Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Toward an integrative molecular approach to wildlife disease</title><author><name sortKey="Decandia, Alexandra L" sort="Decandia, Alexandra L" uniqKey="Decandia A" first="Alexandra L." last="Decandia">Alexandra L. Decandia</name><affiliation><nlm:aff id="cobi13083-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Dobson, Andrew P" sort="Dobson, Andrew P" uniqKey="Dobson A" first="Andrew P." last="Dobson">Andrew P. Dobson</name><affiliation><nlm:aff id="cobi13083-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Vonholdt, Bridgett M" sort="Vonholdt, Bridgett M" uniqKey="Vonholdt B" first="Bridgett M." last="Vonholdt">Bridgett M. Vonholdt</name><affiliation><nlm:aff id="cobi13083-aff-0001"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29380417</idno><idno type="pmc">7162296</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162296</idno><idno type="RBID">PMC:7162296</idno><idno type="doi">10.1111/cobi.13083</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000635</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000635</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Toward an integrative molecular approach to wildlife disease</title><author><name sortKey="Decandia, Alexandra L" sort="Decandia, Alexandra L" uniqKey="Decandia A" first="Alexandra L." last="Decandia">Alexandra L. Decandia</name><affiliation><nlm:aff id="cobi13083-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Dobson, Andrew P" sort="Dobson, Andrew P" uniqKey="Dobson A" first="Andrew P." last="Dobson">Andrew P. Dobson</name><affiliation><nlm:aff id="cobi13083-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Vonholdt, Bridgett M" sort="Vonholdt, Bridgett M" uniqKey="Vonholdt B" first="Bridgett M." last="Vonholdt">Bridgett M. Vonholdt</name><affiliation><nlm:aff id="cobi13083-aff-0001"></nlm:aff></affiliation></author></analytic><series><title level="j">Conservation Biology</title><idno type="ISSN">0888-8892</idno><idno type="eISSN">1523-1739</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host–parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (<italic>Sarcophilus harrisii</italic>) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Conserv Biol</journal-id><journal-id journal-id-type="iso-abbrev">Conserv. Biol</journal-id><journal-id journal-id-type="doi">10.1111/(ISSN)1523-1739</journal-id><journal-id journal-id-type="publisher-id">COBI</journal-id><journal-title-group><journal-title>Conservation Biology</journal-title></journal-title-group><issn pub-type="ppub">0888-8892</issn><issn pub-type="epub">1523-1739</issn><publisher><publisher-name>John Wiley and Sons Inc.</publisher-name><publisher-loc>Hoboken</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29380417</article-id><article-id pub-id-type="pmc">7162296</article-id><article-id pub-id-type="doi">10.1111/cobi.13083</article-id><article-id pub-id-type="publisher-id">COBI13083</article-id><article-categories><subj-group subj-group-type="overline"><subject>Essay</subject></subj-group><subj-group subj-group-type="heading"><subject>Essays</subject></subj-group></article-categories><title-group><article-title>Toward an integrative molecular approach to wildlife disease</article-title><alt-title alt-title-type="left-running-head">DeCandia et al.</alt-title><alt-title alt-title-type="right-running-head">Wildlife Disease</alt-title></title-group><contrib-group><contrib id="cobi13083-cr-0001" contrib-type="author" corresp="yes"><name><surname>DeCandia</surname><given-names>Alexandra L.</given-names></name><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-8485-5556</contrib-id><xref ref-type="aff" rid="cobi13083-aff-0001"><sup>1</sup></xref><address><email>decandia@princeton.edu</email></address></contrib><contrib id="cobi13083-cr-0002" contrib-type="author"><name><surname>Dobson</surname><given-names>Andrew P.</given-names></name><xref ref-type="aff" rid="cobi13083-aff-0001"><sup>1</sup></xref></contrib><contrib id="cobi13083-cr-0003" contrib-type="author"><name><surname>vonHoldt</surname><given-names>Bridgett M.</given-names></name><xref ref-type="aff" rid="cobi13083-aff-0001"><sup>1</sup></xref></contrib></contrib-group><aff id="cobi13083-aff-0001"><label><sup>1</sup></label><named-content content-type="organisation-division">Department of Ecology and Evolutionary Biology</named-content><institution>Princeton University</institution><named-content content-type="street">106A Guyot Hall</named-content><city>Princeton</city><named-content content-type="country-part">NJ 08544</named-content><country country="US">U.S.A.</country></aff><author-notes><corresp id="correspondenceTo"><label>*</label>email <email>decandia@princeton.edu</email></corresp></author-notes><pub-date pub-type="epub"><day>13</day><month>3</month><year>2018</year></pub-date><pub-date pub-type="ppub"><month>8</month><year>2018</year></pub-date><volume>32</volume><issue>4</issue><issue-id pub-id-type="doi">10.1111/cobi.2018.32.issue-4</issue-id><fpage>798</fpage><lpage>807</lpage><history><date date-type="received"><day>25</day><month>8</month><year>2017</year></date><date date-type="rev-recd"><day>12</day><month>12</month><year>2017</year></date><date date-type="accepted"><day>19</day><month>1</month><year>2018</year></date></history><permissions><pmc-comment> © 2018, Society for Conservation Biology </pmc-comment>
<copyright-statement content-type="article-copyright">© 2018 Society for Conservation Biology</copyright-statement><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="file:COBI-32-798.pdf"></self-uri><abstract><title>Abstract</title><p>Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host–parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (<italic>Sarcophilus harrisii</italic>) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern.</p></abstract><abstract abstract-type="short"><p><italic>Article impact statement</italic>: Applying genetic, epigenetic, and microbial analyses to wildlife disease can inform active management and improve conservation outcomes.</p></abstract><trans-abstract xml:lang="es" abstract-type="main"><sec id="cobi13083-sec-0010" xml:lang="es"><p xml:lang="es">Hacia una Estrategia Molecular Integrada para las Enfermedades de Fauna Silvestre</p><sec id="cobi13083-sec-0020" xml:lang="es"><title>Resumen</title><p xml:lang="es">Los patógenos presentan amenazas serias para la salud humana, la inversión agrícola, y la conservación de la biodiversidad debido al surgimiento de zoonosis, el paso de estos hacia el ganado doméstico, y los brotes epizoóticos. Por esto, los manejadores de fauna comúnmente tienen que mitigar los efectos negativos de las enfermedades. A pesar de esto, los parásitos forman un componente importante de la biodiversidad que generalmente persiste. Esto se debe a los obstáculos logísticos de la implementación de estrategias de manejo y al poco entendimiento de las dinámicas hospedero – parásito. Abogamos por un entendimiento incluyente de la diversidad molecular en la causa de las infecciones parasitarias y los estados variables de los hospederos en sistemas de fauna y examinamos los papeles de la variación microbiana genética, epigenética y comensal en la patogénesis de las enfermedades. Estos papeles incluyen mecanismos subyacentes de la virulencia parasitaria y la resistencia y tolerancia del hospedero, así como el desarrollo, regulación y subversión parasitaria de las vías inmunes, entre otros procesos. Estudios de caso de la enfermedad del tumor facial de los demonios de Tasmania (<italic>Sarcophilus harrisii</italic>) y la quitridiomicosis en anfibios con distribución mundial ejemplifican la amplia gama de preguntas que pueden abordarse examinando las diferentes facetas de la diversidad molecular. Para sistemas particularmente complejos, los análisis moleculares integrados presentan una frontera prometedora que puede proporcionar conocimiento crítico necesario para elucidar las dinámicas de las enfermedades que operan a lo largo de las escalas. Este conocimiento permite la evaluación más precisa del riesgo, la reconstrucción de las vías de transmisión, el discernimiento de las estrategias óptimas de intervención, y el desarrollo de tratamientos más efectivos y ecológicamente sensatos que minimicen el daño a la población hospedera y al ambiente. Dichas medidas son cruciales cuando se mitigan las amenazas que presentan las enfermedades de fauna silvestre para los humanos, los animales domésticos y las especies de importancia para la conservación.</p></sec></sec></trans-abstract><trans-abstract xml:lang="zh" abstract-type="main"><title>摘要</title><p xml:lang="zh">随着人畜共患病的发生、向家畜中蔓延和动物流行病的爆发, 病原体对人类健康、农业投资及生物多样性保护都造成了很大的威胁。因而, 野生动物管理者时常要负责减轻疾病带来的负面影响。但寄生生物却常常存在, 是生物多样性的一个重要组成部分。这将导致管理策略的实施面临挑战, 以及对寄主—寄生生物动力学认识的不足。我们提议要包容性地理解野生生物系统中驱动寄生生物感染和寄主疾病状态变异的分子多样性, 并研究遗传学、表观遗传学和共生微生物变异在疾病发病机制中的作用。这就要理解寄生生物毒性、寄主抗性和耐受性的机制, 以及在其它过程中免疫通路的发展、调控和受到寄生生物的破坏。我们以袋獾 (<italic>Sarcophilus harrisii)</italic> 的面部肿瘤病和全球两栖动物的壶菌病为例, 证明不同方面的分子多样性研究可以解决许多问题。对于特别复杂的系统而言, 整合分子生物学分析提供的研究前沿很有希望帮助我们更好地在不同尺度上理解疾病动力学。这些关键的认识让我们可以更准确地进行风险评估、重建传播途径、找出最优的干预策略, 并发展对寄主种群和环境影响最小、更加有效且环保的处理方法。这样的措施对于减轻野生动物疾病对人类、家养动物和需要保护的物种的威胁来说至关重要。<bold>翻译: 胡怡思; 审校: 魏辅文</bold></p></trans-abstract><kwd-group kwd-group-type="author-generated"><kwd id="cobi13083-kwd-0001">epigenetics</kwd><kwd id="cobi13083-kwd-0002">genetics</kwd><kwd id="cobi13083-kwd-0003">microbiome</kwd><kwd id="cobi13083-kwd-0004">transcriptomics</kwd><kwd id="cobi13083-kwd-0005">wildlife disease management</kwd><kwd id="cobi13083-kwd-0006">zoonoses</kwd><kwd id="cobi13083-kwd-0007">epigenética</kwd><kwd id="cobi13083-kwd-0008">genética</kwd><kwd id="cobi13083-kwd-0009">manejo de enfermedades de fauna silvestre</kwd><kwd id="cobi13083-kwd-0010">microbioma</kwd><kwd id="cobi13083-kwd-0011">transcriptómica</kwd><kwd id="cobi13083-kwd-0012">zoonosis</kwd><kwd id="cobi13083-kwd-0013">遗传学</kwd><kwd id="cobi13083-kwd-0014">表观遗传学</kwd><kwd id="cobi13083-kwd-0015">转录组学</kwd><kwd id="cobi13083-kwd-0016">微生物组</kwd><kwd id="cobi13083-kwd-0017">人畜共患病</kwd><kwd id="cobi13083-kwd-0018">野生动物疫病管理</kwd></kwd-group><funding-group><award-group id="funding-0001"><funding-source><institution-wrap><institution>National Science Foundation </institution><institution-id institution-id-type="open-funder-registry">10.13039/100000001</institution-id></institution-wrap></funding-source><award-id>Graduate Research Fellowship / DGE1656466</award-id></award-group></funding-group><counts><fig-count count="2"></fig-count><table-count count="1"></table-count><page-count count="10"></page-count><word-count count="6489"></word-count></counts><custom-meta-group><custom-meta><meta-name>source-schema-version-number</meta-name><meta-value>2.0</meta-value></custom-meta><custom-meta><meta-name>cover-date</meta-name><meta-value>August 2018</meta-value></custom-meta><custom-meta><meta-name>details-of-publishers-convertor</meta-name><meta-value>Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020</meta-value></custom-meta></custom-meta-group></article-meta><notes><fn-group><fn id="cobi13083-note-0001"><p><bold>Article impact statement</bold>: Applying genetic, epigenetic, and microbial analyses to wildlife disease can inform active management and improve conservation outcomes.</p></fn></fn-group></notes></front><body><sec id="cobi13083-sec-0030"><title>Introduction</title><p>Integrative molecular approaches have yielded novel insights into human disease at a variety of scales. Independent and concurrent analysis of genetic, epigenetic, and commensal microbial diversity has elucidated proximate and ultimate drivers of disease state and transformed understanding of pathogenesis, transmission, and treatment (Pacis et al. <xref rid="cobi13083-bib-0053" ref-type="ref">2014</xref>; Hand <xref rid="cobi13083-bib-0028" ref-type="ref">2016</xref>). Similar analyses have only recently appeared within the context of wildlife disease and conservation science. We argue that adoption of diverse molecular methods in wildlife disease will provide more thorough appreciation of mechanisms that underlie host disease state and ultimately translate into more effective population monitoring, management, and conservation.