading to the eventual release of the inter-species boundary from its geographic localization. Asymmetries between the species in the characteristics of their associated 'pathogen packages' could have generated feedback that allowed modern humans to overcome disease burden earlier than Neanderthals, giving them an advantage in their subsequent spread into Eurasia.
      Cover page: Disease transmission and introgression can explain the long-lasting contact zone of modern humans and Neanderthals
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2019)
      Neanderthals and modern humans both occupied the Levant for tens of thousands of years prior to the spread of modern humans into the rest of Eurasia and their replacement of the Neanderthals. That the inter-species boundary remained geographically localized for so long is a puzzle, particularly in light of the rapidity of its subsequent movement. Here, we propose that infectious-disease dynamics can explain the localization and persistence of the inter-species boundary. We further propose, and support with dynamical-systems models, that introgression-based transmission of alleles related to the immune system would have gradually diminished this barrier to pervasive inter-species interaction, leading to the eventual release of the inter-species boundary from its geographic localization. Asymmetries between the species in the characteristics of their associated pathogen packages could have generated feedback that allowed modern humans to overcome disease burden earlier than Neanderthals, giving them an advantage in their subsequent spread into Eurasia.
        Cover page: Disease transmission and introgression can explain the long-lasting contact zone of modern humans and Neanderthals.
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2016)
        [This corrects the article DOI: 10.1371/journal.pgen.1005527.].
          Cover page: Correction: Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele.
          • Article
          • Peer Reviewed
          Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, Volume 20, Issue 6 (2019)

          Introduction: Musculoskeletal injuries (MSI) comprise a large portion of the trauma burden in low- and middle-income countries (LMIC). Rwanda recently launched its first emergency medicine training program (EMTP) at the University Teaching Hospital-Kigali (UTH-K), which may help to treat such injuries; yet no current epidemiological data is available on MSI in Rwanda.

          Methods: We conducted this pre-post study during two data collection periods at the UTH-K from November 2012 to July 2016. Data collection for MSI is limited and thus is specific to fractures. We included all patients with open, closed, or mixed fractures, hereafter referred to as MSI. Gathered information included demographics and outcomes including death, traumatic complications, and length of hospital stay, before and after the implementation of the EMTP.

          Results: We collected data from 3609 patients. Of those records, 691 patients were treated for fractures, and 674 of them had sufficient EMTP data measured for inclusion in the analysis of results (279 from pre-EMTP and 375 from post-EMTP). Patient demographics demonstrate that a majority of MSI cases are male (71.6% male vs 28.4% female) and young (64.3% below 35 years of age). Among mechanisms of injury, major causes included road traffic accidents (48.1%), falls (34.2%), and assault (6.0%). There was also an observed association between EMTP and trends of the three primary outcomes: a reduction of death in the emergency department (ED) from those with MSI by 89.9%, from 2.51% to 0.25% (p = 0.0077); a reduction in traumatic complications for MSI patients by 71.7%, from 3.58% to 1.01% (p = 0.0211); and a reduction in duration of stay in the ED among those with MSI by 52.7% or 2.81 days on average, from 5.33 to 2.52 days (p = 0.0437).

          Conclusion: This study reveals the current epidemiology of MSI morbidity and mortality for a major Rwandan teaching hospital and the potential impacts of EM training implementation among those with MSI. Residency training programs such as EMTP appear capable of reducing mortality, complications, and ED length of stay among those with MSI caused by fractures. Such findings underscore the efficacy and importance of investments in educating the next generation of health professionals to combat prevalent MSI within their communities.

          • 1 supplemental file
          Cover page: Musculoskeletal Injuries and Outcomes Pre- and Post- Emergency Medicine Training ProgramCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2005)
          We resequenced 876 short fragments in a sample of 96 individuals of Arabidopsis thaliana that included stock center accessions as well as a hierarchical sample from natural populations. Although A. thaliana is a selfing weed, the pattern of polymorphism in general agrees with what is expected for a widely distributed, sexually reproducing species. Linkage disequilibrium decays rapidly, within 50 kb. Variation is shared worldwide, although population structure and isolation by distance are evident. The data fail to fit standard neutral models in several ways. There is a genome-wide excess of rare alleles, at least partially due to selection. There is too much variation between genomic regions in the level of polymorphism. The local level of polymorphism is negatively correlated with gene density and positively correlated with segmental duplications. Because the data do not fit theoretical null distributions, attempts to infer natural selection from polymorphism data will require genome-wide surveys of polymorphism in order to identify anomalous regions. Despite this, our data support the utility of A. thaliana as a model for evolutionary functional genomics.
            Cover page: The Pattern of Polymorphism in Arabidopsis thaliana
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