The genetic impact of an Ebola outbreak on a wild gorilla population

Background Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. Results Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. Conclusion This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival.

High levels of pathological jaundice in the first 24 hours and neonatal hyperbilirubinaemia in an epidemiological cohort study on the Thailand-Myanmar border

Population risks for neonatal hyperbilirubinaemia (NH) vary. Knowledge of local risks permits interventions that may reduce the proportion becoming severe. Between January 2015 and May 2016, in a resource-limited setting on the Thailand-Myanmar border, neonates from 28 weeks’ gestation were enrolled into a prospective birth cohort. Each neonate had total serum bilirubin measurements: scheduled (24, 48, 72 and 144 hours of life) and clinically indicated; and weekly follow up until 1 month of age. Risk factors for developing NH were evaluated using Cox proportional hazard mixed model. Of 1710 neonates, 22% (376) developed NH (83% preterm, 19% term). All neonates born <35 weeks, four in five born 35–37 weeks, and three in twenty born ≥38 weeks had NH, giving an overall incidence of 249 per 1000 livebirths [95%CI 225, 403]. Mortality from acute bilirubin encephalopathy was 10% (2/20) amongst the 5.3% (20/376) who reached the severe NH threshold. One-quarter (26.3%) of NH occurred within 24 hours. NH onset varied with gestational age: at a median [IQR] 24 hours [24, 30] for neonates born 37 weeks or prematurely vs 59 hours [48, 84] for neonates born ≥38 weeks. Risk factors for NH in the first week of life independent of gestational age were: neonatal G6PD deficiency, birth bruising, Sgaw Karen ethnicity, primigravidae, pre-eclampsia, and prolonged rupture of membranes. The genetic impact of G6PD deficiency on NH was partially interpreted by using the florescent spot test and further genotyping work is in progress. The risk of NH in Sgaw Karen refugees may be overlooked internationally as they are most likely regarded as Burmese in countries of resettlement. Given high levels of pathological jaundice in the first 24 hours and overall high NH burden, guidelines changes were implemented including preventive PT for all neonates <35 weeks and for those 35–37 weeks with risk factors.

GPEdit: the genetic and pharmacogenomic landscape of A-to-I RNA editing in cancers

Altered A-to-I RNA editing has been widely observed in many human cancers and some editing sites are associated with drug sensitivity, implicating its therapeutic potential. Increasing evidence has demonstrated that a quantitative trait loci mapping approach is effective to understanding the genetic basis of RNA editing. We systematically performed RNA editing quantitative trait loci (edQTL) analysis in 33 human cancer types for &gt;10 000 cancer samples and identified 320 029 edQTLs. We also identified 1688 ed-QTLs associated with patient overall survival and 4672 ed-QTLs associated with GWAS risk loci. Furthermore, we demonstrated the associations between RNA editing and &gt;1000 anti-cancer drug response with ∼3.5 million significant associations. We developed GPEdit (https://hanlab.uth.edu/GPEdit/) to facilitate a global map of the genetic and pharmacogenomic landscape of RNA editing. GPEdit is a user-friendly and comprehensive database that provides an opportunity for a better understanding of the genetic impact and the effects on drug response of RNA editing in cancers.

Integrative Network Analysis Revealed Genetic Impact of Pyruvate Kinase L/R on Hepatocyte Proliferation and Graft Survival after Liver Transplantation

Background. Pyruvate kinase L/R (PKLR) has been suggested to affect the proliferation of hepatocytes via regulation of the cell cycle and lipid metabolism. However, its impact on the global metabolome and its clinical implications remain unclear. Aims. We aimed to clarify the genetic impact of PKLR on the metabolomic profiles of hepatoma cells and its potential effects on grafts for liver transplantation (LT). Methods. Nontargeted and targeted metabolomic assays were performed in human hepatoma cells transfected with lentiviral vectors causing PKLR overexpression and silencing, respectively. We then constructed a molecular network based on integrative analysis of transcriptomic and metabolomic data. We also assessed the biological functions of PKLR in the global metabolome in LT grafts in patients via a weighted correlation network model. Results. Multiomic analysis revealed that PKLR perturbations significantly affected the pyruvate, citrate, and glycerophospholipid metabolism pathways, as crucial steps in de novo lipogenesis (DNL). We also confirmed the importance of phosphatidylcholines (PC) and its derivative lyso-PC supply on improved survival of LT grafts in patients. Coexpression analysis revealed beneficial effects of PKLR overexpression on posttransplant prognosis by alleviating arachidonic acid metabolism of the grafts, independent of operational risk factors. Conclusion. This systems-level analysis indicated that PKLR affected hepatoma cell viability via impacts on the whole process of DNL, from glycolysis to final PC synthesis. PKLR also improved prognosis after LT, possibly via its impact on the increased genesis of beneficial glycerophospholipids.