</p><p>Wildlife disease can pose significant threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks (Daszak et al. <xref rid="cobi13083-bib-0017" ref-type="ref">2000</xref>). Initially, theoretical models suggested that disease‐mediated declines would halt transmission before host extinction could occur (Anderson & May <xref rid="cobi13083-bib-0002" ref-type="ref">1979</xref>). Although this is true for many pathogens with density‐dependent transmission, these well‐defined thresholds are often nonexistent for host–parasite systems with more nuanced transmission structures (Getz & Pickering <xref rid="cobi13083-bib-0023" ref-type="ref">1983</xref>). Complications include free‐living parasite stages, endangered hosts sharing parasites with abundant reservoir populations, and systems with frequency‐dependent transmission (Lafferty & Gerber <xref rid="cobi13083-bib-0042" ref-type="ref">2002</xref>; Lafferty et al. <xref rid="cobi13083-bib-0041" ref-type="ref">2015</xref>). Consequently, managers are tasked with mitigating wildlife disease in systems of varying complexity. Yet, elimination of harmful parasites remains elusive due to logistical challenges of reaching adequate proportions of wildlife, limited monetary and veterinary resources, and insufficient understanding of the numerous drivers underlying host disease state.</p><p>Environmental, immunological, behavioral, demographic, physiological, and molecular mechanisms contribute to the expression of host disease phenotype (Fig. <xref rid="cobi13083-fig-0001" ref-type="fig">1</xref>). Although many of these factors have been reviewed elsewhere, comprehensive understanding of molecular diversity in the context of wildlife disease is lacking. In many studies, <italic>molecular diversity</italic> is considered synonymous with <italic>genetic diversity</italic>, but this fails to consider 2 additional components critical to proper immune functioning in hosts: epigenetic gene regulation and commensal microbial communities.</p><fig fig-type="Figure" xml:lang="en" id="cobi13083-fig-0001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Factors affecting host disease state. Though presented as discrete categories, factors and subfactors often co‐occur and interact to form a complex web of connections driving host disease state across scales. See examples in Supporting Information for more information on factors, subfactors, and interactions.</p></caption><graphic id="nlm-graphic-1" xlink:href="COBI-32-798-g001"></graphic></fig><p>We reviewed recent advances in understanding the molecular underpinnings of wildlife disease and examined how molecular methods can inform management of disease dynamics operating across scales. We considered numerous examples to highlight questions that can be addressed with each molecular data type (i.e., parasite genetics, host genetics, epigenetic gene regulation, and commensal microbial variation). Two pathogens serve as our primary examples: devil facial tumor disease (DFTD) in Tasmanian devils (<italic>Sarcophilus harrisii</italic>) and chytridiomycosis in globally distributed amphibians (Table <xref rid="cobi13083-tbl-0001" ref-type="table">1</xref>). These diseases lie at the frontier of applying an integrative molecular approach to wildlife disease, and demonstrate the numerous insights that can be gleaned from adopting these methods.</p><table-wrap id="cobi13083-tbl-0001" xml:lang="en" orientation="portrait" position="float"><label>Table 1</label><caption><p>Background information on devil facial tumor disease and chytridiomycosis</p></caption><table frame="hsides" rules="groups"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><thead><tr style="border-bottom:solid 1px #000000"><th align="left" rowspan="1" colspan="1">Disease characteristic</th><th align="center" rowspan="1" colspan="1">Devil facial tumor disease (DFTD)</th><th align="center" rowspan="1" colspan="1">Chytridiomycosis</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Host</td><td align="left" rowspan="1" colspan="1">Tasmanian devils (<italic>Sarcophilus harrisii</italic>)</td><td align="left" rowspan="1" colspan="1">Amphibians</td></tr><tr><td align="left" rowspan="1" colspan="1">Infectious agent</td><td align="left" rowspan="1" colspan="1">Transmissible cancer cells</td><td align="left" rowspan="1" colspan="1"><italic>Batrachochytrium dendrobatidis</italic> fungus</td></tr><tr><td align="left" rowspan="1" colspan="1">Distribution</td><td align="left" rowspan="1" colspan="1">Tasmania, Australia</td><td align="left" rowspan="1" colspan="1">Global</td></tr><tr><td align="left" rowspan="1" colspan="1">Transmission mode</td><td align="left" rowspan="1" colspan="1">Allograft cells from contact with infected devils (especially biting)</td><td align="left" rowspan="1" colspan="1">Contact with infected individuals or local environment</td></tr><tr><td align="left" rowspan="1" colspan="1">Pathology and conservation concern</td><td align="left" rowspan="1" colspan="1">DFTD is characterized by aggressive, ulcerated tumors on the face and mouth of infected devils. Infection and mortality rates are extremely high, with most deaths caused by starvation or metastases and organ failure occurring within 6 months of tumor development. Since first observation in 1996, DFTD has rapidly spread throughout the natural range of Tasmanian devils and remains the primary conservation concern threatening this iconic species. DFTD's status as a transmissible cancer renders it an ideal candidate for integrative molecular analyses, as these techniques can elucidate origin, transmission mode, and mechanisms of immune evasion.</td><td align="left" rowspan="1" colspan="1">Chytridiomycosis is an infectious skin disease implicated in driving amphibian declines on a global scale. Since formal description in 1997, chytridiomycosis has been documented in over 700 amphibian species with multiple fungal strains, interacting in a variety of environmental contexts. Perhaps unsurprisingly, it is characterized by high levels of variability in morbidity and mortality of hosts. Integrative molecular analyses of chytridiomycosis can address the molecular bases of host resistance and tolerance, fungal virulence, and environmental mediation of disease progression, and ultimately lead to novel management strategies.</td></tr><tr><td align="left" rowspan="1" colspan="1">Disease caused by a similar infectious agent</td><td align="left" rowspan="1" colspan="1">Canine transmissible venereal tumor in dogs</td><td align="left" rowspan="1" colspan="1"><italic>Pseudogymnoascus destructans</italic> causes white‐nose syndrome in bats</td></tr><tr><td align="left" rowspan="1" colspan="1">Sources</td><td align="left" rowspan="1" colspan="1">Bender et al. <xref rid="cobi13083-bib-0006" ref-type="ref">2014</xref>; Pye et al. <xref rid="cobi13083-bib-0056" ref-type="ref">2016</xref></td><td align="left" rowspan="1" colspan="1">Van Rooij et al. <xref rid="cobi13083-bib-0072" ref-type="ref">2015</xref>; Lips <xref rid="cobi13083-bib-0045" ref-type="ref">2016</xref></td></tr></tbody></table><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></table-wrap></sec><sec id="cobi13083-sec-0040"><title>Genetic Analyses of Wildlife Disease</title><p>Two central concepts have emerged in the history of genetic analyses and disease: parasite virulence and host resistance and tolerance are genetically based traits, and hosts and parasites are locked in a coevolutionary arms race, constantly evolving to obtain a mutational advantage over one another. Although this race is often asymmetrical due to the shorter generation time of pathogens, variation is the key driver of evolutionary change for both players. Thus, the application of molecular genetic techniques to the study of wildlife disease has typically focused on characterizing genetic diversity in parasites and their hosts and leveraging that information to discern selection on parasite transmission and host immunity. Technology has evolved from microsatellite markers through gene sequences to genomic data sets, but the core questions remain. It is the ability to address these questions that is considerably enhanced by large‐scale data sets and the increasing array of programs with which to analyze them.</p><sec id="cobi13083-sec-0050"><title>Parasite Genetics</title><p>The study of parasite genetics has moved from broad‐brush pathogen identification (McManus & Bowles <xref rid="cobi13083-bib-0046" ref-type="ref">1996</xref>) to more nuanced elucidation of complex transmission dynamics (Webster et al. <xref rid="cobi13083-bib-0073" ref-type="ref">2016</xref>). This is particularly important when managing endangered populations threatened by generalist parasites. Under these scenarios, multihost transmission can be the difference between population persistence and local extinction. For example, disease remains a primary threat to endangered Ethiopian wolves (<italic>Canis simensis</italic>) (Randall et al. <xref rid="cobi13083-bib-0058" ref-type="ref">2004</xref>; Gordon et al. <xref rid="cobi13083-bib-0025" ref-type="ref">2015</xref>). Though their population is too small to sustain pathogens such as canine distemper virus and rabies, the large population of dogs nearby is consistently identified as the source of disease outbreaks through viral sequencing. This renders both wolves and dogs critical targets for management.</p><p>Studies of parasite genetics can also be used to identify the subtle mechanisms underlying infection and <italic>virulence</italic> or damage to the host through parasite interactions (Schmid‐Hempel <xref rid="cobi13083-bib-0064" ref-type="ref">2011</xref>). These mechanisms can arise through mutation or horizontal gene transfer and facilitate processes such as toxin production, host cell invasion, and immune evasion that enable parasites to infect, propagate, transmit, and in some cases switch hosts (Hacker & Kaper <xref rid="cobi13083-bib-0027" ref-type="ref">2000</xref>; Geoghegan et al. <xref rid="cobi13083-bib-0022" ref-type="ref">2016</xref>). Avian influenza, for example, undergoes frequent mutation to sequentially infect the host respiratory tract and avoid sites of infection that limit transmission (Reperant et al. <xref rid="cobi13083-bib-0061" ref-type="ref">2012</xref>). For <italic>Mycoplasma gallisepticum</italic>, the bacterial pathogen that causes conjunctivitis in House Finches (<italic>Haemorhous mexicanus</italic>), quantitative genetic tools paired with disease phenotype data suggest rapid evolution of increased transmission potential and virulence upon emergence in a new host population (Hawley et al. <xref rid="cobi13083-bib-0030" ref-type="ref">2013</xref>).</p><p>By elucidating the specific molecular mechanisms underlying infection and virulence, one can pursue refined diagnostic tools, vaccination strategies, and therapeutic interventions (Johnston et al. <xref rid="cobi13083-bib-0035" ref-type="ref">1999</xref>). Genomic analyses comparing pathogenic <italic>Batrachochytrium</italic> spp., the causative agent of chytridiomycosis, with free‐living relatives, for example, reveal evolutionary adaptations for pathogenicity and infection strategies employed by different species (Farrer et al. <xref rid="cobi13083-bib-0020" ref-type="ref">2017</xref>). This represents a promising direction in chytridiomycosis research because parasite variability has been implicated in driving disease outcomes in hosts. Similar analyses of <italic>Plasmodium</italic> spp. suggest mechanisms of immune evasion in mosquito vectors (Molina‐Cruz et al. <xref rid="cobi13083-bib-0048" ref-type="ref">2015</xref>) and have identified loci associated with antimalarial drug resistance under positive selection (Shen et al. <xref rid="cobi13083-bib-0067" ref-type="ref">2017</xref>). Genetic tools have also located hotspots of polygenomic malaria infection, where hosts harbor multiple parasite strains simultaneously (Rice et al. <xref rid="cobi13083-bib-0062" ref-type="ref">2016</xref>). Considered together, this information enables better monitoring where malaria transmission and polygenomic infection rates are high and suggests possible molecular mechanisms for disease control.</p><p>To pursue these research and management goals, genetic analyses have been conducted on a wide range of parasite taxa (Supporting Information). Going forward, it is critical to focus on additional pathogens in multihost systems occurring in geographically diverse populations, particularly where spillover is likely. Further, it is important to perform comparative analyses in the contexts of host phenotype, genotype, and environment (Lazzaro & Little <xref rid="cobi13083-bib-0043" ref-type="ref">2009</xref>).