Browsing by Author "Fralin Life Sciences Institute"

Now showing 1 - 20 of 260
  • Thumbnail Image
    3,4-Dihydroxyphenylacetaldehyde synthase and cuticle formation in insects
    Liao, Chenghong; Liang, Jing; Han, Qian; Li, Jianyong (2018-06-02)
    Cuticle is the most important structure that protects mosquitoes and other insect species from adverse environmental conditions and infections of microorganism. The physiology and biochemistry of insect cuticle formation have been studied for many years and our understanding of cuticle formation and hardening has increased considerably. This is especially true for flexible cuticle. The recent discovery of a novel enzyme that catalyzes the production of 3,4-dihydroxyphenylacetaldehyde (DOPAL) in insects provides intriguing insights concerning the flexible cuticle formation in insects. For convenience, the enzyme that catalyzes the production DOPAL from L-dopa is named DOPAL synthase. In this mini-review, we summarize the biochemical pathways of cuticle formation and hardening in general and discuss DOPAL synthase-mediated protein crosslinking in insect flexible cuticle in particular.
  • Thumbnail Image
    Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects
    Cornish-Bowden, Athel; Rasnick, David; Heng, Henry H.; Horne, Steven; Abdallah, Batoul; Liu, Guo; Ye, Christine J.; Bloomfield, Mathew; Vincent, Mark D.; Aldaz, C. M.; Karlsson, Jenny; Valind, Anders; Jansson, Caroline; Gisselsson, David; Graves, Jennifer A. M.; Stepanenko, Aleksei A.; Andreieva, Svitlana V.; Korets, Kateryna V.; Mykytenko, Dmytro O.; Huleyuk, Nataliya L.; Baklaushev, Vladimir P.; Kovaleva, Oksana A.; Chekhonin, Vladimir P.; Vassetzky, Yegor S.; Avdieiev, Stanislav S.; Bakker, Bjorn; Taudt, Aaron S.; Belderbos, Mirjam E.; Porubsky, David; Spierings, Diana C. J.; de Jong, Tristan V.; Halsema, Nancy; Kazemier, Hinke G.; Hoekstra-Wakker, Karina; Bradley, Allan; de Bont, Eveline S. J. M.; van den Berg, Anke; Guryev, Victor; Lansdorp, Peter M.; Tatché, Maria C.; Foijer, Floris; Liehr, Thomas; Baudoin, Nicolaas C.; Nicholson, Joshua M.; Soto, Kimberly; Quintanilla, Isabel; Camps, Jordi; Cimini, Daniela; Dürrbaum, M.; Donnelly, N.; Passerini, V.; Kruse, C.; Habermann, B.; Storchová, Z.; Mandrioli, Daniele; Belpoggi, Fiorella; Silbergeld, Ellen K.; Perry, Melissa J.; Skotheim, Rolf I.; Løvf, Marthe; Johannessen, Bjarne; Hoff, Andreas M.; Zhao, Sen; SveeStrømme, Jonas M.; Sveen, Anita; Lothe, Ragnhild A.; Hehlmann, R.; Voskanyan, A.; Fabarius, A.; Böcking, Alfred; Biesterfeld, Stefan; Berynskyy, Leonid; Börgermann, Christof; Engers, Rainer; Dietz, Josef; Fritz, A.; Sehgal, N.; Vecerova, J.; Stojkovicz, B.; Ding, H.; Page, N.; Tye, C.; Bhattacharya, S.; Xu, J.; Stein, G.; Stein, J.; Berezney, R.; Gong, Xue; Grasedieck, Sarah; Swoboda, Julian; Rücker, Frank G.; Bullinger, Lars; Pollack, Jonathan R.; Roumelioti, Fani-Marlen; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis; Duesberg, Peter; Bloomfield, Mathew; Hwang, Sunyoung; Gustafsson, Hans T.; O’Sullivan, Ciara; Acevedo-Colina, Aracelli; Huang, Xinhe; Klose, Christian; Schevchenko, Andrej; Dickson, Robert C.; Cavaliere, Paola; Dephoure, Noah; Torres, Eduardo M.; Stampfer, Martha R.; Vrba, Lukas; LaBarge, Mark A.; Futscher, Bernard; Garbe, James C.; Trinh, Andrew L.; Zhou, Yi-Hong; Digman, Michelle (2017-06-22)
  • Thumbnail Image
    Accurate human microsatellite genotypes from high-throughput resequencing data using informed error profiles
    Highnam, Gareth; Franck, Christopher T.; Martin, Andy; Stephens, Calvin; Puthige, Ashwin; Mittelman, David (Oxford University Press, 2013-01)
    Repetitive sequences are biologically and clinically important because they can influence traits and disease, but repeats are challenging to analyse using short-read sequencing technology. We present a tool for genotyping microsatellite repeats called RepeatSeq, which uses Bayesian model selection guided by an empirically derived error model that incorporates sequence and read properties. Next, we apply RepeatSeq to high-coverage genomes from the 1000 Genomes Project to evaluate performance and accuracy. The software uses common formats, such as VCF, for compatibility with existing genome analysis pipelines. Source code and binaries are available at http://github.com/adaptivegenome/repeatseq.
