Phenotype of normal spirometry in an aging population.

Science.gov (United States)

Vaz Fragoso, Carlos A; McAvay, Gail; Van Ness, Peter H; Casaburi, Richard; Jensen, Robert L; MacIntyre, Neil; Gill, Thomas M; Yaggi, H Klar; Concato, John

2015-10-01

In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the

Distance from Africa, not climate, explains within-population phenotypic diversity in humans

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Betti, Lia; Balloux, François; Amos, William; Hanihara, Tsunehiko; Manica, Andrea

2008-01-01

The relative importance of ancient demography and climate in determining worldwide patterns of human within-population phenotypic diversity is still open to debate. Several morphometric traits have been argued to be under selection by climatic factors, but it is unclear whether climate affects the global decline in morphological diversity with increasing geographical distance from sub-Saharan Africa. Using a large database of male and female skull measurements, we apply an explicit framework to quantify the relative role of climate and distance from Africa. We show that distance from sub-Saharan Africa is the sole determinant of human within-population phenotypic diversity, while climate plays no role. By selecting the most informative set of traits, it was possible to explain over half of the worldwide variation in phenotypic diversity. These results mirror those previously obtained for genetic markers and show that ‘bones and molecules’ are in perfect agreement for humans. PMID:19129123

Phenotypic variability of Rhodnius ecuadoriensis populations at the Ecuadorian central and southern Andean region.

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Villacís, Anita G; Grijalva, Mario J; Catalá, Silvia S

2010-11-01

Rhodnius ecuadoriensis is an important vector of Chagas disease in Ecuador. Whereas only sylvatic and peridomestic populations are common in Manabi province, this species occupies domestic, peridomestic, and sylvatic habitats in Loja province where high reinfestation of houses was observed. To explore the existence of phenetic changes linked to the domiciliation of the species, this study set out to analyze the wing and antennal phenotypes of R. ecuadoriensis in these two provinces where the vector presents different affinity for domestic habitats. The antennal phenotype and the wing size and shape distinguish the two geographical populations of R. ecuadoriensis. In Manabí, sylvatic and peridomestic specimens were very similar. In Loja, sylvatic and nonsylvatic (domestic and peridomestic) populations showed distinctive characteristics. Remarkable sexual dimorphism of wing and antenna, exclusive of domestic specimens, and high metric disparity in the wing shape of the domestic females point out the existence of a particular situation in this habitat. The results of this phenotypic analysis and previous evidence of behavioral differences support the hypothesis of disruptive selection acting upon R. ecuadoriensis populations.

A probabilistic model for cell population phenotyping using HCS data.

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Edouard Pauwels

Full Text Available High Content Screening (HCS platforms allow screening living cells under a wide range of experimental conditions and give access to a whole panel of cellular responses to a specific treatment. The outcome is a series of cell population images. Within these images, the heterogeneity of cellular response to the same treatment leads to a whole range of observed values for the recorded cellular features. Consequently, it is difficult to compare and interpret experiments. Moreover, the definition of phenotypic classes at a cell population level remains an open question, although this would ease experiments analyses. In the present work, we tackle these two questions. The input of the method is a series of cell population images for which segmentation and cellular phenotype classification has already been performed. We propose a probabilistic model to represent and later compare cell populations. The model is able to fully exploit the HCS-specific information: "dependence structure of population descriptors" and "within-population variability". The experiments we carried out illustrate how our model accounts for this specific information, as well as the fact that the model benefits from considering them. We underline that these features allow richer HCS data analysis than simpler methods based on single cellular feature values averaged over each well. We validate an HCS data analysis method based on control experiments. It accounts for HCS specificities that were not taken into account by previous methods but have a sound biological meaning. Biological validation of previously unknown outputs of the method constitutes a future line of work.

Emergence of cooperation in phenotypically heterogeneous populations: a replicator dynamics analysis

International Nuclear Information System (INIS)

Barreira da Silva Rocha, A; Escobedo, R; Laruelle, A

2015-01-01

The emergence of cooperation is analyzed in heterogeneous populations where two kinds of individuals exist according to their phenotypic appearance. Phenotype recognition is assumed for all individuals: individuals are able to identify the type of every other individual, but fail to recognize their own type. Individuals thus behave under partial information conditions. The interactions between individuals are described by the snowdrift game, where individuals can either cooperate or defect. The evolution of such populations is studied in the framework of evolutionary game theory by means of the replicator dynamics. Overlapping generations are considered, so the replicator equations are formulated in discrete-time form. The stability analysis of the dynamical system is carried out and a detailed description of the behavior of trajectories starting from the interior of the state-space is given. We find that the four monomorphic states are unstable and that a polymorphic state exists which is a global attractor for non-degenerate initial states of the population. The result for the discrete-time replicator coincides with the one of the continuous case. (paper)

Genotypic and phenotypic diversity in populations of plant-probiotic Pseudomonas spp. colonizing roots

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Picard, Christine; Bosco, Marco

2008-01-01

Several soil microorganisms colonizing roots are known to naturally promote the health of plants by controlling a range of plant pathogens, including bacteria, fungi, and nematodes. The use of theses antagonistic microorganisms, recently named plant-probiotics, to control plant-pathogenic fungi is receiving increasing attention, as they may represent a sustainable alternative to chemical pesticides. Many years of research on plant-probiotic microorganisms (PPM) have indicated that fluorescent pseudomonads producing antimicrobial compounds are largely involved in the suppression of the most widespread soilborne pathogens. Phenotype and genotype analysis of plant-probiotic fluorescent pseudomonads (PFP) have shown considerable genetic variation among these types of strains. Such variability plays an important role in the rhizosphere competence and the biocontrol ability of PFP strains. Understanding the mechanisms by which genotypic and phenotypic diversity occurs in natural populations of PFP could be exploited to choose those agricultural practices which best exploit the indigenous PFP populations, or to isolate new plant-probiotic strains for using them as inoculants. A number of different methods have been used to study diversity within PFP populations. Because different resolutions of the existing microbial diversity can be revealed depending on the approach used, this review first describes the most important methods used for the assessment of fluorescent Pseudomonas diversity. Then, we focus on recent data relating how differences in genotypic and phenotypic diversity within PFP communities can be attributed to geographic location, climate, soil type, soil management regime, and interactions with other soil microorganisms and host plants. It becomes evident that plant-related parameters exert the strongest influence on the genotypic and phenotypic variations in PFP populations.

Experimental evolution reveals differences between phenotypic and evolutionary responses to population density.

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McNamara, K B; Simmons, L W

2017-09-01

Group living can select for increased immunity, given the heightened risk of parasite transmission. Yet, it also may select for increased male reproductive investment, given the elevated risk of female multiple mating. Trade-offs between immunity and reproduction are well documented. Phenotypically, population density mediates both reproductive investment and immune function in the Indian meal moth, Plodia interpunctella. However, the evolutionary response of populations to these traits is unknown. We created two replicated populations of P. interpunctella, reared and mated for 14 generations under high or low population densities. These population densities cause plastic responses in immunity and reproduction: at higher numbers, both sexes invest more in one index of immunity [phenoloxidase (PO) activity] and males invest more in sperm. Interestingly, our data revealed divergence in PO and reproduction in a different direction to previously reported phenotypic responses. Males evolving at low population densities transferred more sperm, and both males and females displayed higher PO than individuals at high population densities. These positively correlated responses to selection suggest no apparent evolutionary trade-off between immunity and reproduction. We speculate that the reduced PO activity and sperm investment when evolving under high population density may be due to the reduced population fitness predicted under increased sexual conflict and/or to trade-offs between pre- and post-copulatory traits. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Linking individual phenotype to density-dependent population growth: the influence of body size on the population dynamics of malaria vectors

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Russell, Tanya L.; Lwetoijera, Dickson W.; Knols, Bart G. J.; Takken, Willem; Killeen, Gerry F.; Ferguson, Heather M.

2011-01-01

Understanding the endogenous factors that drive the population dynamics of malaria mosquitoes will facilitate more accurate predictions about vector control effectiveness and our ability to destabilize the growth of either low- or high-density insect populations. We assessed whether variation in phenotypic traits predict the dynamics of Anopheles gambiae sensu lato mosquitoes, the most important vectors of human malaria. Anopheles gambiae dynamics were monitored over a six-month period of seasonal growth and decline. The population exhibited density-dependent feedback, with the carrying capacity being modified by rainfall (97% wAICc support). The individual phenotypic expression of the maternal (p = 0.0001) and current (p = 0.040) body size positively influenced population growth. Our field-based evidence uniquely demonstrates that individual fitness can have population-level impacts and, furthermore, can mitigate the impact of exogenous drivers (e.g. rainfall) in species whose reproduction depends upon it. Once frontline interventions have suppressed mosquito densities, attempts to eliminate malaria with supplementary vector control tools may be attenuated by increased population growth and individual fitness. PMID:21389034

Application of the asthma phenotype algorithm from the Severe Asthma Research Program to an urban population.

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Paru Patrawalla

Full Text Available Identification and characterization of asthma phenotypes are challenging due to disease complexity and heterogeneity. The Severe Asthma Research Program (SARP used unsupervised cluster analysis to define 5 phenotypically distinct asthma clusters that they replicated using 3 variables in a simplified algorithm. We evaluated whether this simplified SARP algorithm could be used in a separate and diverse urban asthma population to recreate these 5 phenotypic clusters.The SARP simplified algorithm was applied to adults with asthma recruited to the New York University/Bellevue Asthma Registry (NYUBAR to classify patients into five groups. The clinical phenotypes were summarized and compared.Asthma subjects in NYUBAR (n = 471 were predominantly women (70% and Hispanic (57%, which were demographically different from the SARP population. The clinical phenotypes of the five groups generated by the simplified SARP algorithm were distinct across groups and distributed similarly to those described for the SARP population. Groups 1 and 2 (6 and 63%, respectively had predominantly childhood onset atopic asthma. Groups 4 and 5 (20% were older, with the longest duration of asthma, increased symptoms and exacerbations. Group 4 subjects were the most atopic and had the highest peripheral eosinophils. Group 3 (10% had the least atopy, but included older obese women with adult-onset asthma, and increased exacerbations.Application of the simplified SARP algorithm to the NYUBAR yielded groups that were phenotypically distinct and useful to characterize disease heterogeneity. Differences across NYUBAR groups support phenotypic variation and support the use of the simplified SARP algorithm for classification of asthma phenotypes in future prospective studies to investigate treatment and outcome differences between these distinct groups.Clinicaltrials.gov NCT00212537.

Phenotypic switching of populations of cells in a stochastic environment

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Hufton, Peter G.; Lin, Yen Ting; Galla, Tobias

2018-02-01

In biology phenotypic switching is a common bet-hedging strategy in the face of uncertain environmental conditions. Existing mathematical models often focus on periodically changing environments to determine the optimal phenotypic response. We focus on the case in which the environment switches randomly between discrete states. Starting from an individual-based model we derive stochastic differential equations to describe the dynamics, and obtain analytical expressions for the mean instantaneous growth rates based on the theory of piecewise-deterministic Markov processes. We show that optimal phenotypic responses are non-trivial for slow and intermediate environmental processes, and systematically compare the cases of periodic and random environments. The best response to random switching is more likely to be heterogeneity than in the case of deterministic periodic environments, net growth rates tend to be higher under stochastic environmental dynamics. The combined system of environment and population of cells can be interpreted as host-pathogen interaction, in which the host tries to choose environmental switching so as to minimise growth of the pathogen, and in which the pathogen employs a phenotypic switching optimised to increase its growth rate. We discuss the existence of Nash-like mutual best-response scenarios for such host-pathogen games.

Comparative Analyses of Phenotypic Trait Covariation within and among Populations.

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Peiman, Kathryn S; Robinson, Beren W

2017-10-01

Many morphological, behavioral, physiological, and life-history traits covary across the biological scales of individuals, populations, and species. However, the processes that cause traits to covary also change over these scales, challenging our ability to use patterns of trait covariance to infer process. Trait relationships are also widely assumed to have generic functional relationships with similar evolutionary potentials, and even though many different trait relationships are now identified, there is little appreciation that these may influence trait covariation and evolution in unique ways. We use a trait-performance-fitness framework to classify and organize trait relationships into three general classes, address which ones more likely generate trait covariation among individuals in a population, and review how selection shapes phenotypic covariation. We generate predictions about how trait covariance changes within and among populations as a result of trait relationships and in response to selection and consider how these can be tested with comparative data. Careful comparisons of covariation patterns can narrow the set of hypothesized processes that cause trait covariation when the form of the trait relationship and how it responds to selection yield clear predictions about patterns of trait covariation. We discuss the opportunities and limitations of comparative approaches to evaluate hypotheses about the evolutionary causes and consequences of trait covariation and highlight the importance of evaluating patterns within populations replicated in the same and in different selective environments. Explicit hypotheses about trait relationships are key to generating effective predictions about phenotype and its evolution using covariance data.

Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

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Yosef, Ido; Edgar, Rotem; Qimron, Udi

2016-11-01

Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population.

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Auger, Julie; Baptiste, Amandine; Benabbad, Imane; Thierry, Gaëlle; Costa, Jean-Marc; Amouyal, Mélanie; Kottler, Marie-Laure; Leheup, Bruno; Touraine, Renaud; Schmitt, Sébastien; Lebrun, Marine; Cormier Daire, Valérie; Bonnefont, Jean-Paul; de Roux, Nicolas; Elie, Caroline; Rosilio, Myriam

2016-01-01

The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions. © 2016 S. Karger AG, Basel.

Phenotypic plasticity despite source-sink population dynamics in a long-lived perennial plant.

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Anderson, Jill T; Sparks, Jed P; Geber, Monica A

2010-11-01

• Species that exhibit adaptive plasticity alter their phenotypes in response to environmental conditions, thereby maximizing fitness in heterogeneous landscapes. However, under demographic source-sink dynamics, selection should favor traits that enhance fitness in the source habitat at the expense of fitness in the marginal habitat. Consistent with source-sink dynamics, the perennial blueberry, Vaccinium elliottii (Ericaceae), shows substantially higher fitness and population sizes in dry upland forests than in flood-prone bottomland forests, and asymmetrical gene flow occurs from upland populations into bottomland populations. Here, we examined whether this species expresses plasticity to these distinct environments despite source-sink dynamics. • We assessed phenotypic responses to a complex environmental gradient in the field and to water stress in the glasshouse. • Contrary to expectations, V. elliottii exhibited a high degree of plasticity in foliar and root traits (specific leaf area, carbon isotope ratios, foliar nitrogen content, root : shoot ratio, root porosity and root architecture). • We propose that plasticity can be maintained in source-sink systems if it is favored within the source habitat and/or a phylogenetic artifact that is not costly. Additionally, plasticity could be advantageous if habitat-based differences in fitness result from incipient niche expansion. Our results illuminate the importance of evaluating phenotypic traits and fitness components across heterogeneous landscapes. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

Phylogeography and population dynamics of the white-sided dolphin (Lagenorhynchus acutus) in the North Atlantic

KAUST Repository

Banguera-Hinestroza, E.; Evans, P. G H; Mirimin, L.; Reid, R. J.; Mikkelsen, B.; Couperus, A. S.; Deaville, R.; Rogan, E.; Hoelzel, A. R.

2014-01-01

Highly mobile species in the marine environment may be expected to show little differentiation at the population level, but this is often not the case. Instead cryptic population structure is common, and effective conservation will require an understanding of how these patterns evolve. Here we present an assessment from both sides of the North Atlantic of differentiation among populations of a dolphin species that inhabits mainly pelagic waters, the Atlantic white-sided dolphin. We compare eleven putative populations in the western and eastern North Atlantic at mtDNA and microsatellite DNA loci and find reduced nucleotide diversity and signals for historical bottlenecks and post-bottleneck expansions in all regions. We calculate expansion times to have occurred during the early Holocene, following the last glacial maximum (LGM). We find evidence for connectivity among populations from either side of the North Atlantic, and differentiation between putative populations in the far northeast compared with all other areas sampled. Some data suggest the possibility of separate refugia during the LGM explaining this pattern, although ongoing ecological processes may also be a factor. We discuss the implications for developing effective programs of conservation and management in the context of ongoing anthropogenic impact. © 2014 Springer Science+Business Media Dordrecht.

Phylogeography and population dynamics of the white-sided dolphin (Lagenorhynchus acutus) in the North Atlantic

KAUST Repository

Banguera-Hinestroza, E.

2014-02-27

Highly mobile species in the marine environment may be expected to show little differentiation at the population level, but this is often not the case. Instead cryptic population structure is common, and effective conservation will require an understanding of how these patterns evolve. Here we present an assessment from both sides of the North Atlantic of differentiation among populations of a dolphin species that inhabits mainly pelagic waters, the Atlantic white-sided dolphin. We compare eleven putative populations in the western and eastern North Atlantic at mtDNA and microsatellite DNA loci and find reduced nucleotide diversity and signals for historical bottlenecks and post-bottleneck expansions in all regions. We calculate expansion times to have occurred during the early Holocene, following the last glacial maximum (LGM). We find evidence for connectivity among populations from either side of the North Atlantic, and differentiation between putative populations in the far northeast compared with all other areas sampled. Some data suggest the possibility of separate refugia during the LGM explaining this pattern, although ongoing ecological processes may also be a factor. We discuss the implications for developing effective programs of conservation and management in the context of ongoing anthropogenic impact. © 2014 Springer Science+Business Media Dordrecht.

Phenotypic and allelic distribution of the ABO and Rhesus (D) blood groups in the Cameroonian population.

Science.gov (United States)

Ndoula, S T; Noubiap, J J N; Nansseu, J R N; Wonkam, A

2014-06-01

Data on blood group phenotypes are important for blood transfusion programs, for disease association and population genetics studies. This study aimed at reporting the phenotypic and allelic distribution of ABO and Rhesus (Rh) groups in various ethnolinguistic groups in the Cameroonians. We obtained ABO and Rhesus blood groups and self-identified ethnicity from 14,546 Cameroonian students. Ethnicity was classified in seven major ethnolinguistic groups: Afro-Asiatic, Nilo-Saharan, Niger-Kordofanian/West Atlantic, Niger-Kordofanian/Adamawa-Ubangui, Niger-Kordofanian/Benue-Congo/Bantu/Grassfield, Niger-Kordofanian/Benue-Congo/Bantu/Mbam and Niger-Kordofanian/Benue-Congo/Bantu/Equatorial. ABO allelic frequencies were determined using the Bernstein method. Differences in phenotypic distribution of blood groups were assessed using the chi-square test; a P value blood groups O, A, B and AB were 48.62%, 25.07%, 21.86% and 4.45%, respectively. Rhesus-positive was 96.32%. The allelic frequencies of O, A and B genes were 0.6978, 0.1605 and 0.1416, respectively. Phenotypic frequencies of the blood groups in the general study population and in the different ethnolinguistic groups were in agreement with Hardy-Weinberg equilibrium expectations (P > 0.05). The frequencies of O, A, and B blood phenotypes were significantly lower, respectively, in the Nilo-Saharan group (P = 0.009), the Niger-Kordofanian/Benue-Congo/Bantu groups (P = 0.021) and the Niger-Kordofanian/West-Atlantic group. AB blood group was most frequent in the Niger-Kordofanian/Adamawa-Ubangui group (P = 0.024). Our study provides the first data on ethnic distribution of ABO and Rhesus blood groups in the Cameroonian population and suggests that its general profile is similar to those of several sub-Saharan African populations. We found some significant differences in phenotypic distribution amongst major ethnolinguistic groups. These data may be important for blood donor recruitment policy and blood transfusion

Concomitant targeting of multiple key transcription factors effectively disrupts cancer stem cells enriched in side population of human pancreatic cancer cells.

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Xiyan Wang

Full Text Available A major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs.To identify side population (SP cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.Flow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.CSCs were enriched in the side proportion (SP cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.The findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a

Habitat Fragmentation Differentially Affects Genetic Variation, Phenotypic Plasticity and Survival in Populations of a Gypsum Endemic

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Silvia Matesanz

2017-05-01

Full Text Available Habitat fragmentation, i.e., fragment size and isolation, can differentially alter patterns of neutral and quantitative genetic variation, fitness and phenotypic plasticity of plant populations, but their effects have rarely been tested simultaneously. We assessed the combined effects of size and connectivity on these aspects of genetic and phenotypic variation in populations of Centaurea hyssopifolia, a narrow endemic gypsophile that previously showed performance differences associated with fragmentation. We grew 111 maternal families sampled from 10 populations that differed in their fragment size and connectivity in a common garden, and characterized quantitative genetic variation, phenotypic plasticity to drought for key functional traits, and plant survival, as a measure of population fitness. We also assessed neutral genetic variation within and among populations using eight microsatellite markers. Although C. hyssopifolia is a narrow endemic gypsophile, we found substantial neutral genetic variation and quantitative variation for key functional traits. The partition of genetic variance indicated that a higher proportion of variation was found within populations, which is also consistent with low population differentiation in molecular markers, functional traits and their plasticity. This, combined with the generally small effect of habitat fragmentation suggests that gene flow among populations is not restricted, despite large differences in fragment size and isolation. Importantly, population’s similarities in genetic variation and plasticity did not reflect the lower survival observed in isolated populations. Overall, our results indicate that, although the species consists of genetically variable populations able to express functional plasticity, such aspects of adaptive potential may not always reflect populations’ survival. Given the differential effects of habitat connectivity on functional traits, genetic variation and fitness

Induction of mutagenized tomato populations for investigation on agronomic traits and mutant phenotyping

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Rafiul Amin Laskar

2018-01-01

Full Text Available Global demand for tomato production increased tremendously due to its diverse utility in raw, cooked and processed form of food. This necessitates the continued supply of highly nutritious and better yielding improved cultivars to the producers, considering the rapid changing agro-climatic condition. In this study, induced mutant tomato populations of widely recommended tomato genotype Arka Vikas (Sel-22 were generated using chemical mutagen ethyl methane sulfonate (EMS, hydrazine hydrates (HZ and their combined treatments. In the in vitro study, a gradual reduction in germination percentage and seedling height occurred with the increasing concentrations of mutagens. Combination of EMS and HZ caused maximum biological inhibition followed by EMS and HZ treatments alone in M1 generation. The rate of survival and fertility in M1 plants of tomato was found highly affected due to mutagenic treatment, in which sensitivity toward combined treatment was found highest followed by EMS and HZ. Inspection on induced phenotypic variations in individual plants of M2 population resulted in identification and isolation of wide range of mutants with altered phenotypes. Highest mutation frequency was resulted by combined mutagens followed by the EMS and HZ treatment. Agronomic trait analyses showed intra and inter treatment variations in three quantitative traits (Plant height, fertile branch per plant and fruits per plant of M2 mutagenized population. Assessment on rate of mutant recovery in M2 population showed highest mutant recovery is possible with combination treatments and then 0.02% HZ followed by 0.02% EMS. In the present study, phenotyping of the mutants revealed that vegetative organs (‘plant size’, ‘plant habit’ and ‘leaf morphology’ was the most sensitive category (69.33% to which most of the mutant belongs, followed by ‘fruit color and size’ (20.27% and ‘germination’ (9.79%. Comparative investigation on number of mutants and

Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

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Wong, Mark K L; Woodman, James D; Rowell, David M

2017-07-01

Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

Wolbachia wSinvictaA infections in natural populations of the fire ant Solenopsis invicta: testing for phenotypic effects.

Science.gov (United States)

Bouwma, Andrew M; Shoemaker, Dewayne

2011-01-01

Wolbachia are intracellular bacteria that commonly infect many arthropods and some nematodes. In arthropods, these maternally transmitted bacteria often induce a variety of phenotypic effects to enhance their own spread within host populations. Wolbachia phenotypic effects generally either provide benefits to infected host females (cytoplasmic incompatibility, positive fitness effects) or bias host sex ratio in favor of females (male-killing, parthenogenesis, feminization), all of which increase the relative production of infected females in host populations. Wolbachia surveys have found infections to be exceedingly common in ants, but little is known at this juncture as to what phenotypic effects, if any, they induce in this group. Previous studies have demonstrated that individuals from native populations of the invasive fire ant Solenopsis invicta commonly harbor one or more of three Wolbachia variants. One of the variants, wSinvictaA, typically occurs at low prevalence in S. invicta populations, appears to have been transmitted horizontally into S. invicta three or more times, and has been lost repeatedly from host lineages over time. In order to determine the phenotypic effects and likely population dynamics of wSinvictaA infections in these ants, brood production patterns of newly mated fire ant queens were studied during simulated claustral founding and measured wSinvictaA transmission fidelity within mature single-queen families. No clear evidence was found for Wolbachia-induced cytoplasmic incompatibility, significant fitness effects, or male-killing. Maternal transmission was perfect to both virgin queens and males. Possible mechanisms for how this variant could be maintained in host populations are discussed.

Differential factors associated with challenge-proven food allergy phenotypes in a population cohort of infants: a latent class analysis.

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Peters, R L; Allen, K J; Dharmage, S C; Lodge, C J; Koplin, J J; Ponsonby, A-L; Wake, M; Lowe, A J; Tang, M L K; Matheson, M C; Gurrin, L C

2015-05-01

Food allergy, eczema and wheeze are early manifestations of allergic disease and commonly co-occur in infancy although their interrelationship is not well understood. Data from population studies are essential to determine whether there are differential drivers of multi-allergy phenotypes. We aimed to define phenotypes and risk factors of allergic disease using latent class analysis (LCA). The HealthNuts study is a prospective, population-based cohort of 5276 12-month-old infants in Melbourne, Australia. LCA was performed using the following baseline data collected at age 12 months: food sensitization (skin prick test ≥ 2 mm) and allergy (oral food challenge) to egg, peanut and sesame; early (food-sensitized eczema (16%), single egg allergy (9%), multiple food allergies (predominantly peanut) (3%) and multiple food allergies (predominantly egg) (2%). Compared to the baseline group of no allergic disease, shared risk factors for all allergic phenotypes were parents born overseas (particularly Asia), delayed introduction of egg, male gender (except for single egg allergy) and family history of allergic disease, whilst exposure to pet dogs was protective for all phenotypes. Other factors including filaggrin mutations, vitamin D and the presence of older siblings differed by phenotype. Multiple outcomes in infancy can be used to determine five distinct allergy phenotypes at the population level, which have both shared and separate risk factors suggesting differential mechanisms of disease. © 2014 John Wiley & Sons Ltd.

Population FBA predicts metabolic phenotypes in yeast.

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Piyush Labhsetwar

2017-09-01

Full Text Available Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism, Population flux balance analysis (Population FBA successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined medium. We extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media. We find the partitioning of flux between fermentation and respiration predicted by our model agrees with recent 13C fluxomics experiments, and that our model largely recovers the Crabtree effect (the experimentally known bias among certain yeast species toward fermentation with the production of ethanol even in the presence of oxygen, while FBA without proteomics constraints predicts respirative metabolism almost exclusively. The comparisons to the 13C study showed improvement upon inclusion of the correlations and motivated a technique to systematically identify inconsistent kinetic parameters in the literature. The minor secretion fluxes for glycerol and acetate are underestimated by our method, which indicate a need for further refinements to the metabolic model. For yeast cells grown in synthetic defined (SD medium, the calculated broad distribution of growth rates matches experimental observations from single cell studies, and we characterize several metabolic phenotypes within our modeled populations that make use of diverse pathways. Fast growing yeast cells are predicted to perform significant amount of respiration, use serine-glycine cycle and produce ethanol in mitochondria as opposed to slow growing cells. We use a genetic algorithm to determine the proteomics constraints necessary to reproduce the growth rate distributions seen experimentally. We find that a core set of 51 constraints are essential but

Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations.

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Paul Moran

Full Text Available Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

Use of genetic data to infer population-specific ecological and phenotypic traits from mixed aggregations

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Moran, Paul; Bromaghin, Jeffrey F.; Masuda, Michele

2014-01-01

Many applications in ecological genetics involve sampling individuals from a mixture of multiple biological populations and subsequently associating those individuals with the populations from which they arose. Analytical methods that assign individuals to their putative population of origin have utility in both basic and applied research, providing information about population-specific life history and habitat use, ecotoxins, pathogen and parasite loads, and many other non-genetic ecological, or phenotypic traits. Although the question is initially directed at the origin of individuals, in most cases the ultimate desire is to investigate the distribution of some trait among populations. Current practice is to assign individuals to a population of origin and study properties of the trait among individuals within population strata as if they constituted independent samples. It seemed that approach might bias population-specific trait inference. In this study we made trait inferences directly through modeling, bypassing individual assignment. We extended a Bayesian model for population mixture analysis to incorporate parameters for the phenotypic trait and compared its performance to that of individual assignment with a minimum probability threshold for assignment. The Bayesian mixture model outperformed individual assignment under some trait inference conditions. However, by discarding individuals whose origins are most uncertain, the individual assignment method provided a less complex analytical technique whose performance may be adequate for some common trait inference problems. Our results provide specific guidance for method selection under various genetic relationships among populations with different trait distributions.

Genotype-phenotype correlation of xeroderma pigmentosum in a Chinese Han population.

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Sun, Z; Zhang, J; Guo, Y; Ni, C; Liang, J; Cheng, R; Li, M; Yao, Z

2015-04-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to sunlight, freckle-like pigmentation and a greatly increased incidence of skin cancers. Genetic mutation detection and genotype-phenotype analysis of XP are rarely reported in the Chinese Han population. To investigate the mutational spectrum of XP in a Chinese Han population, to discover any genotype-phenotype correlation and, consequently, to propose a simple and effective tool for the molecular diagnosis of XP. This study was carried out on 12 unrelated Chinese families that included 13 patients with clinically suspected XP. Genomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron-exon boundaries for the entire coding region of eight XP genes. In 12 patients, direct sequencing of the whole coding region of eight XP genes revealed pathogenic mutations, including seven compound heterozygous mutations, three homozygous mutations and a Japanese founder mutation. Thirteen mutations have not been previously identified. This cohort was composed of four patients with XP-C (XPC), two with XP-G (ERCC5), three with XP-A (XPA) and three with XP-V (POLH). This study identified 13 novel mutations and extended the mutation spectrum of XP in the Chinese Han population. In this cohort, we found that patients with XP-G have no neurological symptoms, and patients with XP-A and XP-V have a high incidence of malignancy. Furthermore, lack of stringent protection against sunlight, late diagnosis and long duration of disease play an important role. © 2014 British Association of Dermatologists.

Changes related to gender, geographic population and habitat in the antennal phenotype of Triatoma patagonica Del Ponte, 1929 (Hemiptera: Reduviidae).

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Rodríguez, Claudia S; Crocco, Liliana; Altamirano, Alejandra; Catalá, Silvia

2013-02-01

Triatomines undergo morphological changes as an adaptive response to different habitats (wild, peridomestic, domestic, laboratory). The characterization of the antennal phenotype provides information on intraspecific variation caused by geographical origin and/or habitat. Triatoma patagonica Del Ponte, 1929 is known to occur in peridomiciles of rural areas in Argentina, where it also invades non-colonized dwellings. Here we describe and compare the antennal phenotype of T. patagonica in populations of different geographic origin, and explore possible modifications induced by laboratory rearing with the aim of investigating the range of phenotypic variation of the species for the first time. Sixty antennas of adult males and females of T. patagonica belonging to two peridomiciliary populations of different geographical origin were analyzed. Four types of sensilla were observed in three antennal segments, showing sexual dimorphism in the species. The multivariate analysis separated the populations of similar habitat (peridomicile) but different geographical origin, without showing differences between the peridomiciliary and laboratory populations of the same geographical origin. These results suggest phenotypic plasticity in T. patagonica, which would allow the species to adapt to a wide range of habitats without having a close association with a given host and its environment. The range of antennal phenotypic variation of T. patagonica would also be an indicator of its current stage of adaptation to the human environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Perfluorocarbons and Gilbert syndrome (phenotype) in the C8 Health Study Population

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Fan, Hongmin [Cancer Center, School of Public Health, West Virginia University, Morgantown, WV 265050-9190 (United States); Department of Epidemiology and Statistics, School of Public Health, Hebei United University, Hebei 063000 (China); Ducatman, Alan [Department of Occupational and Environmental Health, School of Public Health, West Virginia University (United States); Department of Medicine, School of Medicine, West Virginia University (United States); Clinical Translational Science Institute, West Virginia University (United States); Zhang, Jianjun [Department of Biostatistics, School Public Health, West Virginia University (United States)

2014-11-15

Background: Gilbert syndrome (GS) is an inherited defect of bilirubin conjugation, most commonly caused by a gene mutation for the enzyme UGT1A. GS is known to affect the metabolism and excretion of drugs and xenobiotics. Perfluorocarbon compounds (PFCs) are bio-persistent environmental contaminants that affect metabolic regulation. In this study, we examined the associations of GS phenotype and serum PFCs in the C8 Health Study Population. Materials and methods: Using 2005–2006 data from a large PFC-exposure population survey, we compared serum PFCs concentrations between GS and non GS clinical phenotypes, in a cross sectional design, adjusting for standard risk factors, including age, BMI, smoking status, socioeconomic status and gender. Results: Among 10 PFC compounds considered, only perfluorohexanoic acid (PFHxA) was seen at a significantly higher concentration in GS men and women. Conclusion: PFHxA exposure may be associated with GS. Our findings do not support increased exposure in GS for other PFCs. - Highlights: • Most serum PFCs are not associated with clinically evident Gilbert syndrome. • However, serum perfluorohexanoic acid is positively associated. • The investigation addresses the clinical presentation, not the genetic mutation.

Genetic and phenotypic variability of iris color in Buenos Aires population

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Diana María Hohl

Full Text Available Abstract The aim of this work was to describe the phenotypic and genotypic variability related to iris color for the population of Buenos Aires province (Argentina, and to assess the usefulness of current methods of analysis for this country. We studied five Single Nucleotide Polymorphisms (SNPs included in the IrisPlex kit, in 118 individuals, and we quantified eye color with Digital Iris Analysis Tool. The markers fit Hardy-Weinberg equilibrium for the whole sample, but not for rs12913832 within the group of brown eyes (LR=8.429; p=0.004. We found a remarkable association of HERC2 rs12913832 GG with blue color (p < 0.01 but the other markers did not show any association with iris color. The results for the Buenos Aires population differ from those of other populations of the world for these polymorphisms (p < 0,01. The differences we found might respond to the admixed ethnic composition of Argentina; therefore, methods of analysis used in European populations should be carefully applied when studying the population of Argentina. These findings reaffirm the importance of this investigation in the Argentinian population for people identification based on iris color.

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

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Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Sex differences in correlates of intermediate phenotypes and prevalent cardiovascular disease in the general population

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Renate B. Schnabel

2015-04-01

Full Text Available Background-There are marked sex differences in cardiovascular disease [CVD] manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences.Methods and Results-In 5000 individuals of the population-based Gutenberg Health Study, mean age 55±11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD (coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease [LEAD] N=561.We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes towards less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses age, systolic blood pressure and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R² 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. Conclusions-In a population-based cohort we observed sex differences in risk factors and a broad range of intermediate phenotypes of noninvasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.

Phenotypic selection in natural populations: what limits directional selection?

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Kingsolver, Joel G; Diamond, Sarah E

2011-03-01

Studies of phenotypic selection document directional selection in many natural populations. What factors reduce total directional selection and the cumulative evolutionary responses to selection? We combine two data sets for phenotypic selection, representing more than 4,600 distinct estimates of selection from 143 studies, to evaluate the potential roles of fitness trade-offs, indirect (correlated) selection, temporally varying selection, and stabilizing selection for reducing net directional selection and cumulative responses to selection. We detected little evidence that trade-offs among different fitness components reduced total directional selection in most study systems. Comparisons of selection gradients and selection differentials suggest that correlated selection frequently reduced total selection on size but not on other types of traits. The direction of selection on a trait often changes over time in many temporally replicated studies, but these fluctuations have limited impact in reducing cumulative directional selection in most study systems. Analyses of quadratic selection gradients indicated stabilizing selection on body size in at least some studies but provided little evidence that stabilizing selection is more common than disruptive selection for most traits or study systems. Our analyses provide little evidence that fitness trade-offs, correlated selection, or stabilizing selection strongly constrains the directional selection reported for most quantitative traits.

DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics.

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Giri, Anil K; Bharadwaj, Soham; Banerjee, Priyanka; Chakraborty, Shraddha; Parekatt, Vaisak; Rajashekar, Donaka; Tomar, Abhishek; Ravindran, Aarthi; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

2017-06-01

Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.

Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress.

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Fernández, Jesús; Toro, Miguel Á; Sonesson, Anna K; Villanueva, Beatriz

2014-01-01

The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in the initial founders. Traditionally, base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and, therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during 10 generations of phenotypic selection applied in the subsequent breeding program.

Phenotypic selection varies with pollination intensity across populations of Sabatia angularis.

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Emel, Sarah L; Franks, Steven J; Spigler, Rachel B

2017-07-01

Pollinators are considered primary selective agents acting on plant traits, and thus variation in the strength of the plant-pollinator interaction might drive variation in the opportunity for selection and selection intensity across plant populations. Here, we examine whether these critical evolutionary parameters covary with pollination intensity across wild populations of the biennial Sabatia angularis. We quantified pollination intensity in each of nine S. angularis populations as mean stigmatic pollen load per population. For female fitness and three components, fruit number, fruit set (proportion of flowers setting fruit) and number of seeds per fruit, we evaluated whether the opportunity for selection varied with pollination intensity. We used phenotypic selection analyses to test for interactions between pollination intensity and selection gradients for five floral traits, including flowering phenology. The opportunity for selection via fruit set and seeds per fruit declined significantly with increasing pollen receipt, as expected. We demonstrated significant directional selection on multiple traits across populations. We also found that selection intensity for all traits depended on pollination intensity. Consistent with general theory about the relationship between biotic interaction strength and the intensity of selection, our study suggests that variation in pollination intensity drives variation in selection across S. angularis populations. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Cigarette smoking in male patients with chronic schizophrenia in a Chinese population: prevalence and relationship to clinical phenotypes.

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Xiang Yang Zhang

Full Text Available The high prevalence of smoking in schizophrenia of European background may be related to smoking's reducing clinical symptoms and medication side effects. Because smoking prevalence and its associations with clinical phenotypes are less well characterized in Chinese than European patients with schizophrenia, we assessed these smoking behaviors using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND in 776 Chinese male schizophrenia and 560 control subjects. Patients also were rated on the Positive and Negative Symptom Scale (PANSS, the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES, and the Abnormal Involuntary Movement Scale (AIMS. We found that the schizophrenia patients had a higher lifetime incidence of smoking (79% vs 63%, were more likely to be heavy smokers (61% vs 31%, and had lower smoking cessation rates (4% vs 9% (all p0.05 than the non-smoking patients. These results suggest that Chinese males with schizophrenia smoke more frequently than the general population. Further, smokers with schizophrenia may display fewer negative symptoms and possibly less parkinsonism than non-smokers with schizophrenia.

Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population.

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Guilherme Suarez-Kurtz

Full Text Available The influence of self-reported "race/color", geographical origin and genetic ancestry on the distribution of three functional CYP3A5 polymorphisms, their imputed haplotypes and inferred phenotypes was examined in 909 healthy, adult Brazilians, self-identified as White, Brown or Black ("race/color" categories of the Brazilian census. The cohort was genotyped for CYP3A5*3 (rs776746, CYP3A5*6 (rs10264272 and CYP3A5*7 (rs41303343, CYP3A5 haplotypes were imputed and CYP3A5 metabolizer phenotypes were inferred according to the number of defective CYP3A5 alleles. Estimates of the individual proportions of Amerindian, African and European ancestry were available for the entire cohort. Multinomial log-linear regression models were applied to infer the statistical association between the distribution of CYP3A5 alleles, haplotypes and phenotypes (response variables, and self-reported Color, geographical region and ancestry (explanatory variables. We found that Color per se or in combination with geographical region associates significantly with the distribution of CYP3A5 variant alleles and CYP3A5 metabolizer phenotypes, whereas geographical region per se influences the frequency distribution of CYP3A5 variant alleles. The odds of having the default CYP3A5*3 allele and the poor metabolizer phenotype increases continuously with the increase of European ancestry and decrease of African ancestry. The opposite trend is observed in relation to CYP3A5*6, CYP3A5*7, the default CYP3A5*1 allele, and both the extensive and intermediate phenotypes. No significant effect of Amerindian ancestry on the distribution of CYP3A5 alleles or phenotypes was observed. In conclusion, this study strongly supports the notion that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies, and dealt with as a continuous variable, rather than proportioned in arbitrary categories that do not capture the

Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

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Wang, Lei; Liang, Rui; Zhou, Ting; Zheng, Jing; Liang, Bing Miao; Zhang, Hong Ping; Luo, Feng Ming; Gibson, Peter G; Wang, Gang

2017-10-01

Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Population structure and genotype-phenotype associations in a collection of oat landraces and historic cultivars

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Louisa Rosemarie Winkler

2016-07-01

Full Text Available Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L. remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent; with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae resistance, days to anthesis and growth habit (winter/spring. In addition, two novel loci were

Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

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Douglas J Conrad

Full Text Available Cystic Fibrosis (CF is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1 a low lung health scores phenotype, 2 a younger, well-nourished, male-dominated class, 3 various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.

Using species distribution model to estimate the wintering population size of the endangered scaly-sided merganser in China.

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Qing Zeng

Full Text Available Scaly-sided Merganser is a globally endangered species restricted to eastern Asia. Estimating its population is difficult and considerable gap exists between populations at its breeding grounds and wintering sites. In this study, we built a species distribution model (SDM using Maxent with presence-only data to predict the potential wintering habitat for Scaly-sided Merganser in China. Area under the receiver operating characteristic curve (AUC method suggests high predictive power of the model (training and testing AUC were 0.97 and 0.96 respectively. The most significant environmental variables included annual mean temperature, mean temperature of coldest quarter, minimum temperature of coldest month and precipitation of driest quarter. Suitable conditions for Scaly-sided Merganser are predicted in the middle and lower reaches of the Yangtze River, especially in Jiangxi, Hunan and Hubei Provinces. The predicted suitable habitat embraces 6,984 km of river. Based on survey results from three consecutive winters (2010-2012 and previous studies, we estimated that the entire wintering population of Scaly-sided Merganser in China to be 3,561 ± 478 individuals, which is consistent with estimate in its breeding ground.

Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal Populations.

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UnJin Lee

Full Text Available There has been increasing awareness in the wider biological community of the role of clonal phenotypic heterogeneity in playing key roles in phenomena such as cellular bet-hedging and decision making, as in the case of the phage-λ lysis/lysogeny and B. Subtilis competence/vegetative pathways. Here, we report on the effect of stochasticity in growth rate, cellular memory/intermittency, and its relation to phenotypic heterogeneity. We first present a linear stochastic differential model with finite auto-correlation time, where a randomly fluctuating growth rate with a negative average is shown to result in exponential growth for sufficiently large fluctuations in growth rate. We then present a non-linear stochastic self-regulation model where the loss of coherent self-regulation and an increase in noise can induce a shift from bounded to unbounded growth. An important consequence of these models is that while the average change in phenotype may not differ for various parameter sets, the variance of the resulting distributions may considerably change. This demonstrates the necessity of understanding the influence of variance and heterogeneity within seemingly identical clonal populations, while providing a mechanism for varying functional consequences of such heterogeneity. Our results highlight the importance of a paradigm shift from a deterministic to a probabilistic view of clonality in understanding selection as an optimization problem on noise-driven processes, resulting in a wide range of biological implications, from robustness to environmental stress to the development of drug resistance.

Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

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Melo, Thaise P; Takada, Luciana; Baldi, Fernando; Oliveira, Henrique N; Dias, Marina M; Neves, Haroldo H R; Schenkel, Flavio S; Albuquerque, Lucia G; Carvalheiro, Roberto

2016-06-21

QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

Phenotypic variability in a population of globe artichoke

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Angélica Reolon da Costa

2014-11-01

Full Text Available The existence of variability is a prerequisite for genetic improvement in plants. Globe artichoke is a high nutritious vegetable with medical value, representing a profitable alternative for rural producers. This research was conducted with the aim of evaluating the phenotypic variability in a commercial cultivar of artichoke (Cynara cardunculus var. scolymus L established from seeds. Field plants were assessed when primary head reached commercial stage. An amount of 21 quantitative and 5 multicategoric characters were assessed. The quantitative data were submitted to multivariate analysis. For quantitative characters the distance between individuals varied from 3.0 to 50.9, revealing high intrapopulation variability. The greater relative contribution characters for genetic divergence were the primary head fresh mass (79.88% and bottom fresh mass (8.43%. This indicates the possibility of plant selection for head quality in this population. The clustering analysis through UPGMA method, based on quantitative characters, allowed the formation of five groups. For multicategoric traits, the similarity among individuals varied from 1.22% to 100%. Within the existing population variability, it was possible to select plants with superior quantitative traits desirable for in natura consumption, as primary head fresh weight and length, bottom fresh mass, bract basis length and width, as well as non-quantitative traits as round head shape, absence of thorn and presence of violet color in the head.