</p></sec><sec id="cobi13083-sec-0060"><title>Host Genetics</title><p>Studies of host genetics tend to focus on resistance, tolerance, and diversity. <italic>Resistance</italic> can be defined as the ability to eliminate parasites from the host, whereas <italic>tolerance</italic> imposes limits on the parasite's negative effects (Best et al. <xref rid="cobi13083-bib-0008" ref-type="ref">2008</xref>, <xref rid="cobi13083-bib-0009" ref-type="ref">2009</xref>; Råberg et al. <xref rid="cobi13083-bib-0057" ref-type="ref">2009</xref>). Host fitness is intimately coupled with these traits and forms a significant component of their underlying mechanistic and molecular processes. In both cases, the prevailing paradigm is based on the assumption that genetic diversity at immune loci buffers hosts from disease risk. As such, demography resulting in genomic diversity loss (e.g., inbreeding) is often associated with increased likelihood of disease‐mediated population decline (Spielman et al. <xref rid="cobi13083-bib-0070" ref-type="ref">2004</xref>).</p><p>Early researchers examining host genetics in wildlife disease adopted a broad definition of <italic>genetic diversity</italic>. Employing neutral microsatellite markers, they calculated summary statistics to determine whether host genetics correlated with disease state. Although many reported significant relationships (Coltman et al. <xref rid="cobi13083-bib-0016" ref-type="ref">1999</xref>), others failed to identify strong associations between neutral diversity and disease (Schwensow et al. <xref rid="cobi13083-bib-0065" ref-type="ref">2007</xref>). This led many to question the efficacy of using neutral markers as a proxy for genome‐wide variation (Väli et al. <xref rid="cobi13083-bib-0071" ref-type="ref">2008</xref>) and ultimately shifted the field toward a more targeted immunogenetic approach.</p><p>In vertebrate systems, the major histocompatibility complex (MHC) dominated the literature. Critical to adaptive immunity, this hypervariable gene family encodes for MHC molecules that bind to antigens and display them on cell surfaces to initiate an immune response. This renders MHC variation a convenient target for candidate gene approaches. For example, analyses of Tasmanian devils threatened by DFTD suggest that low MHC diversity in hosts may provide means of immune evasion for this transmissible cancer (Siddle et al. <xref rid="cobi13083-bib-0068" ref-type="ref">2007</xref>). Similar analyses in amphibians show associations between MHC diversity and survival in frogs experimentally infected with the pathogenic fungus <italic>Batrachochytrium dendrobatidis</italic> (Bd) and host species known to be Bd resistant (Fu & Waldman <xref rid="cobi13083-bib-0021" ref-type="ref">2017</xref>).</p><p>The MHC‐based explorations of host disease state consider only one aspect of immunity, however. Many other genes (e.g., Toll‐like receptors) also aid host defense (Acevedo‐Whitehouse & Cunningham <xref rid="cobi13083-bib-0001" ref-type="ref">2006</xref>). Further, specific genes often associate with disease state more strongly than summary statistics of genetic variation (Bateson et al. <xref rid="cobi13083-bib-0004" ref-type="ref">2016</xref>); thus, treating MHC diversity as a proxy for larger scale immunogenetic variation may eventually prove too reductionist.</p><p>Genomic methods are increasingly used by conservation scientists to pursue more comprehensive analyses. Since publication of the first human genome, technological advances have rendered whole genome sequencing accessible for wildlife studies. Even when whole genomes are unavailable, restriction enzyme‐based methods rapidly and affordably generate genome‐wide data (Davey & Blaxter <xref rid="cobi13083-bib-0018" ref-type="ref">2010</xref>). For example, genomic analyses confirmed low levels of standing variation in Tasmanian devils, identified geographic structuring of host populations, enabled reconstruction of DFTD emergence and transmission pathways, and supported allograft transmission of this contagious cancer (Murchison et al. <xref rid="cobi13083-bib-0052" ref-type="ref">2012</xref>; Grueber et al. <xref rid="cobi13083-bib-0026" ref-type="ref">2015</xref>; Morris et al. <xref rid="cobi13083-bib-0050" ref-type="ref">2015</xref>; Hendricks et al. <xref rid="cobi13083-bib-0031" ref-type="ref">2017</xref>). Although in accordance with earlier MHC‐based studies, genomic analyses enabled deeper understanding of the roles host and cancer genomics play in DFTD pathogenesis. They additionally positioned genetic diversity maintenance as a top conservation priority for wild and captive devil management.</p><p>We hope that more systems will benefit from similarly comprehensive analyses. Although the trend toward genome‐level data comes with inherent difficulties, it provides critical insight into complex disease dynamics. By integrating the study of parasite and host genomics, wildlife managers can leverage better understanding of parasite virulence, transmission, and host disease state toward more effective prevention and management.</p></sec></sec><sec id="cobi13083-sec-0070"><title>Host Gene Regulation in Immunity</title><p>For the immune system to properly function, genes must produce their corresponding antigen binding, recognition, and signaling proteins. Gene regulatory variation therefore arises as another contributor to host disease state. If an underlying genotype for host immunity is transcriptionally silenced, infection becomes likely. For example, suppression of inflammatory response genes in bats may allow them to asymptomatically harbor viruses that are highly damaging to nonvolant mammals (Brook & Dobson <xref rid="cobi13083-bib-0011" ref-type="ref">2015</xref>; Banerjee et al. <xref rid="cobi13083-bib-0003" ref-type="ref">2017</xref>).</p><p>Epigenetic mechanisms (e.g., DNA methylation, histone modification, etc.) can alter the expression of immune genes in response to environmental stimuli, thereby inducing or preventing an immune response (Morandini et al. <xref rid="cobi13083-bib-0049" ref-type="ref">2016</xref>). Thus, effective immunity requires action from both genetic and epigenetic dimensions of the host genome: the genetic capacity to recognize and respond to a diverse array of parasites, the concerted expression of those genes, and the ability to overcome immune escape efforts.</p><p>The functional link between epigenetics and immunity is a burgeoning field. Although many studies focus on tumor growth, autoimmune disorders, and developmental changes, increasing attention is being paid to epigenetic mechanisms operating in infectious disease (Pacis et al. <xref rid="cobi13083-bib-0053" ref-type="ref">2014</xref>; Zhao et al. <xref rid="cobi13083-bib-0075" ref-type="ref">2015</xref>). From the perspective of resistant hosts, fine‐tuned regulation of immune genes and tissues targeted by pathogens may enable early detection and eradication of infecting parasites, as seen in some frogs experimentally infected with Bd (Ellison et al. <xref rid="cobi13083-bib-0019" ref-type="ref">2014</xref>). Where tolerance is preferred, suppression of these genes and their resultant processes (e.g., strong inflammatory responses) may ultimately lessen morbidity, as seen in bats infected with viruses (Banerjee et al. <xref rid="cobi13083-bib-0003" ref-type="ref">2017</xref>).</p><p>Yet, it often appears that epigenetic alterations worsen disease outcomes for hosts. In accordance with the coevolutionary arms race, many parasites manipulate host epigenomes to facilitate immune evasion and within‐host proliferation (Paschos & Allday <xref rid="cobi13083-bib-0054" ref-type="ref">2010</xref>). For example, <italic>Leishmania</italic> protozoans are hypothesized to alter DNA methylation patterns in macrophages to downregulate host defenses and promote parasite survival (McMaster et al. <xref rid="cobi13083-bib-0047" ref-type="ref">2016</xref>). Similarly, infection with influenza viruses and coronaviruses may induce histone modifications that alter immune signaling in favor of infecting parasites (Schäfer & Baric <xref rid="cobi13083-bib-0063" ref-type="ref">2017</xref>). Such phenomena remain active areas of research, as scientists seek to uncover the diverse mechanisms used by parasites to circumvent host immunity (Supporting Information).</p><p>Within wildlife systems, the field of ecological epigenetics has focused primarily on changes induced by behavior, diet, and environmental conditions. Only a few researchers have linked these changes to immune processes (Isaksson <xref rid="cobi13083-bib-0033" ref-type="ref">2015</xref>), and fewer still have examined differences in gene regulation between host populations. In 1 example, Ellison et al. (<xref rid="cobi13083-bib-0019" ref-type="ref">2014</xref>) compared transcriptome data from 4 sympatric frog species with different Bd susceptibility. When exposed to a pathogenic strain of Bd, resistant species exhibited downregulation of skin inflammatory pathways and upregulation of genes pertaining to skin‐barrier integrity and cell‐mediated immune responses. These patterns suggests that resistant hosts maintain skin and immune functioning during infection. This contrasts susceptible species, which often succumb to immunosuppression and disease‐mediated disruption of the skin barrier. Together, these results reveal important processes involved in chytridiomycosis morbidity and mortality across species.</p><p>Perhaps the strongest example of an integrative genomic, transcriptomic, and epigenetic approach to understanding disease pathogenesis occurs at the intersection of cancer and infectious disease with DFTD. Although genomic analyses revealed insights about host diversity and disease transmission, they have not elucidated specific mechanisms underlying emergence and immune evasion of this transmissible cancer. To address these questions, Murchison et al. (<xref rid="cobi13083-bib-0051" ref-type="ref">2010</xref>) considered functional variation alongside traditional genetic markers. Host and parasite genetics confirmed that tumors were genetically distinct from hosts and clonal in origin. Analyses of devil and tumor transcriptomes suggest that DFTD first arose in a mutated Schwann cell. Even though these cells function in local immunity, the Schwann cell origin of DFTD does not sufficiently explain the capacity of tumor cells to evade the immune system. More likely mechanisms appeared in analysis of expression profiles, which revealed upregulation in molecules associated with immune evasion and downregulation in molecules associated with tumor suppression. Considered alongside MHC‐based and genomic analyses (Grueber et al. <xref rid="cobi13083-bib-0026" ref-type="ref">2015</xref>; Morris et al. <xref rid="cobi13083-bib-0050" ref-type="ref">2015</xref>), it seems that low immunogenetic diversity in hosts decreases the immune system's probability of detecting tumors that fail to display MHC class I molecules on their cell surfaces (Siddle et al. <xref rid="cobi13083-bib-0068" ref-type="ref">2007</xref>, <xref rid="cobi13083-bib-0069" ref-type="ref">2013</xref>). This failure appears to result from epigenetic changes that induce downregulation of antigen‐processing genes in cancerous cells, which then allows tumor cells to slip under the immune system's radar. Critically, this may be reversible through epigenetic or immunological manipulation, which suggests a promising new direction for treatment (Siddle et al. <xref rid="cobi13083-bib-0069" ref-type="ref">2013</xref>).</p><p>In the case of DFTD, chytridiomycosis, and other wildlife diseases, analyses of gene regulation provide a powerful tool for identifying mechanisms underlying pathogenesis and pursuing novel targets for treatment (Kungulovski & Jeltsch <xref rid="cobi13083-bib-0040" ref-type="ref">2016</xref>). Yet, questions remain about the factors that operate alongside hosts and parasites to induce these changes. Recent evidence suggests that epigenetic mechanisms interact with commensal microbial communities inhabiting hosts, thus participating in regulatory cross‐talk between the immune system, epigenome, and microbiome (Levy et al. <xref rid="cobi13083-bib-0044" ref-type="ref">2015</xref>; Celluzzi & Masotti <xref rid="cobi13083-bib-0013" ref-type="ref">2016</xref>). The importance of this cross‐talk has yet to be elucidated, but mounting evidence suggests that a more complex understanding of immune regulation is needed.</p></sec><sec id="cobi13083-sec-0080"><title>Commensal Microbes and Dysbiosis</title><p>Studies of humans and model systems increasingly extol the importance of microbiomes in immunity. Commensal microbes have been implicated in developing the host immune system, shielding hosts from infection by competing with invaders, regulating immune responses through altered gene expression and immune signaling, and aiding resolution of responses once parasites are cleared (Supporting Information). Extreme examples are the fungal microbiomes of many plants that have self‐organized into symbiotic immune systems that possess all the classic features of vertebrate immune systems (e.g., self‐ and nonself recognition and short‐ and long‐term memory) (Berendsen et al. <xref rid="cobi13083-bib-0007" ref-type="ref">2012</xref>).