  • Thumbnail Image
    Accurate Strand-Specific Quantification of Viral RNA
    Plaskon, Nicole E.; Adelman, Zach N.; Myles, Kevin M. (PLOS, 2009-10-22)
    The presence of full-length complements of viral genomic RNA is a hallmark of RNA virus replication within an infected cell. As such, methods for detecting and measuring specific strands of viral RNA in infected cells and tissues are important in the study of RNA viruses. Strand-specific quantitative real-time PCR (ssqPCR) assays are increasingly being used for this purpose, but the accuracy of these assays depends on the assumption that the amount of cDNA measured during the quantitative PCR (qPCR) step accurately reflects amounts of a specific viral RNA strand present in the RT reaction. To specifically test this assumption, we developed multiple ssqPCR assays for the positive-strand RNA virus o'nyong-nyong (ONNV) that were based upon the most prevalent ssqPCR assay design types in the literature. We then compared various parameters of the ONNV-specific assays. We found that an assay employing standard unmodified virus-specific primers failed to discern the difference between cDNAs generated from virus specific primers and those generated through false priming. Further, we were unable to accurately measure levels of ONNV (−) strand RNA with this assay when higher levels of cDNA generated from the (+) strand were present. Taken together, these results suggest that assays of this type do not accurately quantify levels of the anti-genomic strand present during RNA virus infectious cycles. However, an assay permitting the use of a tag-specific primer was able to distinguish cDNAs transcribed from ONNV (−) strand RNA from other cDNAs present, thus allowing accurate quantification of the anti-genomic strand. We also report the sensitivities of two different detection strategies and chemistries, SYBR® Green and DNA hydrolysis probes, used with our tagged ONNV-specific ssqPCR assays. Finally, we describe development, design and validation of ssqPCR assays for chikungunya virus (CHIKV), the recent cause of large outbreaks of disease in the Indian Ocean region.
  • Thumbnail Image
    ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra
    Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard C. (2011-07-20)
    Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics.
  • Thumbnail Image
    Advancing livestock genomics education and research in developing countries using strategies from the Virginia Tech PREP and IMSD training programs
    Smith, Edward J. (2019-07-11)
    Our unique and impactful research and education program plan includes distinct activities that target three overlapping phases of each trainee’s tenure, which we define as the “moving in,” “moving through,” and “moving out” phases. During the “moving in” phase, 8 trainees “who need a PREP” will be recruited and assigned to mentors using our proven strategy that is “scholar-driven” and combines mentor qualities such as prior experience, which has resulted in a 98% retention for each of our 3 funding cycles.  $409,537 annually or ~2.1 Million for five years. our successful interdisciplinary Initiative for Maximizing Student Development (IMSD) program for pre-doctoral (graduate) and pre-baccalaureate (undergraduate) students from groups underrepresented in careers in the biomedical and behavioral sciences. Our training program is a partnership with departments and interdisciplinary graduate programs which takes advantage of Virginia Tech’s (VT) history of excellence in Engineering and the Behavioral and Life Sciences. With lessons learned in the last eight years, we will continue to recruit across disciplines and from diverse geographic areas and institutions. From the first cycle, 2007-12, a total of 23 pre-doctoral students participated in the VT IMSD program. A total of 16 (or 69.5%) have completed and received the PhD degree; Total Year 1: $467,489.
