Evolution, Medicine, and Public Health最新文献

{"title":"An orally administered drug prevents selection for antibiotic-resistant bacteria in the gut during daptomycin therapy.","authors":"Valerie J Morley,&nbsp;Derek G Sim,&nbsp;Aline Penkevich,&nbsp;Robert J Woods,&nbsp;Andrew F Read","doi":"10.1093/emph/eoac035","DOIUrl":"https://doi.org/10.1093/emph/eoac035","url":null,"abstract":"<p><strong>Background and objectives: </strong>Previously, we showed proof-of-concept in a mouse model that oral administration of cholestyramine prevented enrichment of daptomycin-resistant <i>Enterococcus faecium</i> in the gastrointestinal (GI) tract during daptomycin therapy. Cholestyramine binds daptomycin in the gut, which removes daptomycin selection pressure and so prevents the enrichment of resistant clones. Here, we investigated two open questions related to this approach: (i) can cholestyramine prevent the enrichment of diverse daptomycin mutations emerging <i>de novo</i> in the gut? and (ii) how does the timing of cholestyramine administration impact its ability to suppress resistance?</p><p><strong>Methodology: </strong>Mice with GI <i>E. faecium</i> were treated with daptomycin with or without cholestyramine, and <i>E. faecium</i> was cultured from feces to measure changes in daptomycin susceptibility. A subset of clones was sequenced to investigate the genomic basis of daptomycin resistance.</p><p><strong>Results: </strong>Cholestyramine prevented the enrichment of diverse resistance mutations that emerged <i>de novo</i> in daptomycin-treated mice. Whole-genome sequencing revealed that resistance emerged through multiple genetic pathways, with most candidate resistance mutations observed in the <i>clsA</i> gene. In addition, we observed that cholestyramine was most effective when administration started prior to the first dose of daptomycin. However, beginning cholestyramine after the first daptomycin dose reduced the frequency of resistant <i>E. faecium</i> compared to not using cholestyramine at all.</p><p><strong>Conclusions and implications: </strong>Cholestyramine prevented the enrichment of diverse daptomycin-resistance mutations in intestinal <i>E. faecium</i> populations during daptomycin treatment, and it is a promising tool for managing the transmission of daptomycin-resistant <i>E. faecium</i>.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"439-446"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10336334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cesarean section and breastfeeding outcomes in an Indigenous Qom community with high breastfeeding support.","authors":"Melanie Martin,&nbsp;Monica Keith,&nbsp;Sofía Olmedo,&nbsp;Deja Edwards,&nbsp;Alicia Barrientes,&nbsp;Anwesha Pan,&nbsp;Claudia Valeggia","doi":"10.1093/emph/eoab045","DOIUrl":"https://doi.org/10.1093/emph/eoab045","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cesarean section may lead to suboptimal breastfeeding outcomes, though evidence has been mixed. Factors, such as premature birth, birth weight and maternal age may independently increase risk of cesarean and hinder breastfeeding initiation, while maternal preferences, support and sociostructural barriers may influence breastfeeding practices beyond the immediate postpartum period.</p><p><strong>Methodology: </strong>We assessed impacts of cesarean section and gestational factors on breastfeeding duration among Indigenous Qom mothers in Argentina who have strong traditional breastfeeding support. We modeled transitions from exclusive breastfeeding to complementary feeding and from complementary feeding to full weaning in a Bayesian time-to-event framework with birth mode and gestational covariates (<i>n</i> = 89 infants).</p><p><strong>Results: </strong>Estimated median time to full weaning was 30 months. Cesarean-delivered babies were weaned an average of 5 months later adjusting for gestational age, maternal parity and infant sex. No factors were associated with time-to-complementary feeding, and time-to-complementary feeding was not associated with time-to-full weaning.</p><p><strong>Conclusions and implications: </strong>Among Indigenous Qom mothers in Argentina, cesarean section was not associated with suboptimal breastfeeding outcomes. Although some Qom mothers do experience early breastfeeding problems, particularly following first birth, problems are not more frequent following cesarean delivery. Traditional postpartum kin and community support during prolonged postpartum periods may be instrumental in helping mothers to overcome early breastfeeding problems due to cesarean or other risk factors.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"36-46"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution.","authors":"Massimo Amicone,&nbsp;Vítor Borges,&nbsp;Maria João Alves,&nbsp;Joana Isidro,&nbsp;Líbia Zé-Zé,&nbsp;Sílvia Duarte,&nbsp;Luís Vieira,&nbsp;Raquel Guiomar,&nbsp;João Paulo Gomes,&nbsp;Isabel Gordo","doi":"10.1093/emph/eoac010","DOIUrl":"https://doi.org/10.1093/emph/eoac010","url":null,"abstract":"<p><strong>Background and objectives: </strong>To understand how organisms evolve, it is fundamental to study how mutations emerge and establish. Here, we estimated the rate of mutation accumulation of SARS-CoV-2 <i>in vitro</i> and investigated the repeatability of its evolution when facing a new cell type but no immune or drug pressures.</p><p><strong>Methodology: </strong>We performed experimental evolution with two strains of SARS-CoV-2, one carrying the originally described spike protein (CoV-2-D) and another carrying the D614G mutation that has spread worldwide (CoV-2-G). After 15 passages in Vero cells and whole genome sequencing, we characterized the spectrum and rate of the emerging mutations and looked for evidences of selection across the genomes of both strains.</p><p><strong>Results: </strong>From the frequencies of the mutations accumulated, and excluding the genes with signals of selection, we estimate a spontaneous mutation rate of 1.3 × 10 ^<i>-</i>6 ± 0.2 × 10^-6 per-base per-infection cycle (mean across both lineages of SARS-CoV-2 ± 2SEM). We further show that mutation accumulation is larger in the CoV-2-D lineage and heterogeneous along the genome, consistent with the action of positive selection on the spike protein, which accumulated five times more mutations than the corresponding genomic average. We also observe the emergence of mutators in the CoV-2-G background, likely linked to mutations in the RNA-dependent RNA polymerase and/or in the error-correcting exonuclease protein.</p><p><strong>Conclusions and implications: </strong>These results provide valuable information on how spontaneous mutations emerge in SARS-CoV-2 and on how selection can shape its genome toward adaptation to new environments. <b>Lay Summary:</b> Each time a virus replicates inside a cell, errors (mutations) occur. Here, via laboratory propagation in cells originally isolated from the kidney epithelium of African green monkeys, we estimated the rate at which the SARS-CoV-2 virus mutates-an important parameter for understanding how it can evolve within and across humans. We also confirm the potential of its Spike protein to adapt to a new environment and report the emergence of mutators-viral populations where mutations occur at a significantly faster rate.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"142-155"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10514328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How a pregnant woman's relationships with her siblings relate to her mental health: a prenatal allocare perspective.","authors":"Molly Fox, Kyle S Wiley","doi":"10.1093/emph/eoab044","DOIUrl":"10.1093/emph/eoab044","url":null,"abstract":"<p><strong>Background: </strong>In cooperatively breeding species, individuals may promote their inclusive fitness through allomothering. Humans exhibit some features of cooperative breeding, and previous studies have focused on allomothering by grandparents and juvenile siblings in the postnatal period. We hypothesize that a pregnant woman's relationships with her siblings (offspring's maternal aunts and uncles) are beneficial for maternal affect in ways that can enhance the siblings' inclusive fitness. Maternal affect during pregnancy is a salient target of allocare given the detrimental effects of antepartum mood disorders on birth and infant outcomes.</p><p><strong>Methodology: </strong>We test our hypotheses in a cohort of pregnant Latina women in Southern California (<i>N</i> = 201). Predictor variables of interest include number of siblings a participant has, if she has sisters, frequency of seeing siblings, and frequency of communication with siblings. Outcome variables measuring maternal affect include depression, state anxiety, pregnancy-related anxiety and perceived stress.</p><p><strong>Results: </strong>Having at least one sister and greater frequency of communication with siblings were associated with fewer depressive symptoms during pregnancy. No significant associations were found between sibling variables and other measures of affect.</p><p><strong>Conclusion and implications: </strong>Results suggest that how frequently you communicate with, and not how often you see, siblings could be protective against risk of antepartum depression. Sibling allomothering could impart effects through social-emotional support rather than instrumental support, as a strategy to benefit the prenatal environment in which future nieces and nephews develop. Allomothering may be particularly important in cultural contexts that value family relationships. Future studies should investigate other communities.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"1-20"},"PeriodicalIF":3.3,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10754602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daily rhythms of both host and parasite affect antimalarial drug efficacy.","authors":"Alíz T Y Owolabi,&nbsp;Sarah E Reece,&nbsp;Petra Schneider","doi":"10.1093/emph/eoab013","DOIUrl":"https://doi.org/10.1093/emph/eoab013","url":null,"abstract":"<p><strong>Background and objectives: </strong>Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite <i>Plasmodium chabaudi</i>, to test whether the daily rhythms of hosts, parasites and their interactions affect sensitivity to the key antimalarial, artemisinin.</p><p><strong>Methodology: </strong>Asexual malaria parasites develop rhythmically in the host's blood, in a manner timed to coordinate with host daily rhythms. Our experiments coupled or decoupled the timing of parasite and host rhythms, and we administered artemisinin at different times of day to coincide with when parasites were either at an early (ring) or later (trophozoite) developmental stage. We quantified the impacts of parasite developmental stage, and alignment of parasite and host rhythms, on drug sensitivity.</p><p><strong>Results: </strong>We find that rings were less sensitive to artemisinin than trophozoites, and this difference was exacerbated when parasite and host rhythms were misaligned, with little direct contribution of host time-of-day on its own. Furthermore, the blood concentration of haem at the point of treatment correlated positively with artemisinin efficacy but only when parasite and host rhythms were aligned.</p><p><strong>Conclusions and implications: </strong>Parasite rhythms influence drug sensitivity <i>in vivo</i>. The hitherto unknown modulation by alignment between parasite and host daily rhythms suggests that disrupting the timing of parasite development could be a novel chronotherapeutic approach.</p><p><strong>Lay summary: </strong>We reveal that chronotherapy (providing medicines at a particular time-of-day) could improve treatment for malaria infections. Specifically, parasites' developmental stage at the time of treatment and the coordination of timing between parasite and host both affect how well antimalarial drug treatment works.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"9 1","pages":"208-219"},"PeriodicalIF":3.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoab013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10735992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune function during pregnancy varies between ecologically distinct populations.","authors":"Carmen Hové, Benjamin C Trumble, Amy S Anderson, Jonathan Stieglitz, Hillard Kaplan, Michael D Gurven, Aaron D Blackwell","doi":"10.1093/emph/eoaa022","DOIUrl":"10.1093/emph/eoaa022","url":null,"abstract":"<p><strong>Background and objectives: </strong>Among placental mammals, females undergo immunological shifts during pregnancy to accommodate the fetus (i.e. fetal tolerance). Fetal tolerance has primarily been characterized within post-industrial populations experiencing evolutionarily novel conditions (e.g. reduced pathogen exposure), which may shape maternal response to fetal antigens. This study investigates how ecological conditions affect maternal immune status during pregnancy by comparing the direction and magnitude of immunological changes associated with each trimester among the Tsimane (a subsistence population subjected to high pathogen load) and women in the USA.</p><p><strong>Methodology: </strong>Data from the Tsimane Health and Life History Project (<i>N</i> = 935) and the National Health and Nutrition Examination Survey (<i>N</i> = 1395) were used to estimate population-specific effects of trimester on differential leukocyte count and C-reactive protein (CRP), a marker of systemic inflammation.</p><p><strong>Results: </strong>In both populations, pregnancy was associated with increased neutrophil prevalence, reduced lymphocyte and eosinophil count and elevated CRP. Compared to their US counterparts, pregnant Tsimane women exhibited elevated lymphocyte and eosinophil counts, fewer neutrophils and monocytes and lower CRP. Total leukocyte count remained high and unchanged among pregnant Tsimane women while pregnant US women exhibited substantially elevated counts, resulting in overlapping leukocyte prevalence among all third-trimester individuals.