</p><p>Unlike other aspects of host biology, microbial communities are both stable and flexible, rendering them particularly useful to immunity. Core microbiota, or resident commensals that consistently colonize certain body sites, are largely determined by host genetics (Goodrich et al. <xref rid="cobi13083-bib-0024" ref-type="ref">2014</xref>). Healthy community composition is often taxon specific and putatively results from long‐term coevolution (Colston & Jackson <xref rid="cobi13083-bib-0015" ref-type="ref">2016</xref>). Transient and temporary resident microbes primarily derive from environmental and behavioral sources (Candela et al. <xref rid="cobi13083-bib-0012" ref-type="ref">2012</xref>). These can rapidly change to reflect different external conditions or parasitic infections and may even function in larger scale adaptation of hosts (Shapira <xref rid="cobi13083-bib-0066" ref-type="ref">2016</xref>).</p><p>In the absence of infection, commensal microbial communities aid homeostasis and are critical to host defense (Honda & Littman <xref rid="cobi13083-bib-0032" ref-type="ref">2016</xref>). Yet, microbes do not present an impenetrable front. Termed <italic>dysbiosis</italic>, disruption of healthy microbial communities is often associated with autoimmunity and disease pathogenesis (Petersen & Round <xref rid="cobi13083-bib-0055" ref-type="ref">2014</xref>). As a result, microbial analyses of human diseases have skyrocketed in the last decade as researchers seek to elucidate mechanisms underlying pathology and design novel treatments (Knight <xref rid="cobi13083-bib-0036" ref-type="ref">2015</xref>).</p><p>The need for studies examining the role of microbial communities in wildlife disease is increasingly recognized (Redford et al. <xref rid="cobi13083-bib-0060" ref-type="ref">2012</xref>). Many primarily seek to characterize microbiome structure in healthy individuals. For example, Cheng et al. (<xref rid="cobi13083-bib-0014" ref-type="ref">2015</xref>) sequenced microbial communities from wild and captive Tasmanian devils and noted distinct differences between them. This establishes a baseline for comparison with communities disrupted by captivity and DFTD. In other systems, such as chytridiomycosis, research has moved away from descriptive studies toward manipulative experiments seeking novel treatment options. Many amphibian species naturally harbor skin bacteria known to secrete metabolites harmful to Bd. Commensal microbial communities have therefore been associated with differing disease outcomes in host populations (Jani et al. <xref rid="cobi13083-bib-0034" ref-type="ref">2017</xref>). In an effort to commandeer this phenomenon for disease management, treatment of <italic>Rana muscosa</italic> with Bd<italic>‐</italic>resistant bacteria drastically decreased mortality in experimental trials (Harris et al. <xref rid="cobi13083-bib-0029" ref-type="ref">2009</xref>). Similar results were reported for experimental manipulations of <italic>Anaxyrus boreas</italic> microbial communities, where the loss of Bd‐inhibitory bacteria increased infection rates and the application of resistant bacteria increased survival (Kueneman et al. <xref rid="cobi13083-bib-0038" ref-type="ref">2016</xref>). However, probiotic bioaugmentation may not be universally applicable as frog species harbor unique communities that differ in response to manipulation (Kueneman et al. <xref rid="cobi13083-bib-0037" ref-type="ref">2014</xref>; Küng et al. <xref rid="cobi13083-bib-0039" ref-type="ref">2014</xref>). In the case of probiotic‐resistant species, community composition may act as a sentinel for estimating susceptibility across populations (Becker et al. <xref rid="cobi13083-bib-0005" ref-type="ref">2015</xref>). By focusing on community structure and function, adoption of a multiomic approach may mitigate this difficulty through design of more effective taxon‐specific probiotic therapies (Rebollar et al. <xref rid="cobi13083-bib-0059" ref-type="ref">2016</xref>).</p></sec><sec id="cobi13083-sec-0090"><title>Applying an Integrative Molecular Approach to Conservation</title><p>When examined in isolation, genetic, epigenetic, and microbial variation can provide key information about wildlife disease ecology that informs conservation. Although implementing these methods in wildlife comes with the inherent challenges of limited sampling opportunity, lack of reference genomes for nonmodel organisms, and high start‐up costs of learning new laboratory and analytical techniques, it remains a worthwhile and versatile endeavor. Depending on the resources available, ability to collect samples, complexity of the host–parasite system, and questions most relevant to effective conservation, managers can pick and choose the methods that best address their needs (Fig. <xref rid="cobi13083-fig-0002" ref-type="fig">2</xref>). Further, decreased sequencing costs and increasingly user‐friendly analytical pipelines have rendered these methods accessible to studies of nonmodel organisms.</p><fig fig-type="Figure" xml:lang="en" id="cobi13083-fig-0002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Steps in the application of molecular methods to wildlife disease. In step 1, the question of interest must be identified. In step 2, the molecular method selected needs to address the chosen question. In step 3, samples need to fit the selected method and financial and logistical constraints of sampling the host–parasite system. In step 4, the molecular dataset must be appropriate for addressing the question with the collected samples. For complex systems characterized by multiple questions, relevant methods are combined to adopt an integrative molecular approach. See Supporting Information for case studies in which molecular techniques informed management of wildlife disease.</p></caption><graphic id="nlm-graphic-3" xlink:href="COBI-32-798-g002"></graphic></fig><p>When multiple questions arise and resources allow, applying an integrative molecular approach represents an exciting new frontier in wildlife disease ecology. Concurrent examination of interconnected factors within molecular diversity can elucidate patterns and processes relevant to complex wildlife disease systems. As evidenced in case studies of DFTD and chytriodiomycosis, analysis of genetic, gene regulatory, and microbial variation provides important insight into pathology, transmission dynamics, and novel avenues of treatment. For DFTD, genetic and transcriptomic analyses were needed to distinguish host from parasite, confirm allograft transmission and Schwann cell origin of the disease, and discover means of immune evasion through suppression of immune signaling amid minimal immunogenetic diversity in hosts. These insights have since informed management strategies, including ongoing treatment development and management of captive insurance populations (Pye et al. <xref rid="cobi13083-bib-0056" ref-type="ref">2016</xref>). In the case of chytriodiomycosis, genetic and transcriptomic analyses have furthered understanding of immune processes involved in species‐specific resistance to fungal infection, and microbial analyses have provided promising new treatment options through bioaugmentation with naturally Bd<italic>‐</italic>resistant microbes (Bletz et al. <xref rid="cobi13083-bib-0010" ref-type="ref">2013</xref>; Woodhams et al. <xref rid="cobi13083-bib-0074" ref-type="ref">2016</xref>).</p><p>Overall, application of molecular methods will enable more effective monitoring and management of at‐risk populations. Depending on questions and data types examined (Fig. <xref rid="cobi13083-fig-0002" ref-type="fig">2</xref>), understanding of wildlife disease prevalence, pathology, and persistence can be improved. Parasite genetics can refine diagnostic techniques, reconstruct transmission pathways, and identify genes underlying virulence. Similar analyses in hosts can characterize host population structure, patterns of immunogenetic diversity, and specific genes associated with resistance and tolerance strategies. Further examination of gene regulatory diversity can identify specific mechanisms underlying successful parasite invasion and host morbidity that may serve as targets for epigenetic intervention. Finally, commensal microbial analyses can elucidate patterns of dysbiosis associated with host disease state and suggest probiotic bioaugmentation as a novel treatment strategy. Especially when considered alongside other drivers of disease state (Fig. <xref rid="cobi13083-fig-0001" ref-type="fig">1</xref>), molecular analyses present innumerable opportunities to advance management of wildlife disease and mitigate threats posed to human and domestic animal health, agricultural systems, and wildlife populations. From examination of the human literature, it is evident that the technology for molecular analyses exists. The urgency of many conservation problems suggests that it is time these methods are applied to studies of wildlife disease.</p></sec><sec sec-type="supplementary-material"><title>Supporting information</title><supplementary-material content-type="local-data"><caption><p>Tables containing additional citations serving as examples of factors affecting host susceptibility (Appendix S1), genetic analyses of parasites (Appendix S2), epigenetic, microbial, and integrative molecular analyses in human and model systems (Appendix S3), and molecular analyses informing wildlife conservation (Appendix S4) are available online. The authors are solely responsible for the content and functionality of these materials. Queries (other than absence of the material) should be directed to the corresponding author.</p></caption><media xlink:href="COBI-32-798-s001.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data"><caption><p>Supplementary Material</p></caption><media xlink:href="COBI-32-798-s002.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data"><caption><p>Supplementary Material</p></caption><media xlink:href="COBI-32-798-s003.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material><supplementary-material content-type="local-data"><caption><p>Supplementary Material</p></caption><media xlink:href="COBI-32-798-s004.docx"><caption><p>Click here for additional data file.</p></caption></media></supplementary-material></sec></body><back><ack id="cobi13083-sec-0100"><title>Acknowledgments</title><p>This material is based on work supported by the National Science Foundation Graduate Research Fellowship under grant DGE1656466. We thank E. S. Almberg and D. R. Stahler for many insightful discussions.</p></ack><ref-list id="cobi13083-bibl-0001"><title>Literature Cited</title><ref id="cobi13083-bib-0001"><mixed-citation publication-type="journal" id="cobi13083-cit-0001"><string-name><surname>Acevedo‐Whitehouse</surname><given-names>K</given-names></string-name>, <string-name><surname>Cunningham</surname><given-names>AA</given-names></string-name>. <year>2006</year><article-title>Is MHC enough for understanding wildlife immunogenetics?</article-title><source xml:lang="en">Trends in Ecology & Evolution</source><volume>21</volume>:<fpage>433</fpage>–<lpage>438</lpage>.<pub-id pub-id-type="pmid">16764966</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0002"><mixed-citation publication-type="journal" id="cobi13083-cit-0002"><string-name><surname>Anderson</surname><given-names>RM</given-names></string-name>, <string-name><surname>May</surname><given-names>RM</given-names></string-name>. <year>1979</year><article-title>Population biology of infectious diseases: part I</article-title>. <source xml:lang="en">Nature</source><volume>280</volume>:<fpage>361</fpage>–<lpage>367</lpage>.<pub-id pub-id-type="pmid">460412</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0003"><mixed-citation publication-type="journal" id="cobi13083-cit-0003"><string-name><surname>Banerjee</surname><given-names>A</given-names></string-name>, <string-name><surname>Rapin</surname><given-names>N</given-names></string-name>, <string-name><surname>Bollinger</surname><given-names>T</given-names></string-name>, <string-name><surname>Misra</surname><given-names>V</given-names></string-name>. <year>2017</year><article-title>Lack of inflammatory gene expression in bats: a unique role for a transcription repressor</article-title>. <source xml:lang="en">Scientific Reports</source><volume>7</volume>:<fpage>2232</fpage>.