  • Thumbnail Image
    Age-related variations in the methylome associated with gene expression in human monocytes and T cells
    Reynolds, Lindsay M.; Taylor, Jackson R.; Ding, Jingzhong; Lohman, Kurt; Johnson, Craig; Siscovick, David; Burke, Gregory L.; Post, Wendy; Shea, Steven; Jacobs, David R. Jr.; Stunnenberg, Hendrik G.; Kritchevsky, Stephen B.; Hoeschele, Ina; McCall, Charles E.; Herrington, David M.; Tracy, Russell P.; Liu, Yongmei (Springer Nature, 2014-11)
    Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age-and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.
  • Thumbnail Image
    Analysis of global gene expression changes in human bronchial epithelial cells exposed to spores of the allergenic fungus, Alternaria alternata
    Babiceanu, Mihaela; Howard, B. A.; Rumore, A. C.; Kita, H.; Lawrence, Christopher B. (Frontiers, 2013-07-19)
    Exposure and sensitivity to ubiquitous airborne fungi such as Alternaria alternata have long been implicated in the development, onset, and exacerbation of chronic allergic airway disorders. This present study is the first to investigate global changes in host gene expression during the interaction of cultured human bronchial epithelial cells and live Alternaria spores. In in vitro experiments human bronchial epithelial cells (BEAS-2B) were exposed to spores or media alone for 24 h. RNA was collected from three biological replicates per treatment and was used to assess changes in gene expression patterns using Affymetrix Human Genome U133 Plus 2.0 Arrays. In cells treated with Alternaria spores compared to controls, 613 probe sets representing 460 individual genes were found differentially expressed (p <= 0.05). In this set of 460 statistically significant, differentially expressed genes, 397 genes were found to be up-regulated and 63 were down-regulated. Of these 397 up-regulated genes, 156 genes were found to be up-regulated >= 2 fold. Interestingly, none of the 63 down-regulated genes were found differentially expressed at <=-2 fold. Differentially expressed genes were identified following statistical analysis and subsequently used for pathway and network evaluation. Interestingly, many cytokine and chemokine immune response genes were up-regulated with a particular emphasis on interferon-inducible genes. Genes involved in cell death, retinoic acid signaling, and TLR3 response pathways were also significantly up-regulated. Many of the differentially up-regulated genes have been shown in other systems to be associated with innate immunity, inflammation and/or allergic airway diseases. This study now provides substantial information for further investigating specific genes and innate immune system pathways activated by Alternaria in the context of allergic airway diseases.
  • Thumbnail Image
    Analysis of the Aedes albopictus C6/36 genome provides insight into cell line utility for viral propagation
    Miller, Jason R.; Koren, Sergey; Dilley, Kari A.; Puri, Vinita; Brown, David M.; Harkins, Derel M.; Thibaud-Nissen, Françoise; Rosen, Benjamin D.; Xiao-Guang, Chen; Tu, Zhijian Jake; Sharakhov, Igor V.; Sharakhova, Maria V.; Sebra, R.; Stockwell, T. B.; Bergman, N. H.; Sutton, G. G.; Phillippi, A. M.; Pieemarini, P. M.; Shabman, R. S. (2018-03)
    The 50-year old Aedes albopictus C6/36 cell line is a resource for the detection, amplification, and analysis of mosquito-borne viruses including Zika, dengue, and chikungunya. The cell line is derived from an unknown number of larvae from an unspecified strain of Aedes albopictus mosquitoes. Toward improved utility of the cell line for research in virus transmission, we present an annotated assembly of the C6/36 genome.
  • Thumbnail Image
    Apheloria polychroma, a new species of millipede from the Cumberland Mountains (Polydesmida: Xystodesmidae)
    Marek, Paul E.; Means, Jackson C.; Hennen, Derek A. (Zootaxa, 2018-01-25)
    Millipedes of the genus Apheloria Chamberlin, 1921 occur in temperate broadleaf forests throughout eastern North America and west of the Mississippi River in the Ozark and Ouachita Mountains. Chemically defended with toxins made up of cyanide and benzaldehyde, the genus is part of a community of xystodesmid millipedes that compose several Müllerian mimicry rings in the Appalachian Mountains. We describe a model species of these mimicry rings, Apheloria polychroma n. sp., one of the most variable in coloration of all species of Diplopoda with more than six color morphs, each associated with a separate mimicry ring.