Bypassing Evolutionary Roadblocks: Phenotypic Diversity in Isogenic Population Bridges Tradeoff in Evolution of a New Function

Science.gov (United States)

Petrie, K. L.; Meyer, J. R.

2017-07-01

A novel mechanism of innovation bridges fitness valleys by violating the one gene-one phenotype dogma. Protein products of a single gene partition into populations, some of which carry out a new function and some the old, avoiding tradeoffs.

Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

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Kazuyo Yasuda

Full Text Available Cancer stem-like cells (CSCs/cancer-initiaiting cells (CICs are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br cells from ovarian cancer cells. Both SP cells and ALDH(Br cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2, than those of main population (MP cells and ALDH(Low cells, respectively. We analyzed an SP and ALDH(Br overlapping population (SP/ALDH(Br, and the SP/ALDH(Br population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br cells, enabling initiation of tumor with as few as 10(2 cells. Furthermore, SP/ADLH(Br population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low, MP/ALDH(Br and MP/ALDH(Low cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

The effects of stabilizing and directional selection on phenotypic and genotypic variation in a population of RNA enzymes.

Science.gov (United States)

Hayden, Eric J; Bratulic, Sinisa; Koenig, Iwo; Ferrada, Evandro; Wagner, Andreas

2014-02-01

The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.

The Hawk-Dove game in phenotypically homogeneous and heterogeneous populations of finite dimension

Science.gov (United States)

Laruelle, Annick; da Silva Rocha, André Barreira; Escobedo, Ramón

2018-02-01

The Hawk-Dove game played between individuals in populations of finite dimension is analyzed by means of a stochastic model. We take into account both cases when all individuals in the population are either phenotypically homogeneous or heterogeneous. A strategy in the model is a gene representing the probability of playing the Hawk strategy. Individual interactions at the microscopic level are described by a genetic algorithm where evolution results from the interplay among selection, mutation, drift and cross-over of genes. We show that the behavioral patterns observed at the macroscopic level can be reproduced as the emergent result of individual interactions governed by the rules of the Hawk-Dove game at the microscopic level. We study how the results of the genetic algorithm compare with those obtained in evolutionary game theory, finding that, although genes continuously change both their presence and frequency in the population over time, the population average behavior always achieves stationarity and, when this happens, the final average strategy played in the population oscillates around the evolutionarily stable strategy in the homogeneous population case or the neutrally stable set in the heterogeneous population case.

Brain nuclei in actively courting red-sided garter snakes: a paradigm of neural trimorphism.

Science.gov (United States)

Krohmer, Randolph W; DeMarchi, Geno A; Baleckaitis, Daniel D; Lutterschmidt, Deborah I; Mason, Robert T

2011-03-28

During the breeding season, two distinct male phenotypes are exhibited by red-sided garter snakes (Thamnophis sirtalis parietalis), with courtship behavior being directed not only toward females, but also toward a sub-population of males called she-males. She-males are morphologically identical to other males except for a circulating androgen level three times that of normal males and their ability to produce a female-like pheromone. As in other vertebrates, limbic nuclei in the red-sided garter snake brain are involved in the control of sexual behaviors. For example, an intact anterior hypothalamus pre-optic area (AHPOA) is essential for the initiation and maintenance of reproduction. To determine if brain morphology varies among the three behavioral phenotypes (i.e., males, she-males, and females) during the breeding season, we examined the volume, cell size and cell density of the AHPOA as well as a control region, the external nucleus of the optic tract (ENOT). We used Luxol Fast Blue and Ziehl's Fuchsin to visualize neurons and glial cells, respectively. No significant differences were observed among the three behavioral phenotypes in the volume, cell size or density in the control region. In contrast, the volume, cell size and density of the AHPOA of she-males were significantly greater than those of both male and female snakes. While the volume of the AHPOA was significantly greater in females compared to males, no differences were observed in cell size or density. These differences in brain morphology suggest a possible underlying mechanism for phenotypic-specific behavioral patterns. Copyright © 2010 Elsevier Inc. All rights reserved.

Heterogeneity of functional properties of Clone 66 murine breast cancer cells expressing various stem cell phenotypes.

Science.gov (United States)

Mukhopadhyay, Partha; Farrell, Tracy; Sharma, Gayatri; McGuire, Timothy R; O'Kane, Barbara; Sharp, J Graham

2013-01-01

Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous. Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis. The proportion of cells expressing CD44(high)CD24(low/neg), side population (SP) cells, ALDH1(+), CD49f(high), CD133(high), and CD34(high) differed, suggesting heterogeneity. Differences in frequency and size of tumor spheres from these populations were observed. Higher rates of proliferation of non-SP, ALDH1(+), CD34(low), and CD49f(high) suggested properties of transit amplifying cells. Colony formation was higher from ALDH1(-) and non-SP cells than ALDH1(+) and SP cells suggesting a progenitor phenotype. The frequency of clonal colonies that grew in agar varied and was differentially altered by the presence of Matrigel™. In vivo, fewer cells with a stem cell phenotype were needed for tumor formation than "non-stem" cells. Fewer SP cells were needed to form tumors than ALDH1(+) cells suggesting further heterogeneities of cells with stem phenotypes. Different levels of cytokines/chemokines were produced by Clone 66 with RANTES being the highest. Whether the heterogeneity reflects soluble factor production remains to be determined. These data demonstrate that Clone 66 murine breast cancer cells that express stem cell phenotypes are heterogeneous and exhibit different functional properties, and this may also be the case for human breast cancer stem cells.

Dynamics of sexual populations structured by a space variable and a phenotypical trait

KAUST Repository

Mirrahimi, Sepideh

2013-03-01

We study sexual populations structured by a phenotypic trait and a space variable, in a non-homogeneous environment. Departing from an infinitesimal model, we perform an asymptotic limit to derive the system introduced in Kirkpatrick and Barton (1997). We then perform a further simplification to obtain a simple model. Thanks to this simpler equation, we can describe rigorously the dynamics of the population. In particular, we provide an explicit estimate of the invasion speed, or extinction speed of the species. Numerical computations show that this simple model provides a good approximation of the original infinitesimal model, and in particular describes quite well the evolution of the species\\' range. © 2013 Elsevier Inc.

Dynamics of sexual populations structured by a space variable and a phenotypical trait

KAUST Repository

Mirrahimi, Sepideh; Raoul, Gaë l

2013-01-01

We study sexual populations structured by a phenotypic trait and a space variable, in a non-homogeneous environment. Departing from an infinitesimal model, we perform an asymptotic limit to derive the system introduced in Kirkpatrick and Barton (1997). We then perform a further simplification to obtain a simple model. Thanks to this simpler equation, we can describe rigorously the dynamics of the population. In particular, we provide an explicit estimate of the invasion speed, or extinction speed of the species. Numerical computations show that this simple model provides a good approximation of the original infinitesimal model, and in particular describes quite well the evolution of the species' range. © 2013 Elsevier Inc.

Genetic variation in variability: phenotypic variability of fledging weight and its evolution in a songbird population

NARCIS (Netherlands)

Mulder, H.A.; Gienapp, P; Visser, ME

2016-01-01

Variation in traits is essential for natural selection to operate and genetic and environmental effects can contribute to this phenotypic variation. From domesticated populations, we know that families can differ in their level of within-family variance, which leads to the intriguing situation that

Comparing the predictive abilities of phenotypic and marker-assisted selection methods in a biparental lettuce population

Science.gov (United States)

Breeding and selection for the traits with polygenic inheritance is a challenging task that can be done by phenotypic selection, by marker-assisted selection or by genome wide selection. We tested predictive ability of four selection models in a biparental population genotyped with 95 SNP markers an...

Evolution of molecular phenotypes under stabilizing selection

International Nuclear Information System (INIS)

Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

2013-01-01

Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

Landscape patterns of phenotypic variation and population structuring in a selfing grass, Elymus glaucus (blue wildrye).

Science.gov (United States)

Vicky J. Erickson; Nancy L. Mandel; Frank C. Sorensen

2004-01-01

Source-related phenotypic variance was investigated in a common garden study of populations of Elymus glaucus Buckley (blue wildrye) from the Blue Mountain Ecological Province of northeastern Oregon and adjoining Washington. The primary objective of this study was to assess geographic patterns of potentially adaptive differentiation in this self-...

Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR Variants in a Thai Population.

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Rebekah van Bruggen

Full Text Available Pyruvate kinase (PKLR is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41 is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

Quantitative gene expression profiling of CD45+ and CD45- skeletal muscle-derived side population cells

DEFF Research Database (Denmark)

Ditte Caroline Andersen, Ditte Caroline; Kristiansen, Gitte Qvist; Jensen, Line

2012-01-01

The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we desc...... a satellite cell subpopulation) remain in the mSPCD45(-) fraction, and we show that these cells express high levels of many of the known myogenic precursor/stem cell related markers, including Pax7 and Myf5.......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...... describe the isolation of adult mouse normal skeletal muscle residing SPCD45(+) and SPCD45(-) cells from a parent mononuclear muscle-derived cell (MDC) population. Relative quantitative real time PCR (RT-PCR) of 64 genes revealed that mSPCD45(-) compared with mSPCD45(+) was enriched for cells expressing...

A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.

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Jeanette Prinz

2016-09-01

Full Text Available The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.

Drug target identification using side-effect similarity

DEFF Research Database (Denmark)

Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude

2008-01-01

Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

Population structure and strong divergent selection shape phenotypic diversification in maize landraces.

Science.gov (United States)

Pressoir, G; Berthaud, J

2004-02-01

To conserve the long-term selection potential of maize, it is necessary to investigate past and present evolutionary processes that have shaped quantitative trait variation. Understanding the dynamics of quantitative trait evolution is crucial to future crop breeding. We characterized population differentiation of maize landraces from the State of Oaxaca, Mexico for quantitative traits and molecular markers. Qst values were much higher than Fst values obtained for molecular markers. While low values of Fst (0.011 within-village and 0.003 among-villages) suggest that considerable gene flow occurred among the studied populations, high levels of population differentiation for quantitative traits were observed (ie an among-village Qst value of 0.535 for kernel weight). Our results suggest that although quantitative traits appear to be under strong divergent selection, a considerable amount of gene flow occurs among populations. Furthermore, we characterized nonproportional changes in the G matrix structure both within and among villages that are consequences of farmer selection. As a consequence of these differences in the G matrix structure, the response to multivariate selection will be different from one population to another. Large changes in the G matrix structure could indicate that farmers select for genes of major and pleiotropic effect. Farmers' decision and selection strategies have a great impact on phenotypic diversification in maize landraces.

The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin

DEFF Research Database (Denmark)

Wassermann, Tina; Meinike Jørgensen, Karin; Ivanyshyn, Karolina

2016-01-01

Ciprofloxacin is a widely used antibiotic, in the class of quinolones, for treatment of Pseudomonas aeruginosa infections. The immediate response of P. aeruginosa to subinhibitory concentrations of ciprofloxacin has been investigated previously. However, the long-term phenotypic adaptation, which...... populations compared to unexposed populations. Three replicate populations of P. aeruginosa PAO1 and its hypermutable mutant ΔmutS were cultured aerobically for approximately 940 generations by daily passages in LB medium with and without subinhibitory concentration of ciprofloxacin and aliquots...

Genetic divergence in nuclear genomes between populations of Fagus crenata along the Japan Sea and Pacific sides of Japan.

Science.gov (United States)

Hiraoka, Koichi; Tomaru, Nobuhiro

2009-05-01

Genetic diversity and structure in Fagus crenata were studied by analyzing 14 nuclear microsatellite loci in 23 populations distributed throughout the species' range. Although population differentiation was very low (F (ST) = 0.027; R (ST) = 0.041), both neighbor-joining tree and Bayesian clustering analyses provided clear evidence of genetic divergence between populations along the Japan Sea (Japan Sea lineage) and Pacific (Pacific lineage) sides of Japan, indicating that physical barriers to migration and gene flow, notably the mountain ranges separating the populations along the Japan Sea and Pacific sides, have promoted genetic divergence between these populations. The two lineages of the nuclear genome are generally consistent with those of the chloroplast genome detected in a previous study, with several discrepancies between the two genomes. Within-population genetic diversity was generally very high (average H (E) = 0.839), but decreased in a clinal fashion from southwest to northeast, largely among populations of the Japan Sea lineage. This geographical gradient may have resulted from the late-glacial and postglacial recolonization to the northeast, which led to a loss of within-population genetic diversity due to cumulative founder effects.

Phenotypic evaluation of the resistance in F1 carnation populations to vascular wilt caused by Fusarium oxysporum f.sp. dianthi

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Johana Carolina Soto-Sedano

2012-08-01

Full Text Available One of the most important phytosanitary problems of the carnation crops in Colombia and in the entire world is vascular wilting produced by Fusarium oxysporum f.sp. dianthi. Currently, an effective treatment against the pathogen does not exist; the search for resistant varieties has been the most successful method for control of this disease. Breeding programs are vital to solving the problem of the carnation fusariosis. The objective of this research was the phenotypic evaluation of carnation F1 populations, products of contrasting crossing, resistant per susceptible to F. oxysporum f.sp. dianthi, in order to determine if the resistance is inherited in the lines. This information will contribute to the selection of material and to the successful introduction of the resistant characteristic, whose expression is commercially acceptable, to the gene pool. The methodology adopted was a phenotypic evaluation of the response to the parasite in the population (450 individuals and in the parental. This evaluation estimated the area under the curve (AU DPC, using a scale of symptoms reported for carnation vascular wilt. Three different phenotypes were established with this evaluation. The moderately susceptible one is the predominant phenotype and an analysis of phenotypic frequencies was carried out on it. The results show that the individuals of the evaluated F1 population were distributed between two extreme ranges, resistant and susceptible; this shows that there is segregation for the trait resistant to F. oxysporum f.sp dianthi. We did not observe clearly differentiated classes, i.e. with complete absence or presence of the disease, indicating a possible control of the resistance in the evaluated carnation material, governed by more than one gene and with a possible additive genetic action

What role does heritability play in transgenerational phenotypic responses to captivity? Implications for managing captive populations.

Science.gov (United States)

Courtney Jones, Stephanie K; Byrne, Phillip G

2017-12-01

Animals maintained in captivity exhibit rapid changes in phenotypic traits, which may be maladaptive for natural environments. The phenotype can shift away from the wild phenotype via transgenerational effects, with the environment experienced by parents influencing the phenotype and fitness of offspring. There is emerging evidence that controlling transgenerational effects could help mitigate the effects of captivity, improving the success of captively bred animals post release. However, controlling transgenerational effects requires knowledge of the mechanisms driving transgenerational changes. To better understand the genetic mechanisms that contribute to transgenerational effects in captivity we investigated the heritability of behavioral phenotypes using mid parent- and single parent-offspring regressions in a population of captive-reared house mouse (Mus musculus) that we had previously shown exhibit transgenerational changes in boldness and activity behavioral types. Slopes for boldness and activity were all positive, indicating a low to moderate degree of heritability. Though, none of the heritability estimates were statistically significant due to the large surrounding errors. However, the large error surrounding the heritability estimates may also indicate that there is variability in heritability between behavioral traits within the boldness and activity behavioral types. The implication of this finding is that the potential for heritable genetic changes in captivity varies considerably between traits. We conclude that continued investigation of the potential for traits to evolve in captivity is needed to better inform captive breeding and reintroduction programs. © 2017 Wiley Periodicals, Inc.

Phenotypic plasticity and local adaptation in leaf ecophysiological traits of 13 contrasting cork oak populations under different water availabilities.

Science.gov (United States)

Ramírez-Valiente, Jose Alberto; Sánchez-Gómez, David; Aranda, Ismael; Valladares, Fernando

2010-05-01

Plants distributed across a wide range of environmental conditions are submitted to differential selective pressures. Long-term selection can lead to the development of adaptations to the local environment, generating ecotypic differentiation. Additionally, plant species can cope with this environmental variability by phenotypic plasticity. In this study, we examine the importance of both processes in coping with environmental heterogeneity in the Mediterranean sclerophyllous cork oak Quercus suber. For this purpose, we measured growth and key functional traits at the leaf level in 9-year-old plants across 2 years of contrasting precipitation (2005 and 2006) in a common garden. Plants were grown from acorns originated from 13 populations spanning a wide range of climates along the distribution range of the species. The traits measured were: leaf size (LS), specific leaf area (SLA), carbon isotope discrimination (Delta(13)C) and leaf nitrogen content per unit mass (N(mass)). Inter-population differences in LS, SLA and Delta(13)C were found. These differences were associated with rainfall and temperature at the sites of origin, suggesting local adaptation in response to diverging climates. Additionally, SLA and LS exhibited positive responses to the increase in annual rainfall. Year effect explained 28% of the total phenotypic variance in LS and 2.7% in SLA. There was a significant genotype x environment interaction for shoot growth and a phenotypic correlation between the difference in shoot growth among years and the annual mean temperature at origin. This suggests that populations originating from warm sites can benefit more from wet conditions than populations from cool sites. Finally, we investigated the relationships between functional traits and aboveground growth by several regression models. Our results showed that plants with lower SLA presented larger aboveground growth in a dry year and plants with larger leaf sizes displayed larger growth rates in both

Functional heterogeneity of side population cells in skeletal muscle

International Nuclear Information System (INIS)

Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro; Ikemoto, Madoka; Masuda, Satoru; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

2006-01-01

Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31 - CD45 - SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31 - CD45 - SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31 - CD45 - SP cells participate in muscle regeneration

Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

Science.gov (United States)

de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

2017-03-01

An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

Cigarette smoke promotes drug resistance and expansion of cancer stem cell-like side population.

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Yi An

Full Text Available It is well known that many patients continue to smoke cigarettes after being diagnosed with cancer. Although smoking cessation has typically been presumed to possess little therapeutic value for cancer, a growing body of evidence suggests that continued smoking is associated with reduced efficacy of treatment and a higher incidence of recurrence. We therefore investigated the effect of cigarette smoke condensate (CSC on drug resistance in the lung cancer and head and neck cancer cell lines A549 and UMSCC-10B, respectively. Our results showed that CSC significantly increased the cellular efflux of doxorubicin and mitoxantrone. This was accompanied by membrane localization and increased expression of the multi-drug transporter ABCG2. The induced efflux of doxorubicin was reversed upon addition of the specific ABCG2 inhibitor Fumitremorgin C, confirming the role of ABCG2. Treatment with CSC increased the concentration of phosphorylated Akt, while addition of the PI3K inhibitor LY294002 blocked doxorubicin extrusion, suggesting that Akt activation is required for CSC-induced drug efflux. In addition, CSC was found to promote resistance to doxorubicin as determined by MTS assays. This CSC-induced doxurbicin-resistance was mitigated by mecamylamine, a nicotinic acetylcholine receptor inhibitor, suggesting that nicotine is at least partially responsible for the effect of CSC. Lastly, CSC increased the size of the side population (SP, which has been linked to a cancer stem cell-like phenotype. In summary, CSC promotes chemoresistance via Akt-mediated regulation of ABCG2 activity, and may also increase the proportion of cancer stem-like cells, contributing to tumor resilience. These findings underscore the importance of smoking cessation following a diagnosis of cancer, and elucidate the mechanisms of continued smoking that may be detrimental to treatment.

Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

OpenAIRE

Walsh Tom; Rayan Amal; Sa'ed Judeh; Shahin Hashem; Shepshelovich Jeanne; Lee Ming K; Hirschberg Koret; Tekin Mustafa; Salhab Wa'el; Avraham Karen B; King Mary-Claire; Kanaan Moien

2006-01-01

Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 fa...

Phenotypic covariance at species' borders.

Science.gov (United States)

Caley, M Julian; Cripps, Edward; Game, Edward T

2013-05-28

Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species' borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species' borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future.

Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.

Science.gov (United States)

Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

2010-01-01

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.

Prevalence and clinical characteristics of metabolically healthy obese individuals and other obese/non-obese metabolic phenotypes in a working population: results from the Icaria study

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Albert Goday

2016-04-01

Full Text Available Abstract Background Metabolically healthy obese (MHO phenotype may present with distinct characteristics compared with those with a metabolically unhealthy obese phenotype. Epidemiologic data on the distribution of these conditions in the working population are lacking. We aimed to evaluate the prevalence and clinical characteristics of MHO and other obese/non-obese metabolic phenotypes in a working population. Methods Cross-sectional analysis of all subjects who had undergone a medical examination with Ibermutuamur Prevention Society from May 2004 to December 2007. Participants were classified into 5 categories according to their body mass index (BMI; within each of these categories, participants were further classified as metabolically healthy (MH or metabolically unhealthy (MUH according to the modified NCEP-ATPIII criteria. A logistic regression analysis was performed to evaluate some clinically relevant factors associated with a MH status. Results In the overall population, the prevalence of the MHO phenotype was 8.6 %. The proportions of MH individuals in the overweight and obese categories were: 87.1 % (overweight and 55.5 % (obese I-III [58.8, 40.0, and 38.7 % of the obese I, II, and III categories, respectively]. When the overweight and obese categories were considered, compared with individuals who were MUH, those who were MH tended to be younger and more likely to be female or participate in physical exercise; they were also less likely to smoke, or to be a heavy drinker. In the underweight and normal weight categories, compared with individuals who were MH, those who were MUH were more likely to be older, male, manual (blue collar workers, smokers and heavy drinkers. Among participants in the MUH, normal weight group, the proportion of individuals with a sedentary lifestyle was higher relative to those in the MH, normal weight group. The factors more strongly associated with the MUH phenotype were BMI and age, followed by the

Phenotypic selection on flowering phenology and pollination efficiency traits between Primula populations with different pollinator assemblages

OpenAIRE

Wu, Yun; Li, Qing‐Jun

2017-01-01

Abstract Floral traits have largely been attributed to phenotypic selection in plant–pollinator interactions. However, the strength of this link has rarely been ascertained with real pollinators. We conducted pollinator observations and estimated selection through female fitness on flowering phenology and floral traits between two Primula secundiflora populations. We quantified pollinator‐mediated selection by subtracting estimates of selection gradients of plants receiving supplemental hand ...

Adaptive evolution of molecular phenotypes

International Nuclear Information System (INIS)

Held, Torsten; Nourmohammad, Armita; Lässig, Michael

2014-01-01

Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak. (paper)

Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts

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Wang, Qi; Clarkson, Christina; Graham, Melanie; Donahue, Robert; Hering, Bernhard J.; Verfaillie, Catherine M.; Bansal-Pakala, Pratima; O'Brien, Timothy D.

2015-01-01

Background Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4+ and CD8+ lymphocyte populations have not been reported. Methods We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. Results and Conclusions Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable. PMID:24825538

The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk Prospective Population Study

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Arsenault, Benoit J.; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J.; Kastelein, John J.P.; Khaw, Kay-Tee; Boekholdt, S. Matthijs

2010-01-01

Background Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. Methods A total of 21 787 participants aged 45–79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. Results Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02–2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20–4.62) compared with women who did not have the phenotype. Interpretation Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease. PMID:20643837

Systematic identification of proteins that elicit drug side effects

DEFF Research Database (Denmark)

Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica

2013-01-01

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins...... that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause......) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations....

Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples.

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Lundström, Sebastian; Reichenberg, Abraham; Anckarsäter, Henrik; Lichtenstein, Paul; Gillberg, Christopher

2015-04-28

To compare the annual prevalence of the autism symptom phenotype and of registered diagnoses for autism spectrum disorder during a 10 year period in children. Population based study. Child and Adolescent Twin Study and national patient register, Sweden. 19, 993 twins (190 with autism spectrum disorder) and all children (n=1,078,975; 4620 with autism spectrum disorder) born in Sweden over a 10 year period from 1993 to 2002. Annual prevalence of the autism symptom phenotype (that is, symptoms on which the diagnostic criteria are based) assessed by a validated parental telephone interview (the Autism-Tics, ADHD and other Comorbidities inventory), and annual prevalence of reported diagnoses of autism spectrum disorder in the national patient register. The annual prevalence of the autism symptom phenotype was stable during the 10 year period (P=0.87 for linear time trend). In contrast, there was a monotonic significant increase in prevalence of registered diagnoses of autism spectrum disorder in the national patient register (Pautism symptom phenotype has remained stable in children in Sweden while the official prevalence for registered, clinically diagnosed, autism spectrum disorder has increased substantially. This suggests that administrative changes, affecting the registered prevalence, rather than secular factors affecting the pathogenesis, are important for the increase in reported prevalence of autism spectrum disorder. © Lundström et al 2015.

Identification and characterisation of side population cells in the canine pituitary gland.

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van Rijn, Sarah J; Gremeaux, Lies; Riemers, Frank M; Brinkhof, Bas; Vankelecom, Hugo; Penning, Louis C; Meij, Björn P

2012-06-01

To date, stem/progenitor cells have not been identified in the canine pituitary gland. Cells that efficiently exclude the vital dye Hoechst 33342 can be visualised and identified using fluorescence activated cell sorting (FACS) as a 'side population' (SP), distinct from the main population (MP). Such SPs have been identified in several tissues and display stem/progenitor cell characteristics. In this study, a small SP (1.3%, n=6) was detected in the anterior pituitary glands of healthy dogs. Quantitative PCR indicated significantly higher expression of CD34 and Thy1 in this SP, but no differences in the expression of CD133, Bmi-1, Axin2 or Shh. Pro-opiomelanocortin (POMC) and Lhx3 expression were significantly higher in the MP than in the SP, but no differences in the expression of Tpit, GH or PRL were found. The study demonstrated the existence of an SP of cells in the normal canine pituitary gland, encompassing cells with stem cell characteristics and without POMC expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Invasion strategies in clonal aquatic plants: are phenotypic differences caused by phenotypic plasticity or local adaptation?

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Riis, Tenna; Lambertini, Carla; Olesen, Birgit; Clayton, John S.; Brix, Hans; Sorrell, Brian K.

2010-01-01

Background and Aims The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important. Here the primary adaptive strategy in three non-native, clonally reproducing macrophytes (Egeria densa, Elodea canadensis and Lagarosiphon major) in New Zealand freshwaters were examined and an attempt was made to link observed differences in plant morphology to local variation in habitat conditions. Methods Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity of these same populations was also quantified. Key Results For all three species, greater variation in plant characteristics was found before they were grown in standardized conditions. Moreover, field populations displayed remarkably little genetic variation and there was little interaction between habitat conditions and plant morphological characteristics. Conclusions The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis and L. major, but no other relationships between plant characteristics and habitat conditions were apparent. This implies that within-species differences in plant size can be explained

Advanced phenotyping and phenotype data analysis for the plant growth and development study

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Md. Matiur eRahaman

2015-08-01

Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

Success and failure in replication of genotype-phenotype associations: How does replication help in understanding the genetic basis of phenotypic variation in outbred populations?

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Schielzeth, Holger; Rios Villamil, Alejandro; Burri, Reto

2018-03-25

Recent developments in sequencing technologies have facilitated genomewide mapping of phenotypic variation in natural populations. Such mapping efforts face a number of challenges potentially leading to low reproducibility. However, reproducible research forms the basis of scientific progress. We here discuss the options for replication and the reasons for potential nonreproducibility. We then review the evidence for reproducible quantitative trait loci (QTL) with a focus on natural animal populations. Existing case studies of replication fall into three categories: (i) traits that have been mapped to major effect loci (including chromosomal inversion and supergenes) by independent research teams; (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate QTL across multiple populations. Major effect loci, in particular those associated with inversions, have been successfully replicated in several cases within and across populations. Beyond such major effect variants, replication has been more successful within than across populations, suggesting that QTL discovered in natural populations may often be population-specific. This suggests that biological causes (differences in linkage patterns, allele frequencies or context-dependencies of QTL) contribute to nonreproducibility. Evidence from other fields, notably animal breeding and QTL mapping in humans, suggests that a significant fraction of QTL is indeed reproducible in direction and magnitude at least within populations. However, there is also a large number of QTL that cannot be easily reproduced. We put forward that more studies should explicitly address the causes and context-dependencies of QTL signals, in particular to disentangle linkage differences, allele frequency differences and gene-by-environment interactions as biological causes of nonreproducibility of QTL, especially between populations. © 2018 John Wiley & Sons Ltd.

Natural variation of model mutant phenotypes in Ciona intestinalis.

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Paolo Sordino

Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

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Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

2008-01-01

Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

Evolution and ecology meet molecular genetics: adaptive phenotypic plasticity in two isolated Negev desert populations of Acacia raddiana at either end of a rainfall gradient

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Ward, David; Shrestha, Madan K.; Golan-Goldhirsh, Avi

2012-01-01

Background and Aims The ecological, evolutionary and genetic bases of population differentiation in a variable environment are often related to the selection pressures that plants experience. We compared differences in several growth- and defence-related traits in two isolated populations of Acacia raddiana trees from sites at either end of an extreme environmental gradient in the Negev desert. Methods We used random amplified polymorphic DNA (RAPD) to determine the molecular differences between populations. We grew plants under two levels of water, three levels of nutrients and three levels of herbivory to test for phenotypic plasticity and adaptive phenotypic plasticity. Key Results The RAPD analyses showed that these populations are highly genetically differentiated. Phenotypic plasticity in various morphological traits in A. raddiana was related to patterns of population genetic differentiation between the two study sites. Although we did not test for maternal effects in these long-lived trees, significant genotype × environment (G × E) interactions in some of these traits indicated that such plasticity may be adaptive. Conclusions The main selection pressure in this desert environment, perhaps unsurprisingly, is water. Increased water availability resulted in greater growth in the southern population, which normally receives far less rain than the northern population. Even under the conditions that we defined as low water and/or nutrients, the performance of the seedlings from the southern population was significantly better, perhaps reflecting selection for these traits. Consistent with previous studies of this genus, there was no evidence of trade-offs between physical and chemical defences and plant growth parameters in this study. Rather, there appeared to be positive correlations between plant size and defence parameters. The great variation in several traits in both populations may result in a diverse potential for responding to selection pressures in

Studying the Genetics of Complex Disease With Ancestry-Specific Human Phenotype Networks: The Case of Type 2 Diabetes in East Asian Populations.

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Qiu, Jingya; Moore, Jason H; Darabos, Christian

2016-05-01

Genome-wide association studies (GWAS) have led to the discovery of over 200 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes mellitus (T2DM). Additionally, East Asians develop T2DM at a higher rate, younger age, and lower body mass index than their European ancestry counterparts. The reason behind this occurrence remains elusive. With comprehensive searches through the National Human Genome Research Institute (NHGRI) GWAS catalog literature, we compiled a database of 2,800 ancestry-specific SNPs associated with T2DM and 70 other related traits. Manual data extraction was necessary because the GWAS catalog reports statistics such as odds ratio and P-value, but does not consistently include ancestry information. Currently, many statistics are derived by combining initial and replication samples from study populations of mixed ancestry. Analysis of all-inclusive data can be misleading, as not all SNPs are transferable across diverse populations. We used ancestry data to construct ancestry-specific human phenotype networks (HPN) centered on T2DM. Quantitative and visual analysis of network models reveal the genetic disparities between ancestry groups. Of the 27 phenotypes in the East Asian HPN, six phenotypes were unique to the network, revealing the underlying ancestry-specific nature of some SNPs associated with T2DM. We studied the relationship between T2DM and five phenotypes unique to the East Asian HPN to generate new interaction hypotheses in a clinical context. The genetic differences found in our ancestry-specific HPNs suggest different pathways are involved in the pathogenesis of T2DM among different populations. Our study underlines the importance of ancestry in the development of T2DM and its implications in pharmocogenetics and personalized medicine. © 2016 The Authors. *Genetic Epidemiology Published by Wiley Periodicals, Inc.

Recommendations for using standardised phenotypes in genetic association studies

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Naylor Melissa G

2009-07-01

Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

A comparative study on genetic and environmental influences on metabolic phenotypes in Eastern (Chinese) and Western (Danish) populations

DEFF Research Database (Denmark)

Li, Shuxia

2015-01-01

the risk of clinic diseases e.g. diabetes, atherosclerosis, stroke and cardiovascular disease. Metabolic phenotypes, similar to most complex traits, can be influenced by both genetic and environmental factors as well as their interplay. Many family and twin studies have demonstrated both genetic...... and environmental factors play important role in the variation of metabolic phenotypes and intra-individual change over time. Although both genetic and environmental factors are involved the development of metabolic disorders, the role of environment should be emphasized as the expression or function of gene can...... be regulated to adapt to existing environmental circumstance. In other words, adaptive evolution in populations under distinct environmental and cultural circumstances could have resulted in varying genetic basis of metabolic factors and development of metabolic disorders or diseases. Thus, it can...

Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey.

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Li, Jiang; Xiao, Cheng; Yang, Hui; Zhou, Yun; Wang, Rui; Cao, Yongtong

2017-12-09

Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.

The Impact of Marine Protected Areas on Reef-Wide Population Structure and Fishing-Induced Phenotypes in Coral-Reef Fishes

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Fidler, Robert Young, III

Overfishing and destructive fishing practices threaten the sustainability of fisheries worldwide. In addition to reducing population sizes, anthropogenic fishing effort is highly size-selective, preferentially removing the largest individuals from harvested stocks. Intensive, size-selective mortality induces widespread phenotypic shifts toward the predominance of smaller and earlier-maturing individuals. Fish that reach sexual maturity at smaller size and younger age produce fewer, smaller, and less viable larvae, severely reducing the reproductive capacity of exploited populations. These directional phenotypic alterations, collectively known as "fisheries-induced evolution" (FIE) are among the primary causes of the loss of harvestable fish biomass. Marine protected areas (MPAs) are one of the most widely utilized components of fisheries management programs around the world, and have been proposed as a potential mechanism by which the impacts of FIE may be mitigated. The ability of MPAs to buffer exploited populations against fishing pressure, however, remains debated due to inconsistent results across studies. Additionally, empirical evidence of phenotypic shifts in fishes within MPAs is lacking. This investigation addresses both of these issues by: (1) using a categorical meta-analysis of MPAs to standardize and quantify the magnitude of MPA impacts across studies; and (2) conducting a direct comparison of life-history phenotypes known to be influenced by FIE in six reef-fish species inside and outside of MPAs. The Philippines was used as a model system for analyses due to the country's significance in global marine biodiversity and reliance on MPAs as a fishery management tool. The quantitative impact of Philippine MPAs was assessed using a "reef-wide" meta-analysis. This analysis used pooled visual census data from 39 matched pairs of MPAs and fished reefs surveyed twice over a mean period of 3 years. In 17 of these MPAs, two additional surveys were conducted

Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

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Walsh Tom

2006-01-01

Full Text Available Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 families enrolled, hearing loss in 17 families (11 per cent was due to mutations in GJB2 (connexin 26, a smaller fraction of GJB2-associated deafness than in other populations. In order to estimate how many different genes might be responsible for hearing loss in this population, we evaluated ten families for linkage to all 36 known human autosomal deafness-related genes, fully sequencing hearing-related genes at any linked sites in informative relatives. Four families harboured four novel alleles of TMPRSS3 (988ΔA = 352stop, otoancorin (1067A >T = D356V and pendrin (716T > A = V239D and 1001G > T = 346stop. In each family, all affected individuals were homozygous for the critical mutation. Each allele was specific to one or a few families in the cohort; none were widespread. Since epidemiological tests of association of mutations with deafness were not feasible for such rare alleles, we used functional and bioinformatics approaches to evaluate their consequences. In six other families, hearing loss was not linked to any known gene, suggesting that these families harbour novel genes responsible for this phenotype. We conclude that inherited hearing loss is highly heterogeneous in this population, with most extended families acting as genetic isolates in this context. We also conclude that the same genes are responsible for hearing loss in this population as elsewhere, so that gene discovery in these families informs the genetics of hearing loss worldwide.

Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.

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Anupama Yadav

Full Text Available The ability of a genotype to show diverse phenotypes in different environments is called phenotypic plasticity. Phenotypic plasticity helps populations to evade extinctions in novel environments, facilitates adaptation and fuels evolution. However, most studies focus on understanding the genetic basis of phenotypic regulation in specific environments. As a result, while it's evolutionary relevance is well established, genetic mechanisms regulating phenotypic plasticity and their overlap with the environment specific regulators is not well understood. Saccharomyces cerevisiae is highly sensitive to the environment, which acts as not just external stimulus but also as signalling cue for this unicellular, sessile organism. We used a previously published dataset of a biparental yeast population grown in 34 diverse environments and mapped genetic loci regulating variation in phenotypic plasticity, plasticity QTL, and compared them with environment-specific QTL. Plasticity QTL is one whose one allele exhibits high plasticity whereas the other shows a relatively canalised behaviour. We mapped phenotypic plasticity using two parameters-environmental variance, an environmental order-independent parameter and reaction norm (slope, an environmental order-dependent parameter. Our results show a partial overlap between pleiotropic QTL and plasticity QTL such that while some plasticity QTL are also pleiotropic, others have a significant effect on phenotypic plasticity without being significant in any environment independently. Furthermore, while some plasticity QTL are revealed only in specific environmental orders, we identify large effect plasticity QTL, which are order-independent such that whatever the order of the environments, one allele is always plastic and the other is canalised. Finally, we show that the environments can be divided into two categories based on the phenotypic diversity of the population within them and the two categories have

Quantitative gene expression profiling of CD45(+) and CD45(-) skeletal muscle-derived side population cells

DEFF Research Database (Denmark)

Andersen, Ditte Caroline; Kristiansen, Gitte Qvistgaard; Jensen, Line

2011-01-01

transcripts associated with endothelial cells, Notch signaling and myogenic precursors. By comparing the mRNA signatures of mSPs with those of adipose tissue-derived SP populations, a common endothelial component seemed to reside in both muscle and fat-derived SPCD45(-) entities. However, each SP subset......The skeletal muscle-derived side population (mSP) which highly excludes Hoechst 33342 is composed of CD45(+) and CD45(-) subpopulations; yet, rareness of mSP cells in general has complicated extensive quantitative analysis of gene expression profiles in primarily isolated mSP cells. Here, we...... describe the isolation of adult mouse normal skeletal muscle residing SPCD45(+) and SPCD45(-) cells from a parent mononuclear muscle-derived cell (MDC) population. Relative quantitative real time PCR (RT-PCR) of 64 genes revealed that mSPCD45(-) compared with mSPCD45(+) was enriched for cells expressing...

Invasion strategies in clonal aquatic plants: Are phenotypic differences caused by phenotypic plasticity or local adaptation?

DEFF Research Database (Denmark)

Riis, Tenna; Lambertini, Carla; Olesen, Birgit

2010-01-01

conditions and plant morphological characteristics. Conclusions: The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between......Background and Aims: The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important....... Methods: Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity...

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain.

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Domingo, Laia; Salas, Dolores; Zubizarreta, Raquel; Baré, Marisa; Sarriugarte, Garbiñe; Barata, Teresa; Ibáñez, Josefa; Blanch, Jordi; Puig-Vives, Montserrat; Fernández, Ana; Castells, Xavier; Sala, Maria

2014-01-10

Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; cancers, extreme breast density being strongly associated with occult tumors (OR�

Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

International Nuclear Information System (INIS)

Lushaj, Entela B.; Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi

2012-01-01

We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

How accurate is the phenotype? – An analysis of developmental noise in a cotton aphid clone

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Babbitt Gregory A

2008-02-01

Full Text Available Abstract Background The accuracy by which phenotype can be reproduced by genotype potentially is important in determining the stability, environmental sensitivity, and evolvability of morphology and other phenotypic traits. Because two sides of an individual represent independent development of the phenotype under identical genetic and environmental conditions, average body asymmetry (or "fluctuating asymmetry" can estimate the developmental instability of the population. The component of developmental instability not explained by intrapopulational differences in gene or environment (or their interaction can be further defined as internal developmental noise. Surprisingly, developmental noise remains largely unexplored despite its potential influence on our interpretations of developmental stability, canalization, and evolvability. Proponents of fluctuating asymmetry as a bioindicator of environmental or genetic stress, often make the assumption that developmental noise is minimal and, therefore, that phenotype can respond sensitively to the environment. However, biologists still have not measured whether developmental noise actually comprises a significant fraction of the overall environmental response of fluctuating asymmetry observed within a population. Results In a morphometric study designed to partition developmental noise from fluctuating asymmetry in the wing morphology of a monoclonal culture of cotton aphid, Aphis gossipyii, it was discovered that fluctuating asymmetry in the aphid wing was nearly four times higher than in other insect species. Also, developmental noise comprised a surprisingly large fraction (≈ 50% of the overall response of fluctuating asymmetry to a controlled graded temperature environment. Fluctuating asymmetry also correlated negatively with temperature, indicating that environmentally-stimulated changes in developmental instability are mediated mostly by changes in the development time of individuals

An investigation of secondary anti-D immunisation among phenotypically RhD-negative individuals in the Chinese population.

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Wang, Qing-Ping; Dong, Guang-Tao; Wang, Xue-Dong; Gu, Juan; Li, Zheng; Sun, An-Yuan; Shao, Chao-Peng; Pan, Zhao-Lin; Huang, Li-Hua; Xie, Wei-Xing; Sun, Guang-Ming; Chen, Jian-Jiang; Pei, Hao; Yang, Xiao-Juan; Shan, Ping-Nan

2014-04-01

Despite the introduction of anti-D prophylaxis into clinical practice, RhD alloimmunisation remains a problem, particularly in the context of transfusions and pregnancy-induced alloimmunisation. The incidence of RhD alloimmunisation among phenotypically RhD-negative individuals is unknown in most countries. We investigated RhD alloimmmunisation in RhD-negative pregnant women and transfusion recipients in south-east China in order to optimise the prevention of this phenomenon. We analysed the RhD alloimmunisation status of RhD-negative pregnant women and transfusion recipients in south-east China. The RhD blood types of the study population were identified by standard serological methods. The D antigen was further tested with the indirect antiglobulin test to exclude or confirm weak D or partial D types. RhC, c, E and e antigens were typed in all subjects. If anti-D antibody screening was positive, the specificity and titre of the antibody were determined. The Del phenotype was investigated by the polymerase chain reaction sequence-specific primer method. An anti-D antibody was found in 61 of 416 RhD-negative pregnant women (14.66%), and in 11 of 227 RhD-negative transfusion recipients (4.85%). None of the 72 RhD-negative pregnant women or transfusion recipients with anti-D had the Del phenotype. Anti-D antibodies were not detected among Del phenotype individuals and Del phenotypes were not found in anti-D antibody producing individuals. Our study suggests that the risk of alloimmunity-induced neonatal haemolysis increases in true RhD-negative multipara. Perinatal protection would be necessary in these patients, while antenatal anti-D testing and Rh immune globulin prophylaxis would be unnecessary for RhDel pregnant women. Pregnant women and transfusion recipients with the Del type seldom produce anti-D antibody. RhD-negative recipients are not at risk of alloimmunisation after transfusion with Del red blood cells.

Side-by-Side Comparison of the Biological Characteristics of Human Umbilical Cord and Adipose Tissue-Derived Mesenchymal Stem Cells

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Li Hu

2013-01-01

Full Text Available Both human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs have been explored as attractive mesenchymal stem cells (MSCs sources, but very few parallel comparative studies of these two cell types have been made. We designed a side-by-side comparative study by isolating MSCs from the adipose tissue and umbilical cords from mothers delivering full-term babies and thus compared the various biological aspects of ASCs and UC-MSCs derived from the same individual, in one study. Both types of cells expressed cell surface markers characteristic of MSCs. ASCs and UC-MSCs both could be efficiently induced into adipocytes, osteoblasts, and neuronal phenotypes. While there were no significant differences in their osteogenic differentiation, the adipogenesis of ASCs was more prominent and efficient than UC-MSCs. In the meanwhile, ASCs responded better to neuronal induction methods, exhibiting the higher differentiation rate in a relatively shorter time. In addition, UC-MSCs exhibited a more prominent secretion profile of cytokines than ASCs. These results indicate that although ASCs and UC-MSCs share considerable similarities in their immunological phenotype and pluripotentiality, certain biological differences do exist, which might have different implications for future cell-based therapy.

The spatial patterns of directional phenotypic selection

KAUST Repository

Siepielski, Adam M.; Gotanda, Kiyoko M.; Morrissey, Michael B.; Diamond, Sarah E.; DiBattista, Joseph; Carlson, Stephanie Marie

2013-01-01

the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data

Genetic Diversity and Phenotypic Variation in an Introgression Line Population Derived from an Interspecific Cross between Oryza glaberrima and Oryza sativa.