<pub-id pub-id-type="pmid">28533548</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0004"><mixed-citation publication-type="journal" id="cobi13083-cit-0004"><string-name><surname>Bateson</surname><given-names>ZW</given-names></string-name>, <string-name><surname>Hammerly</surname><given-names>SC</given-names></string-name>, <string-name><surname>Johnson</surname><given-names>JA</given-names></string-name>, <string-name><surname>Morrow</surname><given-names>ME</given-names></string-name>, <string-name><surname>Whittingham</surname><given-names>LA</given-names></string-name>, <string-name><surname>Dunn</surname><given-names>PO</given-names></string-name>. <year>2016</year><article-title>Specific alleles at immune genes, rather than genome‐wide heterozygosity, are related to immunity and survival in the critically endangered Attwater's prairie‐chicken</article-title>. <source xml:lang="en">Molecular Ecology</source><volume>25</volume>:<fpage>4730</fpage>–<lpage>4744</lpage>.<pub-id pub-id-type="pmid">27485035</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0005"><mixed-citation publication-type="journal" id="cobi13083-cit-0005"><string-name><surname>Becker</surname><given-names>MH</given-names></string-name>, <string-name><surname>Walke</surname><given-names>JB</given-names></string-name>, <string-name><surname>Cikanek</surname><given-names>S</given-names></string-name>, <string-name><surname>Savage</surname><given-names>AE</given-names></string-name>, <string-name><surname>Mattheus</surname><given-names>N</given-names></string-name>, <string-name><surname>Santiago</surname><given-names>CN</given-names></string-name>, <string-name><surname>Minbiole</surname><given-names>KPC</given-names></string-name>, <string-name><surname>Harris</surname><given-names>RN</given-names></string-name>, <string-name><surname>Belden</surname><given-names>LK</given-names></string-name>, <string-name><surname>Gratwicke</surname><given-names>B</given-names></string-name>. <year>2015</year><article-title>Composition of symbiotic bacteria predicts survival in Panamanian golden frogs infected with a lethal fungus</article-title>. <source xml:lang="en">Proceedings of the Royal Society B</source><volume>282</volume>:<fpage>20142881</fpage>.<pub-id pub-id-type="pmid">25788591</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0006"><mixed-citation publication-type="journal" id="cobi13083-cit-0006"><string-name><surname>Bender</surname><given-names>HS</given-names></string-name>, <string-name><surname>Marshall Graves</surname><given-names>JA</given-names></string-name>, <string-name><surname>Deakin</surname><given-names>JE</given-names></string-name>. <year>2014</year><article-title>Pathogenesis and molecular biology of a transmissible tumor in the Tasmanian devil</article-title>. <source xml:lang="en">Annual Review of Animal Biosciences</source><volume>2</volume>:<fpage>165</fpage>–<lpage>187</lpage>.<pub-id pub-id-type="pmid">25384139</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0007"><mixed-citation publication-type="journal" id="cobi13083-cit-0007"><string-name><surname>Berendsen</surname><given-names>RL</given-names></string-name>, <string-name><surname>Pieterse</surname><given-names>CMJ</given-names></string-name>, <string-name><surname>Bakker</surname><given-names>PAHM</given-names></string-name>. <year>2012</year><article-title>The rhizosphere microbiome and plant health</article-title>. <source xml:lang="en">Trends in Plant Science</source><volume>17</volume>:<fpage>478</fpage>–<lpage>486</lpage>.<pub-id pub-id-type="pmid">22564542</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0008"><mixed-citation publication-type="journal" id="cobi13083-cit-0008"><string-name><surname>Best</surname><given-names>A</given-names></string-name>, <string-name><surname>White</surname><given-names>A</given-names></string-name>, <string-name><surname>Boots</surname><given-names>M</given-names></string-name>. <year>2008</year><article-title>Maintenance of host variation in tolerance to pathogens and parasites</article-title>. <source xml:lang="en">Proceedings of the National Academy of Sciences of the United States of America</source><volume>105</volume>:<fpage>20786</fpage>–<lpage>20791</lpage>.<pub-id pub-id-type="pmid">19088200</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0009"><mixed-citation publication-type="journal" id="cobi13083-cit-0009"><string-name><surname>Best</surname><given-names>A</given-names></string-name>, <string-name><surname>White</surname><given-names>A</given-names></string-name>, <string-name><surname>Boots</surname><given-names>M</given-names></string-name>. <year>2009</year><article-title>The implications of coevolutionary dynamics to host–parasite interactions</article-title>. <source xml:lang="en">The American Naturalist</source><volume>173</volume>:<fpage>779</fpage>–<lpage>791</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0010"><mixed-citation publication-type="journal" id="cobi13083-cit-0010"><string-name><surname>Bletz</surname><given-names>MC</given-names></string-name>, <string-name><surname>Loudon</surname><given-names>AH</given-names></string-name>, <string-name><surname>Becker</surname><given-names>MH</given-names></string-name>, <string-name><surname>Bell</surname><given-names>SC</given-names></string-name>, <string-name><surname>Woodhams</surname><given-names>DC</given-names></string-name>, <string-name><surname>Minbiole</surname><given-names>KPC</given-names></string-name>, <string-name><surname>Harris</surname><given-names>RN</given-names></string-name>. <year>2013</year><article-title>Mitigating amphibian chytridiomycosis with bioaugmentation: characteristics of effective probiotics and strategies for their selection and use</article-title>. <source xml:lang="en">Ecology Letters</source><volume>16</volume>:<fpage>807</fpage>–<lpage>820</lpage>.<pub-id pub-id-type="pmid">23452227</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0011"><mixed-citation publication-type="journal" id="cobi13083-cit-0011"><string-name><surname>Brook</surname><given-names>CE</given-names></string-name>, <string-name><surname>Dobson</surname><given-names>AP</given-names></string-name>. <year>2015</year><article-title>Bats as “special” reservoirs for emerging zoonotic pathogens</article-title>. <source xml:lang="en">Trends in Microbiology</source><volume>23</volume>:<fpage>172</fpage>–<lpage>180</lpage>.<pub-id pub-id-type="pmid">25572882</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0012"><mixed-citation publication-type="journal" id="cobi13083-cit-0012"><string-name><surname>Candela</surname><given-names>M</given-names></string-name>, <string-name><surname>Biagi</surname><given-names>E</given-names></string-name>, <string-name><surname>Maccaferri</surname><given-names>S</given-names></string-name>, <string-name><surname>Turroni</surname><given-names>S</given-names></string-name>, <string-name><surname>Brigidi</surname><given-names>P</given-names></string-name>. <year>2012</year><article-title>Intestinal microbiota is a plastic factor responding to environmental changes</article-title>. <source xml:lang="en">Trends in Microbiology</source><volume>20</volume>:<fpage>385</fpage>–<lpage>391</lpage>.<pub-id pub-id-type="pmid">22672911</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0013"><mixed-citation publication-type="journal" id="cobi13083-cit-0013"><string-name><surname>Celluzzi</surname><given-names>A</given-names></string-name>, <string-name><surname>Masotti</surname><given-names>A</given-names></string-name>. <year>2016</year><article-title>How our other genome controls our epi‐genome</article-title>. <source xml:lang="en">Trends in Microbiology</source><volume>24</volume>:<fpage>777</fpage>–<lpage>787</lpage>.<pub-id pub-id-type="pmid">27289569</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0014"><mixed-citation publication-type="journal" id="cobi13083-cit-0014"><string-name><surname>Cheng</surname><given-names>Y</given-names></string-name>, <string-name><surname>Fox</surname><given-names>S</given-names></string-name>, <string-name><surname>Pemberton</surname><given-names>D</given-names></string-name>, <string-name><surname>Hogg</surname><given-names>C</given-names></string-name>, <string-name><surname>Papenfuss</surname><given-names>AT</given-names></string-name>, <string-name><surname>Belov</surname><given-names>K</given-names></string-name>. <year>2015</year><article-title>The Tasmanian devil microbiome—implications for conservation and management</article-title>. <source xml:lang="en">Microbiome</source><volume>3</volume>:<fpage>76</fpage>.<pub-id pub-id-type="pmid">26689946</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0015"><mixed-citation publication-type="journal" id="cobi13083-cit-0015"><string-name><surname>Colston</surname><given-names>TJ</given-names></string-name>, <string-name><surname>Jackson</surname><given-names>CR</given-names></string-name>. <year>2016</year><article-title>Microbiome evolution along divergent branches of the vertebrate tree of life: what is known and unknown</article-title>. <source xml:lang="en">Molecular Ecology</source><volume>25</volume>:<fpage>3776</fpage>–<lpage>3800</lpage>.<pub-id pub-id-type="pmid">27297628</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0016"><mixed-citation publication-type="journal" id="cobi13083-cit-0016"><string-name><surname>Coltman</surname><given-names>DW</given-names></string-name>, <string-name><surname>Pilkington</surname><given-names>JG</given-names></string-name>, <string-name><surname>Smith</surname><given-names>JA</given-names></string-name>, <string-name><surname>Pemberton</surname><given-names>JM</given-names></string-name>. <year>1999</year><article-title>Parasite‐mediated selection against inbred Soay sheep in a free‐living, island population</article-title>. <source xml:lang="en">Evolution</source><volume>53</volume>:<fpage>1259</fpage>–<lpage>1267</lpage>.<pub-id pub-id-type="pmid">28565537</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0017"><mixed-citation publication-type="journal" id="cobi13083-cit-0017"><string-name><surname>Daszak</surname><given-names>P</given-names></string-name>, <string-name><surname>Cunningham</surname><given-names>AA</given-names></string-name>, <string-name><surname>Hyatt</surname><given-names>AD</given-names></string-name>. <year>2000</year><article-title>Emerging infectious diseases of wildlife—threats to biodiversity and human health</article-title>. <source xml:lang="en">Science</source><volume>287</volume>:<fpage>443</fpage>–<lpage>449</lpage>.<pub-id pub-id-type="pmid">10642539</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0018"><mixed-citation publication-type="journal" id="cobi13083-cit-0018"><string-name><surname>Davey</surname><given-names>JL</given-names></string-name>, <string-name><surname>Blaxter</surname><given-names>MW</given-names></string-name>. <year>2010</year><article-title>RADseq: next‐generation population genetics</article-title>. <source xml:lang="en">Briefings in Functional Genomics</source><volume>9</volume>:<fpage>416</fpage>–<lpage>423</lpage>.<pub-id pub-id-type="pmid">21266344</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0019"><mixed-citation publication-type="journal" id="cobi13083-cit-0019"><string-name><surname>Ellison</surname><given-names>AR</given-names></string-name>, <string-name><surname>Tunstall</surname><given-names>T</given-names></string-name>, <string-name><surname>DiRenzo</surname><given-names>GV</given-names></string-name>, <string-name><surname>Hughey</surname><given-names>MC</given-names></string-name>, <string-name><surname>Rebollar</surname><given-names>EA</given-names></string-name>, <string-name><surname>Belden</surname><given-names>LK</given-names></string-name>, <string-name><surname>Harris</surname><given-names>RN</given-names></string-name>, <string-name><surname>Ibáñez</surname><given-names>R</given-names></string-name>, <string-name><surname>Lips</surname><given-names>KR</given-names></string-name>, <string-name><surname>Zamudio</surname><given-names>KR</given-names></string-name>. <year>2014</year><article-title>More than skin deep: functional genomic basis for resistance to amphibian chytridiomycosis</article-title>. <source xml:lang="en">Genome Biology and Evolution</source><volume>7</volume>:<fpage>286</fpage>–<lpage>298</lpage>.