  • Thumbnail Image
    Assessment of Genetic Diversity and Population Structure in Iranian Cannabis Germplasm
    Soorni, Aboozar; Fatahi, Reza; Haak, David C.; Salami, Seyed Alireza; Bombarely, Aureliano (Nature Publishing Group, 2017-11-15)
    Cannabis sativa has a complex history reflected in both selection on naturally occurring compounds and historical trade routes among humans. Iran is a rich resource of natural populationswhich hold the promise to characterize historical patterns of population structure and genetic diversity within Cannabis. Recent advances in high-throughput DNA sequencing technologies have dramatically increased our ability to produce information to the point that it is now feasible to inexpensively obtain population level genotype information at a large scale. In the present investigation, we have explored the use of Genotyping-By-Sequencing (GBS) in Iranian cannabis. We genotyped 98 cannabis samples 36 from Iranian locations and 26 accessions from two germplasm collections. In total, 24,710 high-quality Single Nucleotide Polymorphisms (SNP) were identified. Clustering analysis by Principal Component Analysis (PCA) identified two genetic clusters among Iranian populations and fineSTRUCTURE analysis identified 19 populations with some geographic partitioning. We defined Iranian cannabis in two main groups using the results of the PCA and discovered some strong signal to define some locations as population according to fineSTRUCTURE analyses. However, single nucleotide variant analysis uncovered a relatively moderate level of variation among Iranian cannabis.
  • Thumbnail Image
  • Thumbnail Image
    Association of Polymorphisms in the Period3 (turPer3) Gene with Growth and Reproductive Traits in Turkeys (Meleagris gallopavo)
    Smith, E.; Adikari, A. M.; Xu, J. (2018)
    Background and objective: Biological clock controls behavioral, physiological and biochemical circadian rhythms of animals. Circadian clock genes including period3 are involved in the circadian clock mechanism. The present study was conducted to test the hypothesis that differences in DNA sequence variations of the turkey period3 (turPer3) gene may be associated with performance traits including growth and reproduction. Methodology: The turPer3 gene was screened for DNA sequence variations and evaluated the relationships among haplogroups with performance traits. The DNA sequences of turPer3 (16.6 kb) gene were screened using 290 turkey birds by re-sequencing the individual amplicons. Results: Seven SNPs, including one each in exon 18 and intron 5, two SNPs in exon 19 and three SNPs in intron 6, were detected. The SNPs detected in the exon 19 were non-synonymous, which changed the amino acids from methionine to threonine and serine to phenylalanine at 953rd and 955th positions, respectively. Linkage disequilibrium (Dʼ) among SNPs ranged from 0.03-1.00. Pairwise FST ranged from 0.01-0.43. Haplogroup frequencies of the turPer3 ranged from 0.02-1.00, were significantly associated with body weight (BW) at 231 days of age, average daily gain (ADG) for the period of 160-231 d of age, FCR for the periods of 69-159 d and 160-231 d, egg production and semen quality traits (p#0.05). Conclusion: The DNA sequence variations of turPer3 gene are significantly associated with BW, ADG, FCR, egg production, egg weight and semen quality traits. turPer3 gene may seem to have some regulatory role in the molecular mechanism of the circadian clock. Genomic reagents reported in the present study would be valuable for future genotype: phenotype evaluation studies in the turkey using a candidate gene approach.
  • Thumbnail Image
    Associations between peer attachment and neural correlates of risk processing across adolescence
    Asscheman, J. Susanne; Deater-Deckard, Kirby; Lauharatanahirun, Nina; van Lier, Pol A. C.; Koot, Susanne; Casas, Brooks; Kim-Spoon, Jungmeen (2020-04)
    Adolescence is a period of increased risk-taking behavior where individual differences in risk taking may relate to both adverse and positive experiences with peers. Yet, knowledge on how risk processing develops in the adolescent brain and whether this development is related to peer attachment is limited. In this longitudinal functional magnetic resonance imaging (fMRI) study, we collected data from 167 adolescents (53% male) followed for four annual assessments across ages 13-17 years. At each assessment, participants completed a lottery choice task to assess neural risk processing and reported on their perceived attachment to peers and parents. Behaviorally, risk-preference on the lottery choice task decreased linearly with age. Neural activation during risk processing was consistently found in the insula and dACC across the four assessments and increased linearly from ages 13-17 years. Furthermore, higher peer attachment was related to greater right insula risk processing for males but not for females, even after controlling for parental attachment. The magnitudes of this association did not change with age. Findings demonstrate that neural risk processing shows maturation across adolescence and high peer attachment may be associated with low risk taking by heightening neural sensitivity to potential risks for male adolescents.
  • Thumbnail Image
    An Atlas of the Speed of Copy Number Changes in Animal Gene Families and Its Implications
    Pan, Deng; Zhang, Liqing (PLOS, 2009-10-23)
    The notion that gene duplications generating new genes and functions is commonly accepted in evolutionary biology. However, this assumption is more speculative from theory rather than well proven in genome-wide studies. Here, we generated an atlas of the rate of copy number changes (CNCs) in all the gene families of ten animal genomes. We grouped the gene families with similar CNC dynamics into rate pattern groups (RPGs) and annotated their function using a novel bottom-up approach. By comparing CNC rate patterns, we showed that most of the species-specific CNC rates groups are formed by gene duplication rather than gene loss, and most of the changes in rates of CNCs may be the result of adaptive evolution. We also found that the functions of many RPGs match their biological significance well. Our work confirmed the role of gene duplication in generating novel phenotypes, and the results can serve as a guide for researchers to connect the phenotypic features to certain gene duplications.
  • Thumbnail Image
    Attentional control mediates fearful responding to an ecologically valid stressor
    Richey, John A.; White, Bradley A.; Valdespino, Andrew; Ghane, M.; Schmidt, N. B. (Taylor & Francis, 2016-01-02)
    Background and Objectives: Attentional control (AC) is defined as the ability to voluntarily shift and disengage attention, and is thought to moderate the relationship between pre-existing risk factors for fear and the actual experience of fear. Design: This longitudinal study elaborates on current models of attentional control by examining whether AC moderates or mediates effects of an ecologically valid stressor (a college exam), and also whether AC is predictive of state-like fear over longer timescales than previously reported. Methods: Based on previous findings we hypothesized that AC would moderate the relationship between trait anxiety and affective distress in response to the exam stressor. We also tested a competing mediational model based on attentional control theory (Eysenck et al., 2007). These models were tested in two separate samples (Sample 1 N=219; Sample 2 N=129; Total N= 348) at two time points, at the beginning of a college semester in a large undergraduate class, and five minutes prior to a college exam. Results: Mediation but not moderation of anxiety by AC was supported in both samples using multiple dependent measures. Conclusion: We conclude that AC may be useful in predicting affective distress in naturalistic settings, particularly in cases where anxiety is anticipatory.
  • Thumbnail Image
    Bed Bugs and Infectious Disease: A Case for the Arboviruses
    Adelman, Zach N.; Miller, Dini M.; Myles, Kevin M. (PLOS, 2013-08-01)
    Bed bug infestations (Cimicidae; Cimex lectularius) have been increasing worldwide over the last few decades [1,2]. Several factors have been posited to explain this resurgence, including widespread insecticide resistance, human population growth, and increased international travel [1]. Clinically, reactions to bed bug bites vary from unapparent, to small (,5 mm) maculopapular lesions, to large wheals (2–6 cm); other reactions include bullous rashes, dermatitis, and asthma [1,3]. However, in the developed world the psychological, social, and economic impacts of bed bugs may be the most troubling aspects of the resurgence [2]. While the bed bug invasion cuts across economic lines, those with sufficient resources are able to clear the infestations, while those without may have to live with their bed bugs into the foreseeable future [2,4].
  • Thumbnail Image
    The Beginning of the End: A Chromosomal Assembly of the New World Malaria Mosquito Ends with a Novel Telomere
    Compton, Austin; Liang, Jiangtao; Chen, Chujia; Lukyanchikova, Varvara; Qi, Yumin; Potters, Mark B.; Settlage, Robert; Miller, Dustin; Deschamps, Stephane; Mao, Chunhong; Llaca, Victor; Sharakhov, Igor V.; Tu, Zhijian Jake (Genetics Society of America, 2020-10-01)
    Chromosome level assemblies are accumulating in various taxonomic groups including mosquitoes. However, even in the few reference-quality mosquito assemblies, a significant portion of the heterochromatic regions including telomeres remain unresolved. Here we produce a de novo assembly of the New World malaria mosquito, Anopheles albimanus by integrating Oxford Nanopore sequencing, Illumina, Hi-C and optical mapping. This 172.6 Mbps female assembly, which we call AalbS3, is obtained by scaffolding polished large contigs (contig N50 = 13.7 Mbps) into three chromosomes. All chromosome arms end with telomeric repeats, which is the first in mosquito assemblies and represents a significant step toward the completion of a genome assembly. These telomeres consist of tandem repeats of a novel 30-32 bp Telomeric Repeat Unit (TRU) and are confirmed by analyzing the termini of long reads and through both chromosomal in situ hybridization and a Bal31 sensitivity assay. The AalbS3 assembly included previously uncharacterized centromeric and rDNA clusters and more than doubled the content of transposable elements and other repetitive sequences. This telomere-to-telomere assembly, although still containing gaps, represents a significant step toward resolving biologically important but previously hidden genomic components. The comparison of different scaffolding methods will also inform future efforts to obtain reference-quality genomes for other mosquito species.
  • Thumbnail Image
    Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis
    Liu, Yongmei; Reynolds, Lindsay M.; Ding, Jingzhong; Hou, Li; Lohman, Kurt; Young, Tracey; Cui, Wei; Huang, Zhiqing; Grenier, Carole; Wan, Ma; Stunnenberg, Hendrik G.; Siscovick, David; Hou, Lifang; Psaty, Bruce M.; Rich, Stephen S.; Rotter, Jerome I.; Kaufman, Joel D.; Burke, Gregory L.; Murphy, Susan F.; Jacobs, David R. Jr.; Post, Wendy; Hoeschele, Ina; Bell, Douglas A.; Herrington, David M.; Parks, John S.; Tracy, Russell P.; McCall, Charles E.; Stein, James H. (Springer Nature, 2017-08-30)
    Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data. Mediation analysis supports assumptions that ARID5B expression mediates effects of cg25953130 methylation and several cardiovascular disease risk factors on atherosclerotic burden. In lipopolysaccharide-stimulated human THP1 monocytes, ARID5B knockdown reduced expression of genes involved in atherosclerosis-related inflammatory and lipid metabolism pathways, and inhibited cell migration and phagocytosis. These data suggest that ARID5B expression, possibly regulated by an epigenetically controlled enhancer, promotes atherosclerosis by dysregulating immunometabolism towards a chronic inflammatory phenotype.
  • Thumbnail Image
    Body Weight Selection Affects Quantitative Genetic Correlated Responses in Gut Microbiota
    Meng, He; Zhang, Yan; Zhao, Lele; Zhao, Wenjing; He, Chuan; Honaker, Christa F.; Zhai, Zhengxiao; Sun, Zikui; Siegel, Paul B. (PLOS, 2014-03-07)
    The abundance of gut microbiota can be viewed as a quantitative trait, which is affected by the genetics and environment of the host. To quantify the effects of host genetics, we calculated the heritability of abundance of specific microorganisms and genetic correlations among them in the gut microbiota of two lines of chickens maintained under the same husbandry and dietary regimes. The lines, which originated from a common founder population, had undergone >50 generations of selection for high (HW) or low (LW) 56-day body weight and now differ by more than 10-fold in body weight at selection age. We identified families of Paenibacillaceae, Streptococcaceae, Helicobacteraceae, and Burkholderiaceae that had moderate heritabilities. Although there were no obvious phenotypic correlations among gut microbiota, significant genetic correlations were observed. Moreover, the effects were modified by genetic selection for body weight, which altered the quantitative genetic background of the host. Heritabilities for Bacillaceae, Flavobacteriaceae, Helicobacteraceae, Comamonadaceae, Enterococcaceae, and Streptococcaceae were moderate in LW line and little to zero in the HW line. These results suggest that loci associated with these microbiota families, while exhibiting genetic variation in LW, have been fixed in HW line. Also, long term selection for body weight has altered the genetic correlations among gut microbiota. No microbiota families had significant heritabilities in both the LW and HW lines suggesting that the presence and/or absence of a particular microbiota family either has a strong growth promoting or inhibiting effect, but not both. These results demonstrate that the quantitative genetics of the host have considerable influence on the gut microbiota.