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Caijin Chen

Full Text Available The introduction of closely related species genomic fragments is an effective way to enrich genetic diversity and creates new germplasms in crops. Here, we studied the genetic diversity of an introgression line (IL population composed of 106 ILs derived from an interspecific tetra cross between O. glaberrima and O. sativa (RAM3/Jin23B//Jin23B///YuetaiB. The proportion of O. glaberrima genome (PGG in the ILs ranged from 0.3% to 36.7%, with an average value of 12.32% which is close to the theoretically expected proportion. A total of 250 polymorphic alleles were amplified by 21 AFLP primer combinations with an average of 12 alleles per primer. Population structure analysis revealed that the IL population can be divided into four genetically distinct subpopulations. Both principal component analysis and neighbor-joining tree analysis showed that ILs with a higher PGG displayed greater genetic diversity. Canonical discriminant analysis identified six phenotypic traits (plant height, yield per plant, filled grain percentage, panicle length, panicle number and days to flowering as the main discriminatory traits among the ILs and between the subpopulations and showed significant phenotypic distances between subpopulations. The effects of PGG on phenotypic traits in the ILs were estimated using a linear admixed model, which showed a significant positive effect on grain yield per plant (0.286±0.117, plant height (0.418 ± 0.132, panicle length (0.663 ± 0.107, and spikelet number per panicle (0.339 ± 0.128, and a significant negative effect on filled grain percentage (-0.267 ± 0.123 and days to flowering (-0.324 ± 0.075. We found that an intermediate range (10% - 20% of PGG was more effective for producing ILs with favorable integrated agronomic traits. Our results confirm that construction of IL population carrying O. glaberrima genomic fragments could be an effective approach to increase the genetic diversity of O. sativa genome and an appropriate

The outbreak fingolimod cardiovascular side effects in relapsing-remitting multiple sclerosis patient: A longitudinal study in an Iranian population

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Morteza Abdar

2017-03-01

Full Text Available BACKGROUND: Fingolimod (FTY-720 has shown efficacy in relapsing multiple sclerosis (MS, while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS patient in an Iranian population. METHODS: This prospective clinical trial study was performed on 200 RRMS patients. The patients received a single daily oral dose of fingolimod 0.5 mg. During the first 6 hours after the first fingolimod dose, the patients’ vital signs and electrocardiographic traces were continuously monitored. Moreover, the patients followed up over 6 months after receiving fingolimod. RESULTS: The results showed that pulse rate (P < 0.001, systolic blood pressure (BP (P < 0.001, and diastolic BP (P < 0.001 were decreased significantly during 6 hours after receiving the first dose of fingolimod. The most reduction in vital sign was observed in 3 hours. Arrhythmia, bradycardia, and dizziness were the other complications of fingolimod, which were detected in our study. CONCLUSION: All the side effects such as hypotension and bradycardia were happened in first 3 hours after receiving the fingolimod. Indeed, we advise clinicians to monitor the patients for first 6 hours after initiation of fingolimod to decrease worse side effects. 

Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

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Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

2013-01-01

AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

The CAPN10 Gene Is Associated with Insulin Resistance Phenotypes in the Spanish Population

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Sáez, María E.; González-Sánchez, José L.; Ramírez-Lorca, Reposo; Martínez-Larrad, María T.; Zabena, Carina; González, Alejandro; Morón, Francisco J.; Ruiz, Agustín; Serrano-Ríos, Manuel

2008-01-01

Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PMID:18698425

The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

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María E Sáez

Full Text Available Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10 has been associated with type 2 diabetes (T2DM, a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS in T2DM and in polycystic ovary syndrome (PCOS. In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

Phenotypic selection on flowering phenology and pollination efficiency traits between Primula populations with different pollinator assemblages.

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Wu, Yun; Li, Qing-Jun

2017-10-01

Floral traits have largely been attributed to phenotypic selection in plant-pollinator interactions. However, the strength of this link has rarely been ascertained with real pollinators. We conducted pollinator observations and estimated selection through female fitness on flowering phenology and floral traits between two Primula secundiflora populations. We quantified pollinator-mediated selection by subtracting estimates of selection gradients of plants receiving supplemental hand pollination from those of plants receiving open pollination. There was net directional selection for an earlier flowering start date at populations where the dominant pollinators were syrphid flies, and flowering phenology was also subjected to stabilized quadratic selection. However, a later flowering start date was significantly selected at populations where the dominant pollinators were legitimate (normal pollination through the corolla tube entrance) and illegitimate bumblebees (abnormal pollination through nectar robbing hole which located at the corolla tube), and flowering phenology was subjected to disruptive quadratic selection. Wider corolla tube entrance diameter was selected at both populations. Furthermore, the strength of net directional selection on flowering start date and corolla tube entrance diameter was stronger at the population where the dominant pollinators were syrphid flies. Pollinator-mediated selection explained most of the between-population variations in the net directional selection on flowering phenology and corolla tube entrance diameter. Our results suggested the important influence of pollinator-mediated selection on floral evolution. Variations in pollinator assemblages not only resulted in variation in the direction of selection but also the strength of selection on floral traits.

Developing visual images for communicating information aboutantiretroviral side effects to a low-literate population.

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Dowse, Ros; Ramela, Thato; Barford, Kirsty-Lee; Browne, Sara

2010-09-01

The side effects of antiretroviral (ARV) therapy are linked to altered quality of life and adherence. Poor adherence has also been associated with low health-literacy skills, with an uninformed patient more likely to make ARV-related decisions that compromise the efficacy of the treatment. Low literacy skills disempower patients in interactions with healthcare providers and preclude the use of existing written patient information materials, which are generally written at a high reading level. Visual images or pictograms used as a counselling tool or included in patient information leaflets have been shown to improve patients' knowledge, particularly in low-literate groups. The objective of this study was to design visuals or pictograms illustrating various ARV side effects and to evaluate them in a low-literate South African Xhosa population. Core images were generated either from a design workshop or from posed photos or images from textbooks. The research team worked closely with a graphic artist. Initial versions of the images were discussed and assessed in group discussions, and then modified and eventually evaluated quantitatively in individual interviews with 40 participants who each had a maximum of 10 years of schooling. The familiarity of the human body, its facial expressions, postures and actions contextualised the information and contributed to the participants' understanding. Visuals that were simple, had a clear central focus and reflected familiar body experiences (e.g. vomiting) were highly successful. The introduction of abstract elements (e.g. fever) and metaphorical images (e.g. nightmares) presented problems for interpretation, particularly to those with the lowest educational levels. We recommend that such visual images should be designed in collaboration with the target population and a graphic artist, taking cognisance of the audience's literacy skills and culture, and should employ a multistage iterative process of modification and

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics.

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Chantreau, Maxime; Grec, Sébastien; Gutierrez, Laurent; Dalmais, Marion; Pineau, Christophe; Demailly, Hervé; Paysant-Leroux, Christine; Tavernier, Reynald; Trouvé, Jean-Paul; Chatterjee, Manash; Guillot, Xavier; Brunaud, Véronique; Chabbert, Brigitte; van Wuytswinkel, Olivier; Bendahmane, Abdelhafid; Thomasset, Brigitte; Hawkins, Simon

2013-10-15

Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. We have developed a flax mutant population that can be used as an efficient

Interleukin-6 Receptor rs7529229 T/C Polymorphism Is Associated with Left Main Coronary Artery Disease Phenotype in a Chinese Population

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Feng He

2014-04-01

Full Text Available Left main coronary artery disease (LMCAD is a particular severe phenotype of coronary artery disease (CAD and heritability. Interleukin (IL may play important roles in the pathogenesis of CAD. Although several single nucleotide polymorphisms (SNPs identified in IL related genes have been evaluated for their roles in inflammatory diseases and CAD predisposition, the investigations between genetic variants and CAD phenotype are limited. We hypothesized that some of these gene SNPs may contribute to LMCAD phenotype susceptibility compared with more peripheral coronary artery disease (MPCAD. In a hospital-based case-only study, we studied IL-1A rs1800587 C/T, IL-1B rs16944 G/A, IL-6 rs1800796 C/G, IL-6R rs7529229 T/C, IL-8 rs4073 T/A, IL-10 rs1800872 A/C, and IL-10 rs1800896 A/G SNPs in 402 LMCAD patients and 804 MPCAD patients in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS and ligation detection reaction (LDR method. When the IL-6R rs7529229 TT homozygote genotype was used as the reference group, the CC or TC/CC genotypes were associated with the increased risk for LMCAD (CC vs. TT, adjusted odds ratio(OR = 1.46, 95% confidence interval (CI = 1.02–2.11, p = 0.042; CC + TC vs. TT, adjusted OR = 1.31, 95% CI = 1.02–1.69, p = 0.037. None of the other six SNPs achieved any significant differences between LMCAD and MPCAD. The present study suggests that IL-6R rs7529229 T/C functional SNP may contribute to the risk of LMCAD in a Chinese population. However, our results were limited. Validation by a larger study from a more diverse ethnic population is needed.

Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.

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Tracey L Weissgerber

Full Text Available Haptoglobin's (Hp antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH. This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393 and a case-control cohort (703 cases, 1,406 controls. The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01 in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.

A robust new metric of phenotypic distance to estimate and compare multiple trait differences among populations

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Rebecca SAFRAN, Samuel FLAXMAN, Michael KOPP, Darren E. IRWIN, Derek BRIGGS, Matthew R. EVANS, W. Chris FUNK, David A. GRAY, Eileen A. HEBE

2012-06-01

Full Text Available Whereas a rich literature exists for estimating population genetic divergence, metrics of phenotypic trait divergence are lacking, particularly for comparing multiple traits among three or more populations. Here, we review and analyze via simulation Hedges’ g, a widely used parametric estimate of effect size. Our analyses indicate that g is sensitive to a combination of unequal trait variances and unequal sample sizes among populations and to changes in the scale of measurement. We then go on to derive and explain a new, non-parametric distance measure, “Δp”, which is calculated based upon a joint cumulative distribution function (CDF from all populations under study. More precisely, distances are measured in terms of the percentiles in this CDF at which each population’s median lies. Δp combines many desirable features of other distance metrics into a single metric; namely, compared to other metrics, p is relatively insensitive to unequal variances and sample sizes among the populations sampled. Furthermore, a key feature of Δp—and our main motivation for developing it—is that it easily accommodates simultaneous comparisons of any number of traits across any number of populations. To exemplify its utility, we employ Δp to address a question related to the role of sexual selection in speciation: are sexual signals more divergent than ecological traits in closely related taxa? Using traits of known function in closely related populations, we show that traits predictive of reproductive performance are, indeed, more divergent and more sexually dimorphic than traits related to ecological adaptation [Current Zoology 58 (3: 423-436, 2012].

Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

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Funk, W Chris; Murphy, Melanie A

2010-02-01

Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

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2014-01-01

Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; screening-detected cancers, extreme breast density

Building bridges across electronic health record systems through inferred phenotypic topics.

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Chen, You; Ghosh, Joydeep; Bejan, Cosmin Adrian; Gunter, Carl A; Gupta, Siddharth; Kho, Abel; Liebovitz, David; Sun, Jimeng; Denny, Joshua; Malin, Bradley

2015-06-01

Data in electronic health records (EHRs) is being increasingly leveraged for secondary uses, ranging from biomedical association studies to comparative effectiveness. To perform studies at scale and transfer knowledge from one institution to another in a meaningful way, we need to harmonize the phenotypes in such systems. Traditionally, this has been accomplished through expert specification of phenotypes via standardized terminologies, such as billing codes. However, this approach may be biased by the experience and expectations of the experts, as well as the vocabulary used to describe such patients. The goal of this work is to develop a data-driven strategy to (1) infer phenotypic topics within patient populations and (2) assess the degree to which such topics facilitate a mapping across populations in disparate healthcare systems. We adapt a generative topic modeling strategy, based on latent Dirichlet allocation, to infer phenotypic topics. We utilize a variance analysis to assess the projection of a patient population from one healthcare system onto the topics learned from another system. The consistency of learned phenotypic topics was evaluated using (1) the similarity of topics, (2) the stability of a patient population across topics, and (3) the transferability of a topic across sites. We evaluated our approaches using four months of inpatient data from two geographically distinct healthcare systems: (1) Northwestern Memorial Hospital (NMH) and (2) Vanderbilt University Medical Center (VUMC). The method learned 25 phenotypic topics from each healthcare system. The average cosine similarity between matched topics across the two sites was 0.39, a remarkably high value given the very high dimensionality of the feature space. The average stability of VUMC and NMH patients across the topics of two sites was 0.988 and 0.812, respectively, as measured by the Pearson correlation coefficient. Also the VUMC and NMH topics have smaller variance of characterizing

Federated Tensor Factorization for Computational Phenotyping

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Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

2017-01-01

Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

Partial phenotyping in voluntary blood donors of Gujarat State

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Maitrey Gajjar

2016-01-01

Full Text Available Introduction: Partial phenotyping of voluntary blood donors has vital role in transfusion practice, population genetic study and in resolving legal issues.The Rh blood group is one of the most complex and highly immunogenic blood group known in humans. The Kell system, discovered in 1946, is the third most potent system at triggering hemolytic transfusion reactions and consists of 25 highly immunogenic antigens. Knowledge of Rh & Kell phenotypes in given population is relevant for better planning and management of blood bank; the main goal is to find compatible blood for patients needing multiple blood transfusions. The aim of this study was to evaluate the frequency of Rh & Kell phenotype of voluntary donors in Gujarat state. Materials and Methods: The present study was conducted by taking 5670 samples from random voluntary blood donors coming in blood donation camp. Written consent was taken for donor phenotyping. The antigen typing of donors was performed by Qwalys-3(manufacturer: Diagast by using electromagnetic technology on Duolys plates. Results: Out of 5670 donors, the most common Rh antigen observed in the study population was e (99.07% followed by D (95.40%, C (88.77%, c (55.89% and E (17.88%. The frequency of the Kell antigen (K was 1.78 %. Discussion: The antigen frequencies among blood donors from Gujarat were compared with those published for other Indian populations. The frequency of D antigen in our study (95.4% and north Indian donors (93.6 was significantly higher than in the Caucasians (85% and lower than in the Chinese (99%. The frequencies of C, c and E antigens were dissimilar to other ethnic groups while the ′e′ antigen was present in high frequency in our study as also in the other ethnic groups. Kell antigen (K was found in only 101 (1.78 % donors out of 5670. Frequency of Kell antigen in Caucasian and Black populations is 9% & 2% respectively. The most common Kell phenotype was K-k+, not just in Indians (96.5% but

Flow Cytometry of the Side Population: Tips & Tricks

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Irene Sales-Pardo

2006-01-01

Full Text Available Background: The Side Population (SP has become an important hallmark for the definition of the stem cell compartment, especially in the detection of these cells and in their physical isolation by fluorescence-activated cell sorting (FACS. SP cells are CD34neg and were discovered using ultraviolet excitation based on the efflux of Hoechst 33342 (Ho342. Although the method works as originally described, we believe that this method is difficult for most investigators. First, because the ability to discriminate SP cells is based on the differential retention of Ho342 during a functional assay; second, because of the difficulties in setting the right experimental and acquisition conditions; and third, because the analysis of the acquired data requires an extensive expertise on flow cytometry to accurately detect the SP events. Methods: First of all and mainly for the SP application, the laser beam paths were exhaustively checked to ensure the lowest coefficients of variation. Blood suspensions were prepared by erythrocyte lysis with ammonium chloride and hematopoietic cells were labeled with Ho342. Results: The Ho342 concentration and the staining procedure are critical for the optimal resolution of the SP cells. Although UV laser alignment is very important to resolve the dim tail that outlines the SP, the problem with Ho342 excitation is not the Hoechst Blue emission, but rather the Hoechst Red's (because of the weak emission. Conclusions: Each laboratory must establish its own expected ranges based on its instrument and results may vary slightly due to instrument differences such as the narrowness of the band pass filters, laser power, laser emission wavelength, nozzle type, differential of pressure, light collection system (cuvette versus jet-in-air and beam shaping optics.

Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

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Relu Cocoş

Full Text Available Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

International Nuclear Information System (INIS)

Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D.; Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D.; Vaigot, P.; Vaigot, P.; Barroca, V.; Barroca, V.; Leboulch, Ph.

2009-01-01

Ionizing radiation (IR) exposure causes rapid and acute bone marrow (BM) suppression that is reversible for nonlethal doses. Evidence is accumulating that IR can also provoke long-lasting residual hematopoietic injury. To better understand these effects, we analyzed phenotypic and functional changes in the stem/progenitor compartment of irradiated mice over a 10-week period. We found that hematopoietic stem cells (HSCs) identified by their repopulating ability continued to segregate within the Hoechst dye excluding 'side population (SP)' early after IR exposure. However, transient phenotypic changes were observed within this cell population: Sca-1 (S) and c-Kit (K) expression levels were increased and severely reduced, respectively, with a concurrent increase in the proportion of SPSK cells positive for established indicators of the presence of HSCs: CD150 and CD105. Ten weeks after IR exposure, expression of Sca-1 and c-Kit at the SP cell surface returned to control levels, and BM cellularity of irradiated mice was restored. However, the c-Kit + Sca-1 + Lin -/low (KSL) stem/progenitor compartment displayed major phenotypic modifications, including an increase and a severe decrease in the frequencies of CD150 + Flk2 - and CD150 - Flk2 + cells, respectively. CD150 + KSL cells also showed impaired reconstituting ability, an increased tendency to apoptosis, and accrued DNA damage. Finally, 15 weeks after exposure, irradiated mice, but not age matched controls, allowed engraftment and significant hematopoietic contribution from transplanted con-genic HSCs without additional host conditioning. These results provide novel insight in our understanding of immediate and delayed IR-induced hematopoietic injury and highlight similarities between HSCs of young irradiated and old mice. (authors)

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

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Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

2015-04-01

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians.

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Ma, Kun

2013-12-01

A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations. © 2013 Wiley Periodicals, Inc.

Genotype-Phenotype Aspects of Type 2 Long QT Syndrome

NARCIS (Netherlands)

Shimizu, Wataru; Moss, Arthur J.; Wilde, Arthur A. M.; Towbin, Jeffrey A.; Ackerman, Michael J.; January, Craig T.; Tester, David J.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Kaufman, Elizabeth S.; Hofman, Nynke; Noda, Takashi; Kamakura, Shiro; Miyamoto, Yoshihiro; Shah, Samit; Amin, Vinit; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott

2009-01-01

Objectives The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Background Previous studies were limited by population size in their ability to examine phenotypic effect of

Phenotypic variation in California populations of valley oak (Quercus lobata Née) sampled along elevational gradients

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Ana L. Albarrán-Lara; Jessica W. Wright; Paul F. Gugger; Annette Delfino-Mix; Juan Manuel Peñaloza-Ramírez; Victoria L. Sork

2015-01-01

California oaks exhibit tremendous phenotypic variation throughout their range. This variation reflects phenotypic plasticity in tree response to local environmental conditions as well as genetic differences underlying those phenotypes. In this study, we analyze phenotypic variation in leaf traits for valley oak adults sampled along three elevational transects and in...

ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

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Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

2017-11-01

A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Phenotypic characterisation of cell populations in the brains of horses experimentally infected with West Nile virus.

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Delcambre, G H; Liu, J; Streit, W J; Shaw, G P J; Vallario, K; Herrington, J; Wenzlow, N; Barr, K L; Long, M T

2017-11-01

West Nile virus (WNV), a mosquito borne member of the Flaviviridae, is one of the most commonly diagnosed agents of viral encephalitis in horses and people worldwide. A cassette of markers for formalin-fixed paraffin-embedded tissue and an archive of tissues from experimental infections in the horse were used to investigate the equine neuroimmune response to WNV meningoencephalomyelitis to phenotype the early response to WNV infection in the horse. Quantitative analysis using archived tissue from experimentally infected horses. The thalamus and hindbrain from 2 groups of 6 horses were compared and consisted of a culture positive tissues from WNV experimentally horses, in the other, normal horses. Formalin-fixed paraffin-embedded tissue from the thalamus and hindbrain were immunolabeled for microglia, astrocytes, B cells, macrophages/neutrophils, CD3 + T cells. Fresh frozen tissues were immunolabeled for CD4 + and CD8 + T lymphocyte cell markers. Cell counts were obtained using a computer software program. Differences, after meeting assumptions of abnormality, were computed using a general linear model with a Tukey test (Phorses, Iba-1 + microglia, CD3 + T lymphocyte and MAC387 + macrophage staining were significantly increased. The T cell response for the WNV-challenged horses was mixed, composed of CD4 + and CD8 + T lymphocytes. A limited astrocyte response was also observed in WNV-challenged horses, and MAC387 + and B cells were the least abundant cell populations. The results of this study were limited by a single collection time post-infection. Furthermore, a comprehensive analysis of cellular phenotypes is needed for naturally infected horses. Unfortunately, in clinical horses, there is high variability of sampling in terms of days post-infection and tissue handling. The data show that WNV-challenged horses recruit a mixed T cell population at the onset of neurologic disease. © 2017 EVJ Ltd.

Phenotypic Changes in Different Spinach Varieties Grown and Selected under Organic Conditions

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Nicolas Schermann

2011-09-01

Full Text Available Organic and low-input agriculture needs flexible varieties that can buffer environmental stress and adapt to the needs of farmers. We implemented an experiment to investigate the evolutionary capacities of a sample of spinach (Spinacia oleracea L. population varieties for a number of phenotypic traits. Three farmers cultivated, selected and multiplied one or several populations over two years on their farms. The third year, the versions of the varieties cultivated and selected by the different farmers were compared to the original seed lots they had been given. After two cycles of cultivation and on-farm mass selection, all the observed varieties showed significant phenotypic changes (differences between the original version and the version cultivated by farmers for morphological and phenological traits. When the divergence among versions within varieties was studied, the results show that the varieties conserved their identity, except for one variety, which evolved in such a way that it may now be considered two different varieties. The heterogeneity of the population varieties was assessed in comparison with a commercial F1 hybrid used as control, and we found no specific differences in phenotypic diversity between the hybrid and population varieties. The phenotypic changes shown by the population varieties in response to on-farm cultivation and selection could be useful for the development of specific adaptation. These results call into question the current European seed legislation and the requirements of phenotypic stability for conservation varieties.

Phenotypic heterogeneity of peripheral monocytes in healthy dogs.

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Gibbons, Natalie; Goulart, Michelle R; Chang, Yu-Mei; Efstathiou, Konstantinos; Purcell, Robert; Wu, Ying; Peters, Laureen M; Turmaine, Mark; Szladovits, Balazs; Garden, Oliver A

2017-08-01

Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By flow cytometry, we demonstrated that canine monocytes can be subdivided into three separate populations: CD14 pos MHC II neg , CD14 pos MHC II pos and CD14 neg MHC II pos . Both light and transmission electron microscopy confirmed the monocytic identity of all three populations. The CD14 pos MHC II neg population could be distinguished on an ultrastructural level by their smaller size, the presence of more numerous, larger granules, and more pseudopodia than both of the other populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.

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Welt, C K; Arason, G; Gudmundsson, J A; Adams, J; Palsdóttir, H; Gudlaugsdóttir, G; Ingadóttir, G; Crowley, W F

2006-11-01

The phenotype of women with polycystic ovary syndrome (PCOS) is variable, depending on the ethnic background. The phenotypes of women with PCOS in Iceland and Boston were compared. The study was observational with a parallel design. Subjects were studied in an outpatient setting. Women, aged 18-45 yr, with PCOS defined by hyperandrogenism and fewer than nine menses per year, were examined in Iceland (n = 105) and Boston (n = 262). PCOS subjects underwent a physical exam, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound. The phenotype of women with PCOS was compared between Caucasian women in Iceland and Boston and among Caucasian, African-American, Hispanic, and Asian women in Boston. Androstenedione (4.0 +/- 1.3 vs. 3.5 +/- 1.2 ng/ml; P PCOS. There were no differences in fasting blood glucose, insulin, or homeostasis model assessment in body mass index-matched Caucasian subjects from Iceland or Boston or in different ethnic groups in Boston. Polycystic ovary morphology was demonstrated in 93-100% of women with PCOS in all ethnic groups. The data demonstrate differences in the reproductive features of PCOS without differences in glucose and insulin in body mass index-matched populations. These studies also suggest that measuring androstenedione is important for the documentation of hyperandrogenism in Icelandic women. Finally, polycystic ovary morphology by ultrasound is an almost universal finding in women with PCOS as defined by hyperandrogenism and irregular menses.

Conventional and right-sided screening for subcutaneous ICD in a population with congenital heart disease at high risk of sudden cardiac death.

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Alonso, Pau; Osca, Joaquín; Rueda, Joaquín; Cano, Oscar; Pimenta, Pedro; Andres, Ana; Sancho, María José; Martinez, Luis

2017-11-01

Information regarding suitability for subcutaneous defibrillator (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is scarce and needs to be further explored. The main objective of our study was to determine the proportion of patients with ToF and systemic right ventricle eligible for sICD with both, standard and right-sided screening methods. Secondary objectives were: (i) to study sICD eligibility specifically in patients at high risk of sudden cardiac death, (ii) to identify independent predictors for sICD eligibility, and (iii) to compare the proportion of eligible patients in a nonselected ICD population. We recruited 102 patients with ToF, 33 with systemic right ventricle, and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left-arm and right-arm electrodes 1 cm right lateral of the xiphoid midline. The Boston Scientific ECG screening tool was utilized. In high-risk patients with ToF, eligibility was higher with right-sided screening in comparison with standard screening (61% vs. 44%; p = .018). Eligibility in high-risk right ventricle population was identical with both screening methods (77%, p = ns). The only independent predictor for sICD eligibility was QRS duration. In high-risk patients with ToF, right-sided implantation of the sICD could be an alternative to a conventional ICD. In patients with a systemic right ventricle, implantation of a sICD is an alternative to a conventional sICD. © 2017 Wiley Periodicals, Inc.

Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease mechanisms using GWAS data.

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Jonathan D Mosley

Full Text Available A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1 non-synonymous SNPs (nsSNPs associated with "mechanistic phenotypes", comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1 thrombosis, evaluated in a population of 1,655 African Americans; and (2 four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs, and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03, driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10-5, FDR p = 0.03 (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L while the additive model showed enrichment related to chromatid segregation (p = 4×10-6, FDR p = 0.005 (KIF25, PINX1. We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms.

Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol.

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Nieuwenhuijsen, Mark J; Kruize, Hanneke; Gidlow, Christopher; Andrusaityte, Sandra; Antó, Josep Maria; Basagaña, Xavier; Cirach, Marta; Dadvand, Payam; Danileviciute, Asta; Donaire-Gonzalez, David; Garcia, Judith; Jerrett, Michael; Jones, Marc; Julvez, Jordi; van Kempen, Elise; van Kamp, Irene; Maas, Jolanda; Seto, Edmund; Smith, Graham; Triguero, Margarita; Wendel-Vos, Wanda; Wright, John; Zufferey, Joris; van den Hazel, Peter Jan; Lawrence, Roderick; Grazuleviciene, Regina

2014-04-16

Growing evidence suggests that close contact with nature brings benefits to human health and well-being, but the proposed mechanisms are still not well understood and the associations with health remain uncertain. The Positive Health Effects of the Natural Outdoor environment in Typical Populations in different regions in Europe (PHENOTYPE) project investigates the interconnections between natural outdoor environments and better human health and well-being. The PHENOTYPE project explores the proposed underlying mechanisms at work (stress reduction/restorative function, physical activity, social interaction, exposure to environmental hazards) and examines the associations with health outcomes for different population groups. It implements conventional and new innovative high-tech methods to characterise the natural environment in terms of quality and quantity. Preventive as well as therapeutic effects of contact with the natural environment are being covered. PHENOTYPE further addresses implications for land-use planning and green space management. The main innovative part of the study is the evaluation of possible short-term and long-term associations of green space and health and the possible underlying mechanisms in four different countries (each with quite a different type of green space and a different use), using the same methodology, in one research programme. This type of holistic approach has not been undertaken before. Furthermore there are technological innovations such as the use of remote sensing and smartphones in the assessment of green space. The project will produce a more robust evidence base on links between exposure to natural outdoor environment and human health and well-being, in addition to a better integration of human health needs into land-use planning and green space management in rural as well as urban areas.

Phenotypic and Functional Changes Induced in Hematopoietic Stem/Progenitor Cells After Gamma-Ray Radiation Exposure

Energy Technology Data Exchange (ETDEWEB)

Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D. [Institute of Emerging Diseases and Innovative Therapies, Functional Bioengineering Laboratory, Commissariat a l' Energie Atomique (CEA), Evry (France); Simonnet, A.J.; Nehme, J.; Leboulch, Ph.; Tronik-Le Roux, D. [Institut National de la Sante et de la Recherche Medicale (INSERM) U733 (Unite Mixte de Recherche) - UMR INSERM CEA Paris XI (France); Vaigot, P. [Institute of Cellular and Molecular Radiation Biology, Department of Genetic Instability, Recombination and Repair, Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France); Vaigot, P. [UMR 217, UMR-CEA-Centre National de la Recherche Scientifique (France); Barroca, V. [Laboratory of Gametogenesis, Apoptosis, Genotoxicity, Institute of Cellular and Molecular Radiation Biology, Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France); Barroca, V. [Institut National de la Sante et de la Recherche Medicale U566 - UMR INSERM-CEA-PARIS VII (France); Leboulch, Ph. [Genetics Division, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (US)

2009-07-01

Ionizing radiation (IR) exposure causes rapid and acute bone marrow (BM) suppression that is reversible for nonlethal doses. Evidence is accumulating that IR can also provoke long-lasting residual hematopoietic injury. To better understand these effects, we analyzed phenotypic and functional changes in the stem/progenitor compartment of irradiated mice over a 10-week period. We found that hematopoietic stem cells (HSCs) identified by their repopulating ability continued to segregate within the Hoechst dye excluding 'side population (SP)' early after IR exposure. However, transient phenotypic changes were observed within this cell population: Sca-1 (S) and c-Kit (K) expression levels were increased and severely reduced, respectively, with a concurrent increase in the proportion of SPSK cells positive for established indicators of the presence of HSCs: CD150 and CD105. Ten weeks after IR exposure, expression of Sca-1 and c-Kit at the SP cell surface returned to control levels, and BM cellularity of irradiated mice was restored. However, the c-Kit{sup +}Sca-1{sup +}Lin{sup -/low} (KSL) stem/progenitor compartment displayed major phenotypic modifications, including an increase and a severe decrease in the frequencies of CD150{sup +}Flk2{sup -} and CD150{sup -}Flk2{sup +} cells, respectively. CD150{sup +} KSL cells also showed impaired reconstituting ability, an increased tendency to apoptosis, and accrued DNA damage. Finally, 15 weeks after exposure, irradiated mice, but not age matched controls, allowed engraftment and significant hematopoietic contribution from transplanted con-genic HSCs without additional host conditioning. These results provide novel insight in our understanding of immediate and delayed IR-induced hematopoietic injury and highlight similarities between HSCs of young irradiated and old mice. (authors)

The GP problem: quantifying gene-to-phenotype relationships.

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Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

2002-01-01

In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

Phenotypic and genetic differentiation among yellow monkeyflower populations from thermal and non-thermal soils in Yellowstone National Park.

Science.gov (United States)

Lekberg, Ylva; Roskilly, Beth; Hendrick, Margaret F; Zabinski, Catherine A; Barr, Camille M; Fishman, Lila

2012-09-01

In flowering plants, soil heterogeneity can generate divergent natural selection over fine spatial scales, and thus promote local adaptation in the absence of geographic barriers to gene flow. Here, we investigate phenotypic and genetic differentiation in one of the few flowering plants that thrives in both geothermal and non-thermal soils in Yellowstone National Park (YNP). Yellow monkeyflowers (Mimulus guttatus) growing at two geothermal ("thermal") sites in YNP were distinct in growth form and phenology from paired populations growing nearby ( 0.34), which were only weakly differentiated from each other (all F (ST) geothermal gradient in Yellowstone.

Phenotypic plasticity as an adaptive response to predictable and unpredictable environmental changes

DEFF Research Database (Denmark)

Manenti, Tommaso

Phenotypic plasticity is the ability of a genotype to modify its phenotype in response to environmental changes as a consequence of an interaction between genes and environment (Bradshaw, 1965). Plasticity contributes to the vast phenotypic variation observed in natural populations. Many examples...... of a plastic response are expected to depend on the environmental conditions experienced by organisms. Thus, in populations exposed to a non-changing environment, the plastic machinery might be a waste of resources. Contrary, in populations experiencing varying environmental conditions, plasticity is expected...... such as anti-predator behaviours or the activation of mechanisms to prevent thermal stress injuries suggest that plasticity is an adaptive response, favoured by natural selection. At the same time, organisms do show limited plastic responses, indicating that this ability is not for free. Costs and benefits...

Study of selected phenotype switching strategies in time varying environment

Energy Technology Data Exchange (ETDEWEB)

Horvath, Denis, E-mail: horvath.denis@gmail.com [Centre of Interdisciplinary Biosciences, Institute of Physics, Faculty of Science, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia); Brutovsky, Branislav, E-mail: branislav.brutovsky@upjs.sk [Department of Biophysics, Institute of Physics, P.J. Šafárik University in Košice, Jesenná 5, 040 01 Košice (Slovakia)

2016-03-22

Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.

Study of selected phenotype switching strategies in time varying environment

International Nuclear Information System (INIS)

Horvath, Denis; Brutovsky, Branislav

2016-01-01

Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback–Leibler functional distances and the Hamming distance. - Highlights: • Relation between phenotype switching and environment is studied. • The Markov chain Monte Carlo based model is developed. • Stochastic and deterministic strategies of phenotype switching are utilized. • Statistical measures of the dynamic heterogeneity reveal universal properties. • The results extend to higher lattice dimensions.

Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

DEFF Research Database (Denmark)

Song, Yong; Schwager, Michelle J; Backer, Vibeke

2017-01-01

The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically...... separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit......-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases....

SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes.

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Ha-Won Jeong

2011-04-01

Full Text Available Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2-4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC drug transport protein family, such as ABCG2 and ABCA3. Using chromatin-immunoprecipitation (ChIP, quantitative reverse transcription polymerase chain reaction (qRT-PCR and electrophoretic mobility shift assay(EMSA, we demonstrated that SALL4 was able to bind to the promoter region of ABCA3 and activate its expression while regulating the expression of ABCG2 indirectly. Furthermore, SALL4 expression was positively correlated to those of ABCG2 and ABCA3 in primary leukemic patient samples. Taken together, our results suggest a novel role for SALL4 in drug sensitivity, at least in part through the maintenance of SP cells, and therefore may be responsible for drug-resistance in leukemia. We are the first to demonstrate a direct link between stem cell factor SALL4, SP and drug resistance in leukemia.

Leaf phenotypic variation and developmental instability in relation to different light regimes

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Henrique Venâncio

2016-06-01

Full Text Available ABSTRACT For pioneer plants, shaded habitats represent a stressful condition, where sunlight exposure is below the optimum level and so leaves expand in order to intercept a greater amount of light. We investigated changes in both phenotypic variation and stress of Bauhinia brevipes in sunny and shaded microhabitats. Leaf area was used as a measure of phenotypic variation, whereas leaf asymmetry (difference between right and left sides of leaves, was used as a measure of stress. We hypothesized an increase in leaf area and stress in shaded locations, which might indicate that B. brevipes was compensating for low light absorption, and elevated levels of stress, respectively. Plants in the sun fitted a fluctuating asymmetry pattern (normal distribution of right minus left sides, while shaded plants were clearly antisymmetric (bimodal distribution of leaf side differences. Leaf asymmetry and area were 5% and 26.8% higher in plants in the shade compared to plants in the sun, respectively. These results were expected since B. brevipes is found predominantly in open areas; so sunlight exposure is important for its development. The presence of antisymmetry is rare in studies of developmental instability, and here it might indicate higher stress compared to plants with fluctuating asymmetry.

The importance of environment on respiratory genotype/phenotype relationships in the Inuit

DEFF Research Database (Denmark)

Candelaria, P V; Backer, V; Khoo, S-K

2010-01-01

Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry.......Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry....

Fire coral clones demonstrate phenotypic plasticity among reef habitats.

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Dubé, Caroline E; Boissin, Emilie; Maynard, Jeffrey A; Planes, Serge

2017-08-01

Clonal populations are often characterized by reduced levels of genotypic diversity, which can translate into lower numbers of functional phenotypes, both of which impede adaptation. Study of partially clonal animals enables examination of the environmental settings under which clonal reproduction is favoured. Here, we gathered genotypic and phenotypic information from 3,651 georeferenced colonies of the fire coral Millepora platyphylla in five habitats with different hydrodynamic regimes in Moorea, French Polynesia. In the upper slope where waves break, most colonies grew as vertical sheets ("sheet tree") making them more vulnerable to fragmentation. Nearly all fire corals in the other habitats are encrusting or massive. The M. platyphylla population is highly clonal (80% of the colonies are clones), while characterized by the highest genotype diversity ever documented for terrestrial or marine populations (1,064 genotypes). The proportion of clones varies greatly among habitats (≥58%-97%) and clones (328 clonal lineages) are distributed perpendicularly from the reef crest, perfectly aligned with wave energy. There are six clonal lineages with clones dispersed in at least two adjacent habitats that strongly demonstrate phenotypic plasticity. Eighty per cent of the colonies in these lineages are "sheet tree" on the upper slope, while 80%-100% are encrusting or massive on the mid slope and back reef. This is a unique example of phenotypic plasticity among reef-building coral clones as corals typically have wave-tolerant growth forms in high-energy reef areas. © 2017 John Wiley & Sons Ltd.

Age is associated with asthma phenotypes.

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Ponte, Eduardo V; Lima, Aline; Almeida, Paula C A; de Jesus, Juliana P V; Lima, Valmar B; Scichilone, Nicola; Souza-Machado, Adelmir; Cruz, Álvaro A

2017-11-01

The relationship between age and asthma phenotypes is important as population is ageing, asthma is becoming common in older ages and recently developed treatments for asthma are guided by phenotypes. The aim of this study is to evaluate whether age is associated with specific asthma phenotypes. This is a cross-sectional study. We included subjects with asthma of varied degrees of severity. Subjects underwent spirometry, skin prick test to aeroallergens, answered the Asthma Control Questionnaire and had blood samples collected. We performed binary logistic regression analysis to evaluate whether age is associated with asthma phenotypes. We enrolled 868 subjects. In comparison with subjects ≤ 40 years, older subjects had high odds of irreversible airway obstruction (from 41 to 64 years, OR: 1.83 (95% CI: 1.32-2.54); ≥65 years, OR: 3.45 (2.12-5.60)) and severe asthma phenotypes (from 41 to 64 years, OR: 3.23 (2.26-4.62); ≥65 years, OR: 4.55 (2.39-8.67)). Older subjects had low odds of atopic (from 41 to 64 years, OR: 0.56 (0.39-0.79); ≥65 years, OR: 0.47 (0.27-0.84)) and eosinophilic phenotypes (from 41 to 64 years, OR: 0.63 (0.46-0.84); ≥65 years, OR: 0.39 (0.24-0.64)). Older subjects with asthma have low odds of atopic and eosinophilic phenotypes, whereas they present high odds of irreversible airway obstruction and severe asthma. © 2017 Asian Pacific Society of Respirology.

Lethal mutagenesis: targeting the mutator phenotype in cancer.

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Fox, Edward J; Loeb, Lawrence A

2010-10-01

The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Starvation induces phenotypic diversification and convergent evolution in Vibrio vulnificus.

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Hwajiun Chen

Full Text Available Starvation is a common stress experienced by bacteria living in natural environments and the ability to adapt to and survive intense stress is of paramount importance for any bacterial population. A series of starvation experiments were conducted using V. vulnificus 93U204 in phosphate-buffered saline and seawater. The starved population entered the death phase during the first week and approximately 1% of cells survived. After that the population entered a long-term stationary phase, and could survive for years. Starvation-induced diversification (SID of phenotypes was observed in starved populations and phenotypic variants (PVs appeared in less than 8 days. The cell density, rather than the population size, had a major effect on the extent of SID. SID was also observed in strain YJ016, where it evolved at a faster pace. PVs appeared to emerge in a fixed order: PV with reduced motility, PV with reduced proteolytic activity, and PV with reduced hemolytic activity. All of the tested PVs had growth advantages in the stationary phase phenotypes and increased fitness compared with 93U204 cells in co-culture competition experiments, which indicates that they had adapted to starvation. We also found that SID occurred in natural seawater with a salinity of 1%-3%, so this mechanism may facilitate bacterial adaptation in natural environments.

Holistic and component plant phenotyping using temporal image sequence.

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Das Choudhury, Sruti; Bashyam, Srinidhi; Qiu, Yumou; Samal, Ashok; Awada, Tala

2018-01-01

Image-based plant phenotyping facilitates the extraction of traits noninvasively by analyzing large number of plants in a relatively short period of time. It has the potential to compute advanced phenotypes by considering the whole plant as a single object (holistic phenotypes) or as individual components, i.e., leaves and the stem (component phenotypes), to investigate the biophysical characteristics of the plants. The emergence timing, total number of leaves present at any point of time and the growth of individual leaves during vegetative stage life cycle of the maize plants are significant phenotypic expressions that best contribute to assess the plant vigor. However, image-based automated solution to this novel problem is yet to be explored. A set of new holistic and component phenotypes are introduced in this paper. To compute the component phenotypes, it is essential to detect the individual leaves and the stem. Thus, the paper introduces a novel method to reliably detect the leaves and the stem of the maize plants by analyzing 2-dimensional visible light image sequences captured from the side using a graph based approach. The total number of leaves are counted and the length of each leaf is measured for all images in the sequence to monitor leaf growth. To evaluate the performance of the proposed algorithm, we introduce University of Nebraska-Lincoln Component Plant Phenotyping Dataset (UNL-CPPD) and provide ground truth to facilitate new algorithm development and uniform comparison. The temporal variation of the component phenotypes regulated by genotypes and environment (i.e., greenhouse) are experimentally demonstrated for the maize plants on UNL-CPPD. Statistical models are applied to analyze the greenhouse environment impact and demonstrate the genetic regulation of the temporal variation of the holistic phenotypes on the public dataset called Panicoid Phenomap-1. The central contribution of the paper is a novel computer vision based algorithm for

Distinct genetic architectures for phenotype means and plasticities in Zea mays.

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Kusmec, Aaron; Srinivasan, Srikant; Nettleton, Dan; Schnable, Patrick S

2017-09-01

Phenotypic plasticity describes the phenotypic variation of a trait when a genotype is exposed to different environments. Understanding the genetic control of phenotypic plasticity in crops such as maize is of paramount importance for maintaining and increasing yields in a world experiencing climate change. Here, we report the results of genome-wide association analyses of multiple phenotypes and two measures of phenotypic plasticity in a maize nested association mapping (US-NAM) population grown in multiple environments and genotyped with ~2.5 million single-nucleotide polymorphisms. We show that across all traits the candidate genes for mean phenotype values and plasticity measures form structurally and functionally distinct groups. Such independent genetic control suggests that breeders will be able to select semi-independently for mean phenotype values and plasticity, thereby generating varieties with both high mean phenotype values and levels of plasticity that are appropriate for the target performance environments.

Population differences in host use by a seed-beetle: local adaptation, phenotypic plasticity and maternal effects.

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Amarillo-Suárez, Angela R; Fox, Charles W

2006-11-01

For insects that develop inside discrete hosts, both host size and host quality constrain offspring growth, influencing the evolution of body size and life history traits. Using a two-generation common garden experiment, we quantified the contribution of maternal and rearing hosts to differences in growth and life history traits between populations of the seed-feeding beetle Stator limbatus that use a large-seeded host, Acacia greggii, and a small-seeded host, Pseudosamanea guachapele. Populations differed genetically for all traits when beetles were raised in a common garden. Contrary to expectations from the local adaptation hypothesis, beetles from all populations were larger, developed faster and had higher survivorship when reared on seeds of A. greggii (the larger host), irrespective of their native host. We observed two host plant-mediated maternal effects: offspring matured sooner, regardless of their rearing host, when their mothers were reared on P. guachapele (this was not caused by an effect of rearing host on egg size), and females laid larger eggs on P. guachapele. This is the first study to document plasticity by S. limbatus in response to P. guachapele, suggesting that plasticity is an ancestral trait in S. limbatus that likely plays an important role in diet expansion. Although differences between populations in growth and life history traits are likely adaptations to their host plants, host-associated maternal effects, partly mediated by maternal egg size plasticity, influence growth and life history traits and likely play an important role in the evolution of the breadth of S. limbatus' diet. More generally, phenotypic plasticity mediates the fitness consequences of using novel hosts, likely facilitating colonization of new hosts, but also buffering herbivores from selection post-colonization. Plasticity in response to novel versus normal hosts varied among our study populations such that disentangling the historical role of plasticity in

Cognitive-behavioral phenotypes of Williams syndrome are associated with genetic variation in the GTF2I gene, in a healthy population.

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Crespi, Bernard J; Hurd, Peter L

2014-11-28

Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated. We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies. These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

History, haldanes and health inequities: exploring phenotypic changes in body size by generation and income level in the US-born White and Black non-Hispanic populations 1959-1962 to 2005-2008.