</p><p><strong>Conclusions and implications: </strong>Our findings indicate that ecological conditions shape non-pregnant immune baselines and the magnitude of immunological shifts during pregnancy via developmental constraints and current trade-offs. Future research should investigate how such flexibility impacts maternal health and disease susceptibility, particularly the degree to which chronic pathogen exposure might dampen inflammatory response to fetal antigens.</p><p><strong>Lay summary: </strong>This study compares immunological changes associated with pregnancy between the Tsimane (an Amazonian subsistence population) and individuals in the USA. Results suggest that while pregnancy enhances non-specific defenses and dampens both antigen-specific immunity and parasite/allergy response, ecological conditions strongly influence immune baselines and the magnitude of shifts during gestation.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2020 1","pages":"114-128"},"PeriodicalIF":3.3,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10783910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative psychopharmacology of autism and psychotic-affective disorders suggests new targets for treatment.","authors":"Bernard J Crespi","doi":"10.1093/emph/eoz022","DOIUrl":"10.1093/emph/eoz022","url":null,"abstract":"<p><p>The first treatments showing effectiveness for some psychiatric disorders, such as lithium for bipolar disorder and chlorpromazine for schizophrenia, were discovered by accident. Currently, psychiatric drug design is seen as a scientific enterprise, limited though it remains by the complexity of brain development and function. Relatively few novel and effective drugs have, however, been developed for many years. The purpose of this article is to demonstrate how evolutionary biology can provide a useful framework for psychiatric drug development. The framework is based on a diametrical nature of autism, compared with psychotic-affective disorders (mainly schizophrenia, bipolar disorder and depression). This paradigm follows from two inferences: (i) risks and phenotypes of human psychiatric disorders derive from phenotypes that have evolved along the human lineage and (ii) biological variation is bidirectional (e.g. higher vs lower, faster vs slower, etc.), such that dysregulation of psychological traits varies in two opposite ways. In this context, the author review the evidence salient to the hypothesis that autism and psychotic-affective disorders represent diametrical disorders in terms of current, proposed and potential psychopharmacological treatments. Studies of brain-derived neurotrophic factor, the PI3K pathway, the NMDA receptor, kynurenic acid metabolism, agmatine metabolism, levels of the endocannabinoid anandamide, antidepressants, anticonvulsants, antipsychotics, and other treatments, demonstrate evidence of diametric effects in autism spectrum disorders and phenotypes compared with psychotic-affective disorders and phenotypes. These findings yield insights into treatment mechanisms and the development of new pharmacological therapies, as well as providing an explanation for the longstanding puzzle of antagonism between epilepsy and psychosis. Lay Summary: Consideration of autism and schizophrenia as caused by opposite alterations to brain development and function leads to novel suggestions for pharmacological treatments.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"149-168"},"PeriodicalIF":3.3,"publicationDate":"2019-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autism and psychosis as diametrical disorders of embodiment.","authors":"Bernard Crespi,&nbsp;Natalie Dinsdale","doi":"10.1093/emph/eoz021","DOIUrl":"https://doi.org/10.1093/emph/eoz021","url":null,"abstract":"<p><p>Humans have evolved an elaborate system of self-consciousness, self-identity, self-agency, and self-embodiment that is grounded in specific neurological structures including an expanded insula. Instantiation of the bodily self has been most-extensively studied via the 'rubber hand illusion', whereby parallel stimulation of a hidden true hand, and a viewed false hand, leads to the felt belief that the false hand is one's own. Autism and schizophrenia have both long been regarded as conditions centrally involving altered development of the self, but they have yet to be compared directly with regard to the self and embodiment. Here, we synthesize the embodied cognition literature for these and related conditions, and describe evidence that these two sets of disorders exhibit opposite susceptibilities from typical individuals to the rubber hand illusion: reduced on the autism spectrum and increased in schizophrenia and other psychotic-affective conditions. Moreover, the opposite illusion effects are mediated by a consilient set of associated phenomena, including empathy, interoception, anorexia risk and phenotypes, and patterns of genetic correlation. Taken together, these findings: (i) support the diametric model of autism and psychotic-affective disorders, (ii) implicate the adaptive human system of self-embodiment, and its neural bases, in neurodevelopmental disorders, and suggest new therapies and (iii) experimentally ground Bayesian predictive coding models with regard to autism compared with psychosis. Lay summary: Humans have evolved a highly developed sense of self and perception of one's own body. The 'rubber hand illusion' can be used to test individual variation in sense of self, relative to connection with others. We show that this illusion is reduced in autism spectrum disorders, and increased in psychotic and mood disorders. These findings have important implications for understanding and treatment of mental disorders.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"121-138"},"PeriodicalIF":3.7,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/emph/eoz021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in mutational processes and intra-tumour heterogeneity between organs: The local selective filter hypothesis.","authors":"Mathieu Giraudeau, Tuul Sepp, Beata Ujvari, François Renaud, Aurélie Tasiemski, Benjamin Roche, Jean-Pascal Capp, Frédéric Thomas","doi":"10.1093/emph/eoz017","DOIUrl":"10.1093/emph/eoz017","url":null,"abstract":"<p><p>Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs' theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis. Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"139-146"},"PeriodicalIF":3.3,"publicationDate":"2019-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41195862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association analysis uncovers variants for reproductive variation across dog breeds and links to domestication.","authors":"Samuel P Smith, Julie B Phillips, Maddison L Johnson, Patrick Abbot, John A Capra, Antonis Rokas","doi":"10.1093/emph/eoz015","DOIUrl":"10.1093/emph/eoz015","url":null,"abstract":"<p><strong>Background and objectives: </strong>The diversity of eutherian reproductive strategies has led to variation in many traits, such as number of offspring, age of reproductive maturity and gestation length. While reproductive trait variation has been extensively investigated and is well established in mammals, the genetic loci contributing to this variation remain largely unknown. The domestic dog, <i>Canis lupus familiaris</i> is a powerful model for studies of the genetics of inherited disease due to its unique history of domestication. To gain insight into the genetic basis of reproductive traits across domestic dog breeds, we collected phenotypic data for four traits, cesarean section rate, litter size, stillbirth rate and gestation length, from primary literature and breeders' handbooks.</p><p><strong>Methodology: </strong>By matching our phenotypic data to genomic data from the Cornell Veterinary Biobank, we performed genome-wide association analyses for these four reproductive traits, using body mass and kinship among breeds as covariates.</p><p><strong>Results: </strong>We identified 12 genome-wide significant associations between these traits and genetic loci, including variants near <i>CACNA2D3</i> with gestation length, <i>MSRB3</i> and <i>MSANTD1</i> with litter size, <i>SMOC2</i> with cesarean section rate and <i>UFM1</i> with stillbirth rate. A few of these loci, such as <i>CACNA2D3</i> and <i>MSRB3</i>, have been previously implicated in human reproductive pathologies, whereas others have been associated with domestication-related traits, including brachycephaly (<i>SMOC2</i>) and coat curl (<i>KRT71</i>).</p><p><strong>Conclusions and implications: </strong>We hypothesize that the artificial selection that gave rise to dog breeds also influenced the observed variation in their reproductive traits. Overall, our work establishes the domestic dog as a system for studying the genetics of reproductive biology and disease.</p><p><strong>Lay summary: </strong>The genetic contributors to variation in mammalian reproductive traits remain largely unknown. We took advantage of the domestic dog, a powerful model system, to test for associations between genome-wide variants and four reproductive traits (cesarean section rate, litter size, stillbirth rate and gestation length) that vary extensively across breeds. We identified associations at a dozen loci, including ones previously associated with domestication-related traits, suggesting that selection on dog breeds also influenced their reproductive traits.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"2019 1","pages":"93-103"},"PeriodicalIF":3.3,"publicationDate":"2019-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10407873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}