Genomic insights into the differentiated population admixture structure and demographic history of North East Asians

North China and South Siberia, mainly populated by Altaic-speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroad for the initial peopling of America and western-eastern trans-continental communication. Yet, the complex scenarios of genetic origin, population structure, and admixture history of North-East Asia remain to be fully characterized, especially for Mongolic people in China with a genome-wide perspective. Thus, we genotyped genome-wide SNPs for 510 individuals from 38 Chinese Mongolic, Tungusic, and Sinitic populations to explore the sharing alleles and haplotypes within the studied groups and following merged it with 3508 modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified significant substructures within Altaic-speaking populations with the primary common ancestry linked to the Neolithic northern East Asians: Western Turkic people harbored more western Eurasian ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed dominant Neolithic Mongolian Plateau (MP) or ARB ancestry; Southern Mongolic people in China owned obvious genetic impact from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians and the latter retained the dominant YRB and ARB Neolithic ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountain possessed a strong genetic affinity with Neolithic MP people, supporting the hypothesis of their eastern Eurasian origin and long-distance migration history. We also illuminated that historic pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to southern ones. We finally found natural signatures in Mongolians associated with alcohol metabolism. Generally, our results not only illuminated that complex population migration and admixture of Neolithic ancestral sources from the MP or ARB played an important role in the spread of Altaic-speaking populations and Proto-Altaic language, which partly supported the Northeast Asia-origin hypothesis, but also demonstrated that the observed multi-sources of genetic diversity contributed significantly to the modern existing extensive ethnolinguistic diversity in North-East Asia.

Lack of detectable genetic isolation in the cyclic rodent Microtus arvalis despite large landscape fragmentation owing to transportation infrastructures

Although roads are widely seen as dispersal barriers, their genetic consequences for animals that experience large fluctuations in population density are poorly documented. We developed a spatially paired experimental design to assess the genetic impacts of roads on cyclic voles (Microtus arvalis) during a high-density phase in North-Western Spain. We compared genetic patterns from 15 paired plots bisected by three different barrier types, using linear mixed models and computing effect sizes to assess the importance of each type, and the influence of road features like width or the age of the infrastructure. Evidence of effects by roads on genetic diversity and differentiation were lacking. We speculate that the recurrent (each 3–5 generations) episodes of massive dispersal associated with population density peaks can homogenize populations and mitigate the possible genetic impact of landscape fragmentation by roads. This study highlights the importance of developing spatially replicated experimental designs that allow us to consider the large natural spatial variation in genetic parameters. More generally, these results contribute to our understanding of the not well explored effects of habitat fragmentation on dispersal in species showing “boom-bust” dynamics.

The genetic impact of an Ebola outbreak on a wild gorilla population

Background: Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. Results: Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. Conclusion: This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival.

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

The oral microbiota contains billions of microbial cells, which could contribute to diseases in a number of body sites. Challenged by eating, drinking and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1,915 individuals, for both the tongue dorsum and saliva. Five genetic loci, APPL2, SLC2A9 and MGST1 associated with tongue dorsum, LOC102723769-OR11H1-POTEH and MTRNR2L1-LOC105371703-MIR4522 associated with salivary microbial features, reached study-wide significance (p < 3.16 * 10-11). Further analyses confirmed 6 genome-wide significant loci shared between tongue dorsum and saliva. For example, the dental caries pathogen Prevotella melaninogenica associated with MARK2-RCOR2; the periodontitis bacteria Treponema associated with CCL26-CCL24 and Porphyromonas associated with CSMD1 at both niches. Human genetics account for at least 10% of oral microbiome differences between individuals. Machine learning models showed that polygenetic risk score dominated over oral microbiome in predicting predisposing risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

Cottonseed Protein, Oil, and Minerals in Cotton (Gossypium hirsutum L.) Lines Differing in Curly Leaf Morphology

Cottonseed is an important source of protein, oil, and minerals for human health and livestock feed. Therefore, understanding the physiological and genetic traits influencing the nutrient content is critical. To our knowledge, there is no information available on the effects of leaf shape—curly leaf (CRL)—on cottonseed protein, oil, and minerals. Therefore, the objective of the current research was to investigate the effect of the curly leaf trait on cottonseed protein, oil, and minerals in cotton lines differing in leaf shape. Our hypothesis was that since leaf shape is known to be associated with nutrient uptake, assimilation, and photosynthesis process, leaf shape can influence seed protein, oil, and minerals. A two-year field experiment using two curly leaf lines (Uzbek CRL and DP 5690 CRL) and one normal leaf (DP 5690 wild type) line was conducted in 2014 and 2015 in Stoneville, MS, USA. The experiment was a randomized complete block design with three replicates. The results showed that both Uzbek CRL and DP 5690 wild type lines had higher seed oil, and nutrients N, P, K, and Mg than DP 5690 CRL. Calcium was higher in DP 5690 CRL for two years and protein was only higher than the parents in 2015. Consistent significant positive and negative correlations between some nutrients were observed, which may be due to environmental conditions, especially heat. This indicates that curly leaf trait may partially regulate the accumulation of these nutrients in seeds. The results demonstrated that leaf shape trait—curly leaf—can affect cottonseed nutritional qualities. This research is important to breeders for cotton selection for high seed oil or protein, and to other researchers to further understand the genetic impact of leaf shapes on seed nutritional quality. It is also important for scientists to use leaf shape as a tool for physiological, biochemical, and morphological research related to leaf development.