<pub-id pub-id-type="pmid">25539724</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0020"><mixed-citation publication-type="journal" id="cobi13083-cit-0020"><string-name><surname>Farrer</surname><given-names>RA</given-names></string-name>, <string-name><surname>Martel</surname><given-names>A</given-names></string-name>, <string-name><surname>Verbrugghe</surname><given-names>E</given-names></string-name>, <string-name><surname>Abouelleil</surname><given-names>A</given-names></string-name>, <string-name><surname>Ducatelle</surname><given-names>R</given-names></string-name>, <string-name><surname>Longcore</surname><given-names>JE</given-names></string-name>, <string-name><surname>James</surname><given-names>TY</given-names></string-name>, <string-name><surname>Pasmans</surname><given-names>F</given-names></string-name>, <string-name><surname>Fisher</surname><given-names>MC</given-names></string-name>, <string-name><surname>Cuomo</surname><given-names>CA</given-names></string-name>. <year>2017</year><article-title>Genomic innovations linked to infection strategies across emerging pathogenic chytrid fungi</article-title>. <source xml:lang="en">Nature Communications</source><volume>8</volume>:<fpage>14742</fpage>.</mixed-citation></ref><ref id="cobi13083-bib-0021"><mixed-citation publication-type="journal" id="cobi13083-cit-0021"><string-name><surname>Fu</surname><given-names>M</given-names></string-name>, <string-name><surname>Waldman</surname><given-names>B</given-names></string-name>. <year>2017</year><article-title>Major histocompatibility complex variation and the evolution of resistance to amphibian chytridiomycosis</article-title>. <source xml:lang="en">Immunogenetics</source><volume>69</volume>:<fpage>529</fpage>–<lpage>536</lpage>.<pub-id pub-id-type="pmid">28695290</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0022"><mixed-citation publication-type="journal" id="cobi13083-cit-0022"><string-name><surname>Geoghegan</surname><given-names>JL</given-names></string-name>, <string-name><surname>Senior</surname><given-names>AM</given-names></string-name>, <string-name><surname>Holmes</surname><given-names>EC</given-names></string-name>. <year>2016</year><article-title>Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence</article-title>. <source xml:lang="en">Proceedings of the Royal Society B</source><volume>283</volume>:<fpage>20160727</fpage>.<pub-id pub-id-type="pmid">27581875</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0023"><mixed-citation publication-type="journal" id="cobi13083-cit-0023"><string-name><surname>Getz</surname><given-names>WM</given-names></string-name>, <string-name><surname>Pickering</surname><given-names>J</given-names></string-name>. <year>1983</year><article-title>Epidemic models: thresholds and population regulation</article-title>. <source xml:lang="en">The American Naturalist</source><volume>121</volume>:<fpage>892</fpage>–<lpage>898</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0024"><mixed-citation publication-type="journal" id="cobi13083-cit-0024"><string-name><surname>Goodrich</surname><given-names>JK</given-names></string-name>, et al. <year>2014</year><article-title>Human genetics shape the gut microbiome</article-title>. <source xml:lang="en">Cell</source><volume>159</volume>:<fpage>789</fpage>–<lpage>799</lpage>.<pub-id pub-id-type="pmid">25417156</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0025"><mixed-citation publication-type="journal" id="cobi13083-cit-0025"><string-name><surname>Gordon</surname><given-names>CH</given-names></string-name>, <string-name><surname>Banyard</surname><given-names>AC</given-names></string-name>, <string-name><surname>Hussein</surname><given-names>A</given-names></string-name>, <string-name><surname>Laurenson</surname><given-names>MK</given-names></string-name>, <string-name><surname>Malcolm</surname><given-names>JR</given-names></string-name>, <string-name><surname>Marino</surname><given-names>J</given-names></string-name>, <string-name><surname>Regassa</surname><given-names>F</given-names></string-name>, <string-name><surname>Stewart</surname><given-names>AME</given-names></string-name>, <string-name><surname>Fooks</surname><given-names>AR</given-names></string-name>, <string-name><surname>Sillero‐Zubiri</surname><given-names>C</given-names></string-name>. <year>2015</year><article-title>Canine distemper in endangered Ethiopian wolves</article-title>. <source xml:lang="en">Emerging Infectious Diseases</source><volume>21</volume>:<fpage>824</fpage>–<lpage>832</lpage>.<pub-id pub-id-type="pmid">25898177</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0026"><mixed-citation publication-type="journal" id="cobi13083-cit-0026"><string-name><surname>Grueber</surname><given-names>CE</given-names></string-name>, <string-name><surname>Peel</surname><given-names>E</given-names></string-name>, <string-name><surname>Gooley</surname><given-names>R</given-names></string-name>, <string-name><surname>Belov</surname><given-names>K</given-names></string-name>. <year>2015</year><article-title>Genomic insights into a contagious cancer in Tasmanian devils</article-title>. <source xml:lang="en">Trends in Genetics</source><volume>31</volume>:<fpage>528</fpage>–<lpage>535</lpage>.<pub-id pub-id-type="pmid">26027792</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0027"><mixed-citation publication-type="journal" id="cobi13083-cit-0027"><string-name><surname>Hacker</surname><given-names>J</given-names></string-name>, <string-name><surname>Kaper</surname><given-names>JB</given-names></string-name>. <year>2000</year><article-title>Pathogenicity islands and the evolution of microbes</article-title>. <source xml:lang="en">Annual Review Microbiology</source><volume>54</volume>:<fpage>641</fpage>–<lpage>679</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0028"><mixed-citation publication-type="journal" id="cobi13083-cit-0028"><string-name><surname>Hand</surname><given-names>TW</given-names></string-name>. <year>2016</year><article-title>The role of the microbiota in shaping infectious immunity</article-title>. <source xml:lang="en">Trends in Immunology</source><volume>37</volume>:<fpage>647</fpage>–<lpage>658</lpage>.<pub-id pub-id-type="pmid">27616558</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0029"><mixed-citation publication-type="journal" id="cobi13083-cit-0029"><string-name><surname>Harris</surname><given-names>RN</given-names></string-name>, et al. <year>2009</year><article-title>Skin microbes on frogs prevent morbidity and mortality caused by a lethal skin fungus</article-title>. <source xml:lang="en">The ISME Journal</source><volume>3</volume>:<fpage>818</fpage>–<lpage>824</lpage>.<pub-id pub-id-type="pmid">19322245</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0030"><mixed-citation publication-type="journal" id="cobi13083-cit-0030"><string-name><surname>Hawley</surname><given-names>DM</given-names></string-name>, <string-name><surname>Osnas</surname><given-names>EE</given-names></string-name>, <string-name><surname>Dobson</surname><given-names>AP</given-names></string-name>, <string-name><surname>Hochachka</surname><given-names>WM</given-names></string-name>, <string-name><surname>Ley</surname><given-names>DH</given-names></string-name>, <string-name><surname>Dhondt</surname><given-names>AA</given-names></string-name>. <year>2013</year><article-title>Parallel patterns of increased virulence in a recently emerged wildlife pathogen</article-title>. <source xml:lang="en">PLOS Biology</source> (<fpage>e1001570</fpage>) <pub-id pub-id-type="doi">10.1371/journal.pbio.1001570</pub-id>.<pub-id pub-id-type="pmid">23723736</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0031"><mixed-citation publication-type="journal" id="cobi13083-cit-0031"><string-name><surname>Hendricks</surname><given-names>S</given-names></string-name>, <string-name><surname>Epstein</surname><given-names>B</given-names></string-name>, <string-name><surname>Schönfeld</surname><given-names>B</given-names></string-name>, <string-name><surname>Wiench</surname><given-names>C</given-names></string-name>, <string-name><surname>Hamede</surname><given-names>R</given-names></string-name>, <string-name><surname>Jones</surname><given-names>M</given-names></string-name>, <string-name><surname>Storfer</surname><given-names>A</given-names></string-name>, <string-name><surname>Hohenlohe</surname><given-names>P</given-names></string-name>. <year>2017</year><article-title>Conservation implications of limited genetic diversity and population structure in Tasmanian devils (<italic>Sarcophilus harrisii</italic>)</article-title>. <source xml:lang="en">Conservation Genetics</source><volume>18</volume>:<fpage>977</fpage>–<lpage>982</lpage>.<pub-id pub-id-type="pmid">28966567</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0032"><mixed-citation publication-type="journal" id="cobi13083-cit-0032"><string-name><surname>Honda</surname><given-names>K</given-names></string-name>, <string-name><surname>Littman</surname><given-names>DR</given-names></string-name>. <year>2016</year><article-title>The microbiota in adaptive immune homeostasis and disease</article-title>. <source xml:lang="en">Nature</source><volume>535</volume>:<fpage>75</fpage>–<lpage>84</lpage>.<pub-id pub-id-type="pmid">27383982</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0033"><mixed-citation publication-type="journal" id="cobi13083-cit-0033"><string-name><surname>Isaksson</surname><given-names>C</given-names></string-name>. <year>2015</year><article-title>Urbanization, oxidative stress and inflammation: a question of evolving, acclimatizing or coping with urban environmental stress</article-title>. <source xml:lang="en">Functional Ecology</source><volume>29</volume>:<fpage>913</fpage>–<lpage>923</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0034"><mixed-citation publication-type="journal" id="cobi13083-cit-0034"><string-name><surname>Jani</surname><given-names>AJ</given-names></string-name>, <string-name><surname>Knapp</surname><given-names>RA</given-names></string-name>, <string-name><surname>Briggs</surname><given-names>CJ</given-names></string-name>. <year>2017</year><article-title>Epidemic and endemic pathogen dynamics correspond to distinct host population microbiomes at a landscape scale</article-title>. <source xml:lang="en">Proceedings of the Royal Society B</source><volume>284</volume>:<fpage>20170944</fpage>.<pub-id pub-id-type="pmid">28637861</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0035"><mixed-citation publication-type="journal" id="cobi13083-cit-0035"><string-name><surname>Johnston</surname><given-names>DA</given-names></string-name>, <string-name><surname>Blaxter</surname><given-names>ML</given-names></string-name>, <string-name><surname>Degrave</surname><given-names>WM</given-names></string-name>, <string-name><surname>Foster</surname><given-names>J</given-names></string-name>, <string-name><surname>Ivens</surname><given-names>AC</given-names></string-name>, <string-name><surname>Melville</surname><given-names>SE</given-names></string-name>. <year>1999</year><article-title>Genomics and the biology of parasites</article-title>. <source xml:lang="en">BioEssays</source><volume>21</volume>:<fpage>131</fpage>–<lpage>147</lpage>.<pub-id pub-id-type="pmid">10193187</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0036"><mixed-citation publication-type="journal" id="cobi13083-cit-0036"><string-name><surname>Knight</surname><given-names>R</given-names></string-name>. <year>2015</year><article-title>Why microbiome treatments could pay off soon</article-title>. <source xml:lang="en">Nature</source><volume>518</volume>:<fpage>S5</fpage>.<pub-id pub-id-type="pmid">25715279</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0037"><mixed-citation publication-type="journal" id="cobi13083-cit-0037"><string-name><surname>Kueneman</surname><given-names>JG</given-names></string-name>, <string-name><surname>Parfrey</surname><given-names>LW</given-names></string-name>, <string-name><surname>Woodhams</surname><given-names>DC</given-names></string-name>, <string-name><surname>Archer</surname><given-names>HM</given-names></string-name>, <string-name><surname>Knight</surname><given-names>R</given-names></string-name>, <string-name><surname>McKenzie</surname><given-names>VJ</given-names></string-name>. <year>2014</year><article-title>The amphibian skin‐associated microbiome across species, space and life history stages</article-title>. <source xml:lang="en">Molecular Ecology</source><volume>23</volume>:<fpage>1238</fpage>–<lpage>1250</lpage>.<pub-id pub-id-type="pmid">24171949</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0038"><mixed-citation publication-type="journal" id="cobi13083-cit-0038"><string-name><surname>Kueneman</surname><given-names>JG</given-names></string-name>, <string-name><surname>Woodhams</surname><given-names>DC</given-names></string-name>, <string-name><surname>Harris</surname><given-names>R</given-names></string-name>, <string-name><surname>Archer</surname><given-names>HM</given-names></string-name>, <string-name><surname>Knight</surname><given-names>R</given-names></string-name>, <string-name><surname>McKenzie</surname><given-names>VJ</given-names></string-name>. <year>2016</year><article-title>Probiotic treatment restores protection against lethal fungal infection lost during amphibian captivity</article-title>. <source xml:lang="en">Proceedings of the Royal Society B</source><volume>283</volume>:<fpage>20161553</fpage>.<pub-id pub-id-type="pmid">27655769</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0039"><mixed-citation publication-type="journal" id="cobi13083-cit-0039"><string-name><surname>Küng</surname><given-names>D</given-names></string-name>, <string-name><surname>Bigler</surname><given-names>L</given-names></string-name>, <string-name><surname>Davis</surname><given-names>LR</given-names></string-name>, <string-name><surname>Gratwicke</surname><given-names>B</given-names></string-name>, <string-name><surname>Griffith</surname><given-names>E</given-names></string-name>, <string-name><surname>Woodhams</surname><given-names>DC</given-names></string-name>. <year>2014</year><article-title>Stability of microbiota facilitated by host immune regulation: informing probiotic strategies to manage amphibian disease</article-title>. <source xml:lang="en">PLOS ONE</source> (<fpage>e87101</fpage>) <pub-id pub-id-type="doi">10.1371/journal.pone.0087101</pub-id>.<pub-id pub-id-type="pmid">24489847</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0040"><mixed-citation publication-type="journal" id="cobi13083-cit-0040"><string-name><surname>Kungulovski</surname><given-names>G</given-names></string-name>, <string-name><surname>Jeltsch</surname><given-names>A</given-names></string-name>. <year>2016</year><article-title>Epigenome editing: state of the art, concepts, and perspectives</article-title>. <source xml:lang="en">Trends in Genetics</source><volume>32</volume>:<fpage>101</fpage>–<lpage>113</lpage>.<pub-id pub-id-type="pmid">26732754</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0041"><mixed-citation publication-type="journal" id="cobi13083-cit-0041"><string-name><surname>Lafferty</surname><given-names>KD</given-names></string-name>, <string-name><surname>DeLeo</surname><given-names>G</given-names></string-name>, <string-name><surname>Briggs</surname><given-names>CJ</given-names></string-name>, <string-name><surname>Dobson</surname><given-names>AP</given-names></string-name>, <string-name><surname>Gross</surname><given-names>T</given-names></string-name>, <string-name><surname>Kuris</surname><given-names>AM</given-names></string-name>. <year>2015</year><article-title>A general consumer‐resource population model</article-title>. <source xml:lang="en">Science</source><volume>349</volume>:<fpage>854</fpage>–<lpage>857</lpage>.<pub-id pub-id-type="pmid">26293960</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0042"><mixed-citation publication-type="journal" id="cobi13083-cit-0042"><string-name><surname>Lafferty</surname><given-names>KD</given-names></string-name>, <string-name><surname>Gerber</surname><given-names>LR</given-names></string-name>. <year>2002</year><article-title>Good medicine for conservation biology: the intersection of epidemiology and conservation theory</article-title>. <source xml:lang="en">Conservation Biology</source><volume>16</volume>:<fpage>593</fpage>–<lpage>604</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0043"><mixed-citation publication-type="journal" id="cobi13083-cit-0043"><string-name><surname>Lazzaro</surname><given-names>BP</given-names></string-name>, <string-name><surname>Little</surname><given-names>TJ</given-names></string-name>. <year>2009</year><article-title>Immunity in a variable world</article-title>. <source xml:lang="en">Philosophical Transactions of the Royal Society B</source><volume>364</volume>:<fpage>15</fpage>–<lpage>26</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0044"><mixed-citation publication-type="journal" id="cobi13083-cit-0044"><string-name><surname>Levy</surname><given-names>M</given-names></string-name>, <string-name><surname>Thaiss</surname><given-names>CA</given-names></string-name>, <string-name><surname>Elinav</surname><given-names>E</given-names></string-name>. <year>2015</year><article-title>Metagenomic cross‐talk: the regulatory interplay between immunogenomics and the microbiome</article-title>. <source xml:lang="en">Genome Medicine</source><volume>7</volume>:<fpage>120</fpage>.<pub-id pub-id-type="pmid">26589591</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0045"><mixed-citation publication-type="journal" id="cobi13083-cit-0045"><string-name><surname>Lips</surname><given-names>KR</given-names></string-name>. <year>2016</year><article-title>Overview of chytrid emergence and impacts on amphibians</article-title>. <source xml:lang="en">Philosophical Transactions of the Royal Society B</source><volume>371</volume>:<fpage>20150465</fpage>.</mixed-citation></ref><ref id="cobi13083-bib-0046"><mixed-citation publication-type="journal" id="cobi13083-cit-0046"><string-name><surname>McManus</surname><given-names>DP</given-names></string-name>, <string-name><surname>Bowles</surname><given-names>J</given-names></string-name>. <year>1996</year><article-title>Molecular genetic approaches to parasite identification: their value in diagnostic parasitology and systematics</article-title>. <source xml:lang="en">International Journal for Parasitology</source><volume>26</volume>:<fpage>687</fpage>–<lpage>704</lpage>.<pub-id pub-id-type="pmid">8894760</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0047"><mixed-citation publication-type="journal" id="cobi13083-cit-0047"><string-name><surname>McMaster</surname><given-names>WR</given-names></string-name>, <string-name><surname>Morrison</surname><given-names>CJ</given-names></string-name>, <string-name><surname>Kobor</surname><given-names>MS</given-names></string-name>. <year>2016</year><article-title>Epigenetics: a new model for intracellular parasite–host cell regulation</article-title>. <source xml:lang="en">Trends in Parasitology</source><volume>32</volume>:<fpage>515</fpage>–<lpage>521</lpage>.<pub-id pub-id-type="pmid">27142564</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0048"><mixed-citation publication-type="journal" id="cobi13083-cit-0048"><string-name><surname>Molina‐Cruz</surname><given-names>A</given-names></string-name>, <string-name><surname>Canepa</surname><given-names>GE</given-names></string-name>, <string-name><surname>Kamath</surname><given-names>N</given-names></string-name>, <string-name><surname>Pavlovic</surname><given-names>NV</given-names></string-name>, <string-name><surname>Mu</surname><given-names>J</given-names></string-name>, <string-name><surname>Ramphul</surname><given-names>UN</given-names></string-name>, <string-name><surname>Ramirez</surname><given-names>JL</given-names></string-name>, <string-name><surname>Barillas‐Mury</surname><given-names>C</given-names></string-name>. <year>2015</year><article-title><italic>Plasmodium</italic> evasion of mosquito immunity and global malaria transmission: the lock‐and‐key theory</article-title>. <source xml:lang="en">Proceedings of the National Academy of Sciences of the United States of America</source><volume>112</volume>:<fpage>15178</fpage>–<lpage>15183</lpage>.<pub-id pub-id-type="pmid">26598665</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0049"><mixed-citation publication-type="journal" id="cobi13083-cit-0049"><string-name><surname>Morandini</surname><given-names>AC</given-names></string-name>, <string-name><surname>Santos</surname><given-names>CF</given-names></string-name>, <string-name><surname>Yilmaz</surname><given-names>Ö</given-names></string-name>. <year>2016</year><article-title>Role of epigenetics in modulation of immune response at the junction of host–pathogen interaction and danger molecule signaling</article-title>. <source xml:lang="en">Pathogens and Disease</source><volume>74</volume>:<fpage>ftw082</fpage>.<pub-id pub-id-type="pmid">27542389</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0050"><mixed-citation publication-type="journal" id="cobi13083-cit-0050"><string-name><surname>Morris</surname><given-names>K</given-names></string-name>, <string-name><surname>Wright</surname><given-names>B</given-names></string-name>, <string-name><surname>Grueber</surname><given-names>C</given-names></string-name>, <string-name><surname>Hogg</surname><given-names>C</given-names></string-name>, <string-name><surname>Belov</surname><given-names>K</given-names></string-name>. <year>2015</year><article-title>Lack of genetic diversity across diverse immune genes in an endangered mammal, the Tasmanian devil (<italic>Sarcophilus harrisii</italic>)</article-title>. <source xml:lang="en">Molecular Ecology</source><volume>24</volume>:<fpage>3860</fpage>–<lpage>3872</lpage>.<pub-id pub-id-type="pmid">26119928</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0051"><mixed-citation publication-type="journal" id="cobi13083-cit-0051"><string-name><surname>Murchison</surname><given-names>EP</given-names></string-name>, et al. <year>2010</year><article-title>The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer</article-title>. <source xml:lang="en">Science</source><volume>327</volume>:<fpage>84</fpage>–<lpage>87</lpage>.<pub-id pub-id-type="pmid">20044575</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0052"><mixed-citation publication-type="journal" id="cobi13083-cit-0052"><string-name><surname>Murchison</surname><given-names>EP</given-names></string-name>, et al. <year>2012</year><article-title>Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer</article-title>. <source xml:lang="en">Cell</source><volume>148</volume>:<fpage>780</fpage>–<lpage>791</lpage>.<pub-id pub-id-type="pmid">22341448</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0053"><mixed-citation publication-type="journal" id="cobi13083-cit-0053"><string-name><surname>Pacis</surname><given-names>A</given-names></string-name>, <string-name><surname>Nédélec</surname><given-names>Y</given-names></string-name>, <string-name><surname>Barreiro</surname><given-names>LB</given-names></string-name>. <year>2014</year><article-title>When genetics meets epigenetics: deciphering the mechanisms controlling inter‐individual variation in immune responses to infection</article-title>. <source xml:lang="en">Current Opinion in Immunology</source><volume>29</volume>:<fpage>119</fpage>–<lpage>126</lpage>.<pub-id pub-id-type="pmid">24981784</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0054"><mixed-citation publication-type="journal" id="cobi13083-cit-0054"><string-name><surname>Paschos</surname><given-names>K</given-names></string-name>, <string-name><surname>Allday</surname><given-names>MJ</given-names></string-name>. <year>2010</year><article-title>Epigenetic reprogramming of host genes in viral and microbial pathogenesis</article-title>. <source xml:lang="en">Trends in Microbiology</source><volume>18</volume>:<fpage>439</fpage>–<lpage>447</lpage>.<pub-id pub-id-type="pmid">20724161</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0055"><mixed-citation publication-type="journal" id="cobi13083-cit-0055"><string-name><surname>Petersen</surname><given-names>C</given-names></string-name>, <string-name><surname>Round</surname><given-names>JL</given-names></string-name>. <year>2014</year><article-title>Defining dysbiosis and its influence on host immunity and disease</article-title>. <source xml:lang="en">Cellular Microbiology</source><volume>16</volume>:<fpage>1024</fpage>–<lpage>1033</lpage>.<pub-id pub-id-type="pmid">24798552</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0056"><mixed-citation publication-type="journal" id="cobi13083-cit-0056"><string-name><surname>Pye</surname><given-names>RJ</given-names></string-name>, <string-name><surname>Woods</surname><given-names>GM</given-names></string-name>, <string-name><surname>Kreiss</surname><given-names>A</given-names></string-name>. <year>2016</year><article-title>Devil facial tumor disease</article-title>. <source xml:lang="en">Veterinary Pathology</source><volume>53</volume>:<fpage>726</fpage>–<lpage>736</lpage>.<pub-id pub-id-type="pmid">26657222</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0057"><mixed-citation publication-type="journal" id="cobi13083-cit-0057"><string-name><surname>Råberg</surname><given-names>L</given-names></string-name>, <string-name><surname>Graham</surname><given-names>AL</given-names></string-name>, <string-name><surname>Read</surname><given-names>AF</given-names></string-name>. <year>2009</year><article-title>Decomposing health: tolerance and resistance to parasites in animals</article-title>. <source xml:lang="en">Philosophical Transactions of the Royal Society B</source><volume>364</volume>:<fpage>37</fpage>–<lpage>49</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0058"><mixed-citation publication-type="journal" id="cobi13083-cit-0058"><string-name><surname>Randall</surname><given-names>DA</given-names></string-name>, et al. <year>2004</year><article-title>Rabies in Ethiopian wolves</article-title>. <source xml:lang="en">Emerging Infectious Diseases</source><volume>10</volume>:<fpage>10</fpage>–<lpage>13</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0059"><mixed-citation publication-type="journal" id="cobi13083-cit-0059"><string-name><surname>Rebollar</surname><given-names>EA</given-names></string-name>, et al. <year>2016</year><article-title>Using “omics” and integrated multi‐omics approaches to guide probiotic selection to mitigate chytridiomycosis and other emerging infectious diseases</article-title>. <source xml:lang="en">Frontiers in Microbiology</source><volume>7</volume>:<fpage>68</fpage>.<pub-id pub-id-type="pmid">26870025</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0060"><mixed-citation publication-type="journal" id="cobi13083-cit-0060"><string-name><surname>Redford</surname><given-names>KH</given-names></string-name>, <string-name><surname>Segre</surname><given-names>JA</given-names></string-name>, <string-name><surname>Salafsky</surname><given-names>N</given-names></string-name>, <string-name><surname>Martinez del Rio</surname><given-names>C</given-names></string-name>, <string-name><surname>McAloose</surname><given-names>D</given-names></string-name>. <year>2012</year><article-title>Conservation and the microbiome</article-title>. <source xml:lang="en">Conservation Biology</source><volume>26</volume>:<fpage>195</fpage>–<lpage>197</lpage>.<pub-id pub-id-type="pmid">22443125</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0061"><mixed-citation publication-type="journal" id="cobi13083-cit-0061"><string-name><surname>Reperant</surname><given-names>LA</given-names></string-name>, <string-name><surname>Kuiken</surname><given-names>T</given-names></string-name>, <string-name><surname>Grenfell</surname><given-names>BT</given-names></string-name>, <string-name><surname>Osterhaus</surname><given-names>ADME</given-names></string-name>, <string-name><surname>Dobson</surname><given-names>AP</given-names></string-name>. <year>2012</year><article-title>Linking influenza virus tissue tropism to population‐level reproductive fitness</article-title>. <source xml:lang="en">PLOS ONE</source> (<fpage>e43115</fpage>) <pub-id pub-id-type="doi">10.1371/journal.pone.0043115</pub-id>.<pub-id pub-id-type="pmid">22952637</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0062"><mixed-citation publication-type="journal" id="cobi13083-cit-0062"><string-name><surname>Rice</surname><given-names>BL</given-names></string-name>, <string-name><surname>Golden</surname><given-names>CD</given-names></string-name>, <string-name><surname>Anjaranirina</surname><given-names>EJG</given-names></string-name>, <string-name><surname>Botelho</surname><given-names>CM</given-names></string-name>, <string-name><surname>Volkman</surname><given-names>SK</given-names></string-name>, <string-name><surname>Hartl</surname><given-names>DL</given-names></string-name>. <year>2016</year><article-title>Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission</article-title>. <source xml:lang="en">Malaria Journal</source><volume>15</volume>:<fpage>596</fpage>.<pub-id pub-id-type="pmid">27998292</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0063"><mixed-citation publication-type="journal" id="cobi13083-cit-0063"><string-name><surname>Schäfer</surname><given-names>A</given-names></string-name>, <string-name><surname>Baric</surname><given-names>R</given-names></string-name>. <year>2017</year><article-title>Epigenetic landscape during coronavirus infection</article-title>. <source xml:lang="en">Pathogens</source><volume>6</volume>:<fpage>8</fpage>.</mixed-citation></ref><ref id="cobi13083-bib-0064"><mixed-citation publication-type="book" id="cobi13083-cit-0064"><string-name><surname>Schmid‐Hempel</surname><given-names>P</given-names></string-name>. <year>2011</year><source xml:lang="en">Evolutionary parasitology: the integrated study of infections, immunology, ecology, and genetics</source>. <publisher-name>Oxford University Press</publisher-name>, <publisher-loc>New York</publisher-loc>.</mixed-citation></ref><ref id="cobi13083-bib-0065"><mixed-citation publication-type="journal" id="cobi13083-cit-0065"><string-name><surname>Schwensow</surname><given-names>N</given-names></string-name>, <string-name><surname>Fietz</surname><given-names>J</given-names></string-name>, <string-name><surname>Dausmann</surname><given-names>KH</given-names></string-name>, <string-name><surname>Sommer</surname><given-names>S</given-names></string-name>. <year>2007</year><article-title>Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free‐ranging primate</article-title>. <source xml:lang="en">Heredity</source><volume>99</volume>:<fpage>265</fpage>–<lpage>277</lpage>.<pub-id pub-id-type="pmid">17519969</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0066"><mixed-citation publication-type="journal" id="cobi13083-cit-0066"><string-name><surname>Shapira</surname><given-names>M</given-names></string-name>. <year>2016</year><article-title>Gut microbiotas and host evolution: scaling up symbiosis</article-title>. <source xml:lang="en">Trends in Ecology and Evolution</source><volume>31</volume>:<fpage>539</fpage>–<lpage>549</lpage>.<pub-id pub-id-type="pmid">27039196</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0067"><mixed-citation publication-type="journal" id="cobi13083-cit-0067"><string-name><surname>Shen</surname><given-names>HM</given-names></string-name>, <string-name><surname>Chen</surname><given-names>SB</given-names></string-name>, <string-name><surname>Wang</surname><given-names>Y</given-names></string-name>, <string-name><surname>Xu</surname><given-names>B</given-names></string-name>, <string-name><surname>Abe</surname><given-names>EM</given-names></string-name>, <string-name><surname>Chen</surname><given-names>JH</given-names></string-name>. <year>2017</year><article-title>Genome‐wide scans for the identification of Plasmodium vivax genes under positive selection</article-title>. <source xml:lang="en">Malaria Journal</source><volume>16</volume>:<fpage>238</fpage>.<pub-id pub-id-type="pmid">28587615</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0068"><mixed-citation publication-type="journal" id="cobi13083-cit-0068"><string-name><surname>Siddle</surname><given-names>HV</given-names></string-name>, <string-name><surname>Kreiss</surname><given-names>A</given-names></string-name>, <string-name><surname>Eldridge</surname><given-names>MDB</given-names></string-name>, <string-name><surname>Noonan</surname><given-names>E</given-names></string-name>, <string-name><surname>Clarke</surname><given-names>CJ</given-names></string-name>, <string-name><surname>Pyecroft</surname><given-names>S</given-names></string-name>, <string-name><surname>Woods</surname><given-names>GM</given-names></string-name>, <string-name><surname>Belov</surname><given-names>K</given-names></string-name>. <year>2007</year><article-title>Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial</article-title>. <source xml:lang="en">Proceedings of the National Academy of Sciences of the United States of America</source><volume>104</volume>:<fpage>16221</fpage>–<lpage>16226</lpage>.<pub-id pub-id-type="pmid">17911263</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0069"><mixed-citation publication-type="journal" id="cobi13083-cit-0069"><string-name><surname>Siddle</surname><given-names>HV</given-names></string-name>, et al. <year>2013</year><article-title>Reversible epigenetic down‐regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer</article-title>. <source xml:lang="en">Proceedings of the National Academy of Sciences of the United States of America</source><volume>110</volume>:<fpage>5103</fpage>–<lpage>5108</lpage>.<pub-id pub-id-type="pmid">23479617</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0070"><mixed-citation publication-type="journal" id="cobi13083-cit-0070"><string-name><surname>Spielman</surname><given-names>D</given-names></string-name>, <string-name><surname>Brook</surname><given-names>BW</given-names></string-name>, <string-name><surname>Briscoe</surname><given-names>DA</given-names></string-name>, <string-name><surname>Frankham</surname><given-names>R</given-names></string-name>. <year>2004</year><article-title>Does inbreeding and loss of genetic diversity decrease disease resistance?</article-title><source xml:lang="en">Conservation Genetics</source><volume>5</volume>:<fpage>439</fpage>–<lpage>448</lpage>.</mixed-citation></ref><ref id="cobi13083-bib-0071"><mixed-citation publication-type="journal" id="cobi13083-cit-0071"><string-name><surname>Väli</surname><given-names>Ü</given-names></string-name>, <string-name><surname>Einarsson</surname><given-names>A</given-names></string-name>, <string-name><surname>Waits</surname><given-names>L</given-names></string-name>, <string-name><surname>Ellegren</surname><given-names>H</given-names></string-name>. <year>2008</year><article-title>To what extent do microsatellite markers reflect genome‐wide genetic diversity in natural populations?</article-title><source xml:lang="en">Molecular Ecology</source><volume>17</volume>:<fpage>3808</fpage>–<lpage>3817</lpage>.<pub-id pub-id-type="pmid">18647238</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0072"><mixed-citation publication-type="journal" id="cobi13083-cit-0072"><string-name><surname>Van Rooij</surname><given-names>P</given-names></string-name>, <string-name><surname>Martel</surname><given-names>A</given-names></string-name>, <string-name><surname>Haesebrouck</surname><given-names>F</given-names></string-name>, <string-name><surname>Pasmans</surname><given-names>F</given-names></string-name>. <year>2015</year><article-title>Amphibian chytridiomycosis: a review with focus on fungus–host interactions</article-title>. <source xml:lang="en">Veterinary Research</source><volume>46</volume>:<fpage>1</fpage>–<lpage>22</lpage>.<pub-id pub-id-type="pmid">25582708</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0073"><mixed-citation publication-type="journal" id="cobi13083-cit-0073"><string-name><surname>Webster</surname><given-names>JP</given-names></string-name>, <string-name><surname>Borlase</surname><given-names>A</given-names></string-name>, <string-name><surname>Rudge</surname><given-names>JW</given-names></string-name>. <year>2016</year><article-title>Who acquires infection from whom, and how?—disentangling multi‐host and multi‐mode transmission dynamics in the “elimination” era</article-title>. <source xml:lang="en">Philosophical Transactions of the Royal Society B</source><volume>372</volume>:<fpage>20160091</fpage>.</mixed-citation></ref><ref id="cobi13083-bib-0074"><mixed-citation publication-type="journal" id="cobi13083-cit-0074"><string-name><surname>Woodhams</surname><given-names>DC</given-names></string-name>, <string-name><surname>Bletz</surname><given-names>M</given-names></string-name>, <string-name><surname>Kueneman</surname><given-names>J</given-names></string-name>, <string-name><surname>McKenzie</surname><given-names>V</given-names></string-name>. <year>2016</year><article-title>Managing amphibian disease with skin microbiota</article-title>. <source xml:lang="en">Trends in Microbiology</source><volume>24</volume>:<fpage>161</fpage>–<lpage>164</lpage>.<pub-id pub-id-type="pmid">26916805</pub-id></mixed-citation></ref><ref id="cobi13083-bib-0075"><mixed-citation publication-type="journal" id="cobi13083-cit-0075"><string-name><surname>Zhao</surname><given-names>M</given-names></string-name>, <string-name><surname>Wang</surname><given-names>Z</given-names></string-name>, <string-name><surname>Yung</surname><given-names>S</given-names></string-name>, <string-name><surname>Lu</surname><given-names>Q</given-names></string-name>. <year>2015</year><article-title>Epigenetic dynamics in immunity and autoimmunity</article-title>. <source xml:lang="en">International Journal of Biochemistry and Cell Biology</source><volume>67</volume>:<fpage>65</fpage>–<lpage>74</lpage>.<pub-id pub-id-type="pmid">26026281</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/StressCovidV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000635 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000635 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= StressCovidV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |