Zoonotic and Non-Zoonotic Diseases in Relation to Human Personality and Societal Values: Support for the Parasite-Stress Model

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Randy Thornhill

2010-04-01

Full Text Available The parasite-stress model of human sociality proposes that humans' ontogenetic experiences with infectious diseases as well as their evolutionary historical interactions with these diseases exert causal influences on human psychology and social behavior. This model has been supported by cross-national relationships between parasite prevalence and human personality traits, and between parasite prevalence and societal values. Importantly, the parasite-stress model emphasizes the causal role of non-zoonotic parasites (which have the capacity for human-to-human transmission, rather than zoonotic parasites (which do not, but previous studies failed to distinguish between these conceptually distinct categories. The present investigation directly tested the differential predictive effects of zoonotic and non-zoonotic (both human-specific and multihost parasite prevalence on personality traits and societal values. Supporting the parasite-stress model, cross-national differences in personality traits (unrestricted sexuality, extraversion, openness to experiences and in societal values (individualism, collectivism, gender equality, democratization are predicted specifically by non-zoonotic parasite prevalence.

Prediction of Complex Human Traits Using the Genomic Best Linear Unbiased Predictor

DEFF Research Database (Denmark)

de los Campos, Gustavo; Vazquez, Ana I; Fernando, Rohan

2013-01-01

Despite important advances from Genome Wide Association Studies (GWAS), for most complex human traits and diseases, a sizable proportion of genetic variance remains unexplained and prediction accuracy (PA) is usually low. Evidence suggests that PA can be improved using Whole-Genome Regression (WGR......) models where phenotypes are regressed on hundreds of thousands of variants simultaneously. The Genomic Best Linear Unbiased Prediction G-BLUP, a ridge-regression type method) is a commonly used WGR method and has shown good predictive performance when applied to plant and animal breeding populations....... However, breeding and human populations differ greatly in a number of factors that can affect the predictive performance of G-BLUP. Using theory, simulations, and real data analysis, we study the erformance of G-BLUP when applied to data from related and unrelated human subjects. Under perfect linkage...

Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

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Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

cis-Acting Complex-Trait-Associated lincRNA Expression Correlates with Modulation of Chromosomal Architecture

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Jennifer Yihong Tan

2017-02-01

Full Text Available Summary: Intergenic long noncoding RNAs (lincRNAs are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits. : Tan et al. identify and characterize 69 human complex trait/disease-associated lincRNAs in LCLs. They show that these loci are often associated with cis-regulation of gene expression and tend to be localized at TAD boundaries, suggesting that these lincRNAs may influence chromosomal architecture. Keywords: intergenic long noncoding RNA, lincRNA, GWAS, expression quantitative trait loci, eQTL, complex trait and disease, enhancer, cis-regulation, topologically associated domains, TAD

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

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Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

2018-03-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Has Human Evolution Stopped?

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Alan R. Templeton

2010-07-01

Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

Neuropsychological and emotional correlates of personality traits in Parkinson's disease.

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Koerts, Janneke; Tucha, Lara; Leenders, Klaus L; Tucha, Oliver

2013-01-01

Parkinson's disease (PD) is, apart from the well-known motor symptoms, also characterized by neuropsychological and emotional disturbances. However, patients also often present with a personality profile of low Novelty Seeking and high Harm Avoidance. This profile can be identified as the disease emerges, which raises the question whether these traits correlate with more fundamental neuropsychological and emotional disturbances. This study determined the neuropsychological and emotional correlates of Novelty Seeking, Harm Avoidance and two other personality traits that are often considered in PD, i.e. Reward Dependence and Persistence. Forty-three patients and 25 healthy participants were assessed with the Temperament and Character Inventory, a symptoms of depression questionnaire and neuropsychological tests. PD patients showed a higher Harm Avoidance than healthy participants, which was predicted by symptoms of depression. Groups did not differ regarding Novelty Seeking, Reward Dependence and Persistence. While cognitive flexibility was a predictor of Reward Dependence, Persistence was predicted by divergent thinking and inhibition. Novelty Seeking was not predicted by cognition or emotion. In conclusion, cognition and emotion are selectively related to personality traits in PD. Whereas Harm Avoidance covaries with emotional symptoms, Persistence and Reward Dependence are related to cognition. Alterations in personality, cognition and emotion in PD are thus not independent from each other.

Evidence for genetic variation in human mate preferences for sexually dimorphic physical traits

NARCIS (Netherlands)

Verweij, K.J.H.; Burri, A.V.; Zietsch, B.P.

2012-01-01

Intersexual selection has been proposed as an important force in shaping a number of morphological traits that differ between human populations and/or between the sexes. Important to these accounts is the source of mate preferences for such traits, but this has not been investigated. In a large

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

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Chande, Aroon T; Wang, Lu; Rishishwar, Lavanya; Conley, Andrew B; Norris, Emily T; Valderrama-Aguirre, Augusto; Jordan, I King

2018-05-18

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.

A genetic basis for mechanosensory traits in humans.

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Henning Frenzel

Full Text Available In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.

Genome-wide quantitative trait loci mapping of the human cerebrospinal fluid proteome.

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Sasayama, Daimei; Hattori, Kotaro; Ogawa, Shintaro; Yokota, Yuuki; Matsumura, Ryo; Teraishi, Toshiya; Hori, Hiroaki; Ota, Miho; Yoshida, Sumiko; Kunugi, Hiroshi

2017-01-01

Cerebrospinal fluid (CSF) is virtually the only one accessible source of proteins derived from the central nervous system (CNS) of living humans and possibly reflects the pathophysiology of a variety of neuropsychiatric diseases. However, little is known regarding the genetic basis of variation in protein levels of human CSF. We examined CSF levels of 1,126 proteins in 133 subjects and performed a genome-wide association analysis of 514,227 single nucleotide polymorphisms (SNPs) to detect protein quantitative trait loci (pQTLs). To be conservative, Spearman's correlation was used to identify an association between genotypes of SNPs and protein levels. A total of 421 cis and 25 trans SNP-protein pairs were significantly correlated at a false discovery rate (FDR) of less than 0.01 (nominal P genome-wide association studies. The present findings suggest that genetic variations play an important role in the regulation of protein expression in the CNS. The obtained database may serve as a valuable resource to understand the genetic bases for CNS protein expression pattern in humans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sex, kings and serial killers and other group-selected human traits.

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Bowles, J T

2000-06-01

(Note: This unorthodox paper contains the first argument for heart disease being a programmed age change and promoted by the dramatic, post age-40 increases in the hormones FSH and hCG seen in some individuals.) A recent issue of Science suggests that the evolutionary purpose of sex is unknown. Surviving to adulthood implies a valuable gene combination which is destroyed by sexual recombination. This should be detrimental to offspring. PROPOSED: Sex is group-selected in prey to allow coalescence of beneficial, and disposal of detrimental, mutations in single individuals enabling rapid adaptation to novel predation. Group selection is a universal force driven by local inter-species (not intra-species) competition. Aging, metabolism, litter size, and fixed body size are directly linked. Sexual recombination and chromosomes destroy gene linkage and exist because mutations are usually detrimental, rarely positive, and occur in linked groups. In unevolving environments, sex is selected against and asexuality emerges. Periodic evolution of novel predators, like man, can explain the 'punctuated equilibria' fossil record. Genes inhibited by methylation or chromatin condensation, expressed at older ages in predation-minimized environments, allow for group selection. Stress increases mutation rates and beneficial mutation likelihood. Females select bigger, brighter, louder, or stronger males that can survive predator attention. Size approximates age and thus predator encounters; male traits represent predation-survival potential. Human male traits include, balding, acne, beard-length, wrinkling, graying, nose/ear growth. Progeria accelerates development of most male traits. Domination of groups by single males allows rapid predation-defense evolution: adolescent males are expelled, brave the wild, and expel another group's male to mate. If expelled and dominant males are culled by predation, males reaching puberty first will reproduce. Hormonal acceleration of puberty

Evidence for genetic variation in human mate preferences for sexually dimorphic physical traits.

Directory of Open Access Journals (Sweden)

Karin J H Verweij

Full Text Available Intersexual selection has been proposed as an important force in shaping a number of morphological traits that differ between human populations and/or between the sexes. Important to these accounts is the source of mate preferences for such traits, but this has not been investigated. In a large sample of twins, we assess forced-choice, dichotomous mate preferences for height, skin colour, hair colour and length, chest hair, facial hair, and breast size. Across the traits, identical twins reported more similar preferences than nonidentical twins, suggesting genetic effects. However, the relative magnitude of estimated genetic and environmental effects differed greatly and significantly between different trait preferences, with heritability estimates ranging from zero to 57%.

Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

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Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

2014-01-01

Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

Microgeographic variation in locomotor traits among lizards in a human-built environment

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Colin Donihue

2016-03-01

Full Text Available Microgeographic variation in fitness-relevant traits may be more common than previously appreciated. The fitness of many vertebrates is directly related to their locomotor capacity, a whole-organism trait integrating behavior, morphology, and physiology. Because locomotion is inextricably related to context, I hypothesized that it might vary with habitat structure in a wide-ranging lizard, Podarcis erhardii, found in the Greek Cyclade Islands. I compared lizard populations living on human-built rock walls, a novel habitat with complex vertical structure, with nearby lizard populations that are naive to human-built infrastructure and live in flat, loose-substrate habitat. I tested for differences in morphology, behavior, and performance. Lizards from built sites were larger and had significantly (and relatively longer forelimbs and hindlimbs. The differences in hindlimb morphology were especially pronounced for distal components—the foot and longest toe. These morphologies facilitated a significant behavioral shift in jumping propensity across a rocky experimental substrate. I found no difference in maximum velocity between these populations; however, females originating from wall sites potentially accelerated faster over the rocky experimental substrate. The variation between these closely neighboring populations suggests that the lizards inhabiting walls have experienced a suite of trait changes enabling them to take advantage of the novel habitat structure created by humans.

A population genetic interpretation of GWAS findings for human quantitative traits

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Bullaughey, Kevin; Hudson, Richard R.; Sella, Guy

2018-01-01

Human genome-wide association studies (GWASs) are revealing the genetic architecture of anthropomorphic and biomedical traits, i.e., the frequencies and effect sizes of variants that contribute to heritable variation in a trait. To interpret these findings, we need to understand how genetic architecture is shaped by basic population genetics processes—notably, by mutation, natural selection, and genetic drift. Because many quantitative traits are subject to stabilizing selection and because genetic variation that affects one trait often affects many others, we model the genetic architecture of a focal trait that arises under stabilizing selection in a multidimensional trait space. We solve the model for the phenotypic distribution and allelic dynamics at steady state and derive robust, closed-form solutions for summary statistics of the genetic architecture. Our results provide a simple interpretation for missing heritability and why it varies among traits. They predict that the distribution of variances contributed by loci identified in GWASs is well approximated by a simple functional form that depends on a single parameter: the expected contribution to genetic variance of a strongly selected site affecting the trait. We test this prediction against the results of GWASs for height and body mass index (BMI) and find that it fits the data well, allowing us to make inferences about the degree of pleiotropy and mutational target size for these traits. Our findings help to explain why the GWAS for height explains more of the heritable variance than the similarly sized GWAS for BMI and to predict the increase in explained heritability with study sample size. Considering the demographic history of European populations, in which these GWASs were performed, we further find that most of the associations they identified likely involve mutations that arose shortly before or during the Out-of-Africa bottleneck at sites with selection coefficients around s = 10−3. PMID

Prevalence of sexual dimorphism in mammalian phenotypic traits

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Karp, Natasha A.; Mason, Jeremy; Beaudet, Arthur L.; Benjamini, Yoav; Bower, Lynette; Braun, Robert E.; Brown, Steve D.M.; Chesler, Elissa J.; Dickinson, Mary E.; Flenniken, Ann M.; Fuchs, Helmut; Angelis, Martin Hrabe de; Gao, Xiang; Guo, Shiying; Greenaway, Simon; Heller, Ruth; Herault, Yann; Justice, Monica J.; Kurbatova, Natalja; Lelliott, Christopher J.; Lloyd, K.C. Kent; Mallon, Ann-Marie; Mank, Judith E.; Masuya, Hiroshi; McKerlie, Colin; Meehan, Terrence F.; Mott, Richard F.; Murray, Stephen A.; Parkinson, Helen; Ramirez-Solis, Ramiro; Santos, Luis; Seavitt, John R.; Smedley, Damian; Sorg, Tania; Speak, Anneliese O.; Steel, Karen P.; Svenson, Karen L.; Obata, Yuichi; Suzuki, Tomohiro; Tamura, Masaru; Kaneda, Hideki; Furuse, Tamio; Kobayashi, Kimio; Miura, Ikuo; Yamada, Ikuko; Tanaka, Nobuhiko; Yoshiki, Atsushi; Ayabe, Shinya; Clary, David A.; Tolentino, Heather A.; Schuchbauer, Michael A.; Tolentino, Todd; Aprile, Joseph Anthony; Pedroia, Sheryl M.; Kelsey, Lois; Vukobradovic, Igor; Berberovic, Zorana; Owen, Celeste; Qu, Dawei; Guo, Ruolin; Newbigging, Susan; Morikawa, Lily; Law, Napoleon; Shang, Xueyuan; Feugas, Patricia; Wang, Yanchun; Eskandarian, Mohammad; Zhu, Yingchun; Nutter, Lauryl M. J.; Penton, Patricia; Laurin, Valerie; Clarke, Shannon; Lan, Qing; Sohel, Khondoker; Miller, David; Clark, Greg; Hunter, Jane; Cabezas, Jorge; Bubshait, Mohammed; Carroll, Tracy; Tondat, Sandra; MacMaster, Suzanne; Pereira, Monica; Gertsenstein, Marina; Danisment, Ozge; Jacob, Elsa; Creighton, Amie; Sleep, Gillian; Clark, James; Teboul, Lydia; Fray, Martin; Caulder, Adam; Loeffler, Jorik; Codner, Gemma; Cleak, James; Johnson, Sara; Szoke-Kovacs, Zsombor; Radage, Adam; Maritati, Marina; Mianne, Joffrey; Gardiner, Wendy; Allen, Susan; Cater, Heather; Stewart, Michelle; Keskivali-Bond, Piia; Sinclair, Caroline; Brown, Ellen; Doe, Brendan; Wardle-Jones, Hannah; Grau, Evelyn; Griggs, Nicola; Woods, Mike; Kundi, Helen; Griffiths, Mark N. D.; Kipp, Christian; Melvin, David G.; Raj, Navis P. S.; Holroyd, Simon A.; Gannon, David J.; Alcantara, Rafael; Galli, Antonella; Hooks, Yvette E.; Tudor, Catherine L.; Green, Angela L.; Kussy, Fiona L.; Tuck, Elizabeth J.; Siragher, Emma J.; Maguire, Simon A.; Lafont, David T.; Vancollie, Valerie E.; Pearson, Selina A.; Gates, Amy S.; Sanderson, Mark; Shannon, Carl; Anthony, Lauren F. E.; Sumowski, Maksymilian T.; McLaren, Robbie S. B.; Swiatkowska, Agnieszka; Isherwood, Christopher M.; Cambridge, Emma L; Wilson, Heather M.; Caetano, Susana S.; Mazzeo, Cecilia Icoresi; Dabrowska, Monika H.; Lillistone, Charlotte; Estabel, Jeanne; Maguire, Anna Karin B.; Roberson, Laura-Anne; Pavlovic, Guillaume; Birling, Marie-Christine; Marie, Wattenhofer-Donze; Jacquot, Sylvie; Ayadi, Abdel; Ali-Hadji, Dalila; Charles, Philippe; André, Philippe; Le Marchand, Elise; El Amri, Amal; Vasseur, Laurent; Aguilar-Pimentel, Antonio; Becker, Lore; Treise, Irina; Moreth, Kristin; Stoeger, Tobias; Amarie, Oana V.; Neff, Frauke; Wurst, Wolfgang; Bekeredjian, Raffi; Ollert, Markus; Klopstock, Thomas; Calzada-Wack, Julia; Marschall, Susan; Brommage, Robert; Steinkamp, Ralph; Lengger, Christoph; Östereicher, Manuela A.; Maier, Holger; Stoeger, Claudia; Leuchtenberger, Stefanie; Yildrim, AliÖ; Garrett, Lillian; Hölter, Sabine M; Zimprich, Annemarie; Seisenberger, Claudia; Bürger, Antje; Graw, Jochen; Eickelberg, Oliver; Zimmer, Andreas; Wolf, Eckhard; Busch, Dirk H; Klingenspor, Martin; Schmidt-Weber, Carsten; Gailus-Durner, Valérie; Beckers, Johannes; Rathkolb, Birgit; Rozman, Jan; Wakana, Shigeharu; West, David; Wells, Sara; Westerberg, Henrik; Yaacoby, Shay; White, Jacqueline K.

2017-01-01

The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans. PMID:28650954

Virulence traits and antibiotic resistance among enterococci isolated from dogs with periodontal disease.

Science.gov (United States)

Oliveira, Manuela; Tavares, Marta; Gomes, Diana; Touret, Tiago; São Braz, Berta; Tavares, Luís; Semedo-Lemsaddek, Teresa

2016-06-01

Periodontal disease - PD - is one of the most widespread diseases in dogs, but the role of this odontogenic infection in the dissemination of pathogenic bacteria present in the oral mucosa to other animals or pet owners is understudied. Trying to unveil the putative pathogenicity of enterococci present in the gums of dogs diagnosed with PD, thirty-two animals were investigated during routine visits to a private veterinary clinic. Seventy-one enterococci were recovered and characterized regarding species, genomic variability, virulence traits, antimicrobial resistance and biofilm-forming ability. Isolates were mainly identified as Enterococcus faecalis, with the large majority (95%) being able to produce biofilm. Regarding antibiotic resistance, all dog-enterococci were susceptible to ampicillin, amoxicillin/clavulanate, gentamicin-120, imipenem and vancomycin; while distinct levels of resistance were observed for chloramphenicol (10%), erythromycin (20%), streptomycin-300 (35%) and tetracycline (95%). For virulence traits incidence levels of 35% were observed for β-hemolysis and 25% for cylA, 25% for gelatinase and 35% for gelE; 85% harbor efaAfs and ebpABC; while ace, agg and esp are present respectively in 50, 30 and 10% of the dog-enterococci; efaAfm and acm were detected in all the Enterococcus faecium. Overall, the widespread prevalence of PD in dogs, associated with the close contact between companion animals, other animals and humans, may act as source for the dissemination of opportunistic pathogenic bacteria. Hence, aforementioned data on virulence and resistance features, emphasizes the need for active surveillance measures, such as the diagnose of PD in companion animals during routine visits to the veterinary clinic. Copyright © 2016 Elsevier Ltd. All rights reserved.

How scientists perceive the evolutionary origin of human traits: Results of a survey study.

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Tuomisto, Hanna; Tuomisto, Matleena; Tuomisto, Jouni T

2018-03-01

Various hypotheses have been proposed for why the traits distinguishing humans from other primates originally evolved, and any given trait may have been explained both as an adaptation to different environments and as a result of demands from social organization or sexual selection. To find out how popular the different explanations are among scientists, we carried out an online survey among authors of recent scientific papers in journals covering relevant fields of science (paleoanthropology, paleontology, ecology, evolution, human biology). Some of the hypotheses were clearly more popular among the 1,266 respondents than others, but none was universally accepted or rejected. Even the most popular of the hypotheses were assessed "very likely" by 70% of the respondents. An ordination of the hypotheses identified two strong gradients. Along one gradient, the hypotheses were sorted by their popularity, measured by the average credibility score given by the respondents. The second gradient separated all hypotheses postulating adaptation to swimming or diving into their own group. The average credibility scores given for different subgroups of the hypotheses were not related to respondent's age or number of publications authored. However, (paleo)anthropologists were more critical of all hypotheses, and much more critical of the water-related ones, than were respondents representing other fields of expertise. Although most respondents did not find the water-related hypotheses likely, only a small minority found them unscientific. The most popular hypotheses were based on inherent drivers; that is, they assumed the evolution of a trait to have been triggered by the prior emergence of another human-specific behavioral or morphological trait, but opinions differed as to which of the traits came first.

Frequency variations of discrete cranial traits in major human populations. III. Hyperostotic variations.

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Hanihara, T; Ishida, H

2001-09-01

Seven discrete cranial traits usually categorised as hyperostotic characters, the medial palatine canal, hypoglossal canal bridging, precondylar tubercle, condylus tertius, jugular foramen bridging, auditory exostosis, and mylohyoid bridging were investigated in 81 major human population samples from around the world. Significant asymmetric occurrences of the bilateral traits were detected in the medial palatine canal and jugular foramen bridging in several samples. Significant intertrait associations were found between some pairs of the traits, but not consistently across the large geographical samples. The auditory exostosis showed a predominant occurrence in males. With the exception of the auditory exostosis and mylohyoid bridging in a few samples, significant sex differences were slight. The frequency distributions of the traits (except for the auditory exostosis) showed some interregional clinality and intraregional discontinuity, suggesting that genetic drift could have contributed to the observed pattern of variation.

Lipidomics of human brain aging and Alzheimer's disease pathology.

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Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2015-01-01

Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

Mice, humans and haplotypes--the hunt for disease genes in SLE.

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Rigby, R J; Fernando, M M A; Vyse, T J

2006-09-01

Defining the polymorphisms that contribute to the development of complex genetic disease traits is a challenging, although increasingly tractable problem. Historically, the technical difficulties in conducting association studies across the entire human genome are such that murine models have been used to generate candidate genes for analysis in human complex diseases, such as SLE. In this article we discuss the advantages and disadvantages of this approach and specifically address some assumptions made in the transition from studying one species to another, using lupus as an example. These issues include differences in genetic structure and genetic organisation which are a reflection on the population history. Clearly there are major differences in the histories of the human population and inbred laboratory strains of mice. Both human and murine genomes do exhibit structure at the genetic level. That is to say, they comprise haplotypes which are genomic regions that carry runs of polymorphisms that are not independently inherited. Haplotypes therefore reduce the number of combinations of the polymorphisms in the DNA in that region and facilitate the identification of disease susceptibility genes in both mice and humans. There are now novel means of generating candidate genes in SLE using mutagenesis (with ENU) in mice and identifying mice that generate antinuclear autoimmunity. In addition, murine models still provide a valuable means of exploring the functional consequences of genetic variation. However, advances in technology are such that human geneticists can now screen large fractions of the human genome for disease associations using microchip technologies that provide information on upwards of 100,000 different polymorphisms. These approaches are aimed at identifying haplotypes that carry disease susceptibility mutations and rely less on the generation of candidate genes.

Survey of the Heritability and Sparse Architecture of Gene Expression Traits across Human Tissues.

Science.gov (United States)

Wheeler, Heather E; Shah, Kaanan P; Brenner, Jonathon; Garcia, Tzintzuni; Aquino-Michaels, Keston; Cox, Nancy J; Nicolae, Dan L; Im, Hae Kyung

2016-11-01

Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR Decomposition (OTD) approach. Through a series of simulations we show that the cross-tissue and tissue-specific components are identifiable via OTD. Heritability and sparsity estimates of these derived expression phenotypes show similar characteristics to the original traits. Consistent properties relative to prior GTEx multi-tissue analysis results suggest that these traits reflect the expected biology. Finally, we apply this knowledge to develop prediction models of gene expression traits for all tissues. The prediction models, heritability, and prediction performance R2 for original and decomposed expression phenotypes are made publicly available (https://github.com/hakyimlab/PrediXcan).

Evolutionary change in physiological phenotypes along the human lineage.

Science.gov (United States)

Vining, Alexander Q; Nunn, Charles L

2016-01-01

Research in evolutionary medicine provides many examples of how evolution has shaped human susceptibility to disease. Traits undergoing rapid evolutionary change may result in associated costs or reduce the energy available to other traits. We hypothesize that humans have experienced more such changes than other primates as a result of major evolutionary change along the human lineage. We investigated 41 physiological traits across 50 primate species to identify traits that have undergone marked evolutionary change along the human lineage. We analysed the data using two Bayesian phylogenetic comparative methods. One approach models trait covariation in non-human primates and predicts human phenotypes to identify whether humans are evolutionary outliers. The other approach models adaptive shifts under an Ornstein-Uhlenbeck model of evolution to assess whether inferred shifts are more common on the human branch than on other primate lineages. We identified four traits with strong evidence for an evolutionary increase on the human lineage (amylase, haematocrit, phosphorus and monocytes) and one trait with strong evidence for decrease (neutrophilic bands). Humans exhibited more cases of distinct evolutionary change than other primates. Human physiology has undergone increased evolutionary change compared to other primates. Long distance running may have contributed to increases in haematocrit and mean corpuscular haemoglobin concentration, while dietary changes are likely related to increases in amylase. In accordance with the pathogen load hypothesis, human monocyte levels were increased, but many other immune-related measures were not. Determining the mechanisms underlying conspicuous evolutionary change in these traits may provide new insights into human disease. The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Kin groups and trait groups: population structure and epidemic disease selection.

Science.gov (United States)

Fix, A G

1984-10-01

A Monte Carlo simulation based on the population structure of a small-scale human population, the Semai Senoi of Malaysia, has been developed to study the combined effects of group, kin, and individual selection. The population structure resembles D.S. Wilson's structured deme model in that local breeding populations (Semai settlements) are subdivided into trait groups (hamlets) that may be kin-structured and are not themselves demes. Additionally, settlement breeding populations are connected by two-dimensional stepping-stone migration approaching 30% per generation. Group and kin-structured group selection occur among hamlets the survivors of which then disperse to breed within the settlement population. Genetic drift is modeled by the process of hamlet formation; individual selection as a deterministic process, and stepping-stone migration as either random or kin-structured migrant groups. The mechanism for group selection is epidemics of infectious disease that can wipe out small hamlets particularly if most adults become sick and social life collapses. Genetic resistance to a disease is an individual attribute; however, hamlet groups with several resistant adults are less likely to disintegrate and experience high social mortality. A specific human gene, hemoglobin E, which confers resistance to malaria, is studied as an example of the process. The results of the simulations show that high genetic variance among hamlet groups may be generated by moderate degrees of kin-structuring. This strong microdifferentiation provides the potential for group selection. The effect of group selection in this case is rapid increase in gene frequencies among the total set of populations. In fact, group selection in concert with individual selection produced a faster rate of gene frequency increase among a set of 25 populations than the rate within a single unstructured population subject to deterministic individual selection. Such rapid evolution with plausible rates of

Methods for meta-analysis of multiple traits using GWAS summary statistics.

Science.gov (United States)

Ray, Debashree; Boehnke, Michael

2018-03-01

. Evidence from larger studies suggest that the variants additionally detected by our test are, indeed, associated with lipid levels in humans. In summary, metaUSAT can provide novel insights into the genetic architecture of a common disease or traits. © 2017 WILEY PERIODICALS, INC.

Humanized mouse models: Application to human diseases.

Science.gov (United States)

Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

Science.gov (United States)

Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

2017-09-15

Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

The association of genotype-based inbreeding coefficient with a range of physical and psychological human traits.

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Karin J H Verweij

Full Text Available Across animal species, offspring of closely related mates exhibit lower fitness, a phenomenon called inbreeding depression. Inbreeding depression in humans is less well understood because mating between close relatives is generally rare and stigmatised, confounding investigation of its effect on fitness-relevant traits. Recently, the availability of high-density genotype data has enabled quantification of variation in distant inbreeding in 'outbred' human populations, but the low variance of inbreeding detected from genetic data in most outbred populations means large samples are required to test effects, and only a few traits have yet been studied. However, it is likely that isolated populations, or those with a small effective population size, have higher variation in inbreeding and therefore require smaller sample sizes to detect inbreeding effects. With a small effective population size and low immigration, Northern Finland is such a population. We make use of a sample of ∼5,500 'unrelated' individuals in the Northern Finnish Birth Cohort 1966 with known genotypes and measured phenotypes across a range of fitness-relevant physical and psychological traits, including birth length and adult height, body mass index (BMI, waist-to-hip ratio, blood pressure, heart rate, grip strength, educational attainment, income, marital status, handedness, health, and schizotypal features. We find significant associations in the predicted direction between individuals' inbreeding coefficient (measured by proportion of the genome in runs of homozygosity and eight of the 18 traits investigated, significantly more than the one or two expected by chance. These results are consistent with inbreeding depression effects on a range of human traits, but further research is needed to replicate and test alternative explanations for these effects.

Genetic parameters for energy balance, fat /protein ratio, body condition score and disease traits in German Holstein cows.

Science.gov (United States)

Buttchereit, N; Stamer, E; Junge, W; Thaller, G

2012-08-01

Various health problems in dairy cows have been related to the magnitude and duration of the energy deficit post partum. Energy balance indicator traits like fat/protein ratio in milk and body condition score could be used in selection programmes to help predicting breeding values for health traits, but currently there is a lack of appropriate genetic parameters. Therefore, genetic correlations among energy balance, fat/protein ratio, and body condition score, and mastitis, claw and leg diseases, and metabolic disorders were estimated using linear and threshold models on data from 1693 primiparous cows recorded within the first 180 days in milk. Average daily energy balance, milk fat/protein ratio and body condition score were 8 MJ NEL, 1.13 and 2.94, respectively. Disease frequencies (% cows with at least one case) were 24.6% for mastitis, 9.7% for metabolic disorders and 28.2% for claw and leg diseases. Heritability estimates were 0.06, 0.30 and 0.34 for energy balance, fat/protein ratio and body condition score, respectively. For the disease traits, heritabilities ranged between 0.04 and 0.15. The genetic correlations were, in general, associated with large standard errors, but, although not significant, the results suggest that an improvement of overall health can be expected if energy balance traits are included into future breeding programmes. A low fat/protein ratio might serve as an indicator for metabolic stability and health of claw and legs. Between body condition and mastitis, a significant negative correlation of -0.40 was estimated. The study provides a new insight into the role energy balance traits can play as auxiliary traits for robustness of dairy cows. It was concluded that both, fat/protein ratio and body condition score, are potential variables to describe how well cows can adapt to the challenge of early lactation. However, the genetic parameters should be re-estimated on a more comprehensive data set. © 2011 Blackwell Verlag GmbH.

Trait impulsivity is associated with the risk of falls in Parkinson's disease.

Science.gov (United States)

Smulders, Katrijn; Esselink, Rianne A; Cools, Roshan; Bloem, Bastiaan R

2014-01-01

Impulsivity is a "tendency to act prematurely without foresight." Clinical experience suggests that such impulsive behavior can impact on the fall risk in Parkinson's disease (PD), but this has never been tested. We investigated whether trait impulsivity is related to fall risk in a large cohort of PD patients. We also investigated whether trait impulsivity affects the fall risk differently for patients with more or less postural instability and gait disability (PIGD). 388 patients with PD (H&Y ≤ 3) completed the Barratt Impulsiveness Scale (BIS-11, higher scores indicating greater impulsivity) to assess trait impulsivity, including three subscales: motor impulsivity (e.g. "I do things without thinking"), attentional impulsivity (e.g. "I concentrate easily") and non-planning (e.g. "I plan tasks carefully"). Falls were registered prospectively for 6 months. Patients classified as non-fallers (0 falls, n = 237) were compared to recurrent PD fallers (>1 fall, n = 78). Total impulsivity scores were higher for recurrent fallers (59.5) compared to non-fallers (56.8; p = .012). This effect was predominantly driven by higher scores on the subscale for attentional impulsivity (p = .003). The difference in attentional impulsivity was independent of gender, disease severity, dopaminergic medication, and cognitive function. Motor and non-planning impulsivity did not differ between recurrent fallers and non-fallers. There was no evidence that impulsivity modulated the association between PIGD and fall risk. This is the first evidence that impulsivity, in particular in the attentional domain, is related to fall risk in PD.

Association mapping of seed and disease resistance traits in Theobroma cacao L.

Science.gov (United States)

Motilal, Lambert A; Zhang, Dapeng; Mischke, Sue; Meinhardt, Lyndel W; Boccara, Michel; Fouet, Olivier; Lanaud, Claire; Umaharan, Pathmanathan

2016-12-01

Microsatellite and single nucleotide polymorphism markers that could be used in marker assisted breeding of cacao were identified for number of filled seeds, black pod resistance and witches' broom disease resistance. An association mapping approach was employed to identify markers for seed number and resistance to black pod and witches' broom disease (WBD) in cacao (Theobroma cacao L.). Ninety-five microsatellites (SSRs) and 775 single nucleotide polymorphisms (SNPs) were assessed on 483 unique trees in the International Cocoa Genebank Trinidad (ICGT). Linkage disequilibrium (LD) and association mapping studies were conducted to identify markers to tag the phenotypic traits. Decay of LD occurred over an average 9.3 cM for chromosomes 1-9 and 2.5 cM for chromosome 10. Marker/trait associations were generally identified based on general linear models (GLMs) that incorporated principal components from molecular information on relatedness factor. Seven markers (mTcCIR 8, 66, 126, 212; TcSNP368, 697, 1370) on chromosomes 1 and 9 were identified for number of filled seeds (NSEED). A single marker was found for black pod resistance (mTcCIR280) on chromosome 3, whereas six markers on chromosomes 4, 5, 6, 8, and 10 were detected for WBD (mTcCIR91, 183; TcSNP375, 720, 1230 and 1374). It is expected that this association mapping study in cacao would contribute to the knowledge of the genetic determinism of cocoa traits and that the markers identified herein would prove useful in marker assisted breeding of cacao.

Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

Energy Technology Data Exchange (ETDEWEB)

Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

1996-09-01

Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

Personality traits and the risk for Parkinson disease: a prospective study.

Science.gov (United States)

Sieurin, Johanna; Gustavsson, Petter; Weibull, Caroline Elise; Feldman, Adina Leiah; Petzinger, Giselle Maria; Gatz, Margaret; Pedersen, Nancy Lee; Wirdefeldt, Karin

2016-02-01

In this study, we explored the association between the personality traits, neuroticism and introversion, and risk of Parkinson disease (PD). A population-based cohort study was conducted using questionnaire data from the Swedish Twin Registry for twins born 1926-1958 (n > 29,000). Personality traits were assessed in 1973 by a short form of Eysenck's Personality Inventory. The cohort was followed from 1974 to 2012 through Swedish patient and cause of death registers for PD ascertainment. Cox proportional hazards regression was used to estimate subsequent risk of PD, adjusting for attained age, sex and smoking. A mediation analysis was performed to further explore the role of smoking in the relationship between personality trait and PD. Confounding by familial factors was explored using a within-pair analysis. During a mean follow-up time of 36.8 years, 197 incident PD cases were identified. Both neuroticism and introversion were associated with an increased risk of PD after adjustment. Smoking was a significant mediator in the relationship between personality traits and PD that partly accounted for the effect of introversion, whereas it acted as a suppressor for the effect of neuroticism on PD risk. In the within-pair analyses, associations for neuroticism and introversion were attenuated. In conclusion, our study provides evidence that neuroticism is associated with an increased risk of PD that is in part suppressed by smoking. There was a weak association between introversion and PD and this effect was at least partly mediated through smoking. The observed effects may partly be explained by familial factors shared by twins.

Human Environmental Disease Network

DEFF Research Database (Denmark)

Taboureau, Olivier; Audouze, Karine

2017-01-01

During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

A knowledge based approach to matching human neurodegenerative disease and animal models

Directory of Open Access Journals (Sweden)

Maryann E Martone

2013-05-01

Full Text Available Neurodegenerative diseases present a wide and complex range of biological and clinical features. Animal models are key to translational research, yet typically only exhibit a subset of disease features rather than being precise replicas of the disease. Consequently, connecting animal to human conditions using direct data-mining strategies has proven challenging, particularly for diseases of the nervous system, with its complicated anatomy and physiology. To address this challenge we have explored the use of ontologies to create formal descriptions of structural phenotypes across scales that are machine processable and amenable to logical inference. As proof of concept, we built a Neurodegenerative Disease Phenotype Ontology and an associated Phenotype Knowledge Base using an entity-quality model that incorporates descriptions for both human disease phenotypes and those of animal models. Entities are drawn from community ontologies made available through the Neuroscience Information Framework and qualities are drawn from the Phenotype and Trait Ontology. We generated ~1200 structured phenotype statements describing structural alterations at the subcellular, cellular and gross anatomical levels observed in 11 human neurodegenerative conditions and associated animal models. PhenoSim, an open source tool for comparing phenotypes, was used to issue a series of competency questions to compare individual phenotypes among organisms and to determine which animal models recapitulate phenotypic aspects of the human disease in aggregate. Overall, the system was able to use relationships within the ontology to bridge phenotypes across scales, returning non-trivial matches based on common subsumers that were meaningful to a neuroscientist with an advanced knowledge of neuroanatomy. The system can be used both to compare individual phenotypes and also phenotypes in aggregate. This proof of concept suggests that expressing complex phenotypes using formal

Testing the prediction from sexual selection of a positive genetic correlation between human mate preferences and corresponding traits

NARCIS (Netherlands)

Verweij, K.J.H.; Burri, A.V.; Zietsch, B.P.

2014-01-01

Sexual selection can cause evolution in traits that affect mating success, and it has thus been implicated in the evolution of human physical and behavioural traits that influence attractiveness. We use a large sample of identical and nonidentical female twins to test the prediction from mate choice

Genome-wide association study identifies candidate genes for male fertility traits in humans.

Science.gov (United States)

Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

2012-06-08

Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Exploring personality traits related to dopamine D2/3 receptor availability in striatal subregions of humans.

Science.gov (United States)

Caravaggio, Fernando; Fervaha, Gagan; Chung, Jun Ku; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

2016-04-01

While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [(11)C]-raclopride in 30 healthy humans. Based on previous the literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Alpha band frequency differences between low-trait and high-trait anxious individuals.

Science.gov (United States)

Ward, Richard T; Smith, Shelby L; Kraus, Brian T; Allen, Anna V; Moses, Michael A; Simon-Dack, Stephanie L

2018-01-17

Trait anxiety has been shown to cause significant impairments on attentional tasks. Current research has identified alpha band frequency differences between low-trait and high-trait anxious individuals. Here, we further investigated the underlying alpha band frequency differences between low-trait and high-trait anxious individuals during their resting state and the completion of an inhibition executive functioning task. Using human participants and quantitative electroencephalographic recordings, we measured alpha band frequency in individuals both high and low in trait anxiety during their resting state, and while they completed an Eriksen Flanker Task. Results indicated that high-trait anxious individuals exhibit a desynchronization in alpha band frequency from a resting state to when they complete the Eriksen Flanker Task. This suggests that high-trait anxious individuals maintain fewer attentional resources at rest and must martial resources for task performance as compared with low-trait anxious individuals, who appear to maintain stable cognitive resources between rest and task performance. These findings add to the cognitive neuroscience literature surrounding the role of alpha band frequency in low-trait and high-trait anxious individuals.

Large-scale in silico mapping of complex quantitative traits in inbred mice.

Directory of Open Access Journals (Sweden)

Pengyuan Liu

2007-07-01

Full Text Available Understanding the genetic basis of common disease and disease-related quantitative traits will aid in the development of diagnostics and therapeutics. The processs of gene discovery can be sped up by rapid and effective integration of well-defined mouse genome and phenome data resources. We describe here an in silico gene-discovery strategy through genome-wide association (GWA scans in inbred mice with a wide range of genetic variation. We identified 937 quantitative trait loci (QTLs from a survey of 173 mouse phenotypes, which include models of human disease (atherosclerosis, cardiovascular disease, cancer and obesity as well as behavioral, hematological, immunological, metabolic, and neurological traits. 67% of QTLs were refined into genomic regions <0.5 Mb with approximately 40-fold increase in mapping precision as compared with classical linkage analysis. This makes for more efficient identification of the genes that underlie disease. We have identified two QTL genes, Adam12 and Cdh2, as causal genetic variants for atherogenic diet-induced obesity. Our findings demonstrate that GWA analysis in mice has the potential to resolve multiple tightly linked QTLs and achieve single-gene resolution. These high-resolution QTL data can serve as a primary resource for positional cloning and gene identification in the research community.

Personality Traits and Mental Symptoms are Associated with Impact of Chronic Obstructive Pulmonary Disease on Patients' Daily Life

DEFF Research Database (Denmark)

Topp, Marie; Vestbo, Jørgen; Mortensen, Erik Lykke

2016-01-01

Previous research has shown that personality traits are associated with self-reported health status in the general population. COPD Assessment Test (CAT) is increasingly used to assess health status such as the impact of chronic obstructive pulmonary disease (COPD) on patients' daily life......, but knowledge about the influence of personality traits on CAT score is lacking. The aim of this study was to examine the influence of Big Five personality traits on CAT score and the relation between personality traits and mental symptoms with respect to their influence on CAT score. A sample of 168 patients...... diagnosed with COPD was consecutively recruited in a secondary care outpatient clinic. All participants completed CAT, NEO Five-Factor Inventory, and Hospital Depression and Anxiety Scale. Multiple linear regression analysis was used to explore the association between personality traits and CAT scores...

Survey of the Heritability and Sparse Architecture of Gene Expression Traits across Human Tissues.

Directory of Open Access Journals (Sweden)

Heather E Wheeler

2016-11-01

Full Text Available Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR < 0.1 in the DGN whole blood cohort. However, current sample sizes (n ≤ 922 do not allow us to compute distal h2. Bayesian Sparse Linear Mixed Model (BSLMM analysis provides strong evidence that the genetic contribution to local expression traits is dominated by a handful of genetic variants rather than by the collective contribution of a large number of variants each of modest size. In other words, the local architecture of gene expression traits is sparse rather than polygenic across all 40 tissues (from DGN and GTEx examined. This result is confirmed by the sparsity of optimal performing gene expression predictors via elastic net modeling. To further explore the tissue context specificity, we decompose the expression traits into cross-tissue and tissue-specific components using a novel Orthogonal Tissue Decomposition (OTD approach. Through a series of simulations we show that the cross-tissue and tissue-specific components are identifiable via OTD. Heritability and sparsity estimates of these derived expression phenotypes show similar characteristics to the original traits. Consistent properties relative to prior GTEx multi-tissue analysis results suggest that these traits reflect the expected biology. Finally, we apply this knowledge to develop prediction models of gene expression traits for all tissues. The prediction models, heritability, and prediction performance R2 for original and decomposed expression phenotypes are made publicly available (https://github.com/hakyimlab/PrediXcan.

Filipino Personality Traits and Values for Social Support : FOW as human resources for work life balance in Japan (1)

OpenAIRE

SAITO, Isamu; IMAMURA, Taiko; MIYAGI, Mariko

2010-01-01

The purpose of this study is to help contribute to solving nursing care problems in Japan by studying the characteristics, personality traits and values of the Filipino people. Filipinos work as nurses and caregivers overseas,serving to be the largest supplier of human resources relating to socialsupport. Literary documents and books were analyzed to gather concrete examples of Filipino personality traits and values. Interview surveys were also conducted. The ten most depicted traits were the...

Evolution of Sex Differences in Trait- and Age-Specific Vulnerabilities.

Science.gov (United States)

Geary, David C

2016-11-01

Traits that facilitate competition for reproductive resources or that influence mate choice generally have a heightened sensitivity to stressors. They have evolved to signal resilience to infectious disease and nutritional and social stressors, and they are compromised by exposure to man-made toxins. Although these traits can differ from one species or sex to the next, an understanding of the dynamics of competition and choice can in theory be used to generate a priori predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species. I provide a review of these dynamics and illustrate associated vulnerabilities in nonhuman species. The age- and sex-specific vulnerability of such traits is then illustrated for stressor-related disruptions of boys' and girls' physical growth and play behavior, as well as for aspects of boys' and girls' and men's and women's personality, language, and spatial abilities. There is much that remains to be determined, but enough is now known to reframe trait sensitivity in ways that will allow scientists and practitioners to better identify and understand vulnerable human traits, and eventually ameliorate or prevent their expression. © The Author(s) 2016.

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits.

Directory of Open Access Journals (Sweden)

Petr Volkov

Full Text Available Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs in cis and 5,342 SNP-CpG pairs in trans showing significant associations between genotype and DNA methylation in adipose tissue after correction for multiple testing, where cis is defined as distance less than 500 kb between a SNP and CpG site. These mQTLs include reported obesity, lipid and type 2 diabetes loci, e.g. ADCY3/POMC, APOA5, CETP, FADS2, GCKR, SORT1 and LEPR. Significant mQTLs were overrepresented in intergenic regions meanwhile underrepresented in promoter regions and CpG islands. We further identified 635 SNPs in significant cis-mQTLs associated with expression of 86 genes in adipose tissue including CHRNA5, G6PC2, GPX7, RPL27A, THNSL2 and ZFP57. SNPs in significant mQTLs were also associated with body mass index (BMI, lipid traits and glucose and insulin levels in our study cohort and public available consortia data. Importantly, the Causal Inference Test (CIT demonstrates how genetic variants mediate their effects on metabolic traits (e.g. BMI, cholesterol, high-density lipoprotein (HDL, hemoglobin A1c (HbA1c and homeostatic model assessment of insulin resistance (HOMA-IR via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dysmetabolic traits associated with the development of

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

NARCIS (Netherlands)

Astle, William J.; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L.; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A.; Lambourne, John J.; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R.; Daugherty, Louise C.; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F.; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M.; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H. A.; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M.; Staley, James R.; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P.; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G.; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W.; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S.; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J.; Ouwehand, Willem H.; Butterworth, Adam S.; Soranzo, Nicole

2016-01-01

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell,

Uncovering the genetic landscape for multiple sleep-wake traits.

Directory of Open Access Journals (Sweden)

Christopher J Winrow

Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

Gene-based Association Approach Identify Genes Across Stress Traits in Fruit Flies

DEFF Research Database (Denmark)

Rohde, Palle Duun; Edwards, Stefan McKinnon; Sarup, Pernille Merete

Identification of genes explaining variation in quantitative traits or genetic risk factors of human diseases requires both good phenotypic- and genotypic data, but also efficient statistical methods. Genome-wide association studies may reveal association between phenotypic variation and variation...... approach grouping variants accordingly to gene position, thus lowering the number of statistical tests performed and increasing the probability of identifying genes with small to moderate effects. Using this approach we identify numerous genes associated with different types of stresses in Drosophila...... melanogaster, but also identify common genes that affects the stress traits....

Hundreds of variants clustered in genomic loci and biological pathways affect human height

DEFF Research Database (Denmark)

Lango Allen, Hana; Estrada, Karol; Lettre, Guillaume

2010-01-01

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions...

Premorbid personality traits in Alzheimer's disease: do they predispose to noncognitive behavioral symptoms?

Science.gov (United States)

Meins, W; Frey, A; Thiesemann, R

1998-12-01

The purpose of this study was to examine whether premorbid personality traits predispose to noncognitive symptoms in Alzheimer's disease (AD). The Munich Personality Test was used to evaluate caregivers' perception of personality prior to symptom onset in 56 outpatients with probable AD. Caregivers also completed the "mood" and "disturbed behavior" scales of the Nurses' Observation Scale for Geriatric Patients. A neuropsychiatrist rated depressive symptoms on the Cornell Scale for Depression and the occurrence of personality change in four domains according to ICD-10. Under statistical control of confounding variables, results showed a moderate association between (high) premorbid neuroticism, subsequent troublesome behavior, and personality change, on the one hand, and (low) frustration tolerance and depression, on the other. Premorbid personality traits may indeed predispose to subsequent noncognitive symptoms in AD.

Genome-wide association studies in Africans and African Americans: Expanding the Framework of the Genomics of Human Traits and Disease

Science.gov (United States)

Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D.

2014-01-01

Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance, and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago, and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent-African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions. PMID:25427668

Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease.

Science.gov (United States)

Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D

2015-01-01

Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions.

Personality traits in patients with Parkinson's disease: assessment and clinical implications.

Science.gov (United States)

Poletti, Michele; Bonuccelli, Ubaldo

2012-06-01

This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed.

Non-Metric Dental Traits in Human Skeletal Remains from Transcaucasian Populations: Phylogenetic and Diachronic Evidence

Directory of Open Access Journals (Sweden)

Khudaverdyan Anahit Yu.

2014-07-01

Full Text Available The aim of the study is the assessment of biological distance between populations from Transcaucasia on the basis of the frequency of dental morphological traits. It is well known that these traits are characterised by a high inter-population differentiation, low sexual dimorphism, and their recording is loaded by relatively small intra and inter observer error. The dental morphological traits are successfully used in the description and explanation of the microevolutionary and ethnogenetic processes. This paper presents the results of the odontological differentiation of human populations from Transcaucasia. The comparative analysis was carried out on the basis of 12 groups. From the obtained results, we can draw the following conclusions: The populations of Armenian Highland and Georgia can be differentiated as far as the frequency of dental morphological traits are concerned. They also do not exhibit similar intragroup variability. Biocultural diversity of ancient Transcaucasian populations has not been studied extensively; therefore, delineating some of the patterns of phenotypic variation may be useful for understanding their ongoing evolution.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

NARCIS (Netherlands)

H.L. Allen; K. Estrada Gil (Karol); G. Lettre (Guillaume); S.I. Berndt (Sonja); F. Rivadeneira Ramirez (Fernando); C.J. Willer (Cristen); A.U. Jackson (Anne); S. Vedantam (Sailaja); S. Raychaudhuri (Soumya); T. Ferreira (Teresa); A.R. Wood (Andrew); R.J. Weyant (Robert); A.V. Segrè (Ayellet); E.K. Speliotes (Elizabeth); E. Wheeler (Eleanor); N. Soranzo (Nicole); J.H. Park; J. Yang (Joanna); D.F. Gudbjartsson (Daniel); N.L. Heard-Costa (Nancy); J.C. Randall (Joshua); L. Qi (Lu); A.V. Smith (Albert Vernon); R. Mägi (Reedik); T. Pastinen (Tomi); L. Liang (Liming); I.M. Heid (Iris); J. Luan; G. Thorleifsson (Gudmar); T.W. Winkler (Thomas); M.E. Goddard (Michael); K.S. Lo; C. Palmer (Cameron); T. Workalemahu (Tsegaselassie); Y.S. Aulchenko (Yurii); A. Johansson (Åsa); M.C. Zillikens (Carola); M.F. Feitosa (Mary Furlan); T. Esko (Tõnu); T. Johnson (Toby); S. Ketkar (Shamika); P. Kraft (Peter); M. Mangino (Massimo); I. Prokopenko (Inga); D. Absher (Devin); E. Albrecht (Eva); F.D.J. Ernst (Florian); N.L. Glazer (Nicole); C. Hayward (Caroline); J.J. Hottenga (Jouke Jan); K.B. Jacobs (Kevin); J.W. Knowles (Joshua); Z. Kutalik (Zoltán); K.L. Monda (Keri); O. Polasek (Ozren); M. Preuss (Michael); N.W. Rayner (Nigel William); N.R. Robertson (Neil); V. Steinthorsdottir (Valgerdur); J.P. Tyrer (Jonathan); B.F. Voight (Benjamin); F. Wiklund (Fredrik); J. Xu (Jianfeng); J.H. Zhao (Jing Hua); D.R. Nyholt (Dale); N. Pellikka (Niina); M. Perola (Markus); J.R.B. Perry (John); I. Surakka (Ida); M.L. Tammesoo; E.L. Altmaier (Elizabeth); N. Amin (Najaf); T. Aspelund (Thor); T. Bhangale (Tushar); G. Boucher (Gabrielle); D.I. Chasman (Daniel); C. Chen (Constance); L. Coin (Lachlan); M.N. Cooper (Matthew); A.L. Dixon (Anna); Q. Gibson (Quince); E. Grundberg (Elin); K. Hao (Ke); M.J. Junttila (Juhani); R.C. Kaplan (Robert); J. Kettunen (Johannes); I.R. König (Inke); T. Kwan (Tony); R.W. Lawrence (Robert); D.F. Levinson (Douglas); M. Lorentzon (Mattias); B. McKnight (Barbara); A.D. Morris (Andrew); M. Müller (Martina); J.S. Ngwa; S. Purcell (Shaun); S. Rafelt (Suzanne); R.M. Salem (Rany); E. Salvi (Erika); S. Sanna (Serena); J. Shi (Jianxin); U. Sovio (Ulla); J.R. Thompson (John); M.C. Turchin (Michael); L. Vandenput (Liesbeth); D.J. Verlaan (Dominique); V. Vitart (Veronique); C.C. White (Charles); A. Ziegler (Andreas); P. Almgren (Peter); A.J. Balmforth (Anthony); H. Campbell (Harry); L. Citterio (Lorena); A. de Grandi (Alessandro); A. Dominiczak (Anna); J. Duan (Jubao); P. Elliott (Paul); R. Elosua (Roberto); J.G. Eriksson (Johan); N.B. Freimer (Nelson); E.J.C. de Geus (Eco); N. Glorioso (Nicola); S. Haiqing (Shen); A.L. Hartikainen; A.S. Havulinna (Aki); A.A. Hicks (Andrew); J. Hui (Jennie); W. Igl (Wilmar); T. Illig (Thomas); A. Jula (Antti); E. Kajantie (Eero); T.O. Kilpeläinen (Tuomas); M. Koiranen (Markku); I. Kolcic (Ivana); S. Koskinen (Seppo); P. Kovacs (Peter); J. Laitinen (Jaana); J. Liu (Jianjun); M.L. Lokki; A. Marusic (Ana); A. Maschio; T. Meitinger (Thomas); A. Mulas (Antonella); G. Paré (Guillaume); A.N. Parker (Alex); J. Peden (John); A. Petersmann (Astrid); I. Pichler (Irene); K.H. Pietilainen (Kirsi Hannele); A. Pouta (Anneli); M. Ridderstråle (Martin); J.I. Rotter (Jerome); J.G. Sambrook (Jennifer); A.R. Sanders (Alan); C.O. Schmidt (Carsten Oliver); J. Sinisalo (Juha); J.H. Smit (Jan); H.M. Stringham (Heather); G.B. Walters (Bragi); E. Widen (Elisabeth); S.H. Wild (Sarah); G.A.H.M. Willemsen (Gonneke); L. Zagato (Laura); L. Zgaga (Lina); P. Zitting (Paavo); H. Alavere (Helene); M. Farrall (Martin); W.L. McArdle (Wendy); M. Nelis (Mari); M.J. Peters (Marjolein); S. Ripatti (Samuli); J.B.J. van Meurs (Joyce); K.K.H. Aben (Katja); J.S. Beckmann (Jacques); J.P. Beilby (John); R.N. Bergman (Richard); S.M. Bergmann (Sven); F.S. Collins (Francis); D. Cusi (Daniele); M. den Heijer (Martin); G. Eiriksdottir (Gudny); P.V. Gejman (Pablo); A.S. Hall (Alistair); A. Hamsten (Anders); H.V. Huikuri (Heikki); C. Iribarren (Carlos); M. Kähönen (Mika); J. Kaprio (Jaakko); S. Kathiresan (Sekar); L.A.L.M. Kiemeney (Bart); T. Kocher (Thomas); L.J. Launer (Lenore); T. Lehtimäki (Terho); O. Melander (Olle); T.H. Mosley (Thomas); A.W. Musk (Arthur); M.S. Nieminen (Markku); C.J. O'Donnell (Christopher); C. Ohlsson (Claes); B.A. Oostra (Ben); O. Raitakari (Olli); P.M. Ridker (Paul); J.D. Rioux (John); A. Rissanen (Aila); C. Rivolta (Carlo); H. Schunkert (Heribert); A.R. Shuldiner (Alan); D.S. Siscovick (David); M. Stumvoll (Michael); A. Tönjes (Anke); J. Tuomilehto (Jaakko); G.J. van Ommen (Gert); J. Viikari (Jorma); A.C. Heath (Andrew); N.G. Martin (Nicholas); G.W. Montgomery (Grant); M.A. Province (Mike); M.H. Kayser (Manfred); A.M. Arnold (Alice); L.D. Atwood (Larry); E.A. Boerwinkle (Eric); S.J. Chanock (Stephen); P. Deloukas (Panagiotis); C. Gieger (Christian); H. Grönberg (Henrik); A.T. Hattersley (Andrew); C. Hengstenberg (Christian); W. Hoffman (Wolfgang); G.M. Lathrop (Mark); V. Salomaa (Veikko); S. Schreiber (Stefan); M. Uda (Manuela); D. Waterworth (Dawn); A.F. Wright (Alan); T.L. Assimes (Themistocles); I.E. Barroso (Inês); A. Hofman (Albert); K.L. Mohlke (Karen); D.I. Boomsma (Dorret); M. Caulfield (Mark); L.A. Cupples (Adrienne); C.S. Fox (Caroline); V. Gudnason (Vilmundur); U. Gyllensten (Ulf); T.B. Harris (Tamara); R.B. Hayes (Richard); M.R. Järvelin; V. Mooser (Vincent); P. Munroe (Patricia); W.H. Ouwehand (Willem); B.W.J.H. Penninx (Brenda); P.P. Pramstaller (Peter Paul); T. Quertermous (Thomas); I. Rudan (Igor); N.J. Samani (Nilesh); T.D. Spector (Timothy); H. Völzke (Henry); H. Watkins (Hugh); J.F. Wilson (James); L. Groop (Leif); T. Haritunians (Talin); F.B. Hu (Frank); A. Metspalu (Andres); K.E. North (Kari); D. Schlessinger; N.J. Wareham (Nick); D.J. Hunter (David); J.R. O´Connell; D.P. Strachan (David); H.E. Wichmann (Heinz Erich); I.B. Borecki (Ingrid); C.M. van Duijn (Cornelia); E.E. Schadt (Eric); U. Thorsteinsdottir (Unnur); L. Peltonen (Leena Johanna); A.G. Uitterlinden (André); P.M. Visscher (Peter); N. Chatterjee (Nilanjan); J. Erdmann (Jeanette); R.J.F. Loos (Ruth); M. Boehnke (Michael); M.I. McCarthy (Mark); E. Ingelsson (Erik); C.M. Lindgren (Cecilia); G.R. Abecasis (Gonçalo); K. Stefansson (Kari); T.M. Frayling (Timothy); J.N. Hirschhorn (Joel); K.G. Ardlie (Kristin); M.N. Weedon (Michael)

2010-01-01

textabstractMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small

Hundreds of variants clustered in genomic loci and biological pathways affect human height

NARCIS (Netherlands)

Allen, Hana Lango; Estrada, Karol; Lettre, Guillaume; Berndt, Sonja I.; Weedon, Michael N.; Rivadeneira, Fernando; Willer, Cristen J.; Jackson, Anne U.; Vedantam, Sailaja; Raychaudhuri, Soumya; Ferreira, Teresa; Wood, Andrew R.; Weyant, Robert J.; Segre, Ayellet V.; Speliotes, Elizabeth K.; Wheeler, Eleanor; Soranzo, Nicole; Park, Ju-Hyun; Yang, Jian; Gudbjartsson, Daniel; Heard-Costa, Nancy L.; Randall, Joshua C.; Qi, Lu; Smith, Albert Vernon; Maegi, Reedik; Pastinen, Tomi; Liang, Liming; Heid, Iris M.; Luan, Jian'an; Thorleifsson, Gudmar; Winkler, Thomas W.; Goddard, Michael E.; Lo, Ken Sin; Palmer, Cameron; Workalemahu, Tsegaselassie; Aulchenko, Yurii S.; Johansson, Asa; Zillikens, M. Carola; Feitosa, Mary F.; Esko, Tonu; Johnson, Toby; Ketkar, Shamika; Kraft, Peter; Mangino, Massimo; Prokopenko, Inga; Absher, Devin; Albrecht, Eva; Ernst, Florian; Zhao, Jing Hua; Chen, Constance

2010-01-01

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions

Personality traits in Huntington's disease: An exploratory study of gene expansion carriers and non-carriers.

Science.gov (United States)

Larsen, Ida Unmack; Mortensen, Erik Lykke; Vinther-Jensen, Tua; Nielsen, Jørgen Erik; Knudsen, Gitte Moos; Vogel, Asmus

2016-12-01

Huntington's disease (HD) is associated with risk for developing psychiatric symptoms. Vulnerability or resilience to psychiatric symptoms may be associated with personality traits. This exploratory study, aimed to investigate personality traits in a large cohort of HD carriers and at risk gene-expansion negative individuals (HD non-carriers), exploring whether carrying the HD gene or growing up in an HD family influences personality traits. Forty-seven HD carriers, Thirty-nine HD non-carriers, and 121 healthy controls answered the Danish version of the revised NEO personality inventory. Comparisons between HD carriers and HD non-carriers were mostly non-significant but the combined group of HD carriers and non-carriers showed significantly higher scores on the facets: "hostility," "assertiveness," and "activity" and on the trait "Conscientiousness" relative to controls, "Conscientiousness" have been associated with resilience to psychiatric symptoms. Twelve HD carriers and non-carriers were classified as depressed and showed significantly lower scores on "Extraversion" and "Conscientiousness" and significantly higher scores on "Neuroticism," which are associated with vulnerability to psychiatric symptoms. Our findings suggest that, there is no direct effect of the HD gene on personality traits, but that personality assessment may be relevant to use when identifying individuals from HD families who are vulnerable to develop psychiatric symptoms. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Perspectives on Human Variation through the Lens of Diversity and Race.

Science.gov (United States)

Chakravarti, Aravinda

2015-09-01

Human populations, however defined, differ in the distribution and frequency of traits they display and diseases to which individuals are susceptible. These need to be understood with respect to three recent advances. First, these differences are multicausal and a result of not only genetic but also epigenetic and environmental factors. Second, the actions of genes, although crucial, turn out to be quite dynamic and modifiable, which contrasts with the classical view that they are inflexible machines. Third, the diverse human populations across the globe have spent too little time apart from our common origin 50,000 years ago to have developed many individually adapted traits. Human trait and disease differences by continental ancestry are thus as much the result of nongenetic as genetic forces. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

DEFF Research Database (Denmark)

Baillie, J. Kenneth; Bretherick, Andrew; Haley, Christopher S.

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcrip...

Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

Science.gov (United States)

Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2016-03-01

Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Dark triad traits and health outcomes: An exploratory study

Directory of Open Access Journals (Sweden)

Jasna Hudek-Knežević

2016-04-01

Full Text Available On the sample of 637 participants (358 women and 279 men we explored the relationshipbetween Dark Triad traits (psychopathy, Machiavellianism and Narcissism and various healthindicators including subjective (positive and negative mood and perceived physical symptoms,protective health behaviors as well as some more objective health indicators (number ofhospitalizations, number of diseases, having specific chronic diseases, injuries and addictions.Because of the moderate relations between Dark Triad and broad personality traits that also exerttheir influence on various health-related indices, we examined the unique effects of Dark Triad traitson health indicators above and beyond five-factor personality traits as well as sociodemographicvariables related to health (gender, age and education.When sociodemographic variables, as well as five-factor personality traits were controlled inhierarchical regression analyses, Dark Triad traits significantly improved the prediction of almostall subjective health indicators, protective health behaviors, number of hospitalizations and numberof diseases. The effect sizes obtained were relatively low, and psychopathy was the most consistentpredictor.Regarding chronic diseases, injuries and addictions, the results of hierarchical binary logisticregressions showed that when sociodemographic variables were controlled, psychopathy was apositive predictor of the risk of digestive diseases, tobacco use and injuries, Machiavellianismnegatively predicted the risk of injuries, while Narcissism negatively predicted the risk of skindiseases and tobacco use. When five-factor personality traits were controlled, psychopathy was alsoa positive predictor of digestive diseases, tobacco use and injuries. Machiavellianism was a positivepredictor of high blood pressure, and negative predictor of cancer, spine and back diseases andinjuries, while Narcissism was a negative predictor of skin diseases.The results obtained are discussed

Personality Traits and Mental Symptoms are Associated with Impact of Chronic Obstructive Pulmonary Disease on Patients' Daily Life.

Science.gov (United States)

Topp, Marie; Vestbo, Jørgen; Mortensen, Erik Lykke

2016-12-01

Previous research has shown that personality traits are associated with self-reported health status in the general population. COPD Assessment Test (CAT) is increasingly used to assess health status such as the impact of chronic obstructive pulmonary disease (COPD) on patients' daily life, but knowledge about the influence of personality traits on CAT score is lacking. The aim of this study was to examine the influence of Big Five personality traits on CAT score and the relation between personality traits and mental symptoms with respect to their influence on CAT score. A sample of 168 patients diagnosed with COPD was consecutively recruited in a secondary care outpatient clinic. All participants completed CAT, NEO Five-Factor Inventory, and Hospital Depression and Anxiety Scale. Multiple linear regression analysis was used to explore the association between personality traits and CAT scores and how this association was influenced by mental symptoms. The personality traits neuroticism, agreeableness and conscientiousness; and the mental symptoms depression and anxiety showed significant influence on CAT score when analysed in separate regression models. Identical R-square (R = 0.24) was found for personality traits and mental symptoms, but combining personality traits and mental symptoms in one regression model showed substantially reduced effect estimates of neuroticism, conscientiousness and anxiety, reflecting the strong correlations between personality traits and mental symptoms. We found that the impact of COPD on daily life measured by CAT was related to personality and mental symptoms, which illustrates the necessity of taking individual differences in personality and mental status into account in the management of COPD.

A Bayesian Framework for Multiple Trait Colo-calization from Summary Association Statistics.

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Giambartolomei, Claudia; Zhenli Liu, Jimmy; Zhang, Wen; Hauberg, Mads; Shi, Huwenbo; Boocock, James; Pickrell, Joe; Jaffe, Andrew E; Pasaniuc, Bogdan; Roussos, Panos

2018-03-19

Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci. We applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes. moloc is available for download as an R package (https://github.com/clagiamba/moloc). We also developed a web site to visualize the biological findings (icahn.mssm.edu/moloc). The browser allows searches by gene, methylation probe, and scenario of interest. claudia.giambartolomei@gmail.com. Supplementary data are available at Bioinformatics online.

Meta-analysis of inter-species liver co-expression networks elucidates traits associated with common human diseases.

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Kai Wang

2009-12-01

Full Text Available Co-expression networks are routinely used to study human diseases like obesity and diabetes. Systematic comparison of these networks between species has the potential to elucidate common mechanisms that are conserved between human and rodent species, as well as those that are species-specific characterizing evolutionary plasticity. We developed a semi-parametric meta-analysis approach for combining gene-gene co-expression relationships across expression profile datasets from multiple species. The simulation results showed that the semi-parametric method is robust against noise. When applied to human, mouse, and rat liver co-expression networks, our method out-performed existing methods in identifying gene pairs with coherent biological functions. We identified a network conserved across species that highlighted cell-cell signaling, cell-adhesion and sterol biosynthesis as main biological processes represented in genome-wide association study candidate gene sets for blood lipid levels. We further developed a heterogeneity statistic to test for network differences among multiple datasets, and demonstrated that genes with species-specific interactions tend to be under positive selection throughout evolution. Finally, we identified a human-specific sub-network regulated by RXRG, which has been validated to play a different role in hyperlipidemia and Type 2 diabetes between human and mouse. Taken together, our approach represents a novel step forward in integrating gene co-expression networks from multiple large scale datasets to leverage not only common information but also differences that are dataset-specific.

Genomic insights into the Ixodes scapularis tick vector of Lyme disease

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Gulia-Nuss, Monika; Nuss, Andrew B.; Meyer, Jason M.

2016-01-01

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects...... proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent....

Transposable element activity, genome regulation and human health.

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Wang, Lu; Jordan, I King

2018-03-02

A convergence of novel genome analysis technologies is enabling population genomic studies of human transposable elements (TEs). Population surveys of human genome sequences have uncovered thousands of individual TE insertions that segregate as common genetic variants, i.e. TE polymorphisms. These recent TE insertions provide an important source of naturally occurring human genetic variation. Investigators are beginning to leverage population genomic data sets to execute genome-scale association studies for assessing the phenotypic impact of human TE polymorphisms. For example, the expression quantitative trait loci (eQTL) analytical paradigm has recently been used to uncover hundreds of associations between human TE insertion variants and gene expression levels. These include population-specific gene regulatory effects as well as coordinated changes to gene regulatory networks. In addition, analyses of linkage disequilibrium patterns with previously characterized genome-wide association study (GWAS) trait variants have uncovered TE insertion polymorphisms that are likely causal variants for a variety of common complex diseases. Gene regulatory mechanisms that underlie specific disease phenotypes have been proposed for a number of these trait associated TE polymorphisms. These new population genomic approaches hold great promise for understanding how ongoing TE activity contributes to functionally relevant genetic variation within and between human populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Linking Microbiota to Human Diseases

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Wu, Hao; Tremaroli, Valentina; Bäckhed, F

2015-01-01

The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...

Genetic effects on gene expression across human tissues

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Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.

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Benjamin F Voight

Full Text Available Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands of loci with promising but not yet compelling association evidence. To establish association at additional loci and to characterize the genome-wide significant loci by fine-mapping, we designed the "Metabochip," a custom genotyping array that assays nearly 200,000 SNP markers. Here, we describe the Metabochip and its component SNP sets, evaluate its performance in capturing variation across the allele-frequency spectrum, describe solutions to methodological challenges commonly encountered in its analysis, and evaluate its performance as a platform for genotype imputation. The metabochip achieves dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping and sequencing studies and advance our understanding of the genetic basis of complex human diseases and traits.

Chronic human disturbance affects plant trait distribution in a seasonally dry tropical forest

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Sfair, Julia C.; de Bello, Francesco; de França, Thaysa Q.; Baldauf, Cristina; Tabarelli, Marcelo

2018-02-01

The effects of human disturbance on biodiversity can be mediated by environmental conditions, such as water availability, climate and nutrients. In general, disturbed, dry or nutrient-depleted soils areas tend to have lower taxonomic diversity. However, little is known about how these environmental conditions affect functional composition and intraspecific variability in tropical dry forests. We studied a seasonally dry tropical forest (SDTF) under chronic anthropogenic disturbance (CAD) along rainfall and soil nutrient gradients to understand how these factors influence the taxonomic and functional composition. Specifically we evaluated two aspects of CAD, wood extraction and livestock pressure (goat and cattle grazing), along soil fertility and rainfall gradients on shrub and tree traits, considering species turnover and intraspecific variability. In addition, we also tested how the traits of eight populations of the most frequent species are affected by wood extraction, livestock pressure, rainfall and soil fertility. In general, although CAD and environmental gradients affected each trait of the most widespread species differently, the most abundant species also had a greater variation of traits. Considering species turnover, wood extraction is associated with species with a smaller leaf area and lower investment in leaf mass, probably due to the indirect effects of this disturbance type on the vegetation, i.e. the removal of branches and woody debris clears the vegetation, favouring species that minimize water loss. Livestock pressure, on the other hand, affected intraspecific variation: the herbivory caused by goats and cattle promoted individuals which invest more in wood density and leaf mass. In this case, the change of functional composition observed is a direct effect of the disturbance, such as the decrease of palatable plant abundance by goat and cattle herbivory. In synthesis, CAD, rainfall and soil fertility can affect trait distribution at community

Comparison of the Big Five personality traits in fibromyalgia and other rheumatic diseases.

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Bucourt, Emilie; Martaillé, Virginie; Mulleman, Denis; Goupille, Philippe; Joncker-Vannier, Isabelle; Huttenberger, Brigitte; Reveillere, Christian; Courtois, Robert

2017-03-01

The personality of patients with fibromyalgia is still under debate. Some studies found high neuroticism associated with low extraversion, while others found that these traits do not differ from the normal population. Personality factors intervene in the emotional regulation and modulation of pain. The aim of the study was to determine the personality traits of patients with fibromyalgia compared to other rheumatic diseases. In a multicentric study, women with fibromyalgia, rheumatoid arthritis, spondyloarthritis or Sjögren's syndrome were asked to complete the Big Five Inventory, which encompasses five main personality dimensions, namely (1) extraversion vs. introversion, (2) agreeableness vs. antagonism, (3) conscientiousness vs. impulsivity, (4) neuroticism vs. emotional stability, and (5) openness vs. closed-mindedness. Variance analysis (Student's t-test and ANOVA with post-hoc comparisons or Bonferroni correction) was performed. We also conducted hierarchical and non-hierarchical cluster analyses. Participants were 163 women with fibromyalgia (n=48), rheumatoid arthritis (n=46), spondyloarthritis (n=46) and Sjögren's syndrome (n=23). The mean age was 47.18years (±10.81years, range 21 to 65). Patients with fibromyalgia had higher scores on agreeableness (F(3, 159)=3.39, Ppersonality in fibromyalgia. It also underlines the protective role of personality traits: in the fibromyalgia group, high neuroticism and low conscientiousness (high impulsivity) were associated with a high level of chronic pain. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Variability of yield traits and disease resistance in winter triticale genetic resources accessions

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Wanda Kociuba

2014-07-01

Full Text Available A systematic gathering of winter triticale accessions was started in Poland in 1982 by the Institute of Genetics, Breeding and Seed Science at the Agricultural University in Lublin (at present its name is: Institute of Genetics, Breeding and Plant Biotechnology at the University of Life Sciences in Lublin. First, breeding lines obtained in local breeding stations were gathered. Next, accessions were imported from the following world gene banks: Beltsville, Gatersleben, and VIR. Interesting hybrid materials obtained in research centers were also included in the collection. Now, the collection includes 2349 accessions (1329 of winter triticale and 1020 of spring triticale. The evaluation is conducted in a 4-year cycle of field experiments using the same methods. The gathered accessions represent a large range of variability of both morphological and commercial traits. The large differentiation of accessions especially concerns traits such as: plant height, number and weight of grains per spi- ke, protein content in grain, field resistance to powdery mildew, brown rust and leaf and spike diseases.

Human Retrotransposon Insertion Polymorphisms Are Associated with Health and Disease via Gene Regulatory Phenotypes

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Lu Wang

2017-08-01

Full Text Available The human genome hosts several active families of transposable elements (TEs, including the Alu, LINE-1, and SVA retrotransposons that are mobilized via reverse transcription of RNA intermediates. We evaluated how insertion polymorphisms generated by human retrotransposon activity may be related to common health and disease phenotypes that have been previously interrogated through genome-wide association studies (GWAS. To address this question, we performed a genome-wide screen for retrotransposon polymorphism disease associations that are linked to TE induced gene regulatory changes. Our screen first identified polymorphic retrotransposon insertions found in linkage disequilibrium (LD with single nucleotide polymorphisms that were previously associated with common complex diseases by GWAS. We further narrowed this set of candidate disease associated retrotransposon polymorphisms by identifying insertions that are located within tissue-specific enhancer elements. We then performed expression quantitative trait loci analysis on the remaining set of candidates in order to identify polymorphic retrotransposon insertions that are associated with gene expression changes in B-cells of the human immune system. This progressive and stringent screen yielded a list of six retrotransposon insertions as the strongest candidates for TE polymorphisms that lead to disease via enhancer-mediated changes in gene regulation. For example, we found an SVA insertion within a cell-type specific enhancer located in the second intron of the B4GALT1 gene. B4GALT1 encodes a glycosyltransferase that functions in the glycosylation of the Immunoglobulin G (IgG antibody in such a way as to convert its activity from pro- to anti-inflammatory. The disruption of the B4GALT1 enhancer by the SVA insertion is associated with down-regulation of the gene in B-cells, which would serve to keep the IgG molecule in a pro-inflammatory state. Consistent with this idea, the B4GALT1 enhancer

Can personality traits predict the future development of heart disease in hospitalized psychiatric veterans?

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Williams, Wright; Kunik, Mark E; Springer, Justin; Graham, David P

2013-11-01

To examine which personality traits are associated with the new onset of chronic coronary heart disease (CHD) in psychiatric inpatients within 16 years after their initial evaluation. We theorized that personality measures of depression, anxiety, hostility, social isolation, and substance abuse would predict CHD development in psychiatric inpatients. We used a longitudinal database of psychological test data from 349 Veterans first admitted to a psychiatric unit between October 1, 1983, and September 30, 1987. Veterans Affairs and national databases were assessed to determine the development of new-onset chronic CHD over the intervening 16-year period. New-onset CHD developed in 154 of the 349 (44.1%) subjects. Thirty-one psychometric variables from five personality tests significantly predicted the development of CHD. We performed a factor analysis of these variables because they overlapped and four factors emerged, with positive adaptive functioning the only significant factor (OR=0.798, p=0.038). These results support previous research linking personality traits to the development of CHD, extending this association to a population of psychiatric inpatients. Compilation of these personality measures showed that 31 overlapping psychometric variables predicted those Veterans who developed a diagnosis of heart disease within 16 years after their initial psychiatric hospitalization. Our results suggest that personality variables measuring positive adaptive functioning are associated with a reduced risk of developing chronic CHD.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

DEFF Research Database (Denmark)

Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns...... the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes...... in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely...

Viral diseases and human evolution

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Leal Élcio de Souza

2000-01-01

Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

Global biogeography of human infectious diseases.

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Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

2015-10-13

The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

The relationship between the Five-Factor Model personality traits and peptic ulcer disease in a large population-based adult sample.

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Realo, Anu; Teras, Andero; Kööts-Ausmees, Liisi; Esko, Tõnu; Metspalu, Andres; Allik, Jüri

2015-12-01

The current study examined the relationship between the Five-Factor Model personality traits and physician-confirmed peptic ulcer disease (PUD) diagnosis in a large population-based adult sample, controlling for the relevant behavioral and sociodemographic factors. Personality traits were assessed by participants themselves and by knowledgeable informants using the NEO Personality Inventory-3 (NEO PI-3). When controlling for age, sex, education, and cigarette smoking, only one of the five NEO PI-3 domain scales - higher Neuroticism - and two facet scales - lower A1: Trust and higher C1: Competence - made a small, yet significant contribution (p personality traits that are associated with the diagnosis of PUD at a particular point in time. Further prospective studies with a longitudinal design and multiple assessments would be needed to fully understand if the FFM personality traits serve as risk factors for the development of PUD. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Personality Traits: A View From the Animal Kingdom.

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Weiss, Alexander

2018-02-01

Given their backgrounds in classical ethology and in comparative psychology, researchers who study animal personality in biology and psychology, respectively, differ in how they measure personality, what questions they see as important, and how they address these questions. Despite these differences, both comparative psychologists and biologists embrace personality traits. By doing so, they have solved empirical and conceptual problems in animal behavior. Studies of animal personality have provided answers to questions about the evolution of human personality and have presented conceptual and empirical anomalies for sociocognitive theories. Animal personality research does not break from trait theories of personality. Instead, it enriches trait theories by conceiving of traits as not belonging to a species, but as expressed, with some modifications, across species. Broadening trait theory in this way has the potential to further enhance its ability to answer questions related to animal and human personality. © 2017 The Authors. Journal of Personality published by Wiley Periodicals, Inc.

The relationship between traits optimism and anxiety and health-related quality of life in patients hospitalized for chronic diseases: data from the SATISQOL study

Science.gov (United States)

2013-01-01

Background The impact of psychological factors is often taken into account in the evaluation of quality of life. However, the effect of optimism and trait anxiety remains controversial and they are rarely studied simultaneously. We aimed to study the effect of this factor on health-related quality of life (HRQOL) of patients after a hospitalization in relation with their chronic disease. Methods Using cross-sectional data from the SATISQOL cohort, we conducted a multicentric study, including patients hospitalized for an intervention in connection with their chronic disease. Six months after hospitalization, patients completed a generic HRQOL questionnaire (SF-36), and the STAI and LOT-R questionnaires to evaluate optimism and trait anxiety. We studied the effect of each trait on HRQOL separately, and simultaneously, taking account of their interaction in 3 models, using an ANOVA. Results In this study, 1529 patients were included in three participating hospitals and there existed wide diversity in the chronic diseases in our population. The HRQOL score increased for all dimensions of SF36 between 15,8 and 44,5 when the level of anxiety decreased (p optimism (optimism on HRQOL. In the model 3, assessing the effect of both anxiety and optimism on HRQOL, and their interaction, the HRQOL score for all dimensions of the SF36 increased when the level of anxiety decreased (p optimism (p optimism was significant for the Social Functioning dimension (p = 0.0021). Conclusions Optimism and trait anxiety appeared to be significantly correlated with HRQOL. Furthermore, an interaction existed between the trait anxiety and optimism for some dimensions of SF36. Contrary to optimism, it seems essential to evaluate trait anxiety in future studies about HRQOL, since it could represent a confounding factor. PMID:23914779

Genetics of Lipid and Lipoprotein Disorders and Traits.

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Dron, Jacqueline S; Hegele, Robert A

2016-01-01

Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1 , APOC3 , LDLR , APOA5 , and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4. Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a "one stop shop" for the interested reader.

Wildlife disease prevalence in human-modified landscapes.

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Brearley, Grant; Rhodes, Jonathan; Bradley, Adrian; Baxter, Greg; Seabrook, Leonie; Lunney, Daniel; Liu, Yan; McAlpine, Clive

2013-05-01

Human-induced landscape change associated with habitat loss and fragmentation places wildlife populations at risk. One issue in these landscapes is a change in the prevalence of disease which may result in increased mortality and reduced fecundity. Our understanding of the influence of habitat loss and fragmentation on the prevalence of wildlife diseases is still in its infancy. What is evident is that changes in disease prevalence as a result of human-induced landscape modification are highly variable. The importance of infectious diseases for the conservation of wildlife will increase as the amount and quality of suitable habitat decreases due to human land-use pressures. We review the experimental and observational literature of the influence of human-induced landscape change on wildlife disease prevalence, and discuss disease transmission types and host responses as mechanisms that are likely to determine the extent of change in disease prevalence. It is likely that transmission dynamics will be the key process in determining a pathogen's impact on a host population, while the host response may ultimately determine the extent of disease prevalence. Finally, we conceptualize mechanisms and identify future research directions to increase our understanding of the relationship between human-modified landscapes and wildlife disease prevalence. This review highlights that there are rarely consistent relationships between wildlife diseases and human-modified landscapes. In addition, variation is evident between transmission types and landscape types, with the greatest positive influence on disease prevalence being in urban landscapes and directly transmitted disease systems. While we have a limited understanding of the potential influence of habitat loss and fragmentation on wildlife disease, there are a number of important areas to address in future research, particularly to account for the variability in increased and decreased disease prevalence. Previous studies

Human diseases associated with defective DNA repair

International Nuclear Information System (INIS)

Friedberg, E.C.; Ehmann, U.K.; Williams, J.I.

1979-01-01

The observations on xeroderma pigmentosum (XP) cells in culture were the first indications of defective DNA repair in association with human disease. Since then, a wealth of information on DNA repair in XP, and to a lesser extent in other diseases, has accumulated in the literature. Rather than clarifying the understanding of DNA repair mechanisms in normal cells and of defective DNA repair in human disease, the literature suggests an extraordinary complexity of both of the phenomena. In this review a number of discrete human diseases are considered separately. An attempt was made to systematically describe the pertinent clinical features and cellular and biochemical defects in these diseases, with an emphasis on defects in DNA metabolism, particularly DNA repair. Wherever possible observations have been correlated and unifying hypotheses presented concerning the nature of the basic defect(s) in these diseases. Discussions of the following diseases are presented: XP, ataxia telangiectasia; Fanconi's anemia; Hutchinson-Gilford progeria syndrome; Bloom's syndrome, Cockayne's syndrome; Down's syndrome; retinoblastoma; chronic lymphocytic leukemia; and other miscellaneous human diseases with possble DNA repair defects

Genomic prediction of complex human traits: relatedness, trait architecture and predictive meta-models

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Spiliopoulou, Athina; Nagy, Reka; Bermingham, Mairead L.; Huffman, Jennifer E.; Hayward, Caroline; Vitart, Veronique; Rudan, Igor; Campbell, Harry; Wright, Alan F.; Wilson, James F.; Pong-Wong, Ricardo; Agakov, Felix; Navarro, Pau; Haley, Chris S.

2015-01-01

We explore the prediction of individuals' phenotypes for complex traits using genomic data. We compare several widely used prediction models, including Ridge Regression, LASSO and Elastic Nets estimated from cohort data, and polygenic risk scores constructed using published summary statistics from genome-wide association meta-analyses (GWAMA). We evaluate the interplay between relatedness, trait architecture and optimal marker density, by predicting height, body mass index (BMI) and high-density lipoprotein level (HDL) in two data cohorts, originating from Croatia and Scotland. We empirically demonstrate that dense models are better when all genetic effects are small (height and BMI) and target individuals are related to the training samples, while sparse models predict better in unrelated individuals and when some effects have moderate size (HDL). For HDL sparse models achieved good across-cohort prediction, performing similarly to the GWAMA risk score and to models trained within the same cohort, which indicates that, for predicting traits with moderately sized effects, large sample sizes and familial structure become less important, though still potentially useful. Finally, we propose a novel ensemble of whole-genome predictors with GWAMA risk scores and demonstrate that the resulting meta-model achieves higher prediction accuracy than either model on its own. We conclude that although current genomic predictors are not accurate enough for diagnostic purposes, performance can be improved without requiring access to large-scale individual-level data. Our methodologically simple meta-model is a means of performing predictive meta-analysis for optimizing genomic predictions and can be easily extended to incorporate multiple population-level summary statistics or other domain knowledge. PMID:25918167

Sexual imprinting on facial traits of opposite-sex parents in humans.

Science.gov (United States)

Marcinkowska, Urszula M; Rantala, Markus J

2012-09-05

Positive sexual imprinting is a process by which individuals use the phenotype of their opposite-sex parent as a template for acquiring mates. Recent studies in humans have concluded that an imprinting-like mechanism influences human mate choice in facial traits. However, some of the previous studies have had methodological problems or flaws which might have invalidated or led to an overgeneralization of the original interpretation of their results. In this study, 70 heterosexual adults were used to test if their partners resembled facially their opposite-sex parent as the sexual imprinting hypothesis predicts. Judges assessed the subjective facial similarity between each participant's partner and their parent. We found that there was no perceived facial similarity between women's partners and their fathers. However, men tended to pair more often with women that were perceived as resembling the men's own mothers. In contrast to previous studies, the quality of the relationship between participants and their parents did not predict the level of facial resemblance between the participant's spouse and their parent.

Sexual Imprinting on Facial Traits of Opposite-Sex Parents in Humans

Directory of Open Access Journals (Sweden)

Urszula M Marcinkowska

2012-07-01

Full Text Available Positive sexual imprinting is a process by which individuals use the phenotype of their opposite-sex parent as a template for acquiring mates. Recent studies in humans have concluded that an imprinting-like mechanism influences human mate choice in facial traits. However, some of the previous studies have had methodological problems or flaws which might have invalidated or led to an overgeneralization of the original interpretation of their results. In this study, 70 heterosexual adults were used to test if their partners resembled facially their opposite-sex parent as the sexual imprinting hypothesis predicts. Judges assessed the subjective facial similarity between each participant's partner and their parent. We found that there was no perceived facial similarity between women's partners and their fathers. However, men tended to pair more often with women that were perceived as resembling the men's own mothers. In contrast to previous studies, the quality of the relationship between participants and their parents did not predict the level of facial resemblance between the participant's spouse and their parent.

Invited review: overview of new traits and phenotyping strategies in dairy cattle with a focus on functional traits.

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Egger-Danner, C; Cole, J B; Pryce, J E; Gengler, N; Heringstad, B; Bradley, A; Stock, K F

2015-02-01

For several decades, breeding goals in dairy cattle focussed on increased milk production. However, many functional traits have negative genetic correlations with milk yield, and reductions in genetic merit for health and fitness have been observed. Herd management has been challenged to compensate for these effects and to balance fertility, udder health and metabolic diseases against increased production to maximize profit without compromising welfare. Functional traits, such as direct information on cow health, have also become more important because of growing concern about animal well-being and consumer demands for healthy and natural products. There are major concerns about the impact of drugs used in veterinary medicine on the spread of antibiotic-resistant strains of bacteria that can negatively impact human health. Sustainability and efficiency are also increasingly important because of the growing competition for high-quality, plant-based sources of energy and protein. Disruptions to global environments because of climate change may encourage yet more emphasis on these traits. To be successful, it is vital that there be a balance between the effort required for data recording and subsequent benefits. The motivation of farmers and other stakeholders involved in documentation and recording is essential to ensure good data quality. To keep labour costs reasonable, existing data sources should be used as much as possible. Examples include the use of milk composition data to provide additional information about the metabolic status or energy balance of the animals. Recent advances in the use of mid-infrared spectroscopy to measure milk have shown considerable promise, and may provide cost-effective alternative phenotypes for difficult or expensive-to-measure traits, such as feed efficiency. There are other valuable data sources in countries that have compulsory documentation of veterinary treatments and drug use. Additional sources of data outside of the farm

A Strategy for Identifying Quantitative Trait Genes Using Gene Expression Analysis and Causal Analysis

Directory of Open Access Journals (Sweden)

Akira Ishikawa

2017-11-01

Full Text Available Large numbers of quantitative trait loci (QTL affecting complex diseases and other quantitative traits have been reported in humans and model animals. However, the genetic architecture of these traits remains elusive due to the difficulty in identifying causal quantitative trait genes (QTGs for common QTL with relatively small phenotypic effects. A traditional strategy based on techniques such as positional cloning does not always enable identification of a single candidate gene for a QTL of interest because it is difficult to narrow down a target genomic interval of the QTL to a very small interval harboring only one gene. A combination of gene expression analysis and statistical causal analysis can greatly reduce the number of candidate genes. This integrated approach provides causal evidence that one of the candidate genes is a putative QTG for the QTL. Using this approach, I have recently succeeded in identifying a single putative QTG for resistance to obesity in mice. Here, I outline the integration approach and discuss its usefulness using my studies as an example.

A Strategy for Identifying Quantitative Trait Genes Using Gene Expression Analysis and Causal Analysis.

Science.gov (United States)

Ishikawa, Akira

2017-11-27

Large numbers of quantitative trait loci (QTL) affecting complex diseases and other quantitative traits have been reported in humans and model animals. However, the genetic architecture of these traits remains elusive due to the difficulty in identifying causal quantitative trait genes (QTGs) for common QTL with relatively small phenotypic effects. A traditional strategy based on techniques such as positional cloning does not always enable identification of a single candidate gene for a QTL of interest because it is difficult to narrow down a target genomic interval of the QTL to a very small interval harboring only one gene. A combination of gene expression analysis and statistical causal analysis can greatly reduce the number of candidate genes. This integrated approach provides causal evidence that one of the candidate genes is a putative QTG for the QTL. Using this approach, I have recently succeeded in identifying a single putative QTG for resistance to obesity in mice. Here, I outline the integration approach and discuss its usefulness using my studies as an example.

Disease emergence and resurgence—the wildlife-human connection

Science.gov (United States)

Friend, Milton; Hurley, James W.; Nol, Pauline; Wesenberg, Katherine

2006-01-01

In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network. Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.Aside from human disease concerns, H5N1 avian influenza has major economic consequences for the poultry industry worldwide. Many other emerging diseases, such as severe acute respiratory syndrome (SARS), monkeypox, Ebola fever, and West Nile fever, also have an important wildlife component. Despite these wildlife associations, the true integration of the wildlife component in approaches towards disease emergence remains elusive. This separation between wildlife and other species’ interests is counterproductive because the emergence of zoonotic viruses and other pathogens maintained by wildlife reservoir hosts is poorly understood.This book is about the wildlife component of emerging diseases. It is intended to enhance the reader’s awareness of the role of wildlife in disease emergence. By doing so, perhaps a more holistic approach to disease prevention and control will emerge for the benefit of human, domestic animal, and free-ranging wildlife populations alike. The perspectives offered are influenced by more than four decades of my experiences as a wildlife disease practitioner. Although wildlife are victims to many of the same disease agents affecting humans and domestic animals, many aspects of disease in free-ranging wildlife require different approaches than those commonly applied to address disease in humans or domestic animals. Nevertheless, the broader community of disease investigators and health care professionals has largely pursued a separatist approach for

An F2 pig resource population as a model for genetic studies of obesity and obesity-related diseases in humans

DEFF Research Database (Denmark)

Kogelman, Lisette; Kadarmideen, Haja; Mark, Thomas

2013-01-01

Obesity is a rising worldwide public health problem. Difficulties to precisely measure various obesity traits and the genetic heterogeneity in human have been major impediments to completely disentangle genetic factors causing obesity. The pig is a relevant model for studying human obesity...... and obesity-related (OOR) traits. Using founder breeds divergent with respect to obesity traits we have created an F2 pig resource population (454 pigs), which has been intensively phenotyped for 36 OOR traits. The main rationale for our study is to characterize the genetic architecture of OOR traits in the F...... and genetic variation in the F2 population, respectively. This fulfills the purpose of creating a resource population divergent for OOR traits. Strong genetic correlations were found between weight and lean mass at dual energy x-ray absorptiometry (DXA) scanning (0.56 – 0.97). Weight and conformation also...

Effects of environmental changes on natural selection active on human polygenic traits.

Science.gov (United States)

Ulizzi, L

1993-06-01

During the last century, industrialized countries experienced such an improvement in socioeconomic conditions and in sanitation that it is likely that the selective forces active on human metric traits have been modified. Perinatal mortality as a function of birth weight is one of the clearest examples of natural selection in humans. Here, trends over time of stabilizing and directional selection associated with birth weight have been analyzed in Japan from 1969 to 1989. The population of newborns has been subdivided according to gestational age, which is one of the main covariates of birth weight. The results show that in full-term babies both stabilizing and directional selection are coming to an end, whereas in babies born after 8 months of gestation these selective forces are still active, even if at much lower levels than in the past. The peculiar results found in the 7-month-gestation population are probably due to grossly abnormal cases of immaturity.

Open reading frames associated with cancer in the dark matter of the human genome.

Science.gov (United States)

Delgado, Ana Paula; Brandao, Pamela; Chapado, Maria Julia; Hamid, Sheilin; Narayanan, Ramaswamy

2014-01-01

The uncharacterized proteins (open reading frames, ORFs) in the human genome offer an opportunity to discover novel targets for cancer. A systematic analysis of the dark matter of the human proteome for druggability and biomarker discovery is crucial to mining the genome. Numerous data mining tools are available to mine these ORFs to develop a comprehensive knowledge base for future target discovery and validation. Using the Genetic Association Database, the ORFs of the human dark matter proteome were screened for evidence of association with neoplasms. The Phenome-Genome Integrator tool was used to establish phenotypic association with disease traits including cancer. Batch analysis of the tools for protein expression analysis, gene ontology and motifs and domains was used to characterize the ORFs. Sixty-two ORFs were identified for neoplasm association. The expression Quantitative Trait Loci (eQTL) analysis identified thirteen ORFs related to cancer traits. Protein expression, motifs and domain analysis and genome-wide association studies verified the relevance of these OncoORFs in diverse tumors. The OncoORFs are also associated with a wide variety of human diseases and disorders. Our results link the OncoORFs to diverse diseases and disorders. This suggests a complex landscape of the uncharacterized proteome in human diseases. These results open the dark matter of the proteome to novel cancer target research. Copyright© 2014, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

"Are we there yet?": Deciding when one has demonstrated specific genetic causation in complex diseases and quantitative traits.

Science.gov (United States)

Page, Grier P; George, Varghese; Go, Rodney C; Page, Patricia Z; Allison, David B

2003-10-01

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, "Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it." We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what "causation" means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called "causative."

Understanding reproducibility of human IVF traits to predict next IVF cycle outcome.

Science.gov (United States)

Wu, Bin; Shi, Juanzi; Zhao, Wanqiu; Lu, Suzhen; Silva, Marta; Gelety, Timothy J

2014-10-01

Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome. The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome. The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae. The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient's stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly.

Genome-enabled predictions for binomial traits in sugar beet populations.

Science.gov (United States)

Biscarini, Filippo; Stevanato, Piergiorgio; Broccanello, Chiara; Stella, Alessandra; Saccomani, Massimo

2014-07-22

Genomic information can be used to predict not only continuous but also categorical (e.g. binomial) traits. Several traits of interest in human medicine and agriculture present a discrete distribution of phenotypes (e.g. disease status). Root vigor in sugar beet (B. vulgaris) is an example of binomial trait of agronomic importance. In this paper, a panel of 192 SNPs (single nucleotide polymorphisms) was used to genotype 124 sugar beet individual plants from 18 lines, and to classify them as showing "high" or "low" root vigor. A threshold model was used to fit the relationship between binomial root vigor and SNP genotypes, through the matrix of genomic relationships between individuals in a genomic BLUP (G-BLUP) approach. From a 5-fold cross-validation scheme, 500 testing subsets were generated. The estimated average cross-validation error rate was 0.000731 (0.073%). Only 9 out of 12326 test observations (500 replicates for an average test set size of 24.65) were misclassified. The estimated prediction accuracy was quite high. Such accurate predictions may be related to the high estimated heritability for root vigor (0.783) and to the few genes with large effect underlying the trait. Despite the sparse SNP panel, there was sufficient within-scaffold LD where SNPs with large effect on root vigor were located to allow for genome-enabled predictions to work.

Physiochemical basis of human degenerative disease.

Science.gov (United States)

Zeliger, Harold I; Lipinski, Boguslaw

2015-03-01

The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

Physiochemical basis of human degenerative disease

Directory of Open Access Journals (Sweden)

Zeliger Harold I.

2015-03-01

Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

Genetic Characterization of Dog Personality Traits.

Science.gov (United States)

Ilska, Joanna; Haskell, Marie J; Blott, Sarah C; Sánchez-Molano, Enrique; Polgar, Zita; Lofgren, Sarah E; Clements, Dylan N; Wiener, Pamela

2017-06-01

The genetic architecture of behavioral traits in dogs is of great interest to owners, breeders, and professionals involved in animal welfare, as well as to scientists studying the genetics of animal (including human) behavior. The genetic component of dog behavior is supported by between-breed differences and some evidence of within-breed variation. However, it is a challenge to gather sufficiently large datasets to dissect the genetic basis of complex traits such as behavior, which are both time-consuming and logistically difficult to measure, and known to be influenced by nongenetic factors. In this study, we exploited the knowledge that owners have of their dogs to generate a large dataset of personality traits in Labrador Retrievers. While accounting for key environmental factors, we demonstrate that genetic variance can be detected for dog personality traits assessed using questionnaire data. We identified substantial genetic variance for several traits, including fetching tendency and fear of loud noises, while other traits revealed negligibly small heritabilities. Genetic correlations were also estimated between traits; however, due to fairly large SEs, only a handful of trait pairs yielded statistically significant estimates. Genomic analyses indicated that these traits are mainly polygenic, such that individual genomic regions have small effects, and suggested chromosomal associations for six of the traits. The polygenic nature of these traits is consistent with previous behavioral genetics studies in other species, for example in mouse, and confirms that large datasets are required to quantify the genetic variance and to identify the individual genes that influence behavioral traits. Copyright © 2017 by the Genetics Society of America.

The transition to modernity and chronic disease: mismatch and natural selection.

Science.gov (United States)

Corbett, Stephen; Courtiol, Alexandre; Lummaa, Virpi; Moorad, Jacob; Stearns, Stephen

2018-05-09

The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.

"Touching Triton": Building Student Understanding of Complex Disease Risk.

Science.gov (United States)

Loftin, Madelene; East, Kelly; Hott, Adam; Lamb, Neil

2016-01-01

Life science classrooms often emphasize the exception to the rule when it comes to teaching genetics, focusing heavily on rare single-gene and Mendelian traits. By contrast, the vast majority of human traits and diseases are caused by more complicated interactions between genetic and environmental factors. Research indicates that students have a deterministic view of genetics, generalize Mendelian inheritance patterns to all traits, and have unrealistic expectations of genetic technologies. The challenge lies in how to help students analyze complex disease risk with a lack of curriculum materials. Providing open access to both content resources and an engaging storyline can be achieved using a "serious game" model. "Touching Triton" was developed as a serious game in which students are asked to analyze data from a medical record, family history, and genomic report in order to develop an overall lifetime risk estimate of six common, complex diseases. Evaluation of student performance shows significant learning gains in key content areas along with a high level of engagement.

Long Non-Coding RNAs Associated with Metabolic Traits in Human White Adipose Tissue

Directory of Open Access Journals (Sweden)

Hui Gao

2018-04-01

Full Text Available Long non-coding RNAs (lncRNAs belong to a recently discovered class of molecules proposed to regulate various cellular processes. Here, we systematically analyzed their expression in human subcutaneous white adipose tissue (WAT and found that a limited set was differentially expressed in obesity and/or the insulin resistant state. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs, ASMER-1 and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1 or ASMER-2 by antisense oligonucleotides in in vitro differentiated human adipocytes revealed that both genes regulated adipogenesis, lipid mobilization and adiponectin secretion. The observed effects could be attributed to crosstalk between ASMERs and genes within the master regulatory pathways for adipocyte function including PPARG and INSR. Altogether, our data demonstrate that lncRNAs are modulators of the metabolic and secretory functions in human fat cells and provide an emerging link between WAT and common metabolic conditions. Keywords: White adipose tissue, Adipocytes, Long non-coding RNAs, Metabolic traits, Lipolysis, Adiponectin

Annotating the human genome with Disease Ontology

Science.gov (United States)

Osborne, John D; Flatow, Jared; Holko, Michelle; Lin, Simon M; Kibbe, Warren A; Zhu, Lihua (Julie); Danila, Maria I; Feng, Gang; Chisholm, Rex L

2009-01-01

Background The human genome has been extensively annotated with Gene Ontology for biological functions, but minimally computationally annotated for diseases. Results We used the Unified Medical Language System (UMLS) MetaMap Transfer tool (MMTx) to discover gene-disease relationships from the GeneRIF database. We utilized a comprehensive subset of UMLS, which is disease-focused and structured as a directed acyclic graph (the Disease Ontology), to filter and interpret results from MMTx. The results were validated against the Homayouni gene collection using recall and precision measurements. We compared our results with the widely used Online Mendelian Inheritance in Man (OMIM) annotations. Conclusion The validation data set suggests a 91% recall rate and 97% precision rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98% precision using OMIM. Our thesaurus-based approach allows for comparisons to be made between disease containing databases and allows for increased accuracy in disease identification through synonym matching. The much higher recall rate of our approach demonstrates that annotating human genome with Disease Ontology and GeneRIF for diseases dramatically increases the coverage of the disease annotation of human genome. PMID:19594883

Genetic analyses for conformation traits in South African Jersey and ...

African Journals Online (AJOL)

JACO

Genetic trends for conformation traits of the South African Holstein show that ... conformation traits can be used to improve stayability, fertility and disease resistance (Rogers et al., 1999; .... Genetic correlations among protein yield, productive.

A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease

NARCIS (Netherlands)

Biemans, Floor; Jong, de Mart C.M.; Bijma, Piter

2017-01-01

Background: Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of

Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait.

Science.gov (United States)

Vayá, Amparo; Alis, Rafael; Suescún, Marta; Rivera, Leonor; Murado, Julian; Romagnoli, Marco; Solá, Eva; Hernandez-Mijares, Antonio

2015-01-01

Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

Proteomic approach in human health and disease: Preventive and cure studies

Directory of Open Access Journals (Sweden)

Khaled MM Koriem

2018-01-01

Full Text Available Proteomic is a branch of science that deals with various numbers of proteins where proteins are essential human constituents. Proteomic has a lot of functions inside the human and animal living organisms. This review helps to make a thought on the importance of proteomic application in human health and disease with special reference to preventive and cure studies. The human health can be divided into physical and mental health. The physical health relates to keeping human body state in a good health and to nutritional type and environmental factors. The mental health correlates to human psychological state. The main factors that affect the status of human health are human diet, exercise and sleep. The healthy diet is very important and needs to maintain the human health. The training program exercise improves human fitness and overall health and wellness. The sleep is a vital factor to sustain the human health. The human disease indicates abnormal human condition which influences the specific human part or the whole human body. There are external and internal factors which induce human disease. The external factors include pathogens while internal factors include allergies and autoimmunity. There are 4 principle types of human diseases: (1 infectious disease, (2 deficiency disease, (3 genetic disease and (4 physiological disease. There are many and various external microbes' factors that induce human infectious disease and these agents include viruses, bacteria, fungi and protozoa. The lack of necessary and vital dietary rudiments such as vitamins and minerals is the main cause of human deficiency disease. The genetic disease is initiated by hereditary disturbances that occur in the human genetic map. The physiological disease occurs when the normal human function body is affected due to human organs become malfunction. In conclusion, proteomic plays a vital and significant role in human health and disease.

疾病与人格特征及生命质量的相关性研究%Correlation study between disease personality traits and quality of life

Institute of Scientific and Technical Information of China (English)

曹楠; 刘启贵

2017-01-01

介绍了人格特征、生命质量的定义,简述了人格特征、生命质量的研究方法及评估工具、疾病与人格特征之间的关系、疾病与人格特征及生命质量的关系,希望能够提高人们对心理健康的重视程度,从而减轻疾病带给病人的痛苦,提高病人的生命质量.%It introduced the definition of personality traits and quality of life,and briefly introduced the research methods and evaluation tools of personality traits and quality of life,the relationship between disease and per-sonality traits,the relationship between disease,personality traits and quality of life.It hoped that people could pay more attention to mental health,so as to alleviate the suffering of patients and improve their quality of life.

Relationship between leukocyte telomere length and personality traits in healthy subjects.

Science.gov (United States)

Sadahiro, R; Suzuki, A; Enokido, M; Matsumoto, Y; Shibuya, N; Kamata, M; Goto, K; Otani, K

2015-02-01

It has been shown that certain personality traits are related to mortality and disease morbidity, but the biological mechanism linking them remains unclear. Telomeres are tandem repeat DNA sequences located at the ends of chromosomes, and shorter telomere length is a predictor of mortality and late-life disease morbidity. Thus, it is possible that personality traits influence telomere length. In the present study, we examined the relationship of leukocyte telomere length with personality traits in healthy subjects. The subjects were 209 unrelated healthy Japanese who were recruited from medical students at 4th-5th grade. Assessment of personality traits was performed by the Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI). Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. In the stepwise multiple regression analysis, shorter telomere length was related to lower scores of neuroticism (Ppersonality traits, and this association may be implicated in the relationship between personality traits and mortality. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A Genetic Epidemiological Study of Behavioral Traits

NARCIS (Netherlands)

N. Amin (Najaf)

2011-01-01

textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to

Personality Traits of Minority Arab Teachers in the Arab Educational System in Israel

Science.gov (United States)

Abu Hussain, Jamal; Abu Hussain, Nadia

2017-01-01

The present research examined the personality traits prevalent among Arab teachers as a minority in the Arab educational system in Israel. Personality traits has much significance in the prediction of human behavior in various situations. Personality traits affect a person's behavior. Usually personality traits do not change, and they are…

Food and fitness: associations between crop yields and life-history traits in a longitudinally monitored pre-industrial human population.

Science.gov (United States)

Hayward, Adam D; Holopainen, Jari; Pettay, Jenni E; Lummaa, Virpi

2012-10-22

Severe food shortage is associated with increased mortality and reduced reproductive success in contemporary and historical human populations. Studies of wild animal populations have shown that subtle variation in environmental conditions can influence patterns of mortality, fecundity and natural selection, but the fitness implications of such subtle variation on human populations are unclear. Here, we use longitudinal data on local grain production, births, marriages and mortality so as to assess the impact of crop yield variation on individual age-specific mortality and fecundity in two pre-industrial Finnish populations. Although crop yields and fitness traits showed profound year-to-year variation across the 70-year study period, associations between crop yields and mortality or fecundity were generally weak. However, post-reproductive individuals of both sexes, and individuals of lower socio-economic status experienced higher mortality when crop yields were low. This is the first longitudinal, individual-based study of the associations between environmental variation and fitness traits in pre-industrial humans, which emphasizes the importance of a portfolio of mechanisms for coping with low food availability in such populations. The results are consistent with evolutionary ecological predictions that natural selection for resilience to food shortage is likely to weaken with age and be most severe on those with the fewest resources.

Human impacts in African savannas are mediated by plant functional traits.

Science.gov (United States)

Osborne, Colin P; Charles-Dominique, Tristan; Stevens, Nicola; Bond, William J; Midgley, Guy; Lehmann, Caroline E R

2018-05-28

Tropical savannas have a ground cover dominated by C 4 grasses, with fire and herbivory constraining woody cover below a rainfall-based potential. The savanna biome covers 50% of the African continent, encompassing diverse ecosystems that include densely wooded Miombo woodlands and Serengeti grasslands with scattered trees. African savannas provide water, grazing and browsing, food and fuel for tens of millions of people, and have a unique biodiversity that supports wildlife tourism. However, human impacts are causing widespread and accelerating degradation of savannas. The primary threats are land cover-change and transformation, landscape fragmentation that disrupts herbivore communities and fire regimes, climate change and rising atmospheric CO 2 . The interactions among these threats are poorly understood, with unknown consequences for ecosystem health and human livelihoods. We argue that the unique combinations of plant functional traits characterizing the major floristic assemblages of African savannas make them differentially susceptible and resilient to anthropogenic drivers of ecosystem change. Research must address how this functional diversity among African savannas differentially influences their vulnerability to global change and elucidate the mechanisms responsible. This knowledge will permit appropriate management strategies to be developed to maintain ecosystem integrity, biodiversity and livelihoods. © 2018 The Authors New Phytologist © 2018 New Phytologist Trust.

Influenza as a human disease

Indian Academy of Sciences (India)

First page Back Continue Last page Graphics. Influenza as a human disease. Commonly perceived as a mild disease, affects every one, sometimes a couple of times in a year. Globally, seasonal influenza epidemics result in about three to five million yearly cases of severe illness and about 250,000 to 500,000 yearly ...

Real-Time Assessment of Wellness and Disease in Daily Life.

Science.gov (United States)

Ausiello, Dennis; Lipnick, Scott

2015-09-01

The next frontier in medicine involves better quantifying human traits, known as "phenotypes." Biological markers have been directly associated with disease risks, but poor measurement of behaviors such as diet and exercise limits our understanding of preventive measures. By joining together an uncommonly wide range of disciplines and expertise, the Kavli HUMAN Project will advance measurement of behavioral phenotypes, as well as environmental factors that impact behavior. By following the same individuals over time, KHP will liberate new understanding of dynamic links between behavioral phenotypes, disease, and the broader environment. As KHP advances understanding of the bio-behavioral complex, it will seed new approaches to the diagnosis, prevention, and treatment of human disease.

“Are We There Yet?”: Deciding When One Has Demonstrated Specific Genetic Causation in Complex Diseases and Quantitative Traits

Science.gov (United States)

Page, Grier P.; George, Varghese; Go, Rodney C.; Page, Patricia Z.; Allison, David B.

2003-01-01

Although mathematical relationships can be proven by deductive logic, biological relationships can only be inferred from empirical observations. This is a distinct disadvantage for those of us who strive to identify the genes involved in complex diseases and quantitative traits. If causation cannot be proven, however, what does constitute sufficient evidence for causation? The philosopher Karl Popper said, “Our belief in a hypothesis can have no stronger basis than our repeated unsuccessful critical attempts to refute it.” We believe that to establish causation, as scientists, we must make a serious attempt to refute our own hypotheses and to eliminate all known sources of bias before association becomes causation. In addition, we suggest that investigators must provide sufficient data and evidence of their unsuccessful efforts to find any confounding biases. In this editorial, we discuss what “causation” means in the context of complex diseases and quantitative traits, and we suggest guidelines for steps that may be taken to address possible confounders of association before polymorphisms may be called “causative.” PMID:13680525

Can soft biometric traits assist user recognition?

Science.gov (United States)

Jain, Anil K.; Dass, Sarat C.; Nandakumar, Karthik

2004-08-01

Biometrics is rapidly gaining acceptance as the technology that can meet the ever increasing need for security in critical applications. Biometric systems automatically recognize individuals based on their physiological and behavioral characteristics. Hence, the fundamental requirement of any biometric recognition system is a human trait having several desirable properties like universality, distinctiveness, permanence, collectability, acceptability, and resistance to circumvention. However, a human characteristic that possesses all these properties has not yet been identified. As a result, none of the existing biometric systems provide perfect recognition and there is a scope for improving the performance of these systems. Although characteristics like gender, ethnicity, age, height, weight and eye color are not unique and reliable, they provide some information about the user. We refer to these characteristics as "soft" biometric traits and argue that these traits can complement the identity information provided by the primary biometric identifiers like fingerprint and face. This paper presents the motivation for utilizing soft biometric information and analyzes how the soft biometric traits can be automatically extracted and incorporated in the decision making process of the primary biometric system. Preliminary experiments were conducted on a fingerprint database of 160 users by synthetically generating soft biometric traits like gender, ethnicity, and height based on known statistics. The results show that the use of additional soft biometric user information significantly improves (approximately 6%) the recognition performance of the fingerprint biometric system.

Defective glycolysis and the use of 2-deoxy-D-glucose in polycystic kidney disease: from animal models to humans.

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Magistroni, Riccardo; Boletta, Alessandra

2017-08-01

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies. Several of these potential treatments have proved effective in slowing down disease progression in pre-clinical animal studies, while only one has subsequently been proven to effectively slow down disease progression in patients, and it has recently been approved for therapy in Europe, Canada and Japan. Among the affected cellular functions and pathways, recent investigations have described metabolic derangement in ADPKD as a major trait offering additional opportunities for targeted therapies. In particular, increased aerobic glycolysis (the Warburg effect) has been described as a prominent feature of ADPKD kidneys and its inhibition using the glucose analogue 2-deoxy-D-glucose (2DG) proved effective in slowing down disease progression in preclinical models of the disease. At the same time, previous clinical experiences have been reported with 2DG, showing that this compound is well tolerated in humans with minimal and reversible side effects. In this work, we review the literature and speculate that 2DG could be a good candidate for a clinical trial in humans affected by ADPKD.

Metabolomic Quantitative Trait Loci (mQTL Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis.

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William E Kraus

2015-11-01

Full Text Available Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA, long-chain dicarboxylacylcarnitine (LCDA and medium chain acylcarnitine (MCA metabolites are heritable and predict cardiovascular disease (CVD events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490, we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1 These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6-2.3x10-10. Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2. Expression quantitative trait loci (eQTL pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk.

Statistical power to detect genetic (covariance of complex traits using SNP data in unrelated samples.

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Peter M Visscher

2014-04-01

Full Text Available We have recently developed analysis methods (GREML to estimate the genetic variance of a complex trait/disease and the genetic correlation between two complex traits/diseases using genome-wide single nucleotide polymorphism (SNP data in unrelated individuals. Here we use analytical derivations and simulations to quantify the sampling variance of the estimate of the proportion of phenotypic variance captured by all SNPs for quantitative traits and case-control studies. We also derive the approximate sampling variance of the estimate of a genetic correlation in a bivariate analysis, when two complex traits are either measured on the same or different individuals. We show that the sampling variance is inversely proportional to the number of pairwise contrasts in the analysis and to the variance in SNP-derived genetic relationships. For bivariate analysis, the sampling variance of the genetic correlation additionally depends on the harmonic mean of the proportion of variance explained by the SNPs for the two traits and the genetic correlation between the traits, and depends on the phenotypic correlation when the traits are measured on the same individuals. We provide an online tool for calculating the power of detecting genetic (covariation using genome-wide SNP data. The new theory and online tool will be helpful to plan experimental designs to estimate the missing heritability that has not yet been fully revealed through genome-wide association studies, and to estimate the genetic overlap between complex traits (diseases in particular when the traits (diseases are not measured on the same samples.

Quantitative trait loci linked to PRNP gene controlling health and production traits in INRA 401 sheep

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Brunel Jean-Claude

2007-07-01

Full Text Available Abstract In this study, the potential association of PrP genotypes with health and productive traits was investigated. Data were recorded on animals of the INRA 401 breed from the Bourges-La Sapinière INRA experimental farm. The population consisted of 30 rams and 852 ewes, which produced 1310 lambs. The animals were categorized into three PrP genotype classes: ARR homozygous, ARR heterozygous, and animals without any ARR allele. Two analyses differing in the approach considered were carried out. Firstly, the potential association of the PrP genotype with disease (Salmonella resistance and production (wool and carcass traits was studied. The data used included 1042, 1043 and 1013 genotyped animals for the Salmonella resistance, wool and carcass traits, respectively. The different traits were analyzed using an animal model, where the PrP genotype effect was included as a fixed effect. Association analyses do not indicate any evidence of an effect of PrP genotypes on traits studied in this breed. Secondly, a quantitative trait loci (QTL detection approach using the PRNP gene as a marker was applied on ovine chromosome 13. Interval mapping was used. Evidence for one QTL affecting mean fiber diameter was found at 25 cM from the PRNP gene. However, a linkage between PRNP and this QTL does not imply unfavorable linkage disequilibrium for PRNP selection purposes.

in Human Liver Diseases

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Minoru Fujimoto

2010-01-01

Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

Genome editing of human pluripotent stem cells to generate human cellular disease models

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Kiran Musunuru

2013-07-01

Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

Exploring the potential relevance of human-specific genes to complex disease

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Cooper David N

2011-01-01

Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

Safety of Pegfilgrastim (Neulasta in Patients with Sickle Cell Trait/Anemia

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Pashtoon Murtaza Kasi

2013-01-01

Full Text Available Pegfilgrastim (Neulasta is a recombinant filgrastim (human granulocyte colony-stimulating factor (G-CSF attached to a polyethylene glycol (PEG molecule and is given as part of chemotherapy regimens that are associated with significant myelosuppression and risk for febrile neutropenia. Prescribing information available on manufacturer’s website for the drug warns us about possible severe sickle cell crises related to the medication but does not report the actual incidence or the use in patients with sickle cell trait. Caution is advised when using it in patients with sickle cell disease. Here we present a case of a Caucasian female with known sickle cell trait (SCT with no prior complications who developed a presumed sickle cell crisis after getting Neulasta, as a part of the chemotherapy regimen used to treat her breast cancer. Based on our literature review, this appears to be the first case report of a patient with SCT developing a sickle cell crisis with the pegylated form of recombinant filgrastim. Given the dearth of literature regarding the use of G-CSF and its related pegylated forms in patients with sickle cell anemia and sickle cell trait, a discussion of potential mechanisms and review of current literature and guidelines is also presented.

Are premorbid abnormal personality traits associated with behavioural and psychological symptoms in dementia?

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Prior, Jack; Abraham, Rajesh; Nicholas, Helen; Chan, Tom; Vanvlymen, Jeremy; Lovestone, Simon; Boothby, Harry

2016-09-01

The study aims to investigate associations between behavioural and psychological symptoms of dementia (BPSD) and abnormal premorbid personality traits. Data were obtained from 217 patients with a diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms of late-onset dementia were assessed with the Neuropsychiatric Inventory. Premorbid personality traits were assessed using the Standardised Assessment of Personality. Abnormal premorbid personality traits were categorised with Diagnostic and Statistical Manual of Mental Disorders fourth edition and International Statistical Classification of Diseases and Related Health Problems-10 diagnostic criteria for personality disorders. Abnormal premorbid personality traits were associated with increased behavioural and psychological symptoms in dementia. Cluster A (solitary/paranoid) premorbid personality traits were associated with anxiety, depression and hallucinations. Cluster C (anxious/dependent) traits were associated with a syndrome of depression. The presence of Clusters A (solitary/paranoid) and C (anxious/dependent) abnormal premorbid personality traits seems to affect the expression of certain behavioural and psychological symptoms in dementia, depression in particular. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Sub capsular splenic hematoma in a sickle cell trait carrier. Case report].

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Ugalde, Diego; Conte, Guillermo; Ugalde, Héctor; Figueroa, Gastón; Cuneo, Marianela; Muñoz, Macarena; Mayor, Javiera

2011-09-01

Drepanocytic anemia is an uncommon hereditary disease in Chile. The heterozygous state of drepanocytic anemia or "sickle trait" has a frequency of 8% among Afro-Americans. A small number of patients carrying hemoglobin S are homozygous, with clinical manifestations of hemolytic anemia and thrombotic disease. Sickle trait is usually asymptomatic. We report a 59-year-old male who presented an acute abdominal pain and dyspnea while staying at high altitude. Six days later, an angio CAT scan showed the presence of a subcapsular splenic hematoma that was managed conservatively. Sickle cell induction with sodium metabisulphite was positive. Hemoglobin electrophoresis confirmed the sickle trait.

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

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Nolan Daniel K

2012-02-01

Full Text Available Abstract Background Coronary artery disease (CAD, and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C. Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage and less dense spacing (one SNP per 50 kb for the flanking regions (117.7-126.6 and 160.2-167.5 MB and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN and the quantitative trait transmission disequilibrium test (QTDT; GENECARD. SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype using linkage and association in the presence of linkage (APL; GENECARD and logistic regression (CATHGEN and aortas. Results We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002. The most significant results for

Peptide biomarkers used for the selective breeding of a complex polygenic trait in honey bees.

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Guarna, M Marta; Hoover, Shelley E; Huxter, Elizabeth; Higo, Heather; Moon, Kyung-Mee; Domanski, Dominik; Bixby, Miriam E F; Melathopoulos, Andony P; Ibrahim, Abdullah; Peirson, Michael; Desai, Suresh; Micholson, Derek; White, Rick; Borchers, Christoph H; Currie, Robert W; Pernal, Stephen F; Foster, Leonard J

2017-08-21

We present a novel way to select for highly polygenic traits. For millennia, humans have used observable phenotypes to selectively breed stronger or more productive livestock and crops. Selection on genotype, using single-nucleotide polymorphisms (SNPs) and genome profiling, is also now applied broadly in livestock breeding programs; however, selection on protein/peptide or mRNA expression markers has not yet been proven useful. Here we demonstrate the utility of protein markers to select for disease-resistant hygienic behavior in the European honey bee (Apis mellifera L.). Robust, mechanistically-linked protein expression markers, by integrating cis- and trans- effects from many genomic loci, may overcome limitations of genomic markers to allow for selection. After three generations of selection, the resulting marker-selected stock outperformed an unselected benchmark stock in terms of hygienic behavior, and had improved survival when challenged with a bacterial disease or a parasitic mite, similar to bees selected using a phenotype-based assessment for this trait. This is the first demonstration of the efficacy of protein markers for industrial selective breeding in any agricultural species, plant or animal.

Linkage of DNA Methylation Quantitative Trait Loci to Human Cancer Risk

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Holger Heyn

2014-04-01

Full Text Available Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence. DNA methylation quantitative trait loci (meQTL have been identified through significant associations between the genetic and epigenetic codes in physiological and pathological contexts. We propose that interrogating the interplay between polymorphic alleles and DNA methylation is a powerful method for improving our interpretation of risk alleles identified in genome-wide association studies that otherwise lack mechanistic explanation. We integrated patient cancer risk genotype data and genome-scale DNA methylation profiles of 3,649 primary human tumors, representing 13 solid cancer types. We provide a comprehensive meQTL catalog containing DNA methylation associations for 21% of interrogated cancer risk polymorphisms. Differentially methylated loci harbor previously reported and as-yet-unidentified cancer genes. We suggest that such regulation at the DNA level can provide a considerable amount of new information about the biology of cancer-risk alleles.

Behavioral Variation in Gorillas: Evidence of Potential Cultural Traits.

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Robbins, Martha M; Ando, Chieko; Fawcett, Katherine A; Grueter, Cyril C; Hedwig, Daniela; Iwata, Yuji; Lodwick, Jessica L; Masi, Shelly; Salmi, Roberta; Stoinski, Tara S; Todd, Angelique; Vercellio, Veronica; Yamagiwa, Juichi

2016-01-01

The question of whether any species except humans exhibits culture has generated much debate, partially due to the difficulty of providing conclusive evidence from observational studies in the wild. A starting point for demonstrating the existence of culture that has been used for many species including chimpanzees and orangutans is to show that there is geographic variation in the occurrence of particular behavioral traits inferred to be a result of social learning and not ecological or genetic influences. Gorillas live in a wide variety of habitats across Africa and they exhibit flexibility in diet, behavior, and social structure. Here we apply the 'method of exclusion' to look for the presence/absence of behaviors that could be considered potential cultural traits in well-habituated groups from five study sites of the two species of gorillas. Of the 41 behaviors considered, 23 met the criteria of potential cultural traits, of which one was foraging related, nine were environment related, seven involved social interactions, five were gestures, and one was communication related. There was a strong positive correlation between behavioral dissimilarity and geographic distance among gorilla study sites. Roughly half of all variation in potential cultural traits was intraspecific differences (i.e. variability among sites within a species) and the other 50% of potential cultural traits were differences between western and eastern gorillas. Further research is needed to investigate if the occurrence of these traits is influenced by social learning. These findings emphasize the importance of investigating cultural traits in African apes and other species to shed light on the origin of human culture.

De-anonymizing Genomic Databases Using Phenotypic Traits

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Humbert Mathias

2015-06-01

Full Text Available People increasingly have their genomes sequenced and some of them share their genomic data online. They do so for various purposes, including to find relatives and to help advance genomic research. An individual’s genome carries very sensitive, private information such as its owner’s susceptibility to diseases, which could be used for discrimination. Therefore, genomic databases are often anonymized. However, an individual’s genotype is also linked to visible phenotypic traits, such as eye or hair color, which can be used to re-identify users in anonymized public genomic databases, thus raising severe privacy issues. For instance, an adversary can identify a target’s genome using known her phenotypic traits and subsequently infer her susceptibility to Alzheimer’s disease. In this paper, we quantify, based on various phenotypic traits, the extent of this threat in several scenarios by implementing de-anonymization attacks on a genomic database of OpenSNP users sequenced by 23andMe. Our experimental results show that the proportion of correct matches reaches 23% with a supervised approach in a database of 50 participants. Our approach outperforms the baseline by a factor of four, in terms of the proportion of correct matches, in most scenarios. We also evaluate the adversary’s ability to predict individuals’ predisposition to Alzheimer’s disease, and we observe that the inference error can be halved compared to the baseline. We also analyze the effect of the number of known phenotypic traits on the success rate of the attack. As progress is made in genomic research, especially for genotype-phenotype associations, the threat presented in this paper will become more serious.

Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

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Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

2014-01-01

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

A Comparative Study of Personality Traits and Brain Behavioral activation Systems and Inhibition in Women with Cancer, Cardiovascular Diseases and Normal Women

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Sohrab Amiri

2017-04-01

Full Text Available Background and Objectives: Chronic diseases are among the most important causes of mortality. The aim of the current study was to compare the Brain/behavioral systems and Dark personality traits of Machiavellianism, narcissism, and psychopathy in cancer, cardiovascular female patients and normal women. Methods: In this study, 60 individuals were selected using available sampling in three groups of 20 cancer patients, cardiovascular patients, and normal subjects. Finally, in order to test the goals and hypotheses of the research, the participants were studied based on Behavioral Activation System and Behavioral Inhibition System, and Dark Triad traits. Data analysis was performed using multivariate ANOVA, univariate ANOVA and post-hoc tests. Results: In this study, there was a significant difference among the three groups in Brain/behavioral systems and traits of Machiavellianism, narcissism, and psychopathy, so that the cancer and cardiovascular patients had higher score in dark triad traits compared to normal individuals. Also, the cancer patients had a higher score in Machiavellianism trait compared to the cardiovascular patients. In the brain/behavioral systems, cardiovascular and cancer patients had higher score in behavioral inhibition system (BIS component compared to the normal individuals in the of behavioral inhibition system (BIS. Also, in the reward seeking subscale of behavioral activation system (BAS-f, cancer patients had a higher score compared to cardiovascular patients, which was significantly different. Conclusion: The results of this study indicated that cancer and cardiovascular patients, have greater extent of social disgusting personality traits as well as behavioral inhibition system as anxiety-predisposing factor.

Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

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Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

2016-01-01

Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gene-trait matching across the Bifidobacterium longum pan-genome reveals considerable diversity in carbohydrate catabolism among human infant strains.

LENUS (Irish Health Repository)

Arboleya, Silvia

2018-01-08

Bifidobacterium longum is a common member of the human gut microbiota and is frequently present at high numbers in the gut microbiota of humans throughout life, thus indicative of a close symbiotic host-microbe relationship. Different mechanisms may be responsible for the high competitiveness of this taxon in its human host to allow stable establishment in the complex and dynamic intestinal microbiota environment. The objective of this study was to assess the genetic and metabolic diversity in a set of 20 B. longum strains, most of which had previously been isolated from infants, by performing whole genome sequencing and comparative analysis, and to analyse their carbohydrate utilization abilities using a gene-trait matching approach.

Cancer and life-history traits: lessons from host-parasite interactions.

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Ujvari, Beata; Beckmann, Christa; Biro, Peter A; Arnal, Audrey; Tasiemski, Aurelie; Massol, Francois; Salzet, Michel; Mery, Frederic; Boidin-Wichlacz, Celine; Misse, Dorothee; Renaud, Francois; Vittecoq, Marion; Tissot, Tazzio; Roche, Benjamin; Poulin, Robert; Thomas, Frederic

2016-04-01

Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host-parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations.

Breeding common bean populations for traits using selection index

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Dayane Cristina Lima

2015-02-01

Full Text Available A common bean (Phaseolus vulgarisL. cultivar must combine desirable genotypes for several traits in order to be accepted by producers and consumers. This study aimed to evaluate selection efficiency when segregating bean populations for traits, by means of a selection index, in order to obtain superior progenies for traits considered. A total of 16 populations from the F4 and F5generations were evaluated in 2011 and 2012, respectively. The traits evaluated were plant architecture, plant disease, grain type and yield. Using standard scores (Z, the sum of the four traits (∑Z was obtained and, based on this information, the best populations were identified. The evaluation of selection effectiveness was performed on 31 progenies from each population. The 496 progenies plus eight controls were evaluated in the F5:6and F5:7 generations for the same traits in July and November 2012, respectively. The selection, using the index based on the sum of standardized variables (∑Z, was efficient for identifying populations with superior progenies for all the traits considered.

[Bartonellosis. II. Other Bartonella responsible for human diseases].

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Piémont, Y; Heller, R

1999-01-01

In addition to Bartonella henselae, five other Bartonella species were involved in human pathology. As for B. henselae, ectoparasites seem to be responsible for the transmission of most or all these bacterial species. B. bacilliformis is responsible for Carrion's disease that occurs in some valleys of Colombia, Ecuador and Peru. This disease is transmitted by biting of infected sandflies. The bacterial reservoir is constituted by humans only. That disease occurs either as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of the bacterium exist. Trench fever was described during the First World War. This non-lethal disease is constituted of recurrent febrile attacks associated particularly with osseous pains. The causative agent of the disease is B. quintana, transmitted by the body louse. Humans seem to be the reservoir of that bacterium. In some patients, B. quintana can be responsible for endocarditis, bacillary angiomatosis and chronic or recurrent bacteremia. Other human infections due to Bartonella sp. have been described: B. vinsonii, isolated from blood of small rodents, and B. elizabethae, the reservoir of which is currently unknown, can be responsible for endocardites. B. clarridgeiae (isolated from blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat scratch disease. All these bartonelloses are diagnosed by non-standard blood culture or by in vitro DNA amplification or by serological testing. Their treatment requires tetracyclines or chloramphenicol or macrolides.

Human genomic disease variants: a neutral evolutionary explanation.

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Dudley, Joel T; Kim, Yuseob; Liu, Li; Markov, Glenn J; Gerold, Kristyn; Chen, Rong; Butte, Atul J; Kumar, Sudhir

2012-08-01

Many perspectives on the role of evolution in human health include nonempirical assumptions concerning the adaptive evolutionary origins of human diseases. Evolutionary analyses of the increasing wealth of clinical and population genomic data have begun to challenge these presumptions. In order to systematically evaluate such claims, the time has come to build a common framework for an empirical and intellectual unification of evolution and modern medicine. We review the emerging evidence and provide a supporting conceptual framework that establishes the classical neutral theory of molecular evolution (NTME) as the basis for evaluating disease- associated genomic variations in health and medicine. For over a decade, the NTME has already explained the origins and distribution of variants implicated in diseases and has illuminated the power of evolutionary thinking in genomic medicine. We suggest that a majority of disease variants in modern populations will have neutral evolutionary origins (previously neutral), with a relatively smaller fraction exhibiting adaptive evolutionary origins (previously adaptive). This pattern is expected to hold true for common as well as rare disease variants. Ultimately, a neutral evolutionary perspective will provide medicine with an informative and actionable framework that enables objective clinical assessment beyond convenient tendencies to invoke past adaptive events in human history as a root cause of human disease.

Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

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Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

2014-09-01

Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

Science.gov (United States)

Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

Temporal stability of personality traits in group-housed gestating sows.

Science.gov (United States)

Horback, K M; Parsons, T D

2016-08-01

The movement of sows (Sus scrofa domesticus) out of individual gestation stalls and into group housing can introduce new sources of stress due to the enhanced environmental and social complexity. Some sows may have the behavioral capacity to adapt to these changes better than others. However, little is known about individual differences in behavioral responses, or personality traits, in gestating sows and how they impact the animal's ability to cope with group housing. The temporal consistency in the assessment of an animal's behavior is a prerequisite to the establishment of personality traits and was addressed at an interval of approximately five months during two consecutive gestation periods in the present study. Forty-six group-housed sows from a commercially available genetic line were assessed for aggressive and social behaviors at mixing into a group, reaction to human approach, ease of handling, exploration of an open field, and reaction to a novel object. Principal component analysis revealed the presence of three traits accounting for over 60% of the variance in behaviors: aggressive/dominant, avoidant of humans and active/exploratory. Individual component scores were significantly correlated between pregnancies demonstrating temporal stability of trait assessment. Significant relationships were found between aggressive/dominant component scores and individual feed rank at electronic sow feeding stations and skin lesion scores, as well as between avoidant of humans component scores and average number of stillbirths per litter. These findings provide evidence for the temporal stability of distinct behaviors contributing to personality traits within a group of genetically similar sows and demonstrate how these traits may be useful in identifying individuals likely to succeed in group housing.

Emerging role of mitophagy in human diseases and physiology.

Science.gov (United States)

Um, Jee-Hyun; Yun, Jeanho

2017-06-01

Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology. [BMB Reports 2017; 50(6): 299-307].

Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

NARCIS (Netherlands)

Chami, N. (Nathalie); M.-H. Chen (Ming-Huei); Slater, A.J. (Andrew J.); Eicher, J.D. (John D.); E. Evangelou (Evangelos); Tajuddin, S.M. (Salman M.); Love-Gregory, L. (Latisha); T. Kacprowski (Tim); U.M. Schick (Ursula); Nomura, A. (Akihiro); Giri, A. (Ayush); Lessard, S. (Samuel); J. Brody (Jennifer); C. Schurmann (Claudia); V.S. Pankratz (Shane); L.R. Yanek (Lisa); A. Manichaikul (Ani); R. Pazoki (Raha); E. Mihailov (Evelin); W.D. Hill (W. David); Raffield, L.M. (Laura M.); A.D. Burt (Alastair); T.M. Bartz (Traci M.); D.M. Becker (Diane); L.C. Becker (Lewis); E.A. Boerwinkle (Eric); J. Bork-Jensen (Jette); E.P. Bottinger (Erwin); M.L. O'Donoghue (Michelle L.); D.R. Crosslin (David); de Denus, S. (Simon); Dubé, M.-P. (Marie-Pierre); P. Elliott (Paul); G. Engström; M. Evans (Michele); J. Floyd (James); M. Fornage (Myriam); Gao, H. (He); A. Greinacher (Andreas); V. Gudnason (Vilmundur); T. Hansen (T.); T.B. Harris (Tamara); C. Hayward (Caroline); Hernesniemi, J. (Jussi); H. Highland (Heather); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Irvin, M.R. (Marguerite R.); M. Kähönen (Mika); E.M. Lange (Ethan); Launer, L.J. (Lenore J.); T. Lehtimäki (Terho); Li, J. (Jin); D.C. Liewald (David C.); A. Linneberg (Allan); Y. Liu (YongMei); Y. Lu (Yingchang); L.-P. Lyytikäinen (Leo-Pekka); R. Mägi (Reedik); J. Mathias (Jasmine); O. Melander (Olle); A. Metspalu (Andres); K. Mononen (Kari); M.A. Nalls (Michael); D.A. Nickerson (Deborah); K. Nikus (Kjell); C.J. O'Donnell (Christopher); M. Orho-Melander (Marju); O. Pedersen (Oluf); A. Petersmann (Astrid); Polfus, L. (Linda); B.M. Psaty (Bruce); O.T. Raitakari (Olli T.); Raitoharju, E. (Emma); Richard, M. (Melissa); K.M. Rice (Kenneth); F. Rivadeneira Ramirez (Fernando); Rotter, J.I. (Jerome I.); Schmidt, F. (Frank); A.V. Smith (Albert Vernon); J.M. Starr (John); K.D. Taylor (Kent); A. Teumer (Alexander); Thuesen, B.H. (Betina H.); Torstenson, E.S. (Eric S.); R.P. Tracy (Russell); I. Tzoulaki; N.A. Zakai (Neil); Vacchi-Suzzi, C. (Caterina); C.M. van Duijn (Cornelia); F.J.A. van Rooij (Frank); M. Cushman (Mary Ann); I.J. Deary (Ian J.); Velez Edwards, D.R. (Digna R.); Vergnaud, A.-C. (Anne-Claire); L.C. Wallentin (Lars); D. Waterworth (Dawn); White, H.D. (Harvey D.); J.F. Wilson (James); A.B. Zonderman; S. Kathiresan (Sekar); N. Grarup (Niels); T. Esko (Tõnu); R.J.F. Loos (Ruth); L.A. Lange (Leslie); Faraday, N. (Nauder); Abumrad, N.A. (Nada A.); T.L. Edwards (Todd L.); S.K. Ganesh (Santhi); P. Auer (Paul); A.D. Johnson (Andrew); A. Reiner (Alexander); G. Lettre (Guillaume)

2016-01-01

textabstractRed blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an

Entomologic index for human risk of Lyme disease.

Science.gov (United States)

Mather, T N; Nicholson, M C; Donnelly, E F; Matyas, B T

1996-12-01

An entomologic index based on density estimates of Lyme disease spirochete-infected nymphal deer ticks (lxodes scapularis) was developed to assess human risk of Lyme disease. The authors used a standardized protocol to determine tick density and infection in numerous forested sites in six Rhode Island towns. An entomologic risk index calculated for each town was compared with the number of human Lyme disease cases reported to the Rhode Island State Health Department for the same year. A strong positive relation between entomologic risk index and the Lyme disease case rate for each town suggested that the entomologic index was predictive of Lyme disease risk.

Multinational corporations and infectious disease: Embracing human rights management techniques.

Science.gov (United States)

Salcito, Kendyl; Singer, Burton H; Weiss, Mitchell G; Winkler, Mirko S; Krieger, Gary R; Wielga, Mark; Utzinger, Jürg

2014-01-01

Global health institutions have called for governments, international organisations and health practitioners to employ a human rights-based approach to infectious diseases. The motivation for a human rights approach is clear: poverty and inequality create conditions for infectious diseases to thrive, and the diseases, in turn, interact with social-ecological systems to promulgate poverty, inequity and indignity. Governments and intergovernmental organisations should be concerned with the control and elimination of these diseases, as widespread infections delay economic growth and contribute to higher healthcare costs and slower processes for realising universal human rights. These social determinants and economic outcomes associated with infectious diseases should interest multinational companies, partly because they have bearing on corporate productivity and, increasingly, because new global norms impose on companies a responsibility to respect human rights, including the right to health. We reviewed historical and recent developments at the interface of infectious diseases, human rights and multinational corporations. Our investigation was supplemented with field-level insights at corporate capital projects that were developed in areas of high endemicity of infectious diseases, which embraced rights-based disease control strategies. Experience and literature provide a longstanding business case and an emerging social responsibility case for corporations to apply a human rights approach to health programmes at global operations. Indeed, in an increasingly globalised and interconnected world, multinational corporations have an interest, and an important role to play, in advancing rights-based control strategies for infectious diseases. There are new opportunities for governments and international health agencies to enlist corporate business actors in disease control and elimination strategies. Guidance offered by the United Nations in 2011 that is widely embraced

Intelligence : shared genetic basis between Mendelian disorders and a polygenic trait

NARCIS (Netherlands)

Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

2015-01-01

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a

Finding aroma clues in the human breath to diagnose diseases

Science.gov (United States)

A. Dan Wilson

2016-01-01

History of human odor analysis in disease diagnosis The use of the sense of smell as an indicator of human disease probably originated with Hippocrates (circa 400 BC). Early medical practitioners recognized that the presence of human diseases changed the odors released from the body and breath. Physicians once relied heavily on their sense of smell to provide useful...

Behavioral Variation in Gorillas: Evidence of Potential Cultural Traits

Science.gov (United States)

Robbins, Martha M.; Ando, Chieko; Fawcett, Katherine A.; Grueter, Cyril C.; Hedwig, Daniela; Iwata, Yuji; Lodwick, Jessica L.; Masi, Shelly; Salmi, Roberta; Stoinski, Tara S.; Todd, Angelique; Vercellio, Veronica; Yamagiwa, Juichi

2016-01-01

The question of whether any species except humans exhibits culture has generated much debate, partially due to the difficulty of providing conclusive evidence from observational studies in the wild. A starting point for demonstrating the existence of culture that has been used for many species including chimpanzees and orangutans is to show that there is geographic variation in the occurrence of particular behavioral traits inferred to be a result of social learning and not ecological or genetic influences. Gorillas live in a wide variety of habitats across Africa and they exhibit flexibility in diet, behavior, and social structure. Here we apply the ‘method of exclusion’ to look for the presence/absence of behaviors that could be considered potential cultural traits in well-habituated groups from five study sites of the two species of gorillas. Of the 41 behaviors considered, 23 met the criteria of potential cultural traits, of which one was foraging related, nine were environment related, seven involved social interactions, five were gestures, and one was communication related. There was a strong positive correlation between behavioral dissimilarity and geographic distance among gorilla study sites. Roughly half of all variation in potential cultural traits was intraspecific differences (i.e. variability among sites within a species) and the other 50% of potential cultural traits were differences between western and eastern gorillas. Further research is needed to investigate if the occurrence of these traits is influenced by social learning. These findings emphasize the importance of investigating cultural traits in African apes and other species to shed light on the origin of human culture. PMID:27603668

Intergenic disease-associated regions are abundant in novel transcripts.

Science.gov (United States)

Bartonicek, N; Clark, M B; Quek, X C; Torpy, J R; Pritchard, A L; Maag, J L V; Gloss, B S; Crawford, J; Taft, R J; Hayward, N K; Montgomery, G W; Mattick, J S; Mercer, T R; Dinger, M E

2017-12-28

Genotyping of large populations through genome-wide association studies (GWAS) has successfully identified many genomic variants associated with traits or disease risk. Unexpectedly, a large proportion of GWAS single nucleotide polymorphisms (SNPs) and associated haplotype blocks are in intronic and intergenic regions, hindering their functional evaluation. While some of these risk-susceptibility regions encompass cis-regulatory sites, their transcriptional potential has never been systematically explored. To detect rare tissue-specific expression, we employed the transcript-enrichment method CaptureSeq on 21 human tissues to identify 1775 multi-exonic transcripts from 561 intronic and intergenic haploblocks associated with 392 traits and diseases, covering 73.9 Mb (2.2%) of the human genome. We show that a large proportion (85%) of disease-associated haploblocks express novel multi-exonic non-coding transcripts that are tissue-specific and enriched for GWAS SNPs as well as epigenetic markers of active transcription and enhancer activity. Similarly, we captured transcriptomes from 13 melanomas, targeting nine melanoma-associated haploblocks, and characterized 31 novel melanoma-specific transcripts that include fusion proteins, novel exons and non-coding RNAs, one-third of which showed allelically imbalanced expression. This resource of previously unreported transcripts in disease-associated regions ( http://gwas-captureseq.dingerlab.org ) should provide an important starting point for the translational community in search of novel biomarkers, disease mechanisms, and drug targets.

Freshwater Biological Traits Database (Traits)

Science.gov (United States)

The traits database was compiled for a project on climate change effects on river and stream ecosystems. The traits data, gathered from multiple sources, focused on information published or otherwise well-documented by trustworthy sources.

Epigenetics and developmental programming of welfare and production traits in farm animals.

Science.gov (United States)

Sinclair, K D; Rutherford, K M D; Wallace, J M; Brameld, J M; Stöger, R; Alberio, R; Sweetman, D; Gardner, D S; Perry, V E A; Adam, C L; Ashworth, C J; Robinson, J E; Dwyer, C M

2016-07-21

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

The Effect of Istighfar on State and Trait Anxiety

Directory of Open Access Journals (Sweden)

Ahmet Canan Karakaş

2017-09-01

Full Text Available Istighfar (seeking forgiveness of Allah and tawbah (repentance are as old as at least the human history. Anxiety is also a need of human nature. Human develops the strategies to cope with challenges. One of them is religious coping. One of the religious coping ways is istighfar. Constantly performing istighfar may make easier to deal with anxiety. Thus, in this study, the state-trait anxiety scale was applied to the final year undergraduate students. The experimental and control groups of 20 persons were comprised of students with higher anxiety level. The experimental group was told to do istighfar 100 times per day during one month. In the end of this practice, a decrease was observed in the state-trait anxiety average of experimental group.

H2DB: a heritability database across multiple species by annotating trait-associated genomic loci.

Science.gov (United States)

Kaminuma, Eli; Fujisawa, Takatomo; Tanizawa, Yasuhiro; Sakamoto, Naoko; Kurata, Nori; Shimizu, Tokurou; Nakamura, Yasukazu

2013-01-01

H2DB (http://tga.nig.ac.jp/h2db/), an annotation database of genetic heritability estimates for humans and other species, has been developed as a knowledge database to connect trait-associated genomic loci. Heritability estimates have been investigated for individual species, particularly in human twin studies and plant/animal breeding studies. However, there appears to be no comprehensive heritability database for both humans and other species. Here, we introduce an annotation database for genetic heritabilities of various species that was annotated by manually curating online public resources in PUBMED abstracts and journal contents. The proposed heritability database contains attribute information for trait descriptions, experimental conditions, trait-associated genomic loci and broad- and narrow-sense heritability specifications. Annotated trait-associated genomic loci, for which most are single-nucleotide polymorphisms derived from genome-wide association studies, may be valuable resources for experimental scientists. In addition, we assigned phenotype ontologies to the annotated traits for the purposes of discussing heritability distributions based on phenotypic classifications.

Directional dominance on stature and cognition in diverse human populations

DEFF Research Database (Denmark)

Joshi, Peter K; Esko, Tonu; Mattsson, Hannele

2015-01-01

is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been....... confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance...

Host Genome Influence on Gut Microbial Composition and Microbial Prediction of Complex Traits in Pigs.

Science.gov (United States)

Camarinha-Silva, Amelia; Maushammer, Maria; Wellmann, Robin; Vital, Marius; Preuss, Siegfried; Bennewitz, Jörn

2017-07-01

The aim of the present study was to analyze the interplay between gastrointestinal tract (GIT) microbiota, host genetics, and complex traits in pigs using extended quantitative-genetic methods. The study design consisted of 207 pigs that were housed and slaughtered under standardized conditions, and phenotyped for daily gain, feed intake, and feed conversion rate. The pigs were genotyped with a standard 60 K SNP chip. The GIT microbiota composition was analyzed by 16S rRNA gene amplicon sequencing technology. Eight from 49 investigated bacteria genera showed a significant narrow sense host heritability, ranging from 0.32 to 0.57. Microbial mixed linear models were applied to estimate the microbiota variance for each complex trait. The fraction of phenotypic variance explained by the microbial variance was 0.28, 0.21, and 0.16 for daily gain, feed conversion, and feed intake, respectively. The SNP data and the microbiota composition were used to predict the complex traits using genomic best linear unbiased prediction (G-BLUP) and microbial best linear unbiased prediction (M-BLUP) methods, respectively. The prediction accuracies of G-BLUP were 0.35, 0.23, and 0.20 for daily gain, feed conversion, and feed intake, respectively. The corresponding prediction accuracies of M-BLUP were 0.41, 0.33, and 0.33. Thus, in addition to SNP data, microbiota abundances are an informative source of complex trait predictions. Since the pig is a well-suited animal for modeling the human digestive tract, M-BLUP, in addition to G-BLUP, might be beneficial for predicting human predispositions to some diseases, and, consequently, for preventative and personalized medicine. Copyright © 2017 by the Genetics Society of America.

Genetics of Adiposity in Large Animal Models for Human Obesity-Studies on Pigs and Dogs.

Science.gov (United States)

Stachowiak, M; Szczerbal, I; Switonski, M

2016-01-01

The role of domestic mammals in the development of human biomedical sciences has been widely documented. Among these model species the pig and dog are of special importance. Both are useful for studies on the etiology of human obesity. Genome sequences of both species are known and advanced genetic tools [eg, microarray SNP for genome wide association studies (GWAS), next generation sequencing (NGS), etc.] are commonly used in such studies. In the domestic pig the accumulation of adipose tissue is an important trait, which influences meat quality and fattening efficiency. Numerous quantitative trait loci (QTLs) for pig fatness traits were identified, while gene polymorphisms associated with these traits were also described. The situation is different in dog population. Generally, excessive accumulation of adipose tissue is considered, similar to humans, as a complex disease. However, research on the genetic background of canine obesity is still in its infancy. Between-breed differences in terms of adipose tissue accumulation are well known in both animal species. In this review we show recent advances of studies on adipose tissue accumulation in pigs and dogs, and their potential importance for studies on human obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased reward value of biological motion among individuals with autistic traits.

Science.gov (United States)

Williams, Elin H; Cross, Emily S

2018-02-01

The Social Motivation Theory posits that a reduced sensitivity to the value of social stimuli, specifically faces, can account for social impairments in Autism Spectrum Disorders (ASD). Research has demonstrated that typically developing (TD) individuals preferentially orient towards another type of salient social stimulus, namely biological motion. Individuals with ASD, however, do not show this preference. While the reward value of faces to both TD and ASD individuals has been well-established, the extent to which individuals from these populations also find human motion to be rewarding remains poorly understood. The present study investigated the value assigned to biological motion by TD participants in an effort task, and further examined whether these values differed among individuals with more autistic traits. The results suggest that TD participants value natural human motion more than rigid, machine-like motion or non-human control motion, but this preference is attenuated among individuals reporting more autistic traits. This study provides the first evidence to suggest that individuals with more autistic traits find a broader conceptualisation of social stimuli less rewarding compared to individuals with fewer autistic traits. By quantifying the social reward value of human motion, the present findings contribute an important piece to our understanding of social motivation in individuals with and without social impairments. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Human figure drawings by children with Duchenne's muscular dystrophy.

Science.gov (United States)

Pope-Grattan, M M; Burnett, C N; Wolfe, C V

1976-02-01

Seventy-two human figure drawings by forty-three patients who had a diagnosis of Duchenne's muscular dystrophy were examined. The study includes a description of these human figure drawings according to eleven emotional indicators and according to directionality quadrants. When the human figure drawings were used as a projective tool, four personality traits of some of the children were identified: physical inadequacy, immaturity, body anxiety, and insecurity. Both the emotional indicators and the quadrant in which the figures appeared were examined in relation to stages of the disease process to see if the human figure drawings of the children might reflect more stress and anxiety at a particular stage of the disease. Suggestions for improvements and recommendations for future study are given.

Relation between observed locomotion traits and locomotion score in dairy cows

NARCIS (Netherlands)

Schlageter Tello, A.A.; Bokkers, E.A.M.; Groot Koerkamp, P.W.G.; Hertem, van T.; Viazzi, S.; Lokhorst, Kees

2015-01-01

Lameness is still an important problem in modern dairy farming. Human observation of locomotion, by looking at different traits in one go, is used in practice to assess locomotion. The objectives of this article were to determine which individual locomotion traits are most related to locomotion

Is beta-thalassemia trait a protective factor against ischemic cerebrovascular accidents?

Science.gov (United States)

Karimi, Mehran; Borhani Haghighi, Afshin; Yazdani, Maryam; Raisi, Hamideh; Giti, Rahil; Namazee, Mohammad Reza

2008-01-01

In this research, we sought to determine the association between beta-thalassemia trait and ischemic cerebrovascular accident (CVA). In acase-control study, 148 patients with thromboembolic cerebrovascular events were evaluated for the presence of hypertension, diabetes mellitus, hyperlipidemia, and beta-thalassemia trait. A total of 156 age- and sex-matched patients with no cardiac or cerebrovascular diseases, serving as the control group, were also investigated for the above-mentioned risk factors. We found that 6.1% of patients with ischemic CVA and 12.2% of the control group had beta-thalassemia trait (P = .066). In male patients, the negative association between ischemic CVA and presence of beta-thalassemia trait was significant (P = .008). In patients, the prevalence of hypertension was also significantly different between those with and without beta-thalassemia trait (P = .01); those with beta-thalassemia trait had a lower mean blood pressure than those without the trait. beta-Thalassemia trait may have a protective effect against ischemic CVA that might be caused by the lower arterial blood pressure observed in those with this trait.

Human heart disease : lessons from human pluripotent stem cell-derived cardiomyocytes

NARCIS (Netherlands)

Giacomelli, E.; Mummery, C.L.; Bellin, M.

2017-01-01

Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current

Genetic Diversity, Population Structure, and Heritability of Fruit Traits in Capsicum annuum

Science.gov (United States)

Naegele, Rachel P.; Mitchell, Jenna; Hausbeck, Mary K.

2016-01-01

Cultivated pepper (Capsicum annuum) is a phenotypically diverse species grown throughout the world. Wild and landrace peppers are typically small-fruited and pungent, but contain many important traits such as insect and disease resistance. Cultivated peppers vary dramatically in size, shape, pungency, and color, and often lack resistance traits. Fruit characteristics (e.g. shape and pericarp thickness) are major determinants for cultivar selection, and their association with disease susceptibility can reduce breeding efficacy. This study evaluated a diverse collection of peppers for mature fruit phenotypic traits, correlation among fruit traits and Phytophthora fruit rot resistance, genetic diversity, population structure, and trait broad sense heritability. Significant differences within all fruit phenotype categories were detected among pepper lines. Fruit from Europe had the thickest pericarp, and fruit from Ecuador had the thinnest. For fruit shape index, fruit from Africa had the highest index, while fruit from Europe had the lowest. Five genetic clusters were detected in the pepper population and were significantly associated with fruit thickness, end shape, and fruit shape index. The genetic differentiation between clusters ranged from little to very great differentiation when grouped by the predefined categories. Broad sense heritability for fruit traits ranged from 0.56 (shoulder height) to 0.98 (pericarp thickness). When correlations among fruit phenotypes and fruit disease were evaluated, fruit shape index was negatively correlated with pericarp thickness, and positively correlated with fruit perimeter. Pepper fruit pericarp, perimeter, and width had a slight positive correlation with Phytophthora fruit rot, whereas fruit shape index had a slight negative correlation. PMID:27415818

Libyan Boy with Autosomal Recessive Trait (P22-phox Defect of Chronic Granulomatous Disease

Directory of Open Access Journals (Sweden)

Ilka Schulze

2006-09-01

Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency disorder of the phagocytes. In this disorder, phagocytic cells (polymorphonuclear leukocytes and monocytes cannot produce active oxygen metabolites, and therefore, cannot destroy the ingested intracellular bacteria. Clinically, patients with CGD usually have recurrent bacterial and fungal infections causing abscess and granuloma formation in the skin, lymph nodes and visceral organs.In this report, we present a boy from Libya with a rare autosomal recessive trait of CGD (defect of p22-phox who has chronic lung disease following multiple severe pneumonia attacks. The case we present suffered from bloody diarrhea since the third month of his life. He also had recurrent episodes of fever, and later, developed persistent cervical lymphadenitis and failure to gain weight. CGD is a very rare condition worldwide. It is also not recognized here in Libya, and usually not in the list of differential diagnosis for chronic pulmonary infections. We advise that pediatricians and general practitioners who treat chronic cases of lung diseases (with or without chronic diarrhea should consider primary immunodeficiency disorders in the hope that early diagnosis and treatment may prevent chronic complications especially of the respiratory tract. Furthermore, we state that, to the best of our knowledge, this is the first documented case of CGD from Libya.

A Novel SCN5A Mutation in a Patient with Coexistence of Brugada Syndrome Traits and Ischaemic Heart Disease

Directory of Open Access Journals (Sweden)

Anders G. Holst

2009-01-01

Full Text Available Brugada syndrome (BrS is a primary electrical heart disease, which can lead to sudden cardiac death. In older patients with BrS, the disease may coexist with ischaemic heart disease (IHD and recent studies support a synergistic proarrhythmic effect of the two disease entities. We report a case that illustrates this. The index patient was a middle-aged patient with BrS traits, IHD, and aborted sudden cardiac death. Mutation analysis discovered a novel mutation P468L in the NaV1.5 sodium channel. Surprisingly, voltage-clamp experiments on the wild-type and mutant NaV1.5 channels expressed in HEK cells revealed no functional effect of the mutation. In a patient like ours, the distinction between IHD and BrS as the cause of an aborted sudden cardiac death is hard to establish and mounting evidence shows that coexistence of the two may have a synergistic proarrhythmic effect.

Brain structure links trait creativity to openness to experience.

Science.gov (United States)

Li, Wenfu; Li, Xueting; Huang, Lijie; Kong, Xiangzhen; Yang, Wenjing; Wei, Dongtao; Li, Jingguang; Cheng, Hongsheng; Zhang, Qinglin; Qiu, Jiang; Liu, Jia

2015-02-01

Creativity is crucial to the progression of human civilization and has led to important scientific discoveries. Especially, individuals are more likely to have scientific discoveries if they possess certain personality traits of creativity (trait creativity), including imagination, curiosity, challenge and risk-taking. This study used voxel-based morphometry to identify the brain regions underlying individual differences in trait creativity, as measured by the Williams creativity aptitude test, in a large sample (n = 246). We found that creative individuals had higher gray matter volume in the right posterior middle temporal gyrus (pMTG), which might be related to semantic processing during novelty seeking (e.g. novel association, conceptual integration and metaphor understanding). More importantly, although basic personality factors such as openness to experience, extroversion, conscientiousness and agreeableness (as measured by the NEO Personality Inventory) all contributed to trait creativity, only openness to experience mediated the association between the right pMTG volume and trait creativity. Taken together, our results suggest that the basic personality trait of openness might play an important role in shaping an individual's trait creativity. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The circle of life: A cross-cultural comparison of children's attribution of life-cycle traits.

Science.gov (United States)

Burdett, Emily R R; Barrett, Justin L

2016-06-01

Do children attribute mortality and other life-cycle traits to all minded beings? The present study examined whether culture influences young children's ability to conceptualize and differentiate human beings from supernatural beings (such as God) in terms of life-cycle traits. Three-to-5-year-old Israeli and British children were questioned whether their mother, a friend, and God would be subject to various life-cycle processes: Birth, death, ageing, existence/longevity, and parentage. Children did not anthropomorphize but differentiated among human and supernatural beings, attributing life-cycle traits to humans, but not to God. Although 3-year-olds differentiated significantly among agents, 5-year-olds attributed correct life-cycle traits more consistently than younger children. The results also indicated some cross-cultural variation in these attributions. Implications for biological conceptual development are discussed. © 2015 The British Psychological Society.

The human genome; you gain some, you lose some

NARCIS (Netherlands)

Kriek, Marjolein

2007-01-01

Copy number variations (CNVs) in the human genome are inherent in both evolutionary progression as well as the etiology of disease. The introduction of this thesis will review CNVs that appear to be neutral as well as CNVs that appear to be related to a phenotypic trait. This will be followed by a

The UK10K project identifies rare variants in health and disease

NARCIS (Netherlands)

K. Walter (Klaudia); J.L. Min (Josine L.); J. Huang (Jie); L. Crooks (Lucy); Y. Memari (Yasin); S. McCarthy (Shane); J.R.B. Perry (John); C. Xu (Changjiang); M. Futema (Marta); D. Lawson (Daniel); V. Iotchkova (Valentina); S. Schiffels (Stephan); A.E. Hendricks (Audrey E.); P. Danecek (Petr); R. Li (Rui); J. Floyd (James); L.V. Wain (Louise); I.E. Barroso (Inês); S.E. Humphries (Steve); M.E. Hurles (Matthew); E. Zeggini (Eleftheria); J.C. Barrett (Jeffrey); V. Plagnol (Vincent); J.B. Richards (Brent); C.M.T. Greenwood (Celia); N.J. Timpson (Nicholas); R. Durbin (Richard); S. Bala (Senduran); P. Clapham (Peter); G. Coates (Guy); T. Cox (Tony); A. Daly (Allan); Y. Du (Yuanping); T. Edkins (Ted); P. Ellis (Peter); P. Flicek (Paul); X. Guo (Xiaosen); X. Guo (Xueqin); L. Huang (Liren); D.K. Jackson (David K.); C. Joyce (Chris); T. Keane (Thomas); A. Kolb-Kokocinski (Anja); C. Langford (Cordelia); Y. Li (Yingrui); J. Liang (Jieqin); H. Lin (Hong); R. Liu (Ryan); J. Maslen (John); D. Muddyman (Dawn); M.A. Quail (Michael A.); J. Stalker (Jim); J. Sun (Jianping); J. Tian (Jing); G. Wang (Guangbiao); J. Wang (Jun); Y. Wang (Yu); K. Wong (Kim); P. Zhang (Pingbo); E. Birney (Ewan); C. Boustred (Chris); L. Chen (Lu); G. Clement (Gail); M. Cocca (Massimiliano); G.D. Smith; I.N.M. Day (Ian N.M.); A.G. Day-Williams (Aaron); T. Down (Thomas); D.M. Dunham (David); D.M. Evans (David M.); T.R. Gaunt (Tom); M. Geihs (Matthias); D. Hart (Deborah); B. Howie (Bryan); T. Hubbard (Tim); P.G. Hysi (Pirro); Y. Jamshidi (Yalda); K.J. Karczewski (Konrad); J.P. Kemp (John); G. Lachance (Genevieve); M. Lek (Monkol); M.C. Lopes (Margarida); D.G. MacArthur (Daniel G.); J. Marchini (Jonathan); M. Mangino (Massimo); I. Mathieson (Iain); S. Metrustry (Sarah); A. Moayyeri (Alireza); K. Northstone (Kate); K. Panoutsopoulou (Kalliope); L. Paternoster (Lavinia); L. Quaye (Lydia); S. Ring (Susan); G.R.S. Ritchie (Graham R.S.); H.A. Shihab (Hashem A.); S.-Y. Shin (So-Youn); K.S. Small (Kerrin); M.S. Artigas; N. Soranzo (Nicole); L. Southam (Lorraine); T.D. Spector (Timothy); B. St Pourcain (Beate); G. Surdulescu (Gabriela); I. Tachmazidou (Ioanna); M.D. Tobin (Martin); A.M. Valdes; P.M. Visscher (Peter); K. Ward (Kirsten); S.G. Wilson (Scott); J. Yang (Joanna); F. Zhang (Feng); H.-F. Zheng (Hou-Feng); R. Anney (Richard); M. Ayub (Muhammad); D.H.R. Blackwood (Douglas); P.F. Bolton (Patrick F.); G. Breen (Gerome); D.A. Collier (David); N.J. Craddock (Nick); S. Curran (Sarah); D. Curtis (David); L. Gallagher (Louise); D. Geschwind (Daniel); H. Gurling (Hugh); P.A. Holmans (Peter A.); I. Lee (Irene); J. Lönnqvist (Jouko); P. McGuffin (Peter); A.M. McIntosh (Andrew); A.G. McKechanie (Andrew G.); A. McQuillin (Andrew); J. Morris (James); M.C. O'donovan (Michael); M.J. Owen (Michael); A. Palotie (Aarno); J.R. Parr (Jeremy R.); T. Paunio (Tiina); O.P.H. Pietiläinen (Olli); K. Rehnström (Karola); S.I. Sharp (Sally I.); D. Skuse (David); D. St. Clair (David); J. Suvisaari (Jaana); J.T. Walters (James); H.J. Williams (Hywel J.); E. Bochukova (Elena); R. Bounds (Rebecca); A. Dominiczak (Anna); I.S. Farooqi (I. Sadaf); J. Keogh (Julia); G. Marenne (Gaëlle); A.D. Morris (Andrew); S. O'Rahilly (Stephen); D.J. Porteous (David J.); B.H. Smith (Blair); E. Wheeler (Eleanor); S.H. Al Turki (Saeed); C. Anderson (Carl); D. Antony (Dinu); P.L. Beales (Philip); J. Bentham (Jamie); S. Bhattacharya (Shoumo); M. Calissano (Mattia); K. Carss (Keren); K. Chatterjee (Krishna); S. Cirak (Sebahattin); C. Cosgrove (Catherine); D.R. Fitzpatrick (David R.); A.R. Foley (A. Reghan); C.S. Franklin (Christopher S.); D. Grozeva (Detelina); H.M. Mitchison (Hannah M.); F. Muntoni; A. Onoufriadis (Alexandros); V. Parker (Victoria); F. Payne (Felicity); F.L. Raymond (F. Lucy); N. Roberts (Nicola); D.B. Savage (David); P.J. Scambler (Peter); M. Schmidts (Miriam); N. Schoenmakers (Nadia); R.K. Semple (Robert K.); E. Serra (Eva); O. Spasic-Boskovic (Olivera); E. Stevens (Elizabeth); M. Van Kogelenberg (Margriet); P. Vijayarangakannan (Parthiban); K.A. Williamson (Kathleen); C. Wilson (Crispian); T. Whyte (Tamieka); A. Ciampi (Antonio); K. Oualkacha (Karim); M. Bobrow (Martin); H. Griffin (Heather); J. Kaye (Jane); K. Kennedy (Karen); A. Kent (Alastair); C. Smee (Carol); R. Charlton (Ruth); R. Ekong (Rosemary); F. Khawaja (Farrah); L.R. Lopes (Luis R.); N. Migone (Nicola); S.J. Payne (Stewart J.); R.C. Pollitt (Rebecca C.); S. Povey (Sue); C.K. Ridout (Cheryl K.); R.L. Robinson (Rachel L.); R.H. Scott (Richard H.); A. Shaw (Adam); P. Syrris (Petros); R. Taylor (Rohan); A.M. Vandersteen (Anthony M.); A. Amuzu (Antoinette); J.P. Casas (Juan); J.C. Chambers (John); G.V. Dedoussis (George); G. Gambaro (Giovanni); P. Gasparini (Paolo); A. Isaacs (Aaron); J. Johnson (Jon); M.E. Kleber (Marcus); J.S. Kooner (Jaspal S.); C. Langenberg (Claudia); J. Luan; G. Malerba (Giovanni); W. März (Winfried); A. Matchan (Angela); R. Morris (Richard); B.G. Nordestgaard (Børge); M. Benn (Marianne); R.A. Scott (Robert); D. Toniolo (Daniela); M. Traglia (Michela); A. Tybjaerg-Hansen; C.M. van Duijn (Cornelia); E.M. van Leeuwen (Elisa); A. Varbo (Anette); P.H. Whincup (Peter); G. Zaza (Gianluigi); W. Zhang (Weihua)

2015-01-01

textabstractThe contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In

Skin Diseases: Cross-section of human skin

Science.gov (United States)

Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

Personality Traits and Cortical Activity Affect Gambling Behavior in Parkinson's Disease.

Science.gov (United States)

Balconi, Michela; Siri, Chiara; Meucci, Nicoletta; Pezzoli, Gianni; Angioletti, Laura

2018-03-26

Pathological gambling (PG) in Parkinson's disease (PD) manifests as a persistent and uncontrollable gambling behavior, characterized by dysfunctional decision-making and emotional impairment related to high-risk decisions. The aim of this study was to explore the relationship between personality traits and prefrontal cortex activity in PD patients with or without PG. Thus, hemodynamic cortical activity measured by functional near-infrared spectroscopy (fNIRS) and Iowa Gambling Task (IGT) performance were recorded in forty-six PD patients, divided into three groups according to their gambling status: PD patients with active gambling behavior (PDG); PD patients who remitted from PG (PDNG); and a control group (CG) composed by patients with PD only. Results indicates that gambling behavior in PD patients is strongly predictive of dysfunctional cognitive strategy; affecting anomalous cortical response with a left hemispheric unbalance in dorsal areas; and it is related to more reward sensitivity than impulsivity personality components. PDG patients differed from PDNG and CG from both behavioral and brain response to decision-making. Overall, these effects confirm a pathological condition related to cognitive and emotional aspects which makes the patients with PGD victims of their dysfunctional behavior.

The Immoral Assumption Effect: Moralization Drives Negative Trait Attributions.

Science.gov (United States)

Meindl, Peter; Johnson, Kate M; Graham, Jesse

2016-04-01

Jumping to negative conclusions about other people's traits is judged as morally bad by many people. Despite this, across six experiments (total N = 2,151), we find that multiple types of moral evaluations--even evaluations related to open-mindedness, tolerance, and compassion--play a causal role in these potentially pernicious trait assumptions. Our results also indicate that moralization affects negative-but not positive-trait assumptions, and that the effect of morality on negative assumptions cannot be explained merely by people's general (nonmoral) preferences or other factors that distinguish moral and nonmoral traits, such as controllability or desirability. Together, these results suggest that one of the more destructive human tendencies--making negative assumptions about others--can be caused by the better angels of our nature. © 2016 by the Society for Personality and Social Psychology, Inc.

Human gene therapy and imaging in neurological diseases

International Nuclear Information System (INIS)

Jacobs, Andreas H.; Winkler, Alexandra; Castro, Maria G.; Lowenstein, Pedro

2005-01-01

Molecular imaging aims to assess non-invasively disease-specific biological and molecular processes in animal models and humans in vivo. Apart from precise anatomical localisation and quantification, the most intriguing advantage of such imaging is the opportunity it provides to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Further, molecular imaging can be used to address basic scientific questions, e.g. transcriptional regulation, signal transduction or protein/protein interaction, and will be essential in developing treatment strategies based on gene therapy. Most importantly, molecular imaging is a key technology in translational research, helping to develop experimental protocols which may later be applied to human patients. Over the past 20 years, imaging based on positron emission tomography (PET) and magnetic resonance imaging (MRI) has been employed for the assessment and ''phenotyping'' of various neurological diseases, including cerebral ischaemia, neurodegeneration and brain gliomas. While in the past neuro-anatomical studies had to be performed post mortem, molecular imaging has ushered in the era of in vivo functional neuro-anatomy by allowing neuroscience to image structure, function, metabolism and molecular processes of the central nervous system in vivo in both health and disease. Recently, PET and MRI have been successfully utilised together in the non-invasive assessment of gene transfer and gene therapy in humans. To assess the efficiency of gene transfer, the same markers are being used in animals and humans, and have been applied for phenotyping human disease. Here, we review the imaging hallmarks of focal and disseminated neurological diseases, such as cerebral ischaemia, neurodegeneration and glioblastoma multiforme, as well as the attempts to translate gene therapy's experimental knowledge into clinical applications and the way in which this process is being promoted through the use of

Evolution of cultural traits occurs at similar relative rates in different world regions.

Science.gov (United States)

Currie, Thomas E; Mace, Ruth

2014-11-22

A fundamental issue in understanding human diversity is whether or not there are regular patterns and processes involved in cultural change. Theoretical and mathematical models of cultural evolution have been developed and are increasingly being used and assessed in empirical analyses. Here, we test the hypothesis that the rates of change of features of human socio-cultural organization are governed by general rules. One prediction of this hypothesis is that different cultural traits will tend to evolve at similar relative rates in different world regions, despite the unique historical backgrounds of groups inhabiting these regions. We used phylogenetic comparative methods and systematic cross-cultural data to assess how different socio-cultural traits changed in (i) island southeast Asia and the Pacific, and (ii) sub-Saharan Africa. The relative rates of change in these two regions are significantly correlated. Furthermore, cultural traits that are more directly related to external environmental conditions evolve more slowly than traits related to social structures. This is consistent with the idea that a form of purifying selection is acting with greater strength on these more environmentally linked traits. These results suggest that despite contingent historical events and the role of humans as active agents in the historical process, culture does indeed evolve in ways that can be predicted from general principles.

Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

DEFF Research Database (Denmark)

Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

2016-01-01

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends...

Natural selection and infectious disease in human populations

Science.gov (United States)

Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.

2015-01-01

The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769

[Oral microbiota: a promising predictor of human oral and systemic diseases].

Science.gov (United States)

Xin, Xu; Junzhi, He; Xuedong, Zhou

2015-12-01

A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.

Genetic diversity of disease-associated loci in Turkish population.

Science.gov (United States)

Karaca, Sefayet; Cesuroglu, Tomris; Karaca, Mehmet; Erge, Sema; Polimanti, Renato

2015-04-01

Many consortia and international projects have investigated the human genetic variation of a large number of ethno-geographic groups. However, populations with peculiar genetic features, such as the Turkish population, are still absent in publically available datasets. To explore the genetic predisposition to health-related traits of the Turkish population, we analyzed 34 genes associated with different health-related traits (for example, lipid metabolism, cardio-vascular diseases, hormone metabolism, cellular detoxification, aging and energy metabolism). We observed relevant differences between the Turkish population and populations with non-European ancestries (that is, Africa and East Asia) in some of the investigated genes (that is, AGT, APOE, CYP1B1, GNB3, IL10, IL6, LIPC and PON1). As most complex traits are highly polygenic, we developed polygenic scores associated with different health-related traits to explore the genetic diversity of the Turkish population with respect to other human groups. This approach showed significant differences between the Turkish population and populations with non-European ancestries, as well as between Turkish and Northern European individuals. This last finding is in agreement with the genetic structure of European and Middle East populations, and may also agree with epidemiological evidences about the health disparities of Turkish communities in Northern European countries.

Lysosomal storage disease 2 - Pompe's disease

NARCIS (Netherlands)

van der Ploeg, Ans T.; Reuser, Arnold J. J.

2008-01-01

Pompe's disease, glycogen-storage disease type II, and acid maltase deficiency are alternative names for the same metabolic disorder. It is a pan-ethnic autosomal recessive trait characterised by acid alpha-glucosidase deficiency leading to lysosomal glycogen storage. Pompe's disease is also

Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken

Science.gov (United States)

Jin, Sihua; Zhu, Feng; Wang, Yanyun; Yi, Guoqiang; Li, Junying; Lian, Ling; Zheng, Jiangxia; Xu, Guiyun; Jiao, Rengang; Gong, Yu; Hou, Zhuocheng; Yang, Ning

2016-01-01

The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders. PMID:27439785

Associations between common intestinal parasites and bacteria in humans as revealed by qPCR

DEFF Research Database (Denmark)

O'Brien Andersen, L.; Karim, A. B.; Roager, Henrik Munch

2016-01-01

Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we...

Genetic architecture of clinical mastitis traits in dairy cattle

DEFF Research Database (Denmark)

Sahana, Goutam; Guldbrandtsen, Bernt; Lund, Mogens Sandø

2012-01-01

investigate the genetic architecture of clinical mastitis and somatic cell score traits in dairy cattle using a high density (HD) SNP panel. Mastitis, an inflammation of the mammary gland most commonly caused by bacterial infection, is a frequent disease in dairy cattle. Clinical mastitis and somatic cell...... score from first three lactations were studied for association with SNP markers in 4,200 progeny-tested Nordic Holstein bulls. Single trait breeding values were used as phenotypes. All the individuals were genotyped with BovineSNP50 Beadchip. Part of this population was also genotyped with the Bovine...... mixed model analysis. After Bonferroni correction 12, 372 SNP exhibited genome-wide significant associations with mastitis related traits. A total 61 QTL regions on 22 chromosomes associated with mastitis related traits were identified. The SNP with highest effect explained 5.6% of the variance...

Impacts of Gut Bacteria on Human Health and Diseases

Science.gov (United States)

Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

2015-01-01

Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

Epidemiological studies on Johne’s disease in ruminants and Crohn’s disease in humans in Egypt

Directory of Open Access Journals (Sweden)

A. Fawzy

2013-12-01

Full Text Available The correlation between Johne’s disease (JD and Crohn’s disease (CD in Egypt was investigated. A total of 371 human and 435 animal sera were collected from the same Egyptian governorates that had a known history of paratuberculosis infection and were subjected to screening for paratuberculosis using ELISA to assess the human/animal risk at a single time point. Five CD patients and five JD clinically infected dairy cattle were also included. Out of 435 animal serum samples, 196 (45.2% were MAP-ELISA positive. Twenty three (6.1% out of 371 human serum samples were MAP-ELISA positive, while 37 (9.9% were positive for anti-Saccharomyces cerevisiae antibodies (ASCA ELISAs. There was a very poor agreement between human MAP and ASCA ELISAs (0.036 by kappa statistics. The prevalence of MAP antibodies among humans is clearly lower than in animals. In conclusion there is an increase in Johne’s disease incidence in animals and a very weak relationship between MAP and Crohn’s disease in humans in Egypt.

Whole Trait Theory

Science.gov (United States)

Fleeson, William; Jayawickreme, Eranda

2014-01-01

Personality researchers should modify models of traits to include mechanisms of differential reaction to situations. Whole Trait Theory does so via five main points. First, the descriptive side of traits should be conceptualized as density distributions of states. Second, it is important to provide an explanatory account of the Big 5 traits. Third, adding an explanatory account to the Big 5 creates two parts to traits, an explanatory part and a descriptive part, and these two parts should be recognized as separate entities that are joined into whole traits. Fourth, Whole Trait Theory proposes that the explanatory side of traits consists of social-cognitive mechanisms. Fifth, social-cognitive mechanisms that produce Big-5 states should be identified. PMID:26097268

Quantitative trait loci for behavioural traits in chicken

NARCIS (Netherlands)

Buitenhuis, A.J.; Rodenburg, T.B.; Siwek, M.Z.; Cornelissen, S.J.B.; Nieuwland, M.G.B.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Koene, P.; Bovenhuis, H.; Poel, van der J.J.

2005-01-01

The detection of quantitative trait loci (QTL) of behavioural traits has mainly been focussed on mouse and rat. With the rapid development of molecular genetics and the statistical tools, QTL mapping for behavioural traits in farm animals is developing. In chicken, a total of 30 QTL involved in

Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

Science.gov (United States)

Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

2013-01-01

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

The regulatory effect of miRNAs is a heritable genetic trait in humans

Directory of Open Access Journals (Sweden)

Geeleher Paul

2012-08-01

Full Text Available Abstract Background microRNAs (miRNAs have been shown to regulate the expression of a large number of genes and play key roles in many biological processes. Several previous studies have quantified the inhibitory effect of a miRNA indirectly by considering the expression levels of genes that are predicted to be targeted by the miRNA and this approach has been shown to be robust to the choice of prediction algorithm. Given a gene expression dataset, Cheng et al. defined the regulatory effect score (RE-score of a miRNA as the difference in the gene expression rank of targets of the miRNA compared to non-targeted genes. Results Using microarray data from parent-offspring trios from the International HapMap project, we show that the RE-score of most miRNAs is correlated between parents and offspring and, thus, inter-individual variation in RE-score has a genetic component in humans. Indeed, the mean RE-score across miRNAs is correlated between parents and offspring, suggesting genetic differences in the overall efficiency of the miRNA biogenesis pathway between individuals. To explore the genetics of this quantitative trait further, we carried out a genome-wide association study of the mean RE-score separately in two HapMap populations (CEU and YRI. No genome-wide significant associations were discovered; however, a SNP rs17409624, in an intron of DROSHA, was significantly associated with mean RE-score in the CEU population following permutation-based control for multiple testing based on all SNPs mapped to the canonical miRNA biogenesis pathway; of 244 individual miRNA RE-scores assessed in the CEU, 214 were associated (p p = 0.04 with mean RE-score in the YRI population. Interestingly, the same SNP was associated with 17 (8.5% of all expressed miRNA expression levels in the CEU. We also show here that the expression of the targets of most miRNAs is more highly correlated with global changes in miRNA regulatory effect than with the expression of

Drosophila tools and assays for the study of human diseases

Directory of Open Access Journals (Sweden)

Berrak Ugur

2016-03-01

Full Text Available Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes.

Emerging arboviral human diseases in Southern Europe.

Science.gov (United States)

Papa, Anna

2017-08-01

Southern Europe is characterized by unique landscape and climate which attract tourists, but also arthropod vectors, some of them carrying pathogens. Among several arboviral diseases that emerged in the region during the last decade, West Nile fever accounted for high number of human cases and fatalities, while Crimean-Congo hemorrhagic fever expanded its geographic distribution, and is considered as a real threat for Europe. Viruses evolve rapidly and acquire mutations making themselves stronger and naive populations more vulnerable. In an effort to tackle efficiently the emerging arboviral diseases, preparedness and strategic surveillance are needed for the early detection of the pathogen and containment and mitigation of probable outbreaks. In this review, the main human arboviral diseases that emerged in Southern Europe are described. © 2017 Wiley Periodicals, Inc.

Investigation of Personality Traits between Infertile Women Submitted to Assisted Reproductive Technology or Surrogacy

OpenAIRE

Najmeh Asgarini; Fariba Yazdkhasti; Mohammad Hossein Nasr Esfahani

2016-01-01

Background: Personality traits affect human relationships, social interactions, treatment procedures, and essentially all human activities. The purpose of this study is to investigate the personality traits -including sensation seeking, flexibility, and happiness - among a variety of infertile women who were apt to choose assisted reproductive technology (ART) or surrogacy. Materials and Methods: This is a cross-sectional study that was performed on 251 infertile women who v...

Effect of genetic architecture on the prediction accuracy of quantitative traits in samples of unrelated individuals.

Science.gov (United States)

Morgante, Fabio; Huang, Wen; Maltecca, Christian; Mackay, Trudy F C

2018-06-01

Predicting complex phenotypes from genomic data is a fundamental aim of animal and plant breeding, where we wish to predict genetic merits of selection candidates; and of human genetics, where we wish to predict disease risk. While genomic prediction models work well with populations of related individuals and high linkage disequilibrium (LD) (e.g., livestock), comparable models perform poorly for populations of unrelated individuals and low LD (e.g., humans). We hypothesized that low prediction accuracies in the latter situation may occur when the genetics architecture of the trait departs from the infinitesimal and additive architecture assumed by most prediction models. We used simulated data for 10,000 lines based on sequence data from a population of unrelated, inbred Drosophila melanogaster lines to evaluate this hypothesis. We show that, even in very simplified scenarios meant as a stress test of the commonly used Genomic Best Linear Unbiased Predictor (G-BLUP) method, using all common variants yields low prediction accuracy regardless of the trait genetic architecture. However, prediction accuracy increases when predictions are informed by the genetic architecture inferred from mapping the top variants affecting main effects and interactions in the training data, provided there is sufficient power for mapping. When the true genetic architecture is largely or partially due to epistatic interactions, the additive model may not perform well, while models that account explicitly for interactions generally increase prediction accuracy. Our results indicate that accounting for genetic architecture can improve prediction accuracy for quantitative traits.

Best Practices for Preventing Vector-Borne Diseases in Dogs and Humans.

Science.gov (United States)

Dantas-Torres, Filipe; Otranto, Domenico

2016-01-01

Vector-borne diseases constitute a diversified group of illnesses, which are caused by a multitude of pathogens transmitted by arthropod vectors, such as mosquitoes, fleas, ticks, and sand flies. Proper management of these diseases is important from both human and veterinary medicine standpoints, given that many of these pathogens are transmissible to humans and dogs, which often live in close contact. In this review, we summarize the most important vector-borne diseases of dogs and humans and the best practices for their prevention. The control of these diseases would ultimately improve animal and human health and wellbeing, particularly in developing countries in the tropics, where the risk of these diseases is high and access to health care is poor. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Pathology of Human Prion Diseases

Directory of Open Access Journals (Sweden)

2009-03-01

Full Text Available Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

The quantitative LOD score: test statistic and sample size for exclusion and linkage of quantitative traits in human sibships.

Science.gov (United States)

Page, G P; Amos, C I; Boerwinkle, E

1998-04-01

We present a test statistic, the quantitative LOD (QLOD) score, for the testing of both linkage and exclusion of quantitative-trait loci in randomly selected human sibships. As with the traditional LOD score, the boundary values of 3, for linkage, and -2, for exclusion, can be used for the QLOD score. We investigated the sample sizes required for inferring exclusion and linkage, for various combinations of linked genetic variance, total heritability, recombination distance, and sibship size, using fixed-size sampling. The sample sizes required for both linkage and exclusion were not qualitatively different and depended on the percentage of variance being linked or excluded and on the total genetic variance. Information regarding linkage and exclusion in sibships larger than size 2 increased as approximately all possible pairs n(n-1)/2 up to sibships of size 6. Increasing the recombination (theta) distance between the marker and the trait loci reduced empirically the power for both linkage and exclusion, as a function of approximately (1-2theta)4.

Bilaterally Asymmetric Effects of Quantitative Trait Loci (QTLs): QTLs That Affect Laxity in the Right Versus Left Coxofemoral (Hip) Joints of the Dog (Canis familiaris)

OpenAIRE

Chase, Kevin; Lawler, Dennis F.; Adler, Fred R.; Ostrander, Elaine A.; Lark, Karl G.

2004-01-01

In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is frequent and heritable, providing a genetic model for some aspects of the human disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait loci (QTLs) that regulate laxity in the hip joint.A population of 286 PWDs, each characterized by ca. 500 molecular genetic markers, was analyzed for subluxation of the hip joint as measured by the Norberg angle, a quantitative radiographic measure of laxit...

Sticking with the nice guy: trait warmth information impairs learning and modulates person perception brain network activity.

Science.gov (United States)

Lee, Victoria K; Harris, Lasana T

2014-12-01

Social learning requires inferring social information about another person, as well as evaluating outcomes. Previous research shows that prior social information biases decision making and reduces reliance on striatal activity during learning (Delgado, Frank, & Phelps, Nature Neuroscience 8 (11): 1611-1618, 2005). A rich literature in social psychology on person perception demonstrates that people spontaneously infer social information when viewing another person (Fiske & Taylor, 2013) and engage a network of brain regions, including the medial prefrontal cortex, temporal parietal junction, superior temporal sulcus, and precuneus (Amodio & Frith, Nature Reviews Neuroscience, 7(4), 268-277, 2006; Haxby, Gobbini, & Montgomery, 2004; van Overwalle Human Brain Mapping, 30, 829-858, 2009). We investigate the role of these brain regions during social learning about well-established dimensions of person perception-trait warmth and trait competence. We test the hypothesis that activity in person perception brain regions interacts with learning structures during social learning. Participants play an investment game where they must choose an agent to invest on their behalf. This choice is guided by cues signaling trait warmth or trait competence based on framing of monetary returns. Trait warmth information impairs learning about human but not computer agents, while trait competence information produces similar learning rates for human and computer agents. We see increased activation to warmth information about human agents in person perception brain regions. Interestingly, activity in person perception brain regions during the decision phase negatively predicts activity in the striatum during feedback for trait competence inferences about humans. These results suggest that social learning may engage additional processing within person perception brain regions that hampers learning in economic contexts.

The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque.

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Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

2013-01-01

Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.

Assessing the Utility of Compound Trait Estimates of Narrow Personality Traits.

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Credé, Marcus; Harms, Peter D; Blacksmith, Nikki; Wood, Dustin

2016-01-01

It has been argued that approximations of narrow traits can be made through linear combinations of broad traits such as the Big Five personality traits. Indeed, Hough and Ones ( 2001 ) used a qualitative analysis of scale content to arrive at a taxonomy of how Big Five traits might be combined to approximate various narrow traits. However, the utility of such compound trait approximations has yet to be established beyond specific cases such as integrity and customer service orientation. Using data from the Eugene-Springfield Community Sample (Goldberg, 2008 ), we explore the ability of linear composites of scores on Big Five traits to approximate scores on 127 narrow trait measures from 5 well-known non-Big-Five omnibus measures of personality. Our findings indicate that individuals' standing on more than 30 narrow traits can be well estimated from 3 different types of linear composites of scores on Big Five traits without a substantial sacrifice in criterion validity. We discuss theoretical accounts for why such relationships exist as well as the theoretical and practical implications of these findings for researchers and practitioners.

An atlas of human long non-coding RNAs with accurate 5′ ends

KAUST Repository

Hon, Chung-Chau

2017-02-28

Long non-coding RNAs (lncRNAs) are largely heterogeneous and functionally uncharacterized. Here, using FANTOM5 cap analysis of gene expression (CAGE) data, we integrate multiple transcript collections to generate a comprehensive atlas of 27,919 human lncRNA genes with high-confidence 5′ ends and expression profiles across 1,829 samples from the major human primary cell types and tissues. Genomic and epigenomic classification of these lncRNAs reveals that most intergenic lncRNAs originate from enhancers rather than from promoters. Incorporating genetic and expression data, we show that lncRNAs overlapping trait-associated single nucleotide polymorphisms are specifically expressed in cell types relevant to the traits, implicating these lncRNAs in multiple diseases. We further demonstrate that lncRNAs overlapping expression quantitative trait loci (eQTL)-associated single nucleotide polymorphisms of messenger RNAs are co-expressed with the corresponding messenger RNAs, suggesting their potential roles in transcriptional regulation. Combining these findings with conservation data, we identify 19,175 potentially functional lncRNAs in the human genome.

Animals models of maladaptive traits: Disorders in sensorimotor gating and attentional quantifiable responses as possible endophenotypes

Directory of Open Access Journals (Sweden)

Juan Pedro Vargas

2016-02-01

Full Text Available Traditional diagnostic scales are based on a number of symptoms to evaluate and classify mental diseases. In many cases, this process becomes subjective, since the patient must calibrate the magnitude of his/her symptoms and therefore the severity of his/her disorder. A completely different approach is based on the study of the more vulnerable traits of cognitive disorders. In this regard, animal models of mental illness could be a useful tool to characterise indicators of possible cognitive dysfunctions in humans. Specifically, several cognitive disorders such as schizophrenia involve a dysfunction in the mesocorticolimbic dopaminergic system during development. These variations in dopamine levels or dopamine receptor sensibility correlate with many behavioural disturbances. These behaviours may be included in a specific phenotype and may be analysed under controlled conditions in the laboratory. The present study provides an introductory overview of different quantitative traits that could be used as a possible risk indicator for different mental disorders, helping to define a specific endophenotype. Specifically, we examine different experimental procedures to measure impaired response in attention linked to sensorimotor gating as a possible personality trait involved in maladaptive behaviours.

Human genetics of infectious diseases: between proof of principle and paradigm.

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Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

2009-09-01

The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proof of principle that infectious diseases may result from various types of inborn errors of immunity, the genetic determinism of most infectious diseases in most patients remains unclear. However, in the future, studies in human genetics are likely to establish a new paradigm for infectious diseases.

Human anthrax as a re-emerging disease.

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Doganay, Mehmet; Demiraslan, Hayati

2015-01-01

Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

What makes a successful species? Traits facilitating survival in altered tropical forests.

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Hirschfeld, Mareike; Rödel, Mark-Oliver

2017-06-28

Ongoing conversion, disturbance and fragmentation of tropical forests stress this ecosystem and cause the decline or disappearance of many species. Particular traits have been identified which indicate an increasing extinction risk of a species, but traits facilitating survival in altered habitats have mostly been neglected. Here we search for traits that make a species tolerant to disturbances, thus independent of pristine forests. We identify the fauna that have an increasing effect on the ecosystem and its functioning in our human-dominated landscapes. We use a unique set of published data on the occurrences of 243 frog species in pristine and altered forests throughout the tropics. We established a forest dependency index with four levels, based on these occurrence data and applied Random Forest classification and binomial Generalized Linear Models to test whether species life history traits, ecological traits or range size influence the likelihood of a species to persist in disturbed habitats. Our results revealed that indirect developing species exhibiting a large range size and wide elevational distribution, being independent of streams, and inhabiting the leaf litter, cope best with modifications of their natural habitats. The traits identified in our study will likely persist in altered tropical forest systems and are comparable to those generally recognized for a low species extinction risk. Hence our findings will help to predict future frog communities in our human-dominated world.

Cancer or no cancer: the influence of trait anxiety and diagnosis on quality of life with breast cancer and benign disease: a prospective, longitudinal study

NARCIS (Netherlands)

Keyzer-Dekker, Claudia M. G.; de Vries, Jolanda; Mertens, Marlies C.; Roukema, Jan A.; van der Steeg, Alida F. W.

2013-01-01

High trait anxiety (HTA) causes an impaired quality of life (QOL) and fatigue in women with breast cancer (BC) and benign breast disease (BBD). We examined whether the lowered QOL was determined solely by the personality characteristic HTA or by the combination of personality and diagnosis. In a

Human endogenous retroviruses in neurologic disease.

Science.gov (United States)

Christensen, Tove

2016-01-01

Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Towards a unified model for leaf trait and trait-environment relationships

Science.gov (United States)

Wang, H.; Harrison, S. P.; Prentice, I. C.; Peng, C.; Yang, Y.

2016-12-01

A widely accepted core set of leaf traits describes key aspects of plant function including the coupling among carbon, nitrogen and water cycles at the leaf, plant and ecosystem scales. Our current research focuses on two questions: (1) what dimensions of correlated variation among traits apply across all vascular plants irrespective of environment; (2) how, and to what extent, can variations in community mean values of leaf traits be predicted along environmental gradients? Based on a large quantitative trait data set covering the major environmental gradients across China, we are tackling these questions via two complementary approaches: multivariate analysis of trait-trait, trait-site, and trait-environment relationships, and the development of conceptual models and testable hypotheses for the dependencies of each trait on other traits and/or specific environmental predictors. Preliminary multivariate analyses suggest the existence of at least two independent axes of variation in leaf traits, and show robust relationships between trait syndromes and growing-season climate variables. A minimal conceptual model then considers nitrogen per unit leaf area (Narea) as a function of leaf mass per unit area (LMA) and carboxylation capacity (Vcmax); LMA as a function of irradiance, temperature and water and/or nutrient stress; Vcmax as a function of irradiance, temperature and the long-term ci:ca ratio (indexed by δ13C); and the ci:ca ratio as a function of vapour pressure deficit, temperature and atmospheric pressure. Each of these dependencies has support from observations, pointing the way towards a comprehensive set of equations to predict community-mean values of core traits in next-generation terrestrial ecosystem models.

Are sickle cell anaemia and sickle cell trait predictive factors for periodontal disease? A cohort study.

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de Carvalho, H L C C; Thomaz, E B A F; Alves, C M C; Souza, S F C

2016-10-01

Periodontal diseases are associated with bacterial challenge and the host immune response, and are also modulated by genetic factors. There is evidence that sickle cell anaemia (SCA) does not represent a risk factor for periodontal diseases. However, it is still unclear whether the heterozygous condition [sickle cell trait (SCT)] is associated with periodontal diseases. SCT is a genetic condition that can cause vaso-occlusive events, which may be associated with a propensity to bacterial infections. The aim of this study was to investigate the association of SCA and SCT with periodontal diseases by evaluating clinical and radiographic characteristics. The sample (n = 369) was selected and divided into two groups: exposed groups [HbSS (SCA genotype) and HbAS (SCT genotype) = 246] and a nonexposed group (HbAA = 123). HbAA consisted of individuals without SCA and SCT. The clinical parameters evaluated were plaque index, gingival index, calculus index, clinical probing depth, clinical attachment level, gingival recession, tooth mobility and furcation involvement. The percentage of alveolar bone loss was measured using a Schei ruler. Binomial and Poisson regressions were used to estimate correlations of interest (α = 0.05). None of the periodontal parameters was associated with SCA. SCT was associated with gingivitis (p = 0.041) and periodontitis (p = 0.002). Individuals with SCT had a lower plaque index (p = 0.044) but a higher calculus index (p = 0.003) and greater alveolar bone loss (p = 0.010) compared with subjects in the HbAA group. SCT can act as a predictor for establishment of periodontal diseases. There was no correlation between SCA and periodontal diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Science.gov (United States)

Gulia-Nuss, Monika; Nuss, Andrew B.; Meyer, Jason M.; Sonenshine, Daniel E.; Roe, R. Michael; Waterhouse, Robert M.; Sattelle, David B.; de la Fuente, José; Ribeiro, Jose M.; Megy, Karine; Thimmapuram, Jyothi; Miller, Jason R.; Walenz, Brian P.; Koren, Sergey; Hostetler, Jessica B.; Thiagarajan, Mathangi; Joardar, Vinita S.; Hannick, Linda I.; Bidwell, Shelby; Hammond, Martin P.; Young, Sarah; Zeng, Qiandong; Abrudan, Jenica L.; Almeida, Francisca C.; Ayllón, Nieves; Bhide, Ketaki; Bissinger, Brooke W.; Bonzon-Kulichenko, Elena; Buckingham, Steven D.; Caffrey, Daniel R.; Caimano, Melissa J.; Croset, Vincent; Driscoll, Timothy; Gilbert, Don; Gillespie, Joseph J.; Giraldo-Calderón, Gloria I.; Grabowski, Jeffrey M.; Jiang, David; Khalil, Sayed M. S.; Kim, Donghun; Kocan, Katherine M.; Koči, Juraj; Kuhn, Richard J.; Kurtti, Timothy J.; Lees, Kristin; Lang, Emma G.; Kennedy, Ryan C.; Kwon, Hyeogsun; Perera, Rushika; Qi, Yumin; Radolf, Justin D.; Sakamoto, Joyce M.; Sánchez-Gracia, Alejandro; Severo, Maiara S.; Silverman, Neal; Šimo, Ladislav; Tojo, Marta; Tornador, Cristian; Van Zee, Janice P.; Vázquez, Jesús; Vieira, Filipe G.; Villar, Margarita; Wespiser, Adam R.; Yang, Yunlong; Zhu, Jiwei; Arensburger, Peter; Pietrantonio, Patricia V.; Barker, Stephen C.; Shao, Renfu; Zdobnov, Evgeny M.; Hauser, Frank; Grimmelikhuijzen, Cornelis J. P.; Park, Yoonseong; Rozas, Julio; Benton, Richard; Pedra, Joao H. F.; Nelson, David R.; Unger, Maria F.; Tubio, Jose M. C.; Tu, Zhijian; Robertson, Hugh M.; Shumway, Martin; Sutton, Granger; Wortman, Jennifer R.; Lawson, Daniel; Wikel, Stephen K.; Nene, Vishvanath M.; Fraser, Claire M.; Collins, Frank H.; Birren, Bruce; Nelson, Karen E.; Caler, Elisabet; Hill, Catherine A.

2016-01-01

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent. PMID:26856261

Animal models for human genetic diseases

African Journals Online (AJOL)

Sharif Sons

The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.

Genetic human prion disease modelled in PrP transgenic Drosophila.

Science.gov (United States)

Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

2017-09-20

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

Human Environmental Disease Network: A computational model to assess toxicology of contaminants.

Science.gov (United States)

Taboureau, Olivier; Audouze, Karine

2017-01-01

During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants associated with diverse human disorders. However, the relationships between diseases based on chemical exposure rarely have been studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration of systems biology and chemical toxicology using information on chemical contaminants and their disease relationships reported in the TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships, allowing inclusion of some degrees of significance in the disease-disease associations. Such a network can be used to identify uncharacterized connections between diseases. Examples are discussed for type 2 diabetes (T2D). Additionally, this computational model allows confirmation of already known links between chemicals and diseases (e.g., between bisphenol A and behavioral disorders) and also reveals unexpected associations between chemicals and diseases (e.g., between chlordane and olfactory alteration), thus predicting which chemicals may be risk factors to human health. The proposed human EDN model allows exploration of common biological mechanisms of diseases associated with chemical exposure, helping us to gain insight into disease etiology and comorbidity. This computational approach is an alternative to animal testing supporting the 3R concept.

Roentgenosemiotics and diagnosis of human diseases

International Nuclear Information System (INIS)

Mikhajlov, A.N.

1989-01-01

Modern concepts concerning roentgenologic semiotics, diagnosis of almost all the human diseases as well as the features of roentgenologic examintion of organs and systems are described. Roentgenologic symptoms and syndroms are systematized and standardized by anatomy branches. 48 refs

Genetic engineering in nonhuman primates for human disease modeling.

Science.gov (United States)

Sato, Kenya; Sasaki, Erika

2018-02-01

Nonhuman primate (NHP) experimental models have contributed greatly to human health research by assessing the safety and efficacy of newly developed drugs, due to their physiological and anatomical similarities to humans. To generate NHP disease models, drug-inducible methods, and surgical treatment methods have been employed. Recent developments in genetic and developmental engineering in NHPs offer new options for producing genetically modified disease models. Moreover, in recent years, genome-editing technology has emerged to further promote this trend and the generation of disease model NHPs has entered a new era. In this review, we summarize the generation of conventional disease model NHPs and discuss new solutions to the problem of mosaicism in genome-editing technology.

A journey from a SSR-based low density map to a SNP-based high density map for identification of disease resistance quantitative trait loci in peanut

Science.gov (United States)

Mapping and identification of quantitative trait loci (QTLs) are important for efficient marker-assisted breeding. Diseases such as leaf spots and Tomato spotted wilt virus (TSWV) cause significant loses to peanut growers. The U.S. Peanut Genome Initiative (PGI) was launched in 2004, and expanded to...

Genetic Analysis of Kernel Traits in Maize-Teosinte Introgression Populations

Directory of Open Access Journals (Sweden)

Zhengbin Liu

2016-08-01

Full Text Available Seed traits have been targeted by human selection during the domestication of crop species as a way to increase the caloric and nutritional content of food during the transition from hunter-gather to early farming societies. The primary seed trait under selection was likely seed size/weight as it is most directly related to overall grain yield. Additional seed traits involved in seed shape may have also contributed to larger grain. Maize (Zea mays ssp. mays kernel weight has increased more than 10-fold in the 9000 years since domestication from its wild ancestor, teosinte (Z. mays ssp. parviglumis. In order to study how size and shape affect kernel weight, we analyzed kernel morphometric traits in a set of 10 maize-teosinte introgression populations using digital imaging software. We identified quantitative trait loci (QTL for kernel area and length with moderate allelic effects that colocalize with kernel weight QTL. Several genomic regions with strong effects during maize domestication were detected, and a genetic framework for kernel traits was characterized by complex pleiotropic interactions. Our results both confirm prior reports of kernel domestication loci and identify previously uncharacterized QTL with a range of allelic effects, enabling future research into the genetic basis of these traits.

Validation of genomic predictions for wellness traits in US Holstein cows.

Science.gov (United States)

McNeel, Anthony K; Reiter, Brenda C; Weigel, Dan; Osterstock, Jason; Di Croce, Fernando A

2017-11-01

The objective of this study was to evaluate the efficacy of wellness trait genetic predictions in commercial herds of US Holstein cows from herds that do not contribute phenotypic information to the evaluation. Tissue samples for DNA extraction were collected from more than 3,400 randomly selected pregnant Holstein females in 11 herds and 2 age groups (69% nulliparous, 31% primiparous) approximately 30 to 60 d before their expected calving date. Lactation records from cows that calved between September 1, 2015, and December 31, 2015, were included in the analysis. Genomically enhanced predicted transmitting abilities for the wellness traits of retained placenta, metritis, ketosis, displaced abomasum, mastitis, and lameness were estimated by the Zoetis genetic evaluation and converted into standardized transmitting abilities. Mean reliabilities of the animals in the study ranged between 45 and 47% for each of the 6 traits. Animals were ranked by their standardized transmitting abilities within herd and age group then assigned to 1 of 4 groups of percentile-based genetic groups of equal size. Adverse health events, including retained placenta, metritis, ketosis, displaced abomasum, mastitis, and lameness, were collected from on-farm herd management software, and animal phenotype was coded as either healthy (0), diseased (1), or excluded for each of the 6 outcomes of interest. Statistical analysis was performed using a generalized linear mixed model with genetic group, age group, and lactation as fixed effects, whereas herd and animal nested within herd were set as random effects. Results of the analysis indicated that the wellness trait predictions were associated with differences in phenotypic disease incidence between the worst and best genetic groups. The difference between the worst and best genetic groups in recorded disease incidence was 2.9% for retained placenta, 10.8% for metritis, 1.1% for displaced abomasum, 1.7% for ketosis, 7.4% for mastitis, and 3

Animal models of human respiratory syncytial virus disease

NARCIS (Netherlands)

Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

2011-01-01

Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

Relationship between personality traits and vocational choice.

Science.gov (United States)

Garcia-Sedeño, Manuel; Navarro, Jose I; Menacho, Inmaculada

2009-10-01

Summary.-The relationship between occupational preferences and personality traits was examined. A randomly chosen sample of 735 students (age range = 17 to 23 years; 50.5% male) in their last year of high school participated in this study. Participants completed Cattell's Sixteen Personality Factor-5 Questionnaire (16PF-5 Questionnaire) and the Kuder-C Professional Tendencies Questionnaire. Initial hierarchical cluster analysis categorized the participants into two groups by Kuder-C vocational factors: one showed a predilection for scientific or technological careers and the other a bias toward the humanities and social sciences. Based on these groupings, differences in 16PF-5 personality traits were analyzed and differences associated with three first-order personality traits (warmth, dominance, and sensitivity), three second-order factors (extraversion, control, and independence), and some areas of professional interest (mechanical, arithmetical artistic, persuasive, and welfare) were identified. The data indicated that there was congruency between personality profiles and vocational interests.

Modeling human disease using organotypic cultures

DEFF Research Database (Denmark)

Schweiger, Pawel J; Jensen, Kim B

2016-01-01

animal models and in vitro cell culture systems. However, it has been exceedingly difficult to model disease at the tissue level. Since recently, the gap between cell line studies and in vivo modeling has been narrowing thanks to progress in biomaterials and stem cell research. Development of reliable 3D...... culture systems has enabled a rapid expansion of sophisticated in vitro models. Here we focus on some of the latest advances and future perspectives in 3D organoids for human disease modeling....

Goss’s wilt incidence in sweet corn is independent of transgenic traits and glyphosate

Science.gov (United States)

Recently claims have been made that the use of glyphosate and transgenic crop traits increases the risk of plant diseases. Transgenic traits used widely for years in dent corn are now available in commercial sweet corn cultivars, specifically, the combination of glyphosate resistance (GR) and Lepid...

Disease modeling using human induced pluripotent stem cells: lessons from the liver.

Science.gov (United States)

Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

2015-01-01

Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

A murine model of human myeloma bone disease

NARCIS (Netherlands)

Garrett, I.R.; Dallas, S.; Radl, J.; Mundy, G.R.

1997-01-01

Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease mould help in

Molecular biology of human muscle disease

Energy Technology Data Exchange (ETDEWEB)

Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

1991-01-01

The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

Multifractal Detrended Fluctuation Analysis of Human gait Diseases

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Srimonti eDutta

2013-10-01

Full Text Available IIn this paper multifractal detrended fluctuation analysis is used to study the human gait time series for normal and diseased sets. It is observed that long range correlation is primarily responsible for the origin of multifractality. The study reveals that the degree of multifractality is more for normal set compared to diseased set. However the method fails to distinguish between the two diseased sets.

Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.

Science.gov (United States)

Gundogdu, Aycan; Nalbantoglu, Ufuk

2017-04-01

A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.

Genetic analysis of some agronomic traits in groundnut (Arachis hypogaea L.

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M.K. Alam

2013-12-01

Full Text Available A 10×10 half diallel experiment was conducted on groundnut (Arachis hypogaea L. to ascertain the gene action and genetic parameters of ten traits including 50% flowering, no. of pods per plant, plant height, harvest index, pod index, 100 pod weight, 100 kernel weight, pod size, diseases infection and yield per plot. The experiments were carried out in the Department of Genetics and Plant Breeding, Bangladesh Agricultural University (BAU, Mymensingh during the cropping season of 2010-2011. The estimates of gene effects indicated that significance of both additive and non-additive variance for pod size, 100 pod weight and diseases infection among the traits and presence of over dominance satisfying assumptions of diallel except dormancy. However, both the additive and non-additive gene affects together importance to control of most quantitative traits in the groundnut. The average degree of dominance (H1/D 1/2 (H1 = dominance variance, D = additive variance was higher than one, indicating over dominance for all the traits. The narrow-sense heritability was high for 50% flowering (38%, harvest index (35%, pod size (52%, 100 pod weight (35% and yield per plot (41% indicating that great genetic gain could be achieved for them.

A framework for annotating human genome in disease context.

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Xu, Wei; Wang, Huisong; Cheng, Wenqing; Fu, Dong; Xia, Tian; Kibbe, Warren A; Lin, Simon M

2012-01-01

Identification of gene-disease association is crucial to understanding disease mechanism. A rapid increase in biomedical literatures, led by advances of genome-scale technologies, poses challenge for manually-curated-based annotation databases to characterize gene-disease associations effectively and timely. We propose an automatic method-The Disease Ontology Annotation Framework (DOAF) to provide a comprehensive annotation of the human genome using the computable Disease Ontology (DO), the NCBO Annotator service and NCBI Gene Reference Into Function (GeneRIF). DOAF can keep the resulting knowledgebase current by periodically executing automatic pipeline to re-annotate the human genome using the latest DO and GeneRIF releases at any frequency such as daily or monthly. Further, DOAF provides a computable and programmable environment which enables large-scale and integrative analysis by working with external analytic software or online service platforms. A user-friendly web interface (doa.nubic.northwestern.edu) is implemented to allow users to efficiently query, download, and view disease annotations and the underlying evidences.

Psychological differences between early- and late-onset psoriasis: a study of personality traits, anxiety and depression in psoriasis.

Science.gov (United States)

Remröd, C; Sjöström, K; Svensson, A

2013-08-01

Onset of psoriasis may occur at any age. Early negative experiences often influence personality development, and may lead to physical disease, anxiety and depression in adulthood. Knowledge about onset of psoriasis and psychopathology is limited. To examine whether patients with early-onset psoriasis differ psychologically from patients with late-onset psoriasis, regarding personality traits, anxiety and depression. A descriptive cross-sectional study was conducted among 101 consecutively recruited outpatients with psoriasis. A psychosocial interview was performed followed by self-assessment of validated questionnaires: Swedish Universities Scales of Personality (SSP), Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory. Psoriasis severity was assessed by the Psoriasis Area and Severity Index. Patients with early-onset psoriasis (age personality traits: SSP-embitterment, -trait irritability, -mistrust and -verbal trait aggression. Our results indicate that early detection of psychological vulnerability when treating children and adolescents with psoriasis seems to be of great importance. Traits of psychological vulnerability and pessimistic personality traits were found to be significantly associated with the early onset of psoriasis, but not with disease duration in this study. These traits may be seen as a consequence of psoriasis, and/or as individual traits modulating and impairing clinical course and efforts to cope with psoriasis. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Genetic architecture of complex traits and accuracy of genomic prediction: coat colour, milk-fat percentage, and type in Holstein cattle as contrasting model traits.

Directory of Open Access Journals (Sweden)

Ben J Hayes

2010-09-01

Full Text Available Prediction of genetic merit using dense SNP genotypes can be used for estimation of breeding values for selection of livestock, crops, and forage species; for prediction of disease risk; and for forensics. The accuracy of these genomic predictions depends in part on the genetic architecture of the trait, in particular number of loci affecting the trait and distribution of their effects. Here we investigate the difference among three traits in distribution of effects and the consequences for the accuracy of genomic predictions. Proportion of black coat colour in Holstein cattle was used as one model complex trait. Three loci, KIT, MITF, and a locus on chromosome 8, together explain 24% of the variation of proportion of black. However, a surprisingly large number of loci of small effect are necessary to capture the remaining variation. A second trait, fat concentration in milk, had one locus of large effect and a host of loci with very small effects. Both these distributions of effects were in contrast to that for a third trait, an index of scores for a number of aspects of cow confirmation ("overall type", which had only loci of small effect. The differences in distribution of effects among the three traits were quantified by estimating the distribution of variance explained by chromosome segments containing 50 SNPs. This approach was taken to account for the imperfect linkage disequilibrium between the SNPs and the QTL affecting the traits. We also show that the accuracy of predicting genetic values is higher for traits with a proportion of large effects (proportion black and fat percentage than for a trait with no loci of large effect (overall type, provided the method of analysis takes advantage of the distribution of loci effects.

Assessing the relative importance of health and conformation traits in the cavalier king Charles spaniel.

Science.gov (United States)

Wijnrocx, Katrien; François, Liesbeth; Goos, Peter; Buys, Nadine; Janssens, Steven

2018-01-01

The selection of a future breeding dog is a complicated task, in which disease characteristics and different traits have to be combined and weighed against one another. Truncation selection, that is the exclusion of affected animals, may be very inefficient when selecting on a large number of traits, and may result in a reduction of the genetic diversity in a population or breed. Selection could be facilitated by the use of a selection index that combines multiple traits or breeding values into one score. This however requires a consideration of their relative value according to their economic weight, which is difficult to express in monetary units for health traits. The use of a choice experiment to derive non-market values might be a solution to this problem. This is a pilot study to assess the potential use of choice experiments to ascertain the public preference and relative importance attached to health- and conformation traits in the selection of a Cavalier King Charles spaniel. The focus was on two prevalent disorders, mitral valve disease and syringomyelia, and on several important conformation traits such as muzzle length and eye shape. Based on available prior information, a Bayesian D-optimal design approach was used to develop a choice experiment and the resulting choice sets. Every participant (breeder or owner) in the choice experiment was presented with a total of 17 choice sets, in which at most four traits could vary to reduce the cognitive burden. A total of 114 respondents participated in the choice experiment and results showed that respondents (breeders/owners) current attitudes were directed towards health (syringomyelia and mitral valve disease), followed by eye shape and level of inbreeding. This approach identifies the value breeders and owners attach to certain traits in the breeding objective. The resulting relative weights, represented as the logworths obtained from the choice experiment, could be an alternative to economic weights. They

A power study of bivariate LOD score analysis of a complex trait and fear/discomfort with strangers.

Science.gov (United States)

Ji, Fei; Lee, Dayoung; Mendell, Nancy Role

2005-12-30

Complex diseases are often reported along with disease-related traits (DRT). Sometimes investigators consider both disease and DRT phenotypes separately and sometimes they consider individuals as affected if they have either the disease or the DRT, or both. We propose instead to consider the joint distribution of the disease and the DRT and do a linkage analysis assuming a pleiotropic model. We evaluated our results through analysis of the simulated datasets provided by Genetic Analysis Workshop 14. We first conducted univariate linkage analysis of the simulated disease, Kofendrerd Personality Disorder and one of its simulated associated traits, phenotype b (fear/discomfort with strangers). Subsequently, we considered the bivariate phenotype, which combined the information on Kofendrerd Personality Disorder and fear/discomfort with strangers. We developed a program to perform bivariate linkage analysis using an extension to the Elston-Stewart peeling method of likelihood calculation. Using this program we considered the microsatellites within 30 cM of the gene pleiotropic for this simulated disease and DRT. Based on 100 simulations of 300 families we observed excellent power to detect linkage within 10 cM of the disease locus using the DRT and the bivariate trait.

Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.

Science.gov (United States)

Haïk, Stéphane; Brandel, Jean-Philippe

2014-08-01

In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential overexpression of SERPINA3 in human prion diseases.

Science.gov (United States)

Vanni, S; Moda, F; Zattoni, M; Bistaffa, E; De Cecco, E; Rossi, M; Giaccone, G; Tagliavini, F; Haïk, S; Deslys, J P; Zanusso, G; Ironside, J W; Ferrer, I; Kovacs, G G; Legname, G

2017-11-15

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

Quantitative trait loci for fertility traits in Finnish Ayrshire cattle

Directory of Open Access Journals (Sweden)

Viitala Sirja M

2008-03-01

Full Text Available Abstract A whole genome scan was carried out to detect quantitative trait loci (QTL for fertility traits in Finnish Ayrshire cattle. The mapping population consisted of 12 bulls and 493 sons. Estimated breeding values for days open, fertility treatments, maternal calf mortality and paternal non-return rate were used as phenotypic data. In a granddaughter design, 171 markers were typed on all 29 bovine autosomes. Associations between markers and traits were analysed by multiple marker regression. Multi-trait analyses were carried out with a variance component based approach for the chromosomes and trait combinations, which were observed significant in the regression method. Twenty-two chromosome-wise significant QTL were detected. Several of the detected QTL areas were overlapping with milk production QTL previously identified in the same population. Multi-trait QTL analyses were carried out to test if these effects were due to a pleiotropic QTL affecting fertility and milk yield traits or to linked QTL causing the effects. This distinction could only be made with confidence on BTA1 where a QTL affecting milk yield is linked to a pleiotropic QTL affecting days open and fertility treatments.

Under the lash: Demodex mites in human diseases.

Science.gov (United States)

Lacey, Noreen; Kavanagh, Kevin; Tseng, Scheffer C G

2009-08-01

Demodex mites, class Arachnida and subclass Acarina, are elongated mites with clear cephalothorax and abdomens, the former with four pairs of legs. There are more than 100 species of Demodex mite, many of which are obligatory commensals of the pilosebaceous unit of mammals including cats, dogs, sheep, cattle, pigs, goats, deer, bats, hamsters, rats and mice. Among them, Demodex canis, which is found ubiquitously in dogs, is the most documented and investigated. In excessive numbers D. canis causes the inflammatory disease termed demodicosis (demodectic mange, follicular mange or red mange), which is more common in purebred dogs and has a hereditary predisposition in breeding kennels1. Two distinct Demodex species have been confirmed as the most common ectoparasite in man. The larger Demodex folliculorum, about 0.3-0.4 mm long, is primarily found as a cluster in the hair follicle (Figure 1a), while the smaller Demodex brevis, about 0.2-0.3 mm long with a spindle shape and stubby legs, resides solitarily in the sebaceous gland (Figure 1b). These two species are also ubiquitously found in all human races without gender preference. The pathogenic role of Demodex mites in veterinary medicine is not as greatly disputed as in human diseases. In this article, we review the key literature and our joint research experience regarding the pathogenic potential of these two mites in causing inflammatory diseases of human skin and eye. We hope that the evidence summarized herein will invite readers to take a different look at the life of Demodex mites in several common human diseases.

Does biodiversity protect humans against infectious disease? Reply

Science.gov (United States)

Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

2016-01-01

The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

Big data collision: the internet of things, wearable devices and genomics in the study of neurological traits and disease.

Science.gov (United States)

Talboom, Joshua S; Huentelman, Matthew J

2018-05-01

Advances in information technology (IT) hardware in the last decade have led to the advent of small connected devices broadly referred to as the Internet of Things (IoT). The IoT and its subcategory of wearable devices (wearables) both have the potential to greatly impact biomedical research. This focused review covers recent biomedical research using the IoT and wearables in the area of neurological traits and disease. In addition, a look into the future of biomedical research using IoT devices and wearables as well as some areas requiring further consideration by the field will be discussed.

Extracellular RNAs: development as biomarkers of human disease

Directory of Open Access Journals (Sweden)

Joseph F. Quinn

2015-08-01

Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

Leveraging human-centered design in chronic disease prevention.

Science.gov (United States)

Matheson, Gordon O; Pacione, Chris; Shultz, Rebecca K; Klügl, Martin

2015-04-01

Bridging the knowing-doing gap in the prevention of chronic disease requires deep appreciation and understanding of the complexities inherent in behavioral change. Strategies that have relied exclusively on the implementation of evidence-based data have not yielded the desired progress. The tools of human-centered design, used in conjunction with evidence-based data, hold much promise in providing an optimal approach for advancing disease prevention efforts. Directing the focus toward wide-scale education and application of human-centered design techniques among healthcare professionals will rapidly multiply their effective ability to bring the kind of substantial results in disease prevention that have eluded the healthcare industry for decades. This, in turn, would increase the likelihood of prevention by design. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

Science.gov (United States)

Raguideau, Sébastien; Plancade, Sandra; Pons, Nicolas; Leclerc, Marion; Laroche, Béatrice

2016-12-01

Whole Genome Shotgun (WGS) metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs) accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF) problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other metabolic processes in

Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

Directory of Open Access Journals (Sweden)

Sébastien Raguideau

2016-12-01

Full Text Available Whole Genome Shotgun (WGS metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other

Genetic correlations between methane production and fertility, health, and body type traits in Danish Holstein cows.

Science.gov (United States)

Zetouni, L; Kargo, M; Norberg, E; Lassen, J

2018-03-01

Our aim was to investigate the genetic correlations between CH 4 production and body conformation, fertility, and health traits in dairy cows. Data were collected from 10 commercial Holstein herds in Denmark, including 5,758 cows with records for body conformation traits, 7,390 for fertility traits, 7,439 for health traits, and 1,397 with individual CH 4 measurements. Methane production was measured during milking in automatic milking systems, using a sniffer approach. Correlations between CH 4 and several different traits were estimated. These traits were interval between calving and first insemination, interval between first and last insemination, number of inseminations, udder diseases, other diseases, height, body depth, chest width, dairy character, top line, and body condition score. Bivariate linear models were used to estimate the genetic parameters within and between CH 4 and the other traits. In general, the genetic correlations between CH 4 and the traits investigated were low. The heritability of CH 4 was 0.25, and ranged from 0.02 to 0.07 for fertility and health traits, and from 0.17 to 0.74 for body conformation traits. Further research with a larger data set should be performed to more accurately establish how CH 4 relates to fertility, health, and body conformation traits in dairy cattle. This will be useful in the design of future breeding goals that consider the production of CH 4 . The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Quantitative Trait Loci Affecting Calving Traits in Danish Holstein Cattle

DEFF Research Database (Denmark)

Thomasen, J R; Guldbrandtsen, B; Sørensen, P

2008-01-01

The objectives of this study were 1) to detect quantitative trait loci (QTL) affecting direct and maternal calving traits at first calving in the Danish Holstein population, 2) to distinguish between pleiotropic and linked QTL for chromosome regions affecting more than one trait, and 3) to detect...

Trends in popularity of some morphological traits of purebred dogs in Australia.

Science.gov (United States)

Teng, Kendy T; McGreevy, Paul D; Toribio, Jenny-Ann L M L; Dhand, Navneet K

2016-01-01

The morphology of dogs can provide information about their predisposition to some disorders. For example, larger breeds are predisposed to hip dysplasia and many neoplastic diseases. Therefore, longitudinal trends in popularity of dog morphology can reveal potential disease pervasiveness in the future. There have been reports on the popularity of particular breeds and behavioural traits but trends in the morphological traits of preferred breeds have not been studied. This study investigated trends in the height, dog size and head shape (cephalic index) of Australian purebred dogs. One hundred eighty-one breeds derived from Australian National Kennel Council (ANKC) registration statistics from 1986 to 2013 were analysed. Weighted regression analyses were conducted to examine trends in the traits by using them as outcome variables, with year as the explanatory variable and numbers of registered dogs as weights. Linear regression investigated dog height and cephalic index (skull width/skull length), and multinomial logistic regression studied dog size. The total number of ANKC registration had decreased gradually from 95,792 in 1986 to 66,902 in 2013. Both weighted minimal height (p = 0.014) and weighted maximal height (p popular over time. Mean cephalic index has increased, which indicates that Australians have gradually favoured breeds with shorter and wider heads (brachycephalic). These significant trends indicate that the dog morphological traits reported here may potentially influence how people select companion dogs in Australia and provide valuable predictive information on the pervasiveness of diseases in dogs.

The missing link between human ecology and public health: the case of cancer.

Science.gov (United States)

Modonesi, Carlo; Oddone, Enrico; Panizza, Celestino; Imbriani, Marcello

2017-11-01

The primary role played by the 'ecological context' in clarifying the causes and dynamics of human health and disease is the topic of this article. It emphasizes that the challenging incidence of cancer and other diseases can be charged primarily to the effects of the worldwide dominant economic model. Human culture may act as a powerful force affecting the environment, biology and health of humans and other species. Human culture can be viewed as a special and extreme case of 'niche construction', where human-specific traits, technologies and beliefs act together. The feedback between human activities and the environment can promote different trends in public health. This should provide the opportunity to rethink the consequences that our economic model produces both on the environment and on physical, mental and social health of our species. Copyright© by Aracne Editrice, Roma, Italy.

Association analysis of multiple traits by an approach of combining ...

Indian Academy of Sciences (India)

Lili Chen

diseases. Joint analysis of multiple traits can increase statistical power of association analysis and uncover the underlying genetic ... genthaler and Thilly 2007), the combined multivariate and ... Because of using reverse regression model, our.

Reduced penetrance in human inherited disease

African Journals Online (AJOL)

Rabah M. Shawky

2014-01-31

Jan 31, 2014 ... tant role in cellular senescence, tumorigenesis and in several diseases including type ... between epigenetic DNA modifications and human life span has also been shown .... penetrance mutation that is age dependent especially when compared with the ..... on healthy aging and longevity. Immunity Aging ...

Human Embryonic Stem Cell Therapy in Crohn's Disease: A Case Report.

Science.gov (United States)

Shroff, Geeta

2016-02-29

Crohn's disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565,000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn's disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn's disease. A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn's disease.

Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

Science.gov (United States)

Nalbantoglu, Ufuk

2017-01-01

A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome–human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis. PMID:28785422

[Leprosy, a pillar of human genetics of infectious diseases].

Science.gov (United States)

Gaschignard, J; Scurr, E; Alcaïs, A

2013-06-01

Despite a natural reservoir of Mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. This disease remains a major cause of disability and social stigma worldwide. The cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. An important contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability between individuals sustainably exposed to M. leprae. Given the inability to cultivate M. leprae in vitro and in the absence of relevant animal model, genetic epidemiology is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. Recent genome-wide studies have identified new pathophysiological pathways which importance is only beginning to be understood. In addition, the prism of human genetics placed leprosy at the crossroads of other common diseases such as Crohn's disease, asthma or myocardial infarction. Therefore, novel lights on the pathogenesis of many common diseases could eventually emerge from the detailed understanding of a disease of the shadows. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study.

Directory of Open Access Journals (Sweden)

Mark Bi

2010-07-01

Full Text Available The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD, and stroke over up mean follow-up times of 8, 15, and 15 years, respectively.Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models.Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10(-7 and insulin levels (p = 10(-6, lower insulin resistance (HOMA-IR, p = 10(-9, less prevalent diabetes (p = 10(-6, and higher CRP (p = 10(-8, 2-h postprandial glucose (OGTT, p = 10(-6, and triglyceride levels (p = 10(-31. Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022, metabolic syndrome prevalence (p = 0.043, and lower beta-cell function measured as HOMA-B (p = 0.011. Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004 and lower insulin levels (p = 0.002 and HOMA-IR (p = 0.013. Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10(-4 among white participants, but not with incidence of CHD or stroke.Our findings indicate rs780094 has independent associations with multiple

Attributing the human disease burden of foodborne infections to specific sources.

NARCIS (Netherlands)

Pires, S.M.; Evers, E.G.; van Pelt, W.; Ayers, T.; Scallan, E.; Angulo, F.J.; Havelaar, A.H.; Hald, T.

2009-01-01

Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However, information

Attributing the Human Disease Burden of Foodborne Infections to Specific Sources

DEFF Research Database (Denmark)

Pires, Sara Monteiro; Evers, Eric E.; Van Pely, Wilfrid

2009-01-01

Foodborne diseases are an important cause of human illness worldwide. Humans acquire these infections from a variety of sources and routes of transmission. Many efforts have been made in the last decades to prevent and control foodborne diseases, particularly foodborne zoonoses. However...

Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis.

Science.gov (United States)

Pornprasert, Sakorn; Saoboontan, Supansa; Wiengkum, Thanatcha

2016-06-01

Hemoglobin Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)] is often missed by routine laboratory testing, especially in subjects with co-inheritance of β-thalassemia or β-variants. We reported the case of a 1-year-old female with Hb H-CS disease who was born from a father with heterozygous of α-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [β26 (B8) Glu→Lys, GAG>AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease.

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

Science.gov (United States)

Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

2014-11-18

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.

Science.gov (United States)

Borsotti, Chiara; Danzl, Nichole M; Nauman, Grace; Hölzl, Markus A; French, Clare; Chavez, Estefania; Khosravi-Maharlooei, Mohsen; Glauzy, Salome; Delmotte, Fabien R; Meffre, Eric; Savage, David G; Campbell, Sean R; Goland, Robin; Greenberg, Ellen; Bi, Jing; Satwani, Prakash; Yang, Suxiao; Bathon, Joan; Winchester, Robert; Sykes, Megan

2017-10-24

B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.

Comparison of whole-genome prediction models for traits with contrasting genetic architecture in a diversity panel of maize inbred lines

Directory of Open Access Journals (Sweden)

Riedelsheimer Christian

2012-09-01

Full Text Available Abstract Background There is increasing empirical evidence that whole-genome prediction (WGP is a powerful tool for predicting line and hybrid performance in maize. However, there is a lack of knowledge about the sensitivity of WGP models towards the genetic architecture of the trait. Whereas previous studies exclusively focused on highly polygenic traits, important agronomic traits such as disease resistances, nutrifunctional or climate adaptational traits have a genetic architecture which is either much less complex or unknown. For such cases, information about model robustness and guidelines for model selection are lacking. Here, we compared five WGP models with different assumptions about the distribution of the underlying genetic effects. As contrasting model traits, we chose three highly polygenic agronomic traits and three metabolites each with a major QTL explaining 22 to 30% of the genetic variance in a panel of 289 diverse maize inbred lines genotyped with 56,110 SNPs. Results We found the five WGP models to be remarkable robust towards trait architecture with the largest differences in prediction accuracies ranging between 0.05 and 0.14 for the same trait, most likely as the result of the high level of linkage disequilibrium prevailing in elite maize germplasm. Whereas RR-BLUP performed best for the agronomic traits, it was inferior to LASSO or elastic net for the three metabolites. We found the approach of genome partitioning of genetic variance, first applied in human genetics, as useful in guiding the breeder which model to choose, if prior knowledge of the trait architecture is lacking. Conclusions Our results suggest that in diverse germplasm of elite maize inbred lines with a high level of LD, WGP models differ only slightly in their accuracies, irrespective of the number and effects of QTL found in previous linkage or association mapping studies. However, small gains in prediction accuracies can be achieved if the WGP model is

Mouse Chromosome Engineering for Modeling Human Disease

OpenAIRE

van der Weyden, Louise; Bradley, Allan

2006-01-01

Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...

Unusual configurations of personality traits indicate multiple patterns of their coalescence

Czech Academy of Sciences Publication Activity Database

Allik, J.; Hřebíčková, Martina; Realo, A.

2018-01-01

Roč. 9, únor (2018), s. 1-14, č. článku 187. ISSN 1664-1078 R&D Projects: GA ČR GA406/01/1507; GA ČR(CZ) GA17-14387S Institutional support: RVO:68081740 Keywords : personality traits * five-factor model * trait configurations * NEO PI-R/3 * personality mutants Subject RIV: AN - Psychology OBOR OECD: Psychology (including human - machine relations) Impact factor: 2.323, year: 2016

Human genetics of infectious diseases: a unified theory

Science.gov (United States)

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

Affective traits link to reliable neural markers of incentive anticipation.

Science.gov (United States)

Wu, Charlene C; Samanez-Larkin, Gregory R; Katovich, Kiefer; Knutson, Brian

2014-01-01

While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n=52) as they played a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and trait Negative Arousal. In a subsample (n=14) retested over 2.5years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (-$5.00) showed significant test-retest reliability (intraclass correlations>0.50, p'santicipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms. © 2013. Published by Elsevier Inc. All rights reserved.

Phenotypic, genetic, and single nucleotide polymorphism marker associations between calf diseases and subsequent performance and disease occurrences of first-lactation German Holstein cows.

Science.gov (United States)

Mahmoud, M; Yin, T; Brügemann, K; König, S

2017-03-01

A total of 31,396 females born from 2010 to 2013 in 43 large-scale Holstein-Friesian herds were phenotyped for calf and cow disease traits using a veterinarian diagnosis key. Calf diseases were general disease status (cGDS), calf diarrhea (cDIA), and calf respiratory disease (cRD) recorded from birth to 2 mo of age. Incidences were 0.48 for cGDS, 0.28 for cRD, and 0.21 for cDIA. Cow disease trait recording focused on the early period directly after calving in first parity, including the interval from 10 d before calving to 200 d in lactation. For cows, at least one entry for the respective disease implied a score = 1 (sick); otherwise, score = 0 (healthy). Corresponding cow diseases were first-lactation general disease status (flGDS), first-lactation diarrhea (flDIA), and first-lactation respiratory disease (flRD). Additional cow disease categories included mastitis (flMAST), claw disorders (flCLAW), female fertility disorders (flFF), and metabolic disorders (flMET). A further cow trait category considered first-lactation test-day production traits from official test-days 1 and 2 after calving. The genotype data set included 41,256 single nucleotide polymorphisms (SNP) from 9,388 females with phenotypes. Linear and generalized linear mixed models with a logit link-function were applied to Gaussian and categorical cow traits, respectively, considering the calf disease as a fixed effect. Most of the calf diseases were not significantly associated with the occurrence of any cow disease. By trend, increasing risks for the occurrence of cow diseases were observed for healthy calves, indicating mechanisms of disease resistance with aging. Also by trend, occurrence of calf diseases was associated with decreasing milk, protein, and fat yields. Univariate linear and threshold animal models were used to estimate heritabilities and breeding values (EBV) for all calf and cow traits. Heritabilities for cGDS and cRD were 0.06 and 0.07 for cDIA. Genetic correlations among all

GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human GWAS.

Directory of Open Access Journals (Sweden)

Anselm S Hoppmann

Full Text Available Genome-wide association studies (GWAS evaluate associations between genetic variants and a trait or disease of interest free of prior biological hypotheses. GWAS require stringent correction for multiple testing, with genome-wide significance typically defined as association p-value <5*10-8. This study presents a new tool that uses external information about genes to prioritize SNP associations (GenToS. For a given list of candidate genes, GenToS calculates an appropriate statistical significance threshold and then searches for trait-associated variants in summary statistics from human GWAS. It thereby allows for identifying trait-associated genetic variants that do not meet genome-wide significance. The program additionally tests for enrichment of significant candidate gene associations in the human GWAS data compared to the number expected by chance. As proof of principle, this report used external information from a comprehensive resource of genetically manipulated and systematically phenotyped mice. Based on selected murine phenotypes for which human GWAS data for corresponding traits were publicly available, several candidate gene input lists were derived. Using GenToS for the investigation of candidate genes underlying murine skeletal phenotypes in data from a large human discovery GWAS meta-analysis of bone mineral density resulted in the identification of significantly associated variants in 29 genes. Index variants in 28 of these loci were subsequently replicated in an independent GWAS replication step, highlighting that they are true positive associations. One signal, COL11A1, has not been discovered through GWAS so far and represents a novel human candidate gene for altered bone mineral density. The number of observed genes that contained significant SNP associations in human GWAS based on murine candidate gene input lists was much greater than the number expected by chance across several complex human traits (enrichment p-value as

Farmers' breeding practices and traits of economic importance for indigenous chicken in RWANDA.

Science.gov (United States)

Mahoro, J; Muasya, T K; Mbuza, F; Mbuthia, J; Kahi, A K

2018-01-01

Data on breeding practices and traits of economic importance for the indigenous chicken (IC) were collected through personal interviews using structured questionnaires and direct observations of chicken management practices. The study was conducted from November 2015 to January 2016 in Rwamagana, Rulindo, Ruhango, Kicukiro and Muhanga districts of Rwanda. Data were collected and analysed through computation of indices, which represented a weighted average of all rankings of a specific trait. Spearman's non-parametric rank correlation was calculated for ranking of traits of economic importance to indicate the directional effects. The results on chicken ecotypes and their attributes showed that prolificacy, mature weight, disease tolerance, egg number and heat tolerance were highly preferred. The dwarf ecotype was most abundantly reared (38.84%) and considered to be significantly smaller and to have poorer growth rate, but to have better prolificacy than other indigenous chicken ecotypes. Selection of breeding cock and hen was based on disease tolerance, body weight at sexual maturity, body size and growth rate. In addition, for hen, mothering ability and egg fertility (Fer) were considered. Indices for the traits perceived by farmers as of primary economic importance were egg yield (0.093), disease tolerance (0.091), high growth rate (0.089), prolificacy (0.088), high body weight (0.087) and egg fertility (0.083). The most important traits considered by the marketers were body weight (BW), disease tolerance (Dtol), plumage colour (Pcol), egg yolk colour (EYC), meat quality (MQ), growth rate (GR) and egg yield (EY) whereas for consumers, meat quality, egg yolk colour, egg yield, body weight and growth rate were considered. Among traits perceived as important by farmers, a positive and significant correlation was found between BW and GR and Fer. Correlation was moderate for BW and prolificacy, drought tolerance (Drtol), Dtol and EYC. BW was negatively correlated with

Strategies for Enriching Variant Coverage in Candidate Disease Loci on a Multiethnic Genotyping Array.

Directory of Open Access Journals (Sweden)

Stephanie A Bien

Full Text Available Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II, Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA was designed to substantially improve fine-mapping and functional discovery by increasing variant coverage across multiple ethnicities at known loci for metabolic, cardiovascular, renal, inflammatory, anthropometric, and a variety of lifestyle traits. Studying the frequency distribution of clinically relevant mutations, putative risk alleles, and known functional variants across multiple populations will provide important insight into the genetic architecture of complex diseases and facilitate the discovery of novel, sometimes population-specific, disease associations. DNA samples from 51,650 self-identified African ancestry (17,328, Hispanic/Latino (22,379, Asian/Pacific Islander (8,640, and American Indian (653 and an additional 2,650 participants of either South Asian or European ancestry, and other reference panels have been genotyped on MEGA by PAGE II. MEGA was designed as a new resource for studying ancestrally diverse populations. Here, we describe the methodology for selecting trait-specific content for use in multi-ethnic populations and how enriching MEGA for this content may contribute to deeper biological understanding of the genetic etiology of complex disease.

Insect Peptides - Perspectives in Human Diseases Treatment.

Science.gov (United States)

Chowanski, Szymon; Adamski, Zbigniew; Lubawy, Jan; Marciniak, Pawel; Pacholska-Bogalska, Joanna; Slocinska, Malgorzata; Spochacz, Marta; Szymczak, Monika; Urbanski, Arkadiusz; Walkowiak-Nowicka, Karolina; Rosinski, Grzegorz

2017-01-01

Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

System and method for leveraging human physiological traits to control microprocessor frequency

Energy Technology Data Exchange (ETDEWEB)

Shye, Alex; Pan, Yan; Scholbrock, Benjamin; Miller, J. Scott; Memik, Gokhan; Dinda, Peter A; Dick, Robert P

2014-03-25

A system and method for leveraging physiological traits to control microprocessor frequency are disclosed. In some embodiments, the system and method may optimize, for example, a particular processor-based architecture based on, for example, end user satisfaction. In some embodiments, the system and method may determine, for example, whether their users are satisfied to provide higher efficiency, improved reliability, reduced power consumption, increased security, and a better user experience. The system and method may use, for example, biometric input devices to provide information about a user's physiological traits to a computer system. Biometric input devices may include, for example, one or more of the following: an eye tracker, a galvanic skin response sensor, and/or a force sensor.

Personality Traits Are Associated with Academic Achievement in Medical School: A Nationally Representative Study.

Science.gov (United States)

Sobowale, Kunmi; Ham, Sandra A; Curlin, Farr A; Yoon, John D

2018-06-01

This nationally representative study sought to identify personality traits that are associated with academic achievement in medical school. Third-year medical students, who completed an initial questionnaire in January 2011, were mailed a second questionnaire several months later during their fourth year. Controlling for sociodemographic characteristics and burnout, the authors used multivariate logistic regressions to determine whether Big Five personality traits were associated with receiving honors/highest grade in clinical clerkships, failing a course or rotation, and being selected for the Alpha Omega Alpha or Gold Humanism Honor Society. The adjusted response rates for the two surveys were 61 (n = 564/919) and 84% (n = 474/564). The personality trait conscientiousness predicted obtaining honors/highest grade in all clinical clerkships. In contrast, students high in neuroticism were less likely to do well in most specialties. Students with higher conscientiousness were more likely to be inducted into the Alpha Omega Alpha Honor Society, while students high in openness or agreeableness traits were more likely to be inducted into the Gold Humanism Honor Society. Burnout was not associated with any clinical performance measures. This study suggests the importance of personality traits, particularly conscientiousness, in predicting success during the clinical years of medical school. Medical educators should consider a nuanced examination of personality traits and other non-cognitive factors, particularly for psychiatry.

Human Embryonic Stem Cell Therapy in Crohn’s Disease: A Case Report

Science.gov (United States)

Shroff, Geeta

2016-01-01

Patient: Male, 21 Final Diagnosis: Crohn’s disease Symptoms: Intolerance to specific foods • abdominal pain and diarrhea Medication: Human embryonic stem cell therapy Clinical Procedure: Human embryonic stem cell transplantation Specialty: Gastroenterology Objective: Unusual or unexpected effect of treatment Background: Crohn’s disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565 000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn’s disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn’s disease. Case Report: A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Conclusions: Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn’s disease. PMID:26923312

Human genetics of infectious diseases: between proof of principle and paradigm

OpenAIRE

Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

2009-01-01

The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proo...

Proteins aggregation and human diseases

International Nuclear Information System (INIS)

Hu, Chin-Kun

2015-01-01

Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease. (paper)

Proteins aggregation and human diseases

Science.gov (United States)

Hu, Chin-Kun

2015-04-01

Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

[Diseases transmitted through water for human consumption].

Science.gov (United States)

Franco, E; Dentamaro, M

2003-01-01

The water for human consumption maintains a biological risk and can transmit diseases. The classical waterborne and the presently frequent diseases caused by protozoi Giardia and Cryptosporidium are considered and Arcobacter butzleri, a new waterborne pathogen, is described. Many measures have been adopted by institutions to ensure the quality of the drinking water. Managers and public health operators is working in order to verify the efficiency of more suitable indicators for its monitoring.

Quantitative trait locus (QTL) analysis of pod related traits in different ...

African Journals Online (AJOL)

Administrator

2011-09-26

Sep 26, 2011 ... assistant breeding selection. Key words: Soybean, pod traits, QTL, different environments. INTRODUCTION. Yield related traits in soybean are generally controlled by multiple genes and environmental dependent (Kwon and. Torrie, 1964). Epigenetics of genes controlling these traits also affect the yield.

Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

Science.gov (United States)

Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

2015-01-01

In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

Longevity Candidate Genes and Their Association With Personality Traits in the Elderly

NARCIS (Netherlands)

Luciano, M.; Lopez, L.M.; de Moor, M.H.M.; Harris, S.E.; Davies, G.; Nutile, T.; Krueger, R.F.; Esko, T.; Schlessinger, D.; Toshiko, T.; Derringer, J.; Realo, A.; Hansell, N.K.; Pergadia, M.L.; Pesonen, A.-K.; Sanna, S.; Terracciano, A.; Madden, P.A.F.; Penninx, B.W.J.H.; Spinhoven, Ph.D.; Hartman, C.A.; Oostra, B.A.; Janssens, A.C.J.W.; Eriksson, J.G.; Starr, J.M.; Cannas, A.; Ferrucci, L.; Metspalu, A.; Wright, M.J.; Heath, A.C.; van Duijn, C.M.; Bierut, L.J.; Raikkonen, K.; Martin, N.G.; Ciullo, M.; Rujescu, D.; Boomsma, D.I.; Deary, I.J.

2012-01-01

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI

Longevity candidate genes and their association with personality traits in the elderly

NARCIS (Netherlands)

Luciano, Michelle; Lopez, Lorna M.; de Moor, Marleen H. M.; Harris, Sarah E.; Davies, Gail; Nutile, Teresa; Krueger, Robert F.; Esko, Tonu; Schlessinger, David; Toshiko, Tanaka; Derringer, Jaime L.; Realo, Anu; Hansell, Narelle K.; Pergadia, Michele L.; Pesonen, Anu-Katriina; Sanna, Serena; Terracciano, Antonio; Madden, Pamela A. F.; Penninx, Brenda; Spinhoven, Philip; Hartman, Catherina A.; Oostra, Ben A.; Janssens, A. Cecile J. W.; Eriksson, Johan G.; Starr, John M.; Cannas, Alessandra; Ferrucci, Luigi; Metspalu, Andres; Wright, Margeret J.; Heath, Andrew C.; van Duijn, Cornelia M.; Bierut, Laura J.; Raikkonen, Katri; Martin, Nicholas G.; Ciullo, Marina; Rujescu, Dan; Boomsma, Dorret I.; Deary, Ian J.

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI

Primatology. Human diseases threaten great apes.

Science.gov (United States)

Ferber, D

2000-08-25

Researchers are uncovering disturbing evidence that scientists and tourists are infecting wild primates with human pathogens. In response, ape specialists, including the American Society of Primatologists, are now calling for stricter health standards for researchers and tourists. They are also urging researchers to learn how to diagnose disease in their study animals.

Traits traded off

NARCIS (Netherlands)

Rueffler, Claus

2006-01-01

The course of evolution is restricted by constraints. A special type of constraint is a trade-off where different traits are negatively correlated. In this situation a mutant type that shows an improvement in one trait suffers from a decreased performance through another trait. In a fixed fitness

Perception of young adults with sickle cell disease or sickle cell trait about participation in the CHOICES randomized controlled trial.

Science.gov (United States)

Hershberger, Patricia E; Gallo, Agatha M; Molokie, Robert; Thompson, Alexis A; Suarez, Marie L; Yao, Yingwei; Wilkie, Diana J

2016-06-01

To gain an in-depth understanding of the perceptions of young adults with sickle cell disease and sickle cell trait about parenthood and participating in the CHOICES randomized controlled trial that used computer-based, educational programmes. In the USA, there is insufficient education to assure that all young adults with sickle cell disease or sickle cell trait understand genetic inheritance risks and reproductive options to make informed reproductive decisions. To address this educational need, we developed a computer-based, multimedia program (CHOICES) and reformatted usual care into a computer-based (e-Book) program. We then conducted a two-year randomized controlled trial that included a qualitative component that would deepen understanding of young adults' perceptions of parenthood and use of computer-based, educational programmes. A qualitative descriptive approach completed after a randomized controlled trial. Sixty-eight men and women of childbearing age participated in semi-structured interviews at the completion of the randomized controlled trial from 2012-2013. Thematic content analysis guided the qualitative description. Three main themes were identified: (1) increasing knowledge and new ways of thinking and behaving; (2) rethinking parenting plans; and (3) appraising the program design and delivery. Most participants reported increased knowledge and rethinking of their parenting plans and were supportive of computer-based learning. Some participants expressed difficulty in determining individual transmission risks. Participants perceived the computer programs as beneficial to their learning. Future development of an Internet-based educational programme is warranted, with emphasis on providing tailored education or memory boosters about individual transmission risks. © 2015 John Wiley & Sons Ltd.

Personality traits modulate emotional and physiological responses to stress.

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Childs, Emma; White, Tara L; de Wit, Harriet

2014-09-01

An individual's susceptibility to psychological and physical disorders associated with chronic stress exposure, for example, cardiovascular and infectious disease, may also be predicted by their reactivity to acute stress. One factor associated with both stress resilience and health outcomes is personality. An understanding of how personality influences responses to acute stress may shed light upon individual differences in susceptibility to chronic stress-linked disease. This study examined the relationships between personality and acute responses to stress in 125 healthy adults, using hierarchical linear regression. We assessed personality traits using the Multidimensional Personality Questionnaire (MPQ-BF), and responses to acute stress (cortisol, heart rate, blood pressure, mood) using a standardized laboratory psychosocial stress task, the Trier Social Stress Test. Individuals with high Negative Emotionality exhibited greater emotional distress and lower blood pressure responses to the Trier Social Stress Test. Individuals with high agentic Positive Emotionality exhibited prolonged heart rate responses to stress, whereas those with high communal Positive Emotionality exhibited smaller cortisol and blood pressure responses. Separate personality traits differentially predicted emotional, cardiovascular, and cortisol responses to a psychosocial stressor in healthy volunteers. Future research investigating the association of personality with chronic stress-related disease may provide further clues to the relationship between acute stress reactivity and susceptibility to disease.

HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease.

Science.gov (United States)

Ward, Lucas D; Kellis, Manolis

2016-01-04

More than 90% of common variants associated with complex traits do not affect proteins directly, but instead the circuits that control gene expression. This has increased the urgency of understanding the regulatory genome as a key component for translating genetic results into mechanistic insights and ultimately therapeutics. To address this challenge, we developed HaploReg (http://compbio.mit.edu/HaploReg) to aid the functional dissection of genome-wide association study (GWAS) results, the prediction of putative causal variants in haplotype blocks, the prediction of likely cell types of action, and the prediction of candidate target genes by systematic mining of comparative, epigenomic and regulatory annotations. Since first launching the website in 2011, we have greatly expanded HaploReg, increasing the number of chromatin state maps to 127 reference epigenomes from ENCODE 2012 and Roadmap Epigenomics, incorporating regulator binding data, expanding regulatory motif disruption annotations, and integrating expression quantitative trait locus (eQTL) variants and their tissue-specific target genes from GTEx, Geuvadis, and other recent studies. We present these updates as HaploReg v4, and illustrate a use case of HaploReg for attention deficit hyperactivity disorder (ADHD)-associated SNPs with putative brain regulatory mechanisms. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Quantitative trait loci associated with anthracnose resistance in sorghum

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With an aim to develop a durable resistance to the fungal disease anthracnose, two unique genetic sources of resistance were selected to create genetic mapping populations to identify regions of the sorghum genome that encode anthracnose resistance. A series of quantitative trait loci were identifi...

Human prion diseases in the United States.

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Robert C Holman

Full Text Available BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD, occurs worldwide. Variant CJD (vCJD, a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths. The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8% of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%; the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively. Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

Associations between animal traits, carcass traits and carcass ...

African Journals Online (AJOL)

In this study the associations between animal traits, carcass traits and carcass classification within cattle, sheep and pigs slaughtered in a high throughput abattoir were determined. Classes of carcasses from cattle, sheep and pigs delivered for slaughter at this abattoir were recorded and analysed. Significant associations ...

Immunotherapy of Human Papilloma Virus Induced Disease

Science.gov (United States)

van der Burg, Sjoerd H

2012-01-01

Immunotherapy is the generic name for treatment modalities aiming to reinforce the immune system against diseases in which the immune system plays a role. The design of an optimal immunotherapeutic treatment against chronic viruses and associated diseases requires a detailed understanding of the interactions between the target virus and its host, in order to define the specific strategies that may have the best chance to deliver success at each stage of disease. Recently, a first series of successes was reported for the immunotherapy of Human Papilloma Virus (HPV)-induced premalignant diseases but there is definitely room for improvement. Here I discuss a number of topics that in my opinion require more study as the answers to these questions allows us to better understand the underlying mechanisms of disease and as such to tailor treatment. PMID:23341861

The role of chemerin in human disease

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Magdalena Stojek

2017-02-01

Full Text Available Adipose tissue is not merely a storage depot of triacylglycerols but also a major endocrine organ. Its cells, including adipocytes, synthesize and secrete a range of biologically active molecules termed adipokines. Adipokines that display the properties of cytokines are often called adipocytokines. In recent years there has been increasing interest in a new adipokine called chemerin. Chemerin is a protein synthesized mostly by the adipose tissue and the liver as inactive pre-pro-chemerin. After the intracellular hydrolytic cutting off of the 20-amino-acid N-terminal polypeptide, it is secreted into the bloodstream as inactive pro-chemerin. Biologically active chemerin is then derived from pro-chemerin after cleavage of the C-terminal fragment by serum proteases involved in inflammation, coagulation and fibrinolysis. Proteolytic cleavage leads to formation of several chemerin-derived peptides, both biologically active (often with opposing functions and inactive.Within the last decade, there has been a growing number of publications regarding the role of chemerin in human disease. It seems to be implicated in the inflammatory response, metabolic syndrome, cardiovascular disease and alimentary tract disorders. The article presents the most recent information on the role of chemerin in human disease, and specifically alimentary tract disorders. The available evidence suggests that chemerin is an important link between adipose tissue mass, metabolic processes, the immune system and inflammation, and therefore plays a major role in human pathophysiology.

Effects of Bos taurus autosome 9-located quantitative trait loci haplotypes on the disease phenotypes of dairy cows with experimentally induced Escherichia coli mastitis

DEFF Research Database (Denmark)

Khatun, Momena; Sørensen, Peter; Jørgensen, Hanne Birgitte Hede

2013-01-01

Several quantitative trait loci (QTL) affecting mastitis incidence and mastitis-related traits such as somatic cell score exist in dairy cows. Previously, QTL haplotypes associated with susceptibility to Escherichia coli mastitis in Nordic Holstein-Friesian (HF) cows were identified on Bos taurus...... autosome 9. In the present study, we induced experimental E. coli mastitis in Danish HF cows to investigate the effect of 2 E. coli mastitis-associated QTL haplotypes on the cows' disease phenotypes and recovery in early lactation. Thirty-two cows were divided in 2 groups bearing haplotypes with either low...... the HH group did. However, we also found interactions between the effects of haplotype and biopsy for body temperature, heart rate, and PMNL. In conclusion, when challenged with E. coli mastitis, HF cows with the specific Bos taurus autosome 9-located QTL haplotypes were associated with differences...

DEGAS: de novo discovery of dysregulated pathways in human diseases.

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Igor Ulitsky

Full Text Available BACKGROUND: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. METHODOLOGY/PRINCIPAL FINDINGS: We present DEGAS (DysrEgulated Gene set Analysis via Subnetworks, a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied DEGAS to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of mRNA splicing, cell proliferation, and the 14-3-3 complex in the disease progression. DEGAS is available as part of the MATISSE software package (http://acgt.cs.tau.ac.il/matisse. CONCLUSIONS/SIGNIFICANCE: The subnetworks identified by DEGAS can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.

Formation of adjectives referring to human physical traits in the speech of the Svrljig area

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Savić-Grujić Ana R.

2016-01-01

Full Text Available Our analysis focuses on all the adjectives which refer to human physical traits in the speech of the villages in the Svrljig area. This derivational analysis included more than 300 derivative adjectives which, from a synchronic point of view, belong to the category of derived words. The analysis included derivatives which have been formed through prefixation and suffixation, as well as derivatives which occurred as the result of compound-suffix derivation. Special attention was paid to suffixation as the basic and most frequently available means of adjective formation. Suffixes are represented in combination with the base they are bound to, with an indication of their productivity and meaning in derivational terms. A study of the material indicates that adjective derivation by means of suffixation is made possible with the use of 20 suffixes and suffix derivatives, 10 of which have one confirmation each. The greatest productivity has been found for the noun base and suffix -av (52 which a total number of recorded derivative adjectives is 200. The prefix-suffix derivation process is the least frequent, and thus only 12 adjectives were derived in this way. Contrary to the mainstream opinion that complex words are not characteristic of our diasystem, the derivation process involving adjectives referring to humans based on physical traits shows great productivity in the compound-suffix derivation process. More than 90 complex words were derived from the binding the suffix -av (4, -as / -es (54 and the zero suffix (37 to complex bases. Another difference compared to the literary language is reflected in the occurrence of various forms of one suffix, which came about as the consequence of vowel changes (-as / -es : -ast. It is also not infrequent that during derivation, various forms of bases are used, or that a nonproductive basis in one system is productive in another. So for example it has been confirmed that in the speech of the Svrljig area the

The DNA-damage response in human biology and disease

DEFF Research Database (Denmark)

Jackson, Stephen P; Bartek, Jiri

2009-01-01

, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

Science.gov (United States)

Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

2015-09-01

Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function. © 2015 John Wiley & Sons Ltd.

ICD-11 and DSM-5 personality trait domains capture categorical personality disorders: Finding a common ground.

Science.gov (United States)

Bach, Bo; Sellbom, Martin; Skjernov, Mathias; Simonsen, Erik

2018-05-01

The five personality disorder trait domains in the proposed International Classification of Diseases, 11th edition and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition are comparable in terms of Negative Affectivity, Detachment, Antagonism/Dissociality and Disinhibition. However, the International Classification of Diseases, 11th edition model includes a separate domain of Anankastia, whereas the Diagnostic and Statistical Manual of Mental Disorders, 5th edition model includes an additional domain of Psychoticism. This study examined associations of International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition trait domains, simultaneously, with categorical personality disorders. Psychiatric outpatients ( N = 226) were administered the Structured Clinical Interview for DSM-IV Axis II Personality Disorders Interview and the Personality Inventory for DSM-5. International Classification of Diseases, 11th edition and Diagnostic and Statistical Manual of Mental Disorders, 5th edition trait domain scores were obtained using pertinent scoring algorithms for the Personality Inventory for DSM-5. Associations between categorical personality disorders and trait domains were examined using correlation and multiple regression analyses. Both the International Classification of Diseases, 11th edition and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition domain models showed relevant continuity with categorical personality disorders and captured a substantial amount of their information. As expected, the International Classification of Diseases, 11th edition model was superior in capturing obsessive-compulsive personality disorder, whereas the Diagnostic and Statistical Manual of Mental Disorders, 5th edition model was superior in capturing schizotypal personality disorder. These preliminary findings suggest that little information is 'lost' in a transition to trait domain

Transfer RNA and human disease

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Jamie A Abbott

2014-06-01

Full Text Available Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA genes are hotspots for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase, mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing. Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

Transfer RNA and human disease.

Science.gov (United States)

Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

2014-01-01

Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

Simultaneous discovery, estimation and prediction analysis of complex traits using a bayesian mixture model.

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Gerhard Moser

2015-04-01

Full Text Available Gene discovery, estimation of heritability captured by SNP arrays, inference on genetic architecture and prediction analyses of complex traits are usually performed using different statistical models and methods, leading to inefficiency and loss of power. Here we use a Bayesian mixture model that simultaneously allows variant discovery, estimation of genetic variance explained by all variants and prediction of unobserved phenotypes in new samples. We apply the method to simulated data of quantitative traits and Welcome Trust Case Control Consortium (WTCCC data on disease and show that it provides accurate estimates of SNP-based heritability, produces unbiased estimators of risk in new samples, and that it can estimate genetic architecture by partitioning variation across hundreds to thousands of SNPs. We estimated that, depending on the trait, 2,633 to 9,411 SNPs explain all of the SNP-based heritability in the WTCCC diseases. The majority of those SNPs (>96% had small effects, confirming a substantial polygenic component to common diseases. The proportion of the SNP-based variance explained by large effects (each SNP explaining 1% of the variance varied markedly between diseases, ranging from almost zero for bipolar disorder to 72% for type 1 diabetes. Prediction analyses demonstrate that for diseases with major loci, such as type 1 diabetes and rheumatoid arthritis, Bayesian methods outperform profile scoring or mixed model approaches.

Trends in population-based studies of human genetics in infectious diseases.

Science.gov (United States)

Rowell, Jessica L; Dowling, Nicole F; Yu, Wei; Yesupriya, Ajay; Zhang, Lyna; Gwinn, Marta

2012-01-01

Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention.

Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

Science.gov (United States)

Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

2017-04-01

Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

The effect of shovel trait on Carabelli's trait in Taiwan Chinese and Aboriginal populations.

Science.gov (United States)

Hsu, J W; Tsai, P L; Hsiao, T H; Chang, H P; Lin, L M; Liu, K M; Yu, H S; Ferguson, D

1997-09-01

Chinese and other Mongoloid populations differ from Caucasoids by having a high prevalence of shovel trait and a low prevalence of Carabelli's trait. This study was conducted to compare the association between the shovel and the Carabelli's traits between Chinese and aboriginal Mongoloid populations. The research is designed to sample randomly a Chinese population and an aboriginal population having low admixture with neighboring populations. The Mongoloid aboriginal group was from the Bunun tribe who resides in an isolated alpine area in Taiwan. The effects of sex and age on Carabelli's trait were controlled in this study, as was the association between tooth size and Carabelli's trait. Our results show that males had more Carabelli's trait expressed on teeth than females in both of these two Mongoloid populations. The buccolingual diameter of Carabelli's trait teeth was larger than that of teeth without the trait. After controlling for sex, age, and tooth size, the existence of the shovel trait significantly increased the likelihood of having Carabelli's trait, especially in Chinese, which implies another significant ethnic feature for Mongoloid identification.

Human transporter database: comprehensive knowledge and discovery tools in the human transporter genes.

Directory of Open Access Journals (Sweden)

Adam Y Ye

Full Text Available Transporters are essential in homeostatic exchange of endogenous and exogenous substances at the systematic, organic, cellular, and subcellular levels. Gene mutations of transporters are often related to pharmacogenetics traits. Recent developments in high throughput technologies on genomics, transcriptomics and proteomics allow in depth studies of transporter genes in normal cellular processes and diverse disease conditions. The flood of high throughput data have resulted in urgent need for an updated knowledgebase with curated, organized, and annotated human transporters in an easily accessible way. Using a pipeline with the combination of automated keywords query, sequence similarity search and manual curation on transporters, we collected 1,555 human non-redundant transporter genes to develop the Human Transporter Database (HTD (http://htd.cbi.pku.edu.cn. Based on the extensive annotations, global properties of the transporter genes were illustrated, such as expression patterns and polymorphisms in relationships with their ligands. We noted that the human transporters were enriched in many fundamental biological processes such as oxidative phosphorylation and cardiac muscle contraction, and significantly associated with Mendelian and complex diseases such as epilepsy and sudden infant death syndrome. Overall, HTD provides a well-organized interface to facilitate research communities to search detailed molecular and genetic information of transporters for development of personalized medicine.

Logistic analysis of the effects of shovel trait on Carabelli's trait in a Mongoloid population.

Science.gov (United States)

Tsai, P L; Hsu, J W; Lin, L M; Liu, K M

1996-08-01

Mongoloid populations differ from Caucasoids by having a high prevalence of shovel trait and a low prevalence of Carabelli's trait. This study was conducted to investigate the effects of the shovel trait on Carabelli's trait in a Mongoloid population. The research design sought a population that resides in an isolated area and exhibits low admixture with neighboring populations. The Mongoloid group selected for study was the Bunun tribe of aborigines who inhabit an alpine area in Taiwan. The effects of sex and age on Carabelli's trait were controlled in this investigation, as was the association between tooth size and Carabelli's trait. Results show that males were more likely to have Carabelli's trait expressed on teeth than females. The buccolingual diameter of Carabelli's trait teeth was larger than that of teeth without the trait. After adjusting for sex, age, and tooth size, the existence of the shovel trait increased the likelihood of having Carabelli's trait by a factor of three, an effect that is significant.

Human impact gradient on mammalian biodiversity

Directory of Open Access Journals (Sweden)

Mariana Munguía

2016-04-01

Full Text Available Drastic changes have been caused by human influence in natural landscapes, which may exert an intensive effect on species loss. However, species loss from human pressure is not random but depends on a series of environmentally associated factors. Linking species traits to environmental attributes may allow us to detect the ecological impacts of habitat so that meaningful habitat degradation gradients can be identified. The relationships between environmental factors and species traits provide the basis for identifying those biological traits that make species more sensitive to disturbance. These relationships are also helpful to detect the geographic distribution of latent risk to reveal areas where biodiversity is threatened. Here, we identify a “Human Impact Gradient for Biodiversity (HIGB” based on a three-table ordination method (RLQ analysis and fourth-corner analysis to identify key species traits that are associated with environmental gradient. Species distribution and environmental geographic data were gathered nationwide to analyze 68 localities, which represent 27% of Mexico’s surface, including 211 species of mammals. Nine environmental variables (including biophysical, geophysical and land-use impacts were analyzed by using the Geographic Information System. Three types of species’ traits were evaluated: locomotion, trophic habit and body size. We identified a human impact gradient, which was mainly determined by the percentage of the area that was covered by seedlings, the plant richness, the understory coverage percentage and the human settlement index. The most important species traits that are associated with non-human-impacted sites were carnivores, frugivores–herbivores and a body size that was greater than 17.8 kg; 25 species were selected by the decision criteria framework for species that were sensitive to degradation based on ecological function information. Conversely, granivores, fossorial and semifossorial

The Investigation Report on the Personality Traits and Mental Behavior of Patients with Common Skin Disease%常见皮肤病患者人格特征和行为方式调查报告

Institute of Scientific and Technical Information of China (English)

刘素群

2012-01-01

用调查分析得到的常见皮肤病患者实际的心理行为特点来证实,我们应该接受、采纳和实践生物心理社会医学模式.调查结果显示:不同种类皮肤病患者有不同的人格特征和行为方式；相同种类皮肤病患者在人格特征和行为方式层面上有更多共同性；不同人格特征和行为方式的人对不同皮肤病有不同的易罹患性.%The investigation and analysis on the personality traits and mental behavior of patients with common skin disease proves that we should accept, use and put into practice the modern new medical model. The investigation shows that patients with different skin disease have different personality traits and behave differently and that patients with similar skin diseases have much in common from the perspective of personality and behavior. Besides this, the research proves that people with different personality traits and patterns of behavior vary from one another in the possibility to suffer from a particular skin disease.

Diseases of Poverty and Lifestyle, Well-Being and Human Development

OpenAIRE

Singh, Ajai R.; Singh, Shakuntala A.

2008-01-01

The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical c...

Coping skills: role of trait sport confidence and trait anxiety.

Science.gov (United States)

Cresswell, Scott; Hodge, Ken

2004-04-01

The current research assesses relationships among coping skills, trait sport confidence, and trait anxiety. Two samples (n=47 and n=77) of international competitors from surf life saving (M=23.7 yr.) and touch rugby (M=26.2 yr.) completed the Athletic Coping Skills Inventory, Trait Sport Confidence Inventory, and Sport Anxiety Scale. Analysis yielded significant correlations amongst trait anxiety, sport confidence, and coping. Specifically confidence scores were positively associated with coping with adversity scores and anxiety scores were negatively associated. These findings support the inclusion of the personality characteristics of confidence and anxiety within the coping model presented by Hardy, Jones, and Gould, Researchers should be aware that confidence and anxiety may influence the coping processes of athletes.

Severe infectious diseases of childhood as monogenic inborn errors of immunity.

Science.gov (United States)

Casanova, Jean-Laurent

2015-12-22

This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

NARCIS (Netherlands)

Xu, J.; Saunders, C.; Hu, P.; Grant, R.A.; Boekhout, T.; Kuramae, E.E.; Kronstad, J.W.; DeAngelis, Y.M.; Reeder, N.L.; Johnstone, K.R.; Leland, M.; Fieno, A.M.; Begley, W.M.; Sun, Y.; Lacey, M.P.; Chaudhary, T.; Keough, T.; Chu, L.; Sears, R.; Yuan, B.; Dawson Jr., T.L.

2007-01-01

Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

NARCIS (Netherlands)

Xu, Jun; Saunders, Charles W.; Hu, Ping; Grant, Raymond A.; Boekhout, Teun; Kuramae, Eiko E.; Kronstad, James W.; DeAngelis, Yvonne M.; Reeder, Nancy L.; Johnstone, Kevin R.; Leland, Meredith; Fieno, Angela M.; Begley, William M.; Sun, Yiping; Lacey, Martin P.; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L.

2007-01-01

Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect > 50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

Motivational Basis of Personality Traits: A Meta-Analysis of Value-Personality Correlations.

Science.gov (United States)

Fischer, Ronald; Boer, Diana

2015-10-01

We investigated the relationships between personality traits and basic value dimensions. Furthermore, we developed novel country-level hypotheses predicting that contextual threat moderates value-personality trait relationships. We conducted a three-level v-known meta-analysis of correlations between Big Five traits and Schwartz's (1992) 10 values involving 9,935 participants from 14 countries. Variations in contextual threat (measured as resource threat, ecological threat, and restrictive social institutions) were used as country-level moderator variables. We found systematic relationships between Big Five traits and human values that varied across contexts. Overall, correlations between Openness traits and the Conservation value dimension and Agreeableness traits and the Transcendence value dimension were strongest across all samples. Correlations between values and all personality traits (except Extraversion) were weaker in contexts with greater financial, ecological, and social threats. In contrast, stronger personality-value links are typically found in contexts with low financial and ecological threats and more democratic institutions and permissive social context. These effects explained on average more than 10% of the variability in value-personality correlations. Our results provide strong support for systematic linkages between personality and broad value dimensions, but they also point out that these relations are shaped by contextual factors. © 2014 Wiley Periodicals, Inc.

The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

Science.gov (United States)

Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; Vasant, Drashtti; Brookes, Anthony J.; Zankl, Andreas; Washington, Nicole L.; Mungall, Christopher J.; Lewis, Suzanna E.; Haendel, Melissa A.; Parkinson, Helen; Robinson, Peter N.

2015-01-01

The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available. PMID:26119816

Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Qiongshi Lu

2017-07-01

Full Text Available Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD. Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

Science.gov (United States)

Lu, Qiongshi; Powles, Ryan L; Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-07-01

Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

Comparison of statistical tests for association between rare variants and binary traits.

OpenAIRE

Bacanu, SA; Nelson, MR; Whittaker, JC

2012-01-01

: Genome-wide association studies have found thousands of common genetic variants associated with a wide variety of diseases and other complex traits. However, a large portion of the predicted genetic contribution to many traits remains unknown. One plausible explanation is that some of the missing variation is due to the effects of rare variants. Nonetheless, the statistical analysis of rare variants is challenging. A commonly used method is to contrast, within the same region (gene), the fr...

Separation of trait and state in stuttering.

Science.gov (United States)

Connally, Emily L; Ward, David; Pliatsikas, Christos; Finnegan, Sarah; Jenkinson, Mark; Boyles, Rowan; Watkins, Kate E

2018-04-06

Stuttering is a disorder in which the smooth flow of speech is interrupted. People who stutter show structural and functional abnormalities in the speech and motor system. It is unclear whether functional differences reflect general traits of the disorder or are specifically related to the dysfluent speech state. We used a hierarchical approach to separate state and trait effects within stuttering. We collected sparse-sampled functional MRI during two overt speech tasks (sentence reading and picture description) in 17 people who stutter and 16 fluent controls. Separate analyses identified indicators of: (1) general traits of people who stutter; (2) frequency of dysfluent speech states in subgroups of people who stutter; and (3) the differences between fluent and dysfluent states in people who stutter. We found that reduced activation of left auditory cortex, inferior frontal cortex bilaterally, and medial cerebellum were general traits that distinguished fluent speech in people who stutter from that of controls. The stuttering subgroup with higher frequency of dysfluent states during scanning (n = 9) had reduced activation in the right subcortical grey matter, left temporo-occipital cortex, the cingulate cortex, and medial parieto-occipital cortex relative to the subgroup who were more fluent (n = 8). Finally, during dysfluent states relative to fluent ones, there was greater activation of inferior frontal and premotor cortex extending into the frontal operculum, bilaterally. The above differences were seen across both tasks. Subcortical state effects differed according to the task. Overall, our data emphasise the independence of trait and state effects in stuttering. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Positions of human dwellings affect few tropical diseases near ...

African Journals Online (AJOL)

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Some factors that possibly affect tropical disease distribution was investigated in about 500 randomize human dwellings. The studied factors include wild animals, domestic animals, wild plants, cultivated plants, nature of soil, nature of water, positions of human dwellings, nature of building material and position of animal ...

Fish functional traits correlated with environmental variables in a temperate biodiversity hotspot.

Directory of Open Access Journals (Sweden)

Benjamin P Keck

Full Text Available The global biodiversity crisis has invigorated the search for generalized patterns in most disciplines within the natural sciences. Studies based on organismal functional traits attempt to broaden implications of results by identifying the response of functional traits, instead of taxonomic units, to environmental variables. Determining the functional trait responses enables more direct comparisons with, or predictions for, communities of different taxonomic composition. The North American freshwater fish fauna is both diverse and increasingly imperiled through human mediated disturbances, including climate change. The Tennessee River, USA, contains one of the most diverse assemblages of freshwater fish in North America and has more imperiled species than other rivers, but there has been no trait-based study of community structure in the system. We identified 211 localities in the upper Tennessee River that were sampled by the Tennessee Valley Authority between 2009 and 2011 and compiled fish functional traits for the observed species and environmental variables for each locality. Using fourth corner analysis, we identified significant correlations between many fish functional traits and environmental variables. Functional traits associated with an opportunistic life history strategy were correlated with localities subject to greater land use disturbance and less flow regulation, while functional traits associated with a periodic life history strategy were correlated with localities subject to regular disturbance and regulated flow. These are patterns observed at the continental scale, highlighting the generalizability of trait-based methods. Contrary to studies that found no community structure differences when considering riparian buffer zones, we found that fish functional traits were correlated with different environmental variables between analyses with buffer zones vs. entire catchment area land cover proportions. Using existing databases

Fish functional traits correlated with environmental variables in a temperate biodiversity hotspot.

Science.gov (United States)

Keck, Benjamin P; Marion, Zachary H; Martin, Derek J; Kaufman, Jason C; Harden, Carol P; Schwartz, John S; Strange, Richard J

2014-01-01

The global biodiversity crisis has invigorated the search for generalized patterns in most disciplines within the natural sciences. Studies based on organismal functional traits attempt to broaden implications of results by identifying the response of functional traits, instead of taxonomic units, to environmental variables. Determining the functional trait responses enables more direct comparisons with, or predictions for, communities of different taxonomic composition. The North American freshwater fish fauna is both diverse and increasingly imperiled through human mediated disturbances, including climate change. The Tennessee River, USA, contains one of the most diverse assemblages of freshwater fish in North America and has more imperiled species than other rivers, but there has been no trait-based study of community structure in the system. We identified 211 localities in the upper Tennessee River that were sampled by the Tennessee Valley Authority between 2009 and 2011 and compiled fish functional traits for the observed species and environmental variables for each locality. Using fourth corner analysis, we identified significant correlations between many fish functional traits and environmental variables. Functional traits associated with an opportunistic life history strategy were correlated with localities subject to greater land use disturbance and less flow regulation, while functional traits associated with a periodic life history strategy were correlated with localities subject to regular disturbance and regulated flow. These are patterns observed at the continental scale, highlighting the generalizability of trait-based methods. Contrary to studies that found no community structure differences when considering riparian buffer zones, we found that fish functional traits were correlated with different environmental variables between analyses with buffer zones vs. entire catchment area land cover proportions. Using existing databases and fourth corner

An evolutionary medicine approach to understanding factors that contribute to chronic obstructive pulmonary disease.

Science.gov (United States)

Aoshiba, Kazutetsu; Tsuji, Takao; Itoh, Masayuki; Yamaguchi, Kazuhiro; Nakamura, Hiroyuki

2015-01-01

Although many studies have been published on the causes and mechanisms of chronic obstructive pulmonary disease (COPD), the reason for the existence of COPD and the reasons why COPD develops in humans have hardly been studied. Evolutionary medical approaches are required to explain not only the proximate factors, such as the causes and mechanisms of a disease, but the ultimate (evolutionary) factors as well, such as why the disease is present and why the disease develops in humans. According to the concepts of evolutionary medicine, disease susceptibility is acquired as a result of natural selection during the evolutionary process of traits linked to the genes involved in disease susceptibility. In this paper, we discuss the following six reasons why COPD develops in humans based on current evolutionary medical theories: (1) evolutionary constraints; (2) mismatch between environmental changes and evolution; (3) co-evolution with pathogenic microorganisms; (4) life history trade-off; (5) defenses and their costs, and (6) reproductive success at the expense of health. Our perspective pursues evolutionary answers to the fundamental question, 'Why are humans susceptible to this common disease, COPD, despite their long evolutionary history?' We believe that the perspectives offered by evolutionary medicine are essential for researchers to better understand the significance of their work.

Isolation, characterization, and evaluation of multi-trait plant growth promoting rhizobacteria for their growth promoting and disease suppressing effects on ginger.

Science.gov (United States)

Dinesh, Raghavan; Anandaraj, Muthuswamy; Kumar, Aundy; Bini, Yogiyar Kundil; Subila, Kizhakke Purayil; Aravind, Ravindran

2015-04-01

In this study, 100 PGPR strains isolated from different varieties of ginger (Zingiber officinale Rosc.) were first characterized for their morphological, biochemical, and nutrient mobilization traits in vitro. The PGPR were also screened in vitro for inhibition of Pythium myriotylum causing soft rot in ginger. Results revealed that only five PGPR showed >70% suppression of P. myriotylum. These 5 PGPR viz., GRB (Ginger rhizobacteria) 25--Burkholderia cepacia, GRB35--Bacillus amyloliquefaciens; GRB58--Serratia marcescens; GRB68--S. marcescens; GRB91--Pseudomonas aeruginosa were used for further growth promotion and biocontrol studies in the green house and field. The green house study revealed that GRB35 (B. amyloliquefaciens) and GRB68 (S. marcescens) registered markedly higher sprouting (96.3%) and lower disease incidence (48.1%) and greater rhizome yield (365.6 g pot(-1) and 384.4 g pot(-1), respectively), while control registered the lowest sprouting (66%), maximum soft rot incidence (100%) and lowest rhizome yield (134.4 g pot(-1)). In the field experiments also, GRB68 (S. marcescens) and GRB35 (B. amyloliquefaciens) registered the greatest sprouting (80% each), markedly lower soft rot incidence (5.2% and 7.3%, respectively) and higher yield (5.0 and 4.3 kg(3)m(-2), respectively) compared to chemicals like Streptomycin sulphate (73.0%, 18.5% and 2.3 kg(3)m(-2), respectively), Metalaxyl-Mancozeb (73.0%, 14.0% and 3.8 kg(3)m(-2), respectively) and control (73.0%, 25.1% and 2.2 kg 3m(-2), respectively). Overall, the results suggested that for growth promotion and management of soft rot disease in ginger, GRB35 B. amyloliquefaciens and GRB68 S. marcescens could be good alternatives to chemical measures. Since, the latter has been reported to be an opportunistic human pathogen, we recommend the use of B. amyloliquefaciens for integration into nutrient and disease management schedules for ginger cultivation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Human genetics of infectious diseases: a unified theory

OpenAIRE

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predispos...

Human drivers of ecological and evolutionary dynamics in emerging and disappearing infectious disease systems.

Science.gov (United States)

Rogalski, Mary A; Gowler, Camden D; Shaw, Clara L; Hufbauer, Ruth A; Duffy, Meghan A

2017-01-19

Humans have contributed to the increased frequency and severity of emerging infectious diseases, which pose a significant threat to wild and domestic species, as well as human health. This review examines major pathways by which humans influence parasitism by altering (co)evolutionary interactions between hosts and parasites on ecological timescales. There is still much to learn about these interactions, but a few well-studied cases show that humans influence disease emergence every step of the way. Human actions significantly increase dispersal of host, parasite and vector species, enabling greater frequency of infection in naive host populations and host switches. Very dense host populations resulting from urbanization and agriculture can drive the evolution of more virulent parasites and, in some cases, more resistant host populations. Human activities that reduce host genetic diversity or impose abiotic stress can impair the ability of hosts to adapt to disease threats. Further, evolutionary responses of hosts and parasites can thwart disease management and biocontrol efforts. Finally, in rare cases, humans influence evolution by eradicating an infectious disease. If we hope to fully understand the factors driving disease emergence and potentially control these epidemics we must consider the widespread influence of humans on host and parasite evolutionary trajectories.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.

Science.gov (United States)

Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan

2017-11-02

Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

How functional traits of estuarine macrobenthic assemblages respond to metal contamination?

KAUST Repository

Piló, D.

2016-08-06

The effects of metal contamination on estuarine macrobenthic communities were investigated using the Biological Traits Analysis (BTA). The study was carried out in the Tagus estuary (western Portugal). Samples of macrobenthic communities and associated environmental variables were taken in four surveys (September 2012, and February, May and October 2013) across the contamination gradient from three main zones: a slightly contaminated, a moderately contaminated and a highly contaminated zone. Functional traits for the most abundant species were assigned using seven categories based on “Feeding mode”, “Life span”, “Body size”, “Motility”, “Position in sediments”, “Larval type” and “AMBI ecological group”. To investigate whether the macroinvertebrate community structure was associated with the environmental parameters and biological traits an integrative multivariate analysis, combining the RLQ analysis and the fourth-corner method, was applied. Within this analysis, human-induced estuarine variables (metals) were rendered independent from natural ones (sediment fine particles) through partial correlations. Following this approach, it was possible to decouple the effects of two typically highly correlated environmental descriptors with different origins. Overall, the study identified significant relationships between sediment environmental descriptors and the functional traits of macrobenthic communities. Further, RLQ/Fourth-corner combined analysis successfully isolated the traits and corresponding species that were most correlated with the measured concentration of trace metals in sediments, supporting the knowledge that benthic organisms exhibit distinct responses to different levels of disturbance. A shift in species dominance occurred along the contamination gradient with epifaunal tolerant species with very small size, long life span, and crawling motility dominating the highest contaminated area. This area was also related with

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Science.gov (United States)

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

Different level of population differentiation among human genes.

Science.gov (United States)

Wu, Dong-Dong; Zhang, Ya-Ping

2011-01-14

During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations. Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher FST SNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection. Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

Full genotyping of a highly polymorphic human gene trait by time-resolved fluorescence resonance energy transfer.

Directory of Open Access Journals (Sweden)

Edoardo Totè

Full Text Available The ability of detecting the subtle variations occurring, among different individuals, within specific DNA sequences encompassed in highly polymorphic genes discloses new applications in genomics and diagnostics. DQB1 is a gene of the HLA-II DQ locus of the Human Leukocyte Antigens (HLA system. The polymorphisms of the trait of the DQB1 gene including codons 52-57 modulate the susceptibility to a number of severe pathologies. Moreover, the donor-receiver tissue compatibility in bone marrow transplantations is routinely assessed through crossed genotyping of DQB and DQA. For the above reasons, the development of rapid, reliable and cost-effective typing technologies of DQB1 in general, and more specifically of the codons 52-57, is a relevant although challenging task. Quantitative assessment of the fluorescence resonance energy transfer (FRET efficiency between chromophores labelling the opposite ends of gene-specific oligonucleotide probes has proven to be a powerful tool to type DNA polymorphisms with single-nucleotide resolution. The FRET efficiency can be most conveniently quantified by applying a time-resolved fluorescence analysis methodology, i.e. time-correlated single-photon counting, which allows working on very diluted template specimens and in the presence of fluorescent contaminants. Here we present a full in-vitro characterization of the fluorescence responses of two probes when hybridized to oligonucleotide mixtures mimicking all the possible genotypes of the codons 52-57 trait of DQB1 (8 homozygous and 28 heterozygous. We show that each genotype can be effectively tagged by the combination of the fluorescence decay constants extrapolated from the data obtained with such probes.

Biodiversity loss, emerging infectious diseases and impact on human and crops

International Nuclear Information System (INIS)

Shinwari, Z.K.; Gilani, S.A.; Khan, A.L.

2012-01-01

We are losing biodiversity through several factors ranging from global warming, climatic change, unsustainable use of natural resources, human settlements, demand for food, medicine etc. Consequently, the biodiversity losses are causing emergence of infectious diseases (EIDs) which are making them more virulent than the past. Both biodiversity loss and emergence of diseases significantly impact the human derived benefits in-terms of economy and food. Ecological stability, productivity and food-web interactions are indirectly correlated with biodiversity and any change in these will cause losses in biodiversity that would certainly influence the human derived benefits and crops. The current article reviews the biodiversity losses and emerging infectious diseases at various levels reported by recent literature which will help in current status of EIDs and future recommendations. (author)

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

NARCIS (Netherlands)

Macé, Aurélien; Tuke, Marcus A; Deelen, Patrick; Kristiansson, Kati; Mattsson, Hannele; Nõukas, Margit; Sapkota, Yadav; Schick, Ursula; Porcu, Eleonora; Rüeger, Sina; McDaid, Aaron F; Porteous, David; Winkler, Thomas W; Salvi, Erika; Shrine, Nick; Liu, Xueping; Ang, Wei Q; Zhang, Weihua; Feitosa, Mary F; Venturini, Cristina; van der Most, Peter J; Rosengren, Anders; Wood, Andrew R; Beaumont, Robin N; Jones, Samuel E; Ruth, Katherine S; Yaghootkar, Hanieh; Tyrrell, Jessica; Havulinna, Aki S; Boers, Harmen; Mägi, Reedik; Kriebel, Jennifer; Müller-Nurasyid, Martina; Perola, Markus; Nieminen, Markku; Lokki, Marja-Liisa; Kähönen, Mika; Viikari, Jorma S; Geller, Frank; Lahti, Jari; Palotie, Aarno; Koponen, Päivikki; Lundqvist, Annamari; Rissanen, Harri; Bottinger, Erwin P; Afaq, Saima; Wojczynski, Mary K; Lenzini, Petra; Nolte, Ilja M; Sparsø, Thomas; Schupf, Nicole; Christensen, Kaare; Perls, Thomas T; Newman, Anne B; Werge, Thomas; Snieder, Harold; Spector, Timothy D; Chambers, John C; Koskinen, Seppo; Melbye, Mads; Raitakari, Olli T; Lehtimäki, Terho; Tobin, Martin D; Wain, Louise V; Sinisalo, Juha; Peters, Annette; Meitinger, Thomas; Martin, Nicholas G; Wray, Naomi R; Montgomery, Grant W; Medland, Sarah E; Swertz, Morris A; Vartiainen, Erkki; Borodulin, Katja; Männistö, Satu; Murray, Anna; Bochud, Murielle; Jacquemont, Sébastien; Rivadeneira, Fernando; Hansen, Thomas F; Oldehinkel, Albertine J; Mangino, Massimo; Province, Michael A; Deloukas, Panos; Kooner, Jaspal S; Freathy, Rachel M; Pennell, Craig; Feenstra, Bjarke; Strachan, David P; Lettre, Guillaume; Hirschhorn, Joel; Cusi, Daniele; Heid, Iris M; Hayward, Caroline; Männik, Katrin; Beckmann, Jacques S; Loos, Ruth J F; Nyholt, Dale R; Metspalu, Andres; Eriksson, Johan G; Weedon, Michael N; Salomaa, Veikko; Franke, Lude; Reymond, Alexandre; Frayling, Timothy M; Kutalik, Zoltán

2017-01-01

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at

Estimates of combining ability and heterosis for growth traits in a full ...

African Journals Online (AJOL)

user

freshwater fisheries research center; PCA, principal component analysis; PCs, principal components. .... protein. No severe disease outbreaks were found during the experiment. The research ..... interactions in terms of expression of traits. The.

Missing heritability : Is the gap closing? An analysis of 32 complex traits in the Lifelines Cohort Study

NARCIS (Netherlands)

Nolte, Ilja M.; van der Most, Peter J.; Alizadeh, Behrooz Z.; de Bakker, Paul I. W.; Boezen, H. Marike; Bruinenberg, Marcel; Franke, Lude; van der Harst, Pim; Navis, Gerjan; Postma, Dirkje S.; Rots, Marianne G.; Stolk, Ronald P.; Swertz, Morris A.; Wolffenbuttel, Bruce H. R.; Wijmenga, Cisca; Snieder, Harold

Despite the recent explosive rise in number of genetic markers for complex disease traits identified in genome-wide association studies, there is still a large gap between the known heritability of these traits and the part explained by these markers. To gauge whether this 'heritability gap' is

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Directory of Open Access Journals (Sweden)

Jingjing Liang

2017-05-01

Full Text Available Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8 for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4 and multiple-trait analyses identified one novel locus (FRMD3 for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

A Comprehensive Analysis of the Correlations between Resting-State Oscillations in Multiple-Frequency Bands and Big Five Traits.

Science.gov (United States)

Ikeda, Shigeyuki; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Sakaki, Kohei; Nozawa, Takayuki; Yokota, Susumu; Magistro, Daniele; Kawashima, Ryuta

2017-01-01

Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz) of resting-state functional magnetic resonance imaging (fMRI) activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI), and the fractional amplitude of low-frequency fluctuation (fALFF) at four distinct frequency bands (slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz) and slow-2 (0.198-0.25 Hz)). We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands.

White-Matter Structural Connectivity Underlying Human Laughter-Related Traits Processing.

Science.gov (United States)

Wu, Ching-Lin; Zhong, Suyu; Chan, Yu-Chen; Chen, Hsueh-Chih; Gong, Gaolang; He, Yong; Li, Ping

2016-01-01

Most research into the neural mechanisms of humor has not explicitly focused on the association between emotion and humor on the brain white matter networks mediating this connection. However, this connection is especially salient in gelotophobia (the fear of being laughed at), which is regarded as the presentation of humorlessness, and two related traits, gelotophilia (the enjoyment of being laughed at) and katagelasticism (the enjoyment of laughing at others). Here, we explored whether the topological properties of white matter networks can account for the individual differences in the laughter-related traits of 31 healthy adults. We observed a significant negative correlation between gelotophobia scores and the clustering coefficient, local efficiency and global efficiency, but a positive association between gelotophobia scores and path length in the brain's white matter network. Moreover, the current study revealed that with increasing individual fear of being laughed at, the linking efficiencies in superior frontal gyrus, anterior cingulate cortex, parahippocampal gyrus, and middle temporal gyrus decreased. However, there were no significant correlations between either gelotophilia or katagelasticism scores or the topological properties of the brain white matter network. These findings suggest that the fear of being laughed at is directly related to the level of local and global information processing of the brain network, which might provide new insights into the neural mechanisms of the humor information processing.

The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits

DEFF Research Database (Denmark)

Voight, Benjamin F; Kang, Hyun Min; Ding, Jun

2012-01-01

Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands...... dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping...

Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

DEFF Research Database (Denmark)

Hall, Vanessa Jane

2016-01-01

Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

Tribbles-1: a novel regulator of hepatic lipid metabolism in humans.

Science.gov (United States)

Bauer, Robert C; Yenilmez, Batuhan O; Rader, Daniel J

2015-10-01

The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target. © 2015 Authors; published by Portland Press Limited.

Evolution and the Growth Process: Natural Selection of Entrepreneurial Traits.

Science.gov (United States)

Galor, Oded; Michalopoulos, Stelios

2012-03-01

This research suggests that a Darwinian evolution of entrepreneurial spirit played a significant role in the process of economic development and the dynamics of inequality within and across societies. The study argues that entrepreneurial spirit evolved non-monotonically in the course of human history. In early stages of development, risk-tolerant, growth promoting traits generated an evolutionary advantage and their increased representation accelerated the pace of technological progress and the process of economic development. In mature stages of development, however, risk-averse traits gained an evolutionary advantage, diminishing the growth potential of advanced economies and contributing to convergence in economic growth across countries.

Automatic prediction of facial trait judgments: appearance vs. structural models.

Directory of Open Access Journals (Sweden)

Mario Rojas

Full Text Available Evaluating other individuals with respect to personality characteristics plays a crucial role in human relations and it is the focus of attention for research in diverse fields such as psychology and interactive computer systems. In psychology, face perception has been recognized as a key component of this evaluation system. Multiple studies suggest that observers use face information to infer personality characteristics. Interactive computer systems are trying to take advantage of these findings and apply them to increase the natural aspect of interaction and to improve the performance of interactive computer systems. Here, we experimentally test whether the automatic prediction of facial trait judgments (e.g. dominance can be made by using the full appearance information of the face and whether a reduced representation of its structure is sufficient. We evaluate two separate approaches: a holistic representation model using the facial appearance information and a structural model constructed from the relations among facial salient points. State of the art machine learning methods are applied to a derive a facial trait judgment model from training data and b predict a facial trait value for any face. Furthermore, we address the issue of whether there are specific structural relations among facial points that predict perception of facial traits. Experimental results over a set of labeled data (9 different trait evaluations and classification rules (4 rules suggest that a prediction of perception of facial traits is learnable by both holistic and structural approaches; b the most reliable prediction of facial trait judgments is obtained by certain type of holistic descriptions of the face appearance; and c for some traits such as attractiveness and extroversion, there are relationships between specific structural features and social perceptions.

A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study

Directory of Open Access Journals (Sweden)

Pearce Elizabeth N

2007-09-01

Full Text Available Abstract Background Glomerular filtration rate (GFR and urinary albumin excretion (UAE are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism (SNP set and measures of kidney function and endocrine traits. Methods Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C (cysC; n = 981 were measured at the seventh examination cycle (1998–2001; GFR (n = 1010 was estimated via the Modification of Diet in Renal Disease (MDRD equation; UAE was measured on spot urine samples during the sixth examination cycle (1995–1998 and was indexed to urinary creatinine (n = 822. Thyroid stimulating hormone (TSH was measured at the third and fourth examination cycles (1981–1984; 1984–1987 and mean value of the measurements were used (n = 810. Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations (GEE and family-based association tests (FBAT models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value ≥ 0.001, and call rates of at least 80%. Results The top SNPs associated with these traits using the GEE method were rs2839235 with GFR (p-value 1.6*10-05, rs1158167 with cysC (p-value 8.5*10-09, rs1712790 with UAE (p-value 1.9*10-06, and rs6977660 with TSH (p-value 3.7*10-06, respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR(p-value 2.4*10-5, rs563754 with cysC (p-value 4.7*10-5, rs1243400 with UAE (p-value 4.8*10-6, and rs4128956 with TSH (p-value 3.6*10-5, respectively. Detailed

Association of porcine UCP3 gene polymorphisms with fatness traits ...

African Journals Online (AJOL)

Administrator

2011-04-25

Apr 25, 2011 ... ... for fatness traits in pig. Polymorphism in UCP3 gene may change the function ... NM_214049) and human UCP3 gene DNA sequence (GenBank accession No. NC_000011). ..... Sleep, 29: 645-649. Zhao J, Li H, Kong X, ...

The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

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Amr T. M. Saeb

2016-01-01

Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

Parameters in dynamic models of complex traits are containers of missing heritability.

Directory of Open Access Journals (Sweden)

Yunpeng Wang

Full Text Available Polymorphisms identified in genome-wide association studies of human traits rarely explain more than a small proportion of the heritable variation, and improving this situation within the current paradigm appears daunting. Given a well-validated dynamic model of a complex physiological trait, a substantial part of the underlying genetic variation must manifest as variation in model parameters. These parameters are themselves phenotypic traits. By linking whole-cell phenotypic variation to genetic variation in a computational model of a single heart cell, incorporating genotype-to-parameter maps, we show that genome-wide association studies on parameters reveal much more genetic variation than when using higher-level cellular phenotypes. The results suggest that letting such studies be guided by computational physiology may facilitate a causal understanding of the genotype-to-phenotype map of complex traits, with strong implications for the development of phenomics technology.

Animal models for human genetic diseases | Sharif | African Journal ...

African Journals Online (AJOL)

The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...

Chronic Inflammatory Periodontal Disease in Patients with Human Immunodeficiency Virus.

OpenAIRE

Vania López Rodríguez; Emilio Carpio Muñoz; Vicente Fardales Macías; Iralys Benítez Guzmán

2009-01-01

Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determi...

PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

Energy Technology Data Exchange (ETDEWEB)

Baker, Lindsey A. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States); Allis, C. David [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: alliscd@rockefeller.edu; Wang, Gang G. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: gwang@rockefeller.edu

2008-12-01

Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies

PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

International Nuclear Information System (INIS)

Baker, Lindsey A.; Allis, C. David; Wang, Gang G.

2008-01-01

Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies wherein 'chromatin readers' stand as potential drug

Functional modules, mutational load and human genetic disease.

Science.gov (United States)

Zaghloul, Norann A; Katsanis, Nicholas

2010-04-01

The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders.

Science.gov (United States)

Aghajani, Moji; Colins, Olivier F; Klapwijk, Eduard T; Veer, Ilya M; Andershed, Henrik; Popma, Arne; van der Wee, Nic J; Vermeiren, Robert R J M

2016-11-01

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017-4033, 2016. © 2016 The Authors Human

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

OpenAIRE

Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Smith, Jennifer A.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Yanek, Lisa R.; Schwander, Karen; Tajuddin, Salman M.; Sofer, Tamar; Kim, Wonji; Kayima, James

2017-01-01

© 2017 Public Library of Science. All Rights Reserved. Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genom...

Annotating Diseases Using Human Phenotype Ontology Improves Prediction of Disease-Associated Long Non-coding RNAs.

Science.gov (United States)

Le, Duc-Hau; Dao, Lan T M

2018-05-23

Recently, many long non-coding RNAs (lncRNAs) have been identified and their biological function has been characterized; however, our understanding of their underlying molecular mechanisms related to disease is still limited. To overcome the limitation in experimentally identifying disease-lncRNA associations, computational methods have been proposed as a powerful tool to predict such associations. These methods are usually based on the similarities between diseases or lncRNAs since it was reported that similar diseases are associated with functionally similar lncRNAs. Therefore, prediction performance is highly dependent on how well the similarities can be captured. Previous studies have calculated the similarity between two diseases by mapping exactly each disease to a single Disease Ontology (DO) term, and then use a semantic similarity measure to calculate the similarity between them. However, the problem of this approach is that a disease can be described by more than one DO terms. Until now, there is no annotation database of DO terms for diseases except for genes. In contrast, Human Phenotype Ontology (HPO) is designed to fully annotate human disease phenotypes. Therefore, in this study, we constructed disease similarity networks/matrices using HPO instead of DO. Then, we used these networks/matrices as inputs of two representative machine learning-based and network-based ranking algorithms, that is, regularized least square and heterogeneous graph-based inference, respectively. The results showed that the prediction performance of the two algorithms on HPO-based is better than that on DO-based networks/matrices. In addition, our method can predict 11 novel cancer-associated lncRNAs, which are supported by literature evidence. Copyright © 2018 Elsevier Ltd. All rights reserved.

Androgen receptor polyglutamine repeat length (AR-CAGn) modulates the effect of testosterone on androgen-associated somatic traits in Filipino young adult men.

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Ryan, Calen P; Georgiev, Alexander V; McDade, Thomas W; Gettler, Lee T; Eisenberg, Dan T A; Rzhetskaya, Margarita; Agustin, Sonny S; Hayes, M Geoffrey; Kuzawa, Christopher W

2017-06-01

The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels. We tested whether relationships between AR-CAGn and several androgen-associated somatic traits (waist circumference, lean mass, arm muscle area, and grip strength) were modified by salivary (waking and pre-bed) and circulating (total) testosterone (T) levels in young adult males living in metropolitan Cebu, Philippines (n = 675). When men's waking T was low, they had a reduction in three out of four androgen-associated somatic traits with lengthening AR-CAGn (p AR-CAGn was associated with an increase in these same somatic traits. Our finding that longer AR-CAGn predicts greater androgen-associated trait expression among high-T men runs counter to in vitro work, but is generally consistent with the few prior studies to evaluate similar interactions in human populations. Collectively, these results raise questions about the applicability of findings derived from in vitro AR-CAGn studies to the receptor's role in maintaining androgen-associated somatic traits in human populations. © 2017 Wiley Periodicals, Inc.

Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease

Science.gov (United States)

Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K.; Zhao, Hongyu

2017-01-01

Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer’s disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson’s disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline. PMID:28742084

Modelling the influence of human behaviour on the spread of infectious diseases: a review.

Science.gov (United States)

Funk, Sebastian; Salathé, Marcel; Jansen, Vincent A A

2010-09-06

Human behaviour plays an important role in the spread of infectious diseases, and understanding the influence of behaviour on the spread of diseases can be key to improving control efforts. While behavioural responses to the spread of a disease have often been reported anecdotally, there has been relatively little systematic investigation into how behavioural changes can affect disease dynamics. Mathematical models for the spread of infectious diseases are an important tool for investigating and quantifying such effects, not least because the spread of a disease among humans is not amenable to direct experimental study. Here, we review recent efforts to incorporate human behaviour into disease models, and propose that such models can be broadly classified according to the type and source of information which individuals are assumed to base their behaviour on, and according to the assumed effects of such behaviour. We highlight recent advances as well as gaps in our understanding of the interplay between infectious disease dynamics and human behaviour, and suggest what kind of data taking efforts would be helpful in filling these gaps.

Implications of prion adaptation and evolution paradigm for human neurodegenerative diseases.

Science.gov (United States)

Kabir, M Enamul; Safar, Jiri G

2014-01-01

There is a growing body of evidence indicating that number of human neurodegenerative diseases, including Alzheimer disease, Parkinson disease, fronto-temporal dementias, and amyotrophic lateral sclerosis, propagate in the brain via prion-like intercellular induction of protein misfolding. Prions cause lethal neurodegenerative diseases in humans, the most prevalent being sporadic Creutzfeldt-Jakob disease (sCJD); they self-replicate and spread by converting the cellular form of prion protein (PrP(C)) to a misfolded pathogenic conformer (PrP(Sc)). The extensive phenotypic heterogeneity of human prion diseases is determined by polymorphisms in the prion protein gene, and by prion strain-specific conformation of PrP(Sc). Remarkably, even though informative nucleic acid is absent, prions may undergo rapid adaptation and evolution in cloned cells and upon crossing the species barrier. In the course of our investigation of this process, we isolated distinct populations of PrP(Sc) particles that frequently co-exist in sCJD. The human prion particles replicate independently and undergo competitive selection of those with lower initial conformational stability. Exposed to mutant substrate, the winning PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to the lowest stability. Thus, the evolution and adaptation of human prions is enabled by a dynamic collection of distinct populations of particles, whose evolution is governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers. This fundamental biological mechanism may explain the drug resistance that some prions gained after exposure to compounds targeting PrP(Sc). Whether the phenotypic heterogeneity of other neurodegenerative diseases caused by protein misfolding is determined by the spectrum of misfolded conformers (strains) remains to be established. However, the prospect that these conformers may evolve and

Quantitative Trait Loci for Fertility Traits in Finnish Ayrshire Cattle

DEFF Research Database (Denmark)

Schulman, Nina F; Sahana, Goutam; Lund, Mogens S

2008-01-01

A whole genome scan was carried out to detect quantitative trait loci (QTL) for fertility traits in Finnish Ayrshire cattle. The mapping population consisted of 12 bulls and 493 sons. Estimated breeding values for days open, fertility treatments, maternal calf mortality and paternal non-return rate...... combinations, which were observed significant in the regression method. Twenty-two chromosome-wise significant QTL were detected. Several of the detected QTL areas were overlapping with milk production QTL previously identified in the same population. Multi-trait QTL analyses were carried out to test...... if these effects were due to a pleiotropic QTL affecting fertility and milk yield traits or to linked QTL causing the effects. This distinction could only be made with confidence on BTA1 where a QTL affecting milk yield is linked to a pleiotropic QTL affecting days open and fertility treatments...

Personality traits and emotional patterns in irritable bowel syndrome.

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Muscatello, Maria Rosaria A; Bruno, Antonio; Mento, Carmela; Pandolfo, Gianluca; Zoccali, Rocco A

2016-07-28

The review focuses on those personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness), constructs (alexithymia and distressed - Type D personality) and emotional patterns (negative and positive) that are of particular concern in health psychology, with the aim to highlight their potential role on the pathogenesis, onset, symptom clusters, clinical course, and outcome of irritable bowel syndrome (IBS). Personality traits and emotional patterns play key roles in affecting autonomic, immune, inflammatory, and endocrine functions, thus contributing not only to IBS clinical expression and symptomatic burden, but also to disease physiopathology. In this sense, psychological treatments should address those personality traits and emotional features that are constitutive of, and integral to IBS. The biopsychosocial model of illness applied to IBS acknowledges the interaction between biological, psychological, environmental, and social factors in relation to pain and functional disability. A holistic approach to IBS should take into account the heterogeneous nature of the disorder, and differentiate treatments for different types of IBS, also considering the marked individual differences in prevalent personality traits and emotional patterns. Beyond medications, and lifestyle/dietary interventions, psychological and educational treatments may provide the optimal chance of addressing clinical symptoms, comorbid conditions, and quality of life in IBS patients.

Affective touch awareness in mental health and disease relates to autistic traits - An explorative neurophysiological investigation.

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Croy, Ilona; Geide, Helen; Paulus, Martin; Weidner, Kerstin; Olausson, Håkan

2016-11-30

Affective touch is important for social interaction within families and groups and there is evidence that unmyelinated C tactile fibers are involved in this process. Individuals with autism spectrum disorders show alterations in the perception and processing of affective touch. sThus, we hypothesized that affective touch awareness based on C tactile fiber activation is impaired in individuals with high levels of autistic trait. The pleasantness perception of optimal and suboptimal C tactile stimuli was tested in an explorative study in 70 patients recruited from an outpatient psychotherapy clinic and 69 healthy comparison subjects. All participants completed questionnaires about autistic traits, depressive symptomatology, childhood maltreatment, and about the daily amount of touch. Relative to comparison subjects, patients reported engaging in touch less frequently in daily life and rated touch less pleasant. Reduced valence ratings of touch were explained by childhood maltreatment but not by any particular disorder or depression severity. Among all tested variables, the affective touch awareness correlated with autistic traits only - in patients as well as in comparison subjects. Taken together, individuals with mental health issues have a lower baseline of expression and reception of affective touch. Autistic traits and childhood maltreatment modulate the experience of affective touch. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Credit scores, cardiovascular disease risk, and human capital.

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Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

2014-12-02

Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

Functional gastrointestinal diseases and psychological maladjustment, personality traits and quality of life.

Science.gov (United States)

Ranasinghe, Nishadi; Devanarayana, Niranga Manjuri; Rajindrajith, Shaman; Perera, Madusanka S; Nishanthinie, Samudu; Warnakulasuriya, Tania; de Zoysa, Piyanjali Thamesha

2018-02-27

Chronic abdominal pain is a common worldwide problem and known to be associated with psychological problems. This study evaluated the association between abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs), psychological maladjustment and personality traits in adolescents. Adolescents aged 13-18 years were recruited from 5 randomly selected schools in Ampara district of Sri Lanka. AP-FGIDs were diagnosed using Rome III criteria. Translated and validated Rome III questionnaire (Child report form), personality questionnaire (PAQ) and PedsQL (Pediatric Quality of Life) inventory were used in data collection. Written consent was obtained from a parent and assent was obtained from every child recruited. The questionnaire was distributed in an examination setting to ensure confidentiality and privacy. Research assistants were present during data collection to assist on any necessary clarifications. A total of 1697 subjects were recruited [males 779 (45.9%), mean age 15.1 years, SD 1.6 years]. AP-FGIDs were present in 202 (11.9%). Those with AP-FGIDs had significantly higher mean scores for all personality traits (hostility and aggression, negative self-esteem, emotional unresponsiveness, emotional instability and negative world view), except dependency. Affected children had lower scores for all 4 domains of HRQoL (physical, emotional, social and school functioning), compared to controls (p PAQ scores within that of psychological maladjustment (p PAQ negatively correlated with scores obtained for HRQoL (r = - 0.52, p PAQ and lower HRQoL scores (p < 0.05). Adolescents with AP-FGIDs have more psychological maladjustment and abnormal personality traits than healthy controls. Affected adolescents with higher psychological maladjustments have lower HRQoL. Greater psychological maladjustment and lower HRQoL are associated with healthcare seeking behaviour in adolescents with AP-FGIDs.

Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies

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Karina O. Brandão

2017-09-01

Full Text Available It is now a decade since human induced pluripotent stem cells (hiPSCs were first described. The reprogramming of adult somatic cells to a pluripotent state has become a robust technology that has revolutionised our ability to study human diseases. Crucially, these cells capture all the genetic aspects of the patient from which they were derived. Combined with advances in generating the different cell types present in the human heart, this has opened up new avenues to study cardiac disease in humans and investigate novel therapeutic approaches to treat these pathologies. Here, we provide an overview of the current state of the field regarding the generation of cardiomyocytes from human pluripotent stem cells and methods to assess them functionally, an essential requirement when investigating disease and therapeutic outcomes. We critically evaluate whether treatments suggested by these in vitro models could be translated to clinical practice. Finally, we consider current shortcomings of these models and propose methods by which they could be further improved.

Twins for epigenetic studies of human aging and development

DEFF Research Database (Denmark)

Tan, Qihua; Christiansen, Lene; Thomassen, Mads

2013-01-01

Most of the complex traits including aging phenotypes are caused by the interaction between genome and environmental conditions and the interface of epigenetics may be a central mechanism. Although modern technologies allow us high-throughput profiling of epigenetic patterns already at genome level...... and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable sample of twins is helping to bridge the gap between gene activity and the environments through epigenetic mechanisms unlimited by DNA sequence variations. We propose to extend the classical twin...... design to study the aging-related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Different study designs and application issues will be highlighted and novel approaches introduced with aim at making uses of twins in assessing the environmental...

The consequences of human actions on risks for infectious diseases: a review

OpenAIRE

Lindahl, Johanna F.; Grace, Delia

2015-01-01

The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating ...

Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

Science.gov (United States)

Zhang, Shujun

2018-01-01

Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

Directory of Open Access Journals (Sweden)

Xingjie Hao

2018-01-01

Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

Single-Domain Antibodies As Therapeutics against Human Viral Diseases

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Yanling Wu

2017-12-01

Full Text Available In full-size formats, monoclonal antibodies have been highly successful as therapeutics against cancer and immune diseases. However, their large size leads to inaccessibility of some epitopes and relatively high production costs. As an alternative, single-domain antibodies (sdAbs offer special advantages compared to full-size antibodies, including smaller size, larger number of accessible epitopes, relatively low production costs and improved robustness. Currently, sdAbs are being developed against a number of viruses, including human immunodeficiency virus-1 (HIV-1, influenza viruses, hepatitis C virus (HCV, respiratory syncytial virus (RSV, and enteric viruses. Although sdAbs are very potent inhibitors of viral infections, no sdAbs have been approved for clinical use against virial infection or any other diseases. In this review, we discuss the current state of research on sdAbs against viruses and their potential as therapeutics against human viral diseases.

Novel applications of multitask learning and multiple output regression to multiple genetic trait prediction.

Science.gov (United States)

He, Dan; Kuhn, David; Parida, Laxmi

2016-06-15

Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait prediction is usually represented as linear regression models. In many cases, for the same set of samples and markers, multiple traits are observed. Some of these traits might be correlated with each other. Therefore, modeling all the multiple traits together may improve the prediction accuracy. In this work, we view the multitrait prediction problem from a machine learning angle: as either a multitask learning problem or a multiple output regression problem, depending on whether different traits share the same genotype matrix or not. We then adapted multitask learning algorithms and multiple output regression algorithms to solve the multitrait prediction problem. We proposed a few strategies to improve the least square error of the prediction from these algorithms. Our experiments show that modeling multiple traits together could improve the prediction accuracy for correlated traits. The programs we used are either public or directly from the referred authors, such as MALSAR (http://www.public.asu.edu/~jye02/Software/MALSAR/) package. The Avocado data set has not been published yet and is available upon request. dhe@us.ibm.com. © The Author 2016. Published by Oxford University Press.

Same Traits, Different Variance

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Jamie S. Churchyard

2014-02-01

Full Text Available Personality trait questionnaires are regularly used in individual differences research to examine personality scores between participants, although trait researchers tend to place little value on intra-individual variation in item ratings within a measured trait. The few studies that examine variability indices have not considered how they are related to a selection of psychological outcomes, so we recruited 160 participants (age M = 24.16, SD = 9.54 who completed the IPIP-HEXACO personality questionnaire and several outcome measures. Heterogenous within-subject differences in item ratings were found for every trait/facet measured, with measurement error that remained stable across the questionnaire. Within-subject standard deviations, calculated as measures of individual variation in specific item ratings within a trait/facet, were related to outcomes including life satisfaction and depression. This suggests these indices represent valid constructs of variability, and that researchers administering behavior statement trait questionnaires with outcome measures should also apply item-level variability indices.

Glutathione dysregulation and the etiology and progression of human diseases.

NARCIS (Netherlands)

Ballatori, N.; Krance, S.M.; Notenboom, S.; Shi, S.; Tieu, K.; Hammond, C.L.

2009-01-01

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases

Economic values for health and feed efficiency traits of dual-purpose cattle in marginal areas.

Science.gov (United States)

Krupová, Z; Krupa, E; Michaličková, M; Wolfová, M; Kasarda, R

2016-01-01

Economic values of clinical mastitis, claw disease, and feed efficiency traits along with 16 additional production and functional traits were estimated for the dairy population of the Slovak Pinzgau breed using a bioeconomic approach. In the cow-calf population (suckler cow population) of the same breed, the economic values of feed efficiency traits along with 15 further production and functional traits were calculated. The marginal economic values of clinical mastitis and claw disease incidence in the dairy system were -€ 70.65 and -€ 26.73 per case per cow and year, respectively. The marginal economic values for residual feed intake were -€ 55.15 and -€ 54.64/kg of dry matter per day for cows and breeding heifers in the dairy system and -€ 20.45, -€ 11.30, and -€ 6.04/kg of dry matter per day for cows, breeding heifers, and fattened animals in the cow-calf system, respectively, all expressed per cow and year. The sums of the relative economic values for the 2 new health traits in the dairy system and for residual feed intake across all cattle categories in both systems were 1.4 and 8%, respectively. Within the dairy production system, the highest relative economic values were for milk yield (20%), daily gain of calves (20%), productive lifetime (10%), and cow conception rate (8%). In the cow-calf system, the most important traits were weight gain of calves from 120 to 210 d and from birth to 120 d (19 and 14%, respectively), productive lifetime (17%), and cow conception rate (13%). Based on the calculation of economic values for traits in the dual-purpose Pinzgau breed, milk production and growth traits remain highly important in the breeding goal, but their relative importance should be adapted to new production and economic conditions. The economic importance of functional traits (especially of cow productive lifetime and fertility) was sufficiently high to make the inclusion of these traits into the breeding goal necessary. An increased interest

The nuclear envelopathies and human diseases

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Jeang Kuan-Teh

2009-10-01

Full Text Available Abstract The nuclear envelope (NE consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies.

Borna disease virus and its role in the pathology of animals and humans

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A. O. Mikheev

2017-12-01

Full Text Available Infectious diseases that are caused by numerous pathogenic microorganisms – bacteria, viruses, protozoa or fungi – can be transmitted from patients or carriers to healthy people or animals. A large group of infectious disease is caused by pathogens of animal infections – zoonoses. The issue of zoonoses is of great significance in human pathology and requires comprehensive study. This is of particular relevance to Ukraine, as the question of prevalence, level within the population and threats to human life and health from zoonoses, though highly important, has remained insufficiently studied. Information about many of these pathogens is absent in the existing scientific literature accessible in Ukraine – both veterinary and medical. This applies, in particular, to a causative agent of viral zoonoses the Borna disease virus or Bornavirus. For this purpose, an analysis of the literature concerning the role of the Bornavirus in the pathology of animals and humans was conducted. It is well known that a large number of pathogens of animal infections (zoonoses, including viral, pose a potential threat to human health. Among these potential threats is the Borna disease virus belonging to the family of Bornaviridae, order Mononegavirales. This order includes representatives of deadly human diseases like rabies (family Rhabdoviridae, Ebola virus (family Filoviridae and Nipah virus (family Paramyxoviridae. Borna virus disease affects mainly mammals, but can infect birds and even reptiles (Aspid bornavirus. It is established that Bornaviruses have a wide range of natural hosts (horses, sheeps, cats, bats and various birds, including domestic animals, which poses a potential threat to human health. This is evidenced by numerous, although contradictory, research into the role of the Borna disease virus in human pathologies such as schizophrenia, depression, prolonged fatigue syndrome, multiple sclerosis and others. Analysis of the literature clearly

Individual differences and reasoning: a study on personality traits.

Science.gov (United States)

Bensi, Luca; Giusberti, Fiorella; Nori, Raffaella; Gambetti, Elisa

2010-08-01

Personality can play a crucial role in how people reason and decide. Identifying individual differences related to how we actively gather information and use evidence could lead to a better comprehension and predictability of human reasoning. Recent findings have shown that some personality traits are related to similar decision-making patterns showed by people with mental disorders. We performed research with the aim to investigate delusion-proneness, obsessive-like personality, anxiety (trait and state), and reasoning styles in individuals from the general population. We introduced personality trait and state anxiety scores in a regression model to explore specific associations with: (1) amount of data-gathered prior to making a decision; and (2) the use of confirmatory and disconfirmatory evidence. Results showed that all our independent variables were positively or negatively associated with the amount of data collected in order to make simple probabilistic decisions. Anxiety and obsessiveness were the only predictors of the weight attributed to evidence in favour or against a hypothesis. Findings were discussed in relation to theoretical assumptions, predictions, and clinical implications. Personality traits can predict peculiar ways to reason and decide that, in turn, could be involved to some extent in the formation and/or maintenance of psychological disorders.

Global burden of human brucellosis: a systematic review of disease frequency.

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Anna S Dean

Full Text Available BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY estimate for brucellosis. METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden. CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a

Systematic review of brucellosis in Kenya: disease frequency in humans and animals and risk factors for human infection.

Science.gov (United States)

Njeru, J; Wareth, G; Melzer, F; Henning, K; Pletz, M W; Heller, R; Neubauer, H

2016-08-22

Brucellosis is a debilitating zoonotic disease affecting humans and animals. A comprehensive, evidence-based assessment of literature and officially available data on animal and human brucellosis for Kenya are missing. The aim of the current review is to provide frequency estimates of brucellosis in humans, animals and risk factors for human infection, and help to understand the current situation in Kenya. A total of accessible 36 national and international publications on brucellosis from 1916 to 2016 were reviewed to estimate the frequency of brucellosis in humans and animals, and strength of associations between potential risk factors and seropositivity in humans in Kenya. The conducted studies revealed only few and fragmented evidence of the disease spatial and temporal distribution in an epidemiological context. Bacteriological evidence revealed the presence of Brucella (B.) abortus and B. melitensis in cattle and human patients, whilst B. suis was isolated from wild rodents only. Similar evidence for Brucella spp infection in small ruminants and other animal species is unavailable. The early and most recent serological studies revealed that animal brucellosis is widespread in all animal production systems. The animal infection pressure in these systems has remained strong due to mixing of large numbers of animals from different geographical regions, movement of livestock in search of pasture, communal sharing of grazing land, and the concentration of animals around water points. Human cases are more likely seen in groups occupationally or domestically exposed to livestock or practicing risky social-cultural activities such as consumption of raw blood and dairy products, and slaughtering of animals within the homesteads. Many brucellosis patients are misdiagnosed and probably mistreated due to lack of reliable laboratory diagnostic support resulting to adverse health outcomes of the patients and routine disease underreporting. We found no studies of disease

Quantitative trait loci for udder conformation and other udder traits in Finnish Ayrshire cattle

Directory of Open Access Journals (Sweden)

N.F. SCHULMAN

2008-12-01

Full Text Available Udder traits are important due to their correlation with clinical mastitis which causes major economic losses to the dairy farms. Chromosomal areas associated with udder conformation traits, milking speed and leakage could be used in breeding programs to improve both udder traits and mastitis resistance. Quantitative trait loci (QTL mapping for udder traits was carried out on bovine chromosomes (BTA 9, 11, 14, 18, 20, 23, and 29, where earlier studies have indicated QTL for mastitis. A granddaughter design with 12 Ayrshire sire families and 360 sons was used. The sires and sons were typed for 35 markers. The traits analysed were udder depth, fore udder attachment, central ligament, distance from udder to floor, body stature, fore teat length, udder balance, rear udder height, milking speed, and leakage. Associations between markers and traits were analysed with multiple marker regression. Five genome-wise significant QTL were detected: stature on BTA14 and 23, udder balance on BTA23, rear udder height on BTA11, and central ligament on BTA23. On BTA11 and 14 the suggested QTL positions for udder traits are at the same position as previously detected QTL for mastitis and somatic cell count.;

Using therapeutic cloning to fight human disease: a conundrum or reality?

Science.gov (United States)

Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

2006-07-01

The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

Analogs of human genetic skin disease in domesticated animals

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Justin Finch, MD

2017-09-01

The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.