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Krieger, Nancy; Chen, Jarvis T; Waterman, Pamela D; Kosheleva, Anna; Beckfield, Jason

2013-02-01

Most public health literature on trends in population health and health inequities pertains to observed or targeted changes in rates or proportions per year or decade. We explore, in novel analyses, whether additional insight can be gained by using the 'haldane', a metric developed by evolutionary biologists to measure change in traits in standard deviations per generation, thereby enabling meaningful comparisons across species and time periods. We analysed the phenotypic embodied traits of body height, weight and body mass index of US-born White and Black non-Hispanic adults ages 20 to 44 as measured in six large nationally representative population samples spanning from the 1959-1962 National Health Examination Survey I to the 2005-2008 National Health and Nutrition Examination Survey. Setting the former as baseline, we computed the haldane for each outcome for each racial/ethnic group for each survey, overall and stratified by family income quintile. For height, high rates of phenotypic change (haldane ≥ 0.3) occurred chiefly between 1960 and 1980, especially for the Black population in the higher income quintiles. By contrast, for weight, high rates of phenotypic change became evident for both the White and Black populations in the late 1980s and increased thereafter; for body mass index, the shift to high rates of change started in both groups in the late 1990s, especially in the middle income quintiles. Our results support use of the haldane as a supplemental metric to place changes in population health and health inequities in a larger biological and historical context.

Contemporary and historical evolutionary processes interact to shape patterns of within-lake phenotypic divergences in polyphenic pumpkinseed sunfish, Lepomis gibbosus.

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Weese, Dylan J; Ferguson, Moira M; Robinson, Beren W

2012-03-01

Historical and contemporary evolutionary processes can both contribute to patterns of phenotypic variation among populations of a species. Recent studies are revealing how interactions between historical and contemporary processes better explain observed patterns of phenotypic divergence than either process alone. Here, we investigate the roles of evolutionary history and adaptation to current environmental conditions in structuring phenotypic variation among polyphenic populations of sunfish inhabiting 12 postglacial lakes in eastern North America. The pumpkinseed sunfish polyphenism includes sympatric ecomorphs specialized for littoral or pelagic lake habitats. First, we use population genetic methods to test the evolutionary independence of within-lake phenotypic divergences of ecomorphs and to describe patterns of genetic structure among lake populations that clustered into three geographical groupings. We then used multivariate analysis of covariance (MANCOVA) to partition body shape variation (quantified with geometric morphometrics) among the effects of evolutionary history (reflecting phenotypic variation among genetic clusters), the shared phenotypic response of all populations to alternate habitats within lakes (reflecting adaptation to contemporary conditions), and unique phenotypic responses to habitats within lakes nested within genetic clusters. All effects had a significant influence on body form, but the effects of history and the interaction between history and contemporary habitat were larger than contemporary processes in structuring phenotypic variation. This highlights how divergence can be better understood against a known backdrop of evolutionary history.

Flow cytometric monitoring of bacterioplankton phenotypic diversity predicts high population-specific feeding rates by invasive dreissenid mussels.

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Props, Ruben; Schmidt, Marian L; Heyse, Jasmine; Vanderploeg, Henry A; Boon, Nico; Denef, Vincent J

2018-02-01

Species invasion is an important disturbance to ecosystems worldwide, yet knowledge about the impacts of invasive species on bacterial communities remains sparse. Using a novel approach, we simultaneously detected phenotypic and derived taxonomic change in a natural bacterioplankton community when subjected to feeding pressure by quagga mussels, a widespread aquatic invasive species. We detected a significant decrease in diversity within 1 h of feeding and a total diversity loss of 11.6 ± 4.1% after 3 h. This loss of microbial diversity was caused by the selective removal of high nucleic acid populations (29 ± 5% after 3 h). We were able to track the community diversity at high temporal resolution by calculating phenotypic diversity estimates from flow cytometry (FCM) data of minute amounts of sample. Through parallel FCM and 16S rRNA gene amplicon sequencing analysis of environments spanning a broad diversity range, we showed that the two approaches resulted in highly correlated diversity measures and captured the same seasonal and lake-specific patterns in community composition. Based on our results, we predict that selective feeding by invasive dreissenid mussels directly impacts the microbial component of the carbon cycle, as it may drive bacterioplankton communities toward less diverse and potentially less productive states. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Environmental change, phenotypic plasticity, and genetic compensation.

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Grether, Gregory F

2005-10-01

When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

Rapid plant invasion in distinct climates involves different sources of phenotypic variation.

Directory of Open Access Journals (Sweden)

Arnaud Monty

Full Text Available When exotic species spread over novel environments, their phenotype will depend on a combination of different processes, including phenotypic plasticity (PP, local adaptation (LA, environmental maternal effects (EME and genetic drift (GD. Few attempts have been made to simultaneously address the importance of those processes in plant invasion. The present study uses the well-documented invasion history of Senecio inaequidens (Asteraceae in southern France, where it was introduced at a single wool-processing site. It gradually invaded the Mediterranean coast and the Pyrenean Mountains, which have noticeably different climates. We used seeds from Pyrenean and Mediterranean populations, as well as populations from the first introduction area, to explore the phenotypic variation related to climatic variation. A reciprocal sowing experiment was performed with gardens under Mediterranean and Pyrenean climates. We analyzed climatic phenotypic variation in germination, growth, reproduction, leaf physiology and survival. Genetic structure in the studied invasion area was characterized using AFLP. We found consistent genetic differentiation in growth traits but no home-site advantage, so weak support for LA to climate. In contrast, genetic differentiation showed a relationship with colonization history. PP in response to climate was observed for most traits, and it played an important role in leaf trait variation. EME mediated by seed mass influenced all but leaf traits in a Pyrenean climate. Heavier, earlier-germinating seeds produced larger individuals that produced more flower heads throughout the growing season. However, in the Mediterranean garden, seed mass only influenced the germination rate. The results show that phenotypic variation in response to climate depends on various ecological and evolutionary processes associated with geographical zone and life history traits. Seeing the relative importance of EME and GD, we argue that a "local

“Side effects affected my daily activities a lot”: a qualitative exploration of the impact of contraceptive side effects in Bangladesh

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Jain A

2017-07-01

Full Text Available Aparna Jain,1 Laura Reichenbach,1 Iqbal Ehsan,2 Ubaidur Rob2 1Evidence Project, Population Council, Washington, DC, USA; 2Evidence Project, Population Council, Dhaka, Bangladesh Purpose: In a country like Bangladesh that has made great progress in contraceptive use with one of the lowest levels of fertility and highest levels of contraceptive use, understanding what factors influence women’s decisions to discontinue a contraceptive method and not switch to a new method is critical in designing interventions and programs that will help enable Bangladesh to reach its FP2020 goals. Research on side effects has focused on physical manifestations like headaches, moodiness, abdominal pain, and menstrual irregularities. While physical effects alone may stop women from continuing a contraceptive method, less is known about how side effects influence women’s daily activities and lives. The purpose of this study is to understand the ways that side effects affect Bangladeshi women’s participation in different social settings.Methods: Thirty-five in-depth interviews with married women who recently discontinued or switched to a different contraceptive method were conducted in Sylhet and Khulna Divisions. Interviews explored reasons for discontinuation including experience of side effects and impact of side effects on women’s lives.Results: Key themes emerged including that side effects are not only experienced physically but are barriers to women’s participation in many aspects of their lives. The spheres of life that most commonly appeared to be influenced by side effects include religion, household, and sexual intimacy irrespective of method used or residence.Conclusion: Family planning providers need to be aware of these additional consequences associated with contraceptive side effects to provide tailored counseling that recognizes these issues and helps women to mitigate them. For Bangladesh to achieve its FP2020 goals, understanding the

The Details in the Distributions: Why and how to study phenotypic variability

Science.gov (United States)

Geiler-Samerotte, KA; Bauer, CR; Li, S; Ziv, N; Gresham, D; Siegal, ML

2013-01-01

Phenotypic variability is present even when genetic and environmental differences between cells are reduced to the greatest possible extent. For example, genetically identical bacteria display differing levels of resistance to antibiotics, clonal yeast populations demonstrate morphological and growth-rate heterogeneity, and mouse blastomeres from the same embryo have stochastic differences in gene expression. However, the distributions of phenotypes present among isogenic organisms are often overlooked; instead, many studies focus on population aggregates such as the mean. The details of these distributions are relevant to major questions in diverse fields, including the evolution of antimicrobial-drug and chemotherapy resistance. We review emerging experimental and statistical techniques that allow rigorous analysis of phenotypic variability and thereby may lead to advances across the biological sciences. PMID:23566377

The phenotypic diversity and fruit characterization of winter squash ...

African Journals Online (AJOL)

PRECIOUS

2010-01-11

Jan 11, 2010 ... collected from different provinces of the Black Sea region in 2006 and 2007 and phenotypic ... Picture of the diversity fruit size, shape and color for Cucurbita maxima ... Fruit traits used winter squash (C. maxima Duch) population characterization. S/N ..... Group J: There were a total of 18 populations in this.

Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

Science.gov (United States)

Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

2013-01-01

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

Rethinking the evolution of specialization: A model for the evolution of phenotypic heterogeneity.

Science.gov (United States)

Rubin, Ilan N; Doebeli, Michael

2017-12-21

Phenotypic heterogeneity refers to genetically identical individuals that express different phenotypes, even when in the same environment. Traditionally, "bet-hedging" in fluctuating environments is offered as the explanation for the evolution of phenotypic heterogeneity. However, there are an increasing number of examples of microbial populations that display phenotypic heterogeneity in stable environments. Here we present an evolutionary model of phenotypic heterogeneity of microbial metabolism and a resultant theory for the evolution of phenotypic versus genetic specialization. We use two-dimensional adaptive dynamics to track the evolution of the population phenotype distribution of the expression of two metabolic processes with a concave trade-off. Rather than assume a Gaussian phenotype distribution, we use a Beta distribution that is capable of describing genotypes that manifest as individuals with two distinct phenotypes. Doing so, we find that environmental variation is not a necessary condition for the evolution of phenotypic heterogeneity, which can evolve as a form of specialization in a stable environment. There are two competing pressures driving the evolution of specialization: directional selection toward the evolution of phenotypic heterogeneity and disruptive selection toward genetically determined specialists. Because of the lack of a singular point in the two-dimensional adaptive dynamics and the fact that directional selection is a first order process, while disruptive selection is of second order, the evolution of phenotypic heterogeneity dominates and often precludes speciation. We find that branching, and therefore genetic specialization, occurs mainly under two conditions: the presence of a cost to maintaining a high phenotypic variance or when the effect of mutations is large. A cost to high phenotypic variance dampens the strength of selection toward phenotypic heterogeneity and, when sufficiently large, introduces a singular point into

Red hair is the null phenotype of MC1R.

Science.gov (United States)

Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

2008-08-01

The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

Phenotypic characterisation and molecular polymorphism of ...

African Journals Online (AJOL)

The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was achieved on 121 ...

A Multidisciplinary Phenotyping and Genotyping Analysis of a Mapping Population Enables Quality to Be Combined with Yield in Rice

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Mariafe Calingacion

2017-05-01

Full Text Available In this study a mapping population (F8 of ca 200 progeny from a cross between the commercial rice varieties Apo and IR64 has been both genotyped and phenotyped. A genotyping-by-sequencing approach was first used to identify 2,681 polymorphic SNP markers which gave dense coverage of the genome with a good distribution across all 12 chromosomes. The coefficient of parentage was also low, at 0.13, confirming that the parents are genetically distant from each other. The progeny, together with both parents, were grown under irrigated and water restricted conditions in a randomised block design. All grain was harvested to determine variation in yield across the population. The grains were then polished following standard procedures prior to performing the phenotyping analyses. A Gas Chromatography—Mass Spectrometry approach was used to determine the volatile biochemical profiles of each line and after data curation and processing, discriminatory metabolites were putatively identified based on in-house and commercial spectral libraries. These data were used to predict the potential role of these metabolites in determining differences in aroma between genotypes. A number of QTLs for yield and for individual metabolites have been identified. Following these combined multi-disciplinary analyses, it proved possible to identify a number of lines which appeared to combine the favourable aroma attributes of IR64 with the favourable (higher yield potential of Apo. As such, these lines are excellent candidates to assess further as potential genotypes to work up into a new variety of rice which has both good yield and good quality, thus meeting the needs of both farmer and consumer alike.

Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease

DEFF Research Database (Denmark)

Jakobsen, Christian; Bartek, Jiri; Wewer, Anne Vibeke

2011-01-01

Background Few studies have compared phenotype and disease course in children and adults with inflammatory bowel disease (IBD). Aim To compare phenotype, treatment and disease course in children (<15 years) and adults (=18 years) with IBD. Methods Two population-based cohorts comprising paediatri...

Lamin A/C mutation affecting primarily the right side of the heart

Directory of Open Access Journals (Sweden)

Laura Ollila

2013-04-01

Full Text Available LMNA mutations are amongst the most important causes of familial dilated cardiomyopathy. The most important cause of arrhythmogenic right ventricular cardiomyopathy (ARVC is desmosomal pathology. The aim of the study was to elucidate the role of LMNA mutations among Finnish cardiomyopathy patients. We screened 135 unrelated cardiomyopathy patients for LMNA mutations. Because of unusual phenotype, two patients were screened for the known Finnish ARVC-related mutations of desmosomal genes, and their Plakophilin-2b gene was sequenced. Myocardial samples from two patients were examined by immunohistochemical plakoglobin staining and in one case by electron microscopy. We found a new LMNA mutation Phe237Ser in a family of five affected members with a cardiomyopathy affecting primarily the right side of the heart. The phenotype resembles ARVC but does not fulfill the Task Force Criteria. The main clinical manifestations of the mutation were severe tricuspid insufficiency, right ventricular enlargement and failure. Three of the affected patients died of the heart disease, and the two living patients received heart transplants at ages 44 and 47. Electron microscopy showed nuclear blebbing compatible with laminopathy. Immunohisto - chemical analysis did not suggest desmosomal pathology. No desmosomal mutations were found. The Phe237Ser LMNA mutation causes a phenotype different from traditional cardiolaminopathy. Our findings suggest that cardiomyopathy affecting primarily the right side of the heart is not always caused by desmosomal pathology. Our observations highlight the challenges in classifying cardiomyopathies, as there often is significant overlap between the traditional categories.

Phenotypic and genotypic characterization of antioxidant enzyme system in human population exposed to radiation from mobile towers.

Science.gov (United States)

Gulati, Sachin; Yadav, Anita; Kumar, Neeraj; Priya, Kanu; Aggarwal, Neeraj K; Gupta, Ranjan

2018-03-01

In the present era, cellular phones have changed the life style of human beings completely and have become an essential part of their lives. The number of cell phones and cell towers are increasing in spite of their disadvantages. These cell towers transmit radiation continuously without any interruption, so people living within 100s of meters from the tower receive 10,000 to 10,000,000 times stronger signal than required for mobile communication. In the present study, we have examined superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, lipid peroxidation assay, and effect of functional polymorphism of SOD and CAT antioxidant genes against mobile tower-induced oxidative stress in human population. From our results, we have found a significantly lower mean value of manganese superoxide dismutase (MnSOD) enzyme activity, catalase (CAT) enzyme activity, and a high value of lipid peroxidation assay in exposed as compared to control subjects. Polymorphisms in antioxidant MnSOD and CAT genes significantly contributed to its phenotype. In the current study, a significant association of genetic polymorphism of antioxidant genes with genetic damage has been observed in human population exposed to radiations emitted from mobile towers.

Phenotypic selection on leaf water use efficiency and related ecophysiological traits for natural populations of desert sunflowers.

Science.gov (United States)

Donovan, Lisa A; Dudley, Susan A; Rosenthal, David M; Ludwig, Fulco

2007-05-01

Plant water-use efficiency (WUE) is expected to affect plant fitness and thus be under natural selection in arid habitats. Although many natural population studies have assessed plant WUE, only a few related WUE to fitness. The further determination of whether selection on WUE is direct or indirect through functionally related traits has yielded no consistent results. For natural populations of two desert annual sunflowers, Helianthus anomalus and H. deserticola, we used phenotypic selection analysis with vegetative biomass as the proxy for fitness to test (1) whether there was direct and indirect selection on WUE (carbon isotope ratio) and related traits (leaf N, area, succulence) and (2) whether direct selection was consistent with hypothesized drought/dehydration escape and avoidance strategies. There was direct selection for lower WUE in mesic and dry H. anomalus populations, consistent with dehydration escape, even though it is the longer lived of the two species. For mesic H. anomalus, direct selection favored lower WUE and higher N, suggesting that plants may be "wasting water" to increase N delivery via the transpiration stream. For the shorter lived H. deserticola in the direr habitat, there was indirect selection for lower WUE, inconsistent with drought escape. There was also direct selection for higher leaf N, succulence and leaf size. There was no direct selection for higher WUE consistent with dehydration avoidance in either species. Thus, in these natural populations of two desert dune species higher fitness was associated with some combination direct and indirect selection for lower WUE, higher leaf N and larger leaf size. Our understanding of the adaptive value of plant ecophysiological traits will benefit from further consideration of related traits such as leaf nitrogen and more tests in natural populations.

Prevalence of weak RhD phenotype in the blood donor population ...

African Journals Online (AJOL)

Background: The weak RhD phenotype is a form of RhD antigen that, in routine RhD typing, does not react by agglutination with potent monoclonal anti-D serum, but requires addition of antiglobulin serum to demonstrate the presence of the antigen. However, the weak D antigen can cause immunization or sensitization ...

FeNO as biomarker for asthma phenotyping and management.

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Ricciardolo, Fabio L M; Sorbello, Valentina; Ciprandi, Giorgio

2015-01-01

The current review aims to revisit literature on exhaled nitric oxide (FeNO) in asthma phenotyping and management to clarify the utility of this test in clinical practice. It is increasingly evident that multiple profiles characterize asthma as a complex disease for which is necessary to find tools able to discriminate among these phenotypes to achieve the best therapeutic strategy for all asthmatic patients. Current findings indicate that FeNO, a noninvasive and easy-to-obtain biomarker, can be considered a useful tool in predicting asthma developing and exacerbation, in identifying specific asthma phenotypes, in improving asthma diagnosis and management in a selected population, and in monitoring efficacy of standard corticosteroid and biologic therapy. Based on this evidence, FeNO might become an appropriate tool for physicians to better define specific asthma phenotypes and to better deal with asthma worsening.

Adaptation to different climates results in divergent phenotypic ...

Indian Academy of Sciences (India)

The phenotypic plasticity of wing size and wing shape of Zaprionus indianus was ... C) in two natural populations living under different climates, equatorial and ... size and shape in an invasive drosophilid. J. Genet. 87, 209–217]. Introduction.

Crickets are not a free lunch: protein capture from scalable organic side-streams via high-density populations of Acheta domesticus.

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Mark E Lundy

Full Text Available It has been suggested that the ecological impact of crickets as a source of dietary protein is less than conventional forms of livestock due to their comparatively efficient feed conversion and ability to consume organic side-streams. This study measured the biomass output and feed conversion ratios of house crickets (Acheta domesticus reared on diets that varied in quality, ranging from grain-based to highly cellulosic diets. The measurements were made at a much greater population scale and density than any previously reported in the scientific literature. The biomass accumulation was strongly influenced by the quality of the diet (p99% mortality without reaching a harvestable size. Therefore, the potential for A. domesticus to sustainably supplement the global protein supply, beyond what is currently produced via grain-fed chickens, will depend on capturing regionally scalable organic side-streams of relatively high-quality that are not currently being used for livestock production.

A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

NARCIS (Netherlands)

Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P.M.A.; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

2016-01-01

Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA)

Gene-environment and protein degradation signatures characterize genomic and phenotypic diversity in wild Caenorhabditis elegans populations

NARCIS (Netherlands)

Volkers, J.M.; Snoek, L.B.; Hellenberg Hubar, van C.J.; Coopman, R.; Chen, W.; Yang, Wentao; Sterken, M.G.; Schulenburg, H.; Braeckman, B.; Kammenga, J.E.

2013-01-01

Background: Analyzing and understanding the relationship between genotypes and phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis elegans has been instrumental for unraveling genotype-phenotype relations, and has important implications for understanding the biology of

No association of CpG island methylator phenotype and colorectal cancer survival: population-based study.

Science.gov (United States)

Jia, Min; Jansen, Lina; Walter, Viola; Tagscherer, Katrin; Roth, Wilfried; Herpel, Esther; Kloor, Matthias; Bläker, Hendrik; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

2016-11-22

Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC. The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group. CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.

Musculoskeletal phenotype through the life course: the role of nutrition.

Science.gov (United States)

Ward, Kate

2012-02-01

This review considers the definition of a healthy bone phenotype through the life course and the modulating effects of muscle function and nutrition. In particular, it will emphasise that optimal bone strength (and how that is regulated) is more important than simple measures of bone mass. The forces imposed on bone by muscle loading are the primary determinants of musculoskeletal health. Any factor that changes muscle loading on the bone, or the response of bone to loading results in alterations of bone strength. Advances in technology have enhanced the understanding of a healthy bone phenotype in different skeletal compartments. Multiple components of muscle strength can also be quantified. The critical evaluation of emerging technologies for assessment of bone and muscle phenotype is vital. Populations with low and moderate/high daily Ca intakes and/or different vitamin D status illustrate the importance of nutrition in determining musculoskeletal phenotype. Changes in mass and architecture maintain strength despite low Ca intake or vitamin D status. There is a complex interaction between body fat and bone which, in addition to protein intake, is emerging as a key area of research. Muscle and bone should be considered as an integrative unit; the role of body fat requires definition. There remains a lack of longitudinal evidence to understand how nutrition and lifestyle define musculoskeletal health. In conclusion, a life-course approach is required to understand the definition of healthy skeletal phenotype in different populations and at different stages of life.

Gaucher disease types 1 and 3: Phenotypic characterization of large populations from the ICGG Gaucher Registry.

Science.gov (United States)

Grabowski, Gregory A; Zimran, Ari; Ida, Hiroyuki

2015-07-01

Study of the natural history of Gaucher disease has revealed marked phenotypic variation. Correlations to genotypes could provide insight into individual susceptibility to varying disease severity, which may impact whole-life medical care, reproductive decisions, and therapeutic choices for affected families. Importantly, pre-symptomatic or prospective interventions or the use of therapies with significant risk require accurate risk-benefit analyses based on the prognosis for individual patients. The body of international data held within the International Collaborative Gaucher Group (ICGG) Gaucher Registry provides an unprecedented opportunity to characterize the phenotypes of Gaucher disease types 1 and 3 and to appreciate demographic and ethnic factors that may influence phenotypes. The diversity of GBA gene mutations from patients with Gaucher disease represented in the ICGG Gaucher Registry database and in the literature provides the basis for initial genotype/phenotype correlations, the outcomes of which are summarized here. © 2015 Wiley Periodicals, Inc.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

Science.gov (United States)

2009-01-01

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504

Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across two abiotic environmental gradients in Poecilia mexicana.

Science.gov (United States)

Tobler, Michael; Dewitt, Thomas J; Schlupp, Ingo; García de León, Francisco J; Herrmann, Roger; Feulner, Philine G D; Tiedemann, Ralph; Plath, Martin

2008-10-01

Divergent natural selection drives evolutionary diversification. It creates phenotypic diversity by favoring developmental plasticity within populations or genetic differentiation and local adaptation among populations. We investigated phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along two abiotic environmental gradients. These fish typically inhabit nonsulfidic surface rivers, but also colonized sulfidic and cave habitats. We assessed phenotypic variation among a factorial combination of habitat types using geometric and traditional morphometrics, and genetic divergence using quantitative and molecular genetic analyses. Fish in caves (sulfidic or not) exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface or cave) exhibited larger heads and longer gill filaments. Common-garden rearing suggested that these morphological differences are partly heritable. Population genetic analyses using microsatellites as well as cytochrome b gene sequences indicate high population differentiation over small spatial scale and very low rates of gene flow, especially among different habitat types. This suggests that divergent environmental conditions constitute barriers to gene flow. Strong molecular divergence over short distances as well as phenotypic and quantitative genetic divergence across habitats in directions classic to fish ecomorphology suggest that divergent selection is structuring phenotypic variation in this system.

[The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study].

Science.gov (United States)

Krylov, M Yu; Ananyeva, L P; Koneva, О А; Starovoytova, M N; Desinova, O V; Ovsyannikova, O B; Aleksandrova, E N; Novikov, A A; Guseva, I A; Konovalova, N V; Varlamov, D A

To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture.

Directory of Open Access Journals (Sweden)

Devaveena Dey

Full Text Available BACKGROUND: Cancer stem cells exhibit close resemblance to normal stem cells in phenotype as well as function. Hence, studying normal stem cell behavior is important in understanding cancer pathogenesis. It has recently been shown that human breast stem cells can be enriched in suspension cultures as mammospheres. However, little is known about the behavior of these cells in long-term cultures. Since extensive self-renewal potential is the hallmark of stem cells, we undertook a detailed phenotypic and functional characterization of human mammospheres over long-term passages. METHODOLOGY: Single cell suspensions derived from human breast 'organoids' were seeded in ultra low attachment plates in serum free media. Resulting primary mammospheres after a week (termed T1 mammospheres were subjected to passaging every 7th day leading to the generation of T2, T3, and T4 mammospheres. PRINCIPAL FINDINGS: We show that primary mammospheres contain a distinct side-population (SP that displays a CD24(low/CD44(low phenotype, but fails to generate mammospheres. Instead, the mammosphere-initiating potential rests within the CD44(high/CD24(low cells, in keeping with the phenotype of breast cancer-initiating cells. In serial sphere formation assays we find that even though primary (T1 mammospheres show telomerase activity and fourth passage T4 spheres contain label-retaining cells, they fail to initiate new mammospheres beyond T5. With increasing passages, mammospheres showed an increase in smaller sized spheres, reduction in proliferation potential and sphere forming efficiency, and increased differentiation towards the myoepithelial lineage. Significantly, staining for senescence-associated beta-galactosidase activity revealed a dramatic increase in the number of senescent cells with passage, which might in part explain the inability to continuously generate mammospheres in culture. CONCLUSIONS: Thus, the self-renewal potential of human breast stem cells is

Direct stamp of technology or origin on the genotypic and phenotypic variation of indigenous Saccharomyces cerevisiae population in a natural model of boiled grape juice fermentation into traditional Msalais wine in China.

Science.gov (United States)

Zhu, Li-Xia; Wang, Guan-Qiong; Xue, Ju-Lan; Gou, Dong-Qi; Duan, Chang-Qing

2017-08-01

Saccharomyces cerevisiae strains worldwide show genetic and phenotypic diversity and their population substructures are greatly affected by their technological application or geographical origins. Msalais is a traditional wine obtained via a unique method of spontaneous fermentation of local boiled grape juice in Southern Xinjiang. We analyzed 436 indigenous S. cerevisiae strains associated with Msalais fermentation. These strains were highly diverse with respect to the interdelta region and 24 phenotypic traits, with apparent differentiation according to strain origins and technologies used to produce Msalais. The genetic and phenotypic diversity of strains from traditional workshops was higher than in strains from modern plants. These local strains had different origin- or technology-specific fermentative characteristics. Strains growing in large-scale fermentation tanks tolerated high temperature, whereas strains from traditional workshops tolerated high alcohol content (16%) and low temperature (13°C). Almost all the strains were characterized by the highest fermenting vigor, with weak H2S production and no histamine, cadaverine, phenethylamine and tryptamine production. Majority of strains had pronounced autolytic activity with high β-glucosidase and polygalacturonase activity and alcohol production. Our study reveals a direct stamp of technology or origin on genotypic and phenotypic variation of an indigenous S. cerevisiae population. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Left-sided congenital heart lesions in mosaic Turner syndrome.

Science.gov (United States)

Bouayed Abdelmoula, Nouha; Abdelmoula, Balkiss; Smaoui, Walid; Trabelsi, Imen; Louati, Rim; Aloulou, Samir; Aloulou, Wafa; Abid, Fatma; Kammoun, Senda; Trigui, Khaled; Bedoui, Olfa; Denguir, Hichem; Mallek, Souad; Ben Aziza, Mustapha; Dammak, Jamila; Kaabi, Oldez; Abdellaoui, Nawel; Turki, Fatma; Kaabi, Asma; Kamoun, Wafa; Jabeur, Jihen; Ltaif, Wided; Chaker, Kays; Fourati, Haytham; M'rabet, Samir; Ben Ameur, Hedi; Gouia, Naourez; Mhiri, Mohamed Nabil; Rebai, Tarek

2018-04-01

In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

The quantitative genetics of phenotypic variation in animals

NARCIS (Netherlands)

Hill, W.G.; Mulder, H.A.; Zhang, X.S.

2007-01-01

Considerable attention has been paid to estimating genetic variability in quantitative traits and to how it is maintained and changed by selection in natural and domesticated populations, but rather little attention has been paid to how levels of environmental and phenotypic variance are influenced.

Genetic versus rearing-environment effects on phenotype: hatchery and natural rearing effects on hatchery- and wild-born coho salmon.

Directory of Open Access Journals (Sweden)

Cedar M Chittenden

Full Text Available With the current trends in climate and fisheries, well-designed mitigative strategies for conserving fish stocks may become increasingly necessary. The poor post-release survival of hatchery-reared Pacific salmon indicates that salmon enhancement programs require assessment. The objective of this study was to determine the relative roles that genotype and rearing environment play in the phenotypic expression of young salmon, including their survival, growth, physiology, swimming endurance, predator avoidance and migratory behaviour. Wild- and hatchery-born coho salmon adults (Oncorhynchus kisutch returning to the Chehalis River in British Columbia, Canada, were crossed to create pure hatchery, pure wild, and hybrid offspring. A proportion of the progeny from each cross was reared in a traditional hatchery environment, whereas the remaining fry were reared naturally in a contained side channel. The resulting phenotypic differences between replicates, between rearing environments, and between cross types were compared. While there were few phenotypic differences noted between genetic groups reared in the same habitat, rearing environment played a significant role in smolt size, survival, swimming endurance, predator avoidance and migratory behaviour. The lack of any observed genetic differences between wild- and hatchery-born salmon may be due to the long-term mixing of these genotypes from hatchery introgression into wild populations, or conversely, due to strong selection in nature--capable of maintaining highly fit genotypes whether or not fish have experienced part of their life history under cultured conditions.

Phenotypic and genetic characteristics of fluoroquinolone- and methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Moreno-Flores, Antonio; Potel-Alvarellos, Carmen; Otero-Fernández, Susana; Álvarez-Fernández, Maximiliano

2017-07-20

Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) has increased in recent years. The objective of this study was to characterise two MRSA populations, one susceptible to fluoroquinolones and other resistant identifying the clonal types and the differential characteristics of both MRSA populations. Molecular typing using PFGE, MLST, spa and SSCmec was performed on 192 MRSA strains isolated from 2009 to 2011, 49 only oxacillin-resistant (OX-R) and 143 oxacillin and levofloxacin-resistant (OX-R-LEV-R). Mutations that conferred resistance to fluoroquinolones, hypermutable phenotypes and the presence of eight microbial surface components recognising adhesive matrix molecules (MSCRAMMs) were also studied. A statistically significant increase in the OX-R-LEV-R phenotype was observed (p<0.05). The most common clone of the OX-R isolates was sequence type (ST) 8 (32.6%), followed by ST72 (26.5%) and ST5 (26.5%). In the OX-R-LEV-R phenotype, the ST5 clone was the most common (65.7%), followed by ST72 (15.4%), and ST125 (12.6%). All isolates except the ST398 clone carried the SCCmecIVc. Clones ST5, ST72, ST125, and ST30 had hypermutable phenotypes. The ST72 clone and the ST30 clone in the OX-R phenotype harboured the highest number of MSCRAMMs. ST5 and ST72 clones were the most frequent clones identified in OX-R-LEV-R phenotype. Both clones showed a hypermutable phenotype that favours their selection as the fluoroquinolone resistant clones. The genetic relationships identified indicate that OX-R-LEV-R clones have evolved from OX-R MRSA clones. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation.

Science.gov (United States)

Ghoraie, Laleh Soltan; Burkowski, Forbes; Li, Shuai Cheng; Zhu, Mu

2014-01-01

Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.

Epigenetics in natural animal populations.

Science.gov (United States)

Hu, J; Barrett, R D H

2017-09-01

Phenotypic plasticity is an important mechanism for populations to buffer themselves from environmental change. While it has long been appreciated that natural populations possess genetic variation in the extent of plasticity, a surge of recent evidence suggests that epigenetic variation could also play an important role in shaping phenotypic responses. Compared with genetic variation, epigenetic variation is more likely to have higher spontaneous rates of mutation and a more sensitive reaction to environmental inputs. In our review, we first provide an overview of recent studies on epigenetically encoded thermal plasticity in animals to illustrate environmentally-mediated epigenetic effects within and across generations. Second, we discuss the role of epigenetic effects during adaptation by exploring population epigenetics in natural animal populations. Finally, we evaluate the evolutionary potential of epigenetic variation depending on its autonomy from genetic variation and its transgenerational stability. Although many of the causal links between epigenetic variation and phenotypic plasticity remain elusive, new data has explored the role of epigenetic variation in facilitating evolution in natural populations. This recent progress in ecological epigenetics will be helpful for generating predictive models of the capacity of organisms to adapt to changing climates. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

Science.gov (United States)

ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

2016-01-01

Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

Differential Impact of Lactose/Lactase Phenotype on Colonic Microflora

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Andrew Szilagyi

2010-01-01

Full Text Available BACKGROUND: The ability to digest lactose divides the world’s population into two phenotypes that may be risk variability markers for several diseases. Prebiotic effects likely favour lactose maldigesters who experience lactose spilling into their colon.

Dissecting molecular stress networks: identifying nodes of divergence between life-history phenotypes.

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Schwartz, Tonia S; Bronikowski, Anne M

2013-02-01

The complex molecular network that underlies physiological stress response is comprised of nodes (proteins, metabolites, mRNAs, etc.) whose connections span cells, tissues and organs. Variable nodes are points in the network upon which natural selection may act. Thus, identifying variable nodes will reveal how this molecular stress network may evolve among populations in different habitats and how it might impact life-history evolution. Here, we use physiological and genetic assays to test whether laboratory-born juveniles from natural populations of garter snakes (Thamnophis elegans), which have diverged in their life-history phenotypes, vary concomitantly at candidate nodes of the stress response network, (i) under unstressed conditions and (ii) in response to an induced stress. We found that two common measures of stress (plasma corticosterone and liver gene expression of heat shock proteins) increased under stress in both life-history phenotypes. In contrast, the phenotypes diverged at four nodes both under unstressed conditions and in response to stress: circulating levels of reactive oxygen species (superoxide, H(2)O(2)); liver gene expression of GPX1 and erythrocyte DNA damage. Additionally, allele frequencies for SOD2 diverge from neutral markers, suggesting diversifying selection on SOD2 alleles. This study supports the hypothesis that these life-history phenotypes have diverged at the molecular level in how they respond to stress, particularly in nodes regulating oxidative stress. Furthermore, the differences between the life-history phenotypes were more pronounced in females. We discuss the responses to stress in the context of the associated life-history phenotype and the evolutionary pressures thought to be responsible for divergence between the phenotypes. © 2012 Blackwell Publishing Ltd.

Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

Directory of Open Access Journals (Sweden)

Ruben t'Kindt

Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

Environmental, phenotypic and genetic variation of wild barley (Hordeum spontaneum) from Israel

NARCIS (Netherlands)

Vanhala, T.; Rijn, C.P.E.; Buntjer, J.; Stam, P.; Nevo, E.; Poorter, H.; Eeuwijk, van F.A.

2004-01-01

Wild relatives of crop plants offer an attractive gene pool for cultivar improvement. We evaluated genetic and phenotypic variation for a set of 72 Israeli accessions of wild barley from 21 populations. These populations were grouped further into four ecotypes. In addition, environmental variables

Wine Expertise Predicts Taste Phenotype.

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Hayes, John E; Pickering, Gary J

2012-03-01

Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

Emergent properties of gene evolution: Species as attractors in phenotypic space

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Reuveni, Eli; Giuliani, Alessandro

2012-02-01

The question how the observed discrete character of the phenotype emerges from a continuous genetic distance metrics is the core argument of two contrasted evolutionary theories: punctuated equilibrium (stable evolution scattered with saltations in the phenotype) and phyletic gradualism (smooth and linear evolution of the phenotype). Identifying phenotypic saltation on the molecular levels is critical to support the first model of evolution. We have used DNA sequences of ∼1300 genes from 6 isolated populations of the budding yeast Saccharomyces cerevisiae. We demonstrate that while the equivalent measure of the genetic distance show a continuum between lineage distance with no evidence of discrete states, the phenotypic space illustrates only two (discrete) possible states that can be associated with a saltation of the species phenotype. The fact that such saltation spans large fraction of the genome and follows by continuous genetic distance is a proof of the concept that the genotype-phenotype relation is not univocal and may have severe implication when looking for disease related genes and mutations. We used this finding with analogy to attractor-like dynamics and show that punctuated equilibrium could be explained in the framework of non-linear dynamics systems.

Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

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Franssen, Nathan R; Stewart, Laura K; Schaefer, Jacob F

2013-11-01

Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

Distinct subspecies or phenotypic plasticity? Genetic and morphological differentiation of mountain honey bees in East Africa.

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Gruber, Karl; Schöning, Caspar; Otte, Marianne; Kinuthia, Wanja; Hasselmann, Martin

2013-09-01

Identifying the forces shaping intraspecific phenotypic and genotypic divergence are of key importance in evolutionary biology. Phenotypic divergence may result from local adaptation or, especially in species with strong gene flow, from pronounced phenotypic plasticity. Here, we examine morphological and genetic divergence among populations of the western honey bee Apis mellifera in the topographically heterogeneous East African region. The currently accepted "mountain refugia hypothesis" states that populations living in disjunct montane forests belong to a different lineage than those in savanna habitats surrounding these forests. We obtained microsatellite data, mitochondrial sequences, and morphometric data from worker honey bees collected from feral colonies in three montane forests and corresponding neighboring savanna regions in Kenya. Honey bee colonies from montane forests showed distinct worker morphology compared with colonies in savanna areas. Mitochondrial sequence data did not support the existence of the two currently accepted subspecies. Furthermore, analyses of the microsatellite data with a Bayesian clustering method did not support the existence of two source populations as it would be expected under the mountain refugia scenario. Our findings suggest that phenotypic plasticity rather than distinct ancestry is the leading cause behind the phenotypic divergence observed between montane forest and savanna honey bees. Our study thus corroborates the idea that high gene flow may select for increased plasticity.

Population genetics without intraspecific data

DEFF Research Database (Denmark)

Thorne, Jeffrey L; Choi, Sang Chul; Yu, Jiaye

2007-01-01

A central goal of computational biology is the prediction of phenotype from DNA and protein sequence data. Recent models of sequence change use in silico prediction systems to incorporate the effects of phenotype on evolutionary rates. These models have been designed for analyzing sequence data...... populations, and parameters of interspecific models should have population genetic interpretations. We show, with two examples, how population genetic interpretations can be assigned to evolutionary models. The first example considers the impact of RNA secondary structure on sequence change, and the second...... reflects the tendency for protein tertiary structure to influence nonsynonymous substitution rates. We argue that statistical fit to data should not be the sole criterion for assessing models of sequence change. A good interspecific model should also yield a clear and biologically plausible population...

Phenotypic differences in leucocyte populations among healthy preterm and full-term newborns.

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Quinello, C; Silveira-Lessa, A L; Ceccon, M E J R; Cianciarullo, M A; Carneiro-Sampaio, M; Palmeira, P

2014-07-01

The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full-term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full-term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80(+) myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR-4 on myeloid DCs in all neonates compared with adults. TLR-2(+) monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR-4(+) monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4(+) T and CD19(+) B cells were higher in the three groups of neonates compared with adults, while CD4(+) effector and effector memory T cells and CD19(+) memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens. © 2014 John Wiley & Sons Ltd.

Why We Should Study the Broader Autism Phenotype in Typically Developing Populations

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Landry, Oriane; Chouinard, Philippe A.

2016-01-01

The broader autism phenotype (BAP) is a term applied to individuals with personality and cognitive traits that are similar to but milder than those observed in autism spectrum disorder (ASD). Subtle autistic traits in the core diagnostic domains of social communication and rigid behavior were described in family members of people with an ASD even…

Conspecific plasticity and invasion: invasive populations of Chinese tallow (Triadica sebifera) have performance advantage over native populations only in low soil salinity.

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Chen, Leiyi; Tiu, Candice J; Peng, Shaolin; Siemann, Evan

2013-01-01

Global climate change may increase biological invasions in part because invasive species may have greater phenotypic plasticity than native species. This may be especially important for abiotic stresses such as salt inundation related to increased hurricane activity or sea level rise. If invasive species indeed have greater plasticity, this may reflect genetic differences between populations in the native and introduced ranges. Here, we examined plasticity of functional and fitness-related traits of Chinese tallow (Triadica sebifera) populations from the introduced and native ranges that were grown along a gradient of soil salinity (control: 0 ppt; Low: 5 ppt; Medium: 10 ppt; High: 15 ppt) in a greenhouse. We used both norm reaction and plasticity index (PIv) to estimate the conspecific phenotypic plasticity variation between invasive and native populations. Overall, invasive populations had higher phenotypic plasticity of height growth rate (HGR), aboveground biomass, stem biomass and specific leaf area (SLA). The plasticity Index (PIv) of height growth rate (HGR) and SLA each were higher for plants from invasive populations. Absolute performance was always comparable or greater for plants from invasive populations versus native populations with the greatest differences at low stress levels. Our results were consistent with the "Master-of-some" pattern for invasive plants in which the fitness of introduced populations was greater in more benign conditions. This suggests that the greater conspecific phenotypic plasticity of invasive populations compared to native populations may increase invasion success in benign conditions but would not provide a potential interspecific competitive advantage in higher salinity soils that may occur with global climate change in coastal areas.

Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins

DEFF Research Database (Denmark)

Li, Shuxia; Kyvik, Kirsten Ohm; Duan, Haiping

2016-01-01

twin study on long-term stability of metabolic phenotypes in Danish and Chinese twins identified a common pattern of high genetic control over phenotype conservation, and at the same time revealed population-specific patterns of genetic and common environmental regulation on the variance as well...

Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the rat bed nucleus of the stria terminalis.

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Carter, David A

2017-07-01

The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype. This BNST population was originally identified by high, but transient expression of the EGR1 transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI). The current results confirm a high level of Egr1 activation in postnatal day 10 (PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of transient activation in female brains. Apparent cellular immaturity in this population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3, was found to be uncorrelated with both key neuronal regulator protein expression (SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co-expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at PN40. The transcriptional basis of the transient and partial catecholaminergic phenotype was investigated by analysing TFs known to maintain adult dopaminergic (TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear receptor that is critical for adult maintenance of midbrain dopamine neurons. These results detail the molecular features

Genetics of phenotypic plasticity and biomass traits in hybrid willows across contrasting environments and years.

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Berlin, Sofia; Hallingbäck, Henrik R; Beyer, Friderike; Nordh, Nils-Erik; Weih, Martin; Rönnberg-Wästljung, Ann-Christin

2017-07-01

Phenotypic plasticity can affect the geographical distribution of taxa and greatly impact the productivity of crops across contrasting and variable environments. The main objectives of this study were to identify genotype-phenotype associations in key biomass and phenology traits and the strength of phenotypic plasticity of these traits in a short-rotation coppice willow population across multiple years and contrasting environments to facilitate marker-assisted selection for these traits. A hybrid Salix viminalis  × ( S. viminalis × Salix schwerinii ) population with 463 individuals was clonally propagated and planted in three common garden experiments comprising one climatic contrast between Sweden and Italy and one water availability contrast in Italy. Several key phenotypic traits were measured and phenotypic plasticity was estimated as the trait value difference between experiments. Quantitative trait locus (QTL) mapping analyses were conducted using a dense linkage map and phenotypic effects of S. schwerinii haplotypes derived from detected QTL were assessed. Across the climatic contrast, clone predictor correlations for biomass traits were low and few common biomass QTL were detected. This indicates that the genetic regulation of biomass traits was sensitive to environmental variation. Biomass QTL were, however, frequently shared across years and across the water availability contrast. Phenology QTL were generally shared between all experiments. Substantial phenotypic plasticity was found among the hybrid offspring, that to a large extent had a genetic origin. Individuals carrying influential S. schwerinii haplotypes generally performed well in Sweden but less well in Italy in terms of biomass production. The results indicate that specific genetic elements of S. schwerinii are more suited to Swedish conditions than to those of Italy. Therefore, selection should preferably be conducted separately for such environments in order to maximize biomass

Ethnic differences: Is there an Asian phenotype for polycystic ovarian syndrome?

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Huang, Zhongwei; Yong, Eu-Leong

2016-11-01

Ethnicity has not been accounted for in the diagnostic criteria for polycystic ovarian syndrome (PCOS). It is increasingly recognised that ethnic differences are likely contributors to the differing manifestations of PCOS. Generally, rates of PCOS may be lower in East Asians. It is clear that East Asians are less hirsute than Caucasians. Hirsutism cut-off thresholds need to be lower in East Asian populations than in Caucasian populations. Despite population-adjusted scoring, Caucasians have higher hirsutism rates among patients diagnosed with PCOS. Rates of hyperandrogenaemia do not appear to differ among PCOS subjects, although serum androstenedione appeared to be higher in Caucasians in one study. Interestingly, higher prevalence of the polycystic ovarian morphology has been reported in East Asian PCOS populations than in Caucasian PCOS subjects. Hence, there is a need for comparative studies across different ethnicities to establish whether epidemiological differences observed reflect a true ethnic difference in the phenotype of PCOS and whether there is an Asian phenotype for PCOS. Copyright © 2016. Published by Elsevier Ltd.

A common reference population from four European Holstein populations increases reliability of genomic predictions

DEFF Research Database (Denmark)

Lund, Mogens Sandø; de Ross, Sander PW; de Vries, Alfred G

2011-01-01

Background Size of the reference population and reliability of phenotypes are crucial factors influencing the reliability of genomic predictions. It is therefore useful to combine closely related populations. Increased accuracies of genomic predictions depend on the number of individuals added to...

Phenotypic and metabolic traits of commercial Saccharomyces cerevisiae yeasts.

Science.gov (United States)

Barbosa, Catarina; Lage, Patrícia; Vilela, Alice; Mendes-Faia, Arlete; Mendes-Ferreira, Ana

2014-01-01

Currently, pursuing yeast strains that display both a high potential fitness for alcoholic fermentation and a favorable impact on quality is a major goal in the alcoholic beverage industry. This considerable industrial interest has led to many studies characterizing the phenotypic and metabolic traits of commercial yeast populations. In this study, 20 Saccharomyces cerevisiae strains from different geographical origins exhibited high phenotypic diversity when their response to nine biotechnologically relevant conditions was examined. Next, the fermentation fitness and metabolic traits of eight selected strains with a unique phenotypic profile were evaluated in a high-sugar synthetic medium under two nitrogen regimes. Although the strains exhibited significant differences in nitrogen requirements and utilization rates, a direct relationship between nitrogen consumption, specific growth rate, cell biomass, cell viability, acetic acid and glycerol formation was only observed under high-nitrogen conditions. In contrast, the strains produced more succinic acid under the low-nitrogen regime, and a direct relationship with the final cell biomass was established. Glucose and fructose utilization patterns depended on both yeast strain and nitrogen availability. For low-nitrogen fermentation, three strains did not fully degrade the fructose. This study validates phenotypic and metabolic diversity among commercial wine yeasts and contributes new findings on the relationship between nitrogen availability, yeast cell growth and sugar utilization. We suggest that measuring nitrogen during the stationary growth phase is important because yeast cells fermentative activity is not exclusively related to population size, as previously assumed, but it is also related to the quantity of nitrogen consumed during this growth phase.

Population structure of Vibrio fischeri within the light organs of Euprymna scolopes squid from Two Oahu (Hawaii) populations.

Science.gov (United States)

Wollenberg, M S; Ruby, E G

2009-01-01

We resolved the intraspecific diversity of Vibrio fischeri, the bioluminescent symbiont of the Hawaiian sepiolid squid Euprymna scolopes, at two previously unexplored morphological and geographical scales. These scales ranged from submillimeter regions within the host light organ to the several kilometers encompassing two host populations around Oahu. To facilitate this effort, we employed both novel and standard genetic and phenotypic assays of light-organ symbiont populations. A V. fischeri-specific fingerprinting method and five phenotypic assays were used to gauge the genetic richness of V. fischeri populations; these methods confirmed that the symbiont population present in each adult host's light organ is polyclonal. Upon statistical analysis of these genetic and phenotypic population data, we concluded that the characteristics of symbiotic populations were more similar within individual host populations than between the two distinct Oahu populations of E. scolopes, providing evidence that local geographic symbiont population structure exists. Finally, to better understand the genesis of symbiont diversity within host light organs, the process of symbiosis initiation in newly hatched juvenile squid was examined both experimentally and by mathematical modeling. We concluded that, after the juvenile hatches, only one or two cells of V. fischeri enter each of six internal epithelium-lined crypts present in the developing light organ. We hypothesize that the expansion of different, crypt-segregated, clonal populations creates the polyclonal adult light-organ population structure observed in this study. The stability of the luminous-bacterium-sepiolid squid mutualism in the presence of a polyclonal symbiont population structure is discussed in the context of contemporary evolutionary theory.

Stimulation of angiogenesis, neurogenesis and regeneration by side population cells from dental pulp.

Science.gov (United States)

Ishizaka, Ryo; Hayashi, Yuki; Iohara, Koichiro; Sugiyama, Masahiko; Murakami, Masashi; Yamamoto, Tsubasa; Fukuta, Osamu; Nakashima, Misako

2013-03-01

Mesenchymal stem cells (MSCs) have been used for cell therapy in various experimental disease models. However, the regenerative potential of MSCs from different tissue sources and the influence of the tissue niche have not been investigated. In this study, we compared the regenerative potential of dental pulp, bone marrow and adipose tissue-derived CD31(-) side population (SP) cells isolated from an individual porcine source. Pulp CD31(-) SP cells expressed the highest levels of angiogenic/neurotrophic factors and had the highest migration activity. Conditioned medium from pulp CD31(-) SP cells produced potent anti-apoptotic activity and neurite outgrowth, compared to those from bone marrow and adipose CD31(-) SP cells. Transplantation of pulp CD31(-) SP cells in a mouse hindlimb ischemia model produced higher blood flow and capillary density than transplantation of bone marrow and adipose CD31(-) SP cells. Motor function recovery and infarct size reduction were greater with pulp CD31(-) SP cells. Pulp CD31(-) SP cells induced maximal angiogenesis, neurogenesis and pulp regeneration in ectopic transplantation models compared to other tissue sources. These results demonstrate that pulp stem cells have higher angiogenic, neurogenic and regenerative potential and may therefore be superior to bone marrow and adipose stem cells for cell therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

A mathematical model of cancer cells with phenotypic plasticity

Directory of Open Access Journals (Sweden)

Da Zhou

2015-12-01

Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

Past climate change on Sky Islands drives novelty in a core developmental gene network and its phenotype.

Science.gov (United States)

Favé, Marie-Julie; Johnson, Robert A; Cover, Stefan; Handschuh, Stephan; Metscher, Brian D; Müller, Gerd B; Gopalan, Shyamalika; Abouheif, Ehab

2015-09-04

A fundamental and enduring problem in evolutionary biology is to understand how populations differentiate in the wild, yet little is known about what role organismal development plays in this process. Organismal development integrates environmental inputs with the action of gene regulatory networks to generate the phenotype. Core developmental gene networks have been highly conserved for millions of years across all animals, and therefore, organismal development may bias variation available for selection to work on. Biased variation may facilitate repeatable phenotypic responses when exposed to similar environmental inputs and ecological changes. To gain a more complete understanding of population differentiation in the wild, we integrated evolutionary developmental biology with population genetics, morphology, paleoecology and ecology. This integration was made possible by studying how populations of the ant species Monomorium emersoni respond to climatic and ecological changes across five 'Sky Islands' in Arizona, which are mountain ranges separated by vast 'seas' of desert. Sky Islands represent a replicated natural experiment allowing us to determine how repeatable is the response of M. emersoni populations to climate and ecological changes at the phenotypic, developmental, and gene network levels. We show that a core developmental gene network and its phenotype has kept pace with ecological and climate change on each Sky Island over the last ~90,000 years before present (BP). This response has produced two types of evolutionary change within an ant species: one type is unpredictable and contingent on the pattern of isolation of Sky lsland populations by climate warming, resulting in slight changes in gene expression, organ growth, and morphology. The other type is predictable and deterministic, resulting in the repeated evolution of a novel wingless queen phenotype and its underlying gene network in response to habitat changes induced by climate warming. Our

Phenotypic assortment mediates the effect of social selection in a wild beetle population

NARCIS (Netherlands)

Formica, Vincent A.; McGlothlin, Joel W.; Wood, Corlett W.; Augat, Malcolm E.; Butterfield, Rebecca E.; Barnard, Mollie E.; Brodie, Edmund D.

2011-01-01

Social interactions often have major fitness consequences, but little is known about how specific interacting phenotypes affect the strength of natural selection. Social influences on the evolutionary process can be assessed using a multilevel selection approach that partitions the effects of social

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates.

Science.gov (United States)

Storz, Jay F; Scott, Graham R; Cheviron, Zachary A

2010-12-15

High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

Population-genetic analysis of seven qualitative traits in the population of the municipality Maglaj (Bosnia and Herzegovina

Directory of Open Access Journals (Sweden)

Mrehić Elma

2015-01-01

Full Text Available On the basis of the complex seven monogenic qualitative characteristics (shape of the earlobes, hairiness of middle phalange, flexibility of lateral tongue edges, the extensiveness of the distal and proximal joint of the thumb and the flexibility of the distal phalanx of the little finger and one sexually conditioned property (digital index we analyzed the genetic structure of four populations of rural municipality Maglaj: Kosova, Novi Šeher, Jablanica, Moševac, then one isolated local population Ravna and one urban population area called Maglaj. The survey covered a total of 440 students (213 girls and 227 boys aged 11-18 years. According to the degree of genetic heterogeneity, values of Wahlund variance that are obtained for each trait belong in the category of low genetic differentiation. The maximum value of Wahlund variance was identified for the property shape of the earlobes (by Cavalli - Sforza, Bodmer = 0.0452, and the lowest for phenotypic system flexibility of lateral tongue edges (by Cavalli - Sforza, Bodmer = 0.0000. Studied set of population is the most heterogeneous according to the frequency of recessive allelogene for phenotypic characteristic shape of the earlobes, and the most homogeneous for the phenotypic trait flexibility of lateral tongue edge. Based on the analysis of genetic distance for seven phenotypic traits in populations of municipality Maglaj we established the minimum genetic distance between populations of Kosova and Maglaj (fθ = 0.0007, and the largest genetic distance between populations of Jablanica and Moševac (fθ = 0.0144. It was noted that the lowest average coefficient of kinship has a local population of Kosova (fθ = 0.0028, while the highest average coefficient of kinship has a population Moševac (fθ = 0.0081. The greatest characteristic has a population of Moševac (fθs = 0.7556, and the lowest characteristic has a population of Novi Šeher (fθs = -0.0795. Based on the obtained values of

Mechanisms by Which Phenotypic Plasticity Affects Adaptive Divergence and Ecological Speciation.

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Nonaka, Etsuko; Svanbäck, Richard; Thibert-Plante, Xavier; Englund, Göran; Brännström, Åke

2015-11-01

Phenotypic plasticity is the ability of one genotype to produce different phenotypes depending on environmental conditions. Several conceptual models emphasize the role of plasticity in promoting reproductive isolation and, ultimately, speciation in populations that forage on two or more resources. These models predict that plasticity plays a critical role in the early stages of speciation, prior to genetic divergence, by facilitating fast phenotypic divergence. The ability to plastically express alternative phenotypes may, however, interfere with the early phase of the formation of reproductive barriers, especially in the absence of geographic barriers. Here, we quantitatively investigate mechanisms under which plasticity can influence progress toward adaptive genetic diversification and ecological speciation. We use a stochastic, individual-based model of a predator-prey system incorporating sexual reproduction and mate choice in the predator. Our results show that evolving plasticity promotes the evolution of reproductive isolation under diversifying environments when individuals are able to correctly select a more profitable habitat with respect to their phenotypes (i.e., adaptive habitat choice) and to assortatively mate with relatively similar phenotypes. On the other hand, plasticity facilitates the evolution of plastic generalists when individuals have a limited capacity for adaptive habitat choice. We conclude that plasticity can accelerate the evolution of a reproductive barrier toward adaptive diversification and ecological speciation through enhanced phenotypic differentiation between diverging phenotypes.

The finite state projection approach to analyze dynamics of heterogeneous populations

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Johnson, Rob; Munsky, Brian

2017-06-01

Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity. The finite state projection (FSP) approach has often been used to analyze the statistics of independent cells. Here, we extend the FSP analysis to explore the coupling of cell dynamics and biomolecule dynamics within a population. This extension allows a general framework with which to model the state occupations of a heterogeneous, isogenic population of dividing and expiring cells. The method is demonstrated with a simple model of cell-cycle progression, which we use to explore possible dynamics of drug resistance phenotypes in dividing cells. We use this method to show how stochastic single-cell behaviors affect population level efficacy of drug treatments, and we illustrate how slight modifications to treatment regimens may have dramatic effects on drug efficacy.

Conspecific plasticity and invasion: invasive populations of Chinese tallow (Triadica sebifera have performance advantage over native populations only in low soil salinity.

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Leiyi Chen

Full Text Available Global climate change may increase biological invasions in part because invasive species may have greater phenotypic plasticity than native species. This may be especially important for abiotic stresses such as salt inundation related to increased hurricane activity or sea level rise. If invasive species indeed have greater plasticity, this may reflect genetic differences between populations in the native and introduced ranges. Here, we examined plasticity of functional and fitness-related traits of Chinese tallow (Triadica sebifera populations from the introduced and native ranges that were grown along a gradient of soil salinity (control: 0 ppt; Low: 5 ppt; Medium: 10 ppt; High: 15 ppt in a greenhouse. We used both norm reaction and plasticity index (PIv to estimate the conspecific phenotypic plasticity variation between invasive and native populations. Overall, invasive populations had higher phenotypic plasticity of height growth rate (HGR, aboveground biomass, stem biomass and specific leaf area (SLA. The plasticity Index (PIv of height growth rate (HGR and SLA each were higher for plants from invasive populations. Absolute performance was always comparable or greater for plants from invasive populations versus native populations with the greatest differences at low stress levels. Our results were consistent with the "Master-of-some" pattern for invasive plants in which the fitness of introduced populations was greater in more benign conditions. This suggests that the greater conspecific phenotypic plasticity of invasive populations compared to native populations may increase invasion success in benign conditions but would not provide a potential interspecific competitive advantage in higher salinity soils that may occur with global climate change in coastal areas.

Phenotypic differentiation is associated with gender plasticity and its responsive delay to environmental changes in Alternanthera philoxeroides--phenotypic differentiation in alligator weed.

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Wei Liu

Full Text Available Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel

Phenotypic divergence among west European populations of Reed Bunting Emberiza schoeniclus: the effects of migratory and foraging behaviours.

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Júlio M Neto

Full Text Available Divergent selection and local adaptation are responsible for many phenotypic differences between populations, potentially leading to speciation through the evolution of reproductive barriers. Here we evaluated the morphometric divergence among west European populations of Reed Bunting in order to determine the extent of local adaptation relative to two important selection pressures often associated with speciation in birds: migration and diet. We show that, as expected by theory, migratory E. s. schoeniclus had longer and more pointed wings and a slightly smaller body mass than the resident subspecies, with the exception of E. s. lusitanica, which despite having rounder wings was the smallest of all subspecies. Tail length, however, did not vary according to the expectation (shorter tails in migrants probably because it is strongly correlated with wing length and might take longer to evolve. E. s. witherbyi, which feed on insects hiding inside reed stems during the winter, had a very thick, stubby bill. In contrast, northern populations, which feed on seeds, had thinner bills. Despite being much smaller, the southern E. s. lusitanica had a significantly thicker, longer bill than migratory E. s. schoeniclus, whereas birds from the UK population had significantly shorter, thinner bills. Geometric morphometric analyses revealed that the southern subspecies have a more convex culmen than E. s. schoeniclus, and E. s. lusitanica differs from the nominate subspecies in bill shape to a greater extent than in linear bill measurements, especially in males. Birds with a more convex culmen are thought to exert a greater strength at the bill tip, which is in agreement with their feeding technique. Overall, the three subspecies occurring in Western Europe differ in a variety of traits following the patterns predicted from their migratory and foraging behaviours, strongly suggesting that these birds have became locally adapted through natural selection.

Phenotype variations affect genetic association studies of degenerative disc disease: conclusions of analysis of genetic association of 58 single nucleotide polymorphisms with highly specific phenotypes for disc degeneration in 332 subjects.

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Rajasekaran, S; Kanna, Rishi Mugesh; Senthil, Natesan; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Subramaniam, Sakthikanal; Shetty, Ajoy Prasad

2013-10-01

Although the influence of genetics on the process of disc degeneration is well recognized, in recently published studies, there is a wide variation in the race and selection criteria for such study populations. More importantly, the radiographic features of disc degeneration that are selected to represent the disc degeneration phenotype are variable in these studies. The study presented here evaluates the association between single nucleotide polymorphisms (SNPs) of candidate genes and three distinct radiographic features that can be defined as the degenerative disc disease (DDD) phenotype. The study objectives were to examine the allelic diversity of 58 SNPs related to 35 candidate genes related to lumbar DDD, to evaluate the association in a hitherto unevaluated ethnic Indian population that represents more than one-sixth of the world population, and to analyze how genetic associations can vary in the same study subjects with the choice of phenotype. A cross-sectional, case-control study of an ethnic Indian population was carried out. Fifty-eight SNPs in 35 potential candidate genes were evaluated in 342 subjects and the associations were analyzed against three highly specific markers for DDD, namely disc degeneration by Pfirrmann grading, end-plate damage evaluated by total end-plate damage score, and annular tears evaluated by disc herniations and hyperintense zones. Genotyping of cases and controls was performed on a genome-wide SNP array to identify potential associated disease loci. The results from the genome-wide SNP array were then used to facilitate SNP selection and genotype validation was conducted using Sequenom-based genotyping. Eleven of the 58 SNPs provided evidence of association with one of the phenotypes. For annular tears, rs1042631 SNP of AGC1 and rs467691 SNP of ADAMTS5 were highly significantly associated (p<.01) and SNPs in NGFB, IL1B, IL18RAP, and MMP10 were also significantly associated (p<.05). The rs4076018 SNP of NGFB was highly

Genetic architecture and phenotypic plasticity of thermally-regulated traits in an eruptive species, Dendroctonus ponderosae

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Barbara J. Bentz; Ryan B. Bracewell; Karen E. Mock; Michael E. Pfrender

2011-01-01

Phenotypic plasticity in thermally-regulated traits enables close tracking of changing environmental conditions, and can thereby enhance the potential for rapid population increase, a hallmark of outbreak insect species. In a changing climate, exposure to conditions that exceed the capacity of existing phenotypic plasticity may occur. Combining information on genetic...

The Phenotype/Genotype Correlation of Lactase Persistence among Omani Adults

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Abdulrahim Al-Abri

2013-09-01

Full Text Available Objective: To examine the correlation of lactase persistence phenotype with genotype in Omani adults.Methods: Lactase persistence phenotype was tested by hydrogen breath test in 52 Omani Adults using the Micro H2 analyzer. Results were checked against genotyping using direct DNA sequencing.Results: Forty one individuals with C/C-13910 and T/T-13915 genotypes had positive breath tests (≥20 ppm; while eight of nine individuals with T/C-13910 or T/G-13915 genotypes had negative breath tests (<20 ppm and two subjects were non-hydrogen producers. The agreement between phenotype and genotype using Kappa value was very good (0.93.Conclusion: Genotyping both T/C-13910 and T/G-13915 alleles can be used to assist diagnosis and predict lactose intolerance in the Omani population.

The phenotypic equilibrium of cancer cells: From average-level stability to path-wise convergence.

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Niu, Yuanling; Wang, Yue; Zhou, Da

2015-12-07

The phenotypic equilibrium, i.e. heterogeneous population of cancer cells tending to a fixed equilibrium of phenotypic proportions, has received much attention in cancer biology very recently. In the previous literature, some theoretical models were used to predict the experimental phenomena of the phenotypic equilibrium, which were often explained by different concepts of stabilities of the models. Here we present a stochastic multi-phenotype branching model by integrating conventional cellular hierarchy with phenotypic plasticity mechanisms of cancer cells. Based on our model, it is shown that: (i) our model can serve as a framework to unify the previous models for the phenotypic equilibrium, and then harmonizes the different kinds of average-level stabilities proposed in these models; and (ii) path-wise convergence of our model provides a deeper understanding to the phenotypic equilibrium from stochastic point of view. That is, the emergence of the phenotypic equilibrium is rooted in the stochastic nature of (almost) every sample path, the average-level stability just follows from it by averaging stochastic samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Animal biometrics: quantifying and detecting phenotypic appearance.

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Kühl, Hjalmar S; Burghardt, Tilo

2013-07-01

Animal biometrics is an emerging field that develops quantified approaches for representing and detecting the phenotypic appearance of species, individuals, behaviors, and morphological traits. It operates at the intersection between pattern recognition, ecology, and information sciences, producing computerized systems for phenotypic measurement and interpretation. Animal biometrics can benefit a wide range of disciplines, including biogeography, population ecology, and behavioral research. Currently, real-world applications are gaining momentum, augmenting the quantity and quality of ecological data collection and processing. However, to advance animal biometrics will require integration of methodologies among the scientific disciplines involved. Such efforts will be worthwhile because the great potential of this approach rests with the formal abstraction of phenomics, to create tractable interfaces between different organizational levels of life. Copyright © 2013 Elsevier Ltd. All rights reserved.

The spatial patterns of directional phenotypic selection.

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Siepielski, Adam M; Gotanda, Kiyoko M; Morrissey, Michael B; Diamond, Sarah E; DiBattista, Joseph D; Carlson, Stephanie M

2013-11-01

Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

The spatial patterns of directional phenotypic selection

KAUST Repository

Siepielski, Adam M.

2013-09-12

Local adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta-analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection. © 2013 John Wiley & Sons Ltd/CNRS.

Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

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Božić-Antić, Ivana; Ilić, Dušan; Bjekić-Macut, Jelica; Bogavac, Tamara; Vojnović-Milutinović, Danijela; Kastratovic-Kotlica, Biljana; Milić, Nataša; Stanojlović, Olivera; Andrić, Zoran; Macut, Djuro

2016-12-01

There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 European Society of Endocrinology.

Integrating modelling and phenotyping approaches to identify and screen complex traits - Illustration for transpiration efficiency in cereals.

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Chenu, K; van Oosterom, E J; McLean, G; Deifel, K S; Fletcher, A; Geetika, G; Tirfessa, A; Mace, E S; Jordan, D R; Sulman, R; Hammer, G L

2018-02-21

Following advances in genetics, genomics, and phenotyping, trait selection in breeding is limited by our ability to understand interactions within the plants and with their environments, and to target traits of most relevance for the target population of environments. We propose an integrated approach that combines insights from crop modelling, physiology, genetics, and breeding to identify traits valuable for yield gain in the target population of environments, develop relevant high-throughput phenotyping platforms, and identify genetic controls and their values in production environments. This paper uses transpiration efficiency (biomass produced per unit of water used) as an example of a complex trait of interest to illustrate how the approach can guide modelling, phenotyping, and selection in a breeding program. We believe that this approach, by integrating insights from diverse disciplines, can increase the resource use efficiency of breeding programs for improving yield gains in target populations of environments.

The ecology and evolution of animal medication: genetically fixed response versus phenotypic plasticity.

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Choisy, Marc; de Roode, Jacobus C

2014-08-01

Animal medication against parasites can occur either as a genetically fixed (constitutive) or phenotypically plastic (induced) behavior. Taking the tritrophic interaction between the monarch butterfly Danaus plexippus, its protozoan parasite Ophryocystis elektroscirrha, and its food plant Asclepias spp. as a test case, we develop a game-theory model to identify the epidemiological (parasite prevalence and virulence) and environmental (plant toxicity and abundance) conditions that predict the evolution of genetically fixed versus phenotypically plastic forms of medication. Our model shows that the relative benefits (the antiparasitic properties of medicinal food) and costs (side effects of medicine, the costs of searching for medicine, and the costs of plasticity itself) crucially determine whether medication is genetically fixed or phenotypically plastic. Our model suggests that animals evolve phenotypic plasticity when parasite risk (a combination of virulence and prevalence and thus a measure of the strength of parasite-mediated selection) is relatively low to moderately high and genetically fixed medication when parasite risk becomes very high. The latter occurs because at high parasite risk, the costs of plasticity are outweighed by the benefits of medication. Our model provides a simple and general framework to study the conditions that drive the evolution of alternative forms of animal medication.

Homeostasis in leaf water potentials on leeward and windward sides of desert shrub crowns: water loss control vs. high hydraulic efficiency.

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Iogna, Patricia A; Bucci, Sandra J; Scholz, Fabián G; Goldstein, Guillermo

2013-11-01

Phenotypic plasticity in morphophysiological leaf traits in response to wind was studied in two dominant shrub species of the Patagonian steppe, used as model systems for understanding effects of high wind speed on leaf water relations and hydraulic properties of small woody plants. Morpho-anatomical traits, hydraulic conductance and conductivity and water relations in leaves of wind-exposed and protected crown sides were examined during the summer with nearly continuous high winds. Although exposed sides of the crowns were subjected to higher wind speeds and air saturation deficits than the protected sides, leaves throughout the crown had similar minimum leaf water potential (ΨL). The two species were able to maintain homeostasis in minimum ΨL using different physiological mechanisms. Berberis microphylla avoided a decrease in the minimum ΨL in the exposed side of the crown by reducing water loss by stomatal control, loss of cell turgor and low epidermal conductance. Colliguaja integerrima increased leaf water transport efficiency to maintain transpiration rates without increasing the driving force for water loss in the wind-exposed crown side. Leaf physiological changes within the crown help to prevent the decrease of minimum ΨL and thus contribute to the maintenance of homeostasis, assuring the hydraulic integrity of the plant under unfavorable conditions. The responses of leaf traits that contribute to mechanical resistance (leaf mass per area and thickness) differed from those of large physiological traits by exhibiting low phenotypic plasticity. The results of this study help us to understand the unique properties of shrubs which have different hydraulic architecture compared to trees.

Physiological and skill demands of 'on-side' and 'off-side' games.

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Gabbett, Tim J; Jenkins, David G; Abernethy, Bruce

2010-11-01

This study investigated the physiological and skill demands of 'on-side' and 'off-side' games in elite rugby league players. Sixteen male rugby league players participated in 'on-side' and 'off-side' games. Both small-sided games were played in a 40- × 40-m playing area. The 'off-side' game permitted players to have 3 'plays' while in possession of the ball. Players were permitted to pass backward or forward (to an 'off-side' player). The 'on-side' game also permitted players to have 3 'plays' while in possession of the ball. However, players were only permitted to pass backward to players in an 'on-side' position. Heart rate and movement patterns (via global positioning system) were recorded continuously throughout both games. Data were collected on the distance covered, number of high-acceleration and velocity efforts, and recovery between efforts. Video footage was also taken to track the performance of the players. Post hoc inspection of the footage was undertaken to count the number of possessions and the number and quality of disposals. In comparison to 'on-side' games, 'off-side' games had a greater number of involvements ("touches"), passes, and effective passes. However, the cognitive demands of 'on-side' games were greater than 'off-side' games. 'Off-side' games resulted in a greater total distance covered, greater distance covered in mild and moderate accelerations, and greater distance covered in low, moderate, and high-velocity efforts. There were also a greater number of short duration recovery periods between efforts in 'off-side' games. The results of this study demonstrate that 'off-side' games provide greater physiological and skill demands than 'on-side' games. 'Off-side' games may provide a practical alternative to 'on-side' games for the development of skill and fitness in elite rugby league players.

TOMATOMA Update: Phenotypic and Metabolite Information in the Micro-Tom Mutant Resource.

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Shikata, Masahito; Hoshikawa, Ken; Ariizumi, Tohru; Fukuda, Naoya; Yamazaki, Yukiko; Ezura, Hiroshi

2016-01-01

TOMATOMA (http://tomatoma.nbrp.jp/) is a tomato mutant database providing visible phenotypic data of tomato mutant lines generated by ethylmethane sulfonate (EMS) treatment or γ-ray irradiation in the genetic background of Micro-Tom, a small and rapidly growing variety. To increase mutation efficiency further, mutagenized M3 seeds were subjected to a second round of EMS treatment; M3M1 populations were generated. These plants were self-pollinated, and 4,952 lines of M3M2 mutagenized seeds were generated. We checked for visible phenotypes in the M3M2 plants, and 618 mutant lines with 1,194 phenotypic categories were identified. In addition to the phenotypic information, we investigated Brix values and carotenoid contents in the fruits of individual mutants. Of 466 samples from 171 mutant lines, Brix values and carotenoid contents were between 3.2% and 11.6% and 6.9 and 37.3 µg g(-1) FW, respectively. This metabolite information concerning the mutant fruits would be useful in breeding programs as well as for the elucidation of metabolic regulation. Researchers are able to browse and search this phenotypic and metabolite information and order seeds of individual mutants via TOMATOMA. Our new Micro-Tom double-mutagenized populations and the metabolic information could provide a valuable genetic toolkit to accelerate tomato research and potential breeding programs. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

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Kellom, Matthew; Raymond, Jason

2016-01-01

The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

Directory of Open Access Journals (Sweden)

Matthew Kellom

Full Text Available The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

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Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

2016-08-01

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

Side Effects

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Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

Population-expression models of immune response

International Nuclear Information System (INIS)

Stromberg, Sean P; Antia, Rustom; Nemenman, Ilya

2013-01-01

The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable. (paper)

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

AlShahrani, Mona; Hoehndorf, Robert

2018-01-01

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

KAUST Repository

Alshahrani, Mona

2018-04-30

In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

Phenotypic and genetic effects of contrasting ethanol environments on physiological and developmental traits in Drosophila melanogaster.

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Luis E Castañeda

Full Text Available A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (covariances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile, using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (covariances of developmental traits, whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster.

Phenotypic and Genetic Effects of Contrasting Ethanol Environments on Physiological and Developmental Traits in Drosophila melanogaster

Science.gov (United States)

Castañeda, Luis E.; Nespolo, Roberto F.

2013-01-01

A central problem in evolutionary physiology is to understand the relationship between energy metabolism and fitness-related traits. Most attempts to do so have been based on phenotypic correlations that are not informative for the evolutionary potential of natural populations. Here, we explored the effect of contrasting ethanol environments on physiological and developmental traits, their genetic (co)variances and genetic architecture in Drosophila melanogaster. Phenotypic and genetic parameters were estimated in two populations (San Fernando and Valdivia, Chile), using a half-sib family design where broods were split into ethanol-free and ethanol-supplemented conditions. Our findings show that metabolic rate, body mass and development times were sensitive (i.e., phenotypic plasticity) to ethanol conditions and dependent on population origin. Significant heritabilities were found for all traits, while significant genetic correlations were only found between larval and total development time and between development time and metabolic rate for flies of the San Fernando population developed in ethanol-free conditions. Posterior analyses indicated that the G matrices differed between ethanol conditions for the San Fernando population (mainly explained by differences in genetic (co)variances of developmental traits), whereas the Valdivia population exhibited similar G matrices between ethanol conditions. Our findings suggest that ethanol-free environment increases the energy available to reduce development time. Therefore, our results indicate that environmental ethanol could modify the process of energy allocation, which could have consequences on the evolutionary response of natural populations of D. melanogaster. PMID:23505567

Adaptive phenotypic plasticity in the Midas cichlid fish pharyngeal jaw and its relevance in adaptive radiation

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Salzburger Walter

2011-04-01

Full Text Available Abstract Background Phenotypic evolution and its role in the diversification of organisms is a central topic in evolutionary biology. A neglected factor during the modern evolutionary synthesis, adaptive phenotypic plasticity, more recently attracted the attention of many evolutionary biologists and is now recognized as an important ingredient in both population persistence and diversification. The traits and directions in which an ancestral source population displays phenotypic plasticity might partly determine the trajectories in morphospace, which are accessible for an adaptive radiation, starting from the colonization of a novel environment. In the case of repeated colonizations of similar environments from the same source population this "flexible stem" hypothesis predicts similar phenotypes to arise in repeated subsequent radiations. The Midas Cichlid (Amphilophus spp. in Nicaragua has radiated in parallel in several crater-lakes seeded by populations originating from the Nicaraguan Great Lakes. Here, we tested phenotypic plasticity in the pharyngeal jaw of Midas Cichlids. The pharyngeal jaw apparatus of cichlids, a second set of jaws functionally decoupled from the oral ones, is known to mediate ecological specialization and often differs strongly between sister-species. Results We performed a common garden experiment raising three groups of Midas cichlids on food differing in hardness and calcium content. Analyzing the lower pharyngeal jaw-bones we find significant differences between diet groups qualitatively resembling the differences found between specialized species. Observed differences in pharyngeal jaw expression between groups were attributable to the diet's mechanical resistance, whereas surplus calcium in the diet was not found to be of importance. Conclusions The pharyngeal jaw apparatus of Midas Cichlids can be expressed plastically if stimulated mechanically during feeding. Since this trait is commonly differentiated - among

Adaptive phenotypic plasticity in the Midas cichlid fish pharyngeal jaw and its relevance in adaptive radiation.

Science.gov (United States)

Muschick, Moritz; Barluenga, Marta; Salzburger, Walter; Meyer, Axel

2011-04-30

Phenotypic evolution and its role in the diversification of organisms is a central topic in evolutionary biology. A neglected factor during the modern evolutionary synthesis, adaptive phenotypic plasticity, more recently attracted the attention of many evolutionary biologists and is now recognized as an important ingredient in both population persistence and diversification. The traits and directions in which an ancestral source population displays phenotypic plasticity might partly determine the trajectories in morphospace, which are accessible for an adaptive radiation, starting from the colonization of a novel environment. In the case of repeated colonizations of similar environments from the same source population this "flexible stem" hypothesis predicts similar phenotypes to arise in repeated subsequent radiations. The Midas Cichlid (Amphilophus spp.) in Nicaragua has radiated in parallel in several crater-lakes seeded by populations originating from the Nicaraguan Great Lakes. Here, we tested phenotypic plasticity in the pharyngeal jaw of Midas Cichlids. The pharyngeal jaw apparatus of cichlids, a second set of jaws functionally decoupled from the oral ones, is known to mediate ecological specialization and often differs strongly between sister-species. We performed a common garden experiment raising three groups of Midas cichlids on food differing in hardness and calcium content. Analyzing the lower pharyngeal jaw-bones we find significant differences between diet groups qualitatively resembling the differences found between specialized species. Observed differences in pharyngeal jaw expression between groups were attributable to the diet's mechanical resistance, whereas surplus calcium in the diet was not found to be of importance. The pharyngeal jaw apparatus of Midas Cichlids can be expressed plastically if stimulated mechanically during feeding. Since this trait is commonly differentiated--among other traits--between Midas Cichlid species, its plasticity

Playing by the rules? Phenotypic adaptation to temperate environments in an American marsupial

Science.gov (United States)

Harrigan, Ryan J.; Wayne, Robert K.

2018-01-01

Phenotypic variation along environmental gradients can provide evidence suggesting local adaptation has shaped observed morphological disparities. These differences, in traits such as body and extremity size, as well as skin and coat pigmentation, may affect the overall fitness of individuals in their environments. The Virginia opossum (Didelphis virginiana) is a marsupial that shows phenotypic variation across its range, one that has recently expanded into temperate environments. It is unknown, however, whether the variation observed in the species fits adaptive ecogeographic patterns, or if phenotypic change is associated with any environmental factors. Using phenotypic measurements of over 300 museum specimens of Virginia opossum, collected throughout its distribution range, we applied regression analysis to determine if phenotypes change along a latitudinal gradient. Then, using predictors from remote-sensing databases and a random forest algorithm, we tested environmental models to find the most important variables driving the phenotypic variation. We found that despite the recent expansion into temperate environments, the phenotypic variation in the Virginia opossum follows a latitudinal gradient fitting three adaptive ecogeographic patterns codified under Bergmann’s, Allen’s and Gloger’s rules. Temperature seasonality was an important predictor of body size variation, with larger opossums occurring at high latitudes with more seasonal environments. Annual mean temperature predicted important variation in extremity size, with smaller extremities found in northern populations. Finally, we found that precipitation and temperature seasonality as well as low temperatures were strong environmental predictors of skin and coat pigmentation variation; darker opossums are distributed at low latitudes in warmer environments with higher precipitation seasonality. These results indicate that the adaptive mechanisms underlying the variation in body size, extremity

Playing by the rules? Phenotypic adaptation to temperate environments in an American marsupial

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Sergio F. Nigenda-Morales

2018-03-01

Full Text Available Phenotypic variation along environmental gradients can provide evidence suggesting local adaptation has shaped observed morphological disparities. These differences, in traits such as body and extremity size, as well as skin and coat pigmentation, may affect the overall fitness of individuals in their environments. The Virginia opossum (Didelphis virginiana is a marsupial that shows phenotypic variation across its range, one that has recently expanded into temperate environments. It is unknown, however, whether the variation observed in the species fits adaptive ecogeographic patterns, or if phenotypic change is associated with any environmental factors. Using phenotypic measurements of over 300 museum specimens of Virginia opossum, collected throughout its distribution range, we applied regression analysis to determine if phenotypes change along a latitudinal gradient. Then, using predictors from remote-sensing databases and a random forest algorithm, we tested environmental models to find the most important variables driving the phenotypic variation. We found that despite the recent expansion into temperate environments, the phenotypic variation in the Virginia opossum follows a latitudinal gradient fitting three adaptive ecogeographic patterns codified under Bergmann’s, Allen’s and Gloger’s rules. Temperature seasonality was an important predictor of body size variation, with larger opossums occurring at high latitudes with more seasonal environments. Annual mean temperature predicted important variation in extremity size, with smaller extremities found in northern populations. Finally, we found that precipitation and temperature seasonality as well as low temperatures were strong environmental predictors of skin and coat pigmentation variation; darker opossums are distributed at low latitudes in warmer environments with higher precipitation seasonality. These results indicate that the adaptive mechanisms underlying the variation in

Interspecific competition alters natural selection on shade avoidance phenotypes in Impatiens capensis.

Science.gov (United States)

McGoey, Brechann V; Stinchcombe, John R

2009-08-01

Shade avoidance syndrome is a known adaptive response for Impatiens capensis growing in dense intraspecific competition. However, I. capensis also grow with dominant interspecific competitors in marshes. Here, we compare the I. capensis shade-avoidance phenotypes produced in the absence and presence of heterospecific competitors, as well as selection on those traits. Two treatments were established in a marsh; in one treatment all heterospecifics were removed, while in the other, all competitors remained. We compared morphological traits, light parameters, seed output and, using phenotypic selection analysis, examined directional and nonlinear selection operating in the different competitive treatments. Average phenotypes, light parameters and seed production all varied depending on competitive treatment. Phenotypic selection analyses revealed different directional, disruptive, stabilizing and correlational selection. The disparities seen in both phenotypes and selection between the treatments related to the important differences in elongation timing depending on the presence of heterospecifics, although environmental covariances between traits and fitness could also contribute. Phenotypes produced by I. capensis depend on their competitive environment, and differing selection on shade-avoidance traits between competitive environments could indirectly select for increased plasticity given gene flow between populations in different competitive contexts.

Phenotypic plasticity, costs of phenotypes, and costs of plasticity

DEFF Research Database (Denmark)

Callahan, Hilary S; Maughan, Heather; Steiner, Uli

2008-01-01

Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

Biomechanics of side impact: Injury criteria, aging occupants, and airbag technology

OpenAIRE

Yoganandan, Narayan; Pintar, Frank A.; Stemper, Brian D.; Gennarelli, Thomas A.; Weigelt, John A.

2006-01-01

This paper presents a survey of side impact trauma-related biomedical investigations with specific reference to certain aspects of epidemiology relating to the growing elderly population, improvements in technology such as side airbags geared toward occupant safety, and development of injury criteria. The first part is devoted to the involvement of the elderly by identifying variables contributing to injury including impact severity, human factors, and national and international field data. T...

Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment.

Science.gov (United States)

Moreno, Elena; Gallego, Isabel; Gregori, Josep; Lucía-Sanz, Adriana; Soria, María Eugenia; Castro, Victoria; Beach, Nathan M; Manrubia, Susanna; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M; Gómez, Jordi; Gastaminza, Pablo; Domingo, Esteban; Perales, Celia

2017-05-15

Viral quasispecies evolution upon long-term virus replication in a noncoevolving cellular environment raises relevant general issues, such as the attainment of population equilibrium, compliance with the molecular-clock hypothesis, or stability of the phenotypic profile. Here, we evaluate the adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of 200 passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus. Adaptation to the cells was evidenced by increase in progeny production. The rate of accumulation of mutations in the genomic consensus sequence deviated slightly from linearity, and mutant spectrum analyses revealed a complex dynamic of mutational waves, which was sustained beyond passage 100. The virus underwent several phenotypic changes, some of which impacted the virus-host relationship, such as enhanced cell killing, a shift toward higher virion density, and increased shutoff of host cell protein synthesis. Fluctuations in progeny production and failure to reach population equilibrium at the genomic level suggest internal instabilities that anticipate an unpredictable HCV evolution in the complex liver environment. IMPORTANCE Long-term virus evolution in an unperturbed cellular environment can reveal features of virus evolution that cannot be explained by comparing natural viral isolates. In the present study, we investigate genetic and phenotypic changes that occur upon prolonged passage of hepatitis C virus (HCV) in human hepatoma cells in an experimental design in which host cell evolutionary change is prevented. Despite replication in a noncoevolving cellular environment, the virus exhibited internal population disequilibria that did not decline with increased adaptation to the host cells. The diversification of phenotypic traits suggests that disequilibria inherent to viral populations may provide a selective advantage to viruses that can

Quantitative Seq-LGS: Genome-Wide Identification of Genetic Drivers of Multiple Phenotypes in Malaria Parasites

KAUST Repository

Abkallo, Hussein M.

2016-10-01

Identifying the genetic determinants of phenotypes that impact on disease severity is of fundamental importance for the design of new interventions against malaria. Traditionally, such discovery has relied on labor-intensive approaches that require significant investments of time and resources. By combining Linkage Group Selection (LGS), quantitative whole genome population sequencing and a novel mathematical modeling approach (qSeq-LGS), we simultaneously identified multiple genes underlying two distinct phenotypes, identifying novel alleles for growth rate and strain specific immunity (SSI), while removing the need for traditionally required steps such as cloning, individual progeny phenotyping and marker generation. The detection of novel variants, verified by experimental phenotyping methods, demonstrates the remarkable potential of this approach for the identification of genes controlling selectable phenotypes in malaria and other apicomplexan parasites for which experimental genetic crosses are amenable.

Structural determinants of phenotypic diversity and replication rate of human prions.

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Jiri G Safar

2015-04-01

Full Text Available The infectious pathogen responsible for prion diseases is the misfolded, aggregated form of the prion protein, PrPSc. In contrast to recent progress in studies of laboratory rodent-adapted prions, current understanding of the molecular basis of human prion diseases and, especially, their vast phenotypic diversity is very limited. Here, we have purified proteinase resistant PrPSc aggregates from two major phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD, determined their conformational stability and replication tempo in vitro, as well as characterized structural organization using recently emerged approaches based on hydrogen/deuterium (H/D exchange coupled with mass spectrometry. Our data clearly demonstrate that these phenotypically distant prions differ in a major way with regard to their structural organization, both at the level of the polypeptide backbone (as indicated by backbone amide H/D exchange data as well as the quaternary packing arrangements (as indicated by H/D exchange kinetics for histidine side chains. Furthermore, these data indicate that, in contrast to previous observations on yeast and some murine prion strains, the replication rate of sCJD prions is primarily determined not by conformational stability but by specific structural features that control the growth rate of prion protein aggregates.

Phenotypes of asthma revisited upon the presence of atopy.

Science.gov (United States)

Nieves, Ana; Magnan, Antoine; Boniface, Stéphanie; Proudhon, Hervé; Lanteaume, André; Romanet, Stéphanie; Vervloet, Daniel; Godard, Philippe

2005-03-01

Immunological studies claimed that atopic and non-atopic asthma share more similarities than differences. However, these two phenotypes of asthma are considered to be distinguishable upon distinct clinical patterns, which were not systematically assessed before in a large population. We studied characteristics discriminating atopic from non-atopic asthma among 751 asthmatic patients and 80 factors were analysed in univariate and multivariate analysis. Age, age of onset of asthma, female/male ratio were higher in non-atopic (n=200) than in atopic (n=551) asthmatics. Familial asthma, seasonal symptoms, rhinitis, conjunctivitis, allergen-triggered symptoms, improvement in altitude, exercise-induced asthma were associated with atopy. Non-atopic asthmatics displayed lower FEV(1) and FVC. Smoking was more frequent and asthma was more severe in these patients. Younger age, early onset, male sex, rhinitis and smoking were independent factors discriminating atopic from non-atopic asthma. This study establishes in a large population of asthmatics that although similarities exist between atopic and non-atopic asthma, two clinical phenotypes can still distinguish both kinds of asthma.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

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Adrian Biddle

2016-02-01

Full Text Available Cancer stem cells (CSCs drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT and mesenchymal-to-epithelial transition (MET to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC, we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

Science.gov (United States)

Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

2016-02-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape.

Science.gov (United States)

Bernstein, Rachel; Schmidt, Kierstin L; Harbury, Pehr B; Marqusee, Susan

2011-06-28

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated.

The incidence of inflammatory bowel disease in Northern China: a prospective population-based study.

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Hong Yang

Full Text Available AIMS & BACKGROUNDS: Although inflammatory bowel diseases (IBD are emerging and increasing in China, epidemiologic data are rarely available. This study was to investigate the epidemiological and clinical characteristics of IBD in Northern China. METHODS: This is a prospective, population-based study of incidence of IBD in Daqing, Heilongjiang province of Northern China from March 1, 2012 to February 28, 2013. All incident patients with IBD were clinically identified by IBD specialist group from five main General Hospitals covering the healthcare service for 1,343,364 residents in the urban areas of Daqing. IBD cases included in this study were followed-up for three months for diagnosis confirmation. RESULTS: A total of 27 new IBD cases including 25 cases of ulcerative colitis (UC and 2 cases of Crohn's disease (CD were identified. The population at risk was 1,343,364 person years. Age-adjusted incidence for total IBD, CD and UC were 1.77, 0.13, and 1.64 per 100,000 population, respectively. A male predominance was found in CD patients (male to female ratio was 2 ∶ 0. In contrast, no obvious gender predominance was found in UC patients (male to female ratio was 1 ∶ 1.1. CD patients were diagnosed at an average age of 39.5 years. The main disease phenotypes of UC were distal colitis with a 24% of proctitis and 56% of left-sided colitis. The mean diagnostic age of UC patients was 48.9 years. CONCLUSIONS: This is the first report on the incidence of IBD in the Northern Chinese population. A lower incidence of IBD, similar male predominance for CD, similar disease phenotype of UC, and lower disease activity was observed in Daqing compared to that in Southern China.

Predictable Phenotypes of Antibiotic Resistance Mutations.

Science.gov (United States)

Knopp, M; Andersson, D I

2018-05-15

Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

Nonlinear electron acoustic structures generated on the high-potential side of a double layer

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R. Pottelette

2009-04-01

Full Text Available High-time resolution measurements of the electron distribution function performed in the auroral upward current region reveals a large asymmetry between the low- and high-potential sides of a double-layer. The latter side is characterized by a large enhancement of a locally trapped electron population which corresponds to a significant part (~up to 30% of the total electron density. As compared to the background hot electron population, this trapped component has a very cold temperature in the direction parallel to the static magnetic field. Accordingly, the differential drift between the trapped and background hot electron populations generates high frequency electron acoustic waves in a direction quasi-parallel to the magnetic field. The density of the trapped electron population can be deduced from the frequency where the electron acoustic spectrum maximizes. In the auroral midcavity region, the electron acoustic waves may be modulated by an additional turbulence generated in the ion acoustic range thanks to the presence of a pre-accelerated ion beam located on the high-potential side of the double layer. Electron holes characterized by bipolar pulses in the electric field are sometimes detected in correlation with these electron acoustic wave packets.

Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

DEFF Research Database (Denmark)

Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang

2016-01-01

OBJECTIVE: The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic...... pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23-64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype. RESULTS: Moderate to high...... contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated...

Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

Energy Technology Data Exchange (ETDEWEB)

Wang, Daniel [Iowa State University; Phan, Ngoc [Iowa State University; Isely, Christopher [Iowa State University; Bruene, Lucas [Iowa State University; Bratlie, Kaitlin M [Ames Laboratory

2014-11-10

Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

Reciprocal osmotic challenges reveal mechanisms of divergence in phenotypic plasticity in the killifish Fundulus heteroclitus.

Science.gov (United States)

Brennan, Reid S; Galvez, Fernando; Whitehead, Andrew

2015-04-15

The killifish Fundulus heteroclitus is an estuarine species with broad physiological plasticity, enabling acclimation to diverse stressors. Previous work suggests that freshwater populations expanded their physiology to accommodate low salinity environments; however, it is unknown whether this compromises their tolerance to high salinity. We used a comparative approach to investigate the mechanisms of a derived freshwater phenotype and the fate of an ancestral euryhaline phenotype after invasion of a freshwater environment. We compared physiological and transcriptomic responses to high- and low-salinity stress in fresh and brackish water populations and found an enhanced plasticity to low salinity in the freshwater population coupled with a reduced ability to acclimate to high salinity. Transcriptomic data identified genes with a conserved common response, a conserved salinity-dependent response and responses associated with population divergence. Conserved common acclimation responses revealed stress responses and alterations in cell-cycle regulation as important mechanisms in the general osmotic response. Salinity-specific responses included the regulation of genes involved in ion transport, intracellular calcium, energetic processes and cellular remodeling. Genes diverged between populations were primarily those showing salinity-specific expression and included those regulating polyamine homeostasis and the cell cycle. Additionally, when populations were matched with their native salinity, expression patterns were consistent with the concept of 'transcriptomic resilience', suggesting local adaptation. These findings provide insight into the fate of a plastic phenotype after a shift in environmental salinity and help to reveal mechanisms allowing for euryhalinity. © 2015. Published by The Company of Biologists Ltd.

The importance of environment on respiratory genotype/phenotype relationships in the Inuit

DEFF Research Database (Denmark)

Candelaria, P V; Backer, Vibeke; Khoo, S-K

2010-01-01

Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry....

Genome-wide recombination dynamics are associated with phenotypic variation in maize.

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Pan, Qingchun; Li, Lin; Yang, Xiaohong; Tong, Hao; Xu, Shutu; Li, Zhigang; Li, Weiya; Muehlbauer, Gary J; Li, Jiansheng; Yan, Jianbing

2016-05-01

Meiotic recombination is a major driver of genetic diversity, species evolution, and agricultural improvement. Thus, an understanding of the genetic recombination landscape across the maize (Zea mays) genome will provide insight and tools for further study of maize evolution and improvement. Here, we used c. 50 000 single nucleotide polymorphisms to precisely map recombination events in 12 artificial maize segregating populations. We observed substantial variation in the recombination frequency and distribution along the ten maize chromosomes among the 12 populations and identified 143 recombination hot regions. Recombination breakpoints were partitioned into intragenic and intergenic events. Interestingly, an increase in the number of genes containing recombination events was accompanied by a decrease in the number of recombination events per gene. This kept the overall number of intragenic recombination events nearly invariable in a given population, suggesting that the recombination variation observed among populations was largely attributed to intergenic recombination. However, significant associations between intragenic recombination events and variation in gene expression and agronomic traits were observed, suggesting potential roles for intragenic recombination in plant phenotypic diversity. Our results provide a comprehensive view of the maize recombination landscape, and show an association between recombination, gene expression and phenotypic variation, which may enhance crop genetic improvement. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Digest: Plants adapt under attack: genotypic selection and phenotypic plasticity under herbivore pressure.

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Hawkins, Nichola J

2018-03-31

Plant species adapt to changing environmental conditions through phenotypic plasticity and natural selection. Agrawal et al. (2018) found that dandelions responded to the presence of insect pests by producing higher levels of defensive compounds. This defensive response resulted both from phenotypic plasticity, with individual plants' defenses triggered by insect attack, and from evolution by natural selection acting on genetic variation in the plant population. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Advanced phenotyping offers opportunities for improved breeding of forage and turf species

DEFF Research Database (Denmark)

Walter, Achim; Studer, Bruno; Kölliker, Roland

2012-01-01

Background and Aims Advanced phenotyping, i.e. the application of automated, high-throughput methods to characterize plant architecture and performance, has the potential to accelerate breeding progress but is far from being routinely used in current breeding approaches. In forage and turf...... improvement programmes, in particular, where breeding populations and cultivars are characterized by high genetic diversity and substantial genotype × environment interactions, precise and efficient phenotyping is essential to meet future challenges imposed by climate change, growing demand and declining...... resources. Scope This review highlights recent achievements in the establishment of phenotyping tools and platforms. Some of these tools have originally been established in remote sensing, some in precision agriculture, while others are laboratory-based imaging procedures. They quantify plant colour...

Cardiovascular malformations caused by NOTCH1 mutations do not keep left : data on 428 probands with left-sided CHD and their families

NARCIS (Netherlands)

Kerstjens-Frederikse, Wilhelmina S.; van de Laar, Ingrid M. B. H.; Vos, Yvonne J.; Verhagen, Judith M. A.; Berger, Rolf M. F.; Lichtenbelt, Klaske D.; Wassink-Ruiter, Jolien S. Klein; van der Zwaag, Paul A.; Sarvaas, Gideon J. du Marchie; Bergman, Klasien A.; Bilardo, Catia M.; Roos-Hesselink, Jolien W.; Janssen, Johan H. P.; Frohn-Mulder, Ingrid M.; van Spaendonck-Zwarts, Karin Y.; Melle, van Joost P.; Hofstra, Robert M. W.; Wessels, M. W.

Purpose: We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, and hypoplastic left heart syndrome. Methods: NOTCH1 was screened for

A single nucleotide polymorphism (SNP) assay for population ...

African Journals Online (AJOL)

A single nucleotide polymorphism (SNP) assay for population stratification test ... phenotypes and unlinked candidate loci in case-control and cohort studies of ... Key words: Chinese, Japanese, population stratification, ancestry informative ...

Reported Sildenafil Side Effects in Pediatric Pulmonary Hypertension Patients

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Stephanie Leigh Siehr

2015-03-01

Full Text Available Background: Sildenafil, a phosphodiestase type 5 inhibitor, was approved in 2005 for the treatment of pulmonary arterial hypertension (PAH in adults, and is commonly used off-label for pediatric patients. Little is known, however, about sildenafil’s side effects in this population.Methods: Single institution, longitudinal survey-based study performed in an outpatient pediatric cardiology clinic. Pediatric patients on sildenafil (alone or in combination with other PH therapies completed questionnaires regarding frequency of vascular, gastrointestinal, neurologic and hematologic side effects. Results: Between January 2011 and May 2014, 66 pediatric patients with PH on sildenafil filled out 214 surveys, 32 patients (96 surveys on monotherapy, and 43 patients (118 surveys on sildenafil plus an endothelin receptor antagonist (bosentan or ambrisentan and/or a prostacyclin (epoprostenol or treprostinil. Overall, 30% of respondents identified at least one side effect. For all patients on sildenafil, incidence of side effects by system was 37% gastrointestinal, 35% vascular and 22% neurologic. For patients on sildenafil monotherapy, incidence of side effects by system was 24% gastrointestinal, 21% vascular and 18% neurologic compared to patients on combination therapy who reported an incidence of 48% gastrointestinal, 45% vascular and 25% neurologic.Conclusion: Incidence of vascular, gastrointestinal and neurologic side effect in pediatric patients on sildenafil therapy for pulmonary arterial hypertension was 30%. Side effects were more common in patients on combination therapy with an endothelin receptor antagonist and/or prostacyclin than in patients on sildenafil monotherapy.

SOX10 mutation causes Waardenburg syndrome associated with distinctive phenotypic features in an Iranian family: A clue for phenotype-directed genetic analysis.

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Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Alimadadi, Hossein; Noori-Daloii, Mohammad Reza

2017-05-01

Waardenburg syndrome (WS) is a neurocristopathy characterized by hearing impairment and pigmentary disturbances in hair, eyes, and skin. WS is clinically heterogeneous and can be subdivided into four major types (WS1-WS4) where WS4 or Shah-Waardenburg is diagnosed when WS2 is accompanied by Hirschsprung disease (HD). Mutations of SOX10, EDN3/EDNRB have been identified in association with WS4. This study was aimed to determine the pathogenic variant in an Iranian pedigree affected with WS4. A two-generation pedigree with three affected members and considerable phenotypic heterogeneity was recruited. The proband was a 15-year-old boy, with severe to profound sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eyes and Hirschprung disease. The other two also presented characteristics of WS2 and complained of chronic constipation with normal anorectal reflex. Sequencing of all exons and exon-intron boundaries of SOX10, EDN3/EDNRB revealed a heterozygous variant c.422T > C in exon 3 of SOX10 confirmed by a series of evidence to be pathogenic. It resulted in p.L141P at the protein level. Leucin 141 is located in Nuclear Export signal, HMG box of the protein. This study is the first report of a WS4 family in the Iranian population. The mutation is associated with distinctive phenotypic profile (association of anosmia and chronic constipation with SOX10 mutations) and could further improve diagnosis and counseling of WS in the Iranian population and can contribute to phenotype-directed genetic analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of environment and core-margin effects on range-wide phenotypic variation in a montane grasshopper.

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Noguerales, V; García-Navas, V; Cordero, P J; Ortego, J

2016-11-01

The integration of genetic information with ecological and phenotypic data constitutes an effective approach to gain insight into the mechanisms determining interpopulation variability and the evolutionary processes underlying local adaptation and incipient speciation. Here, we use the Pyrenean Morales grasshopper (Chorthippus saulcyi moralesi) as study system to (i) analyse the relative role of genetic drift and selection in range-wide patterns of phenotypic differentiation and (ii) identify the potential selective agents (environment, elevation) responsible for variation. We also test the hypothesis that (iii) the development of dispersal-related traits is associated with different parameters related to population persistence/turnover, including habitat suitability stability over the last 120 000 years, distance to the species distribution core and population genetic variability. Our results indicate that selection shaped phenotypic differentiation across all the studied morphological traits (body size, forewing length and shape). Subsequent analyses revealed that among-population differentiation in forewing length was significantly explained by a temperature gradient, suggesting an adaptive response to thermoregulation or flight performance under contrasting temperature regimes. We found support for our hypothesis predicting a positive association between the distance to the species distribution core and the development of dispersal-related morphology, which suggests an increased dispersal capability in populations located at range edges that, in turn, exhibit lower levels of genetic variability. Overall, our results indicate that range-wide patterns of phenotypic variation are partially explained by adaptation in response to local environmental conditions and differences in habitat persistence between core and peripheral populations. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary

Environmental and phenotype-related risk factors for owner-reported allergic/atopic skin symptoms and for canine atopic dermatitis verified by veterinarian in a Finnish dog population.

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Anturaniemi, Johanna; Uusitalo, Liisa; Hielm-Björkman, Anna

2017-01-01

The aim of this cross-sectional study was to observe whether environmental factors and phenotypic traits are associated with owner-reported skin problems and with veterinary diagnosed canine atopic dermatitis (CAD). Data were collected using the validated online DOGRISK questionnaire. Out of the data that the questionnaire provides for analysis, focus was first turned towards addressing questions regarding 'Atopy/allergy (skin symptoms)' using a total of 8643 dogs: 1585 dogs with owner-reported allergic/atopic skin symptoms and 7058 dogs without. A subsequent analysis compared dogs with veterinary-verified CAD (n = 322) as a case group against the 7058 dogs without owner-reported skin symptoms. The association between 21 factors related to the environment, canine phenotypes and breed groups within both populations were analysed using univariable and multivariable logistic regression. The environmental factors that showed a significant inverse association with the risk of owner-reported allergic/atopic skin symptoms were as following: whether the dog was living in a detached house, whether there were other dogs in the household, and whether the dog was born in the current household. Having over 50% white colour in the coat and living in an extremely clean household were significantly associated with an increased risk of owner-reported allergic/atopic skin symptoms. The five breeds demonstrating the highest proportion of owner-reported allergic/atopic skin symptoms were West Highland white terrier, Boxer, English bulldog, Dalmatian and French bulldog. The Fédération Cynologique Internationale dog breed groups 3 (Terriers) and 6 (Scent hounds and related breeds) showed a significantly higher risk for owner-reported allergic/atopic skin symptoms than mixed breed dogs. In the second population, the inverse association was observed between the risk of CAD and the presence of other dogs in the household, and whether the dog had been born in the current household. The

Environmental and phenotype-related risk factors for owner-reported allergic/atopic skin symptoms and for canine atopic dermatitis verified by veterinarian in a Finnish dog population.

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Johanna Anturaniemi

Full Text Available The aim of this cross-sectional study was to observe whether environmental factors and phenotypic traits are associated with owner-reported skin problems and with veterinary diagnosed canine atopic dermatitis (CAD. Data were collected using the validated online DOGRISK questionnaire. Out of the data that the questionnaire provides for analysis, focus was first turned towards addressing questions regarding 'Atopy/allergy (skin symptoms' using a total of 8643 dogs: 1585 dogs with owner-reported allergic/atopic skin symptoms and 7058 dogs without. A subsequent analysis compared dogs with veterinary-verified CAD (n = 322 as a case group against the 7058 dogs without owner-reported skin symptoms. The association between 21 factors related to the environment, canine phenotypes and breed groups within both populations were analysed using univariable and multivariable logistic regression. The environmental factors that showed a significant inverse association with the risk of owner-reported allergic/atopic skin symptoms were as following: whether the dog was living in a detached house, whether there were other dogs in the household, and whether the dog was born in the current household. Having over 50% white colour in the coat and living in an extremely clean household were significantly associated with an increased risk of owner-reported allergic/atopic skin symptoms. The five breeds demonstrating the highest proportion of owner-reported allergic/atopic skin symptoms were West Highland white terrier, Boxer, English bulldog, Dalmatian and French bulldog. The Fédération Cynologique Internationale dog breed groups 3 (Terriers and 6 (Scent hounds and related breeds showed a significantly higher risk for owner-reported allergic/atopic skin symptoms than mixed breed dogs. In the second population, the inverse association was observed between the risk of CAD and the presence of other dogs in the household, and whether the dog had been born in the current

Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population

DEFF Research Database (Denmark)

Nissen, Peter H; Christensen, Signe E; Heickendorff, Lene

2007-01-01

CONTEXT: The autosomal dominantly inherited condition familial hypocalciuric hypercalcemia (FHH) is characterized by elevated plasma calcium levels, relative or absolute hypocalciuria, and normal to moderately elevated plasma PTH. The condition is difficult to distinguish clinically from primary...... hyperparathyroidism and is caused by inactivating mutations in the calcium sensing receptor (CASR) gene. OBJECTIVE: We sought to define the mutation spectrum of the CASR gene in a Danish FHH population and to establish genotype-phenotype relationships regarding the different mutations. DESIGN AND PARTICIPANTS...

Population genomics of parallel adaptation in threespine stickleback using sequenced RAD tags.

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Paul A Hohenlohe

2010-02-01

Full Text Available Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus. We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP-based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such

Identification of extreme motor phenotypes in Huntington's disease.

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Braisch, Ulrike; Hay, Birgit; Muche, Rainer; Rothenbacher, Dietrich; Landwehrmeyer, G Bernhard; Long, Jeffrey D; Orth, Michael

2017-04-01

The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using quantile regression for longitudinal data. More than 15% of HD participants had an extreme TMS phenotype for at least one visit. In contrast, only about 4% of participants were consistent TMS extremes at two or more visits. Data from healthy controls revealed an upper cut-off of 13 for the TMS representing the extreme of motor ratings for a normal aging population. In HD, boundaries of motor age-at-onset based on diagnostic confidence or derived from the TMS data cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an individual carrying the HD mutation indicates a high likelihood of motor manifestations of HD irrespective of CAG repeat length or age. The identification of motor phenotype extremes can be useful in the search for disease modifiers, for example, genetic or environmental such as medication. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6∗10 on Interindividual Variation in a Chinese Population

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Pei Hu

2017-05-01

Full Text Available Purpose: Asian populations have around 40–60% frequency of reduced function allele CYP2D6∗10 compared to 1–2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6∗10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6∗10 allele or two CYP2D6∗10 alleles has not been reported in large Asian populations.Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing. A total of 235 subjects with CYP2D6∗1/∗1 (n = 22, CYP2D6∗1/∗10 (n = 93, CYP2D6∗10/∗10 (n = 85, and CYP2D6∗5/∗10 (n = 35 were phenotyped for CYP2D6 using dextromethorphan as the probe drug. Metabolic ratios (MR were calculated as the ratio of parent drug to metabolite in 0–3 h urine, 3 h plasma, and 3 h saliva for each sample type.Results: The urinary, plasma, or salivary MRs increased successively in subjects with CYP2D6∗1/∗1, ∗1/∗10, ∗10/∗10, and ∗5/∗10 (all P < 0.001. In the normal metabolizer group, homozygous CYP2D6∗10/∗10 decreased the CYP2D6 enzyme activity further than heterozygous CYP2D6∗1/∗10. Urinary, plasma, and salivary MRs were highly correlated.Conclusion: The normal metabolizer group calls for a more detailed classification. The activity score system could more accurately predict enzyme activity than by grouping a number of genotypes into a single phenotype group. Single-point plasma samples and saliva samples could be used as alternative phenotyping methods for clinical convenience.

Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments.

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Rubio de Casas, R; Vargas, P; Pérez-Corona, E; Cano, E; Manrique, E; García-Verdugo, C; Balaguer, L

2009-05-01

Evergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and beta-carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.

Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

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Yook Karen

2011-01-01

Full Text Available Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO. The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and

The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

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Paulina Krzyszczyk

2018-05-01

Full Text Available Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes to anti-inflammatory (M2-like phenotypes. Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1 expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds.

The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

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Krzyszczyk, Paulina; Schloss, Rene; Palmer, Andre; Berthiaume, François

2018-01-01

Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds. PMID:29765329

Ecological genetics of freshwater fish: a short review of the genotype–phenotype connection

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Vidal, O.

2011-12-01

Full Text Available Molecular ecology or ecological genetics is an expanding application of population genetics which has flourished in the last two decades but it is dominated by systematic and phylogeographic studies, with relatively little emphasis on the study of the genetic basis of the process of adaptation to different ecological conditions. The relationship between genotype and adaptive phenotypes is weak because populations are often difficult to quantify and experiments are logistically challenging or unfeasible. Interestingly, in freshwater fish, studies to characterize the genetic architecture of adaptive traits are not as rare as in other vertebrate groups. In this review, we summarize the few cases where the relationship between the ecology and genetics of freshwater fish is more developed, namely the relationship between genetic markers and ecological phenotypes.

Toward understanding of the role of reversibility of phenotypic switching in the evolution of resistance to therapy

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Horvath, D.; Brutovsky, B.

2018-06-01

Reversibility of state transitions is intensively studied topic in many scientific disciplines over many years. In cell biology, it plays an important role in epigenetic variation of phenotypes, known as phenotypic plasticity. More interestingly, the cell state reversibility is probably crucial in the adaptation of population phenotypic heterogeneity to environmental fluctuations by evolving bet-hedging strategy, which might confer to cancer cells resistance to therapy. In this article, we propose a formalization of the evolution of highly reversible states in the environments of periodic variability. Two interrelated models of heterogeneous cell populations are proposed and their behavior is studied. The first model captures selection dynamics of the cell clones for the respective levels of phenotypic reversibility. The second model focuses on the interplay between reversibility and drug resistance in the particular case of cancer. Overall, our results show that the threshold dependencies are emergent features of the investigated model with eventual therapeutic relevance. Presented examples demonstrate importance of taking into account cell to cell heterogeneity within a system of clones with different reversibility quantified by appropriately chosen genetic and epigenetic entropy measures.

Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure.

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Sophie Roetynck

Full Text Available Multiparameter flow cytometry has revealed extensive phenotypic and functional heterogeneity of CD4 T cell responses in mice and humans, emphasizing the importance of assessing multiple aspects of the immune response in correlation with infection or vaccination outcome. The aim of this study was to establish and validate reliable and feasible flow cytometry assays, which will allow us to characterize CD4 T cell population in humans in field studies more fully.We developed polychromatic flow cytometry antibody panels for immunophenotyping the major CD4 T cell subsets as well as broadly characterizing the functional profiles of the CD4 T cells in peripheral blood. We then validated these assays by conducting a pilot study comparing CD4 T cell responses in distinct populations of healthy adults living in either rural or urban Kenya. This study revealed that the expression profile of CD4 T cell activation and memory markers differed significantly between African and European donors but was similar amongst African individuals from either rural or urban areas. Adults from rural Kenya had, however, higher frequencies and greater polyfunctionality among cytokine producing CD4 T cells compared to both urban populations, particularly for "Th1" type of response. Finally, endemic exposure to malaria in rural Kenya may have influenced the expansion of few discrete CD4 T cell populations with specific functional signatures.These findings suggest that environmentally driven T cell activation does not drive the dysfunction of CD4 T cells but is rather associated with greater magnitude and quality of CD4 T cell response, indicating that the level or type of microbial exposure and antigenic experience may influence and shape the functionality of CD4 T cell compartment. Our data confirm that it is possible and mandatory to assess multiple functional attributes of CD4 T cell response in the context of infection.

Morphological analysis and DNA methylation in Conyza bonariensis L. cronquist (Asteraceae phenotypes

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Juliana Maria de Paula

2017-08-01

Full Text Available ABSTRACT The species Conyza bonariensis (L. cause losses in agriculture due to their invasive capacity and resistance to herbicides like glyphosate. The species of this genus exhibit phenotypic plasticity, which complicates their identification and characterization. Thus, experiments were performed with 2 extreme C. bonariensis phenotypes (called broad leaf and narrow leaf in greenhouse conditions and in the laboratory, in order to verify if the morphological differences among these phenotypes are a genetic character or result from environmental effects. In addition to the comparative morphological analysis, assessment of DNA methylation profile was performed to detect the occurrence, or not, of differences in the epigenetic level. The morphological characteristics evaluated were length, width, shape, margin and leaves indument; plant height and stem indument; the number of capitula, flowers and seeds. The Methylation Sensitive Amplified Polymorphism technique was used to investigate the methylation levels. The morphological differences of phenotypes supposed to be C. bonariensis are probably genetic in origin and not the result of environmental effects, since, after 6 crop cycles in a greenhouse under the same environmental conditions, these phenotypes remained with the same morphological characteristics and seed production in relation to the original phenotypes found in the collection site. The different phenotypes did not show differences corresponding to DNA methylation patterns that could indicate an epigenetic effect as the cause of the differences between the 2 phenotypes. The results of morphological analysis and methylation probably indicate that maybe they are individuals of populations from different taxa not registered yet in the literature.

Homogenizing bacterial cell factories: Analysis and engineering of phenotypic heterogeneity.

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Binder, Dennis; Drepper, Thomas; Jaeger, Karl-Erich; Delvigne, Frank; Wiechert, Wolfgang; Kohlheyer, Dietrich; Grünberger, Alexander

2017-07-01

In natural habitats, microbes form multispecies communities that commonly face rapidly changing and highly competitive environments. Thus, phenotypic heterogeneity has evolved as an innate and important survival strategy to gain an overall fitness advantage over cohabiting competitors. However, in defined artificial environments such as monocultures in small- to large-scale bioreactors, cell-to-cell variations are presumed to cause reduced production yields as well as process instability. Hence, engineering microbial production toward phenotypic homogeneity is a highly promising approach for synthetic biology and bioprocess optimization. In this review, we discuss recent studies that have unraveled the cell-to-cell heterogeneity observed during bacterial gene expression and metabolite production as well as the molecular mechanisms involved. In addition, current single-cell technologies are briefly reviewed with respect to their applicability in exploring cell-to-cell variations. We highlight emerging strategies and tools to reduce phenotypic heterogeneity in biotechnological expression setups. Here, strain or inducer modifications are combined with cell physiology manipulations to achieve the ultimate goal of equalizing bacterial populations. In this way, the majority of cells can be forced into high productivity, thus reducing less productive subpopulations that tend to consume valuable resources during production. Modifications in uptake systems, inducer molecules or nutrients represent valuable tools for diminishing heterogeneity. Finally, we address the challenge of transferring homogeneously responding cells into large-scale bioprocesses. Environmental heterogeneity originating from extrinsic factors such as stirring speed and pH, oxygen, temperature or nutrient distribution can significantly influence cellular physiology. We conclude that engineering microbial populations toward phenotypic homogeneity is an increasingly important task to take biotechnological

Phenotypic variability in unicellular organisms: from calcium signalling to social behaviour.

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Vogel, David; Nicolis, Stamatios C; Perez-Escudero, Alfonso; Nanjundiah, Vidyanand; Sumpter, David J T; Dussutour, Audrey

2015-11-22

Historically, research has focused on the mean and often neglected the variance. However, variability in nature is observable at all scales: among cells within an individual, among individuals within a population and among populations within a species. A fundamental quest in biology now is to find the mechanisms that underlie variability. Here, we investigated behavioural variability in a unique unicellular organism, Physarum polycephalum. We combined experiments and models to show that variability in cell signalling contributes to major differences in behaviour underpinning some aspects of social interactions. First, following thousands of cells under various contexts, we identified distinct behavioural phenotypes: 'slow-regular-social', 'fast-regular-social' and 'fast-irregular-asocial'. Second, coupling chemical analysis and behavioural assays we found that calcium signalling is responsible for these behavioural phenotypes. Finally, we show that differences in signalling and behaviour led to alternative social strategies. Our results have considerable implications for our understanding of the emergence of variability in living organisms. © 2015 The Author(s).

Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany - Tattoos are not restricted to a specific social phenotype.

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Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

2017-01-01

Background : More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective : To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods : We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results : Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations : The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion : The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit.

Phenotypic variations in chondrocyte subpopulations and their response to in vitro culture and external stimuli.

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Coates, Emily E; Fisher, John P

2010-11-01

Articular cartilage defects have limited capacity to self-repair, and cost society up to 60 billion dollars annually in both medical treatments and loss of working days. Recent developments in cartilage tissue engineering have resulted in many new products coming to market or entering clinical trials. However, there is a distinct lack of treatments which aim to recreate the complex zonal organization of articular cartilage. Cartilage tissue withstands repetitive strains throughout an individual's lifetime and provides frictionless movement between joints. The structure and composition of its intricately organized extracellular matrix varies with tissue depth to provide optimal resistance to loading, ensure ease of movement, and integrate with the subchondral bone. Each tissue zone is specially designed to resist the load it experiences, and maximize the tissue properties needed for its location. It is unlikely that a homogenous solution to tissue repair will be able to optimally restore the function of such a heterogeneous tissue. For zonal engineering of articular cartilage to become practical, maintenance of phenotypically stable zonal cell populations must be achieved. The chondrocyte phenotype varies considerably by zone, and it is the activity of these cells that help achieve the structural organization of the tissue. This review provides an examination of literature which has studied variations in cellular phenotype between cartilage zones. By doing so, we have identified critical differences between cell populations and highlighted areas of research which show potential in the field. Current research has made the morphological and metabolic variations between these cell populations clear, but an ideal way of maintaining these differences in vitro culture is yet to be established. Combinations of delivered growth factors, mechanical loading, and layered three-dimensional culture systems all show potential for achieving this goal. Furthermore, differentiation

The down syndrome behavioral phenotype: implications for practice and research in occupational therapy.

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Daunhauer, Lisa A; Fidler, Deborah J

2011-01-01

ABSTRACT Down syndrome (DS) is the most common chromosomal cause of intellectual disability. The genetic causes of DS are associated with characteristic outcomes, such as relative strengths in visual-spatial skills and relative challenges in motor planning. This profile of outcomes, called the DS behavioral phenotype, may be a critical tool for intervention planning and research in this population. In this article, aspects of the DS behavioral phenotype potentially relevant to occupational therapy practice are reviewed. Implications and challenges for etiology-informed research and practice are discussed.

Laparoscopic side-to-side pancreaticojejunostomy for chronic pancreatitis in children

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Kyoichi Deie

2016-01-01

Full Text Available Surgical pancreatic duct (PD drainage for chronic pancreatitis in children is relatively rare. It is indicated in cases of recurrent pancreatitis and PD dilatation that have not responded to medical therapy and therapeutic endoscopy. We performed laparoscopic side-to-side pancreaticojejunostomy for two paediatric patients with chronic pancreatitis. The main PD was opened easily by electrocautery after locating the dilated PD by intraoperative ultrasonography. The dilated PD was split longitudinally from the pancreatic tail to the pancreatic head by laparoscopic coagulation shears or electrocautery after pancreatography. A laparoscopic side-to-side pancreaticojejunostomy was performed by a one-layered technique using continuous 4-0 polydioxanone (PDS sutures from the pancreatic tail to the pancreatic head. There were no intraoperative or postoperative complications or recurrences. This procedure has cosmetic advantages compared with open surgery for chronic pancreatitis. Laparoscopic side-to-side pancreaticojejunostomy in children is feasible and effective for the treatment of chronic pancreatitis.

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting.

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Howe, B J; Cooper, M E; Vieira, A R; Weinberg, S M; Resick, J M; Nidey, N L; Wehby, G L; Marazita, M L; Moreno Uribe, L M

2015-07-01

Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the

Flow and wall shear stress in end-to-side and side-to-side anastomosis of venous coronary artery bypass grafts

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Poulikakos Dimos

2007-09-01

Full Text Available Abstract Purpose Coronary artery bypass graft (CABG surgery represents the standard treatment of advanced coronary artery disease. Two major types of anastomosis exist to connect the graft to the coronary artery, i.e., by using an end-to-side or a side-to-side anastomosis. There is still controversy because of the differences in the patency rates of the two types of anastomosis. The purpose of this paper is to non-invasively quantify hemodynamic parameters, such as mass flow and wall shear stress (WSS, in end-to-side and side-to-side anastomoses of patients with CABG using computational fluid dynamics (CFD. Methods One patient with saphenous CABG and end-to-side anastomosis and one patient with saphenous CABG and side-to-side anastomosis underwent 16-detector row computed tomography (CT. Geometric models of coronary arteries and bypasses were reconstructed for CFD analysis. Blood flow was considered pulsatile, laminar, incompressible and Newtonian. Peri-anastomotic mass flow and WSS were quantified and flow patterns visualized. Results CFD analysis based on in-vivo CT coronary angiography data was feasible in both patients. For both types of CABG, flow patterns were characterized by a retrograde flow into the native coronary artery. WSS variations were found in both anastomoses types, with highest WSS values at the heel and lowest WSS values at the floor of the end-to-side anastomosis. In contrast, the highest WSS values of the side-to-side anastomosis configuration were found in stenotic vessel segments and not in the close vicinity of the anastomosis. Flow stagnation zones were found in end-to-side but not in side-to-side anastomosis, the latter also demonstrating a smoother stream division throughout the cardiac cycle. Conclusion CFD analysis of venous CABG based on in-vivo CT datasets in patients was feasible producing qualitative and quantitative information on mass flow and WSS. Differences were found between the two types of anastomosis

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

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Unwin, Nigel; Howitt, Christina; Rose, Angela Mc; Samuels, T Alafia; Hennis, Anselm Jm; Hambleton, Ian R

2017-12-01

Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population.

Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

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Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

2017-08-03

To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, pmovement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Climate change in the oceans: evolutionary versus phenotypically plastic responses of marine animals and plants.

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Reusch, Thorsten B H

2014-01-01

I summarize marine studies on plastic versus adaptive responses to global change. Due to the lack of time series, this review focuses largely on the potential for adaptive evolution in marine animals and plants. The approaches were mainly synchronic comparisons of phenotypically divergent populations, substituting spatial contrasts in temperature or CO2 environments for temporal changes, or in assessments of adaptive genetic diversity within populations for traits important under global change. The available literature is biased towards gastropods, crustaceans, cnidarians and macroalgae. Focal traits were mostly environmental tolerances, which correspond to phenotypic buffering, a plasticity type that maintains a functional phenotype despite external disturbance. Almost all studies address coastal species that are already today exposed to fluctuations in temperature, pH and oxygen levels. Recommendations for future research include (i) initiation and analyses of observational and experimental temporal studies encompassing diverse phenotypic traits (including diapausing cues, dispersal traits, reproductive timing, morphology) (ii) quantification of nongenetic trans-generational effects along with components of additive genetic variance (iii) adaptive changes in microbe-host associations under the holobiont model in response to global change (iv) evolution of plasticity patterns under increasingly fluctuating environments and extreme conditions and (v) joint consideration of demography and evolutionary adaptation in evolutionary rescue approaches.

Asthma phenotypes in childhood.

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Reddy, Monica B; Covar, Ronina A

2016-04-01

This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

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Danti, S; Toschi, N; Diciotti, S; Tessa, C; Poletti, M; Del Dotto, P; Lucetti, C

2015-12-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. © 2015 EAN.

A stochastic algorithm for global optimization and for best populations: A test case of side chains in proteins

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Glick, Meir; Rayan, Anwar; Goldblum, Amiram

2002-01-01

The problem of global optimization is pivotal in a variety of scientific fields. Here, we present a robust stochastic search method that is able to find the global minimum for a given cost function, as well as, in most cases, any number of best solutions for very large combinatorial “explosive” systems. The algorithm iteratively eliminates variable values that contribute consistently to the highest end of a cost function's spectrum of values for the full system. Values that have not been eliminated are retained for a full, exhaustive search, allowing the creation of an ordered population of best solutions, which includes the global minimum. We demonstrate the ability of the algorithm to explore the conformational space of side chains in eight proteins, with 54 to 263 residues, to reproduce a population of their low energy conformations. The 1,000 lowest energy solutions are identical in the stochastic (with two different seed numbers) and full, exhaustive searches for six of eight proteins. The others retain the lowest 141 and 213 (of 1,000) conformations, depending on the seed number, and the maximal difference between stochastic and exhaustive is only about 0.15 Kcal/mol. The energy gap between the lowest and highest of the 1,000 low-energy conformers in eight proteins is between 0.55 and 3.64 Kcal/mol. This algorithm offers real opportunities for solving problems of high complexity in structural biology and in other fields of science and technology. PMID:11792838

Maternal Vitamin D Levels and the Autism Phenotype among Offspring

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Whitehouse, Andrew J. O.; Holt, Barbara J.; Serralha, Michael; Holt, Patrick G.; Hart, Prue H.; Kusel, Merci M. H.

2013-01-01

We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean.…

Crop 3D-a LiDAR based platform for 3D high-throughput crop phenotyping.

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Guo, Qinghua; Wu, Fangfang; Pang, Shuxin; Zhao, Xiaoqian; Chen, Linhai; Liu, Jin; Xue, Baolin; Xu, Guangcai; Li, Le; Jing, Haichun; Chu, Chengcai

2018-03-01

With the growing population and the reducing arable land, breeding has been considered as an effective way to solve the food crisis. As an important part in breeding, high-throughput phenotyping can accelerate the breeding process effectively. Light detection and ranging (LiDAR) is an active remote sensing technology that is capable of acquiring three-dimensional (3D) data accurately, and has a great potential in crop phenotyping. Given that crop phenotyping based on LiDAR technology is not common in China, we developed a high-throughput crop phenotyping platform, named Crop 3D, which integrated LiDAR sensor, high-resolution camera, thermal camera and hyperspectral imager. Compared with traditional crop phenotyping techniques, Crop 3D can acquire multi-source phenotypic data in the whole crop growing period and extract plant height, plant width, leaf length, leaf width, leaf area, leaf inclination angle and other parameters for plant biology and genomics analysis. In this paper, we described the designs, functions and testing results of the Crop 3D platform, and briefly discussed the potential applications and future development of the platform in phenotyping. We concluded that platforms integrating LiDAR and traditional remote sensing techniques might be the future trend of crop high-throughput phenotyping.

The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

NARCIS (Netherlands)

Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

2014-01-01

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

Using whole-genome sequence data to predict quantitative trait phenotypes in Drosophila melanogaster.

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Ulrike Ober

Full Text Available Predicting organismal phenotypes from genotype data is important for plant and animal breeding, medicine, and evolutionary biology. Genomic-based phenotype prediction has been applied for single-nucleotide polymorphism (SNP genotyping platforms, but not using complete genome sequences. Here, we report genomic prediction for starvation stress resistance and startle response in Drosophila melanogaster, using ∼2.5 million SNPs determined by sequencing the Drosophila Genetic Reference Panel population of inbred lines. We constructed a genomic relationship matrix from the SNP data and used it in a genomic best linear unbiased prediction (GBLUP model. We assessed predictive ability as the correlation between predicted genetic values and observed phenotypes by cross-validation, and found a predictive ability of 0.239±0.008 (0.230±0.012 for starvation resistance (startle response. The predictive ability of BayesB, a Bayesian method with internal SNP selection, was not greater than GBLUP. Selection of the 5% SNPs with either the highest absolute effect or variance explained did not improve predictive ability. Predictive ability decreased only when fewer than 150,000 SNPs were used to construct the genomic relationship matrix. We hypothesize that predictive power in this population stems from the SNP-based modeling of the subtle relationship structure caused by long-range linkage disequilibrium and not from population structure or SNPs in linkage disequilibrium with causal variants. We discuss the implications of these results for genomic prediction in other organisms.

Integrating Evolutionary Game Theory into Mechanistic Genotype-Phenotype Mapping.

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Zhu, Xuli; Jiang, Libo; Ye, Meixia; Sun, Lidan; Gragnoli, Claudia; Wu, Rongling

2016-05-01

Natural selection has shaped the evolution of organisms toward optimizing their structural and functional design. However, how this universal principle can enhance genotype-phenotype mapping of quantitative traits has remained unexplored. Here we show that the integration of this principle and functional mapping through evolutionary game theory gains new insight into the genetic architecture of complex traits. By viewing phenotype formation as an evolutionary system, we formulate mathematical equations to model the ecological mechanisms that drive the interaction and coordination of its constituent components toward population dynamics and stability. Functional mapping provides a procedure for estimating the genetic parameters that specify the dynamic relationship of competition and cooperation and predicting how genes mediate the evolution of this relationship during trait formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

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Alexander D Malkin

2015-10-01

Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

Body composition and bone density during and after childhood cancer therapy : The flip side of therapy

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den Hoed, M.A.H.

2017-01-01

In the Netherlands, there are approximately 8000 childhood cancer survivors, and this population of survivors is expanding due to improved therapy. However, therapy has a consequent flip side, namely their inherent side effects. Approximately 75% of the CCS will develop one or more severe chronic

Progress toward a genotype/phenotype correlation in galactosemia

Energy Technology Data Exchange (ETDEWEB)

Reichardt, J.K.V.; Lin, Hsien-Chin; Ng, Won G. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States)

1994-09-01

Galactosemia is secondary to deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). If untreated this condition results in severe neonatal symptoms and can be fatal. Most symptoms disappear upon the institution of a galactose-restricted diet. Therefore, most states in the US and many developed countries have implemented newborn screening programs for galactosemia. We have characterized thus far twelve disease-causing point mutations, four protein polymorphisms, one silent nucleotide substitution and a RFLP (restriction fragment length polymorphism) in over 200 patients. The most common galactosemia mutation, Q188R, is present on about 64% of Caucasian galactosemia alleles in the US. This mutation is present on 67% of {open_quotes}classic{close_quotes} Caucasian alleles with severe neonatal symptoms and undetectable crythrocytic GALT activity. Thus, Q188R almost defines the {open_quotes}classic{close_quotes} phenotype in Caucasian galactosemia patients. This mutation, however, is present on only 16% of the milder {open_quotes}variant{close_quotes} alleles and never in the homozygous state. Variant patients have up to 10% residual GALT activity in their red cells. Therefore, one or more as of yet uncharacterized mutations other than Q188R must be present in {open_quotes}variant{close_quotes} patients. The Q188R mutations is very rare in other ethnic and racial groups. Thus, Galactosemia is panethnic but the mutational basis of this disease differs among human populations. The frequency of Q188R is intermediate in Hispanic-American patients, probably reflecting the Spanish contribution to the gene pool in this population. We conclude that the Q188R mutation encodes the severe {open_quotes}classic{close_quotes}galactosemia phenotype in Caucasians and that other mutations produce the {open_quotes}variant{close_quotes} galactosemia phenotype.

Measurement Equivalence of the Autism Symptom Phenotype in Children and Youth

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Duku, Eric; Szatmari, Peter; Vaillancourt, Tracy; Georgiades, Stelios; Thompson, Ann; Liu, Xiao-Qing; Paterson, Andrew D.; Bennett, Terry

2013-01-01

Background: The Autism Diagnostic Interview-Revised (ADI-R) is a gold standard assessment of Autism Spectrum Disorder (ASD) symptoms and behaviours. A key underlying assumption of studies using the ADI-R is that it measures the same phenotypic constructs across different populations (i.e. males/females, younger/older, verbal/nonverbal). The…

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

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Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Checklist for the Structural Description of the Deep Phenotype in Disorders of Sexual Development

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L. Wünsch

2012-01-01

Full Text Available This paper addresses the question, how the variations of the deep phenotype in disorders of sex development (DSD are appropriately described. This is a relevant question, because extensive phenotypic variability occurs in gonads and sex ducts. With the advance of video endoscopy and laparoscopy, fresh insight in gonadal and sex duct anatomy is emerging. So far, an attempt to standardize the diagnostic approach and, in particular, how to document these findings has not been published. We propose a standardized examination schedule for these procedures. It consists of 5 pictures of relevant anatomic features. For laparoscopy, it includes two pictures each of gonads and sex ducts on either side and an image of the retrovesical space. For endoscopy, the examination of the ureteric orifices, the posterior urethra, and the urogenital sinus derivates is recommended. Adherence of a standardized schedule and image storing enhances patient autonomy, because they can carry their examination for a second opinion without need for repeated examination. Physicians and scientists create a structured image library that facilitates the comparison of clinical outcomes, research on genotype phenotype associations and may lead to better classifications.

Genetic variation and co-variation for fitness between intra-population and inter-population backgrounds in the red flour beetle, Tribolium castaneum

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Drury, Douglas W.; Wade, Michael J.

2010-01-01

Hybrids from crosses between populations of the flour beetle, Tribolium castaneum, express varying degrees of inviability and morphological abnormalities. The proportion of allopatric population hybrids exhibiting these negative hybrid phenotypes varies widely, from 3% to 100%, depending upon the pair of populations crossed. We crossed three populations and measured two fitness components, fertility and adult offspring numbers from successful crosses, to determine how genes segregating within populations interact in inter-population hybrids to cause the negative phenotypes. With data from crosses of 40 sires from each of three populations to groups of 5 dams from their own and two divergent populations, we estimated the genetic variance and covariance for breeding value of fitness between the intra- and inter-population backgrounds and the sire × dam-population interaction variance. The latter component of the variance in breeding values estimates the change in genic effects between backgrounds owing to epistasis. Interacting genes with a positive effect, prior to fixation, in the sympatric background but a negative effect in the hybrid background cause reproductive incompatibility in the Dobzhansky-Muller speciation model. Thus, the sire × dam-population interaction provides a way to measure the progress toward speciation of genetically differentiating populations on a trait by trait basis using inter-population hybrids. PMID:21044199

Stochastic switching in biology: from genotype to phenotype

International Nuclear Information System (INIS)

Bressloff, Paul C

2017-01-01

There has been a resurgence of interest in non-equilibrium stochastic processes in recent years, driven in part by the observation that the number of molecules (genes, mRNA, proteins) involved in gene expression are often of order 1–1000. This means that deterministic mass-action kinetics tends to break down, and one needs to take into account the discrete, stochastic nature of biochemical reactions. One of the major consequences of molecular noise is the occurrence of stochastic biological switching at both the genotypic and phenotypic levels. For example, individual gene regulatory networks can switch between graded and binary responses, exhibit translational/transcriptional bursting, and support metastability (noise-induced switching between states that are stable in the deterministic limit). If random switching persists at the phenotypic level then this can confer certain advantages to cell populations growing in a changing environment, as exemplified by bacterial persistence in response to antibiotics. Gene expression at the single-cell level can also be regulated by changes in cell density at the population level, a process known as quorum sensing. In contrast to noise-driven phenotypic switching, the switching mechanism in quorum sensing is stimulus-driven and thus noise tends to have a detrimental effect. A common approach to modeling stochastic gene expression is to assume a large but finite system and to approximate the discrete processes by continuous processes using a system-size expansion. However, there is a growing need to have some familiarity with the theory of stochastic processes that goes beyond the standard topics of chemical master equations, the system-size expansion, Langevin equations and the Fokker–Planck equation. Examples include stochastic hybrid systems (piecewise deterministic Markov processes), large deviations and the Wentzel–Kramers–Brillouin (WKB) method, adiabatic reductions, and queuing/renewal theory. The major aim of

Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis

Energy Technology Data Exchange (ETDEWEB)

Santamaria-Martinez, Albert [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat de Barcelona, Barcelona (Spain); Barquinero, Jordi [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Banc de Sang i Teixits, Barcelona (Spain); Barbosa-Desongles, Anna; Hurtado, Antoni; Pinos, Tomas [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Seoane, Joan [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Medical Oncology program, Vall d' Hebron Institute of Oncology, Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Poupon, Marie-France [Institut Curie, Paris (France); Morote, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Servei d' Urologia. Hospital Vall d' Hebron, Barcelona (Spain); Reventos, Jaume [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain); Munell, Francina, E-mail: fmunell@ir.vhebron.net [Institut de Recerca Hospital Vall d' Hebron, Barcelona (Spain); Universitat Autonoma de Barcelona, Barcelona (Spain)

2009-10-15

Cancer stem cells are a distinct cellular population that is believed to be responsible for tumor initiation and maintenance. Recent data suggest that solid tumors also contain another type of stem cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs), which contribute to the formation of tumor-associated stroma. The Hoechst 33342 efflux assay has proved useful to identify a rare cellular fraction, named Side Population (SP), enriched in cells with stem-like properties. Using this assay, we identified SP cells in a prostate cancer xenograft containing human prostate cancer cells and mouse stromal cells. The SP isolation, subculture and sequential sorting allowed the generation of single-cell-derived clones of murine origin that were recognized as MSC by their morphology, plastic adherence, proliferative potential, adipogenic and osteogenic differentiation ability and immunophenotype (CD45{sup -}, CD81{sup +} and Sca-1{sup +}). We also demonstrated that SP clonal cells secrete transforming growth factor {beta}1 (TGF-{beta}1) and that their inhibition reduces proliferation and accelerates differentiation. These results reveal the existence of SP cells in the stroma of a cancer xenograft, and provide evidence supporting their MSC nature and the role of TGF-{beta}1 in maintaining their proliferation and undifferentiated status. Our data also reveal the usefulness of the SP assay to identify and isolate MSC cells from carcinomas.

A systematic review of the psychiatric side-effects of efavirenz.

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Kenedi, Christopher A; Goforth, Harold W

2011-11-01

Concerns regarding the use of efavirenz in patients with a history of mental illness may predispose clinicians to not offer this agent to psychiatrically ill populations in spite of the convenience of once daily dosing, which can result in improved adherence in these at-risk populations. This systematic review examines the current data regarding the neuropsychiatric effects of efavirenz, and also attempts to provide guidance to clinicians using efavirenz to treat patients with mental illness. The review identified high rates of neuropsychiatric side effects including vivid dreams, insomnia and mood changes in approximately 50% of patients who initiate efavirenz. The effects begin quickly, commonly peak in the first 2 weeks, and are generally mild and transient in nature. Isolated case reports and uncontrolled data suggest higher rates of severe side effects; however, there is no clear evidence of a broadly increased risk of suicide or dangerous behavior for patients taking efavirenz as part of their antiretroviral regimen.

The life of a dead ant -the expression of an adaptive extended phenotype

DEFF Research Database (Denmark)

Andersen, Sandra Breum; Gerritsma, Sylvia; Yusah, Kalsum M.

2009-01-01

to make hosts bite onto vegetation prior to killing them. We show that this represents a fine-tuned fungal adaptation: an extended phenotype. Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings ca. 25 cm above the soil, where temperature and humidity conditions......Specialized parasites are expected to express complex adaptations to their hosts. Manipulation of host behavior is such an adaptation. We studied the fungus Ophiocordyceps unilateralis, a locally specialized parasite of arboreal Camponotus leonardi ants. Ant-infecting Ophiocordyceps are known...

Phenotypic plasticity or speciation? A case from a clonal marine organism

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Yoshioka Paul M

2008-02-01

Full Text Available Abstract Background Clonal marine organisms exhibit high levels of morphological variation. Morphological differences may be a response to environmental factors but also they can be attributed to accumulated genetic differences due to disruption of gene flow among populations. In this study, we examined the extensive morphological variation (of 14 characters in natural populations observed in the gorgonian Eunicea flexuosa, a widely distributed Caribbean octocoral. Eco-phenotypic and genetic effects were evaluated by reciprocal transplants of colonies inhabiting opposite ends of the depth gradient and analysis of population genetics of mitochondrial and nuclear genes, respectively. Results Significant differences (P 17 m. A discriminant function analysis based on a priori univariate and multivariate analyses (which separated the colonies in morphotypes correctly classified 93% of the colonies for each environment. Light, water motion and sediment transport might influence the distribution of the two morphotypes. Reaction norms of morphological characters of colonies reciprocally transplanted showed gradual significant changes through the 15 months of transplantation. Sclerites of shallow water colonies became larger when transplanted to deeper environments and vice versa, but neither of the two transplanted groups overlapped with the residents' morphology. Genetic analysis of mitochondrial and nuclear genes suggested that such discrete morphology and non-overlapping phenotypic plasticity is correlated with the presence of two independent evolutionary lineages. The distribution of the lineages is non-random and may be related to adaptational responses of each lineage to the environmental demands of each habitat. Conclusion The extensive distribution and ample morphological variation of Eunicea flexuosa corresponds to two distinct genetic lineages with narrower distributions and more rigid phenotypic plasticity than the original description. The

Knowledge-based analysis of phenotypes

KAUST Repository

Hoendorf, Robert

2016-01-27

Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

Phenotypic and genetic diversification of Pseudanabaena spp. (cyanobacteria).

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Acinas, Silvia G; Haverkamp, Thomas H A; Huisman, Jef; Stal, Lucas J

2009-01-01

Pseudanabaena species are poorly known filamentous bloom-forming cyanobacteria closely related to Limnothrix. We isolated 28 Pseudanabaena strains from the Baltic Sea (BS) and the Albufera de Valencia (AV; Spain). By combining phenotypic and genotypic approaches, the phylogeny, diversity and evolutionary diversification of these isolates were explored. Analysis of the in vivo absorption spectra of the Pseudanabaena strains revealed two coexisting pigmentation phenotypes: (i) phycocyanin-rich (PC-rich) strains and (ii) strains containing both PC and phycoerythrin (PE). Strains of the latter phenotype were all capable of complementary chromatic adaptation (CCA). About 65 kb of the Pseudanabaena genomes were sequenced through a multilocus sequencing approach including the sequencing of the16 and 23S rRNA genes, the ribosomal intergenic spacer (IGS), internal transcribed spacer 1 (ITS-1), the cpcBA operon encoding PC and the IGS between cpcA and cpcB. In addition, the presence of nifH, one of the structural genes of nitrogenase, was investigated. Sequence analysis of ITS and cpcBA-IGS allowed the differentiation between Pseudanabaena isolates exhibiting high levels of microdiversity. This multilocus sequencing approach revealed specific clusters for the BS, the AV and a mixed cluster with strains from both ecosystems. The latter comprised exclusively CCA phenotypes. The phylogenies of the 16 and 23S rRNA genes are consistent, but analysis of other loci indicated the loss of substructure, suggesting that the recombination between these loci has occurred. Our preliminary results on population genetic analyses of the PC genes suggest an evolutionary diversification of Pseudanabaena through purifying selection.

Mixed Phenotype Acute Leukemia with Two Immunophenotypically Distinct B and T Blasts Populations, Double Chromosome and Complex Karyotype: Report of an Unusual Case

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Samah A. Kohla

2015-01-01

Full Text Available Mixed phenotype acute leukemia (MPAL is considered as a rare type of leukemia with an incidence of less than 4% of all acute leukemia based on the most recent 2008 WHO classification. Common subtypes are the B/myeloid and T/myeloid; B/T and trilineage MPAL being extremely rare. We present a case of a male in his 20s, whose peripheral blood smears showed 34% blast cells and bone marrow with 70% blasts. Immunophenotyping by multiparametric flow cytometry showed two populations of blasts, the major one with B-lineage and the minor one with T-lineage. Conventional karyotyping revealed complex karyotype with the presence of double Philadelphia chromosome ( Ph + . BCR/ABL1 rearrangement was confirmed by fluorescent in situ hybridization (FISH analysis. The BCR/ABL1 ES probe on interphase cells indicated pl90 minor m-BCR/ABL fusion in 46% and a second abnormal clone with double Ph + in 16% of the cells analyzed confirmed by reverse transcription-PCR (RT-PCR. The case was diagnosed as MPAL with double Philadelphia chromosome Ph + . The patient was treated with dasatinib, four cycle hyper CVAD/methotrexate cytarabin protocol, and allogeneic transplant. He is still alive in complete hematological, cytogenetic, and molecular remission. Mixed phenotype B/T acute leukemia is an extremely rare disease, particularly those with double Philadelphia chromosomes and clinically presents challenges in diagnosis and treatment.

Population structure, fluctuating asymmetry and genetic variability in an endemic and highly isolated Astyanax fish population (Characidae

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Maria Claudia Gross

2004-01-01

Full Text Available Morphological and chromosomal markers were used to infer the structure and genetic variability of a population of fish of the genus Astyanax, geographically isolated at sinkhole 2 of Vila Velha State Park, Paraná, Brazil. Two morphotypes types were observed, the standard phenotype I and phenotype II which showed an anatomical alteration probably due to an inbreeding process. Fluctuating asymmetry (FA analysis of different characters showed low levels of morphological variation among the population from sinkhole 2 and in another population from the Tibagi river (Paraná, Brazil. The Astyanax karyotype was characterized in terms of chromosomal morphology, constitutive heterochromatin and nucleolar organizer regions. Males and females presented similar karyotypes (2n=48, 6M+18SM+14ST+10A with no evidence of a sex chromosome system. One female from sinkhole 2 was a natural triploid with 2n=3x=72 chromosomes (9M+27SM+21ST+15A. The data are discussed regarding the maintenance of population structure and their evolutionary importance, our data suggesting that Astyanax from the Vila Velha State Park sinkhole 2 is a recently isolated population.

Guidance for the utility of linear models in meta-analysis of genetic association studies of binary phenotypes.

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Cook, James P; Mahajan, Anubha; Morris, Andrew P

2017-02-01

Linear mixed models are increasingly used for the analysis of genome-wide association studies (GWAS) of binary phenotypes because they can efficiently and robustly account for population stratification and relatedness through inclusion of random effects for a genetic relationship matrix. However, the utility of linear (mixed) models in the context of meta-analysis of GWAS of binary phenotypes has not been previously explored. In this investigation, we present simulations to compare the performance of linear and logistic regression models under alternative weighting schemes in a fixed-effects meta-analysis framework, considering designs that incorporate variable case-control imbalance, confounding factors and population stratification. Our results demonstrate that linear models can be used for meta-analysis of GWAS of binary phenotypes, without loss of power, even in the presence of extreme case-control imbalance, provided that one of the following schemes is used: (i) effective sample size weighting of Z-scores or (ii) inverse-variance weighting of allelic effect sizes after conversion onto the log-odds scale. Our conclusions thus provide essential recommendations for the development of robust protocols for meta-analysis of binary phenotypes with linear models.

Age at onset and Parkinson disease phenotype

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Pagano, Gennaro; Ferrara, Nicola; Brooks, David J.

2016-01-01

Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD. Methods: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50–59 years, 60–69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers. Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups. Conclusions: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials. PMID:26865518

EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer.

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Singh, Sandeep; Trevino, Jose; Bora-Singhal, Namrata; Coppola, Domenico; Haura, Eric; Altiok, Soner; Chellappan, Srikumar P

2012-09-25

Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs), Hoechst 33342 dye effluxing side population (SP) cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549), as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of stem-like cells from NSCLC. Therefore, the outcome of the

EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer

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Singh Sandeep

2012-09-01

Full Text Available Abstract Background Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs, Hoechst 33342 dye effluxing side population (SP cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. Results SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549, as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Conclusions Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of

Genetic and phenotypic variation of the malaria vector Anopheles atroparvus in southern Europe

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Romi Roberto

2011-01-01

Full Text Available Abstract Background There is a growing concern that global climate change will affect the potential for pathogen transmission by insect species that are vectors of human diseases. One of these species is the former European malaria vector, Anopheles atroparvus. Levels of population differentiation of An. atroparvus from southern Europe were characterized as a first attempt to elucidate patterns of population structure of this former malaria vector. Results are discussed in light of a hypothetical situation of re-establishment of malaria transmission. Methods Genetic and phenotypic variation was analysed in nine mosquito samples collected from five European countries, using eight microsatellite loci and geometric morphometrics on 21 wing landmarks. Results Levels of genetic diversity were comparable to those reported for tropical malaria vectors. Low levels of genetic (0.004 FST An. atroparvus populations spanning over 3,000 km distance. Genetic differentiation (0.202 FST An. atroparvus and Anopheles maculipennis s.s. Differentiation between sibling species was not so evident at the phenotype level. Conclusions Levels of population differentiation within An. atroparvus were low and not correlated with geographic distance or with putative physical barriers to gene flow (Alps and Pyrenées. While these results may suggest considerable levels of gene flow, other explanations such as the effect of historical population perturbations can also be hypothesized.

Allele-specific gene expression in a wild nonhuman primate population

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Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

Global change and the evolution of phenotypic plasticity in plants.

Science.gov (United States)

Matesanz, Silvia; Gianoli, Ernesto; Valladares, Fernando

2010-09-01

Global change drivers create new environmental scenarios and selective pressures, affecting plant species in various interacting ways. Plants respond with changes in phenology, physiology, and reproduction, with consequences for biotic interactions and community composition. We review information on phenotypic plasticity, a primary means by which plants cope with global change scenarios, recommending promising approaches for investigating the evolution of plasticity and describing constraints to its evolution. We discuss the important but largely ignored role of phenotypic plasticity in range shifts and review the extensive literature on invasive species as models of evolutionary change in novel environments. Plasticity can play a role both in the short-term response of plant populations to global change as well as in their long-term fate through the maintenance of genetic variation. In new environmental conditions, plasticity of certain functional traits may be beneficial (i.e., the plastic response is accompanied by a fitness advantage) and thus selected for. Plasticity can also be relevant in the establishment and persistence of plants in novel environments that are crucial for populations at the colonizing edge in range shifts induced by climate change. Experimental studies show taxonomically widespread plastic responses to global change drivers in many functional traits, though there is a lack of empirical support for many theoretical models on the evolution of phenotypic plasticity. Future studies should assess the adaptive value and evolutionary potential of plasticity under complex, realistic global change scenarios. Promising tools include resurrection protocols and artificial selection experiments. © 2010 New York Academy of Sciences.

Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

OpenAIRE

Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

2017-01-01

High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

The Human Phenotype Ontology in 2017

International Nuclear Information System (INIS)

Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

2016-01-01

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

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Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Phenotypic plasticity in response to the social environment: effects of density and sex ratio on mating behaviour following ecotype divergence.

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Kristina Karlsson

Full Text Available The ability to express phenotypically plastic responses to environmental cues might be adaptive in changing environments. We studied phenotypic plasticity in mating behaviour as a response to population density and adult sex ratio in a freshwater isopod (Asellus aquaticus. A. aquaticus has recently diverged into two distinct ecotypes, inhabiting different lake habitats (reed Phragmites australis and stonewort Chara tomentosa, respectively. In field surveys, we found that these habitats differ markedly in isopod population densities and adult sex ratios. These spatially and temporally demographic differences are likely to affect mating behaviour. We performed behavioural experiments using animals from both the ancestral ecotype ("reed" isopods and from the novel ecotype ("stonewort" isopods population. We found that neither ecotype adjusted their behaviour in response to population density. However, the reed ecotype had a higher intrinsic mating propensity across densities. In contrast to the effects of density, we found ecotype differences in plasticity in response to sex ratio. The stonewort ecotype show pronounced phenotypic plasticity in mating propensity to adult sex ratio, whereas the reed ecotype showed a more canalised behaviour with respect to this demographic factor. We suggest that the lower overall mating propensity and the phenotypic plasticity in response to sex ratio have evolved in the novel stonewort ecotype following invasion of the novel habitat. Plasticity in mating behaviour may in turn have effects on the direction and intensity of sexual selection in the stonewort habitat, which may fuel further ecotype divergence.

Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

International Nuclear Information System (INIS)

Sharrow, S.O.; Singer, A.; Hammerling, U.; Mathieson, B.J.

1983-01-01

The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

Phenotypic assays for the determination of coreceptor tropism in HIV-1 infected individuals.

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Braun, Patrick; Wiesmann, Frank

2007-10-15

Coreceptor tropism antagonists represent a new class of antiretrovirals for the treatment of HIV infection. The knowledge of patients' viral population tropism before the initiation of and during therapy with such compounds may be critical in order to optimize treatment strategies. In this review we focus on the characteristics of phenotypic assays for the determination of HIV coreceptor tropism. Beside traditional phenotypic assays, there are at least four phenotypic recombinant virus assays (RVA) available to predict coreceptor usage: Trofile (Monogram Biosciences), Phenoscript (VIRalliance), XtrackC/ PhenX-R (inPheno) and a platform developed by Virco. Trofile and Phenoscript represent single-cycle assays and are able to determine coreceptor tropism without cocultivation of HIV particles in cell culture. Trofile offers the most clinically validated data with currently about 25,000 analysed samples. The detection of minority variants is a limitation of all population-based assays and varies between 1 and 10%, depending on the assay used. XtrackC/PhenX-R and Virco's platform combine genotypic and phenotypic assays to analyze a patient's sample for tropism. Although all assays are validated for the assessment of coreceptor tropism in different HIV-1 subtypes, there is still a need for further evaluations. Furthermore, the establishment of cut-offs for X4 minority species will be difficult, and is affected by many factors like patient sample quality, the input volume, viral load, the detection limits and PCR variations. Overall, RVAs confirm efficiency and accuracy thus making them suitable for the clinical management of HIV infected individuals treated with coreceptor antagonists.

Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in Germany – Tattoos are not restricted to a specific social phenotype

Science.gov (United States)

Müller, Cornelia Sigrid Lissi; Oertel, Angela; Körner, Rebecca; Pföhler, Claudia; Vogt, Thomas

2017-01-01

ABSTRACT Background: More and more people of all age classes have a tattoo. Intriguingly, there are multiple prejudices in the general population and published data that concern tattooed persons, such as being criminals, having a low education, being alcohol or drug abusers, or more risky in their life style. Objective: To obtain and to evaluate sociodemographic data on tattooed persons, to investigate the incidence of tattoo-related cutaneous complications and to define personal risk factors and course of the persons after being tattooed concerning behavior of personal environment. Patients and Methods: We interviewed 426 participants with already existing tattoos and 20 participants just before getting a new tattoo by using an online questionnaire. The participators were asked about socio-epidemiologic aspects of tattoos in general and special aspects of their own tattoo(s) in particular. There were no exclusion criteria. Results: Tattoos are interesting for people seeking popular body art, esp. university graduates and financially-secure individuals. 446 persons participated in this study. Most of the persons were female with a mean age of 35. Local pruritus around the tattooed area was the most common cutaneous side effect among the participants. 93.5% of the participants did not want a tattoo removal. Intriguingly, most of the participants experienced no career problems related to the tattoo(s). Limitations: The study population is not representative as we included only persons being tattooed prior to or getting newly tattooed. Furthermore, there is a potential selection bias as the participation in this study was voluntary. Only persons that felt involved by the flyer did answer the questionnaire. Conclusion: The present data shows that common tattooed persons are not low educated criminals with any drug or alcohol abuse or with risky life style. Nowadays being tattooed encompasses a kind of body art and displays a certain kind of lifestyle habit. PMID

Hypertriglyceridemic waist phenotype in primary health care: comparison of two cutoff points

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Braz MAD

2017-09-01

Full Text Available Marina Augusta Dias Braz,1 Jallyne Nunes Vieira,1 Flayane Oliveira Gomes,1 Priscilla Rafaella da Silva,1 Ohanna Thays de Medeiros Santos,1 Ilanna Marques Gomes da Rocha,2 Iasmin Matias de Sousa,2 Ana Paula Trussardi Fayh2 1Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte (UFRN, Santa Cruz, 2Department of Nutrition, Centro de Ciências da Saúde, UFRN, Natal, Rio Grande do Norte, Brazil Objective: We aimed to evaluate the prevalence of hypertriglyceridemic waist (HTGW phenotype among users of primary health care using two different cutoff points used in the literature. Methods: We evaluated adults and elderly individuals of both sexes who attended the same level of primary health care. HTGW phenotype was determined with measurements of waist circumference (WC and triglyceride levels and compared using cutoff points proposed by the National Cholesterol Education Program – NCEP/ATP III (WC ≥102 cm for men and ≥88 cm for women; triglyceride levels ≥150 mg/dL for both sexes and by Lemieux et al (WC ≥90 cm for men and ≥85 cm for women; triglyceride levels ≥177 mg/dL for both. Results: Within the sample of 437 individuals, 73.7% was female. The prevalence of HTGW phenotype was high and statistically different with the use of different cutoff points from the literature. The prevalence was higher using the NCEP/ATP III criteria compared to those proposed by Lemieux et al (36.2% and 32.5%, respectively, p<0.05. Individuals with the presence of the phenotype also presented alterations in other traditional cardiovascular risk markers. Conclusion: The HTGW phenotype identified high prevalence of cardiovascular risk in the population, with higher cutoff points from the NCEP/ATP III criteria. The difference in frequency of risk alerts us to the need to establish cutoff points for the Brazilian population. Keywords: abdominal obesity, cardiovascular disease, dyslipidemia, cardiovascular risk

GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations

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Eva Y. G. De Vilder

2017-01-01

Full Text Available Gamma-carboxylation, performed by gamma-glutamyl carboxylase (GGCX, is an enzymatic process essential for activating vitamin K-dependent proteins (VKDP with important functions in various biological processes. Mutations in the encoding GGCX gene are associated with multiple phenotypes, amongst which vitamin K-dependent coagulation factor deficiency (VKCFD1 is best known. Other patients have skin, eye, heart or bone manifestations. As genotype–phenotype correlations were never described, literature was systematically reviewed in search of patients with at least one GGCX mutation with a phenotypic description, resulting in a case series of 47 patients. Though this number was too low for statistically valid correlations—a frequent problem in orphan diseases—we demonstrate the crucial role of the horizontally transferred transmembrane domain in developing cardiac and bone manifestations. Moreover, natural history suggests ageing as the principal determinant to develop skin and eye symptoms. VKCFD1 symptoms seemed more severe in patients with both mutations in the same protein domain, though this could not be linked to a more perturbed coagulation factor function. Finally, distinct GGCX functional domains might be dedicated to carboxylation of very specific VKDP. In conclusion, this systematic review suggests that there indeed may be genotype–phenotype correlations for GGCX-related phenotypes, which can guide patient counseling and management.

Determination of urine caffeine and its metabolites by use of high-performance liquid chromatography-tandem mass spectrometry: estimating dietary caffeine exposure and metabolic phenotyping in population studies.

Science.gov (United States)

Rybak, Michael E; Pao, Ching-I; Pfeiffer, Christine M

2014-01-01

We have developed and validated a high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determining urine caffeine and 14 caffeine metabolites suitable for estimating caffeine exposure and metabolic phenotyping in population studies. Sample preparation consisted solely of a series of simple reagent treatments at room temperature. Stable isotope-labeled analogs were used as internal standards for all analytes. We developed rapid LC-MS/MS separations for both positive and negative ion mode electrospray ionizations to maximize measurement sensitivity. Limits of detection were 0.05-0.1 μmol/L depending on the analytes. Method imprecision, based on total coefficients of variation, was generally 1 μmol/L. Analyte recoveries were typically within 10 % of being quantitative (100 %), and good agreement was observed among analytes measured across different MS/MS transitions. We applied this method to the analysis of a convenience set of human urine samples (n = 115) and were able to detect a majority of the analytes in ≥99 % of samples as well as calculate caffeine metabolite phenotyping ratios for cytochrome P450 1A2 and N-acetyltransferase 2. Whereas existing LC-MS/MS methods are limited in number of caffeine metabolites for which they are validated, or are designed for studies in which purposely elevated caffeine levels are expected, our method is the first of its kind designed specifically for the rapid, sensitive, accurate, and precise measurement of urine caffeine and caffeine metabolites at concentrations relevant to population studies.

Interoperability between phenotype and anatomy ontologies.

Science.gov (United States)

Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

2010-12-15

Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

Surgical management of colonic diverticular disease: discrepancy between right- and left-sided diseases.

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Oh, Heung-Kwon; Han, Eon Chul; Ha, Heon-Kyun; Choe, Eun Kyung; Moon, Sang Hui; Ryoo, Seung-Bum; Jeong, Seung-Yong; Park, Kyu Joo

2014-08-07

To compare the outcome of the surgical management of left-sided and right-sided diverticular disease. The medical records of 77 patients who were surgically treated for diverticular disease between 1999 and 2010 in a tertiary referral hospital were retrospectively reviewed. The study population was limited to cases wherein the surgical specimen was confirmed as diverticulosis by pathology. Right-sided diverticula were classified as those arising from the cecum, ascending colon, and transverse colon, and those from the descending colon, sigmoid colon, and rectum were classified as left-sided diverticulosis. To assess the changing trend of occurrence of diverticulosis, data were compared with two previous studies of 51 patients. The proportion of left-sided disease cases was significantly increased compared to the results of our previous studies in 1994 and 2001, (27.5% vs 48.1%, P disease. However, patients with right-sided disease were significantly younger (50.9 year vs 64.0 year, P disease was significantly associated with a higher incidence of complicated diverticulitis (89.2% vs 57.5%, P diverticular disease, the incidence of left-sided disease in Korea has increased since 2001 and is associated with worse surgical outcomes.

Metabolic heterogeneity in clonal microbial populations.

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Takhaveev, Vakil; Heinemann, Matthias

2018-02-21

In the past decades, numerous instances of phenotypic diversity were observed in clonal microbial populations, particularly, on the gene expression level. Much less is, however, known about phenotypic differences that occur on the level of metabolism. This is likely explained by the fact that experimental tools probing metabolism of single cells are still at an early stage of development. Here, we review recent exciting discoveries that point out different causes for metabolic heterogeneity within clonal microbial populations. These causes range from ecological factors and cell-inherent dynamics in constant environments to molecular noise in gene expression that propagates into metabolism. Furthermore, we provide an overview of current methods to quantify the levels of metabolites and biomass components in single cells. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Epigenetic population differentiation in field- and common garden-grown Scabiosa columbaria plants

NARCIS (Netherlands)

Groot, Maartje P; Wagemaker, Niels CAM; Ouborg, N Joop; Verhoeven, Koen J F; Vergeer, Philippine

Populations often differ in phenotype and these differences can be caused by adaptation by natural selection, random neutral processes, and environmental responses. The most straightforward way to divide mechanisms that influence phenotypic variation is heritable variation and environmental-induced

Cataplexy as a side effect of modafinil in a patient without narcolepsy☆

Science.gov (United States)

Lopes, Eduardo; Pereira, Danielle; da Silva Behrens, Nilce Sanny Costa; de Almeida Fonseca, Hassana; Calvancanti, Paola Oliveira; de Araújo Lima, Taís Figueiredo; Pradella-Hallinan, Marcia; Castro, Juliana; Tufik, Sergio; Coelho, Fernando Morgadinho Santos

2014-01-01

Narcolepsy is a disease in which there is diurnal excessive sleepiness with sleep attacks and a prevalence in the general population of 1/4000 individuals. Classically, it is characterized by cataplexy, sleep paralysis, hypnagogic hallucinations and fragmented sleep. The use of modafinil in the treatment of narcolepsy is the first option of treatment for diurnal excessive sleepiness. Although considered a safe drug for use in patients with narcolepsy, being utilized for more than 20 years, modafinil possesses a series of side effects, some of them still not fully researched or described. Side effects such as headache, nausea, anxiety, insomnia, lumbago, diarrhea, dyspepsia, rhinitis and vertigo are the most frequent. However, the clinical follow-up of patients under treatment with modafinil must be intensive and the side effects ought to be noted and evaluated. The under-response to treatment or the unexpected side effects must always be directed to differential diagnostics. The objective of this article is to describe an unexpected side effect of the use of modafinil in a patient with incorrect diagnosis of narcolepsy. PMID:26483900

Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1

OpenAIRE

Suri, Mohnish; Evers, Jochem M. G.; Laskowski, Roman A.; O'Brien, Sinead; Baker, Kate; Clayton‐Smith, Jill; Dabir, Tabib; Josifova, Dragana; Joss, Shelagh; Kerr, Bronwyn; Kraus, Alison; McEntagart, Meriel; Morton, Jenny; Smith, Audrey; Splitt, Miranda

2017-01-01

Abstract Background Syntaxin‐binding protein 1, encoded by STXBP1, is highly expressed in the brain and involved in fusing synaptic vesicles with the plasma membrane. Studies have shown that pathogenic loss‐of‐function variants in this gene result in various types of epilepsies, mostly beginning early in life. We were interested to model pathogenic missense variants on the protein structure to investigate the mechanism of pathogenicity and genotype–phenotype correlations. Methods We report 11...

MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system.

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Hur, Matthew; Gistelinck, Charlotte A; Huber, Philippe; Lee, Jane; Thompson, Marjorie H; Monstad-Rios, Adrian T; Watson, Claire J; McMenamin, Sarah K; Willaert, Andy; Parichy, David M; Coucke, Paul; Kwon, Ronald Y

2017-09-08

Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of phenotypic measures comprised of morphological and densitometric traits at a large number of sites within the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ system. Analyzing phenotypic patterns may increase productivity in genetic screens, and facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

Energy Technology Data Exchange (ETDEWEB)

Sachse, C.; Brockmoeller, J.; Bauer, S.; Roots, I. [Humboldt Univ., Berlin (Germany)

1997-02-01

Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015, respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.

Phenotypic heterogeneity in modeling cancer evolution.

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Ali Mahdipour-Shirayeh

Full Text Available The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous population of stem cells (SCs and their associated progenitors. The fate of a malignant mutation is determined not only by overall stem cell and non-stem cell growth rates but also differentiation and dedifferentiation rates. We investigate the effect of such a complex population structure on the evolution of malignant mutations. We derive exactly calculated results for the fixation probability of a mutant arising in each of the subpopulations. The exactly calculated results are in almost perfect agreement with the numerical simulations. Moreover, a condition for evolutionary advantage of a mutant cell versus the wild type population is given in the present study. We also show that microenvironment-induced plasticity in invading mutants leads to more aggressive mutants with higher fixation probability. Our model predicts that decreasing polarity between stem and non-stem cells' turnover would raise the survivability of non-plastic mutants; while it would suppress the development of malignancy for plastic mutants. The derived results are novel and general with potential applications in nature; we discuss our model in the context of colorectal/intestinal cancer (at the epithelium. However, the model clearly needs to be validated through appropriate experimental data. This novel mathematical framework can be applied more generally to a variety of problems concerning selection in heterogeneous populations, in other contexts such as population genetics, and ecology.

Trajectories of the healthy ageing phenotype among middle-aged and older Britons, 2004-2013.

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Tampubolon, Gindo

2016-06-01

Since the ageing population demands a response to ensure older people remain healthy and active, we studied the dynamics of a recently proposed healthy ageing phenotype. We drew the phenotype's trajectories and tested whether their levels and rates of change are influenced by health behaviours, comorbidities and socioeconomic positions earlier in the life course. The English Longitudinal Ageing Study, a prospective, nationally representative sample of people aged ≥50 years, measured a set of eight biomarkers which make up the outcome of the healthy ageing phenotype three times over nearly a decade (N2004=5009, N2008=5301, N2013=4455). A cluster of health behaviours, comorbidities and socioeconomic positions were also measured repeatedly. We assessed the phenotype's distribution non-parametrically, then fitted linear mixed models to phenotypic change and further examined time interactions with gender and socioeconomic position. We ran additional analyses to test robustness. Women had a wider distribution of the healthy ageing phenotype than men had. The phenotype declined annually by -0.242 (95% confidence interval [CI]: -0.352, -0.131). However, there was considerable heterogeneity in the levels and rates of phenotypic change. Women started at higher levels, then declined more steeply by -0.293 (CI: -0.403, -0.183) annually, leading to crossover in the trajectories. Smoking and physical activity assessed on the Allied Dunbar scale were strongly associated with the trajectories. Though marked by secular decline, the trajectories of the healthy ageing phenotype showed distinct socioeconomic gradients. The trajectories were also susceptible to variations in health behaviours, strengthening the case for serial interventions to attain healthy and active ageing. Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

Nonequilibrium population dynamics of phenotype conversion of cancer cells.

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Joseph Xu Zhou

Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

[Phenotypic plasticity and its regulation of tillers prolonged reproductive growth of Puccinellia tenuiflora population on alkalized meadow in Songnen Plains of China].

Science.gov (United States)

Sun, Ju; Yang, Yun-Fei

2007-04-01

Puccinellia tenuiflora is a salt-tolerant plant of grass family. By the method of random sampling, big samples of reproductive tillers of P. tenuiflora population on the alkalized meadow in the Songnen Plains of China were collected at early heading, heading, flowering, and milky stages, respectively, and the plasticity of their quantitative characters was analyzed. The results showed that except some fluctuations at flowering stage, the tiller height, tiller biomass, spike length and spike biomass of the reproductive tillers at other three growth stages increased significantly every five days with the increasing time of reproductive growth. At each growth stage, tiller height had a significant positive correlation with spike biomass, but a negative correlation with reproductive allocation. With the time of reproductive growth prolonged, the increasing rate of spike biomass at early heading, flowering and milky stages increased in power function with the increase of tiller height. The reproductive allocation decreased linearly by 43.2% and 44.31% at early heading and heading stages, respectively when the reproductive growth time increased ten days, and by 130% at milky stage when the time increased five days. The regulation of the tiller phenotypic plasticity of P. tenuiflora population at its reproductive growth stage followed definite patterns.

Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

DEFF Research Database (Denmark)

Ansari-Mahyari, S; Berg, P; Lund, M S

2009-01-01

disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals sampled across...... the whole population based on LDC. The results showed that selecting individuals with similar haplotypes to the paternal haplotypes (minimum recombination criterion) using LAC compared to random phenotyping gave at least the same power to detect a QTL but decreased the accuracy of the QTL position. However...

A population of human brain cells expressing phenotypic markers of more than one lineage can be induced in vitro to differentiate into mesenchymal cells

International Nuclear Information System (INIS)

Rieske, Piotr; Augelli, Brian J.; Stawski, Robert; Gaughan, John; Azizi, S. Ausim; Krynska, Barbara

2009-01-01

Proliferating astrocytic cells from germinal, as well as mature areas of brain parenchyma, have the characteristics of neural stem/progenitor cells and are capable of generating both neurons and glia. We previously reported that primary fetal human brain cells, designated as Normal Human Astrocytes (NHA), expressed, in addition to GFAP, Vimentin and Nestin, low levels of βIII-Tubulin, an early neuronal marker, and differentiated into neurons and astrocytes in vitro. Here, we showed that primary NHA cells co-express low levels of mesenchymal markers Fibronectin and Collagen-1 in culture. These cells transitioned into mesenchymal-like cells when cultured in adherent conditions in serum containing media. The mesenchymal-like derivatives of these cells were characterized based on their morphological changes, high expression of Vimentin and extracellular matrix (ECM) proteins, Collagen-1 and Fibronectin, and decline of neural markers. When incubated in osteogenic and adipogenic induction media, the mesenchymal-like cells differentiated into osteoblasts and adipocytes. Furthermore, NHA cells express markers of neural crest cells, SOX-10 and p75. These data support the idea of ectoderm-derived mesenchymal lineages. These findings suggest that a population of primitive fetal brain cells with neural/neural crest/mesenchymal phenotype, resembles the remarkable phenotypic plasticity of neural crest cells, and differentiates into adipocytes and osteocytes under the influence of environmental factors

Sex hormone binding globulin phenotypes

DEFF Research Database (Denmark)

Cornelisse, M M; Bennett, Patrick; Christiansen, M

1994-01-01

Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis.

Science.gov (United States)

Lee, Jessica J Y; Gottlieb, Michael M; Lever, Jake; Jones, Steven J M; Blau, Nenad; van Karnebeek, Clara D M; Wasserman, Wyeth W

2018-05-01

Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the benefits of phenomics into the field of inborn errors of metabolism (IEM), we have recently launched IEMbase, an expert-curated knowledgebase of IEM and their disease-characterizing phenotypes. While our efforts with IEMbase have realized benefits, taking full advantage of phenomics requires a comprehensive curation of IEM phenotypes in core phenomics projects, which is dependent upon contributions from the IEM clinical and research community. Here, we assess the inclusion of IEM biochemical phenotypes in a core phenomics project, the Human Phenotype Ontology. We then demonstrate the utility of biochemical phenotypes using a text-based phenomics method to predict gene-disease relationships, showing that the prediction of IEM genes is significantly better using biochemical rather than clinical profiles. The findings herein provide a motivating goal for the IEM community to expand the computationally accessible descriptions of biochemical phenotypes associated with IEM in phenomics resources.

Investigating genotype-phenotype relationships in Rett syndrome using an international data set.

Science.gov (United States)

Bebbington, A; Anderson, A; Ravine, D; Fyfe, S; Pineda, M; de Klerk, N; Ben-Zeev, B; Yatawara, N; Percy, A; Kaufmann, W E; Leonard, H

2008-03-11

Rett syndrome is an uncommon neurodevelopmental disorder with an incidence of 1:9,000 live female births. The principal genetic cause was first reported in 1999 when the association with mutations in the methyl-CpG-binding protein 2 (or MECP2) gene was identified. This study uses data from a large international database, InterRett, to examine genotype-phenotype relationships and compares these with previous findings in a population-based cohort. The data set for these analyses was derived from a subset of InterRett cases with subject information collected from the family, the clinician, or both. Individual phenotypic characteristics and clinical severity using three scales were compared among those with eight known recurrent pathogenic MECP2 mutations as well as those with C-terminal deletions (n = 272). Overall, p.R270X and p.R255X were the most severe and p.R133C and p.R294X were the mildest mutations. Significant differences by mutation were seen for individual phenotypic characteristics such as hand use, ambulation, and language. This multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations. Although the modifying influence of X inactivation on clinical severity could not be included in the analysis, the findings confirm clear genotype-phenotype relationships in Rett syndrome and show the benefits of collaboration crucial to effective research in rare disorders.

Infra-red thermography for high throughput field phenotyping in Solanum tuberosum.

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Ankush Prashar

Full Text Available The rapid development of genomic technology has made high throughput genotyping widely accessible but the associated high throughput phenotyping is now the major limiting factor in genetic analysis of traits. This paper evaluates the use of thermal imaging for the high throughput field phenotyping of Solanum tuberosum for differences in stomatal behaviour. A large multi-replicated trial of a potato mapping population was used to investigate the consistency in genotypic rankings across different trials and across measurements made at different times of day and on different days. The results confirmed a high degree of consistency between the genotypic rankings based on relative canopy temperature on different occasions. Genotype discrimination was enhanced both through normalising data by expressing genotype temperatures as differences from image means and through the enhanced replication obtained by using overlapping images. A Monte Carlo simulation approach was used to confirm the magnitude of genotypic differences that it is possible to discriminate. The results showed a clear negative association between canopy temperature and final tuber yield for this population, when grown under ample moisture supply. We have therefore established infrared thermography as an easy, rapid and non-destructive screening method for evaluating large population trials for genetic analysis. We also envisage this approach as having great potential for evaluating plant response to stress under field conditions.

Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

International Nuclear Information System (INIS)

Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean; Larsen, Annette K.; Escargueil, Alexandre

2016-01-01

We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences

Energy Technology Data Exchange (ETDEWEB)

Lorenzi, Tommaso [Centre de Mathématiques et de Leurs Applications, ENS Cachan, CNRS, Cachan 94230 Cedex, France & INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Chisholm, Rebecca H. [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052 (Australia); Lorz, Alexander; Neves de Almeida, Luís; Clairambault, Jean [Sorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); CNRS, UMR 7598, Laboratoire Jacques-Louis Lions, F-75005, Paris (France); INRIA-Paris-Rocquencourt, MAMBA Team, Domaine de Voluceau, BP105, 78153 Le Chesnay Cedex (France); Larsen, Annette K.; Escargueil, Alexandre [Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris (France); INSERM, UMR-S 938, Laboratory of “Cancer Biology and Therapeutics”, F-75012, Paris (France)

2016-06-08

We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

A matter of identity — Phenotype and differentiation potential of human somatic stem cells

Directory of Open Access Journals (Sweden)

S.E.P. New

2015-07-01

Full Text Available Human somatic stem cells with neural differentiation potential can be valuable for developing cell-based therapies, including treatment of birth-related defects, while avoiding issues associated with cell reprogramming. Precisely defining the “identity” and differentiation potential of somatic stem cells from different sources, has proven difficult, given differences in sets of specific markers, protocols used and lack of side-by-side characterization of these cells in different studies. Therefore, we set to compare expression of mesenchymal and neural markers in human umbilical cord-derived mesenchymal stem cells (UC-MSCs, pediatric adipose-derived stem cells (p-ADSCs in parallel with human neural stem cells (NSCs. We show that UC-MSCs at a basal level express mesenchymal and so-called “neural” markers, similar to that we previously reported for the p-ADSCs. All somatic stem cell populations studied, independently from tissue and patient of origin, displayed a remarkably similar expression of surface markers, with the main difference being the restricted expression of CD133 and CD34 to NSCs. Expression of certain surface and neural markers was affected by the expansion medium used. As predicted, UC-MSCs and p-ADSCs demonstrated tri-mesenchymal lineage differentiation potential, though p-ADSCs display superior chondrogenic differentiation capability. UC-MSCs and p-ADSCs responded also to neurogenic induction by up-regulating neuronal markers, but crucially they appeared morphologically immature when compared with differentiated NSCs. This highlights the need for further investigation into the use of these cells for neural therapies. Crucially, this study demonstrates the lack of simple means to distinguish between different cell types and the effect of culture conditions on their phenotype, and indicates that a more extensive set of markers should be used for somatic stem cell characterization, especially when developing therapeutic

Morphological variation among populations of Hemigrammus coeruleus (Characiformes: Characidae in a Negro River tributary, Brazilian Amazon

Directory of Open Access Journals (Sweden)

Henrique Lazzarotto

2017-03-01

Full Text Available ABSTRACT We explored patterns of phenotypic variation in Hemigrammus coeruleus from the Unini River basin, a blackwater river in the Brazilian Amazon. Geometric morphometrics was used to evaluate variation in body shape among populations from four tributaries (UN2-UN5. We found no evidence for sexual dimorphism in body size and shape. However, morphological differences among populations were detected as the analyses recovered significant groups corresponding to each sub-basin, with some overlap among them. The populations from UN2, UN3 and UN5 had more elongate bodies than fish from UN4. The most morphologically divergent population belonged to UN4, the tributary with the most divergent environmental conditions and the only one with seasonally-muddy waters. The morphological variation found among these populations is likely due to phenotypic plasticity or local adaptation, arising as a product of divergent ecological selection pressures among sub-basins. This work constitutes one of the first to employ a population-level geometric morphometric approach to assess phenotypic variation in Amazonian fishes. This method was able to distinguish subtle differences in body morphology, and its use with additional species can bring novel perspectives on the evaluation of general patterns of phenotypic differentiation in the Amazon.

Childhood asthma-predictive phenotype.

Science.gov (United States)

Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

2014-01-01

Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Transitions in optimal adaptive strategies for populations in fluctuating environments

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Mayer, Andreas; Mora, Thierry; Rivoire, Olivier; Walczak, Aleksandra M.

2017-09-01

Biological populations are subject to fluctuating environmental conditions. Different adaptive strategies can allow them to cope with these fluctuations: specialization to one particular environmental condition, adoption of a generalist phenotype that compromises between conditions, or population-wise diversification (bet hedging). Which strategy provides the largest selective advantage in the long run depends on the range of accessible phenotypes and the statistics of the environmental fluctuations. Here, we analyze this problem in a simple mathematical model of population growth. First, we review and extend a graphical method to identify the nature of the optimal strategy when the environmental fluctuations are uncorrelated. Temporal correlations in environmental fluctuations open up new strategies that rely on memory but are mathematically challenging to study: We present analytical results to address this challenge. We illustrate our general approach by analyzing optimal adaptive strategies in the presence of trade-offs that constrain the range of accessible phenotypes. Our results extend several previous studies and have applications to a variety of biological phenomena, from antibiotic resistance in bacteria to immune responses in vertebrates.

The Structure of The Extended Psychosis Phenotype in Early Adolescence-A Cross-sample Replication

NARCIS (Netherlands)

Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study

Science.gov (United States)

Koblizek, Vladimir; Milenkovic, Branislava; Barczyk, Adam; Tkacova, Ruzena; Somfay, Attila; Zykov, Kirill; Tudoric, Neven; Kostov, Kosta; Zbozinkova, Zuzana; Svancara, Jan; Sorli, Jurij; Krams, Alvils; Miravitlles, Marc

2017-01-01

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes. PMID:28495687

Genetic and environmental dissections of sub-phenotypes of metabolic syndrome in the chinese population: a twin-based heritability study

DEFF Research Database (Denmark)

Duan, Haiping; Pang, Zengchang; Zhang, Dongfeng

2011-01-01

contains 654 twins collected in the Qingdao municipality. A total of 10 phenotypes covering anthropometric measurements, plasma glucose levels, lipids, blood pressures etc. were examined. Univariate and bivariate structural equation models were fitted for assessing the genetic and environmental...... contributions. Results: The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for all phenotypes except for triglyceride. Modest to high heritability estimates were obtained in univariate analysis ranging from 0.5 for total cholesterol to 0.78 for weight...

A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

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Michael Hiller

2012-10-01

Full Text Available Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that—given only an independently lost phenotype and whole genomes—matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys, and the forthcoming availability of many new genomes all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.

Macrophage Phenotype and Function in Different Stages of Atherosclerosis

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Tabas, Ira; Bornfeldt, Karin E.

2016-01-01

The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

Seasonal cues induce phenotypic plasticity of Drosophila suzukii to enhance winter survival.

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Shearer, Peter W; West, Jessica D; Walton, Vaughn M; Brown, Preston H; Svetec, Nicolas; Chiu, Joanna C

2016-03-22

As global climate change and exponential human population growth intensifies pressure on agricultural systems, the need to effectively manage invasive insect pests is becoming increasingly important to global food security. Drosophila suzukii is an invasive pest that drastically expanded its global range in a very short time since 2008, spreading to most areas in North America and many countries in Europe and South America. Preliminary ecological modeling predicted a more restricted distribution and, for this reason, the invasion of D. suzukii to northern temperate regions is especially unexpected. Investigating D. suzukii phenology and seasonal adaptations can lead to a better understanding of the mechanisms through which insects express phenotypic plasticity, which likely enables invasive species to successfully colonize a wide range of environments. We describe seasonal phenotypic plasticity in field populations of D. suzukii. Specifically, we observed a trend of higher proportions of flies with the winter morph phenotype, characterized by darker pigmentation and longer wing length, as summer progresses to winter. A laboratory-simulated winter photoperiod and temperature (12:12 L:D and 10 °C) were sufficient to induce the winter morph phenotype in D. suzukii. This winter morph is associated with increased survival at 1 °C when compared to the summer morph, thus explaining the ability of D. suzukii to survive cold winters. We then used RNA sequencing to identify gene expression differences underlying seasonal differences in D. suzukii physiology. Winter morph gene expression is consistent with known mechanisms of cold-hardening such as adjustments to ion transport and up-regulation of carbohydrate metabolism. In addition, transcripts involved in oogenesis and DNA replication were down-regulated in the winter morph, providing the first molecular evidence of a reproductive diapause in D. suzukii. To date, D. suzukii cold resistance studies suggest that this

Surviving bacterial sibling rivalry: inducible and reversible phenotypic switching in Paenibacillus dendritiformis.

Science.gov (United States)

Be'er, Avraham; Florin, E-L; Fisher, Carolyn R; Swinney, Harry L; Payne, Shelley M

2011-01-01

Natural habitats vary in available nutrients and room for bacteria to grow, but successful colonization can lead to overcrowding and stress. Here we show that competing sibling colonies of Paenibacillus dendritiformis bacteria survive overcrowding by switching between two distinct vegetative phenotypes, motile rods and immotile cocci. Growing colonies of the rod-shaped bacteria produce a toxic protein, Slf, which kills cells of encroaching sibling colonies. However, sublethal concentrations of Slf induce some of the rods to switch to Slf-resistant cocci, which have distinct metabolic and resistance profiles, including resistance to cell wall antibiotics. Unlike dormant spores of P. dendritiformis, the cocci replicate. If cocci encounter conditions that favor rods, they secrete a signaling molecule that induces a switch to rods. Thus, in contrast to persister cells, P. dendritiformis bacteria adapt to changing environmental conditions by inducible and reversible phenotypic switching. In favorable environments, species may face space and nutrient limits due to overcrowding. Bacteria provide an excellent model for analyzing principles underlying overcrowding and regulation of density in nature, since their population dynamics can be easily and accurately assessed under controlled conditions. We describe a newly discovered mechanism for survival of a bacterial population during overcrowding. When competing with sibling colonies, Paenibacillus dendritiformis produces a lethal protein (Slf) that kills cells at the interface of encroaching colonies. Slf also induces a small proportion of the cells to switch from motile, rod-shaped cells to nonmotile, Slf-resistant, vegetative cocci. When crowding is reduced and nutrients are no longer limiting, the bacteria produce a signal that induces cocci to switch back to motile rods, allowing the population to spread. Genes encoding components of this phenotypic switching pathway are widespread among bacterial species, suggesting

Phenotypic plasticity in Drosophila cactophilic species: the effect of competition, density, and breeding sites.

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Fanara, Juan Jose; Werenkraut, Victoria

2017-08-01

Changes in the environmental conditions experienced by naturally occurring populations are frequently accompanied by changes in adaptive traits allowing the organism to cope with environmental unpredictability. Phenotypic plasticity is a major aspect of adaptation and it has been involved in population dynamics of interacting species. In this study, phenotypic plasticity (i.e., environmental sensitivity) of morphological adaptive traits were analyzed in the cactophilic species Drosophila buzzatii and Drosophila koepferae (Diptera: Drosophilidae) considering the effect of crowding conditions (low and high density), type of competition (intraspecific and interspecific competition) and cacti hosts (Opuntia and Columnar cacti). All traits (wing length, wing width, thorax length, wing loading and wing aspect) showed significant variation for each environmental factor considered in both Drosophila species. The phenotypic plasticity pattern observed for each trait was different within and between these cactophilic Drosophila species depending on the environmental factor analyzed suggesting that body size-related traits respond almost independently to environmental heterogeneity. The effects of ecological factors analyzed in this study are discussed in order to elucidate the causal factors investigated (type of competition, crowding conditions and alternative host) affecting the election of the breeding site and/or the range of distribution of these cactophilic species. © 2016 Institute of Zoology, Chinese Academy of Sciences.

Psychotic-like experiences in the general population: characterizing a high-risk group for psychosis.

LENUS (Irish Health Repository)

Kelleher, I

2011-01-01

Recent research shows that psychotic symptoms, or psychotic-like experiences (PLEs), are reported not only by psychosis patients but also by healthy members of the general population. Healthy individuals who report these symptoms are considered to represent a non-clinical psychosis phenotype, and have been demonstrated to be at increased risk of schizophrenia-spectrum disorder. Converging research now shows that this non-clinical psychosis phenotype is familial, heritable and covaries with familial schizophrenia-spectrum disorder. A review of the research also shows that the non-clinical phenotype is associated extensively with schizophrenia-related risk factors, including social, environmental, substance use, obstetric, developmental, anatomical, motor, cognitive, linguistic, intellectual and psychopathological risk factors. The criterion and construct validity of the non-clinical psychosis phenotype with schizophrenia demonstrates that it is a valid population in which to study the aetiology of psychosis. Furthermore, it suggests shared genetic variation between the clinical and non-clinical phenotypes. Much remains to be learned about psychosis by broadening the scope of research to include the non-clinical psychosis phenotype.

Genetic association analysis of vitamin D receptor gene polymorphisms and obesity-related phenotypes.

Science.gov (United States)

Correa-Rodríguez, M; Carrillo-Ávila, J A; Schmidt-RioValle, J; González-Jiménez, E; Vargas, S; Martín, J; Rueda-Medina, B

2018-01-15

Vitamin D has been established as a key factor in the development of obesity through the vitamin D receptor (VDR). The aim of this study was to investigate the contribution of the VDR gene to obesity-related phenotypes in a population of Caucasian young adults. The study population consisted of 701 healthy Spanish young adults (mean age 20.41±2.48). Three single-nucleotide polymorphisms (SNPs) of VDR (TaqI, BsmI and FokI) were selected as genetic markers. Body composition measurements including weight, body mass index (BMI), fat mass (FM), percentage of fat mass (PFM), fat-free mass (FFM) and visceral fat level (VFL) were analysed. Differences in obesity traits across the genotypes were determined using analysis of covariance (ANCOVA). The FokI polymorphism showed a significant association with PFM across the whole population after adjusting for age and sex (p=0.022). Age-adjusted analysis revealed an association between body weight and the TaqI and BsmI SNPs in males (p=0.033 and p=0.028, respectively). However, these positive findings did not remain significant after applying the Bonferroni correction for multiple testing. Our findings suggest that VDR genetic variants are unlikely to play a major role in obesity-related phenotypes in a population of Caucasian young adults. Copyright © 2017 Elsevier B.V. All rights reserved.

Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the Di@bet.es study.

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Gutiérrez-Repiso, Carolina; Soriguer, Federico; Rojo-Martínez, Gemma; García-Fuentes, Eduardo; Valdés, Sergio; Goday, Albert; Calle-Pascual, Alfonso; López-Alba, Alfonso; Castell, Conxa; Menéndez, Edelmiro; Bordiú, Elena; Delgado, Elías; Ortega, Emilio; Pascual-Manich, Gemma; Urrutia, Inés; Mora-Peces, Inmaculada; Vendrell, Joan; Vázquez, José Antonio; Franch, Josep; Girbés, Juan; Castaño, Luis; Serrano-Ríos, Manuel; Martínez-Larrad, María Teresa; Catalá, Miguel; Carmena, Rafael; Gomis, Ramón; Casamitjana, Roser; Gaztambide, Sonia

2014-09-01

Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations. Di@bet.es study is a national, cross-sectional population-based survey of 5728 adults conducted in 2009-2010. Clinical, metabolic, sociodemographic, and anthropometric data and information about lifestyle habits, such as physical activity, smoking habit, alcohol intake and food consumption, were collected. Subjects were classified according to their body mass index (BMI) (normal-weight, 30 kg/m(2)). CA included elevated blood pressure; elevated levels of triglycerides, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP); and elevated homeostasis model assessment of insulin resistance (HOMA-IR) value and low high-density lipoprotein cholesterol (HDL-c) level. Two phenotypes were defined: metabolically healthy phenotype (0-1 CA) and metabolically abnormal phenotype (≥2 CA). The prevalence of metabolically abnormal normal-weight phenotype was slightly lower in the Spanish population (6.5% vs. 8.1%). The prevalence of metabolically healthy overweight and MHO subjects was 20.9% and 7.0%, respectively, while in NHANES study it was 17.9% and 9.7%, respectively. Cigarette smoking was associated with CA in each phenotype, while moderate physical activity and moderate alcohol

Phenotypes of asthma in low-income children and adolescents: cluster analysis

Directory of Open Access Journals (Sweden)

Anna Lucia Barros Cabral

Full Text Available ABSTRACT Objective: Studies characterizing asthma phenotypes have predominantly included adults or have involved children and adolescents in developed countries. Therefore, their applicability in other populations, such as those of developing countries, remains indeterminate. Our objective was to determine how low-income children and adolescents with asthma in Brazil are distributed across a cluster analysis. Methods: We included 306 children and adolescents (6-18 years of age with a clinical diagnosis of asthma and under medical treatment for at least one year of follow-up. At enrollment, all the patients were clinically stable. For the cluster analysis, we selected 20 variables commonly measured in clinical practice and considered important in defining asthma phenotypes. Variables with high multicollinearity were excluded. A cluster analysis was applied using a twostep agglomerative test and log-likelihood distance measure. Results: Three clusters were defined for our population. Cluster 1 (n = 94 included subjects with normal pulmonary function, mild eosinophil inflammation, few exacerbations, later age at asthma onset, and mild atopy. Cluster 2 (n = 87 included those with normal pulmonary function, a moderate number of exacerbations, early age at asthma onset, more severe eosinophil inflammation, and moderate atopy. Cluster 3 (n = 108 included those with poor pulmonary function, frequent exacerbations, severe eosinophil inflammation, and severe atopy. Conclusions: Asthma was characterized by the presence of atopy, number of exacerbations, and lung function in low-income children and adolescents in Brazil. The many similarities with previous cluster analyses of phenotypes indicate that this approach shows good generalizability.

Network science meets respiratory medicine for OSAS phenotyping and severity prediction

Directory of Open Access Journals (Sweden)

Stefan Mihaicuta

2017-05-01

Full Text Available Obstructive sleep apnea syndrome (OSAS is a common clinical condition. The way that OSAS risk factors associate and converge is not a random process. As such, defining OSAS phenotypes fosters personalized patient management and population screening. In this paper, we present a network-based observational, retrospective study on a cohort of 1,371 consecutive OSAS patients and 611 non-OSAS control patients in order to explore the risk factor associations and their correlation with OSAS comorbidities. To this end, we construct the Apnea Patients Network (APN using patient compatibility relationships according to six objective parameters: age, gender, body mass index (BMI, blood pressure (BP, neck circumference (NC and the Epworth sleepiness score (ESS. By running targeted network clustering algorithms, we identify eight patient phenotypes and corroborate them with the co-morbidity types. Also, by employing machine learning on the uncovered phenotypes, we derive a classification tree and introduce a computational framework which render the Sleep Apnea Syndrome Score (SASScore; our OSAS score is implemented as an easy-to-use, web-based computer program which requires less than one minute for processing one individual. Our evaluation, performed on a distinct validation database with 231 consecutive patients, reveals that OSAS prediction with SASScore has a significant specificity improvement (an increase of 234% for only 8.2% sensitivity decrease in comparison with the state-of-the-art score STOP-BANG. The fact that SASScore has bigger specificity makes it appropriate for OSAS screening and risk prediction in big, general populations.

Medications and Side Effects

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... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

Science.gov (United States)

Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

2014-07-21

Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

Differential response to ocean acidification in physiological traits of Concholepas concholepas populations

Science.gov (United States)

Lardies, Marco A.; Arias, María Belén; Poupin, María Josefina; Manríquez, Patricio H.; Torres, Rodrigo; Vargas, Cristian A.; Navarro, Jorge M.; Lagos, Nelson A.

2014-07-01

Phenotypic adaptation to environmental fluctuations frequently occurs by preexisting plasticity and its role as a major component of variation in physiological diversity is being widely recognized. Few studies have considered the change in phenotypic flexibility among geographic populations in marine calcifiers to ocean acidification projections, despite the fact that this type of study provides understanding about how the organism may respond to this chemical change in the ocean. We examined the geographic variation in CO2 seawater concentrations in the phenotype and in the reaction norm of physiological traits using a laboratory mesocosm approach with short-term acclimation in two contrasting populations (Antofagasta and Calfuco) of the intertidal snail Concholepas concholepas. Our results show that elevated pCO2 conditions increase standard metabolic rates in both populations of the snail juveniles, likely due to the higher energy cost of homeostasis. Juveniles of C. concholepas in the Calfuco (southern) population showed a lower increment of metabolic rate in high-pCO2 environments concordant with a lesser gene expression of a heat shock protein with respect to the Antofagasta (northern) population. Combined these results indicate a negative effect of ocean acidification on whole-organism functioning of C. concholepas. Finally, the significant Population × pCO2 level interaction in both studied traits indicates that there is variation between populations in response to high-pCO2 conditions.

Biomechanics of side impact: injury criteria, aging occupants, and airbag technology.

Science.gov (United States)

Yoganandan, Narayan; Pintar, Frank A; Stemper, Brian D; Gennarelli, Thomas A; Weigelt, John A

2007-01-01

This paper presents a survey of side impact trauma-related biomedical investigations with specific reference to certain aspects of epidemiology relating to the growing elderly population, improvements in technology such as side airbags geared toward occupant safety, and development of injury criteria. The first part is devoted to the involvement of the elderly by identifying variables contributing to injury including impact severity, human factors, and national and international field data. This is followed by a survey of various experimental models used in the development of injury criteria and tolerance limits. The effects of fragility of the elderly coupled with physiological changes (e.g., visual, musculoskeletal) that may lead to an abnormal seating position (termed out-of-position) especially for the driving population are discussed. Fundamental biomechanical parameters such as thoracic, abdominal and pelvic forces; upper and lower spinal and sacrum accelerations; and upper, middle and lower chest deflections under various initial impacting conditions are evaluated. Secondary variables such as the thoracic trauma index and pelvic acceleration (currently adopted in the United States Federal Motor Vehicle Safety Standards), peak chest deflection, and viscous criteria are also included in the survey. The importance of performing research studies with specific focus on out-of-position scenarios of the elderly and using the most commonly available torso side airbag as the initial contacting condition in lateral impacts for occupant injury assessment is emphasized.

Computer program determines exact two-sided tolerance limits for normal distributions

Science.gov (United States)

Friedman, H. A.; Webb, S. R.

1968-01-01

Computer program determines by numerical integration the exact statistical two-sided tolerance limits, when the proportion between the limits is at least a specified number. The program is limited to situations in which the underlying probability distribution for the population sampled is the normal distribution with unknown mean and variance.

Parkinson Disease: The Relationship Between Non-motor Symptoms and Motor Phenotype.

Science.gov (United States)

Ba, Fang; Obaid, Mona; Wieler, Marguerite; Camicioli, Richard; Martin, W R Wayne

2016-03-01

Parkinson disease (PD) presents with motor and non-motor symptoms (NMS). The NMS often precede the onset of motor symptoms, but may progress throughout the disease course. Tremor dominant, postural instability gait difficulty (PIGD), and indeterminate phenotypes can be distinguished using Unified PD Rating scales (UPDRS-III). We hypothesized that the PIGD phenotype would be more likely to develop NMS, and that the non-dopamine-responsive axial signs would correlate with NMS severity. We conducted a retrospective cross-sectional chart review to assess the relationship between NMS and PD motor phenotypes. PD patients were administered the NMS Questionnaire, the UPDRS-III, and the Mini-Mental State Examination score. The relationship between NMS burden and PD subtypes was examined using linear regression models. The prevalence of each NMS among difference PD motor subtypes was analyzed using chi-square test. PD patients with more advanced disease based on their UPDRS-III had higher NMS Questionnaire scores. The axial component of UPDRS-III correlated with higher NMS. There was no correlation between NMS and tremor scores. There was a significant correlation between PIGD score and higher NMS burden. PIGD group had higher prevalence in most NMS domains when compared with tremor dominant and indeterminate groups independent of disease duration and severity. NMS profile and severity vary according to motor phenotype. We conclude that in the PD population, patients with a PIGD phenotype who have more axial involvement, associated with advanced disease and poor motor response, have a higher risk for a higher NMS burden.

Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping

DEFF Research Database (Denmark)

Vaysse, Amaury; Ratnakumar, Abhirami; Derrien, Thomas

2011-01-01

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse br...

The Moon's near side megabasin and far side bulge

CERN Document Server

Byrne, Charles

2013-01-01

Since Luna and Lunar Orbiter photographed the far side of the Moon, the mysterious dichotomy between the face of the Moon as we see it from Earth and the side of the Moon that is hidden has puzzled lunar scientists. As we learned more from the Apollo sample return missions and later robotic satellites, the puzzle literally deepened, showing asymmetry of the crust and mantle, all the way to the core of the Moon. This book summarizes the author’s successful search for an ancient impact feature, the Near Side Megabasin of the Moon and the extensions to impact theory needed to find it. The implications of this ancient event are developed to answer many of the questions about the history of the Moon.

Side Effects (Management)

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... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

Profiling the extended phenotype of plant pathogens: Challenges in Bacterial Molecular Plant Pathology.

Science.gov (United States)

Preston, Gail M

2017-04-01

One of the most fundamental questions in plant pathology is what determines whether a pathogen grows within a plant? This question is frequently studied in terms of the role of elicitors and pathogenicity factors in the triggering or overcoming of host defences. However, this focus fails to address the basic question of how the environment in host tissues acts to support or restrict pathogen growth. Efforts to understand this aspect of host-pathogen interactions are commonly confounded by several issues, including the complexity of the plant environment, the artificial nature of many experimental infection systems and the fact that the physiological properties of a pathogen growing in association with a plant can be very different from the properties of the pathogen in culture. It is also important to recognize that the phenotype and evolution of pathogen and host are inextricably linked through their interactions, such that the environment experienced by a pathogen within a host, and its phenotype within the host, is a product of both its interaction with its host and its evolutionary history, including its co-evolution with host plants. As the phenotypic properties of a pathogen within a host cannot be defined in isolation from the host, it may be appropriate to think of pathogens as having an 'extended phenotype' that is the product of their genotype, host interactions and population structure within the host environment. This article reflects on the challenge of defining and studying this extended phenotype, in relation to the questions posed below, and considers how knowledge of the phenotype of pathogens in the host environment could be used to improve disease control. What determines whether a pathogen grows within a plant? What aspects of pathogen biology should be considered in describing the extended phenotype of a pathogen within a host? How can we study the extended phenotype in ways that provide insights into the phenotypic properties of pathogens

Targeting the latest hallmark of cancer: another attempt at 'magic bullet' drugs targeting cancers' metabolic phenotype.

Science.gov (United States)

Cuperlovic-Culf, M; Culf, A S; Touaibia, M; Lefort, N

2012-10-01

The metabolism of tumors is remarkably different from the metabolism of corresponding normal cells and tissues. Metabolic alterations are initiated by oncogenes and are required for malignant transformation, allowing cancer cells to resist some cell death signals while producing energy and fulfilling their biosynthetic needs with limiting resources. The distinct metabolic phenotype of cancers provides an interesting avenue for treatment, potentially with minimal side effects. As many cancers show similar metabolic characteristics, drugs targeting the cancer metabolic phenotype are, perhaps optimistically, expected to be 'magic bullet' treatments. Over the last few years there have been a number of potential drugs developed to specifically target cancer metabolism. Several of these drugs are currently in clinical and preclinical trials. This review outlines examples of drugs developed for different targets of significance to cancer metabolism, with a focus on small molecule leads, chemical biology and clinical results for these drugs.

Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes

Directory of Open Access Journals (Sweden)

Chris L. Smith

2016-06-01

Full Text Available Glioblastoma multiforme is a heterogeneous and infiltrative cancer with dismal prognosis. Studying the migratory behavior of tumor-derived cell populations can be informative, but it places a high premium on the precision of in vitro methods and the relevance of in vivo conditions. In particular, the analysis of 2D cell migration may not reflect invasion into 3D extracellular matrices in vivo. Here, we describe a method that allows time-resolved studies of primary cell migration with single-cell resolution on a fibrillar surface that closely mimics in vivo 3D migration. We used this platform to screen 14 patient-derived glioblastoma samples. We observed that the migratory phenotype of a subset of cells in response to platelet-derived growth factor was highly predictive of tumor location and recurrence in the clinic. Therefore, migratory phenotypic classifiers analyzed at the single-cell level in a patient-specific way can provide high diagnostic and prognostic value for invasive cancers.

Epistasis can accelerate adaptive diversification in haploid asexual populations.

Science.gov (United States)

Griswold, Cortland K

2015-03-07

A fundamental goal of the biological sciences is to determine processes that facilitate the evolution of diversity. These processes can be separated into ecological, physiological, developmental and genetic. An ecological process that facilitates diversification is frequency-dependent selection caused by competition. Models of frequency-dependent adaptive diversification have generally assumed a genetic basis of phenotype that is non-epistatic. Here, we present a model that indicates diversification is accelerated by an epistatic basis of phenotype in combination with a competition model that invokes frequency-dependent selection. Our model makes use of a genealogical model of epistasis and insights into the effects of balancing selection on the genealogical structure of a population to understand how epistasis can facilitate diversification. The finding that epistasis facilitates diversification may be informative with respect to empirical results that indicate an epistatic basis of phenotype in experimental bacterial populations that experienced adaptive diversification. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460.

Science.gov (United States)

Choi, Seon Young; Kim, Hang-Rae; Ryu, Pan Dong; Lee, So Yeong

2017-02-21

Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.

A test for pre-adapted phenotypic plasticity in the invasive tree Acer negundo L.

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Lamarque, Laurent J; Porté, Annabel J; Eymeric, Camille; Lasnier, Jean-Baptiste; Lortie, Christopher J; Delzon, Sylvain

2013-01-01

Phenotypic plasticity is a key mechanism associated with the spread of exotic plants and previous studies have found that invasive species are generally more plastic than co-occurring species. Comparatively, the evolution of phenotypic plasticity in plant invasion has received less attention, and in particular, the genetic basis of plasticity is largely unexamined. Native from North America, Acer negundo L. is aggressively impacting the riparian forests of southern and eastern Europe thanks to higher plasticity relative to co-occurring native species. We therefore tested here whether invasive populations have evolved increased plasticity since introduction. The performance of 1152 seedlings from 8 native and 8 invasive populations was compared in response to nutrient availability. Irrespective of nutrients, invasive populations had higher growth and greater allocation to above-ground biomass relative to their native conspecifics. More importantly, invasive genotypes did not show increased plasticity in any of the 20 traits examined. This result suggests that the high magnitude of plasticity to nutrient variation of invasive seedlings might be pre-adapted in the native range. Invasiveness of A. negundo could be explained by higher mean values of traits due to genetic differentiation rather than by evolution of increased plasticity.

Parameters in the estimation of the most suitable F2 population size in conventional maize (Zea mays L. breeding programs

Directory of Open Access Journals (Sweden)

Delić Nenad

2010-01-01

Full Text Available The objective of the present study was to observe differences among four sizes of the F2 populations (100, 200, 300 and 500 plants on the basis of test-crosses for grain yield according to the average values of the populations, genetic and phenotypic variances, genotypic and phenotypic coefficients of variations and broad-sense heritability. The values of genetic variance did not significantly differ over population sizes according to all possible comparisons, including the comparison of values obtained for the phenotypic variance. Furthermore, the values of broadsense heritability (67.8%-69% did not significantly vary over different F2 population sizes. Genetic variability of the observed progenies, as a principal prerequisite of successful selection, was at the satisfactory level in all population sizes.

Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells

International Nuclear Information System (INIS)

Doherty, R.E.; Haywood-Small, S.L.; Sisley, K.; Cross, N.A.

2011-01-01

Highlights: ► Isolated ALDH Hi PC3 cells preferentially form primitive holoclone-type colonies. ► Primitive holoclone colonies are predominantly ALDH Lo but contain rare ALDH Hi cells. ► Holoclone-forming cells are not restricted to the ALDH Hi population. ► ALDH phenotypic plasticity occurs in PC3 cells (ALDH Lo to ALDH Hi and vice versa). ► ALDH Hi cells are observed but very rare in PC3 spheroids grown in stem cell medium. -- Abstract: Aldehyde dehydrogenase 1 (ALDH) activity is considered to be a marker of cancer stem cells (CSCs) in many tumour models, since these cells are more proliferative and tumourigenic than ALDH Lo cells in experimental models. However it is unclear whether all CSC-like cells are within the ALDH Hi population, or whether all ALDH Hi cells are highly proliferative and tumourigenic. The ability to establish a stem cell hierarchy in vitro, whereby sub-populations of cells have differing proliferative and differentiation capacities, is an alternate indication of the presence of stem cell-like populations within cell lines. In this study, we have examined the interaction between ALDH status and the ability to establish a stem cell hierarchy in PC3 prostate cancer cells. We demonstrate that PC3 cells contain a stem cell hierarchy, and isolation of ALDH Hi cells enriches for the most primitive holoclone population, however holoclone formation is not restricted to ALDH Hi cells. In addition, we show that ALDH activity undergoes phenotypic plasticity, since the ALDH Lo population can develop ALDH Hi populations comparable to parental cells within 2 weeks in culture. Furthermore, we show that the majority of ALDH Hi cells are found within the least primitive paraclone population, which is circumvented by culturing PC3 cells as spheroids in defined medium favouring stem cell characteristics. Although ALDH Hi status enriches for holoclone formation, this activity may be mediated by a minority of ALDH Hi cells.

Maintenance of phenotypic variation: repeatibility, heritability, and size-dependent processes in a wild brook trout population

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Benjamin H. Letcher; Jason A Coombs; Keith H. Nislow

2011-01-01

Phenotypic variation in body size can result from within-cohort variation in birth dates, among-individual growth variation and size-selective processes. We explore the relative effects of these processes on the maintenance of wide observed body size variation in stream-dwelling brook trout (Salvelinus fontinalis). Based on the analyses of multiple...

49 CFR 231.4 - Fixed-end low-side gondola and low-side hopper cars.

Science.gov (United States)

2010-10-01

... cars. 231.4 Section 231.4 Transportation Other Regulations Relating to Transportation (Continued... Fixed-end low-side gondola and low-side hopper cars. (Cars with sides 36 inches or less above the floor are low-side cars.) (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see...

Expansive phenotypic landscape of Botrytis cinerea shows differential contribution of genetic diversity and plasticity

DEFF Research Database (Denmark)

Corwin, Jason A; Subedy, Anushriya; Eshbaugh, Robert

2016-01-01

and genetic diversity for virulence-associated phenotypes in a generalist plant pathogen, we grew a population of 15 isolates of Botrytis cinerea from throughout the world, under a variety of in vitro and in planta conditions. Under in planta conditions, phenotypic differences between the isolates were......The modern evolutionary synthesis suggests that both environmental variation and genetic diversity are critical determinants of pathogen success. However, the relative contribution of these two sources of variation is not routinely measured. To estimate the relative contribution of plasticity...... determined by the combination of genotypic variation within the pathogen and environmental variation. In contrast, phenotypic differences between the isolates under in vitro conditions were predominantly determined by genetic variation in the pathogen. Using a correlation network approach, we link...

Clinical phenotypes of asthma

NARCIS (Netherlands)

Bel, Elisabeth H.

2004-01-01

PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

Science.gov (United States)

Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

2016-02-01

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

A Study of Clinicopathological Differences Between Right-sided and Left-sided Colon Cancers

OpenAIRE

芳賀, 駿介; 遠藤, 俊吾; 加藤, 博之; 高橋, 直樹; 吉松, 和彦; 橋本, 雅彦; 石橋, 敬一郎; 梅原, 有弘; 横溝, 肇; 梶原, 哲郎; Shunsuke, HAGA; Shungo, ENDO; Hiroyuki, KATO; Naoki, TAKAHASHI; Kazuhiko, YOSHIMATSU

1996-01-01

The present study was aimed to determine the clinicopathological features of cancers of the right-sided colon (cecum, ascending colon, transverse colon) and left-sided colon (descending colon, sigmoid colon) in order to help improve the efficacy of their treatment. Excluding multiple cancer cases, 364 patients with primary colon cancer underwent surgey at our department between 1974 and 1994; they comprised 171 individuals with right-sided colon cancer and 193 with left-sided colon cancer. A ...

Side-View Face Recognition

NARCIS (Netherlands)

Santemiz, P.; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.

2010-01-01

Side-view face recognition is a challenging problem with many applications. Especially in real-life scenarios where the environment is uncontrolled, coping with pose variations up to side-view positions is an important task for face recognition. In this paper we discuss the use of side view face

eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

Directory of Open Access Journals (Sweden)

Specht Günther

2010-03-01

Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

Science.gov (United States)

Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

2010-03-09

Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

Single-sided NMR

CERN Document Server

Casanova, Federico; Blümich, Bernhard

2011-01-01

Single-Sided NMR describes the design of the first functioning single-sided tomograph, the related measurement methods, and a number of applications. One of the key advantages to this method is the speed at which the images are obtained.

Incidence of Important Hemobilia Following Transhepatic Biliary Drainage: Left-Sided Versus Right-Sided Approaches

International Nuclear Information System (INIS)

Rivera-Sanfeliz, G. M.; Assar, O. S. A.; LaBerge, J. M.; Wilson, M. W.; Gordon, R. L.; Ring, E. J.; Kerlan, R. K. Jr.

2004-01-01

Our purpose here is to describe our experience with important hemobilia following PTBD and to determine whether left-sided percutaneous transhepatic biliary drainage (PTBD) is associated with an increased incidence of important hemobilia compared to right-sided drainages. We reviewed 346 transhepatic biliary drainages over a four-year period and identified eight patients (2.3%) with important hemobilia requiring transcatheter embolization. The charts and radiographic files of these patients were reviewed. The side of the PTBD (left versus right), and the order of the biliary ductal branch entered (first, second, or third) were recorded. Of the 346 PTBDs, 269 were right-sided and 77 were left-sided. Of the eight cases of important hemobilia requiring transcatheter embolization, four followed right-sided and four followed left-sided PTBD, corresponding to a bleeding incidence of 1.5% (4/269) for right PTBD and 5.2% (4/77) for left PTBD. The higher incidence of hemobilia associated with left-sided PTBD approached, but did not reach the threshold of statistical significance (p = 0.077). In six of the eight patients requiring transcatheter embolization, first or second order biliary branches were accessed by catheter for PTBD. All patients with left-sided bleeding had first or proximal second order branches accessed by biliary drainage catheters. In conclusion, a higher incidence of hemobilia followed left- versus right-sided PTBD in this study, but the increased incidence did not reach statistical significance

Latitudinal patterns in phenotypic plasticity and fitness-related traits: assessing the climatic variability hypothesis (CVH with an invasive plant species.

Directory of Open Access Journals (Sweden)

Marco A Molina-Montenegro

Full Text Available Phenotypic plasticity has been suggested as the main mechanism for species persistence under a global change scenario, and also as one of the main mechanisms that alien species use to tolerate and invade broad geographic areas. However, contrasting with this central role of phenotypic plasticity, standard models aimed to predict the effect of climatic change on species distributions do not allow for the inclusion of differences in plastic responses among populations. In this context, the climatic variability hypothesis (CVH, which states that higher thermal variability at higher latitudes should determine an increase in phenotypic plasticity with latitude, could be considered a timely and promising hypothesis. Accordingly, in this study we evaluated, for the first time in a plant species (Taraxacum officinale, the prediction of the CVH. Specifically, we measured plastic responses at different environmental temperatures (5 and 20°C, in several ecophysiological and fitness-related traits for five populations distributed along a broad latitudinal gradient. Overall, phenotypic plasticity increased with latitude for all six traits analyzed, and mean trait values increased with latitude at both experimental temperatures, the change was noticeably greater at 20° than at 5°C. Our results suggest that the positive relationship found between phenotypic plasticity and geographic latitude could have very deep implications on future species persistence and invasion processes under a scenario of climate change.

Latitudinal patterns in phenotypic plasticity and fitness-related traits: assessing the climatic variability hypothesis (CVH) with an invasive plant species.

Science.gov (United States)

Molina-Montenegro, Marco A; Naya, Daniel E

2012-01-01

Phenotypic plasticity has been suggested as the main mechanism for species persistence under a global change scenario, and also as one of the main mechanisms that alien species use to tolerate and invade broad geographic areas. However, contrasting with this central role of phenotypic plasticity, standard models aimed to predict the effect of climatic change on species distributions do not allow for the inclusion of differences in plastic responses among populations. In this context, the climatic variability hypothesis (CVH), which states that higher thermal variability at higher latitudes should determine an increase in phenotypic plasticity with latitude, could be considered a timely and promising hypothesis. Accordingly, in this study we evaluated, for the first time in a plant species (Taraxacum officinale), the prediction of the CVH. Specifically, we measured plastic responses at different environmental temperatures (5 and 20°C), in several ecophysiological and fitness-related traits for five populations distributed along a broad latitudinal gradient. Overall, phenotypic plasticity increased with latitude for all six traits analyzed, and mean trait values increased with latitude at both experimental temperatures, the change was noticeably greater at 20° than at 5°C. Our results suggest that the positive relationship found between phenotypic plasticity and geographic latitude could have very deep implications on future species persistence and invasion processes under a scenario of climate change.

Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype.

Science.gov (United States)

Kring, Sofia Inez Iqbal; Larsen, Lesli Hingstrup; Holst, Claus; Toubro, Søren; Hansen, Torben; Astrup, Arne; Pedersen, Oluf; Sørensen, Thorkild I A

2008-01-01

In previous studies of associations of variants in the genes UCP2, UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have used a case-control approach with cases defined by a threshold for BMI. In the present study, we assess the association of seven abdominal, peripheral, and overall obesity phenotypes, which were analyzed quantitatively, and thirteen candidate gene polymorphisms in these ten genes in the same cohort. Obese Caucasian men (n = 234, BMI >or= 31.0 kg/m(2)) and a randomly sampled non-obese group (n = 323), originally identified at the draft board examinations, were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA scanning. Obesity phenotypes included BMI, fat body mass index, waist circumference, waist for given BMI, intra-abdominal adipose tissue, hip circumference and lower body fat mass (%). Using logistic regression models, we estimated the odds for defined genotypes (dominant or recessive genetic transmission) in relation to z-scores of the phenotypes. The minor (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip circumference. The minor allele for UCP2 Ins45bp was associated with increased BMI, increased abdominal obesity, and increased hip circumference. The minor allele for UCP2 -866G>A (rs6593669) was associated with borderline increased fat body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated with reduced abdominal obesity. None of the other genotype-phenotype combinations showed appreciable associations. If replicated in independent studies with focus on the specific phenotypes, our explorative studies suggest significant associations between some candidate gene polymorphisms and distinct obesity phenotypes, predicting beneficial and detrimental effects, depending on compartments for body fat accumulation. Copyright 2008 S. Karger AG, Basel.

Radiation Therapy Side Effects

Science.gov (United States)

Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

Comparative mitochondrial genetics of North American and Eurasian mergansers with an emphasis on the endangered scaly-sided merganser (Mergus squamatus)

Science.gov (United States)

Solovyeva, Diana V.; Pearce, John M.

2011-01-01

The scaly-sided merganser, Mergus squamatus, is considered one of the most threatened sea duck species in the Palearctic with limited breeding and wintering distribution in China and Russia. To provide information for future conservation efforts, we sequenced a portion of the mitochondrial (mt) DNA control region in four species of mergansers and three additional sea duck taxa to characterize the evolutionary history of the scaly-sided merganser, infer population trends that may have led to its limited geographic distribution, and to compare indices of genetic diversity among species of mergansers. Scaly-sided mergansers exhibit substantially lower levels of mtDNA genetic diversity (h = 0.292, π = 0.0007) than other closely related sea ducks and many other avian taxa. The four haplotypes observed differed by a single base pair suggesting that the species has not experienced a recent population decline but has instead been at a low population level for some time. A phylogenetic analysis placed the scaly-sided merganser basal to North American and European forms of the common merganser, M. merganser. Our inclusion of a small number of male samples doubled the number of mtDNA haplotypes observed, suggesting that additional genetic variation likely exists within the global population if there is immigration of males from unsampled breeding areas.

The Genetic Basis of Plant Architecture in 10 Maize Recombinant Inbred Line Populations.

Science.gov (United States)

Pan, Qingchun; Xu, Yuancheng; Li, Kun; Peng, Yong; Zhan, Wei; Li, Wenqiang; Li, Lin; Yan, Jianbing

2017-10-01

Plant architecture is a key factor affecting planting density and grain yield in maize ( Zea mays ). However, the genetic mechanisms underlying plant architecture in diverse genetic backgrounds have not been fully addressed. Here, we performed a large-scale phenotyping of 10 plant architecture-related traits and dissected the genetic loci controlling these traits in 10 recombinant inbred line populations derived from 14 diverse genetic backgrounds. Nearly 800 quantitative trait loci (QTLs) with major and minor effects were identified as contributing to the phenotypic variation of plant architecture-related traits. Ninety-two percent of these QTLs were detected in only one population, confirming the diverse genetic backgrounds of the mapping populations and the prevalence of rare alleles in maize. The numbers and effects of QTLs are positively associated with the phenotypic variation in the population, which, in turn, correlates positively with parental phenotypic and genetic variations. A large proportion (38.5%) of QTLs was associated with at least two traits, suggestive of the frequent occurrence of pleiotropic loci or closely linked loci. Key developmental genes, which previously were shown to affect plant architecture in mutant studies, were found to colocalize with many QTLs. Five QTLs were further validated using the segregating populations developed from residual heterozygous lines present in the recombinant inbred line populations. Additionally, one new plant height QTL, qPH3 , has been fine-mapped to a 600-kb genomic region where three candidate genes are located. These results provide insights into the genetic mechanisms controlling plant architecture and will benefit the selection of ideal plant architecture in maize breeding. © 2017 American Society of Plant Biologists. All Rights Reserved.

Functional characterizations of venom phenotypes in the eastern diamondback rattlesnake (Crotalus adamanteus) and evidence for expression-driven divergence in toxic activities among populations

Science.gov (United States)

Margres, Mark J.; Walls, Robert; Suntravat, Montamas; Lucena, Sara; Sánchez, Elda E.; Rokyta, Darin R.

2016-01-01

Phenotypes frequently vary across and within species. The connection between specific phenotypic effects and function, however, is less understood despite being essential to our understanding of the adaptive process. Snake venoms are ideal for identifying functionally important phenotypic variation because venom variation is common, and venoms can be functionally characterized through simple assays and toxicity measurements. Previous work with the eastern diamondback rattlesnake (Crotalus adamanteus) used multivariate statistical approaches to identify six unique venom phenotypes. We functionally characterized hemolytic, gelatinase, fibrinogenolytic, and coagulant activity for all six phenotypes, as well as one additional venom, to determine if the statistically significant differences in toxin expression levels previously documented corresponded to differences in venom activity. In general, statistical differences in toxin expression predicted the identified functional differences, or lack thereof, in toxic activity, demonstrating that the statistical approach used to characterize C. adamanteus venoms was a fair representation of biologically meaningful differences. Minor differences in activity not accounted for by the statistical model may be the result of amino-acid differences and/or post-translational modifications, but overall we were able to link variation in protein expression levels to variation in function as predicted by multivariate statistical approaches. PMID:27179420

Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K., E-mail: mishima-k@dent.showa-u.ac.jp

2013-05-01

Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.

Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Hayashi, S.; Tanaka, J.; Okada, S.; Isobe, T.; Yamamoto, G.; Yasuhara, R.; Irie, T.; Akiyama, C.; Kohno, Y.; Tachikawa, T.; Mishima, K.

2013-01-01

Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP) cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities