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Sample records for complex genetic structure

  1. Predicting complex mineral structures using genetic algorithms.

    PubMed

    Mohn, Chris E; Kob, Walter

    2015-10-28

    We show that symmetry-adapted genetic algorithms are capable of finding the ground state of a range of complex crystalline phases including layered- and incommensurate super-structures. This opens the way for the atomistic prediction of complex crystal structures of functional materials and mineral phases.

  2. The influence of climatic niche preferences on the population genetic structure of a mistletoe species complex.

    PubMed

    Ramírez-Barahona, Santiago; González, Clementina; González-Rodríguez, Antonio; Ornelas, Juan Francisco

    2017-06-01

    The prevalent view on genetic structuring in parasitic plants is that host-race formation is caused by varying degrees of host specificity. However, the relative importance of ecological niche divergence and host specificity to population differentiation remains poorly understood. We evaluated the factors associated with population differentiation in mistletoes of the Psittacanthus schiedeanus complex (Loranthaceae) in Mexico. We used genetic data from chloroplast sequences and nuclear microsatellites to study population genetic structure and tested its association with host preferences and climatic niche variables. Pairwise genetic differentiation was associated with environmental and host preferences, independent of geography. However, environmental predictors appeared to be more important than host preferences to explain genetic structure, supporting the hypothesis that the occurrence of the parasite is largely determined by its own climatic niche and, to a lesser degree, by host specificity. Genetic structure is significant within this mistletoe species complex, but the processes associated with this structure appear to be more complex than previously thought. Although host specificity was not supported as the major determinant of population differentiation, we consider this to be part of a more comprehensive ecological model of mistletoe host-race formation that incorporates the effects of climatic niche evolution. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  3. Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations.

    PubMed

    Montinaro, Francesco; Busby, George B J; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L; Capelli, Cristian

    2017-01-01

    The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries.

  4. Novel non-canonical genetic rearrangements termed "complex structural variations" in HBV genome.

    PubMed

    Fujiwara, Kei; Matsunami, Kayoko; Iio, Etsuko; Nojiri, Shunsuke; Joh, Takashi

    2017-06-15

    Chronic hepatitis B virus (HBV) infection is an important worldwide public health issue. Further knowledge on the characteristics of HBV will facilitate its eradication. Genome structural variations (SVs) are defined by its canonical form such as duplication, deletion, and insertion. However, recent studies have reported complex SVs that cannot be explained by those canonical SVs. A HBV strain (UK2) with an unusual genome structure rearrangement that was completely different from known mutations or rearrangements was previously reported. Thus, this study was conducted to confirm the rearrangement in UK2 as a novel complex SV, and to find additional HBV strains with complex SVs. Further, the contribution of complex SVs in hepadnavirus variability was investigated. The genome rearrangement pattern in UK2 was analyzed. Further, a search of online databases retrieved additional HBV strains which were candidates to harbor complex SVs. The architecture of each rearrangement in the candidate strains was analyzed by bioinformatical tools. In addition, alignment of woolly monkey hepatitis virus (WMHV) and HBV from human and non-human primates was performed to investigate the contribution of complex SVs to variability of hepadnavirus. The rearrangement in UK2 was confirmed as a complex SV. An additional 15 HBV strains were retrieved from databases, and confirmed as harboring complex SVs. Complex combinations of deletion, insertion, and duplication characterized the novel rearrangements. The complex SVs in six strains (37.5%) were composed of deletion, insertion, and duplication. The complex SVs in another six strains (37.5%) consisted of deletion and insertion, followed by insertions and duplication in three strains (18.8%), and deletion and duplication in one strain (6.3%). In addition, unique preS1 promoter insertions, which contained the hepatocyte nuclear factor 1 binding site, were observed in seven (43.8%) of 16 strains. Further, analysis of the genetic sequences of

  5. Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations

    PubMed Central

    Montinaro, Francesco; Busby, George B. J.; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L.; Capelli, Cristian

    2017-01-01

    The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries. PMID:27838627

  6. Fine-scale genetic structure, phylogeny and systematics of threatened crayfish species complex.

    PubMed

    Chiesa, S; Scalici, M; Negrini, R; Gibertini, G; Nonnis Marzano, F

    2011-10-01

    Systematic uncertainties in the crayfish Austropotamobius pallipes are well grounded by the number of species and subspecies described using different approaches, causing scientists to define this taxon as "complex". However, a key task that conservation programmes are facing regarding the recent and drastic decline of European populations, is the coherent systematic classification of this threatened species. Here we present results obtained by coupling mtDNA and genome analysis suggestive of a novel evolutionary framework to explain the relationships among phylogenetic lineages of A. pallipes. The direct sequencing of mtDNA COI gene fragment revealed a strong geographic structure with four distinct haplogroups separated by a range of 5-25 mutations. However, mitochondrial data were not supported by genomic fingerprinting based on 535 AFLP polymorphisms. Nuclear markers showed an unexpected moderate level of genetic differentiation and the absence of any geographic structure. Consequently, this study proposes that the taxonomic hypothesis of a single species of A. pallipes settling the Italian continental waters, is affected by complex evolutionary events. To solve the paradox, we hypothesized an evolutive scenario in which the separation of ancient mtDNA lineages likely occurred before the latest glacial periods. However, the speciation process remained incomplete due to secondary intensive postglacial contacts that forced the mingling of the genomes, and confounds the phylogeographic signature still detectable within mtDNA. Postglacial dispersion and the following demographic events, such as founder effects, drift and bottlenecks, abruptly depleted the local mtDNA variation, and shaped the current genetic population structure of white-clawed crayfish. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Risk of false positive genetic associations in complex traits with underlying population structure: a case study.

    PubMed

    Finno, Carrie J; Aleman, Monica; Higgins, Robert J; Madigan, John E; Bannasch, Danika L

    2014-12-01

    Genome-wide association (GWA) studies are widely used to investigate the genetic etiology of diseases in domestic animals. In the horse, GWA studies using 40-50,000 single nucleotide polymorphisms (SNPs) in sample sizes of 30-40 individuals, consisting of only 6-14 affected horses, have led to the discovery of genetic mutations for simple monogenic traits. Equine neuroaxonal dystrophy is a common inherited neurological disorder characterized by symmetric ataxia. A case-control GWA study was performed using genotypes from 42,819 SNP marker loci distributed across the genome in 99 clinically phenotyped Quarter horses (37 affected, 62 unaffected). A significant GWA was not achieved although a suggestive association was uncovered when only the most stringently phenotyped NAD-affected horses (n = 10) were included (chromosome 8:62130605 and 62134644 [log(1/P) = 5.56]). Candidate genes (PIK3C3, RIT2, and SYT4) within the associated region were excluded through sequencing, association testing of uncovered variants and quantitative RT-PCR. It was concluded that variants in PIK3C3, RIT2, and SYT4 are not responsible for equine neuroaxonal dystrophy. This study demonstrates the risk of false positive associations when performing GWA studies on complex traits and underlying population structure when using 40-50,000 SNP markers and small sample size.

  8. The Culex pipiens complex in continental Portugal: distribution and genetic structure.

    PubMed

    Gomes, Bruno; Parreira, Ricardo; Sousa, Carla A; Novo, Maria T; Almeida, António P G; Donnelly, Martin J; Pinto, João

    2012-12-01

    Portugal is a southern European country that displays favorable ecological conditions for the establishment of West Nile virus (WNV) transmission cycles. Competent mosquito vector species are present throughout the country. Among the species with reported cases of WNV isolation in Portugal, Culex pipiens is the most ubiquitous and abundant mosquito. This species exhibits two biological forms with differences in host preferences. The molestus form has a greater tendency to feed upon humans and other mammals whereas the pipiens form prefers avian hosts. In northern latitudes, both forms are physically separated, with molestus occupying underground habitats and pipiens being found aboveground. However, the warmer climatic conditions of southern regions such as Portugal may favor the sympatric occurrence of both forms hence promoting interform hybridization. Genetic introgression between molestus and pipiens forms may result in a higher propensity for admixed populations to serve as bridge-vectors of WNV between humans and birds. Here we revise our present knowledge on the distribution, role in WNV transmission and genetic structure of the Cx. pipiens complex in continental Portugal. We focus on recent findings of sympatric molestus and pipiens populations that display considerable levels of hybridization and discuss the epidemiological repercussions of this occurrence.

  9. Evolution and genetic structure of the great tit (Parus major) complex.

    PubMed

    Kvist, Laura; Martens, Jochen; Higuchi, Hiroyoshi; Nazarenko, Alexander A; Valchuk, Olga P; Orell, Markku

    2003-07-22

    The great tit complex is divided into four groups, each containing several subspecies. Even though the groups are known to differ markedly on morphological, vocal and behavioural characters, some hybridization occurs in the regions where they meet. The great tit has often been referred to as an example of a ring species, although this has later been questioned. Here, we have studied the genetic structure and phylogenetic relationships of the subspecies groups to clarify the evolutionary history of the complex using control region sequences of the mitochondrial DNA. The subspecies groups were found to be monophyletic and clearly distinct in mitochondrial haplotypes, and therefore must have had long-independent evolutionary histories. This conflicts with the ring species assignment and supports the formation of secondary contact zones of previously temporarily isolated groups. According to the phylogenetic species concept, all the subspecies groups could be considered as separate species, but if the definition of the biological species concept is followed, none of the subspecies groups is a true species because hybridization still occurs.

  10. Genetic diversity and population genetic structure analysis of Echinococcus granulosus sensu stricto complex based on mitochondrial DNA signature.

    PubMed

    Sharma, Monika; Fomda, Bashir Ahmad; Mazta, Saligram; Sehgal, Rakesh; Singh, Balbir Bagicha; Malla, Nancy

    2013-01-01

    The genetic diversity and population genetics of the Echinococcus granulosus sensu stricto complex were investigated based on sequencing of mitochondrial DNA (mtDNA). Total 81 isolates of hydatid cyst collected from ungulate animals from different geographical areas of North India were identified by sequencing of cytochrome c oxidase subunit1 (coxi) gene. Three genotypes belonging to E. granulosus sensu stricto complex were identified (G1, G2 and G3 genotypes). Further the nucleotide sequences (retrieved from GenBank) for the coxi gene from seven populations of E. granulosus sensu stricto complex covering 6 continents, were compared with sequences of isolates analysed in this study. Molecular diversity indices represent overall high mitochondrial DNA diversity for these populations, but low nucleotide diversity between haplotypes. The neutrality tests were used to analyze signatures of historical demographic events. The Tajima's D test and Fu's FS test showed negative value, indicating deviations from neutrality and both suggested recent population expansion for the populations. Pairwise fixation index was significant for pairwise comparison of different populations (except between South America and East Asia, Middle East and Europe, South America and Europe, Africa and Australia), indicating genetic differentiation among populations. Based on the findings of the present study and those from earlier studies, we hypothesize that demographic expansion occurred in E. granulosus after the introduction of founder haplotype particular by anthropogenic movements.

  11. Genetic structure of pike (Esox lucius) reveals a complex and previously unrecognized colonization history of Ireland

    PubMed Central

    Pedreschi, Debbi; Kelly-Quinn, Mary; Caffrey, Joe; O’Grady, Martin; Mariani, Stefano; Phillimore, Albert

    2014-01-01

    Aim We investigated genetic variation of Irish pike populations and their relationship with European outgroups, in order to elucidate the origin of this species to the island, which is largely assumed to have occurred as a human-mediated introduction over the past few hundred years. We aimed thereby to provide new insights into population structure to improve fisheries and biodiversity management in Irish freshwaters. Location Ireland, Britain and continental Europe. Methods A total of 752 pike (Esox lucius) were sampled from 15 locations around Ireland, and 9 continental European sites, and genotyped at six polymorphic microsatellite loci. Patterns and mechanisms of population genetic structure were assessed through a diverse array of methods, including Bayesian clustering, hierarchical analysis of molecular variance, and approximate Bayesian computation. Results Varying levels of genetic diversity and a high degree of population genetic differentiation were detected. Clear substructure within Ireland was identified, with two main groups being evident. One of the Irish populations showed high similarity with British populations. The other, more widespread, Irish strain did not group with any European population examined. Approximate Bayesian computation suggested that this widespread Irish strain is older, and may have colonized Ireland independently of humans. Main conclusions Population genetic substructure in Irish pike is high and comparable to the levels observed elsewhere in Europe. A comparison of evolutionary scenarios upholds the possibility that pike may have colonized Ireland in two ‘waves’, the first of which, being independent of human colonization, would represent the first evidence for natural colonization of a non-anadromous freshwater fish to the island of Ireland. Although further investigations using comprehensive genomic techniques will be necessary to confirm this, the present results warrant a reappraisal of current management strategies

  12. Exploring the Structural Complexity of Intermetallic Compounds by an Adaptive Genetic Algorithm

    NASA Astrophysics Data System (ADS)

    Zhao, X.; Nguyen, M. C.; Zhang, W. Y.; Wang, C. Z.; Kramer, M. J.; Sellmyer, D. J.; Li, X. Z.; Zhang, F.; Ke, L. Q.; Antropov, V. P.; Ho, K. M.

    2014-01-01

    Solving the crystal structures of novel phases with nanoscale dimensions resulting from rapid quenching is difficult due to disorder and competing polymorphic phases. Advances in computer speed and algorithm sophistication have now made it feasible to predict the crystal structure of an unknown phase without any assumptions on the Bravais lattice type, atom basis, or unit cell dimensions, providing a novel approach to aid experiments in exploring complex materials with nanoscale grains. This approach is demonstrated by solving a long-standing puzzle in the complex crystal structures of the orthorhombic, rhombohedral, and hexagonal polymorphs close to the Zr2Co11 intermetallic compound. From our calculations, we identified the hard magnetic phase and the origin of high coercivity in this compound, thus guiding further development of these materials for use as high performance permanent magnets without rare-earth elements.

  13. Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis.

    PubMed

    Williams, Robert W; Bennett, Beth; Lu, Lu; Gu, Jing; DeFries, John C; Carosone-Link, Phyllis J; Rikke, Brad A; Belknap, John K; Johnson, Thomas E

    2004-08-01

    The set of LXS recombinant inbred (RI) strains is a new and exceptionally large mapping panel that is suitable for the analysis of complex traits with comparatively high power. This panel consists of 77 strains-more than twice the size of other RI sets--and will typically provide sufficient statistical power (beta = 0.8) to map quantitative trait loci (QTLs) that account for approximately 25% of genetic variance with a genomewide p < 0.05. To characterize the genetic architecture of this new set of RI strains, we genotyped 330 MIT microsatellite markers distributed on all autosomes and the X Chromosome and assembled error-checked meiotic recombination maps that have an average F2-adjusted marker spacing of approximately 4 cM. The LXS panel has a genetic structure consistent with random segregation and subsequent fixation of alleles, the expected 3-4 x map expansion, a low level of nonsyntenic association among loci, and complete independence among all 77 strains. Although the parental inbred strains-Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS)--were derived originally by selection from an 8-way heterogeneous stock selected for differential sensitivity to sedative effects of ethanol, the LXS panel is also segregating for many other traits. Thus, the LXS panel provides a powerful new resource for mapping complex traits across many systems and disciplines and should prove to be of great utility in modeling the genetics of complex diseases in human populations.

  14. Application of Genetic Algorithm to the Design Optimization of Complex Energy Saving Glass Coating Structure

    NASA Astrophysics Data System (ADS)

    Johar, F. M.; Azmin, F. A.; Shibghatullah, A. S.; Suaidi, M. K.; Ahmad, B. H.; Abd Aziz, M. Z. A.; Salleh, S. N.; Shukor, M. Md

    2014-04-01

    Attenuation of GSM, GPS and personal communication signal leads to poor communication inside the building using regular shapes of energy saving glass coating. Thus, the transmission is very low. A brand new type of band pass frequency selective surface (FSS) for energy saving glass application is presented in this paper for one unit cell. Numerical Periodic Method of Moment approach according to a previous study has been applied to determine the new optimum design of one unit cell energy saving glass coating structure. Optimization technique based on the Genetic Algorithm (GA) is used to obtain an improved in return loss and transmission signal. The unit cell of FSS is designed and simulated using the CST Microwave Studio software at based on industrial, scientific and medical bands (ISM). A unique and irregular shape of an energy saving glass coating structure is obtained with lower return loss and improved transmission coefficient.

  15. [Characterization of the Structure of the Prokaryotic Complex of Antarctic Permafrost by Molecular Genetic Techniques].

    PubMed

    Manucharova, N A; Trosheva, E V; Kol'tsova, E M; Demkina, E V; Karaevskaya, E V; Rivkina, E M; Mardanov, A V; El'-Registan, G I

    2016-01-01

    A prokaryotic mesophilic organotrophic community responsible for 10% of the total microbial number determined by epifluorescence microscopy was reactivated in the samples ofAntarctic permafrost retrieved from the environment favoring long-term preservation of microbial communities (7500 years). No culturable forms were obtained without resuscitation procedures (CFU = 0). Proteobacteria, Actinobacteria, and Firmicutes were the dominant microbial groups in the complex. Initiation of the reactivated microbial complex by addition of chitin (0.1% wt/vol) resulted in an increased share of metabolically active biomass (up to 50%) due to the functional domination of chitinolytics caused by the target resource. Thus, sequential application of resuscitation procedures and initiation of a specific physiological group (in this case, chitinolytics) to a permafrost-preserved microbial community made it possible to reveal a prokaryotic complex capable of reversion of metabolic activity (FISH data), to determine its phylogenetic structure by metagenomic anal-ysis, and to isolate a pure culture of the dominant microorganism with high chitinolytic activity.

  16. Genetic structure and evolution of Alpine polyploid complexes: Ranunculus kuepferi (Ranunculaceae) as a case study.

    PubMed

    Burnier, J; Buerki, S; Arrigo, N; Küpfer, P; Alvarez, N

    2009-09-01

    The alpine white-flowered buttercup, Ranunculus kuepferi Greuter & Burdet, is a polyploid complex with diploids endemic to the southwestern Alps and polyploids - which have been previously described as apomictic - widespread throughout European mountains. Due to the polymorphic status of both its ploidy level and its reproductive mode, R. kuepferi represents a key species for understanding the evolution of polyploid lineages in alpine habitats. To disentangle the phylogeography of this polyploid taxon, we used cpDNA sequences and AFLP (amplified fragment length polymorphism) markers in 33 populations of R. kuepferi representative of its ploidy level and distribution area. Polyploid individuals were shown to be the result of at least two polyploidization events that may have taken place in the southwestern Alps. From this region, one single main migration of tetraploids colonized the entire Alpine range, the Apennines and Corsica. Genetic recombination among tetraploids was also observed, revealing the facultative nature of the apomictic reproductive mode in R. kuepferi polyploids. Our study shows the contrasting role played by diploid lineages mostly restricted to persistent refugia and by tetraploids, whose dispersal abilities have permitted their range extension all over the previously glaciated Alpine area and throughout neighbouring mountain massifs.

  17. Genetic, structural, and molecular insights into the function of ras of complex proteins domains.

    PubMed

    Civiero, Laura; Dihanich, Sybille; Lewis, Patrick A; Greggio, Elisa

    2014-07-17

    Ras of complex proteins (ROC) domains were identified in 2003 as GTP binding modules in large multidomain proteins from Dictyostelium discoideum. Research into the function of these domains exploded with their identification in a number of proteins linked to human disease, including leucine-rich repeat kinase 2 (LRRK2) and death-associated protein kinase 1 (DAPK1) in Parkinson's disease and cancer, respectively. This surge in research has resulted in a growing body of data revealing the role that ROC domains play in regulating protein function and signaling pathways. In this review, recent advances in the structural information available for proteins containing ROC domains, along with insights into enzymatic function and the integration of ROC domains as molecular switches in a cellular and organismal context, are explored.

  18. Phylogeographic analyses and genetic structure illustrate the complex evolutionary history of Phragmites australis in Mexico.

    PubMed

    Colin, Ricardo; Eguiarte, Luis E

    2016-05-01

    Genetic data suggest that three lineages of Phragmites australis are found in North America: the Native North American lineage, the Gulf Coast lineage, and the Invasive lineage. In Mexico, P. australis is a common species, but nothing is known about the distribution or ecology of these lineages. We examined the phylogeography of P. australis to analyze the current geographic distribution of genetic variation, demographic history, and dispersal patterns to better understand its evolutionary history in Mexico. We sampled 427 individuals from 28 populations. We used two noncoding regions of chloroplast DNA to estimate the levels of genetic variation and identified the genetic groups across the species' geographical range in Mexico. We compared the genealogical relationships among haplotypes with those previously reported. A hypothesis of demographic expansion was also tested for the Mexican P. australis lineages. We found 13 new haplotypes native to Mexico that might be undergoing an active process of expansion and diversification. Genealogical analyses provided evidence that two independent lineages of P. australis are present in Mexico. The invasive lineage was not detected with our sampling. Our estimates of population expansions in Mexico ranged from 0.202 to 0.726 mya. Phragmites australis is a native species that has been in Mexico for thousands of years. Genetic data suggest that climatic changes during the Pleistocene played an important role in the demographic expansion of the populations that constitute the different genetic groups of P. australis in Mexico. © 2016 Botanical Society of America.

  19. Genetic Structure of a Local Population of the Anopheles gambiae Complex in Burkina Faso

    PubMed Central

    Markianos, Kyriacos; Bischoff, Emmanuel; Mitri, Christian; Guelbeogo, Wamdaogo M.; Gneme, Awa; Eiglmeier, Karin; Holm, Inge; Sagnon, N’Fale; Vernick, Kenneth D.; Riehle, Michelle M.

    2016-01-01

    Members of the Anopheles gambiae species complex are primary vectors of human malaria in Africa. Population heterogeneities for ecological and behavioral attributes expand and stabilize malaria transmission over space and time, and populations may change in response to vector control, urbanization and other factors. There is a need for approaches to comprehensively describe the structure and characteristics of a sympatric local mosquito population, because incomplete knowledge of vector population composition may hinder control efforts. To this end, we used a genome-wide custom SNP typing array to analyze a population collection from a single geographic region in West Africa. The combination of sample depth (n = 456) and marker density (n = 1536) unambiguously resolved population subgroups, which were also compared for their relative susceptibility to natural genotypes of Plasmodium falciparum malaria. The population subgroups display fluctuating patterns of differentiation or sharing across the genome. Analysis of linkage disequilibrium identified 19 new candidate genes for association with underlying population divergence between sister taxa, A. coluzzii (M-form) and A. gambiae (S-form). PMID:26731649

  20. Coalgebraic structure of genetic inheritance.

    PubMed

    Tian, Jianjun; Li, Bai-Lian

    2004-09-01

    Although in the broadly defined genetic algebra, multiplication suggests a forward direction of from parents to progeny, when looking from the reverse direction, it also suggests to us a new algebraic structure-coalge- braic structure, which we call genetic coalgebras. It is not the dual coalgebraic structure and can be used in the construction of phylogenetic trees. Math- ematically, to construct phylogenetic trees means we need to solve equations x([n]) = a, or x([n]) = b. It is generally impossible to solve these equations inalgebras. However, we can solve them in coalgebras in the sense of tracing back for their ancestors. A thorough exploration of coalgebraic structure in genetics is apparently necessary. Here, we develop a theoretical framework of the coalgebraic structure of genetics. From biological viewpoint, we defined various fundamental concepts and examined their elementary properties that contain genetic significance. Mathematically, by genetic coalgebra, we mean any coalgebra that occurs in genetics. They are generally noncoassociative and without counit; and in the case of non-sex-linked inheritance, they are cocommutative. Each coalgebra with genetic realization has a baric property. We have also discussed the methods to construct new genetic coalgebras, including cocommutative duplication, the tensor product, linear combinations and the skew linear map, which allow us to describe complex genetic traits. We also put forward certain theorems that state the relationship between gametic coalgebra and gametic algebra. By Brower's theorem in topology, we prove the existence of equilibrium state for the in-evolution operator.

  1. Genetic population structure of Fusarium graminearum species complex in Korean cereals

    USDA-ARS?s Scientific Manuscript database

    Small grain cereals are frequently contaminated with toxigenic Fusarium species. Members of the Fusarium graminearum species complex (FGSC) are known as a head blight pathogens and mycotoxin producers. In order to characterize the FGSC populations associated with cereals in Korea, barley, corn, maiz...

  2. Ecological Distribution and CQ11 Genetic Structure of Culex pipiens Complex (Diptera: Culicidae) in Italy

    PubMed Central

    Di Luca, Marco; Toma, Luciano; Boccolini, Daniela; Severini, Francesco; La Rosa, Giuseppe; Minelli, Giada; Bongiorno, Gioia; Montarsi, Fabrizio; Arnoldi, Daniele; Capelli, Gioia; Rizzoli, Annapaola; Romi, Roberto

    2016-01-01

    Mosquitoes in the Culex pipiens complex are considered to be involved in the transmission of a range of pathogens, including West Nile virus (WNV). Although its taxonomic status is still debated, the complex includes species, both globally distributed or with a more limited distribution, morphologically similar and characterised by different physiological and behavioural traits, which affect their ability as vectors. In many European countries, Cx. pipiens and its sibling species Culex torrentium occur in sympatry, exhibiting similar bionomic and morphological characters, but only Cx. pipiens appears to play a vector role in WNV transmission. This species consists of two biotypes, pipiens and molestus, which can interbreed when in sympatry, and their hybrids can act as WNV-bridge vectors, due to intermediate ecological features. Considering the yearly WNV outbreaks since 2008 and given the morphological difficulties in recognising species and biotypes, our aim was to molecularly identify and characterised Cx. pipiens and Cx. torrentium in Italy, using recently developed molecular assays. Culex torrentium was not detected; as in other European countries, the pipiens and molestus biotypes were widely found in sympatry with hybrids in most environments. The UPGMA cluster analysis applied to CQ11 genotypic frequencies mainly revealed two groups of Cx. pipiens populations that differed in ecological features. The high propensity of the molestus biotype to exist in hypogean environments, where the habitat’s physical characteristics hinder and preclude the gene flow, was shown. These results confirmed the CQ11 assay as a reliable diagnostic method, consistent with the ecological and physiological aspects of the populations analysed. Since the assessment of the actual role of three biotypes in the WNV circulation remains a crucial point to be elucidated, this extensive molecular screening of Cx. pipiens populations can provide new insights into the ecology of the species

  3. Genetic structure and diversity in the Dioscorea cayenensis/D. rotundata complex revealed by morphological and isozyme markers.

    PubMed

    Bressan, E A; Briner Neto, T; Zucchi, M I; Rabello, R J; Veasey, E A

    2014-01-21

    Of the 600 known yam species, only 10 are utilized as food, and the Dioscorea cayenensis/D. rotundata species complex is among the most cultivated. In Brazil, these species are commercially cultivated in the northeast region and are cultivated in the south and southeast regions as subsistence crops by traditional agriculturists. This study aimed to evaluate the genetic diversity of 21 local varieties of D. cayenensis and 2 D. rotundata accessions using 7 isozymic loci and 24 morphological markers, and to investigate the diversity distribution in different levels of organization, such as swidden fields and communities of Vale do Ribeira. Cluster analyses for both the isozymic and morphological data separated the 2 D. rotundata accessions from the D. cayenensis accessions from Vale do Ribeira. The analysis with morphological characteristics showed the presence of 2 subgroups (Iguape and Cananéia) within group I, which included all of the local varieties from Vale do Ribeira; this result may indicate the influence of the cultural units on the morphological variation. Molecular analysis of variance indicated that most of the isozymic variability was concentrated among swiddens within communities (42.5%) and within communities (40.3%). Most of the morphological variability was also concentrated among swidden fields within communities (44.8%). The correlation between geographic and genetic distances indicated that neither morphological (r = 0.17) nor isozymic diversity (r = -0.15) is structured in space. Thus, the traditional agriculturists of Vale do Ribeira maintain and manage a great diversity of D. cayenensis varieties in their communities.

  4. [Genetic structure and peculiarities of earthworms Aporrectodea (superspecies) caliginosa (Oligochaeta: Lumbricidae) complex on the territory of Ukraine].

    PubMed

    Mezhzherin, S V; Vlasenko, R P; Garbar, A V

    2008-01-01

    The investigation of genetic structure of Aporrectodea caliginosa--A. trapezoides diploid--polyploid complex on the territory of Ukraine has been done both with biochemical gene marking of 6 loci (Aat, Es-1,-2,-3, -4, Mdh) and karyotyping. All 646 individuals of 21 samples were analyzed on the biochemical gene level. Karyotype preparations were received from 70 specimens. As a result diploid amphimictic A. caliginosa individuals (2n = 36) forming panmictic populations and triploid (2n = 54) A. trapezoides ones represented by 20 supposed clones were clearly differentiated in 157 specimens. A clear tendency of triploid form domination in the steppe zone of Ukraine where they form 70% in comparison to 12% of all A. (superspecies) caliginosa in the northern forest regions was detected. Taking into account the constant heterozygosity of the investigated loci and chromosome reaction in meiosis, the clone forms are allotriploids formed as a result of close species hybridization, but according to allele pools the amphimictic species living in Ukraine is absent. It means that either apomictic clones of A. trapezoides are not of the local origin and their appearance in the fauna of Ukraine is the result of earthworm introduction into the arid steppe regions or amphimictic A. caliginosa is an invasive species.

  5. Influence of the larval phase on connectivity: strong differences in the genetic structure of brooders and broadcasters in the Ophioderma longicauda species complex.

    PubMed

    Weber, A A-T; Mérigot, B; Valière, S; Chenuil, A

    2015-12-01

    Closely related species with divergent life history traits are excellent models to infer the role of such traits in genetic diversity and connectivity. Ophioderma longicauda is a brittle star species complex composed of different genetic clusters, including brooders and broadcasters. These species diverged very recently and some of them are sympatric and ecologically syntopic, making them particularly suitable to study the consequences of their trait differences. At the scale of the geographic distribution of the broadcasters (Mediterranean Sea and northeastern Atlantic), we sequenced the mitochondrial marker COI and genotyped an intron (i51) for 788 individuals. In addition, we sequenced 10 nuclear loci newly developed from transcriptome sequences, for six sympatric populations of brooders and broadcasters from Greece. At the large scale, we found a high genetic structure within the brooders (COI: 0.07 < F(ST) < 0.65) and no polymorphism at the nuclear locus i51. In contrast, the broadcasters displayed lower genetic structure (0 < F(ST) < 0.14) and were polymorphic at locus i51. At the regional scale, the multilocus analysis confirmed the contrasting genetic structure between species, with no structure in the broadcasters (global F(ST) < 0.001) and strong structure in the brooders (global F(ST) = 0.49), and revealed a higher genetic diversity in broadcasters. Our study showed that the lecithotrophic larval stage allows on average a 50-fold increase in migration rates, a 280-fold increase in effective size and a threefold to fourfold increase in genetic diversity. Our work, investigating complementary genetic markers on sympatric and syntopic taxa, highlights the strong impact of the larval phase on connectivity and genetic diversity.

  6. Ecological distributions, phenological isolation, and genetic structure in sympatric and parapatric populations of the Larrea tridentata polyploid complex.

    PubMed

    Laport, Robert G; Minckley, Robert L; Ramsey, Justin

    2016-07-01

    Polyploidy is widely recognized as a mechanism of diversification. Contributions of polyploidy to specific pre- and postzygotic barriers-and classifications of polyploid speciation as "ecological" vs. "non-ecological"-are more contentious. Evaluation of these issues requires comprehensive studies that test ecological characteristics of cytotypes as well as the coincidence of genetic structure with cytotype distributions. We investigated a classical example of autopolyploid speciation, Larrea tridentata, at multiple areas of cytotype co-occurrence. Habitat and phenological differences were compared between diploid, tetraploid, and hexaploid populations on the basis of edaphic, community composition, and flowering time surveys. Frequency of hybridization between diploids and tetraploids was investigated using a diploid-specific chloroplast DNA (cpDNA) marker; genetic structure for all cytotypes was assessed using amplified fragment length polymorphisms (AFLPs). Across contact zones, we found cytotypes in habitats distinguished by soil and vegetation. We observed modest differences in timing and production of flowers, indicating a degree of assortative mating that was asymmetric between cytotypes. Nonetheless, cpDNA analyses in diploid-tetraploid contact zones suggested that ∼5% of tetraploid plants had hybrid origins involving unilateral sexual polyploidization. Genetic structure of AFLPs largely coincided with cytotype distributions in diploid-tetraploid contact zones. In contrast, there was little structure in areas of contact between tetraploids and hexaploids, suggesting intercytotype gene flow or recurrent hexaploid formation. Diploid, tetraploid, and hexaploid cytotypes of L. tridentata are segregated by environmental distributions and flowering phenology in contact zones, with diploid and tetraploid populations having corresponding differences in genetic structure. © 2016 Botanical Society of America.

  7. Genetic structure of the four wild tomato species in the Solanum peruvianum s.l. species complex.

    PubMed

    Labate, Joanne A; Robertson, Larry D; Strickler, Susan R; Mueller, Lukas A

    2014-03-01

    The most diverse wild tomato species Solanum peruvianum sensu lato (s.l.) has been reclassified into four separate species: Solanum peruvianum sensu stricto (s.s.), Solanum corneliomuelleri, Solanum huaylasense, and Solanum arcanum. However, reproductive barriers among the species are incomplete and this can lead to discrepancies regarding genetic identity of germplasm. We used genotyping by sequencing (GBS) of S. peruvianum s.l., Solanum neorickii, and Solanum chmielewskii to develop tens of thousands of mapped single nucleotide polymorphisms (SNPs) to analyze genetic relationships within and among species. The data set was condensed to 14,043 SNPs with no missing data across 46 sampled plants. Origins of accessions were mapped using geographical information systems (GIS). Isolation by distance, pairwise genetic distances, and number of clusters were estimated using population genetics approaches. Isolation by distance was strongly supported, especially between interspecific pairs. Eriopersicon (S. peruvianum s.s., S. corneliomuelleri, S. huaylasense) and Arcanum (S. arcanum, S. neorickii, S. chmielewskii) species groups were genetically distinct, except for S. huaylasense which showed 50% membership proportions in each group. Solanum peruvianum and S. corneliomuelleri were not significantly differentiated from each other. Many thousands of SNP markers were identified that could potentially be used to distinguish pairs of species, including S. peruvianum versus S. corneliomuelleri, if they are verified on larger numbers of samples. Diagnostic markers will be valuable for delimiting morphologically similar and interfertile species in germplasm management. Approximately 12% of the SNPs rejected a genome-wide test of selective neutrality based on differentiation among species of S. peruvianum s.l. These are candidates for more comprehensive studies of microevolutionary processes within this species complex.

  8. Complex genetic structure of the rabies virus in Bangkok and its surrounding provinces, Thailand: implications for canine rabies control.

    PubMed

    Lumlertdacha, Boonlert; Wacharapluesadee, Supaporn; Denduangboripant, Jessada; Ruankaew, Nipada; Hoonsuwan, Wirongrong; Puanghat, Apirom; Sakarasaeranee, Plyyonk; Briggs, Deborrah; Hemachudha, Thiravat

    2006-03-01

    Dog vaccination and population management have been suggested as priorities in attempts at disease control in canine rabies-endemic countries. Budget limitations and the complexity of social, cultural and religious variables have complicated progress in the developing world. In Bangkok, Thailand, an intensive canine vaccination and sterilization programme has been in place since November 2002. Our objective was to determine if the rabies virus could be mapped according to its genetic variations and geographical location on the small localized scale of Bangkok and its surrounding provinces. Phylogenetic characterization of 69 samples from Bangkok and five neighbouring and two remote provinces, by limited sequence analysis of the rabies virus nucleoprotein gene, distinguished six different clades. Rabies viruses of four clades were intermixed in Bangkok and in the surrounding highly populated regions whereas the other two clades were confined to rural and less populated provinces. Such a complex pattern of gene flow, particularly in Bangkok, may affect the outcome of canine control programmes.

  9. Complex pattern of genetic structuring in the Atlantic salmon (Salmo salar L.) of the River Foyle system in northwest Ireland: disentangling the evolutionary signal from population stochasticity

    PubMed Central

    Ensing, Dennis; Prodöhl, Paulo A; McGinnity, Philip; Boylan, Patrick; O'Maoiléidigh, Niall; Crozier, Walter W

    2011-01-01

    Little is known about the microevolutionary processes shaping within river population genetic structure of aquatic organisms characterized by high levels of homing and spawning site fidelity. Using a microsatellite panel, we observed complex and highly significant levels of intrariver population genetic substructure and Isolation-by-Distance, in the Atlantic salmon stock of a large river system. Two evolutionary models have been considered explaining mechanisms promoting genetic substructuring in Atlantic salmon, the member-vagrant and metapopulation models. We show that both models can be simultaneously used to explain patterns and levels of population structuring within the Foyle system. We show that anthropogenic factors have had a large influence on contemporary population structure observed. In an analytical development, we found that the frequently used estimator of genetic differentiation, FST, routinely underestimated genetic differentiation by a factor three to four compared to the equivalent statistic Jost's Dest (Jost 2008). These statistics also showed a near-perfect correlation. Despite ongoing discussions regarding the usefulness of “adjusted”FST statistics, we argue that these could be useful to identify and quantify qualitative differences between populations, which are important from management and conservation perspectives as an indicator of existence of biologically significant variation among tributary populations or a warning of critical environmental damage. PMID:22393506

  10. Analysis of Genetically Complex Epilepsies

    PubMed Central

    Ottman, Ruth

    2006-01-01

    During the last decade, great progress has been made in the discovery of genes that influence risk for epilepsy. However, these gene discoveries have been in epilepsies with Mendelian modes of inheritance, which comprise only a tiny fraction of all epilepsy. Most people with epilepsy have no affected relatives, suggesting that the great majority of all epilepsies are genetically complex: multiple genes contribute to their etiology, none of which has a major effect on disease risk. Gene discovery in the genetically complex epilepsies is a formidable task. It is unclear which epilepsy phenotypes are most advantageous to study, and chromosomal localization and mutation detection are much more difficult than in Mendelian epilepsies. Association studies are very promising for the identification of complex epilepsy genes, but we are still in the earliest stages of their application in the epilepsies. Future studies should employ very large sample sizes to ensure adequate statistical power, clinical phenotyping methods of the highest quality, designs and analytic techniques that control for population stratification, and state-of-the-art molecular methods. Collaborative studies are essential to achieve these goals. PMID:16359464

  11. Quantifying and analyzing the network basis of genetic complexity.

    PubMed

    Thompson, Ethan G; Galitski, Timothy

    2012-01-01

    Genotype-to-phenotype maps exhibit complexity. This genetic complexity is mentioned frequently in the literature, but a consistent and quantitative definition is lacking. Here, we derive such a definition and investigate its consequences for model genetic systems. The definition equates genetic complexity with a surplus of genotypic diversity over phenotypic diversity. Applying this definition to ensembles of Boolean network models, we found that the in-degree distribution and the number of periodic attractors produced determine the relative complexity of different topology classes. We found evidence that networks that are difficult to control, or that exhibit a hierarchical structure, are genetically complex. We analyzed the complexity of the cell cycle network of Sacchoromyces cerevisiae and pinpointed genes and interactions that are most important for its high genetic complexity. The rigorous definition of genetic complexity is a tool for unraveling the structure and properties of genotype-to-phenotype maps by enabling the quantitative comparison of the relative complexities of different genetic systems. The definition also allows the identification of specific network elements and subnetworks that have the greatest effects on genetic complexity. Moreover, it suggests ways to engineer biological systems with desired genetic properties.

  12. Genetics of brain structure and intelligence.

    PubMed

    Toga, Arthur W; Thompson, Paul M

    2005-01-01

    Genetic influences on brain morphology and IQ are well studied. A variety of sophisticated brain-mapping approaches relating genetic influences on brain structure and intelligence establishes a regional distribution for this relationship that is consistent with behavioral studies. We highlight those studies that illustrate the complex cortical patterns associated with measures of cognitive ability. A measure of cognitive ability, known as g, has been shown highly heritable across many studies. We argue that these genetic links are partly mediated by brain structure that is likewise under strong genetic control. Other factors, such as the environment, obviously play a role, but the predominant determinant appears to be genetic.

  13. Evaluation of genetic diversity and population structure in a commercially important freshwater fish Prochilodus costatus (Characiformes, Prochilodontidae) using complex hypervariable repeats.

    PubMed

    Barroca, T M; Santos, G B; Duarte, N V R; Kalapothakis, E

    2012-12-17

    We used complex hypervariable repeats to evaluate the genetic diversity and structure of Prochilodus costatus (Characiformes), an ecologically and economically important species endemic to the São Francisco River basin. Hydroelectric dams along the river have led to population fragmentation, which can limit gene flow. Restocking from hatcheries has been used to repopulate declining populations. To determine how fragmentation and hatchery supplementation affect P. costatus population structure, we studied populations from three sites up and downstream of the Gafanhoto Dam (Pará River, State of Minas Gerais). High levels of genetic diversity were found within populations (0.926 to 0.873); the three populations showed significant differentiation (F(ST) = 0.16), suggesting that populations from the three sites were affected by fragmentation of the river and by hatchery contributions. These results will be useful for developing a management and conservation plan for fish species in this area.

  14. Impact of population age structure on Wolbachia transgene driver efficacy: ecologically complex factors and release of genetically modified mosquitoes.

    PubMed

    Rasgon, Jason L; Scott, Thomas W

    2004-07-01

    Wolbachia symbionts hold theoretical promise as a way to drive transgenes into insect vector populations for disease prevention. For simplicity, current models of Wolbachia dynamics and spread ignore ecologically complex factors such as the age structure of vector populations and overlapping vector generations. We developed a model including these factors to assess their impact on the process of Wolbachia spread into populations of three mosquito species (Anopheles gambiae, Aedes aegypti and Culex pipiens). Depending on the mosquito species, Wolbachia parameters, released mosquito life stage and initial age structure of the target population, the number of Wolbachia-infected mosquitoes that we predict would need to be released ranged from less than the threshold calculated by the simple model to a 10-30-fold increase. Transgenic releases into age-structured populations, which is an expectation for wild mosquitoes, will be difficult and depending on the circumstances may not be economically or logistically feasible due to the large number of infected mosquitoes that must be released. Our results support the perspective that understanding ecological factors is critical for designing transgenic vector-borne disease control strategies.

  15. Nephelines from the Somma-Vesuvius volcanic complex (Southern Italy): crystal-chemical, structural and genetic investigations

    NASA Astrophysics Data System (ADS)

    Balassone, Giuseppina; Kahlenberg, Volker; Altomare, Angela; Mormone, Angela; Rizzi, Rosanna; Saviano, Michele; Mondillo, Nicola

    2013-05-01

    Sixteen nephelines from different geological occurrences were sampled at the type-locality, the Somma-Vesuvius volcanic complex (southern Italy), and investigated for their chemistry and crystal structure obtained by both single-crystal and powder X-ray diffraction. Nepheline-bearing samples are metamorphic or from magmatic ejecta and pumice deposits. The lower K contents characterize the pumice- and some metamorphic-derived nephelines, whereas the higher ones are found in some samples from magmatic nodules. The amount of the anorthite molecule, quite low on average, can be more variable in the metamorphic nephelines. The crystal-structure investigations on Somma-Vesuvius samples compare well with previous studies of natural nephelines. All 16 nepheline samples adopt space group P63. The observed lattice parameters vary between 9.9768-9.9946 Å (for a) and 8.3614-8.3777 Å (for c), respectively. Furthermore, chemical analysis revealed that all specimens exhibit an excess of Si relative the ideal Si:Al ratio of 1:1. The analysis of the T-O distances in our samples clearly indicates a distinct ordering process of aluminium and silicon on the tetrahedral sites which is an agreement with Loewenstein's rule. A linear correlation between the distance of symmetry equivalent split atoms O(1)-O(1)' and the T(1)-O(1)-T(2) tilt angle was observed. The average (B = Na) distances of all crystals are very similar which is consistent with the outcome of the site population refinement indicating full occupancy with sodium. Oriented precession-type sections of reciprocal space indicated the presence of at least the most intense family of satellite peaks, demonstrating that this group of satellite reflections can occur not only in nephelines from pegmatites and ijolites but also in rocks from completely different petrological settings.

  16. Nephelines from the Somma-Vesuvius volcanic complex (Southern Italy): crystal-chemical, structural and genetic investigations

    NASA Astrophysics Data System (ADS)

    Balassone, Giuseppina; Kahlenberg, Volker; Altomare, Angela; Mormone, Angela; Rizzi, Rosanna; Saviano, Michele; Mondillo, Nicola

    2014-02-01

    Sixteen nephelines from different geological occurrences were sampled at the type-locality, the Somma-Vesuvius volcanic complex (southern Italy), and investigated for their chemistry and crystal structure obtained by both single-crystal and powder X-ray diffraction. Nepheline-bearing samples are metamorphic or from magmatic ejecta and pumice deposits. The lower K contents characterize the pumice- and some metamorphic-derived nephelines, whereas the higher ones are found in some samples from magmatic nodules. The amount of the anorthite molecule, quite low on average, can be more variable in the metamorphic nephelines. The crystal-structure investigations on Somma-Vesuvius samples compare well with previous studies of natural nephelines. All 16 nepheline samples adopt space group P63. The observed lattice parameters vary between 9.9768-9.9946 Å (for a) and 8.3614-8.3777 Å (for c), respectively. Furthermore, chemical analysis revealed that all specimens exhibit an excess of Si relative the ideal Si:Al ratio of 1:1. The analysis of the T-O distances in our samples clearly indicates a distinct ordering process of aluminium and silicon on the tetrahedral sites which is an agreement with Loewenstein's rule. A linear correlation between the distance of symmetry equivalent split atoms O(1)-O(1)' and the T(1)-O(1)- T(2) tilt angle was observed. The average < B-O> ( B = Na) distances of all crystals are very similar which is consistent with the outcome of the site population refinement indicating full occupancy with sodium. Oriented precession-type sections of reciprocal space indicated the presence of at least the most intense family of satellite peaks, demonstrating that this group of satellite reflections can occur not only in nephelines from pegmatites and ijolites but also in rocks from completely different petrological settings.

  17. Genetic structure and contrasting selection pattern at two major histocompatibility complex genes in wild house mouse populations

    PubMed Central

    Čížková, D; de Bellocq, J Gouy; Baird, S J E; Piálek, J; Bryja, J

    2011-01-01

    The mammalian major histocompatibility complex (MHC) is a tightly linked cluster of immune genes, and is often thought of as inherited as a unit. This has led to the hope that studying a single MHC gene will reveal patterns of evolution representative of the MHC as a whole. In this study we analyse a 1000-km transect of MHC variation traversing the European house mouse hybrid zone to compare signals of selection and patterns of diversification at two closely linked MHC class II genes, H-2Aa and H-2Eb. We show that although they are 0.01 cM apart (that is, recombination is expected only once in 10 000 meioses), disparate evolutionary patterns were detected. H-2Aa shows higher allelic polymorphism, faster allelic turnover due to higher mutation rates, stronger positive selection at antigen-binding sites and higher population structuring than H-2Eb. H-2Eb alleles are maintained in the gene pool for longer, including over separation of the subspecies, some H-2Eb alleles are positively and others negatively selected and some of the alleles are not expressed. We conclude that studies on MHC genes in wild-living vertebrates can give substantially different results depending on the MHC gene examined and that the level of polymorphism in a related species is a poor criterion for gene choice. PMID:20823902

  18. Complex postglacial recolonization inferred from population genetic structure of mottled sculpin Cottus bairdii in tributaries of eastern Lake Michigan, U.S.A.

    PubMed

    Homola, J J; Ruetz, C R; Kohler, S L; Thum, R A

    2016-11-01

    This study used analyses of the genetic structure of a non-game fish species, the mottled sculpin Cottus bairdii to hypothesize probable recolonization routes used by cottids and possibly other Laurentian Great Lakes fishes following glacial recession. Based on samples from 16 small streams in five major Lake Michigan, U.S.A., tributary basins, significant interpopulation differentiation was documented (overall FST = 0·235). Differentiation was complex, however, with unexpectedly high genetic similarity among basins as well as occasionally strong differentiation within basins, despite relatively close geographic proximity of populations. Genetic dissimilarities were identified between eastern and western populations within river basins, with similarities existing between eastern and western populations across basins. Given such patterns, recolonization is hypothesized to have occurred on three occasions from more than one glacial refugium, with a secondary vicariant event resulting from reduction in the water level of ancestral Lake Michigan. By studying the phylogeography of a small, non-game fish species, this study provides insight into recolonization dynamics of the region that could be difficult to infer from game species that are often broadly dispersed by humans.

  19. Drainage isolation and climate change-driven population expansion shape the genetic structures of Tuber indicum complex in the Hengduan Mountains region.

    PubMed

    Feng, Bang; Zhao, Qi; Xu, Jianping; Qin, Jiao; Yang, Zhu L

    2016-02-24

    The orogenesis of the Qinghai-Tibetan Plateau and the Quaternary climate changes have played key roles in driving the evolution of flora and fauna in Southwest China, but their effects on higher fungi are poorly addressed. In this study, we investigated the phylogeographic pattern of the Tuber indicum species complex, an economically important fungal group distributed in the Hengduan Mountains region. Our data confirmed the existence of two distinct lineages, T. indicum and T. himalayense, within this species complex. Three geographic groups (Groups W, N and C) were revealed within T. indicum, with Group W found in the paleo-Lancang River region, while Groups N and C corresponded to the two banks along the contemporary Jinsha River, suggesting that rivers have acted as barriers for gene flow among populations from different drainages. Historical range expansion resulted from climate changes was inferred in Group C, contributing to the observed gene flow among geographic populations within this group. Although no significant geographic structure was identified in T. himalayense, evidence of drainage isolation for this species was also detected. Our findings demonstrate that both topographic changes and Quaternary climate oscillations have played important roles in driving the genetic structures of the T. indicum species complex.

  20. Drainage isolation and climate change-driven population expansion shape the genetic structures of Tuber indicum complex in the Hengduan Mountains region

    PubMed Central

    Feng, Bang; Zhao, Qi; Xu, Jianping; Qin, Jiao; Yang, Zhu L.

    2016-01-01

    The orogenesis of the Qinghai-Tibetan Plateau and the Quaternary climate changes have played key roles in driving the evolution of flora and fauna in Southwest China, but their effects on higher fungi are poorly addressed. In this study, we investigated the phylogeographic pattern of the Tuber indicum species complex, an economically important fungal group distributed in the Hengduan Mountains region. Our data confirmed the existence of two distinct lineages, T. indicum and T. himalayense, within this species complex. Three geographic groups (Groups W, N and C) were revealed within T. indicum, with Group W found in the paleo-Lancang River region, while Groups N and C corresponded to the two banks along the contemporary Jinsha River, suggesting that rivers have acted as barriers for gene flow among populations from different drainages. Historical range expansion resulted from climate changes was inferred in Group C, contributing to the observed gene flow among geographic populations within this group. Although no significant geographic structure was identified in T. himalayense, evidence of drainage isolation for this species was also detected. Our findings demonstrate that both topographic changes and Quaternary climate oscillations have played important roles in driving the genetic structures of the T. indicum species complex. PMID:26906144

  1. Genetic structure of the four wil tomato species in the Solanum peruvianum s.l. species complex

    USDA-ARS?s Scientific Manuscript database

    The most diverse wild tomato species Solanum peruvianum sensu lato (s.l.) has been reclassified into four separate species. However, reproductive barriers among the species are incomplete and this can lead to discrepancies regarding genetic identity of germplasm. We used genotyping by sequencing (...

  2. Genetic Basis of a Cognitive Complexity Metric

    PubMed Central

    Hansell, Narelle K.; Halford, Graeme S.; Andrews, Glenda; Shum, David H. K.; Harris, Sarah E.; Davies, Gail; Franic, Sanja; Christoforou, Andrea; Zietsch, Brendan; Painter, Jodie; Medland, Sarah E.; Ehli, Erik A.; Davies, Gareth E.; Steen, Vidar M.; Lundervold, Astri J.; Reinvang, Ivar; Montgomery, Grant W.; Espeseth, Thomas; Hulshoff Pol, Hilleke E.; Starr, John M.; Martin, Nicholas G.; Le Hellard, Stephanie; Boomsma, Dorret I.; Deary, Ian J.; Wright, Margaret J.

    2015-01-01

    Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the molecular level, we found preliminary support for four single-marker loci (one in the gene DGKB), and at a gene-based level for the NPS gene, having influence on cognition. These results indicate that genetic sources influencing relational processing are a key component of the genetic architecture of broader cognitive abilities. Further, they suggest a genetic cascade, whereby genetic factors influencing capacity limitation in relational processing have a flow-on effect to more complex cognitive traits, including reasoning and working memory, and ultimately, IQ. PMID:25860228

  3. Complex genetic patterns in closely related colonizing invasive species

    PubMed Central

    Zhan, Aibin; Darling, John A; Bock, Dan G; Lacoursière-Roussel, Anaïs; MacIsaac, Hugh J; Cristescu, Melania E

    2012-01-01

    Anthropogenic activities frequently result in both rapidly changing environments and translocation of species from their native ranges (i.e., biological invasions). Empirical studies suggest that many factors associated with these changes can lead to complex genetic patterns, particularly among invasive populations. However, genetic complexities and factors responsible for them remain uncharacterized in many cases. Here, we explore these issues in the vase tunicate Ciona intestinalis (Ascidiacea: Enterogona: Cionidae), a model species complex, of which spA and spB are rapidly spreading worldwide. We intensively sampled 26 sites (N = 873) from both coasts of North America, and performed phylogenetic and population genetics analyses based on one mitochondrial fragment (cytochrome c oxidase subunit 3–NADH dehydrogenase subunit I, COX3-ND1) and eight nuclear microsatellites. Our analyses revealed extremely complex genetic patterns in both species on both coasts. We detected a contrasting pattern based on the mitochondrial marker: two major genetic groups in C. intestinalis spA on the west coast versus no significant geographic structure in C. intestinalis spB on the east coast. For both species, geo-graphically distant populations often showed high microsatellite-based genetic affinities whereas neighboring ones often did not. In addition, mitochondrial and nuclear markers provided largely inconsistent genetic patterns. Multiple factors, including random genetic drift associated with demographic changes, rapid selection due to strong local adaptation, and varying propensity for human-mediated propagule dispersal could be responsible for the observed genetic complexities. PMID:22957143

  4. Population genetic structure and ecotoxicology.

    PubMed Central

    Guttman, S I

    1994-01-01

    Electrophoretic analyses of population genetic structure, both in the laboratory and in the field, have documented significant shifts in allozyme genotype frequencies in a variety of aquatic taxa as a result of environmental impacts. Studies are documented which indicate that contaminants may select for individuals with tolerant allozyme genotypes, causing the potential loss of individuals with sensitive genotypes. This may diminish the genetic variability and fitness of affected populations and make them more susceptible to extinction following a subsequent stress. Future research involving population genetic structure and ecotoxicology should focus on determining the mechanism of sensitivity, documenting multigenerational effects of chronic laboratory exposure on population genetic composition, investigating whether previously stressed and genetically impacted populations are more susceptible to further natural and/or anthropogenic stressors, and establishing the utility of population genetic structure as a sensitive monitor of impacts in aquatic systems and their subsequent remediation. PMID:7713044

  5. Genetics Home Reference: tuberous sclerosis complex

    MedlinePlus

    ... phenotype in tuberous sclerosis. J Med Genet. 2004 Mar;41(3):203-7. Citation on PubMed or ... sclerosis complex: a review. Semin Pediatr Neurol. 2006 Mar;13(1):27-36. Review. Citation on PubMed ...

  6. Genetic complexity at expression quantitative trait loci.

    PubMed

    Cantor, Rita M; Pan, Calvin; Siegmund, Kimberly

    2016-01-01

    Identifying variants that regulate gene expression and delineating their genetic architecture is a critical next step in our endeavors to better understand the genetic etiology of complex diseases. The appropriate genomic tools are in place, and preliminary analytic strategies have been developed. Here we used Genetic Analysis Workshop (GAW) 19 data to investigate the genetic complexity of expression quantitative trait loci (eQTL), chromosomal regions likely to harbor regulatory elements responsible for gene expression. For this investigation, we analyzed the lymphocyte expression profiles of 653 individuals in 20 pedigrees who were also genotyped by single nucleotide polymorphism (SNP) arrays, followed by sequencing and imputation. We used these data to examine the degree of allelic heterogeneity, a contributor to genetic complexity at eQTL, by sequentially conditioning on the most significantly associated SNPs. SOLAR (Sequential Oligogenic Linkage Analysis Routines)-MGA (measured genotype approach) and FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) software allowed us to analyze pedigree data. The power and Type 1 error rates for single SNP association testing and multiple SNP sequential association testing were consistent for these programs. Sequential conditioning of the real expression data revealed substantial levels of allelic heterogeneity at the 2 eQTL examined, illustrating this feature of genetic complexity. eQTL exhibit substantial genetic complexity among and within pedigrees.

  7. Microsatellite markers and cytoplasmic sequences reveal contrasting pattern of spatial genetic structure in the red algae species complex Mazzaella laminarioides.

    PubMed

    Guillemin, Marie-Laure; Valero, Myriam; Morales Collio, Kennia; Pinochet Sanchez, Ramona; Henríquez Espinosa, Miguel; Silva, Andrea X

    2016-10-01

    Mazzaella laminarioides is a common haploid-diploid red alga that forms dense beds. This alga has a wide distributional range, covering 3,500 km of the Chilean coast, but is restricted to high rocky intertidal zones. Recently, the existence of three highly divergent genetic lineages was demonstrated for this taxon, and two cytoplasmic markers were used to determine that these lineages are distributed in strict parapatry. Here, using 454 next-generation sequencing, we developed polymorphic microsatellite loci that cross amplify in all three cytoplasmic lineages. Six sites (i.e., two sites within each lineage) were analyzed using nine microsatellite loci. Our work shows that, although substantial cytoplasmic differentiation occurs within M. laminarioides, the microsatellite loci did not retrieve three nuclear genetic clusters as expected. Indeed, while the northernmost and southernmost cytoplasmic lineages form two strongly divergent nuclear groups characterized by diagnostic alleles, the third cytoplasmic lineage did not form a third nuclear independent group. It is possible that inter-lineage gene exchange has occurred, particularly at sites along the contact zone between the different cytoplasmic lineages. This nuclear-cytoplasmic incongruence in M. laminarioides could be explained by incomplete lineage sorting of the nuclear genes or asymmetric introgressive hybridization between the lineages. Finally, highly significant heterozygote deficiencies (suggesting occurrence of intergametophytic selfing) were observed in the three small northernmost sites while the large southernmost sites generally approached panmixia. © 2016 Phycological Society of America.

  8. Ocean currents help explain population genetic structure

    PubMed Central

    White, Crow; Selkoe, Kimberly A.; Watson, James; Siegel, David A.; Zacherl, Danielle C.; Toonen, Robert J.

    2010-01-01

    Management and conservation can be greatly informed by considering explicitly how environmental factors influence population genetic structure. Using simulated larval dispersal estimates based on ocean current observations, we demonstrate how explicit consideration of frequency of exchange of larvae among sites via ocean advection can fundamentally change the interpretation of empirical population genetic structuring as compared with conventional spatial genetic analyses. Both frequency of larval exchange and empirical genetic difference were uncorrelated with Euclidean distance between sites. When transformed into relative oceanographic distances and integrated into a genetic isolation-by-distance framework, however, the frequency of larval exchange explained nearly 50 per cent of the variance in empirical genetic differences among sites over scales of tens of kilometres. Explanatory power was strongest when we considered effects of multiple generations of larval dispersal via intermediary locations on the long-term probability of exchange between sites. Our results uncover meaningful spatial patterning to population genetic structuring that corresponds with ocean circulation. This study advances our ability to interpret population structure from complex genetic data characteristic of high gene flow species, validates recent advances in oceanographic approaches for assessing larval dispersal and represents a novel approach to characterize population connectivity at small spatial scales germane to conservation and fisheries management. PMID:20133354

  9. Ocean currents help explain population genetic structure.

    PubMed

    White, Crow; Selkoe, Kimberly A; Watson, James; Siegel, David A; Zacherl, Danielle C; Toonen, Robert J

    2010-06-07

    Management and conservation can be greatly informed by considering explicitly how environmental factors influence population genetic structure. Using simulated larval dispersal estimates based on ocean current observations, we demonstrate how explicit consideration of frequency of exchange of larvae among sites via ocean advection can fundamentally change the interpretation of empirical population genetic structuring as compared with conventional spatial genetic analyses. Both frequency of larval exchange and empirical genetic difference were uncorrelated with Euclidean distance between sites. When transformed into relative oceanographic distances and integrated into a genetic isolation-by-distance framework, however, the frequency of larval exchange explained nearly 50 per cent of the variance in empirical genetic differences among sites over scales of tens of kilometres. Explanatory power was strongest when we considered effects of multiple generations of larval dispersal via intermediary locations on the long-term probability of exchange between sites. Our results uncover meaningful spatial patterning to population genetic structuring that corresponds with ocean circulation. This study advances our ability to interpret population structure from complex genetic data characteristic of high gene flow species, validates recent advances in oceanographic approaches for assessing larval dispersal and represents a novel approach to characterize population connectivity at small spatial scales germane to conservation and fisheries management.

  10. Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers

    PubMed Central

    Ilczyszyn, Weronika M.; Sabat, Artur J.; Akkerboom, Viktoria; Szkarlat, Anna; Klepacka, Joanna; Sowa-Sierant, Iwona; Wasik, Barbara; Kosecka-Strojek, Maja; Buda, Aneta; Miedzobrodzki, Jacek; Friedrich, Alexander W.

    2016-01-01

    The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children’s Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5

  11. Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers.

    PubMed

    Ilczyszyn, Weronika M; Sabat, Artur J; Akkerboom, Viktoria; Szkarlat, Anna; Klepacka, Joanna; Sowa-Sierant, Iwona; Wasik, Barbara; Kosecka-Strojek, Maja; Buda, Aneta; Miedzobrodzki, Jacek; Friedrich, Alexander W

    2016-01-01

    The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children's Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5

  12. Complex patterns of population genetic structure of moose, Alces alces, after recent spatial expansion in Poland revealed by sex-linked markers.

    PubMed

    Swisłocka, Magdalena; Czajkowska, Magdalena; Duda, Norbert; Danyłow, Jan; Owadowska-Cornil, Edyta; Ratkiewicz, Mirosław

    2013-01-01

    In recent years, human activity directly and indirectly influenced the demography of moose in Poland. The species was close to extinction, and only a few isolated populations survived after the Second World War; then, unprecedented demographic and spatial expansions had occurred, possibly generating a very complex pattern of population genetic structure at the present-day margins of the species range in Poland. Over 370 moose from seven populations were collected from Poland, and partial sequences of the mitochondrial control region (mtDNA-cr; 607 bp) were obtained. In addition, the entire mtDNA cytochrome b gene (1,140 bp) and Y-chromosome markers (1,982 bp in total) were studied in a chosen set of individuals. Twelve mtDNA haplotypes that all belonged to the European moose phylogroup were recorded. They could be divided into two distinct clades: Central Europe and the Ural Mountains. The first clade consists of three distinct groups/branches: Biebrza, Polesie, and Fennoscandia. The Biebrza group has experienced spatial and demographic expansion in the recent past. Average genetic differentiation among moose populations in Poland at mtDNA-cr was great and significant (ΦST = 0.407, p < 0.001). Using mtDNA-cr data, four separate groups of population were recognized using spatial analysis of molecular variance and principal coordinate analysis, including a relict population in Biebrza National Park, a reintroduced Kampinos National Park population, as well as populations that were descendants of moose that colonized Poland from the east (Lithuania, Belarus, and Ukraine) and the north (former East Prussia). Among all the sequenced Y-chromosome markers, polymorphisms were found in the DBY14 marker in three populations only; four haplotypes were recorded in total. No significant differentiation was detected for this Y-linked marker among moose populations in Poland. Our mtDNA study revealed that a variety of different factors-bottleneck, the presence of

  13. Structural reverse genetics study of the PI5P4Kβ-nucleotide complexes reveals the presence of the GTP bioenergetic system in mammalian cells.

    PubMed

    Takeuchi, Koh; Senda, Miki; Lo, Yu-Hua; Kofuji, Satoshi; Ikeda, Yoshiki; Sasaki, Atsuo T; Senda, Toshiya

    2016-10-01

    Reverse genetic analysis can connect a gene and its protein counterpart to a biological function(s) by knockout or knockdown of the specific gene. However, when a protein has multiple biochemical activities, the conventional genetics strategy is incapable of distinguishing which biochemical activity of the protein is critical for the particular biological function(s). Here, we propose a structural reverse genetics strategy to overcome this problem. In a structural reverse genetics study, multiple biochemical activities of a protein are segregated by mapping those activities to a structural element(s) in the atomic resolution tertiary structure. Based on the structural mapping, a mutant lacking one biochemical activity of interest can be produced with the other activities kept intact. Expression of the mutant by knockin or ectopic expression in the knockout strain along with the following analysis can connect the single biochemical activity of interest to a biological function. Using the structural reverse genetics strategy, we have dissected the newly identified GTP-dependent activity of a lipid kinase PI5P4Kβ from its ATP-dependent activity. The GTP-insensitive mutant has demonstrated the existence of the GTP bioenergetic sensor system in mammalian cells and its critical role in tumorigenesis. As structural reverse genetics can identify in vivo significance of individual biochemical activity, it is a powerful approach to reveal hidden biological functions, which could be a novel pharmacological target for therapeutic intervention. Given the recent expansion of choices in structural biological methods and advances in genome editing technologies, the time is ripe for structural reverse genetics strategies. © 2016 Federation of European Biochemical Societies.

  14. Distilling pathophysiology from complex disease genetics.

    PubMed

    Chakravarti, Aravinda; Clark, Andrew G; Mootha, Vamsi K

    2013-09-26

    Technologies for genome-wide sequence interrogation have dramatically improved our ability to identify loci associated with complex human disease. However, a chasm remains between correlations and causality that stems, in part, from a limiting theoretical framework derived from Mendelian genetics and an incomplete understanding of disease physiology. Here we propose a set of criteria, akin to Koch's postulates for infectious disease, for assigning causality between genetic variants and human disease phenotypes.

  15. [Complex diseases: the importance of genetics].

    PubMed

    Libioulle, C; Bours, V

    2012-01-01

    Complex diseases usually harbour hereditary factors linked with multiple susceptibility genes. The additive effects of genetic and environmental factors are responsible for the pathology. The impact of heredity has been demonstrated through family studies, but also, and mostly, through the study of adopted people and twins. Recently, genome wide association studies (GWAS) allowed the identification of many susceptibility genes for most complex diseases. However, a large part of the heritability is still missing, probably because of insufficient exploration of rare genetic variants and/or epigenetic factors. The ultimate goal of these genetic studies is the definition of an individual risk leading to specific preventive measures (model "predict and prevent"), but this purpose remains very remote for the majority of complex diseases.

  16. Parental and hybrid Daphnia from the D. longispina complex: long-term dynamics in genetic structure and significance of overwintering modes.

    PubMed

    Griebel, J; Gießler, S; Yin, M; Wolinska, J

    2016-04-01

    In recent decades, hybridization has become a focus of attention because of its role in evolutionary processes. However, little is known about changes in genetic structure within and between parental species and hybrids over time. Here, we studied processes of genetic change in parental species and hybrids from the Daphnia longispina complex (Crustacea, Cladocera) over a period of six years across ten habitats. These cyclical parthenogens respond to fluctuating environments by switching from asexual to sexual reproduction. Importantly, sexually produced diapausing eggs, which resist extreme conditions such as low temperatures and serve as dispersal stages, are produced to a lower extent by hybrids. Long-term microsatellite data revealed clear differences between hybrids and parental species. In hybrids, clonal diversity values were lower, whereas heterozygosity and linkage disequilibrium values were higher compared to parental species. Clonal diversity of hybrids responded to the strength of the winter, with cold winters resulting in few genotypes in the following spring. In time windows when only asexual hybrid females survive, priority effects will favour the establishment of the hybrid offspring before hatchlings from parental diapause eggs can enter the community. The constant high levels of heterozygosity maintained by clonal reproduction in hybrids might lead to their successful establishment over time, when they are able to escape competition from both parental species. Although we found evidence that hybrids diversity depends on fluctuating environments, a direct link between hybrid abundance and the strength of winter was missing. Because of reduced adaptability in clonally reproducing hybrids, multiple factors must contribute to promoting their long-term success in fluctuating environments. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  17. High-Level Genetic Diversity and Complex Population Structure of Siberian Apricot (Prunus sibirica L.) in China as Revealed by Nuclear SSR Markers

    PubMed Central

    Wang, Zhe; Kang, Ming; Liu, Huabo; Gao, Jiao; Zhang, Zhengdong; Li, Yingyue; Wu, Rongling; Pang, Xiaoming

    2014-01-01

    Siberian apricot (Prunus sibirica L.), an ecologically and economically important tree species with a high degree of tolerance to a variety of extreme environmental conditions, is widely distributed across the mountains of northeastern and northern China, eastern and southeastern regions of Mongolia, Eastern Siberia, and the Maritime Territory of Russia. However, few studies have examined the genetic diversity and population structure of this species. Using 31 nuclear microsatellites, we investigated the level of genetic diversity and population structure of Siberian apricot sampled from 22 populations across China. The number of alleles per locus ranged from 5 to 33, with an average of 19.323 alleles. The observed heterozygosity and expected heterozygosity ranged from 0.037 to 0.874 and 0.040 to 0.924 with average values of 0.639 and 0.774, respectively. A STRUCTURE-based analysis clustered all of the populations into four genetic clusters. Significant genetic differentiation was observed between all population pairs. A hierarchical analysis of molecular variance attributed about 94% of the variation to within populations. No significant difference was detected between the wild and semi-wild groups, indicating that recent cultivation practices have had little impact on the genetic diversity of Siberian apricot. The Mantel test showed that the genetic distance among the populations was not significantly correlated with geographic distance (r = 0.4651, p = 0.9940). Our study represents the most comprehensive investigation of the genetic diversity and population structure of Siberian apricot in China to date, and it provides valuable information for the collection of genetic resources for the breeding of Siberian apricot and related species. PMID:24516551

  18. High-level genetic diversity and complex population structure of Siberian apricot (Prunus sibirica L.) in China as revealed by nuclear SSR markers.

    PubMed

    Wang, Zhe; Kang, Ming; Liu, Huabo; Gao, Jiao; Zhang, Zhengdong; Li, Yingyue; Wu, Rongling; Pang, Xiaoming

    2014-01-01

    Siberian apricot (Prunus sibirica L.), an ecologically and economically important tree species with a high degree of tolerance to a variety of extreme environmental conditions, is widely distributed across the mountains of northeastern and northern China, eastern and southeastern regions of Mongolia, Eastern Siberia, and the Maritime Territory of Russia. However, few studies have examined the genetic diversity and population structure of this species. Using 31 nuclear microsatellites, we investigated the level of genetic diversity and population structure of Siberian apricot sampled from 22 populations across China. The number of alleles per locus ranged from 5 to 33, with an average of 19.323 alleles. The observed heterozygosity and expected heterozygosity ranged from 0.037 to 0.874 and 0.040 to 0.924 with average values of 0.639 and 0.774, respectively. A STRUCTURE-based analysis clustered all of the populations into four genetic clusters. Significant genetic differentiation was observed between all population pairs. A hierarchical analysis of molecular variance attributed about 94% of the variation to within populations. No significant difference was detected between the wild and semi-wild groups, indicating that recent cultivation practices have had little impact on the genetic diversity of Siberian apricot. The Mantel test showed that the genetic distance among the populations was not significantly correlated with geographic distance (r = 0.4651, p = 0.9940). Our study represents the most comprehensive investigation of the genetic diversity and population structure of Siberian apricot in China to date, and it provides valuable information for the collection of genetic resources for the breeding of Siberian apricot and related species.

  19. Assessing population genetic structure via the maximisation of genetic distance

    PubMed Central

    2009-01-01

    Background The inference of the hidden structure of a population is an essential issue in population genetics. Recently, several methods have been proposed to infer population structure in population genetics. Methods In this study, a new method to infer the number of clusters and to assign individuals to the inferred populations is proposed. This approach does not make any assumption on Hardy-Weinberg and linkage equilibrium. The implemented criterion is the maximisation (via a simulated annealing algorithm) of the averaged genetic distance between a predefined number of clusters. The performance of this method is compared with two Bayesian approaches: STRUCTURE and BAPS, using simulated data and also a real human data set. Results The simulations show that with a reduced number of markers, BAPS overestimates the number of clusters and presents a reduced proportion of correct groupings. The accuracy of the new method is approximately the same as for STRUCTURE. Also, in Hardy-Weinberg and linkage disequilibrium cases, BAPS performs incorrectly. In these situations, STRUCTURE and the new method show an equivalent behaviour with respect to the number of inferred clusters, although the proportion of correct groupings is slightly better with the new method. Re-establishing equilibrium with the randomisation procedures improves the precision of the Bayesian approaches. All methods have a good precision for FST ≥ 0.03, but only STRUCTURE estimates the correct number of clusters for FST as low as 0.01. In situations with a high number of clusters or a more complex population structure, MGD performs better than STRUCTURE and BAPS. The results for a human data set analysed with the new method are congruent with the geographical regions previously found. Conclusion This new method used to infer the hidden structure in a population, based on the maximisation of the genetic distance and not taking into consideration any assumption about Hardy-Weinberg and linkage equilibrium

  20. Systems genetics approaches to understand complex traits

    PubMed Central

    Civelek, Mete; Lusis, Aldons J.

    2014-01-01

    Systems genetics is an approach to understand the flow of biological information that underlies complex traits. It uses a range of experimental and statistical methods to quantitate and integrate intermediate phenotypes, such as transcript, protein or metabolite levels, in populations that vary for traits of interest. Systems genetics studies have provided the first global view of the molecular architecture of complex traits and are useful for the identification of genes, pathways and networks that underlie common human diseases. Given the urgent need to understand how the thousands of loci that have been identified in genome-wide association studies contribute to disease susceptibility, systems genetics is likely to become an increasingly important approach to understanding both biology and disease. PMID:24296534

  1. Population genetic structure in Lahontan cutthroat trout

    USGS Publications Warehouse

    Nielsen, Jennifer L.; Sage, George K.

    2002-01-01

    We used 10 microsatellite loci to examine the genetic population structure of cutthroat trout Oncorhynchus clarki within the Lahontan Basin complex. Genetic diversity was analyzed for trout from Nevada, California, and Utah representing three putative subspecies: Lahontan O. c. henshawi, Paiute O. c. seleniris, and Humboldt (an unnamed subspecies) cutthroat trout. We found significant differences in microsatellite diversity among the three putative subspecies found in this area. Analysis of molecular variance partitioned microsatellite variation as 9.8% among subspecies, 27.7% among populations, and 62.5% within populations of Lahontan Basin cutthroat trout. Genetic distance analyses (Cavalli-Sforza-Edwards and F st) supported unique population structure in cutthroat trout from the Humboldt and Pilot Peak drainages. Pairwise F st values for Lahontan cutthroat trout were not significantly correlated with geographic distance between population pairs (r 2 = 0.008; P < 0.0001), suggesting that they are extremely isolated populations with small effective sizes that are vulnerable to extinction. Two extant hatchery strains of Lahontan cutthroat trout showed genetic associations with different geographic source populations. The Pyramid Lake hatchery strain was most closely associated genetically with fish from Summit Lake. The Pilot Peak hatchery strain was associated genetically with Pilot Peak wild trout (Utah) and Macklin Creek trout (California). The phylogeographic diversity depicted in this study supports unique population structure and suggests important evolutionary relationships needed to evaluate transplanted populations and hatchery supplementation within the basin.

  2. Explaining additional genetic variation in complex traits

    PubMed Central

    Robinson, Matthew R.; Wray, Naomi R.; Visscher, Peter M.

    2015-01-01

    Genome-wide association studies (GWAS) have provided valuable insights into the genetic basis of complex traits, discovering >6000 variants associated with >500 quantitative traits and common complex diseases in humans. The associations identified so far represent only a fraction of those which influence phenotype, as there are likely to be very many variants across the entire frequency spectrum, each of which influences multiple traits, with only a small average contribution to the phenotypic variance. This presents a considerable challenge to further dissection of the remaining unexplained genetic variance within populations, which limits our ability to predict disease risk, identify new drug targets, improve and maintain food sources, and understand natural diversity. This challenge will be met within the current framework through larger sample size, better phenotyping including recording of non-genetic risk factors, focused study designs, and an integration of multiple sources of phenotypic and genetic information. The current evidence supports the application of quantitative genetic approaches, and we argue that one should retain simpler theories until simplicity can be traded for greater explanatory power. PMID:24629526

  3. Complex approaches to study complex trait genetics in multiple sclerosis.

    PubMed

    Kálmán, Bernadette

    2014-09-30

    Multiple sclerosis (MS) is a complex trait disorder defined by several genes and their interactions with environmental factors. A comprehensive exploration of the susceptibility variants had not been feasible until recently when new developments in biotechnology and bioinformatics made possible sequencing of the whole human genome, cataloguing of nucleotide variants and alignments of these variants in haplotypes. Earlier observations from epidemiological, candidate gene and linkage studies provided ample evidence to support a complex genetic determination of MS. New biotechnology and bioinformatics resources have been recently applied to further successful explorations of the disease. These efforts were paralleled by more careful and reliable ascertainments of disease phenotypes, collaborations among specialized centers to generate sufficient sample size and involvement of clinician-scientists capable of working both on the clinical and scientific study sides. Data obtained from the whole genome association studies (GWAS) elevated our understanding of MS genetics to a new level by identifying an extensive list of genetic determinants. Pathway analyses of MS-associated variants provided evidence to support the immune etiology of the disease. Future research will likely explore how environmental factors interact with the genome, and contribute to the abnormal immune activation and inflammation. This review summarizes the outcomes of MS genetic explorations including those of recent GWAS, and highlights practical consequences of genetic and genomic studies by pointing out as to how the derived data facilitate further elucidation of MS pathogenesis. A better understanding of disease processes is necessary for future advancements in therapeutics and the development of disease prevention strategies.

  4. Complex Relationships between Occupation, Environment, DNA Adducts, Genetic Polymorphisms and Bladder Cancer in a Case-Control Study Using a Structural Equation Modeling

    PubMed Central

    Porru, Stefano; Pavanello, Sofia; Carta, Angela; Arici, Cecilia; Simeone, Claudio; Izzotti, Alberto; Mastrangelo, Giuseppe

    2014-01-01

    DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028), whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001), coffee (p<0.001), cumulative AAs exposure (p = 0.041) and MnSOD (p = 0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life

  5. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.

    PubMed

    Porru, Stefano; Pavanello, Sofia; Carta, Angela; Arici, Cecilia; Simeone, Claudio; Izzotti, Alberto; Mastrangelo, Giuseppe

    2014-01-01

    DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028), whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001), coffee (p<0.001), cumulative AAs exposure (p = 0.041) and MnSOD (p = 0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life

  6. Genetics Home Reference: mitochondrial complex III deficiency

    MedlinePlus

    ... Complex III is found in cell structures called mitochondria , which convert the energy from food into a ... CYB gene is found in DNA located in mitochondria, called mitochondrial DNA (mtDNA). This location may help ...

  7. Structural complexity of quantum networks

    SciTech Connect

    Siomau, Michael

    2016-06-10

    Quantum network is a set of nodes connected with channels, through which the nodes communicate photons and classical information. Classical structural complexity of a quantum network may be defined through its physical structure, i.e. mutual position of nodes and channels connecting them. We show here that the classical structural complexity of a quantum network does not restrict the structural complexity of entanglement graphs, which may be created in the quantum network with local operations and classical communication. We show, in particular, that 1D quantum network can simulate both simple entanglement graphs such as lattices and random graphs and complex small-world graphs.

  8. Genetic and environmental pathways to complex diseases

    PubMed Central

    Gohlke, Julia M; Thomas, Reuben; Zhang, Yonqing; Rosenstein, Michael C; Davis, Allan P; Murphy, Cynthia; Becker, Kevin G; Mattingly, Carolyn J; Portier, Christopher J

    2009-01-01

    Background Pathogenesis of complex diseases involves the integration of genetic and environmental factors over time, making it particularly difficult to tease apart relationships between phenotype, genotype, and environmental factors using traditional experimental approaches. Results Using gene-centered databases, we have developed a network of complex diseases and environmental factors through the identification of key molecular pathways associated with both genetic and environmental contributions. Comparison with known chemical disease relationships and analysis of transcriptional regulation from gene expression datasets for several environmental factors and phenotypes clustered in a metabolic syndrome and neuropsychiatric subnetwork supports our network hypotheses. This analysis identifies natural and synthetic retinoids, antipsychotic medications, Omega 3 fatty acids, and pyrethroid pesticides as potential environmental modulators of metabolic syndrome phenotypes through PPAR and adipocytokine signaling and organophosphate pesticides as potential environmental modulators of neuropsychiatric phenotypes. Conclusion Identification of key regulatory pathways that integrate genetic and environmental modulators define disease associated targets that will allow for efficient screening of large numbers of environmental factors, screening that could set priorities for further research and guide public health decisions. PMID:19416532

  9. Genetic dissection of the budding yeast Arp2/3 complex: A comparison of the in vivo and structural roles of individual subunits

    PubMed Central

    Winter, Dirk C.; Choe, Elizabeth Y.; Li, Rong

    1999-01-01

    In previous work, we identified the yeast Arp2/3 complex, which localizes to cortical actin patches and is required for their motility and integrity in vivo. This complex contains proteins homologous to each subunit of the Acanthamoeba and human Arp2/3 complex except for a 40-kDa subunit (p40), which was missing from the purified yeast complex. Here, we demonstrate by using immunoprecipitation and gel-filtration analysis that Arc40p, the homolog of p40 identified from the yeast genome database, associates with the yeast Arp2/3 complex. We have carried out gene disruptions of each subunit of the yeast Arp2/3 complex to study each subunit’s role in the function of the complex. Surprisingly, we find that only ARC40 is fully essential for cell viability. Strains lacking each of the other subunits exhibit varying degrees of defects in cell growth and viability and in assembly and polarization of cortical actin patches. We have also examined each subunit’s role in maintaining the structural integrity of the Arp2/3 complex. Arp2p, Arp3p, and Arc40p fall into the monomer pool in Δarc19 and Δarc35 cells, suggesting that Arc19p and Arc35p are the central scaffolding components of the complex. Arp2p and Arp3p do not have major roles in maintaining complex integrity, and Arc15p is required for association of Arp2p and Arc40p, but not other subunits, with the complex. These results provide evidence that each subunit contributes differently to the assembly and function of the Arp2/3 complex. PMID:10377407

  10. Mitochondrial control region diversity of the houbara bustard Chlamydotis undulata complex and genetic structure along the Atlantic seaboard of North Africa.

    PubMed

    Idaghdour, Youssef; Broderick, Damien; Korrida, Amal; Chbel, Faiza

    2004-01-01

    The houbara bustard, Chlamydotis undulata, is a declining cryptic desert bird whose range extends from North Africa to Central Asia. Three subspecies are currently recognized by geographical distribution and morphology: C.u.fuertaventurae, C.u.undulata and C.u.macqueenii. We have sequenced 854 bp of mitochondrial control region from 73 birds to describe their population genetic structure with a particular sampling focus on the connectivity between C.u.fuertaventurae and C.u.undulata along the Atlantic seaboard of North Africa. Nucleotide and haplotypic diversity varied among the subspecies being highest in C.u.undulata, lowest in C.u.fuertaventurae and intermediate in C.u.macqueenii. C.u.fuertaventurae and C.u.undulata are paraphyletic and an average nucleotide divergence of 2.08% splits the later from C.u.macqueenii. We estimate that C.u.fuertaventurae and C.u.undulata split from C.u.macqueenii approximately 430 000 years ago. C.u.fuertaventurae and C.u.undulata are weakly differentiated (FST = 0.27, Nm = 1.3), indicative of a recent shared history. Archaeological evidence indicates that houbara bustards have been present on the Canary Islands for 130-170 000 years. However, our genetic data point to a more recent separation of C.u.fuertaventurae and C.u.undulata at around 20-25 000 years. Concordant archaeological, climatic opportunities for colonization and genetic data point to a scenario of: (i) initial colonization of the Canary Islands about 130 000 years ago; (ii) a period of secondary contact 19-30 000 years ago homogenizing any pre-existing genetic structure followed by; (iii) a period of relative isolation that persists today.

  11. Molecular Genetic Studies of Complex Phenotypes

    PubMed Central

    Marian, A.J.

    2012-01-01

    The approach to molecular genetic studies of complex phenotypes has evolved considerably during the recent years. The candidate gene approach, restricted to analysis of a few single nucleotide polymorphisms (SNPs) in a modest number of cases and controls, has been supplanted by the unbiased approach of Genome-Wide Association Studies (GWAS), wherein a large number of tagger SNPs are typed in a large number of individuals. GWAS, which are designed upon the common disease- common variant hypothesis (CD-CV), have identified a large number of SNPs and loci for complex phenotypes. However, alleles identified through GWAS are typically not causative but rather in linkage disequilibrium (LD) with the true causal variants. The common alleles, which may not capture the uncommon and rare variants, account only for a fraction of heritability of the complex traits. Hence, the focus is being shifted to rare variants – common disease (RV-CD) hypothesis, surmising that rare variants exert large effect sizes on the phenotype. In conjunctional with this conceptual shift technological advances in DNA sequencing techniques have dramatically enhanced whole genome or whole exome sequencing capacity. The sequencing approach affords identification of not only the rare but also the common variants. The approach – whether used in complementation with GWAS or as a stand-alone approach - could define the genetic architecture of the complex phenotypes. Robust phenotyping and large-scale sequencing studies are essential to extract the information content of the vast number of DNA sequence variants (DSVs) in the genome. To garner meaningful clinical information and link the genotype to a phenotype, identification and characterization of a very large number of causal fields beyond the information content of DNA sequence variants would be necessary. This review provides an update on the current progress and limitations in identifying DSVs that are associated with phenotypic effects. PMID

  12. THE GENETIC BASIS OF A COMPLEX FUNCTIONAL SYSTEM

    PubMed Central

    Parnell, Nicholas F; Hulsey, C Darrin; Streelman, J Todd

    2012-01-01

    The relationship between form and function can have profound effects on evolutionary dynamics and such effects may differ for simple versus complex systems. In particular, functions produced by multiple structural configurations (many-to-one mapping, MTOM) may dampen constituent trade-offs and promote diversification. Unfortunately, we lack information about the genetic architecture of MTOM functional systems. The skulls of teleost fishes contain both simple (lower jaw levers) as well as more complex (jaws modeled as 4-bar linkages) functional systems within the same craniofacial unit. We examined the mapping of form to function and the genetic basis of these systems by identifying quantitative trait loci (QTL) in hybrids of two Lake Malawi cichlid species. Hybrid individuals exhibited novelty (transgressive segregation) in morphological components and function of the simple and complex jaw systems. Functional novelty was proportional to the prevalence of extreme morphologies in the simple levers; by contrast, recombination of parental morphologies produced transgression in the MTOM 4-bar linkage. We found multiple loci of moderate effect and epistasis controlling jaw phenotypes in both the simple and complex systems, with less phenotypic variance explained by QTL for the 4-bar. Genetic linkage between components of the simple and complex systems partly explains phenotypic correlations and may constrain functional evolution. PMID:23106702

  13. Genetic code expansion for multiprotein complex engineering.

    PubMed

    Koehler, Christine; Sauter, Paul F; Wawryszyn, Mirella; Girona, Gemma Estrada; Gupta, Kapil; Landry, Jonathan J M; Fritz, Markus Hsi-Yang; Radic, Ksenija; Hoffmann, Jan-Erik; Chen, Zhuo A; Zou, Juan; Tan, Piau Siong; Galik, Bence; Junttila, Sini; Stolt-Bergner, Peggy; Pruneri, Giancarlo; Gyenesei, Attila; Schultz, Carsten; Biskup, Moritz Bosse; Besir, Hueseyin; Benes, Vladimir; Rappsilber, Juri; Jechlinger, Martin; Korbel, Jan O; Berger, Imre; Braese, Stefan; Lemke, Edward A

    2016-12-01

    We present a baculovirus-based protein engineering method that enables site-specific introduction of unique functionalities in a eukaryotic protein complex recombinantly produced in insect cells. We demonstrate the versatility of this efficient and robust protein production platform, 'MultiBacTAG', (i) for the fluorescent labeling of target proteins and biologics using click chemistries, (ii) for glycoengineering of antibodies, and (iii) for structure-function studies of novel eukaryotic complexes using single-molecule Förster resonance energy transfer as well as site-specific crosslinking strategies.

  14. Approaches to mapping genetically correlated complex traits

    PubMed Central

    George, Andrew W; Basu, Saonli; Li, Na; Rothstein, Joseph H; Sieberts, Solveig K; Stewart, William; Wijsman, Ellen M; Thompson, Elizabeth A

    2003-01-01

    Our Markov chain Monte Carlo (MCMC) methods were used in linkage analyses of the Framingham Heart Study data using all available pedigrees. Our goal was to detect and map loci associated with covariate-adjusted traits log triglyceride (lnTG) and high-density lipoprotein cholesterol (HDL) using multipoint LOD score analysis, Bayesian oligogenic linkage analysis and identity-by-descent (IBD) scoring methods. Each method used all marker data for all markers on a chromosome. Bayesian linkage analysis detected a linkage signal on chromosome 7 for lnTG and HDL, corroborating previously published results. However, these results were not replicated in a classical linkage analysis of the data or by using IBD scoring methods. We conclude that Bayesian linkage analysis provides a powerful paradigm for mapping trait loci but interpretation of the Bayesian linkage signals is subjective. In the absence of a LOD score method accommodating genetically complex traits and linkage heterogeneity, validation of these signals remains elusive. PMID:14975139

  15. The Brisbane Systems Genetics Study: Genetical Genomics Meets Complex Trait Genetics

    PubMed Central

    Powell, Joseph E.; Henders, Anjali K.; McRae, Allan F.; Caracella, Anthony; Smith, Sara; Wright, Margaret J.; Whitfield, John B.; Dermitzakis, Emmanouil T.; Martin, Nicholas G.

    2012-01-01

    There is growing evidence that genetic risk factors for common disease are caused by hereditary changes of gene regulation acting in complex pathways. Clearly understanding the molecular genetic relationships between genetic control of gene expression and its effect on complex diseases is essential. Here we describe the Brisbane Systems Genetics Study (BSGS), a family-based study that will be used to elucidate the genetic factors affecting gene expression and the role of gene regulation in mediating endophenotypes and complex diseases. BSGS comprises of a total of 962 individuals from 314 families, for which we have high-density genotype, gene expression and phenotypic data. Families consist of combinations of both monozygotic and dizygotic twin pairs, their siblings, and, for 72 families, both parents. A significant advantage of the inclusion of parents is improved power to disentangle environmental, additive genetic and non-additive genetic effects of gene expression and measured phenotypes. Furthermore, it allows for the estimation of parent-of-origin effects, something that has not previously been systematically investigated in human genetical genomics studies. Measured phenotypes available within the BSGS include blood phenotypes and biochemical traits measured from components of the tissue sample in which transcription levels are determined, providing an ideal test case for systems genetics approaches. We report results from an expression quantitative trait loci (eQTL) analysis using 862 individuals from BSGS to test for associations between expression levels of 17,926 probes and 528,509 SNP genotypes. At a study wide significance level approximately 15,000 associations were observed between expression levels and SNP genotypes. These associations corresponded to a total of 2,081 expression quantitative trait loci (eQTL) involving 1,503 probes. The majority of identified eQTL (87%) were located within cis-regions. PMID:22563384

  16. Implications of Population Structure and Ancestry on Asthma Genetic Studies

    PubMed Central

    Ortega, Victor E.; Meyers, Deborah A.

    2014-01-01

    Purpose of Review The frequency and severity of asthma differs between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups. Recent Themes The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity. Summary The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatics from different ethnic groups. PMID:25153337

  17. Implications of population structure and ancestry on asthma genetic studies.

    PubMed

    Ortega, Victor E; Meyers, Deborah A

    2014-10-01

    The frequency and severity of asthma differ between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups. The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how the gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity. The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatic patients from different ethnic groups.

  18. Crystal Structure of a Cytochrome P450 2B6 Genetic Variant in Complex with the Inhibitor 4-(4-Chlorophenyl)imidazole at 2.0-Å Resolution

    PubMed Central

    Shah, Manish B.; Talakad, Jyothi C.; Maekawa, Keiko; Roberts, Arthur G.; Wilderman, P. Ross; Sun, Ling; Yang, Jane Y.; Huelga, Stephanie C.; Hong, Wen-Xu; Zhang, Qinghai; Stout, C. David; Halpert, James R.

    2010-01-01

    The structure of the K262R genetic variant of human cytochrome P450 2B6 in complex with the inhibitor 4-(4-chlorophenyl)imidazole (4-CPI) has been determined using X-ray crystallography to 2.0-Å resolution. Production of diffraction quality crystals was enabled through a combination of protein engineering, chaperone coexpression, modifications to the purification protocol, and the use of unique facial amphiphiles during crystallization. The 2B6-4-CPI complex is virtually identical to the rabbit 2B4 structure bound to the same inhibitor with respect to the arrangement of secondary structural elements and the placement of active site residues. The structure supports prior P450 2B6 homology models based on other mammalian cytochromes P450 and is consistent with the limited site-directed mutagenesis studies on 2B6 and extensive studies on P450 2B4 and 2B1. Although the K262R genetic variant shows unaltered binding of 4-CPI, altered binding affinity, kinetics, and/or product profiles have been previously shown with several other ligands. On the basis of new P450 2B6 crystal structure and previous 2B4 structures, substitutions at residue 262 affect a hydrogen-bonding network connecting the G and H helices, where subtle differences could be transduced to the active site. Docking experiments indicate that the closed protein conformation allows smaller ligands such as ticlopidine to bind to the 2B6 active site in the expected orientation. However, it is unknown whether 2B6 undergoes structural reorganization to accommodate bulkier molecules, as previously inferred from multiple P450 2B4 crystal structures. PMID:20061448

  19. Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution.

    PubMed

    Gay, Sean C; Shah, Manish B; Talakad, Jyothi C; Maekawa, Keiko; Roberts, Arthur G; Wilderman, P Ross; Sun, Ling; Yang, Jane Y; Huelga, Stephanie C; Hong, Wen-Xu; Zhang, Qinghai; Stout, C David; Halpert, James R

    2010-04-01

    The structure of the K262R genetic variant of human cytochrome P450 2B6 in complex with the inhibitor 4-(4-chlorophenyl)imidazole (4-CPI) has been determined using X-ray crystallography to 2.0-A resolution. Production of diffraction quality crystals was enabled through a combination of protein engineering, chaperone coexpression, modifications to the purification protocol, and the use of unique facial amphiphiles during crystallization. The 2B6-4-CPI complex is virtually identical to the rabbit 2B4 structure bound to the same inhibitor with respect to the arrangement of secondary structural elements and the placement of active site residues. The structure supports prior P450 2B6 homology models based on other mammalian cytochromes P450 and is consistent with the limited site-directed mutagenesis studies on 2B6 and extensive studies on P450 2B4 and 2B1. Although the K262R genetic variant shows unaltered binding of 4-CPI, altered binding affinity, kinetics, and/or product profiles have been previously shown with several other ligands. On the basis of new P450 2B6 crystal structure and previous 2B4 structures, substitutions at residue 262 affect a hydrogen-bonding network connecting the G and H helices, where subtle differences could be transduced to the active site. Docking experiments indicate that the closed protein conformation allows smaller ligands such as ticlopidine to bind to the 2B6 active site in the expected orientation. However, it is unknown whether 2B6 undergoes structural reorganization to accommodate bulkier molecules, as previously inferred from multiple P450 2B4 crystal structures.

  20. Band-structure parameters by genetic algorithm

    SciTech Connect

    Starrost, F.; Bornholdt, S.; Solterbeck, C.; Schattke, W.

    1996-05-01

    A genetic algorithm has been used to solve a complex multidimensional parameter-fitting problem. We will focus on the parameters of an empirical tight-binding Hamiltonian. The method is used to approximate the electronic energy band structure if energy values are known for a few wave vectors of high symmetry. Compared to the usual manual procedure this method is more accurate and automatic. This approach, based on the extended H{umlt u}ckel theory (EHT), has provided a list of EHT parameters for IV-IV and III-V semiconductors with zinc-blende structure and helped us to find a symmetry in the EHT. {copyright} {ital 1996 The American Physical Society.}

  1. Endocrine autoimmune disease: genetics become complex.

    PubMed

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  2. Network analyses structure genetic diversity in independent genetic worlds

    PubMed Central

    Halary, Sébastien; Leigh, Jessica W.; Cheaib, Bachar; Lopez, Philippe; Bapteste, Eric

    2009-01-01

    DNA flows between chromosomes and mobile elements, following rules that are poorly understood. This limited knowledge is partly explained by the limits of current approaches to study the structure and evolution of genetic diversity. Network analyses of 119,381 homologous DNA families, sampled from 111 cellular genomes and from 165,529 phage, plasmid, and environmental virome sequences, offer challenging insights. Our results support a disconnected yet highly structured network of genetic diversity, revealing the existence of multiple “genetic worlds.” These divides define multiple isolated groups of DNA vehicles drawing on distinct gene pools. Mathematical studies of the centralities of these worlds’ subnetworks demonstrate that plasmids, not viruses, were key vectors of genetic exchange between bacterial chromosomes, both recently and in the past. Furthermore, network methodology introduces new ways of quantifying current sampling of genetic diversity. PMID:20007769

  3. Network analyses structure genetic diversity in independent genetic worlds.

    PubMed

    Halary, Sébastien; Leigh, Jessica W; Cheaib, Bachar; Lopez, Philippe; Bapteste, Eric

    2010-01-05

    DNA flows between chromosomes and mobile elements, following rules that are poorly understood. This limited knowledge is partly explained by the limits of current approaches to study the structure and evolution of genetic diversity. Network analyses of 119,381 homologous DNA families, sampled from 111 cellular genomes and from 165,529 phage, plasmid, and environmental virome sequences, offer challenging insights. Our results support a disconnected yet highly structured network of genetic diversity, revealing the existence of multiple "genetic worlds." These divides define multiple isolated groups of DNA vehicles drawing on distinct gene pools. Mathematical studies of the centralities of these worlds' subnetworks demonstrate that plasmids, not viruses, were key vectors of genetic exchange between bacterial chromosomes, both recently and in the past. Furthermore, network methodology introduces new ways of quantifying current sampling of genetic diversity.

  4. Genetic Structure and Drug Susceptibility Patterns of Mycobacterium tuberculosis Complex Strains Responsible of Human Pulmonary Tuberculosis in the Major Rearing Region in Cameroon

    PubMed Central

    Um Boock, Alphonse; Noeske, Juergen; Gutierrez, Cristina; Kuaban, Christopher; Etoa, François-Xavier; Eyangoh, Sara Irène

    2016-01-01

    Background. Cameroon this last decade continues to present a low contribution of M. africanum and M. bovis in human tuberculosis (TB), while M. bovis was prevalent in cattle but all these pieces of information only concerned West and Center regions. Methods. We carried out the first study in Adamaoua, one of the most rearing regions of Cameroon, on the genetic structure and drug susceptibility of the MTBC strains isolated from newly diagnosed sputum smear-positive patients aged 15 years and above. For that purpose, spoligotyping, a modified 15 standard MIRU/VNTR loci typing, and the proportion method were used. Results. Four hundred and thirty-seven MTBC isolates were analyzed by spoligotyping. Of these, 423 were identified as M. tuberculosis, within the Cameroon family being dominant with 278 (65.7%) isolates; twelve (2.75%) isolates were classified as M. africanum and two as M. bovis. MIRU/VNTR typing of the most prevalent sublineage (SIT 61) suggested that this lineage is not a unique clone as thought earlier but could constitute a group of strains implicated to different pocket of TB transmission. Only M. tuberculosis sublineages were associated with antituberculosis drug resistance. Conclusion. These results showed the weak contribution of M. africanum and M. bovis to human active pulmonary tuberculosis in Cameroon even in the rearing region. PMID:28119925

  5. Genetic Structure and Drug Susceptibility Patterns of Mycobacterium tuberculosis Complex Strains Responsible of Human Pulmonary Tuberculosis in the Major Rearing Region in Cameroon.

    PubMed

    Koro Koro, Francioli; Um Boock, Alphonse; Kaiyven, Afi Leslie; Noeske, Juergen; Gutierrez, Cristina; Kuaban, Christopher; Etoa, François-Xavier; Eyangoh, Sara Irène

    2016-01-01

    Background. Cameroon this last decade continues to present a low contribution of M. africanum and M. bovis in human tuberculosis (TB), while M. bovis was prevalent in cattle but all these pieces of information only concerned West and Center regions. Methods. We carried out the first study in Adamaoua, one of the most rearing regions of Cameroon, on the genetic structure and drug susceptibility of the MTBC strains isolated from newly diagnosed sputum smear-positive patients aged 15 years and above. For that purpose, spoligotyping, a modified 15 standard MIRU/VNTR loci typing, and the proportion method were used. Results. Four hundred and thirty-seven MTBC isolates were analyzed by spoligotyping. Of these, 423 were identified as M. tuberculosis, within the Cameroon family being dominant with 278 (65.7%) isolates; twelve (2.75%) isolates were classified as M. africanum and two as M. bovis. MIRU/VNTR typing of the most prevalent sublineage (SIT 61) suggested that this lineage is not a unique clone as thought earlier but could constitute a group of strains implicated to different pocket of TB transmission. Only M. tuberculosis sublineages were associated with antituberculosis drug resistance. Conclusion. These results showed the weak contribution of M. africanum and M. bovis to human active pulmonary tuberculosis in Cameroon even in the rearing region.

  6. The complex genetic basis of congenital hypogonadotropic hypogonadism.

    PubMed

    Vezzoli, Valeria; Duminuco, Paolo; Bassi, Ivan; Guizzardi, Fabiana; Persani, Luca; Bonomi, Marco

    2016-06-01

    Congenital hypogonadotropic hypogonadism (CHH) is a rare disease characterized by delayed/absent puberty and infertility due to an inadequate secretion or action of gonadotrophin-releasing hormone (GnRH), with an otherwise structurally and functionally normal hypothalamic-pituitary-gonadal (HPG) axis. CHH is genetically heterogeneous but, due to the infertility of affected individuals, most frequently emerges in a sporadic form, though numerous familial cases have also been registered. In around 50-60% of cases, CHH is associated with a variety of non-reproductive abnormalities, most commonly anosmia/hyposmia, which defines Kallmann Syndrome (KS) by its presence. Broadly-speaking, genetic defects that directly impact on hypothalamic secretion, regulation, or action of GnRH result in a pure neuroendocrine phenotype, normosmic CHH (nCHH), whereas genetic defects that impact of embryonic migration of GnRH neurons to the hypothalamus most commonly result in KS, though nCHH can also arise. Hence, the description of several pedigrees, comprising subjects exhibiting KS and others with nCHH. Although more than 24 genes have been described to be involved in CHH, molecular variants of these do not presently explain more than 35-45% of reported cases. Therefore, numerous other unidentified genes (or conceivably, epigenetic mechanisms) remain to be described to fully understand the pathogenesis of CHH, explaining the emergent idea that CHH is a complex genetic disease characterized by variable expressivity and penetrance. This review summarizes the current state of knowledge on the complex genetic basis of congenital hypogonadotropic hypogonadism and aims to be accessible to both researchers and clinicians.

  7. Crystal structures of Streptococcus suis mannonate dehydratase (ManD) and its complex with substrate: genetic and biochemical evidence for a catalytic mechanism.

    PubMed

    Zhang, Qiangmin; Gao, Feng; Peng, Hao; Cheng, Hao; Liu, Yiwei; Tang, Jiaqi; Thompson, John; Wei, Guohua; Zhang, Jingren; Du, Yuguo; Yan, Jinghua; Gao, George F

    2009-09-01

    Mannonate dehydratase (ManD) is found only in certain bacterial species, where it participates in the dissimilation of glucuronate. ManD catalyzes the dehydration of d-mannonate to yield 2-keto-3-deoxygluconate (2-KDG), the carbon and energy source for growth. Selective inactivation of ManD by drug targeting is of therapeutic interest in the treatment of human Streptococcus suis infections. Here, we report the overexpression, purification, functional characterization, and crystallographic structure of ManD from S. suis. Importantly, by Fourier transform mass spectrometry, we show that 2-KDG is formed when the chemically synthesized substrate (d-mannonate) is incubated with ManD. Inductively coupled plasma-mass spectrometry revealed the presence of Mn(2+) in the purified protein, and in the solution state catalytically active ManD exists as a homodimer of two 41-kDa subunits. The crystal structures of S. suis ManD in native form and in complex with its substrate and Mn(2+) ion have been solved at a resolution of 2.9 A. The core structure of S. suis ManD is a TIM barrel similar to that of other members of the xylose isomerase-like superfamily. Structural analyses and comparative amino acid sequence alignments provide evidence for the importance of His311 and Tyr325 in ManD activity. The results of site-directed mutagenesis confirmed the functional role(s) of these residues in the dehydration reaction and a plausible mechanism for the ManD-catalyzed reaction is proposed.

  8. Structural insights into transcription complexes.

    PubMed

    Berger, Imre; Blanco, Alexandre G; Boelens, Rolf; Cavarelli, Jean; Coll, Miquel; Folkers, Gert E; Nie, Yan; Pogenberg, Vivian; Schultz, Patrick; Wilmanns, Matthias; Moras, Dino; Poterszman, Arnaud

    2011-08-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of structural proteomics on our understanding of the molecular basis of gene expression. While most atomic structures were obtained by X-ray crystallography, the impact of solution NMR and cryo-electron microscopy is far from being negligible. Here, we summarize some highlights and illustrate the importance of specific technologies on the structural biology of protein-protein or protein/DNA transcription complexes: structure/function analysis of components the eukaryotic basal and activated transcription machinery with focus on the TFIID and TFIIH multi-subunit complexes as well as transcription regulators such as members of the nuclear hormone receptor families. We also discuss molecular aspects of promoter recognition and epigenetic control of gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Complex DNA structures and structures of DNA complexes

    SciTech Connect

    Chazin, W.J.; Carlstroem, G.; Shiow-Meei Chen; Miick, S.; Gomez-Paloma, L.; Smith, J.; Rydzewski, J.

    1994-12-01

    Complex DNA structures (for example, triplexes, quadruplexes, junctions) and DNA-ligand complexes are more difficult to study by NMR than standard DNA duplexes are because they have high molecular weights, show nonstandard or distorted local conformations, and exhibit large resonance linewidths and severe {sup 1}H spectral overlap. These systems also tend to have limited solubility and may require specialized solution conditions to maintain favorable spectral characteristics, which adds to the spectroscopic difficulties. Furthermore, with more atoms in the system, both assignment and structure calculation become more challenging. In this article, we focus on demonstrating the current status of NMR studies of such systems and the limitations to further progress; we also indicate in what ways isotopic enrichment can be useful.

  10. Predicting Protein Structure Using Parallel Genetic Algorithms.

    DTIC Science & Technology

    1994-12-01

    34 IEEE Transactions on Systems, Man and Cybernetics, 10(9) (September 1980). 16. De Jong, Kenneth A. "On Using Genetic Algoriths to Search Program...By " Predicting rotein Structure D istribticfiar.. ................ Using Parallel Genetic Algorithms ,Avaiu " ’ •"... Dist THESIS I IGeorge H...iiLite-d Approved for public release; distribution unlimited AFIT/ GCS /ENG/94D-03 Predicting Protein Structure Using Parallel Genetic Algorithms

  11. The implementation of long-lasting insecticidal bed nets has differential effects on the genetic structure of the African malaria vectors in the Anopheles gambiae complex in Dielmo, Senegal.

    PubMed

    Sougoufara, Seynabou; Sokhna, Cheikh; Diagne, Nafissatou; Doucouré, Souleymane; Sembène, Pape MBacké; Harry, Myriam

    2017-08-15

    Mosquitoes belonging to the Anopheles gambiae complex are the main vectors of malaria in sub-Saharan Africa. Among these, An. gambiae, Anopheles coluzzii and Anopheles arabiensis are the most efficient vectors and are largely distributed in sympatric locations. However, these species present ecological and behavioural differences that impact their vectorial capacity and complicate vector-control efforts, mainly based on long-lasting insecticidal bed nets (LLINs) and indoor residual spraying (IRS). In this study, the genetic structure of these three species in a Senegalese village (Dielmo) was investigated using microsatellite data in samples collected in 2006 before implementation of LLINs, in 2008, when they were introduced, and in 2010, 2 years after the use of LLINs. In this study 611 individuals were included, namely 136 An. coluzzii, 101 An. gambiae, 6 An. coluzzii/An. gambiae hybrids and 368 An. arabiensis. According to the species, the effect of the implementation of LLINs in Dielmo is differentiated. Populations of the sister species An. coluzzii and An. gambiae regularly experienced bottleneck events, but without significant inbreeding. The Fst values suggested in 2006 a breakdown of assortative mating resulting in hybrids, but the introduction of LLINs was followed by a decrease in the number of hybrids. This suggests a decrease in mating success of hybrids, ecological maladaptation, or a lesser probability of mating between species due to a decrease in An. coluzzii population size. By contrast, the introduction of LLINs has favoured the sibling species An. arabiensis. In this study, some spatial and temporal structuration between An. arabiensis populations were detected, especially in 2008, and the higher genetic diversity observed could result from a diversifying selection. This work demonstrates the complexity of the malaria context and shows the need to study the genetic structure of Anopheles populations to evaluate the effectiveness of vector

  12. Dissecting the complex genetic basis of mate choice.

    PubMed

    Chenoweth, Stephen F; Blows, Mark W

    2006-09-01

    The genetic analysis of mate choice is fraught with difficulties. Males produce complex signals and displays that can consist of a combination of acoustic, visual, chemical and behavioural phenotypes. Furthermore, female preferences for these male traits are notoriously difficult to quantify. During mate choice, genes not only affect the phenotypes of the individual they are in, but can influence the expression of traits in other individuals. How can genetic analyses be conducted to encompass this complexity? Tighter integration of classical quantitative genetic approaches with modern genomic technologies promises to advance our understanding of the complex genetic basis of mate choice.

  13. SHM in complex structural components

    NASA Astrophysics Data System (ADS)

    Croxford, Anthony J.; Wilcox, Paul D.; Courtney, Charles R. P.; Drinkwater, Bruce W.

    2009-03-01

    The use of permanently attached arrays of sensors has made it clear that guided waves can be used for the SHM of structures. The approaches developed have relied on the use of reference signal subtraction to indicate changes to the state of the structure, such as the appearance of damage. The limit of performance of any system is defined by the post subtraction noise. In order to confirm the basic principles at work the majority of this work has been carried out on simple metallic plates. While important to confirm the levels of understanding, this is not sufficient for practical use. This paper looks at the application of SHM techniques in more complex structures, more typical of those any system would be used on in practise. A rib from a BaE 146 aircraft is used to demonstrate the practical difficulties of applying guided wave SHM methods to densely featured structures. A model system comprising a plate with a single stringer is used to demonstrate a method for normalizing signals to give responses directly related to the scattering properties of the change in the system, mitigating the effect of the position of the change, and a method is proposed to generalize the approach to complex systems. Preliminary tests in the region of the stringer are used to identify the experimental challenges to realizing the calibration on complex systems.

  14. Probing genetic overlap among complex human phenotypes.

    PubMed

    Rzhetsky, Andrey; Wajngurt, David; Park, Naeun; Zheng, Tian

    2007-07-10

    Geneticists and epidemiologists often observe that certain hereditary disorders cooccur in individual patients significantly more (or significantly less) frequently than expected, suggesting there is a genetic variation that predisposes its bearer to multiple disorders, or that protects against some disorders while predisposing to others. We suggest that, by using a large number of phenotypic observations about multiple disorders and an appropriate statistical model, we can infer genetic overlaps between phenotypes. Our proof-of-concept analysis of 1.5 million patient records and 161 disorders indicates that disease phenotypes form a highly connected network of strong pairwise correlations. Our modeling approach, under appropriate assumptions, allows us to estimate from these correlations the size of putative genetic overlaps. For example, we suggest that autism, bipolar disorder, and schizophrenia share significant genetic overlaps. Our disease network hypothesis can be immediately exploited in the design of genetic mapping approaches that involve joint linkage or association analyses of multiple seemingly disparate phenotypes.

  15. Structural Complexity of DNA Sequence

    PubMed Central

    Liou, Cheng-Yuan; Cheng, Wei-Chen; Tsai, Huai-Ying

    2013-01-01

    In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results. PMID:23662161

  16. Genetic Network Inference Using Hierarchical Structure

    PubMed Central

    Kimura, Shuhei; Tokuhisa, Masato; Okada-Hatakeyama, Mariko

    2016-01-01

    Many methods for inferring genetic networks have been proposed, but the regulations they infer often include false-positives. Several researchers have attempted to reduce these erroneous regulations by proposing the use of a priori knowledge about the properties of genetic networks such as their sparseness, scale-free structure, and so on. This study focuses on another piece of a priori knowledge, namely, that biochemical networks exhibit hierarchical structures. Based on this idea, we propose an inference approach that uses the hierarchical structure in a target genetic network. To obtain a reasonable hierarchical structure, the first step of the proposed approach is to infer multiple genetic networks from the observed gene expression data. We take this step using an existing method that combines a genetic network inference method with a bootstrap method. The next step is to extract a hierarchical structure from the inferred networks that is consistent with most of the networks. Third, we use the hierarchical structure obtained to assign confidence values to all candidate regulations. Numerical experiments are also performed to demonstrate the effectiveness of using the hierarchical structure in the genetic network inference. The improvement accomplished by the use of the hierarchical structure is small. However, the hierarchical structure could be used to improve the performances of many existing inference methods. PMID:26941653

  17. [Comparative hierarchic structure of the genetic language].

    PubMed

    Ratner, V A

    1993-05-01

    The genetical texts and genetic language are built according to hierarchic principle and contain no less than 6 levels of coding sequences, separated by marks of punctuation, separation and indication: codons, cistrons, scriptons, replicons, linkage groups, genomes. Each level has all the attributes of the language. This hierarchic system expresses some general properties and regularities. The rules of genetic language being determined, the variability of genetical texts is generated by block-modular combinatorics on each level. Between levels there are some intermediate sublevels and module types capable of being combined. The genetic language is compared with two different independent linguistic systems: human natural languages and artificial programming languages. Genetic language is a natural one by its origin, but it is a typical technical language of the functioning genetic regulatory system--by its predestination. All three linguistic systems under comparison have evident similarity of the organization principles and hierarchical structures. This argues for similarity of their principles of appearance and evolution.

  18. Dissecting the genetics of complex traits using summary association statistics

    PubMed Central

    Pasaniuc, Bogdan; Price, Alkes L.

    2017-01-01

    During the past decade, genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants associated with complex traits and diseases. These studies have produced extensive repositories of genetic variation and trait measurements across large numbers of individuals, providing tremendous opportunities for further analyses. However, privacy concerns and other logistical considerations often limit access to individual-level genetic data, motivating the development of methods that analyze summary association statistics. Here we review recent progress on statistical methods that leverage summary association data to gain insights into the genetic basis of complex traits and diseases. PMID:27840428

  19. Dissecting the genetics of complex traits using summary association statistics.

    PubMed

    Pasaniuc, Bogdan; Price, Alkes L

    2017-02-01

    During the past decade, genome-wide association studies (GWAS) have been used to successfully identify tens of thousands of genetic variants associated with complex traits and diseases. These studies have produced extensive repositories of genetic variation and trait measurements across large numbers of individuals, providing tremendous opportunities for further analyses. However, privacy concerns and other logistical considerations often limit access to individual-level genetic data, motivating the development of methods that analyse summary association statistics. Here, we review recent progress on statistical methods that leverage summary association data to gain insights into the genetic basis of complex traits and diseases.

  20. The Genetic Structure of Domestic Rabbits

    PubMed Central

    Carneiro, Miguel; Afonso, Sandra; Geraldes, Armando; Garreau, Hervé; Bolet, Gerard; Boucher, Samuel; Tircazes, Aurélie; Queney, Guillaume; Nachman, Michael W.; Ferrand, Nuno

    2011-01-01

    Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ∼0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (FST = 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r2 higher than 0.2, and some LD extended up to 3,200 kb

  1. Genetic specificity of a plant–insect food web: Implications for linking genetic variation to network complexity

    PubMed Central

    Barbour, Matthew A.; Fortuna, Miguel A.; Bascompte, Jordi; Nicholson, Joshua R.; Julkunen-Tiitto, Riitta; Jules, Erik S.; Crutsinger, Gregory M.

    2016-01-01

    Theory predicts that intraspecific genetic variation can increase the complexity of an ecological network. To date, however, we are lacking empirical knowledge of the extent to which genetic variation determines the assembly of ecological networks, as well as how the gain or loss of genetic variation will affect network structure. To address this knowledge gap, we used a common garden experiment to quantify the extent to which heritable trait variation in a host plant determines the assembly of its associated insect food web (network of trophic interactions). We then used a resampling procedure to simulate the additive effects of genetic variation on overall food-web complexity. We found that trait variation among host-plant genotypes was associated with resistance to insect herbivores, which indirectly affected interactions between herbivores and their insect parasitoids. Direct and indirect genetic effects resulted in distinct compositions of trophic interactions associated with each host-plant genotype. Moreover, our simulations suggest that food-web complexity would increase by 20% over the range of genetic variation in the experimental population of host plants. Taken together, our results indicate that intraspecific genetic variation can play a key role in structuring ecological networks, which may in turn affect network persistence. PMID:26858398

  2. Genetic and Environmental Factors in Complex Neurodevelopmental Disorders

    PubMed Central

    van Loo, K.M.J; Martens, G.J.M

    2007-01-01

    Complex neurodevelopmental disorders, such as schizophrenia, autism, attention deficit (hyperactivity) disorder, (manic) depressive illness and addiction, are thought to result from an interaction between genetic and environmental factors. Association studies on candidate genes and genome-wide linkage analyses have identified many susceptibility chromosomal regions and genes, but considerable efforts to replicate association have been surprisingly often disappointing. Here, we summarize the current knowledge of the genetic contribution to complex neurodevelopmental disorders, focusing on the findings from association and linkage studies. Furthermore, the contribution of the interaction of the genetic with environmental and epigenetic factors to the aetiology of complex neurodevelopmental disorders as well as suggestions for future research are discussed. PMID:19412416

  3. Whole-tree silvic identifications and the microsatellite genetic structure of a red oak species complex in an Indiana old-growth forest

    Treesearch

    Preston R. Aldrich; George R. Parker; Charles H. Michler; Jeanne Romero-Severson

    2003-01-01

    The red oaks (Quercus section Lobatae) include important timber species, but we know little about their gene pools. Red oak species can be difficult to identify, possibly because of extensive interspecific hybridization, although most evidence of this is morphological. We used 15 microsatellite loci to examine the genetic...

  4. Caledonian scots pine: origins and genetic structure

    Treesearch

    Bohun B Kinloch; R. D. Westfall; G. I. Forrest

    1986-01-01

    Monoterpene and isozyme loci, used as markers to study the genetic structure of Scots pine (Pinus sylvestris L.) native to Scotland, showed that the endemic populations are not genetically impoverished, in spite of severe contraction in range and numbers as a result of both natural and anthropogenic causes. On the contrary, variability in the relict...

  5. Efficient Analysis of Complex Structures

    NASA Technical Reports Server (NTRS)

    Kapania, Rakesh K.

    2000-01-01

    Last various accomplishments achieved during this project are : (1) A Survey of Neural Network (NN) applications using MATLAB NN Toolbox on structural engineering especially on equivalent continuum models (Appendix A). (2) Application of NN and GAs to simulate and synthesize substructures: 1-D and 2-D beam problems (Appendix B). (3) Development of an equivalent plate-model analysis method (EPA) for static and vibration analysis of general trapezoidal built-up wing structures composed of skins, spars and ribs. Calculation of all sorts of test cases and comparison with measurements or FEA results. (Appendix C). (4) Basic work on using second order sensitivities on simulating wing modal response, discussion of sensitivity evaluation approaches, and some results (Appendix D). (5) Establishing a general methodology of simulating the modal responses by direct application of NN and by sensitivity techniques, in a design space composed of a number of design points. Comparison is made through examples using these two methods (Appendix E). (6) Establishing a general methodology of efficient analysis of complex wing structures by indirect application of NN: the NN-aided Equivalent Plate Analysis. Training of the Neural Networks for this purpose in several cases of design spaces, which can be applicable for actual design of complex wings (Appendix F).

  6. Efficient Analysis of Complex Structures

    NASA Technical Reports Server (NTRS)

    Kapania, Rakesh K.

    2000-01-01

    Last various accomplishments achieved during this project are : (1) A Survey of Neural Network (NN) applications using MATLAB NN Toolbox on structural engineering especially on equivalent continuum models (Appendix A). (2) Application of NN and GAs to simulate and synthesize substructures: 1-D and 2-D beam problems (Appendix B). (3) Development of an equivalent plate-model analysis method (EPA) for static and vibration analysis of general trapezoidal built-up wing structures composed of skins, spars and ribs. Calculation of all sorts of test cases and comparison with measurements or FEA results. (Appendix C). (4) Basic work on using second order sensitivities on simulating wing modal response, discussion of sensitivity evaluation approaches, and some results (Appendix D). (5) Establishing a general methodology of simulating the modal responses by direct application of NN and by sensitivity techniques, in a design space composed of a number of design points. Comparison is made through examples using these two methods (Appendix E). (6) Establishing a general methodology of efficient analysis of complex wing structures by indirect application of NN: the NN-aided Equivalent Plate Analysis. Training of the Neural Networks for this purpose in several cases of design spaces, which can be applicable for actual design of complex wings (Appendix F).

  7. Protein complexes predictions within protein interaction networks using genetic algorithms.

    PubMed

    Ramadan, Emad; Naef, Ahmed; Ahmed, Moataz

    2016-07-25

    Protein-protein interaction networks are receiving increased attention due to their importance in understanding life at the cellular level. A major challenge in systems biology is to understand the modular structure of such biological networks. Although clustering techniques have been proposed for clustering protein-protein interaction networks, those techniques suffer from some drawbacks. The application of earlier clustering techniques to protein-protein interaction networks in order to predict protein complexes within the networks does not yield good results due to the small-world and power-law properties of these networks. In this paper, we construct a new clustering algorithm for predicting protein complexes through the use of genetic algorithms. We design an objective function for exclusive clustering and overlapping clustering. We assess the quality of our proposed clustering algorithm using two gold-standard data sets. Our algorithm can identify protein complexes that are significantly enriched in the gold-standard data sets. Furthermore, our method surpasses three competing methods: MCL, ClusterOne, and MCODE in terms of the quality of the predicted complexes. The source code and accompanying examples are freely available at http://faculty.kfupm.edu.sa/ics/eramadan/GACluster.zip .

  8. Genetic Diversity and Genome Complexity of Sugarcane

    USDA-ARS?s Scientific Manuscript database

    Sugarcane (Saccharum spp.) as a C4 plant, is one of the most efficient crops in converting solar energy into chemical energy. Sugarcane cultivar improvement programs have not yet systematically utilized the most of the genetic sources of yield potential and resistance to stresses that may exist in t...

  9. Complex genetic patterns in closely related colonizing invasive species

    EPA Science Inventory

    Anthropogenic activities frequently result in both rapidly changing environments and translocation of species from their native ranges (i.e., biological invasions). Empirical studies suggest that many factors associated with these changes can lead to complex genetic patterns, par...

  10. Complex genetic patterns in closely related colonizing invasive species

    EPA Science Inventory

    Anthropogenic activities frequently result in both rapidly changing environments and translocation of species from their native ranges (i.e., biological invasions). Empirical studies suggest that many factors associated with these changes can lead to complex genetic patterns, par...

  11. Controlling complexity: the clinical relevance of mouse complex genetics

    PubMed Central

    Schughart, Klaus; Libert, Claude; Kas, Martien J

    2013-01-01

    Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches. PMID:23632795

  12. Controlling complexity: the clinical relevance of mouse complex genetics.

    PubMed

    Schughart, Klaus; Libert, Claude; Kas, Martien J

    2013-11-01

    Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches.

  13. How spatio-temporal habitat connectivity affects amphibian genetic structure

    USGS Publications Warehouse

    Watts, Alexander G.; Schlichting, P; Billerman, S; Jesmer, B; Micheletti, S; Fortin, M.-J.; Funk, W.C.; Hapeman, P; Muths, Erin L.; Murphy, M.A.

    2015-01-01

    Heterogeneous landscapes and fluctuating environmental conditions can affect species dispersal, population genetics, and genetic structure, yet understanding how biotic and abiotic factors affect population dynamics in a fluctuating environment is critical for species management. We evaluated how spatio-temporal habitat connectivity influences dispersal and genetic structure in a population of boreal chorus frogs (Pseudacris maculata) using a landscape genetics approach. We developed gravity models to assess the contribution of various factors to the observed genetic distance as a measure of functional connectivity. We selected (a) wetland (within-site) and (b) landscape matrix (between-site) characteristics; and (c) wetland connectivity metrics using a unique methodology. Specifically, we developed three networks that quantify wetland connectivity based on: (i) P. maculata dispersal ability, (ii) temporal variation in wetland quality, and (iii) contribution of wetland stepping-stones to frog dispersal. We examined 18 wetlands in Colorado, and quantified 12 microsatellite loci from 322 individual frogs. We found that genetic connectivity was related to topographic complexity, within- and between-wetland differences in moisture, and wetland functional connectivity as contributed by stepping-stone wetlands. Our results highlight the role that dynamic environmental factors have on dispersal-limited species and illustrate how complex asynchronous interactions contribute to the structure of spatially-explicit metapopulations.

  14. How spatio-temporal habitat connectivity affects amphibian genetic structure

    PubMed Central

    Watts, Alexander G.; Schlichting, Peter E.; Billerman, Shawn M.; Jesmer, Brett R.; Micheletti, Steven; Fortin, Marie-Josée; Funk, W. Chris; Hapeman, Paul; Muths, Erin; Murphy, Melanie A.

    2015-01-01

    Heterogeneous landscapes and fluctuating environmental conditions can affect species dispersal, population genetics, and genetic structure, yet understanding how biotic and abiotic factors affect population dynamics in a fluctuating environment is critical for species management. We evaluated how spatio-temporal habitat connectivity influences dispersal and genetic structure in a population of boreal chorus frogs (Pseudacris maculata) using a landscape genetics approach. We developed gravity models to assess the contribution of various factors to the observed genetic distance as a measure of functional connectivity. We selected (a) wetland (within-site) and (b) landscape matrix (between-site) characteristics; and (c) wetland connectivity metrics using a unique methodology. Specifically, we developed three networks that quantify wetland connectivity based on: (i) P. maculata dispersal ability, (ii) temporal variation in wetland quality, and (iii) contribution of wetland stepping-stones to frog dispersal. We examined 18 wetlands in Colorado, and quantified 12 microsatellite loci from 322 individual frogs. We found that genetic connectivity was related to topographic complexity, within- and between-wetland differences in moisture, and wetland functional connectivity as contributed by stepping-stone wetlands. Our results highlight the role that dynamic environmental factors have on dispersal-limited species and illustrate how complex asynchronous interactions contribute to the structure of spatially-explicit metapopulations. PMID:26442094

  15. Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease

    PubMed Central

    2014-01-01

    Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians. PMID:25254043

  16. Human copy number variation and complex genetic disease.

    PubMed

    Girirajan, Santhosh; Campbell, Catarina D; Eichler, Evan E

    2011-01-01

    Copy number variants (CNVs) play an important role in human disease and population diversity. Advancements in technology have allowed for the analysis of CNVs in thousands of individuals with disease in addition to thousands of controls. These studies have identified rare CNVs associated with neuropsychiatric diseases such as autism, schizophrenia, and intellectual disability. In addition, copy number polymorphisms (CNPs) are present at higher frequencies in the population, show high diversity in copy number, sequence, and structure, and have been associated with multiple phenotypes, primarily related to immune or environmental response. However, the landscape of copy number variation still remains largely unexplored, especially for smaller CNVs and those embedded within complex regions of the human genome. An integrated approach including characterization of single nucleotide variants and CNVs in a large number of individuals with disease and normal genomes holds the promise of thoroughly elucidating the genetic basis of human disease and diversity.

  17. Distinct Genetic Influences on Cortical and Subcortical Brain Structures

    PubMed Central

    Wen, Wei; Thalamuthu, Anbupalam; Mather, Karen A.; Zhu, Wanlin; Jiang, Jiyang; de Micheaux, Pierre Lafaye; Wright, Margaret J.; Ames, David; Sachdev, Perminder S.

    2016-01-01

    This study examined the heritability of brain grey matter structures in a subsample of older adult twins (93 MZ and 68 DZ twin pairs; mean age 70 years) from the Older Australian Twins Study. The heritability estimates of subcortical regions ranged from 0.41 (amygdala) to 0.73 (hippocampus), and of cortical regions, from 0.55 (parietal lobe) to 0.78 (frontal lobe). Corresponding structures in the two hemispheres were influenced by the same genetic factors and high genetic correlations were observed between the two hemispheric regions. There were three genetically correlated clusters, comprising (i) the cortical lobes (frontal, temporal, parietal and occipital lobes); (ii) the basal ganglia (caudate, putamen and pallidum) with weak genetic correlations with cortical lobes, and (iii) the amygdala, hippocampus, thalamus and nucleus accumbens grouped together, which genetically correlated with both basal ganglia and cortical lobes, albeit relatively weakly. Our study demonstrates a complex but patterned and clustered genetic architecture of the human brain, with divergent genetic determinants of cortical and subcortical structures, in particular the basal ganglia. PMID:27595976

  18. Network medicine approaches to the genetics of complex diseases.

    PubMed

    Silverman, Edwin K; Loscalzo, Joseph

    2012-08-01

    Complex diseases are caused by perturbations of biological networks. Genetic analysis approaches focused on individual genetic determinants are unlikely to characterize the network architecture of complex diseases comprehensively. Network medicine, which applies systems biology and network science to complex molecular networks underlying human disease, focuses on identifying the interacting genes and proteins which lead to disease pathogenesis. The long biological path between a genetic risk variant and development of a complex disease involves a range of biochemical intermediates, including coding and non-coding RNA, proteins, and metabolites. Transcriptomics, proteomics, metabolomics, and other -omics technologies have the potential to provide insights into complex disease pathogenesis, especially if they are applied within a network biology framework. Most previous efforts to relate genetics to -omics data have focused on a single -omics platform; the next generation of complex disease genetics studies will require integration of multiple types of -omics data sets in a network context. Network medicine may also provide insight into complex disease heterogeneity, serve as the basis for new disease classifications that reflect underlying disease pathogenesis, and guide rational therapeutic and preventive strategies.

  19. Network Medicine Approaches to the Genetics of Complex Diseases

    PubMed Central

    Silverman, Edwin K.; Loscalzo, Joseph

    2013-01-01

    Complex diseases are caused by perturbations of biological networks. Genetic analysis approaches focused on individual genetic determinants are unlikely to characterize the network architecture of complex diseases comprehensively. Network medicine, which applies systems biology and network science to complex molecular networks underlying human disease, focuses on identifying the interacting genes and proteins which lead to disease pathogenesis. The long biological path between a genetic risk variant and development of a complex disease involves a range of biochemical intermediates, including coding and non-coding RNA, proteins, and metabolites. Transcriptomics, proteomics, metabolomics, and other –omics technologies have the potential to provide insights into complex disease pathogenesis, especially if they are applied within a network biology framework. Most previous efforts to relate genetics to –omics data have focused on a single –omics platform; the next generation of complex disease genetics studies will require integration of multiple types of –omics data sets in a network context. Network medicine may also provide insight into complex disease heterogeneity, serve as the basis for new disease classifications that reflect underlying disease pathogenesis, and guide rational therapeutic and preventive strategies. PMID:22935211

  20. Genetic population structure of muskellunge in the Great Lakes

    USGS Publications Warehouse

    Kapuscinski, Kevin L.; Sloss, Brian L.; Farrell, John M.

    2013-01-01

    We quantified genetic relationships among Muskellunge Esox masquinongy from 15 locations in the Great Lakes to determine the extent and distribution of measurable population structure and to identify appropriate spatial scales for fishery management and genetic conservation. We hypothesized that Muskellunge from each area represented genetically distinct populations, which would be evident from analyses of genotype data. A total of 691 Muskellunge were sampled (n = 10–127/site) and genetic data were collected at 13 microsatellite loci. Results from a suite of analyses (including pairwise genetic differentiation, Bayesian admixture prediction, analysis of molecular variance, and tests of isolation by distance) indicated the presence of nine distinct genetic groups, including two that were approximately 50 km apart. Geographic proximity and low habitat complexity seemed to facilitate genetic similarity among areas, whereas Muskellunge from areas of greater habitat heterogeneity exhibited high differentiation. Muskellunge from most areas contained private alleles, and mean within-area genetic variation was similar to that reported for other freshwater fishes. Management programs aimed at conserving the broader diversity and long-term sustainability of Muskellunge could benefit by considering the genetically distinct groups as independent fisheries, and individual spawning and nursery habitats could subsequently be protected to conserve the evolutionary potential of Muskellunge.

  1. Genetic structure of Argentinean hexaploid wheat germplasm

    PubMed Central

    Vanzetti, Leonardo S.; Yerkovich, Nadia; Chialvo, Eugenia; Lombardo, Lucio; Vaschetto, Luis; Helguera, Marcelo

    2013-01-01

    The identification of genetically homogeneous groups of individuals is an ancient issue in population genetics and in the case of crops like wheat, it can be valuable information for breeding programs, genetic mapping and germplasm resources. In this work we determined the genetic structure of a set of 102 Argentinean bread wheat (Triticum aestivum L.) elite cultivars using 38 biochemical and molecular markers (functional, closely linked to genes and neutral ones) distributed throughout 18 wheat chromosomes. Genetic relationships among these lines were examined using model-based clustering methods. In the analysis three subpopulations were identified which correspond largely to the origin of the germplasm used by the main breeding programs in Argentina. PMID:24130447

  2. (Genetic structure of natural populations)

    SciTech Connect

    Not Available

    1988-01-01

    Our efforts in the first eight months were concentrated in obtaining a genomic clone of the copper-zinc superoxide dismutase (SOD) in Drosophila melanogaster and other Drosophila species. This we have now successfully accomplished. We seek to understand the role of SOD in radioresistance; how genetic variation in this enzyme is maintained in populations; and relevant aspects of its evolution that may contribute to these goals as well as to an understanding of molecular evolution in general. To accomplish these goals we are undertaking the following experiments: cloning and sequencing of (at least) one F allele, one S allele, and the null allele for SOD; cloning and sequencing SOD from species related to D. melanogaster; and cloning and sequencing the SOD gene from several independently sampled S and F alleles in D. melanogaster. We are also preparing to test the radioprotective effects of SOD. 67 refs.

  3. Introduction to Protein Structure through Genetic Diseases

    ERIC Educational Resources Information Center

    Schneider, Tanya L.; Linton, Brian R.

    2008-01-01

    An illuminating way to learn about protein function is to explore high-resolution protein structures. Analysis of the proteins involved in genetic diseases has been used to introduce students to protein structure and the role that individual mutations can play in the onset of disease. Known mutations can be correlated to changes in protein…

  4. Introduction to Protein Structure through Genetic Diseases

    ERIC Educational Resources Information Center

    Schneider, Tanya L.; Linton, Brian R.

    2008-01-01

    An illuminating way to learn about protein function is to explore high-resolution protein structures. Analysis of the proteins involved in genetic diseases has been used to introduce students to protein structure and the role that individual mutations can play in the onset of disease. Known mutations can be correlated to changes in protein…

  5. Evolving Roles for Physicians and Genetic Counselors in Managing Complex Genetic Disorders.

    PubMed

    Shelton, Celeste A; Whitcomb, David C

    2015-11-12

    Proponents of personalized medicine predict that genetic information will provide pivotal perspectives for the prevention and management of complex disorders. Personalized medicine differs from traditional Western medicine, in that it focuses on more complex disorders that require mechanistic disease modeling and outcome simulation by integrating genomic risk, environmental stressors, and biomarkers as indicators of disease state. This information could be useful to guide targeted therapy and prevent pathologic outcomes. However, gaps exist in the process of linking the pieces together; currently, genetic data are seldom used to assist physicians in clinical decision making. With rapid growth in genetic data and the requirements for new paradigms for complex disorders comes the need to train professionals to understand and manage the impact of genetic information on patients within these clinical settings. Here we describe the challenges, controversies, and opportunities for genetics and genetic counselors in managing complex disorders and discuss the rationale for modifications in genetic counselor training and function. We conclude that a major paradigm shift is underway and a compelling functional, ethical, and financial argument can be made for employing properly trained genetic counselors to be strategically positioned within the health-care industries that are responsible for managing complex disorders.

  6. The structural diversity of artificial genetic polymers

    PubMed Central

    Anosova, Irina; Kowal, Ewa A.; Dunn, Matthew R.; Chaput, John C.; Van Horn, Wade D.; Egli, Martin

    2016-01-01

    Synthetic genetics is a subdiscipline of synthetic biology that aims to develop artificial genetic polymers (also referred to as xeno-nucleic acids or XNAs) that can replicate in vitro and eventually in model cellular organisms. This field of science combines organic chemistry with polymerase engineering to create alternative forms of DNA that can store genetic information and evolve in response to external stimuli. Practitioners of synthetic genetics postulate that XNA could be used to safeguard synthetic biology organisms by storing genetic information in orthogonal chromosomes. XNA polymers are also under active investigation as a source of nuclease resistant affinity reagents (aptamers) and catalysts (xenozymes) with practical applications in disease diagnosis and treatment. In this review, we provide a structural perspective on known antiparallel duplex structures in which at least one strand of the Watson–Crick duplex is composed entirely of XNA. Currently, only a handful of XNA structures have been archived in the Protein Data Bank as compared to the more than 100 000 structures that are now available. Given the growing interest in xenobiology projects, we chose to compare the structural features of XNA polymers and discuss their potential to access new regions of nucleic acid fold space. PMID:26673703

  7. Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease.

    PubMed

    Moreno-Moral, Aida; Pesce, Francesco; Behmoaras, Jacques; Petretto, Enrico

    2017-01-01

    Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

  8. Complex genetics in idiopathic hypogonadotropic hypogonadism.

    PubMed

    Pitteloud, Nelly; Durrani, Sadia; Raivio, Taneli; Sykiotis, Gerasimos P

    2010-01-01

    Idiopathic hypogonadotropic hypogonadism (IHH) is an important human disease model. Investigations of the genetics of IHH have facilitated insights into critical pathways regulating sexual maturation and fertility. IHH has been traditionally considered a monogenic disorder. This model holds that a single gene defect is responsible for the disease in each patient. In the case of IHH, 30% of cases are explained by mutations in one of eleven genes. In recent years, several lines of evidence have challenged the monogenic paradigm in IHH. First, disease-associated mutations display striking incomplete penetrance and variable expressivity within and across IHH families. Second, each locus is responsible for only a small percentage of cases. Third, more than one disease-associated mutation seems to be segregating in some families with IHH, and their combined or separate presence in individuals accounts for the variability in disease severity. Finally, IHH is not strictly a congenital and life-long disorder; occasionally it manifests itself during adulthood (adult-onset IHH); in other cases, the disease is not permanent, as evidenced by normal activity of the hypothalamic-pituitary-gonadal axis after discontinuation of treatment in adulthood (IHH reversal). Together, these observations suggest that IHH is not strictly a monogenic mendelian disease, as previously thought. Rather, it is emerging as a digenic, and potentially oligogenic disease, in which hormonal and/or environmental factors may critically influence genetic predisposition and clinical course. Future investigations of IHH should characterize the extent of the involvement of multiple genes in disease pathogenesis, and elucidate the contributions of epigenetic factors. Copyright 2010 S. Karger AG, Basel.

  9. Structurally Complex Surface of Europa

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This is a composite of two images of Jupiter's icy moon Europa obtained from a range of 2119 miles (3410 kilometers) by the Galileo spacecraft during its fourth orbit around Jupiter and its first close pass of Europa. The mosaic spans 11 miles by 30 miles (17 km by 49 km) and shows features as small as 230 feet (70 meters) across. This mosaic is the first very high resolution image data obtained of Europa, and has a resolution more than 50 times better than the best Voyager coverage and 500 times better than Voyager coverage in this area. The mosaic shows the surface of Europa to be structurally complex. The sun illuminates the scene from the right, revealing complex overlapping ridges and fractures in the upper and lower portions of the mosaic, and rugged, more chaotic terrain in the center. Lateral faulting is revealed where ridges show offsets along their lengths (upper left of the picture). Missing ridge segments indicate obliteration of pre-existing materials and emplacement of new terrain (center of the mosaic). Only a small number of impact craters can be seen, indicating the surface is not geologically ancient.

    The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

    This image and other images and data received from Galileo are posted on the Galileo mission home page on the World Wide Web at http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

  10. Advances in the genetically-complex autoinflammatory diseases

    PubMed Central

    Ombrello, Michael J.

    2015-01-01

    Monogenic diseases usually demonstrate Mendelian inheritance and are caused by highly penetrant genetic variants of a single gene. In contrast, genetically-complex diseases arise from a combination of multiple genetic and environmental factors. The concept of autoinflammation originally emerged from the identification of individual, activating lesions of the innate immune system as the molecular basis of the hereditary periodic fever syndromes. In addition to these rare, monogenic forms of autoinflammation, genetically-complex autoinflammatory diseases like the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), Behçet’s disease, and systemic arthritis also fulfill the definition of autoinflammatory diseases - namely the development of apparently unprovoked episodes of inflammation without identifiable exogenous triggers and in the absence of autoimmunity. Interestingly, investigations of these genetically-complex autoinflammatory diseases have implicated both innate and adaptive immune abnormalities, blurring the line between autoinflammation and autoimmunity. This reinforces the paradigm of concerted innate and adaptive immune dysfunction leading to genetically-complex autoinflammatory phenotypes. PMID:26077134

  11. Multiple evolutionary processes drive the patterns of genetic differentiation in a forest tree species complex

    PubMed Central

    Jones, Rebecca C; Steane, Dorothy A; Lavery, Martyn; Vaillancourt, René E; Potts, Brad M

    2013-01-01

    Forest trees frequently form species complexes, complicating taxonomic classification and gene pool management. This is certainly the case in Eucalyptus, and well exemplified by the Eucalyptus globulus complex. This ecologically and economically significant complex comprises four taxa (sspp. bicostata, globulus, maidenii, pseudoglobulus) that are geographically and morphologically distinct, but linked by extensive “intergrade” populations. To resolve their genetic affinities, nine microsatellites were used to genotype 1200 trees from throughout the natural range of the complex in Australia, representing 33 morphological core and intergrade populations. There was significant spatial genetic structure (FST = 0.10), but variation was continuous. High genetic diversity in southern ssp. maidenii indicates that this region is the center of origin. Genetic diversity decreases and population differentiation increases with distance from this area, suggesting that drift is a major evolutionary process. Many of the intergrade populations, along with other populations morphologically classified as ssp. pseudoglobulus or ssp. globulus, belong to a “cryptic genetic entity” that is genetically and geographically intermediate between core ssp. bicostata, ssp. maidenii, and ssp. globulus. Geography, rather than morphology, therefore, is the best predictor of overall genetic affinities within the complex and should be used to classify germplasm into management units for conservation and breeding purposes. PMID:23403692

  12. Structural chromosomal anomalies detected by prenatal genetic diagnosis: our experience.

    PubMed

    Farcaş, Simona; Crişan, C D; Andreescu, Nicoleta; Stoian, Monica; Motoc, A G M

    2013-01-01

    The prenatal diagnosis is currently widely spread and facilitates the acquiring of important genetic information about the fetus by a rate extremely accelerate and considered without precedent. In this paper, we like to present our experience concerning the genetic diagnosis and counseling offered for pregnancies in which a structural chromosomal aberration was found. The study group is formed by 528 prenatal samples of amniotic fluid and chorionic villi, received by our laboratory from 2006 through October 2012 for cytogenetic diagnosis. The appropriate genetic investigation was selected based on the indications for prenatal diagnosis. The cases with structural chromosomal anomalies and polymorphic variants were analyzed as regard to the maternal age, gestational age, referral indications and type of chromosomal anomaly found. A total number of 21 structural chromosomal anomalies and polymorphic variants were identified in the study group. Out of 21 structural chromosomal anomalies and polymorphic variants, six deletions and microdeletions, four situations with abnormal long "p" arm of acrocentric chromosomes, two duplications, two reciprocal translocations, two inversions, two additions, one Robertsonian translocation associating trisomy 13, one 9q heteromorphism and one complex chromosome rearrangement were noticed. To the best of our knowledge, this is the first Romanian study in which the diagnostic strategies and the management of the prenatal cases with structural rearrangements are presented. The data provided about the diagnosis strategy and the management of the prenatal cases with structural chromosomal anomalies represents a useful tool in genetic counseling of pregnancies diagnosed with rare structural chromosomal anomalies.

  13. Genetic structure of Daphnia galeata populations in Eastern China.

    PubMed

    Wei, Wenzhi; Gießler, Sabine; Wolinska, Justyna; Ma, Xiaolin; Yang, Zhong; Hu, Wei; Yin, Mingbo

    2015-01-01

    This study presents the first examination of the genetic structure of Daphnia longispina complex populations in Eastern China. Only one species, D. galeata, was present across the eight investigated lakes; as identified by taxon assignment using allelic variation at 15 microsatellite loci. Three genetically differentiated D. galeata subgroups emerged independent of the type of statistical analysis applied. Thus, Bayesian clustering, discriminant analysis based on results from factorial correspondence analysis, and UPGMA clustering consistently showed that populations from two neighbouring lakes were genetically separated from a mixture of genotypes found in other lakes, which formed another two subgroups. Clonal diversity was high in all D. galeata populations, and most samples showed no deviation from Hardy-Weinberg equilibrium, indicating that clonal selection had little effect on the genetic diversity. Overall, populations did not cluster by geographical origin. Further studies will show if the observed pattern can be explained by natural colonization processes or by recent anthropogenic impact on predominantly artificial lakes.

  14. Autoimmune Addison disease: pathophysiology and genetic complexity.

    PubMed

    Mitchell, Anna L; Pearce, Simon H S

    2012-01-31

    Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease.

  15. Genetic Diversity in the Paramecium aurelia Species Complex

    PubMed Central

    Catania, Francesco; Wurmser, François; Potekhin, Alexey A.; Przyboś, Ewa; Lynch, Michael

    2009-01-01

    Current understanding of the population genetics of free-living unicellular eukaryotes is limited, and the amount of genetic variability in these organisms is still a matter of debate. We characterized—reproductively and genetically—worldwide samples of multiple Paramecium species belonging to a cryptic species complex, Paramecium aurelia, whose species have been shown to be reproductively isolated. We found that levels of genetic diversity both in the nucleus and in the mitochondrion are substantial within groups of reproductively compatible P. aurelia strains but drop considerably when strains are partitioned according to their phylogenetic groupings. Our study reveals the existence of discrepancies between the mating behavior of a number of P. aurelia strains and their multilocus genetic profile, a controversial finding that has major consequences for both the current methods of species assignment and the species problem in the P. aurelia complex. PMID:19023087

  16. Taxonomic complexity and breeding system transitions: conservation genetics of the Epipactis leptochila complex (Orchidaceae).

    PubMed

    Squirrell, J; Hollingsworth, P M; Bateman, R M; Tebbitt, M C; Hollingsworth, M L

    2002-10-01

    The genus Epipactis contains a problematical complex of autogamous taxa among which species limits are difficult to define. Different authors have treated these plants in different ways, some recognizing the different taxa as distinct species, others considering them as minor intraspecific variants. These contrasting treatments have a direct impact on the conservation resources and status such plants command; 'endemic orchid species' are perceived as having high conservation value, 'localized minor variants' are not. We used allozyme and chloroplast restriction fragment length polymorphism (RFLP) and sequencing analyses to investigate patterns of population genetic structure underlying the taxonomic complexity in this group. Populations of E. dunensis, E. leptochila and E. muelleri were homozygous and uniform for all loci studied here. There were, however, fixed genetic differences among these taxa. Comparisons with published data from the putative progenitor species for the autogamous taxa (the widespread, allogamous E. helleborine) suggest iterative origins of autogamy, rather than the self-pollinating taxa all being merely mutational variants of a single autogamous lineage.

  17. Genetic structure of populations of Legionella pneumophila.

    PubMed Central

    Selander, R K; McKinney, R M; Whittam, T S; Bibb, W F; Brenner, D J; Nolte, F S; Pattison, P E

    1985-01-01

    The genetic structure of populations of Legionella pneumophila was defined by an analysis of electrophoretically demonstrable allelic variation at structural genes encoding 22 enzymes in 292 isolates from clinical and environmental sources. Nineteen of the loci were polymorphic, and 62 distinctive electrophoretic types (ETs), representing multilocus genotypes, were identified. Principal coordinates and clustering analyses demonstrated that isolates received as L. pneumophila were a heterogeneous array of genotypes that included two previously undescribed species. For 50 ETs of L. pneumophila (strict sense), mean genetic diversity per locus was 0.312, and diversity was equivalent in ETs represented by isolates recovered from clinical sources and those collected from environmental sources. Cluster analysis revealed four major groups or lineages of ETs in L. pneumophila. Genetic diversity among ETs of the same serotype was, on average, 93% of that in the total sample of ETs. Isolates marked by particular patterns of reactivity to a panel of nine monoclonal antibodies were also genetically heterogeneous, mean diversity within patterns being about 75% of the total. Both Pontiac fever and the pneumonic form of legionellosis may be caused by isolates of the same ET. The genetic structure of L. pneumophila is clonal, and many clones apparently are worldwide in distribution. The fact that L. pneumophila is only 60% as variable as Escherichia coli raises the possibility that isolates recovered from clinical cases and man-made environments are a restricted subset of all clones in the species as a whole. PMID:4030689

  18. Complex Genetics and the Etiology of Human Congenital Heart Disease

    PubMed Central

    Gelb, Bruce D.; Chung, Wendy K.

    2014-01-01

    Congenital heart disease (CHD) is the most common birth defect. Despite considerable advances in care, CHD remains a major contributor to newborn mortality and is associated with substantial morbidities and premature death. Genetic abnormalities appear to be the primary cause of CHD, but identifying precise defects has proven challenging, principally because CHD is a complex genetic trait. Mainly because of recent advances in genomic technology such as next-generation DNA sequencing, scientists have begun to identify the genetic variants underlying CHD. In this article, the roles of modifier genes, de novo mutations, copy number variants, common variants, and noncoding mutations in the pathogenesis of CHD are reviewed. PMID:24985128

  19. Genetics of human episodic memory: dealing with complexity.

    PubMed

    Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2011-09-01

    Episodic memory is a polygenic behavioral trait with substantial heritability estimates. Despite its complexity, recent empirical evidence supports the notion that behavioral genetic studies of episodic memory might successfully identify trait-associated molecules and pathways. The development of high-throughput genotyping methods, of elaborated statistical analyses and of phenotypic assessment methods at the neural systems level will facilitate the reliable identification of novel memory-related genes. Importantly, a necessary crosstalk between behavioral genetic studies and investigation of causality by molecular genetic studies will ultimately pave the way towards the identification of biologically important, and hopefully druggable, genes and molecular pathways related to human episodic memory.

  20. The burden of complex genetics in brain disorders.

    PubMed

    Uhl, George R; Grow, Robert W

    2004-03-01

    Few data estimate the impact of complex genetics in neuropsychiatric illness, making it likely that this impact could be underappreciated. To provide estimates of the impact of complex genetics in neuropsychiatric disorders in the United States, based on estimates of disease costs to US society, disease heritability, and mendelian contributions to disease. Costs were estimated from literature sources and Lewin-National Foundation for Brain Research estimates updated for population growth and consumer price index inflation. Heritability estimates came from available twin data. Estimates of mendelian contributions came from the Online Mendelian Inheritance in Man database and our perspectives. Brain and nervous system disorders may cost the United States as much as US dollars 1.2 trillion annually, and affect many millions of Americans each year. Twin data suggest that more than 40% of the societal burden of brain disorders is likely to be genetically mediated. Most of this disease burden arises from complex multigene genetics as well as from environmental influences. The large sizes of these complex genetic burdens should encourage careful molecular and clinical work to link disease-vulnerability allelic variants with the pathogenesis, nosologic characteristics, prevention, diagnostics, and therapeutics of brain disorders.

  1. Teaching Genetic Counseling Skills: Incorporating a Genetic Counseling Adaptation Continuum Model to Address Psychosocial Complexity.

    PubMed

    Shugar, Andrea

    2017-04-01

    Genetic counselors are trained health care professionals who effectively integrate both psychosocial counseling and information-giving into their practice. Preparing genetic counseling students for clinical practice is a challenging task, particularly when helping them develop effective and active counseling skills. Resistance to incorporating these skills may stem from decreased confidence, fear of causing harm or a lack of clarity of psycho-social goals. The author reflects on the personal challenges experienced in teaching genetic counselling students to work with psychological and social complexity, and proposes a Genetic Counseling Adaptation Continuum model and methodology to guide students in the use of advanced counseling skills.

  2. Design space for complex DNA structures.

    PubMed

    Wei, Bryan; Dai, Mingjie; Myhrvold, Cameron; Ke, Yonggang; Jungmann, Ralf; Yin, Peng

    2013-12-04

    Nucleic acids have emerged as effective materials for assembling complex nanoscale structures. To tailor the structures to function optimally for particular applications, a broad structural design space is desired. Despite the many discrete and extended structures demonstrated in the past few decades, the design space remains to be fully explored. In particular, the complex finite-sized structures produced to date have been typically based on a small number of structural motifs. Here, we perform a comprehensive study of the design space for complex DNA structures, using more than 30 distinct motifs derived from single-stranded tiles. These motifs self-assemble to form structures with diverse strand weaving patterns and specific geometric properties, such as curvature and twist. We performed a systematic study to control and characterize the curvature of the structures, and constructed a flat structure with a corrugated strand pattern. The work here reveals the broadness of the design space for complex DNA nanostructures.

  3. Complexity and accountability: the witches' brew of psychiatric genetics.

    PubMed

    Arribas-Ayllon, Michael; Bartlett, Andrew; Featherstone, Katie

    2010-08-01

    This paper examines the role of complexity in descriptions of the aetiology of common psychiatric disorders. While scientists attest to the discovery of an underlying reality of complex inheritance--the so-called 'witches' brew' of genetic and non-genetic factors--we argue that 'complexity' also performs rhetorical work. In our analysis of scientific review papers (1999-2008), we find a relatively stable genre of accountability in which descriptions of complexity appear to neutralize past failures by incorporating different and sometimes competing methodological perspectives. We identify two temporal strategies: retrospective accounting, which reconstructs a history of psychiatric genetics that deals with the recent failures, citing earlier twin studies as proof of the heritability of common psychiatric disorders; and prospective accounting, which engages in the careful reconstruction of expectations by balancing methodological limitations with moderated optimism. Together, these strategies produce a simple-to-complex narrative that belies the ambivalent nature of complexity. We show that the rhetorical construction of complexity in scientific review papers is oriented to bridging disciplinary boundaries, marshalling new resources and reconstructing expectations that justify delays in gene discovery and risk prediction.

  4. Genetic structure among Fijian island populations.

    PubMed

    Shipley, Gerhard P; Taylor, Diana A; Tyagi, Anand; Tiwari, Geetanjali; Redd, Alan J

    2015-02-01

    We examined nine Y chromosome short tandem repeats (Y-STRs) and the mitochondrial DNA (mtDNA) hypervariable segment 1 region in the Fijian island populations of Viti Levu, Vanua Levu, Kadavu, the Lau islands and Rotuma. We found significant genetic structure among these populations for the Y-STRs, both with and without the Rotumans, but not for the mtDNA. We also found that all five populations exhibited the sex-biased admixture associated with areas settled by Austronesian-speaking people, with paternal lineages more strongly associated with Melanesian populations and maternal lineages more strongly associated with Polynesian populations. We also found that the Rotumans in the north and the Lau Islanders in the east were genetically more similar to Polynesian populations than were the other Fijians, but only for the mtDNA. For the Y-STRs, the Rotumans and the Lau Islanders were genetically as similar to Melanesian populations as were the other three populations. Of the five populations, the Rotumans were the most different in almost every regard. Although past genetic studies treated the Fijians as being genetically homogenous despite known geographic, phenotypic, cultural and linguistic variation, our findings show significant genetic variation and a need for a closer examination of individual island populations within Fiji, particularly the Rotumans, in order to better understand the process of the peopling of Fiji and of the surrounding regions.

  5. Protein Complexes are Central in the Yeast Genetic Landscape

    PubMed Central

    Michaut, Magali; Baryshnikova, Anastasia; Costanzo, Michael; Myers, Chad L.; Andrews, Brenda J.; Boone, Charles; Bader, Gary D.

    2011-01-01

    If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for ∼5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available. PMID

  6. Identification of Complex Carbon Nanotube Structures

    NASA Technical Reports Server (NTRS)

    Han, Jie; Saini, Subhash (Technical Monitor)

    1998-01-01

    A variety of complex carbon nanotube (CNT) structures have been observed experimentally. These include sharp bends, branches, tori, and helices. They are believed to be formed by using topological defects such as pentagons and heptagons to connect different CNT. The effects of type, number, and arrangement (separation and orientation) of defects on atomic structures and energetics of complex CNT are investigated using topology, quantum mechanics and molecular mechanics calculations. Energetically stable models are derived for identification of observed complex CNT structures.

  7. Genetic Structure of the Armenian Population.

    PubMed

    Yepiskoposyan, Levon; Hovhannisyan, Anahit; Khachatryan, Zaruhi

    2016-12-01

    Located at the crossroads of Europe and the Middle East, the Armenian Highland served as a transition corridor for major waves of prehistoric and historic migrations. The genetic history of Armenians as an indigenous population of the region attracts keen scientific interest to resolve the puzzle of ancient Middle Eastern populations' expansion and the spread of Indo-European languages. Here, we review the current state of studies on the genetic structure of both modern and ancient inhabitants of the Armenian Highland and outline further steps to be fulfilled in this regard.

  8. The ethics of complexity. Genetics and autism, a literature review.

    PubMed

    Hens, Kristien; Peeters, Hilde; Dierickx, Kris

    2016-04-01

    It is commonly believed that the etiology of autism is at least partly explained through genetics. Given the complexity of autism and the variability of the autistic phenotype, genetic research and counseling in this field are also complex and associated with specific ethical questions. Although the ethics of autism genetics, especially with regard to reproductive choices, has been widely discussed on the public fora, an in depth philosophical or bioethical reflection on all aspects of the theme seems to be missing. With this literature review we wanted to map the basic questions and answers that exist in the bioethical literature on autism genetics, research, counseling and reproduction, and provide suggestions as to how the discussion can proceed. We found 19 papers that fitted the description of "bioethics literature focusing on autism genetics," and analyzed their content to distill arguments and themes. We concluded that because of the complexity of autism, and the uncertainty with regard to its status, more ethical reflection is needed before definite conclusions and recommendations can be drawn. Moreover, there is a dearth of bioethical empirical studies querying the opinions of all parties, including people with autism themselves. Such empirical bioethical studies should be urgently done before bioethical conclusions regarding the aims and desirability of research into autism genes can be done. Also, fundamental philosophical reflection on concepts of disease should accompany research into the etiology of autism. © 2016 Wiley Periodicals, Inc.

  9. Panpsychic organicism: Sewall Wright's philosophy for understanding complex genetic systems.

    PubMed

    Steffes, David M

    2007-01-01

    Sewall Wright first encountered the complex systems characteristic of gene combinations while a graduate student at Harvard's Bussey Institute from 1912 to 1915. In Mendelian breeding experiments, Wright observed a hierarchical dependence of the organism's phenotype on dynamic networks of genetic interaction and organization. An animal's physical traits, and thus its autonomy from surrounding environmental constraints, depended greatly on how genes behaved in certain combinations. Wright recognized that while genes are the material determinants of the animal phenotype, operating with great regularity, the special nature of genetic systems contributes to the animal phenotype a degree of spontaneity and novelty, creating unpredictable trait variations by virtue of gene interactions. As a result of his experimentation, as well as his keen interest in the philosophical literature of his day, Wright was inspired to see genetic systems as conscious, living organisms in their own right. Moreover, he decided that since genetic systems maintain ordered stability and cause unpredictable novelty in their organic wholes (the animal phenotype), it would be necessary for biologists to integrate techniques for studying causally ordered phenomena (experimental method) and chance phenomena (correlation method). From 1914 to 1921 Wright developed his "method of path coefficient" (or "path analysis"), a new procedure drawing from both laboratory experimentation and statistical correlation in order to analyze the relative influence of specific genetic interactions on phenotype variation. In this paper I aim to show how Wright's philosophy for understanding complex genetic systems (panpsychic organicism) logically motivated his 1914-1921 design of path analysis.

  10. Enabling complex genetic circuits to respond to extrinsic environmental signals.

    PubMed

    Hoynes-O'Connor, Allison; Shopera, Tatenda; Hinman, Kristina; Creamer, John Philip; Moon, Tae Seok

    2017-07-01

    Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real-world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real-world applications. A previously identified pH-responsive promoter and a temperature-responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23-fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168-fold change. These circuits provide the first demonstration of complex pH- and temperature-responsive genetic circuits, and lay the groundwork for the use of similar circuits in real-world applications. Biotechnol. Bioeng. 2017;114: 1626-1631. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Dynamic testing of complex structures

    NASA Technical Reports Server (NTRS)

    Birs, C.; Anderson, P.

    1973-01-01

    Response of structure is determined under impulses large enough to create severe strains. Electrodynamic shaker can provide impulses to nearly any point on structure and can deliver repeated pulses of varying force and duration.

  12. Repression and activation by multiprotein complexes that alter chromatin structure.

    PubMed

    Kingston, R E; Bunker, C A; Imbalzano, A N

    1996-04-15

    Recent studies have provided strong evidence that macromolecular complexes are used in the cell to remodel chromatin structure during activation and to create an inaccessible structure during repression, Although there is not yet any rigorous demonstration that modification of chromatin structure plays a direct, causal role in either activation or repression, there is sufficient smoke to indicate the presence of a blazing inferno nearby. It is clear that complexes that remodel chromatin are tractable in vitro; hopefully this will allow the establishment of systems that provide a direct analysis of the role that remodeling might play in activation. These studies indicate that establishment of functional systems to corroborate the elegant genetic studies on repression might also be tractable. As the mechanistic effects of these complexes are sorted out, it will become important to understand how the complexes are regulated. In many of the instances discussed above, the genes whose products make up these complexes were identified in genetic screens for effects on developmental processes. This implies a regulation of the activity of these complexes in response to developmental cues and further implies that the work to fully understand these complexes will occupy a generation of scientists.

  13. Effects of complex life cycles on genetic diversity: cyclical parthenogenesis.

    PubMed

    Rouger, R; Reichel, K; Malrieu, F; Masson, J P; Stoeckel, S

    2016-11-01

    Neutral patterns of population genetic diversity in species with complex life cycles are difficult to anticipate. Cyclical parthenogenesis (CP), in which organisms undergo several rounds of clonal reproduction followed by a sexual event, is one such life cycle. Many species, including crop pests (aphids), human parasites (trematodes) or models used in evolutionary science (Daphnia), are cyclical parthenogens. It is therefore crucial to understand the impact of such a life cycle on neutral genetic diversity. In this paper, we describe distributions of genetic diversity under conditions of CP with various clonal phase lengths. Using a Markov chain model of CP for a single locus and individual-based simulations for two loci, our analysis first demonstrates that strong departures from full sexuality are observed after only a few generations of clonality. The convergence towards predictions made under conditions of full clonality during the clonal phase depends on the balance between mutations and genetic drift. Second, the sexual event of CP usually resets the genetic diversity at a single locus towards predictions made under full sexuality. However, this single recombination event is insufficient to reshuffle gametic phases towards full-sexuality predictions. Finally, for similar levels of clonality, CP and acyclic partial clonality (wherein a fixed proportion of individuals are clonally produced within each generation) differentially affect the distribution of genetic diversity. Overall, this work provides solid predictions of neutral genetic diversity that may serve as a null model in detecting the action of common evolutionary or demographic processes in cyclical parthenogens (for example, selection or bottlenecks).

  14. Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

    PubMed Central

    Goddard, M. E.; Kemper, K. E.; MacLeod, I. M.; Chamberlain, A. J.; Hayes, B. J.

    2016-01-01

    Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement. PMID:27440663

  15. Common genetic variants influence human subcortical brain structures

    PubMed Central

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  16. Common genetic variants influence human subcortical brain structures.

    PubMed

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

    2015-04-09

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  17. Genetic Structure of the Spanish Population

    PubMed Central

    2010-01-01

    Background Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias. Results In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts. Conclusions In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community. PMID:20500880

  18. On indirect genetic effects in structured populations.

    PubMed

    Agrawal, A F; Brodie, E D; Wade, M J

    2001-09-01

    Indirect genetic effects (IGEs) occur when the phenotype of an individual, and possibly its fitness, depends, at least in part, on the genes of its social partners. The effective result is that environmental sources of phenotypic variance can themselves evolve. Simple models have shown that IGEs can alter the rate and direction of evolution for traits involved in interactions. Here we expand the applicability of the theory of IGEs to evolution in metapopulations by including nonlinear interactions between individuals and population genetic structure. Although population subdivision alone generates some dramatic and nonintuitive evolutionary dynamics for interacting phenotypes, the combination of nonlinear interactions with subdivision reveals an even greater importance of IGEs. The presence of genetic structure links the evolution of interacting phenotypes and the traits that influence their expression ("effector traits") even in the absence of genetic correlations. When nonlinear social effects occur in subdivided populations, evolutionary response is altered and can even oppose the direction expected due to direct selection. Because population genetic structure allows for multilevel selection, we also investigate the role of IGEs in determining the response to individual and group selection. We find that nonlinear social effects can cause interference between levels of selection even when they act in the same direction. In some cases, interference can be so extreme that the actual evolutionary response to multilevel selection is opposite in direction to that predicted by summing selection at each level. This theoretical result confirms empirical data that show higher levels of selection cannot be ignored even when selection acts in the same direction at all levels.

  19. Lexical Structure and Parsing Complexity.

    ERIC Educational Resources Information Center

    Stevenson, Suzanne; Merlo, Paolo

    1997-01-01

    Focuses on the consequences that the structural configuration of lexical knowledge has for the timecourse of parsing. Discusses reduced relative clauses and proposes a new lexical-structural analysis for manner of motion verbs. The article examines consequences for frequency-based models and all models whose difficulty derives from the ambiguity…

  20. Structure of DNA-liposome complexes

    SciTech Connect

    Lasic, D.D.; Strey, H.; Podgornik, R.; Stuart, M.C.A.; Frederik, P.M.

    1997-01-29

    Despite numerous studies and commericially available liposome kits, however, the structure of DNA-cationic liposome complexes is still not yet well understood. We have investigated the structure of these complexes using high-resolution cryo electron microscopy (EM) and small angle X-ray scattering (SAXS). 14 refs., 3 figs.

  1. Active impedance matching of complex structural systems

    NASA Technical Reports Server (NTRS)

    Macmartin, Douglas G.; Miller, David W.; Hall, Steven R.

    1991-01-01

    Viewgraphs on active impedance matching of complex structural systems are presented. Topics covered include: traveling wave model; dereverberated mobility model; computation of dereverberated mobility; control problem: optimal impedance matching; H2 optimal solution; statistical energy analysis (SEA) solution; experimental transfer functions; interferometer actuator and sensor locations; active strut configurations; power dual variables; dereverberation of complex structure; dereverberated transfer function; compensators; and relative power flow.

  2. TASI Lectures on Complex Structures

    NASA Astrophysics Data System (ADS)

    Denef, Frederik

    2012-11-01

    These lecture notes give an introduction to a number of ideas and methods that have been useful in the study of complex systems ranging from spin glasses to D-branes on Calabi-Yau manifolds. Topics include the replica formalism, Parisi's solution of the Sherrington-Kirkpatrick model, overlap order parameters, supersymmetric quantum mechanics, D-brane landscapes and their black hole duals.

  3. Genetic analysis of complex traits in the emerging Collaborative Cross

    PubMed Central

    Aylor, David L.; Valdar, William; Foulds-Mathes, Wendy; Buus, Ryan J.; Verdugo, Ricardo A.; Baric, Ralph S.; Ferris, Martin T.; Frelinger, Jeff A.; Heise, Mark; Frieman, Matt B.; Gralinski, Lisa E.; Bell, Timothy A.; Didion, John D.; Hua, Kunjie; Nehrenberg, Derrick L.; Powell, Christine L.; Steigerwalt, Jill; Xie, Yuying; Kelada, Samir N.P.; Collins, Francis S.; Yang, Ivana V.; Schwartz, David A.; Branstetter, Lisa A.; Chesler, Elissa J.; Miller, Darla R.; Spence, Jason; Liu, Eric Yi; McMillan, Leonard; Sarkar, Abhishek; Wang, Jeremy; Wang, Wei; Zhang, Qi; Broman, Karl W.; Korstanje, Ron; Durrant, Caroline; Mott, Richard; Iraqi, Fuad A.; Pomp, Daniel; Threadgill, David; Pardo-Manuel de Villena, Fernando; Churchill, Gary A.

    2011-01-01

    The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites—all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits. PMID:21406540

  4. Population Genetic and Admixture Analyses of Culex pipiens Complex (Diptera: Culicidae) Populations in California, United States

    PubMed Central

    Kothera, Linda; Nelms, Brittany M.; Reisen, William K.; Savage, Harry M.

    2013-01-01

    Microsatellite markers were used to genetically characterize 19 Culex pipiens complex populations from California. Two populations showed characteristics of earlier genetic bottlenecks. The overall FST value and a neighbor-joining tree suggested moderate amounts of genetic differentiation. Analyses using Structure indicated K = 4 genetic clusters: Cx. pipiens form pipiens L., Cx. quinquefasciatus Say, Cx. pipiens form molestus Forskäl, and a group of genetically similar individuals of hybrid origin. A Discriminant Analysis of Principal Components indicated that the latter group is a mixture of the other three taxa, with form pipiens and form molestus contributing somewhat more ancestry than Cx. quinquefasciatus. Characterization of 56 morphologically autogenous individuals classified most as Cx. pipiens form molestus, and none as Cx. pipiens form pipiens or Cx. quinquefasciatus. Comparison of California microsatellite data with those of Cx. pipiens pallens Coquillett from Japan indicated the latter does not contribute significantly to genotypes in California. PMID:23958909

  5. Argument structure frames: a lexical complexity metric?

    PubMed

    Schmauder, A R

    1991-01-01

    The number of semantic argument structure frames associated with a verb has been reported to influence ease of processing during language comprehension. The present experiments tested the generality of the argument structure complexity effect with three dependent measures: eye-fixation times, naming latencies, and lexical decision latencies. Two eye-movement experiments and two experiments using cross-modal tasks failed to provide evidence supporting the argument structure complexity effect. The present experiments indicated that results reflecting verbs' argument structure complexity are not generalizable.

  6. Computational complexity in electronic structure.

    PubMed

    Whitfield, James Daniel; Love, Peter John; Aspuru-Guzik, Alán

    2013-01-14

    In quantum chemistry, the price paid by all known efficient model chemistries is either the truncation of the Hilbert space or uncontrolled approximations. Theoretical computer science suggests that these restrictions are not mere shortcomings of the algorithm designers and programmers but could stem from the inherent difficulty of simulating quantum systems. Extensions of computer science and information processing exploiting quantum mechanics has led to new ways of understanding the ultimate limitations of computational power. Interestingly, this perspective helps us understand widely used model chemistries in a new light. In this article, the fundamentals of computational complexity will be reviewed and motivated from the vantage point of chemistry. Then recent results from the computational complexity literature regarding common model chemistries including Hartree-Fock and density functional theory are discussed.

  7. Structure Formation in Complex Plasma

    DTIC Science & Technology

    2011-08-24

    electrically levitated above the wafer and fell on the wafer when the applied voltage on the wafer was turned off. The Coulomb lattice discovered...such an extreme condition as cryogenic temperature. We also developed an experimental device to study the flow effects of microparticles levitated at...Research Conference (JAXA, Sagamihara, 2011.3.3-3.4) (in Japanese) 5. Y. Nakamura, N. Toma, Y. Saito, and . O. Ishihara, Dust acoustic wave in a complex

  8. Evaluation of large-scale genetic structure in complex demographic and historical scenarios: the mitochondrial DNA and Y-chromosome pools of the Iberian Atlantic façade.

    PubMed

    Pardiñas, Antonio F; Roca, Agustín; García-Vazquez, Eva; López, Belén

    2014-04-01

    Genetic structural patterns of human populations are usually a combination of long-term evolutionary forces and short-term social, cultural, and demographic processes. Recently, using mitochondrial DNA and Y-chromosome loci, various studies in northern Spain have found evidence that the geographical distribution of Iron Age tribal peoples might have influenced current patterns of genetic structuring in several autochthonous populations. Using the wealth of data that are currently available from the whole territory of the Iberian Peninsula, we have evaluated its genetic structuring in the spatial scale of the Atlantic façade. Hierarchical tree modeling procedures, combined with a classic analysis of molecular variance (AMOVA), were used to model known sociocultural divisions from the third century BCE to the eighth century CE, contrasting them with uniparental marker data. Our results show that, while mountainous and abrupt areas of the Iberian North bear the signals of long-term isolation in their maternal and paternal gene pools, the makeup of the Atlantic façade as a whole can be related to tribal population groups that predate the Roman conquest of the Peninsula. The maintenance through time of such a structure can be related to the numerous geographic barriers of the Iberian mainland, which have historically conditioned its settlement patterns and the occurrence of genetic drift processes.

  9. Structure-Based Characterization of Multiprotein Complexes

    PubMed Central

    Wiederstein, Markus; Gruber, Markus; Frank, Karl; Melo, Francisco; Sippl, Manfred J.

    2014-01-01

    Summary Multiprotein complexes govern virtually all cellular processes. Their 3D structures provide important clues to their biological roles, especially through structural correlations among protein molecules and complexes. The detection of such correlations generally requires comprehensive searches in databases of known protein structures by means of appropriate structure-matching techniques. Here, we present a high-speed structure search engine capable of instantly matching large protein oligomers against the complete and up-to-date database of biologically functional assemblies of protein molecules. We use this tool to reveal unseen structural correlations on the level of protein quaternary structure and demonstrate its general usefulness for efficiently exploring complex structural relationships among known protein assemblies. PMID:24954616

  10. Structure-based characterization of multiprotein complexes.

    PubMed

    Wiederstein, Markus; Gruber, Markus; Frank, Karl; Melo, Francisco; Sippl, Manfred J

    2014-07-08

    Multiprotein complexes govern virtually all cellular processes. Their 3D structures provide important clues to their biological roles, especially through structural correlations among protein molecules and complexes. The detection of such correlations generally requires comprehensive searches in databases of known protein structures by means of appropriate structure-matching techniques. Here, we present a high-speed structure search engine capable of instantly matching large protein oligomers against the complete and up-to-date database of biologically functional assemblies of protein molecules. We use this tool to reveal unseen structural correlations on the level of protein quaternary structure and demonstrate its general usefulness for efficiently exploring complex structural relationships among known protein assemblies.

  11. Orthobunyaviruses: recent genetic and structural insights.

    PubMed

    Elliott, Richard M

    2014-10-01

    Orthobunyaviruses, which have small, tripartite, negative-sense RNA genomes and structurally simple virions composed of just four proteins, can have devastating effects on human health and well-being, either by causing disease in humans or by causing disease in livestock and crops. In this Review, I describe the recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication and viral interactions with the host innate immune response. Lastly, I highlight outstanding questions and areas of future research.

  12. Complex and unexpected dynamics in simple genetic regulatory networks

    NASA Astrophysics Data System (ADS)

    Borg, Yanika; Ullner, Ekkehard; Alagha, Afnan; Alsaedi, Ahmed; Nesbeth, Darren; Zaikin, Alexey

    2014-03-01

    One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.

  13. An adaptive genetic algorithm for crystal structure prediction

    SciTech Connect

    Wu, Shunqing; Ji, Min; Wang, Cai-Zhuang; Nguyen, Manh Cuong; Zhao, Xin; Umemoto, K.; Wentzcovitch, R. M.; Ho, Kai-Ming

    2013-12-18

    We present a genetic algorithm (GA) for structural search that combines the speed of structure exploration by classical potentials with the accuracy of density functional theory (DFT) calculations in an adaptive and iterative way. This strategy increases the efficiency of the DFT-based GA by several orders of magnitude. This gain allows a considerable increase in the size and complexity of systems that can be studied by first principles. The performance of the method is illustrated by successful structure identifications of complex binary and ternary intermetallic compounds with 36 and 54 atoms per cell, respectively. The discovery of a multi-TPa Mg-silicate phase with unit cell containing up to 56 atoms is also reported. Such a phase is likely to be an essential component of terrestrial exoplanetary mantles.

  14. Complex ceramic structures. I. Weberites.

    PubMed

    Cai, Lu; Nino, Juan C

    2009-06-01

    The weberite structure (A2B2X7) is an anion-deficient fluorite-related superstructure. Compared with fluorites, the reduction in the number of anions leads to a decrease in the coordination number of the B cations (VI coordination) with respect to the A cations (VIII coordination), thus allowing the accommodation of diverse cations. As a result, weberite compounds have a broad range of chemical and physical properties and great technological potential. This article summarizes the structural features of weberite and describes the structure in several different ways. This is the first time that the stacking vector and stacking angle are used to represent the weberite structure. This paper also discusses the crystallographic relationship between weberite, fluorite and pyrochlore (another fluorite-related structure). The cation sublattices of weberite and pyrochlore are correlated by an axial transformation. It has been shown that the different coordination environment of anions is due to the alternating layering of the AB3 and A3B close-packed cation layers. A stability field of weberite oxides is proposed in terms of the ratio of ionic radius of cations and relative bond ionicity. In addition, a selection of weberite compounds with interesting properties is discussed.

  15. An integrated genetic-demographic model to unravel the origin of genetic structure in European eel (Anguilla anguilla L.)

    PubMed Central

    Andrello, Marco; Bevacqua, Daniele; Maes, Gregory E; De Leo, Giulio A

    2011-01-01

    The evolutionary enlightened management of species with complex life cycles often requires the development of mathematical models integrating demographic and genetic data. The genetic structure of the endangered European eel (Anguilla anguilla L.) has been thoroughly analyzed in several studies in the past years. However, the interpretation of the key demographic and biologic processes that determine the observed spatio-temporal genetic structure has been very challenging owing to the complex life cycle of this catadromous species. Here, we present the first integrated demographic-genetic model applied to the European eel that explicitly accounts for different levels of larval and adult mixing during oceanic migrations and allows us to explore alternative hypotheses on genetic differentiation. Our analyses show that (i) very low levels of mixing occurring during larval dispersal or adult migration are sufficient to erase entirely any genetic differences among sub-populations; (ii) small-scale temporal differentiation in recruitment can arise if the spawning stock is subdivided in distinct reproductive groups; and (iii) the geographic differentiation component might be overestimated if a limited number of temporal recruits are analyzed. Our study can inspire the scientific debate on the interpretation of genetic structure in other species characterized by complex life cycle and long-range migrations. PMID:25568002

  16. Novel gene complex structure determination

    SciTech Connect

    Gatewood, J.M.

    1997-08-01

    This is the final report of a one-year, Laboratory-Directed Research and Development (LORD) project at the Los Alamos National Laboratory. `Operative` chromatin containing exclusively the minor hasten variants was successfully isolated. Linker hasten H1 is quantitatively missing from operative chromatin. One of the aims of this proposal was to determine the proteins responsible for stabilizing operative chromatin. This chromatin is stabilized by microtubule proteins tar and tubulin. Another goal of this project was the structural characterization of operate chromatin nucleosomes. Using solution scattering, nucleosomes containing the minor variants were shown to be structurally distinct from major variant containing nucleosomes. The unusual structure and stabilization of operative chromatin by microtubule proteins provides a possible mechanism for direct interaction of transcription machinery with specific chromatin domains.

  17. Genetic structure of Tribolium castaneum (Coleptera: Tenebrionidae) populations in mills

    USDA-ARS?s Scientific Manuscript database

    The red flour beetle, Tribolium castaneum, is primarily found associated with human structures such as wheat and rice mills, which are spatially isolated resource patches with apparently limited immigration that could produce genetically structured populations. We investigated genetic diversity and...

  18. Genetic Optimization of a Tensegrity Structure

    NASA Technical Reports Server (NTRS)

    Taylor, Jaime R.

    2002-01-01

    Marshall Space Flight Center (MSFC) is charged with developing advanced technologies for space telescopes. The next generation of space optics will be very large and lightweight. Tensegrity structures are built of compressive members (bars), and tensile members (strings). For most materials, the tensile strength of a longitudinal member is larger than its buckling strength; therefore a large stiffness to mass ratio can be achieved by increasing the use of tensile members. Tensegrities are the epitome of lightweight structures, since they take advantage of the larger tensile strength of materials. The compressive members of tensegrity structures are disjoint allowing compact storage of the structure. The structure has the potential to eliminate the requirement for assembly by man in space; it can be deployed by adjustments in its cable tension. A tensegrity structure can be more reliably modeled since none of the individual members experience bending moments. (Members that experience deformation in more than one dimension are much harder to model.) A. Keane and S. Brown designed a satellite boom truss system with an enhanced vibration performance. They started with a standard truss system, then used a genetic algorithm to alter the design, while optimizing the vibration performance. An improvement of over 20,000% in frequency-averaged energy levels was obtained using this approach. In this report an introduction to tensegrity structures is given, along with a description of how to generate the nodal coordinates and connectivity of a multiple stage cylindrical tensegrity structure. A description of how finite elements can be used to develop a stiffness and mass matrix so that the modes of vibration can be determined from the eigenvalue problem is shown. A brief description of a micro genetic algorithm is then presented.

  19. Genetically complex epilepsies, copy number variants and syndrome constellations.

    PubMed

    Mefford, Heather C; Mulley, John C

    2010-10-05

    Epilepsy is one of the most common neurological disorders, with a prevalence of 1% and lifetime incidence of 3%. There are numerous epilepsy syndromes, most of which are considered to be genetic epilepsies. Despite the discovery of more than 20 genes for epilepsy to date, much of the genetic contribution to epilepsy is not yet known. Copy number variants have been established as an important source of mutation in other complex brain disorders, including intellectual disability, autism and schizophrenia. Recent advances in technology now facilitate genome-wide searches for copy number variants and are beginning to be applied to epilepsy. Here, we discuss what is currently known about the contribution of copy number variants to epilepsy, and how that knowledge is redefining classification of clinical and genetic syndromes.

  20. Genetic Architecture Of Declarative Memory: Implications for Complex Illnesses

    PubMed Central

    Bearden, Carrie E.; Karlsgodt, Katherine H.; Bachman, Peter; van Erp, Theo G.M.; Winkler, Anderson M.; Glahn, David C.

    2013-01-01

    Why do memory abilities vary so greatly across individuals and cognitive domains? Although memory functions are highly heritable, what exactly is being genetically transmitted? Here we review evidence for the contribution of both common and partially independent inheritance of distinct aspects of memory function. We begin by discussing the assessment of long-term memory and its underlying neural and molecular basis. We then consider evidence for both specialist and generalist genes underlying individual variability in memory, indicating that carving memory into distinct subcomponents may yield important information regarding its genetic architecture. And finally we review evidence from both complex and single-gene disorders, which provide insight into the molecular mechanisms underlying the genetic basis of human memory function. PMID:21832260

  1. Admixture and the organization of genetic diversity in a butterfly species complex revealed through common and rare genetic variants.

    PubMed

    Gompert, Zachariah; Lucas, Lauren K; Buerkle, C Alex; Forister, Matthew L; Fordyce, James A; Nice, Chris C

    2014-09-01

    Detailed information about the geographic distribution of genetic and genomic variation is necessary to better understand the organization and structure of biological diversity. In particular, spatial isolation within species and hybridization between them can blur species boundaries and create evolutionary relationships that are inconsistent with a strictly bifurcating tree model. Here, we analyse genome-wide DNA sequence and genetic ancestry variation in Lycaeides butterflies to quantify the effects of admixture and spatial isolation on how biological diversity is organized in this group. We document geographically widespread and pervasive historical admixture, with more restricted recent hybridization. This includes evidence supporting previously known and unknown instances of admixture. The genome composition of admixed individuals varies much more among than within populations, and tree- and genetic ancestry-based analyses indicate that multiple distinct admixed lineages or populations exist. We find that most genetic variants in Lycaeides are rare (minor allele frequency <0.5%). Because the spatial and taxonomic distributions of alleles reflect demographic and selective processes since mutation, rare alleles, which are presumably younger than common alleles, were spatially and taxonomically restricted compared with common variants. Thus, we show patterns of genetic variation in this group are multifaceted, and we argue that this complexity challenges simplistic notions concerning the organization of biological diversity into discrete, easily delineated and hierarchically structured entities.

  2. Novel genetic algorithm search procedure for LEED surface structure determination.

    PubMed

    Viana, M L; dos Reis, D D; Soares, E A; Van Hove, M A; Moritz, W; de Carvalho, V E

    2014-06-04

    Low Energy Electron Diffraction (LEED) is one of the most powerful experimental techniques for surface structure analysis but until now only a trial-and-error approach has been successful. So far, fitting procedures developed to optimize structural and nonstructural parameters-by minimization of the R-factor-have had a fairly small convergence radius, suitable only for local optimization. However, the identification of the global minimum among the several local minima is essential for complex surface structures. Global optimization methods have been applied to LEED structure determination, but they still require starting from structures that are relatively close to the correct one, in order to find the final structure. For complex systems, the number of trial structures and the resulting computation time increase so rapidly that the task of finding the correct model becomes impractical using the present methodologies. In this work we propose a new search method, based on Genetic Algorithms, which is able to determine the correct structural model starting from completely random structures. This method-called here NGA-LEED for Novel Genetic Algorithm for LEED-utilizes bond lengths and symmetry criteria to select reasonable trial structures before performing LEED calculations. This allows a reduction of the parameter space and, consequently of the calculation time, by several orders of magnitude. A refinement of the parameters by least squares fit of simulated annealing is performed only at some intermediate stages and in the final step. The method was successfully tested for two systems, Ag(1 1 1)(4 × 4)-O and Au(1 1 0)-(1 × 2), both in theory versus theory and in theory versus experiment comparisons. Details of the implementation as well as the results for these two systems are presented.

  3. Behavioral Genetic Toolkits: Toward the Evolutionary Origins of Complex Phenotypes.

    PubMed

    Rittschof, C C; Robinson, G E

    2016-01-01

    The discovery of toolkit genes, which are highly conserved genes that consistently regulate the development of similar morphological phenotypes across diverse species, is one of the most well-known observations in the field of evolutionary developmental biology. Surprisingly, this phenomenon is also relevant for a wide array of behavioral phenotypes, despite the fact that these phenotypes are highly complex and regulated by many genes operating in diverse tissues. In this chapter, we review the use of the toolkit concept in the context of behavior, noting the challenges of comparing behaviors and genes across diverse species, but emphasizing the successes in identifying genetic toolkits for behavior; these successes are largely attributable to the creative research approaches fueled by advances in behavioral genomics. We have two general goals: (1) to acknowledge the groundbreaking progress in this field, which offers new approaches to the difficult but exciting challenge of understanding the evolutionary genetic basis of behaviors, some of the most complex phenotypes known, and (2) to provide a theoretical framework that encompasses the scope of behavioral genetic toolkit studies in order to clearly articulate the research questions relevant to the toolkit concept. We emphasize areas for growth and highlight the emerging approaches that are being used to drive the field forward. Behavioral genetic toolkit research has elevated the use of integrative and comparative approaches in the study of behavior, with potentially broad implications for evolutionary biologists and behavioral ecologists alike.

  4. Sex differences in genetic architecture of complex phenotypes?

    PubMed

    Vink, Jacqueline M; Bartels, Meike; van Beijsterveldt, Toos C E M; van Dongen, Jenny; van Beek, Jenny H D A; Distel, Marijn A; de Moor, Marleen H M; Smit, Dirk J A; Minica, Camelia C; Ligthart, Lannie; Geels, Lot M; Abdellaoui, Abdel; Middeldorp, Christel M; Hottenga, Jouke Jan; Willemsen, Gonneke; de Geus, Eco J C; Boomsma, Dorret I

    2012-01-01

    We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits) in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA) studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ) same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women.

  5. Isonymy and the genetic structure of Sicily.

    PubMed

    Rodríguez-Larralde, A; Pavesi, A; Scapoli, C; Conterio, F; Siri, G; Barrai, I

    1994-01-01

    The genetic structure of Sicily was analysed through the distribution of surnames of 758,793 users registered in the Italian Telephone Company, corresponding to 371 communes of the island. Estimates of the coefficient of consanguinity due to random isonymy, of Fisher's a, an indicator of abundance of surnames, and of Karlin-McGregor's v, an indicator of immigration rates, were obtained for each commune. Four different estimates of genetic distance between all possible pairs of communes within each province were also obtained, and their relationship with geographic distance was studied. The logarithmic transformation of Lasker's coefficient of relationship showed correlations with the log of geographic distance which range between -0.78 and -0.40; the strongest, for the province of Catania, was attributed to the presence of Mount Etna, and the weakest, for Palermo, to the high population density of this province.

  6. Vascular Calcification: Current Genetics Underlying This Complex Phenomenon

    PubMed Central

    Pérez-Hernández, Nonanzit; Aptilon-Duque, Gad; Blachman-Braun, Ruben; Vargas-Alarcón, Gilberto; Rodríguez-Cortés, Adrián Asael; Azrad-Daniel, Shely; Posadas-Sánchez, Rosalinda; Rodríguez-Pérez, José Manuel

    2017-01-01

    Objective: Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima (atherosclerotic calcification) or tunica media (Mönckenberg's sclerosis). Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Data Sources: We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords “genetics and vascular calcification”, “molecular pathways, genetic and vascular calcification” and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways. Study Selection: The most valuable published original and review articles related to our objective were selected. Results: Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development. Conclusion: Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease. PMID:28469108

  7. Measures of Complexity to quantify Bone Structure

    NASA Astrophysics Data System (ADS)

    Saparin, Peter; Gowin, Wolfgang; Kurths, Jürgen; Felsenberg, Dieter

    1998-03-01

    We propose a technique to assess structure of the bone in its spatial distribution by describing and quantifying the structural architecture as a whole. The concept of measures of complexity based on symbolic dynamics is applied to computed tomography (CT) - images obtained from human lumbar vertebra. CT-images have been transformed into images consisting of 5 different symbols, whereby both statical and dynamical coding are included. Different aspects of the bone structure are quantified by several measures which have been introduced: index of global ensemble of elements composing the bone; complexity, homogeneity and dynamics within the bone architecture; complexity and inhomogeneity of the trabecular net. This leads to new insides to the understanding of bone's internal structure. The results give the first experimental and quantitative evidence of the theoretical prediction that complexity of bone structure declines rapidly with the increased disintegration of bone structures leading to the loss of bone mass and specify experimentally that bone structure is exponentially related to its density. Especially, osteoporotic vertebrae are less complex organized than normal ones. In addition, this method is significantly sensitive to changes in bone structure and provides improvements of diagnostic of pathological structural loss.

  8. Simple Phenotypic Sweeps Hide Complex Genetic Changes in Populations

    PubMed Central

    Maharjan, Ram P.; Liu, Bin; Feng, Lu; Ferenci, Thomas; Wang, Lei

    2015-01-01

    Changes in allele frequencies and the fixation of beneficial mutations are central to evolution. The precise relationship between mutational and phenotypic sweeps is poorly described however, especially when multiple alleles are involved. Here, we investigate these relationships in a bacterial population over 60 days in a glucose-limited chemostat in a large population. High coverage metagenomic analysis revealed a disconnection between smooth phenotypic sweeps and the complexity of genetic changes in the population. Phenotypic adaptation was due to convergent evolution and involved soft sweeps by 7–26 highly represented alleles of several genes in different combinations. Allele combinations spread from undetectably low baselines, indicating that minor subpopulations provide the basis of most innovations. A hard sweep was also observed, involving a single combination of rpoS, mglD, malE, sdhC, and malT mutations sweeping to greater than 95% of the population. Other mutant genes persisted but at lower abundance, including hfq, consistent with its demonstrated frequency-dependent fitness under glucose limitation. Other persistent, newly identified low-frequency mutations were in the aceF, galF, ribD and asm genes, in noncoding regulatory regions, three large indels and a tandem duplication; these were less affected by fluctuations involving more dominant mutations indicating separate evolutionary paths. Our results indicate a dynamic subpopulation structure with a minimum of 42 detectable mutations maintained over 60 days. We also conclude that the massive population-level mutation supply in combination with clonal interference leads to the soft sweeps observed, but not to the exclusion of an occasional hard sweep. PMID:25589261

  9. Genetic Structure of Loach Population in Yatsu Paddy Field

    NASA Astrophysics Data System (ADS)

    Koizumi, Noriyuki; Takemura, Takeshi; Mori, Atsushi; Okushima, Shuji

    Using repeated sequences of microsatellite DNA, we investigated genetic variation and spatial structure of the loach Misgurnus anguillicaudatus population in drainage canals including a main stream in the Shitada River basin composed of Yatsu paddy fields, Chiba Prefecture. Loach population samples of nine to 48 individuals were collected from 54 sampling sites in eight canals and the main stream, and genotype data in eight microsatellite loci were obtained for each sample in the genetic analysis. The average number of alleles per locus was 3.9 to 9.0, and the average observed and expected heterozygosities were 0.444-0.647 and 0.463-0.628, respectively, across samples. All samples seemed to be random mating, which conformed to the Hardy-Weinberg equilibrium. Values of the fixation index FST, were estimated to range between 0-0.161 among all samples, and a part of these values were significant. The pattern of genetic differentiation between samples with principal component analysis indicated that samples in three distinct canals appeared to differentiate, suggesting that the genetic spatial structure of the loach population in Yatsu paddy fields must be complex.

  10. Genetic Networks Controlling Structural Outcome of Glucosinolate Activation across Development

    PubMed Central

    Wentzell, Adam M.; Boeye, Ian; Zhang, Zhiyong; Kliebenstein, Daniel J.

    2008-01-01

    Most phenotypic variation present in natural populations is under polygenic control, largely determined by genetic variation at quantitative trait loci (QTLs). These genetic loci frequently interact with the environment, development, and each other, yet the importance of these interactions on the underlying genetic architecture of quantitative traits is not well characterized. To better study how epistasis and development may influence quantitative traits, we studied genetic variation in Arabidopsis glucosinolate activation using the moderately sized Bayreuth×Shahdara recombinant inbred population, in terms of number of lines. We identified QTLs for glucosinolate activation at three different developmental stages. Numerous QTLs showed developmental dependency, as well as a large epistatic network, centered on the previously cloned large-effect glucosinolate activation QTL, ESP. Analysis of Heterogeneous Inbred Families validated seven loci and all of the QTL×DPG (days post-germination) interactions tested, but was complicated by the extensive epistasis. A comparison of transcript accumulation data within 211 of these RILs showed an extensive overlap of gene expression QTLs for structural specifiers and their homologs with the identified glucosinolate activation loci. Finally, we were able to show that two of the QTLs are the result of whole-genome duplications of a glucosinolate activation gene cluster. These data reveal complex age-dependent regulation of structural outcomes and suggest that transcriptional regulation is associated with a significant portion of the underlying ontogenic variation and epistatic interactions in glucosinolate activation. PMID:18949035

  11. Structural entanglements in protein complexes

    NASA Astrophysics Data System (ADS)

    Zhao, Yani; Chwastyk, Mateusz; Cieplak, Marek

    2017-06-01

    We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both termini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface and increasing the DNA or RNA binding area. We also study the folding and stretching properties of the knotted dimeric proteins MJ0366, YibK, and bacteriophytochrome. These proteins have been studied theoretically in their monomeric versions so far. The dimers are seen to separate on stretching through the tensile mechanism and the characteristic unraveling force depends on the pulling direction.

  12. Genetic and phenotypic characterization of complex hereditary spastic paraplegia

    PubMed Central

    Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S.; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A.; Haridy, Nourelhoda A.; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P.; Korlipara, L.V. Prasad; Singleton, Andrew B.; Hardy, John; Wood, Nicholas W.; Lewis, Patrick A.

    2016-01-01

    The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next

  13. Protein complex compositions predicted by structural similarity

    PubMed Central

    Davis, Fred P.; Braberg, Hannes; Shen, Min-Yi; Pieper, Ursula; Sali, Andrej; Madhusudhan, M.S.

    2006-01-01

    Proteins function through interactions with other molecules. Thus, the network of physical interactions among proteins is of great interest to both experimental and computational biologists. Here we present structure-based predictions of 3387 binary and 1234 higher order protein complexes in Saccharomyces cerevisiae involving 924 and 195 proteins, respectively. To generate candidate complexes, comparative models of individual proteins were built and combined together using complexes of known structure as templates. These candidate complexes were then assessed using a statistical potential, derived from binary domain interfaces in PIBASE (). The statistical potential discriminated a benchmark set of 100 interface structures from a set of sequence-randomized negative examples with a false positive rate of 3% and a true positive rate of 97%. Moreover, the predicted complexes were also filtered using functional annotation and sub-cellular localization data. The ability of the method to select the correct binding mode among alternates is demonstrated for three camelid VHH domain—porcine α–amylase interactions. We also highlight the prediction of co-complexed domain superfamilies that are not present in template complexes. Through integration with MODBASE, the application of the method to proteomes that are less well characterized than that of S.cerevisiae will contribute to expansion of the structural and functional coverage of protein interaction space. The predicted complexes are deposited in MODBASE (). PMID:16738133

  14. Variable Complexity Optimization of Composite Structures

    NASA Technical Reports Server (NTRS)

    Haftka, Raphael T.

    2002-01-01

    The use of several levels of modeling in design has been dubbed variable complexity modeling. The work under the grant focused on developing variable complexity modeling strategies with emphasis on response surface techniques. Applications included design of stiffened composite plates for improved damage tolerance, the use of response surfaces for fitting weights obtained by structural optimization, and design against uncertainty using response surface techniques.

  15. Complex chloroplast RNA metabolism: just debugging the genetic programme?

    PubMed Central

    Maier, Uwe G; Bozarth, Andrew; Funk, Helena T; Zauner, Stefan; Rensing, Stefan A; Schmitz-Linneweber, Christian; Börner, Thomas; Tillich, Michael

    2008-01-01

    Background The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity. Results We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants. Conclusion Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions. PMID:18755031

  16. The Genetic Structure of Marijuana and Hemp.

    PubMed

    Sawler, Jason; Stout, Jake M; Gardner, Kyle M; Hudson, Darryl; Vidmar, John; Butler, Laura; Page, Jonathan E; Myles, Sean

    2015-01-01

    Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fibre, and contain low amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants. Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production. We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity. We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.

  17. The Genetic Structure of Marijuana and Hemp

    PubMed Central

    Sawler, Jason; Stout, Jake M.; Gardner, Kyle M.; Hudson, Darryl; Vidmar, John; Butler, Laura; Page, Jonathan E.; Myles, Sean

    2015-01-01

    Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fibre, and contain low amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants. Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production. We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity. We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains. PMID:26308334

  18. Structure of mammalian respiratory complex I

    PubMed Central

    Hirst, Judy

    2016-01-01

    Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner membrane. Mammalian complex I1 contains 45 subunits, comprising 14 core subunits that house the catalytic machinery and are conserved from bacteria to humans, and a mammalian-specific cohort of 31 supernumerary subunits1,2. Knowledge about the structures and functions of the supernumerary subunits is fragmentary. Here, we describe a 4.2 Å resolution single-particle cryoEM structure of complex I from Bos taurus. We locate and model all 45 subunits to provide the entire structure of the mammalian complex. Furthermore, computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally-dynamic regions and match biochemical descriptions of the ‘active-to-deactive’ enzyme transition that occurs during hypoxia3,4. Thus, our structures provide a foundation for understanding complex I assembly5 and the effects of mutations that cause clinically-relevant complex I dysfunctions6, insights into the structural and functional roles of the supernumerary subunits, and new information on the mechanism and regulation of catalysis. PMID:27509854

  19. Structure and function of cytochrome bc complexes

    SciTech Connect

    Berry, E.A.; Guergova-Kuras, M.; Huang, Li-Shar; Crofts, A.R.

    2000-05-01

    The cytochrome bc complexes represent a phylogenetically diverse group of electron-transfer membrane protein complexes, most familiarly represented by the mitochondrial and bacterial bc1 complexes and the chloroplast and cyanobacterial b6f complex. All these complexes couple electron transfer to protein translocation across a closed lipid bilayer membrane, conserving the free energy released by the oxidation-reduction process in the form of an electrochemical proton gradient across the membrane. Recent exciting developments include the application of site-directed mutagenesis to define the role of conserved residues, and the emergence over the past 5 years of x-ray structures for several mitochondrial complexes, and for two important domains of the b6f complex.

  20. Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling

    PubMed Central

    Bowie, Rachel V.; Li, Chunmei; Kennedy, Julie K.; Ashrafi, Kaveh; Blacque, Oliver E.; Leroux, Michel R.; Reiter, Jeremy F.

    2015-01-01

    Mutations in genes encoding cilia proteins cause human ciliopathies, diverse disorders affecting many tissues. Individual genes can be linked to ciliopathies with dramatically different phenotypes, suggesting that genetic modifiers may participate in their pathogenesis. The ciliary transition zone contains two protein complexes affected in the ciliopathies Meckel syndrome (MKS) and nephronophthisis (NPHP). The BBSome is a third protein complex, affected in the ciliopathy Bardet-Biedl syndrome (BBS). We tested whether mutations in MKS, NPHP and BBS complex genes modify the phenotypic consequences of one another in both C. elegans and mice. To this end, we identified TCTN-1, the C. elegans ortholog of vertebrate MKS complex components called Tectonics, as an evolutionarily conserved transition zone protein. Neither disruption of TCTN-1 alone or together with MKS complex components abrogated ciliary structure in C. elegans. In contrast, disruption of TCTN-1 together with either of two NPHP complex components, NPHP-1 or NPHP-4, compromised ciliary structure. Similarly, disruption of an NPHP complex component and the BBS complex component BBS-5 individually did not compromise ciliary structure, but together did. As in nematodes, disrupting two components of the mouse MKS complex did not cause additive phenotypes compared to single mutants. However, disrupting both Tctn1 and either Nphp1 or Nphp4 exacerbated defects in ciliogenesis and cilia-associated developmental signaling, as did disrupting both Tctn1 and the BBSome component Bbs1. Thus, we demonstrate that ciliary complexes act in parallel to support ciliary function and suggest that human ciliopathy phenotypes are altered by genetic interactions between different ciliary biochemical complexes. PMID:26540106

  1. Genetic approaches for changing the heart and dissecting complex syndromes

    PubMed Central

    Moga, Michael-Alice; Nakamura, Tomoki; Robbins, Jeffrey

    2008-01-01

    The genetic, biochemical and molecular bases of human cardiac disease have been the focus of extensive research efforts for many years. Early animal models of cardiovascular disease used pharmacologic or surgical interventions, or took advantage of naturally occurring genetic abnormalities and the data obtained were largely correlative. The inability to directly alter an organism’s genetic makeup and cellular protein content and accurately measure the results of that manipulation precluded rigorous examination of true cause-effect and structure-function relationships. Directed genetic manipulation in the mouse gave researchers the ability to modify and control the mammalian heart’s protein content, resulting in the rational design of models that could provide critical links between the mutated or absent protein and disease. Two techniques that have proven particularly useful are transgenesis, which involves the random insertion of ectopic genetic material of interest into a “host” genome, and gene targeting, which utilizes homologous recombination at a pre-selected locus. Initially, transgenesis and gene targeting were used to examine systemic loss-of-function and gain-of-function, respectively, but further refinements in both techniques have allowed for investigations of organ-specific, cell type-specific, developmental stage-sensitive and dose-dependent effects. Genetically engineered animal models of pediatric and adult cardiac disease have proven that, when used appropriately, these tools have the power to extend mere observation to the establishment of true causative proof. We illustrate the power of the general approach by showing how genetically engineered mouse models can define the precise signaling pathways that are affected by the gain-of-function mutation that underlies Noonan syndrome. Increasingly precise and modifiable animal models of human cardiac disease will allow researchers to determine not only pathogenesis, but also guide treatment

  2. Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology

    PubMed Central

    Kotlikoff, Michael I

    2007-01-01

    This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed. PMID:17038427

  3. Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology.

    PubMed

    Kotlikoff, Michael I

    2007-01-01

    This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed.

  4. [Genetic structure of the Udmurt population].

    PubMed

    Zinchenko, R A; El'chinova, G I; Petrov, N V; Osipova, E V; Malyshev, P Iu; Poliakov, A V; Ginter, E K

    2007-08-01

    Integrated study of the genetic structure of the Udmurt population with respect to different genetic systems has been performed. Data on the genes of genetic diseases, abiotic parameters analyzed by population statistic methods, and DNA polymorphism are summarized. The populations of six raions (districts) of Udmurt Republic (the Mozhga, Malaya Purga, Sharkan, Debesy, Igra, and Glazov raions) have been studied. The total population studied was 267,655 people (an urban population of 150,119 people and a rural population of 117,536 people), including 155,346 Udmurts. The population structure has been studied in six districts on the basis of the vital statistics, Crow's indices, Malecot's isolation by distance parameters, ethnically assortative marriage parameters, endogamy indices, inbreeding-endogamy (ie) indices, and frequencies of the genotype and allele frequencies of four DNA markers (17 alleles). The prevalences of hereditary diseases have been calculated for different population groups: urban and rural populations, Udmurts and other ethnic groups. These groups, especially the urban and rural populations, substantially differed from one another in the prevalences of autosomal dominant (AR) and autosomal recessive (AR) diseases. The correlation between the prevalence of AD and AR diseases and the ie index is positive and significant. The spectrum of hereditary diseases detected in six districts of Udmurtia comprises 149 diseases (80, 57, and 12 AD, AR, and X-linked diseases, respectively). Accumulation of individual diseases in districts of Udmurtia and accumulation of diseases in Udmurtia as compared to regions studied earlier has been found. Cluster analysis of the frequencies of genes of AD and AR diseases and DNA markers has determined the gene geographic position of Udmurts.

  5. Genomic approaches for understanding the genetics of complex disease

    PubMed Central

    Lowe, William L.; Reddy, Timothy E.

    2015-01-01

    There are thousands of known associations between genetic variants and complex human phenotypes, and the rate of novel discoveries is rapidly increasing. Translating those associations into knowledge of disease mechanisms remains a fundamental challenge because the associated variants are overwhelmingly in noncoding regions of the genome where we have few guiding principles to predict their function. Intersecting the compendium of identified genetic associations with maps of regulatory activity across the human genome has revealed that phenotype-associated variants are highly enriched in candidate regulatory elements. Allele-specific analyses of gene regulation can further prioritize variants that likely have a functional effect on disease mechanisms; and emerging high-throughput assays to quantify the activity of candidate regulatory elements are a promising next step in that direction. Together, these technologies have created the ability to systematically and empirically test hypotheses about the function of noncoding variants and haplotypes at the scale needed for comprehensive and systematic follow-up of genetic association studies. Major coordinated efforts to quantify regulatory mechanisms across genetically diverse populations in increasingly realistic cell models would be highly beneficial to realize that potential. PMID:26430153

  6. Assessing risk assessment: genetic testing and screening for complex disease.

    PubMed

    Cox, S M

    2006-11-01

    This paper reports on the presentations from the second session of a 2-day workshop on genetic diversity and science communication, organized by the Institute of Genetics. The four talks in this session (by Sarah Cunningham-Burley, Gail Geller, Michael Hayden, and Theresa Marteau) focused on the topic of risk assessment in the context of genetic testing, screening and preventive medicine for complex disease. Each talk underscored the urgency and importance of evaluating when and for whom risk assessment may be useful. A recurrent theme was the need to attend closely to the diverse ways that risk is constructed, perceived and communicated in a variety of contexts and the significant implications of this for laypersons as well as experts. Although there was no consensus on when genetic risk assessment ceases (or might begin) to be useful, ensuing dialogue between presenters and participants reflected what is perhaps a new and critical engagement with how risk assessment itself is assessed. In response to this impetus, I use the word RISK as a heuristic to identify, extract and amplify four tendencies that appear to advance understandings of risk assessment towards a more explicitly reflexive, interpretive, and situated form of knowing.

  7. Structure of nucleosome-HMG complexes

    SciTech Connect

    Paton, A.E.

    1982-12-01

    This dissertation concentrates on the structure of HMG-nucleosome complexes, and how they differ from nucleosomes alone. The first chapter provides an introduction to chromatin and an overview of the field. The second and third chapters describe what kinds of nucleosome-HMG protein complexes form in solution, and where the HMG proteins may bind on the nucleosome. A model is proposed that locates the HMG binding sites on the nucleosome core particle. The fourth chapter describes the biophysical characterization of the complex. The methods include thermal denaturation, circular dichroism and sedimentation velocity, all done under variety of solvent conditions. These methods reveal a great deal of information on the stability and interactions of the complex. The fifth chapter describes conformational probes of the complex. These results reveal the structural transitions that occur when HMG protein binds to the nucleosome as well as the parts of the nucleosome essential for the binding reaction.

  8. Structural Studies of Protein-Surfactant Complexes

    SciTech Connect

    Chodankar, S. N.; Aswal, V. K.; Wagh, A. G.

    2008-03-17

    The structure of protein-surfactant complexes of two proteins bovine serum albumin (BSA) and lysozyme in presence of anionic surfactant sodium dodecyl sulfate (SDS) has been studied using small-angle neutron scattering (SANS). It is observed that these two proteins form different complex structures with the surfactant. While BSA protein undergoes unfolding on addition of surfactant, lysozyme does not show any unfolding even up to very high surfactant concentrations. The unfolding of BSA protein is caused by micelle-like aggregation of surfactant molecules in the complex. On the other hand, for lysozyme protein there is only binding of individual surfactant molecules to protein. Lysozyme in presence of higher surfactant concentrations has protein-surfactant complex structure coexisting with pure surfactant micelles.

  9. Complex II from a structural perspective.

    PubMed

    Horsefield, Rob; Iwata, So; Byrne, Bernadette

    2004-04-01

    The super-macromolecular complex, succinate:quinone oxidoreductase (SQR, Complex II, succinate dehydrogenase) couples the oxidation of succinate in the matrix / cytoplasm to the reduction of quinone in the membrane. This function directly connects the Krebs cycle and the aerobic respiratory chain. Until the recent first report of the structure of SQR from Escherichia coli (E. coli) the structure-function relationships in SQR have been inferred from the structures of the homologous QFR, which catalyses the same reaction in the opposite direction. The structure of SQR from E. coli, analogous to the mitochondrial respiratory Complex II, has provided new insight into SQR's molecular design and mechanism, revealing the electron transport pathway through the enzyme. Comparison of the structures of SQR, QFR and other related flavoproteins shows how common amino acid residues at the interface of two domains facilitate the inter-conversion of succinate and fumarate. Additionally, the structure has provided a possible explanation as to why certain organisms utilise both SQR and QFR despite the fact that both can catalyse the inter-conversion of succinate and fumarate, in vitro and in vivo. Here we review how this structure has advanced our knowledge of this important enzyme and compare the structural information to other members of the Complex II superfamily and related flavoproteins.

  10. Stochastic transport through complex comb structures

    SciTech Connect

    Zaburdaev, V. Yu.; Popov, P. V.; Romanov, A. S.; Chukbar, K. V.

    2008-05-15

    A unified rigorous approach is used to derive fractional differential equations describing subdiffusive transport through comb structures of various geometrical complexity. A general nontrivial effect of the initial particle distribution on the subsequent evolution is exposed. Solutions having qualitative features of practical importance are given for joined structures with widely different fractional exponents.

  11. 3D Protein structure prediction with genetic tabu search algorithm

    PubMed Central

    2010-01-01

    Background Protein structure prediction (PSP) has important applications in different fields, such as drug design, disease prediction, and so on. In protein structure prediction, there are two important issues. The first one is the design of the structure model and the second one is the design of the optimization technology. Because of the complexity of the realistic protein structure, the structure model adopted in this paper is a simplified model, which is called off-lattice AB model. After the structure model is assumed, optimization technology is needed for searching the best conformation of a protein sequence based on the assumed structure model. However, PSP is an NP-hard problem even if the simplest model is assumed. Thus, many algorithms have been developed to solve the global optimization problem. In this paper, a hybrid algorithm, which combines genetic algorithm (GA) and tabu search (TS) algorithm, is developed to complete this task. Results In order to develop an efficient optimization algorithm, several improved strategies are developed for the proposed genetic tabu search algorithm. The combined use of these strategies can improve the efficiency of the algorithm. In these strategies, tabu search introduced into the crossover and mutation operators can improve the local search capability, the adoption of variable population size strategy can maintain the diversity of the population, and the ranking selection strategy can improve the possibility of an individual with low energy value entering into next generation. Experiments are performed with Fibonacci sequences and real protein sequences. Experimental results show that the lowest energy obtained by the proposed GATS algorithm is lower than that obtained by previous methods. Conclusions The hybrid algorithm has the advantages from both genetic algorithm and tabu search algorithm. It makes use of the advantage of multiple search points in genetic algorithm, and can overcome poor hill

  12. 3D protein structure prediction with genetic tabu search algorithm.

    PubMed

    Zhang, Xiaolong; Wang, Ting; Luo, Huiping; Yang, Jack Y; Deng, Youping; Tang, Jinshan; Yang, Mary Qu

    2010-05-28

    Protein structure prediction (PSP) has important applications in different fields, such as drug design, disease prediction, and so on. In protein structure prediction, there are two important issues. The first one is the design of the structure model and the second one is the design of the optimization technology. Because of the complexity of the realistic protein structure, the structure model adopted in this paper is a simplified model, which is called off-lattice AB model. After the structure model is assumed, optimization technology is needed for searching the best conformation of a protein sequence based on the assumed structure model. However, PSP is an NP-hard problem even if the simplest model is assumed. Thus, many algorithms have been developed to solve the global optimization problem. In this paper, a hybrid algorithm, which combines genetic algorithm (GA) and tabu search (TS) algorithm, is developed to complete this task. In order to develop an efficient optimization algorithm, several improved strategies are developed for the proposed genetic tabu search algorithm. The combined use of these strategies can improve the efficiency of the algorithm. In these strategies, tabu search introduced into the crossover and mutation operators can improve the local search capability, the adoption of variable population size strategy can maintain the diversity of the population, and the ranking selection strategy can improve the possibility of an individual with low energy value entering into next generation. Experiments are performed with Fibonacci sequences and real protein sequences. Experimental results show that the lowest energy obtained by the proposed GATS algorithm is lower than that obtained by previous methods. The hybrid algorithm has the advantages from both genetic algorithm and tabu search algorithm. It makes use of the advantage of multiple search points in genetic algorithm, and can overcome poor hill-climbing capability in the conventional genetic

  13. No evidence for a genetic blueprint: The case of the "complex" mammalian photoreceptor.

    PubMed

    Kumaramanickavel, G; Denton, M J; Legge, M

    2015-04-01

    Despite the intensity of the search for genes causing inherited retinal degenerations over the past 3 decades, of the approximately 200 disease genes identified to date, all appear to be ordinary housekeeping genes specifying proteins playing basic structural and functional roles in the mature photoreceptor cells. No genes or genetic elements have been identified which can be construed as having a specific morphogenic role, directing the development of the cytoarchitecture of any particular retinal cell. The evidence suggests that the cytoarchitecture of the retinal photoreceptors, although enormously complex, arises from the self-organization of the cells constituents without any regulation or direction from an external genetic blueprint.

  14. "Good enough solutions" and the genetics of complex diseases.

    PubMed

    Weiss, James N; Karma, Alain; MacLellan, W Robb; Deng, Mario; Rau, Christoph D; Rees, Colin M; Wang, Jessica; Wisniewski, Nicholas; Eskin, Eleazar; Horvath, Steve; Qu, Zhilin; Wang, Yibin; Lusis, Aldons J

    2012-08-03

    In this Emerging Science Review, we discuss a systems genetics strategy, which we call gene module association study (GMAS), as a novel approach complementing genome-wide association studies (GWAS), to understand complex diseases by focusing on how genes work together in groups rather than singly. The first step is to characterize phenotypic differences among a genetically diverse population. The second step is to use gene expression microarray (or other high-throughput) data from the population to construct gene coexpression networks. Coexpression analysis typically groups 20 000 genes into 20 to 30 modules containing tens to hundreds of genes, whose aggregate behavior can be represented by the module's "eigengene." The third step is to correlate expression patterns with phenotype, as in GWAS, only applied to eigengenes instead of single nucleotide polymorphisms. The goal of the GMAS approach is to identify groups of coregulated genes that explain complex traits from a systems perspective. From an evolutionary standpoint, we hypothesize that variability in eigengene patterns reflects the "good enough solution" concept, that biological systems are sufficiently complex so that many possible combinations of the same elements (in this case eigengenes) can produce an equivalent output, that is, a "good enough solution" to accomplish normal biological functions. However, when faced with environmental stresses, some "good enough solutions" adapt better than others, explaining individual variability to disease and drug susceptibility. If validated, GMAS may imply that common polygenic diseases are related as much to group interactions between normal genes, as to multiple gene mutations.

  15. Non-coding RNAs and complex distributed genetic networks

    NASA Astrophysics Data System (ADS)

    Zhdanov, Vladimir P.

    2011-08-01

    In eukaryotic cells, the mRNA-protein interplay can be dramatically influenced by non-coding RNAs (ncRNAs). Although this new paradigm is now widely accepted, an understanding of the effect of ncRNAs on complex genetic networks is lacking. To clarify what may happen in this case, we propose a mean-field kinetic model describing the influence of ncRNA on a complex genetic network with a distributed architecture including mutual protein-mediated regulation of many genes transcribed into mRNAs. ncRNA is considered to associate with mRNAs and inhibit their translation and/or facilitate degradation. Our results are indicative of the richness of the kinetics under consideration. The main complex features are found to be bistability and oscillations. One could expect to find kinetic chaos as well. The latter feature has however not been observed in our calculations. In addition, we illustrate the difference in the regulation of distributed networks by mRNA and ncRNA.

  16. The variation game: Cracking complex genetic disorders with NGS and omics data.

    PubMed

    Cui, Hongzhu; Dhroso, Andi; Johnson, Nathan; Korkin, Dmitry

    2015-06-01

    Tremendous advances in Next Generation Sequencing (NGS) and high-throughput omics methods have brought us one step closer towards mechanistic understanding of the complex disease at the molecular level. In this review, we discuss four basic regulatory mechanisms implicated in complex genetic diseases, such as cancer, neurological disorders, heart disease, diabetes, and many others. The mechanisms, including genetic variations, copy-number variations, posttranscriptional variations, and epigenetic variations, can be detected using a variety of NGS methods. We propose that malfunctions detected in these mechanisms are not necessarily independent, since these malfunctions are often found associated with the same disease and targeting the same gene, group of genes, or functional pathway. As an example, we discuss possible rewiring effects of the cancer-associated genetic, structural, and posttranscriptional variations on the protein-protein interaction (PPI) network centered around P53 protein. The review highlights multi-layered complexity of common genetic disorders and suggests that integration of NGS and omics data is a critical step in developing new computational methods capable of deciphering this complexity.

  17. Analyzing Static Loading of Complex Structures

    NASA Technical Reports Server (NTRS)

    Gallear, D. C.

    1986-01-01

    Critical loading conditions determined from analysis of each structural element. Automated Thrust Structures Loads and Stresses (ATLAS) system is series of programs developed to analyze elements of complex structure under static-loading conditions. ATLAS calculates internal loads, beam-bending loads, column- and web-buckling loads, beam and panel stresses, and beam-corner stresses. Programs written in FORTRAN IV and Assembler for batch execution.

  18. Genomic and Genetic Diversity within the Pseudomonas fluorescens Complex.

    PubMed

    Garrido-Sanz, Daniel; Meier-Kolthoff, Jan P; Göker, Markus; Martín, Marta; Rivilla, Rafael; Redondo-Nieto, Miguel

    2016-01-01

    The Pseudomonas fluorescens complex includes Pseudomonas strains that have been taxonomically assigned to more than fifty different species, many of which have been described as plant growth-promoting rhizobacteria (PGPR) with potential applications in biocontrol and biofertilization. So far the phylogeny of this complex has been analyzed according to phenotypic traits, 16S rDNA, MLSA and inferred by whole-genome analysis. However, since most of the type strains have not been fully sequenced and new species are frequently described, correlation between taxonomy and phylogenomic analysis is missing. In recent years, the genomes of a large number of strains have been sequenced, showing important genomic heterogeneity and providing information suitable for genomic studies that are important to understand the genomic and genetic diversity shown by strains of this complex. Based on MLSA and several whole-genome sequence-based analyses of 93 sequenced strains, we have divided the P. fluorescens complex into eight phylogenomic groups that agree with previous works based on type strains. Digital DDH (dDDH) identified 69 species and 75 subspecies within the 93 genomes. The eight groups corresponded to clustering with a threshold of 31.8% dDDH, in full agreement with our MLSA. The Average Nucleotide Identity (ANI) approach showed inconsistencies regarding the assignment to species and to the eight groups. The small core genome of 1,334 CDSs and the large pan-genome of 30,848 CDSs, show the large diversity and genetic heterogeneity of the P. fluorescens complex. However, a low number of strains were enough to explain most of the CDSs diversity at core and strain-specific genomic fractions. Finally, the identification and analysis of group-specific genome and the screening for distinctive characters revealed a phylogenomic distribution of traits among the groups that provided insights into biocontrol and bioremediation applications as well as their role as PGPR.

  19. Genomic and Genetic Diversity within the Pseudomonas fluorescens Complex

    PubMed Central

    Garrido-Sanz, Daniel; Meier-Kolthoff, Jan P.; Göker, Markus; Martín, Marta; Rivilla, Rafael; Redondo-Nieto, Miguel

    2016-01-01

    The Pseudomonas fluorescens complex includes Pseudomonas strains that have been taxonomically assigned to more than fifty different species, many of which have been described as plant growth-promoting rhizobacteria (PGPR) with potential applications in biocontrol and biofertilization. So far the phylogeny of this complex has been analyzed according to phenotypic traits, 16S rDNA, MLSA and inferred by whole-genome analysis. However, since most of the type strains have not been fully sequenced and new species are frequently described, correlation between taxonomy and phylogenomic analysis is missing. In recent years, the genomes of a large number of strains have been sequenced, showing important genomic heterogeneity and providing information suitable for genomic studies that are important to understand the genomic and genetic diversity shown by strains of this complex. Based on MLSA and several whole-genome sequence-based analyses of 93 sequenced strains, we have divided the P. fluorescens complex into eight phylogenomic groups that agree with previous works based on type strains. Digital DDH (dDDH) identified 69 species and 75 subspecies within the 93 genomes. The eight groups corresponded to clustering with a threshold of 31.8% dDDH, in full agreement with our MLSA. The Average Nucleotide Identity (ANI) approach showed inconsistencies regarding the assignment to species and to the eight groups. The small core genome of 1,334 CDSs and the large pan-genome of 30,848 CDSs, show the large diversity and genetic heterogeneity of the P. fluorescens complex. However, a low number of strains were enough to explain most of the CDSs diversity at core and strain-specific genomic fractions. Finally, the identification and analysis of group-specific genome and the screening for distinctive characters revealed a phylogenomic distribution of traits among the groups that provided insights into biocontrol and bioremediation applications as well as their role as PGPR. PMID:26915094

  20. Integrating genetic linkage maps with pachytene chromosome structure in maize.

    PubMed

    Anderson, Lorinda K; Salameh, Naser; Bass, Hank W; Harper, Lisa C; Cande, W Z; Weber, Gerd; Stack, Stephen M

    2004-04-01

    Genetic linkage maps reveal the order of markers based on the frequency of recombination between markers during meiosis. Because the rate of recombination varies along chromosomes, it has been difficult to relate linkage maps to chromosome structure. Here we use cytological maps of crossing over based on recombination nodules (RNs) to predict the physical position of genetic markers on each of the 10 chromosomes of maize. This is possible because (1). all 10 maize chromosomes can be individually identified from spreads of synaptonemal complexes, (2). each RN corresponds to one crossover, and (3). the frequency of RNs on defined chromosomal segments can be converted to centimorgan values. We tested our predictions for chromosome 9 using seven genetically mapped, single-copy markers that were independently mapped on pachytene chromosomes using in situ hybridization. The correlation between predicted and observed locations was very strong (r(2) = 0.996), indicating a virtual 1:1 correspondence. Thus, this new, high-resolution, cytogenetic map enables one to predict the chromosomal location of any genetically mapped marker in maize with a high degree of accuracy. This novel approach can be applied to other organisms as well.

  1. Genetic programming approach to evaluate complexity of texture images

    NASA Astrophysics Data System (ADS)

    Ciocca, Gianluigi; Corchs, Silvia; Gasparini, Francesca

    2016-11-01

    We adopt genetic programming (GP) to define a measure that can predict complexity perception of texture images. We perform psychophysical experiments on three different datasets to collect data on the perceived complexity. The subjective data are used for training, validation, and test of the proposed measure. These data are also used to evaluate several possible candidate measures of texture complexity related to both low level and high level image features. We select four of them (namely roughness, number of regions, chroma variance, and memorability) to be combined in a GP framework. This approach allows a nonlinear combination of the measures and could give hints on how the related image features interact in complexity perception. The proposed complexity measure M exhibits Pearson correlation coefficients of 0.890 on the training set, 0.728 on the validation set, and 0.724 on the test set. M outperforms each of all the single measures considered. From the statistical analysis of different GP candidate solutions, we found that the roughness measure evaluated on the gray level image is the most dominant one, followed by the memorability, the number of regions, and finally the chroma variance.

  2. Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into Crohn disease.

    PubMed

    Elding, Heather; Lau, Winston; Swallow, Dallas M; Maniatis, Nikolas

    2011-12-09

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Frequency and Complexity of De Novo Structural Mutation in Autism.

    PubMed

    Brandler, William M; Antaki, Danny; Gujral, Madhusudan; Noor, Amina; Rosanio, Gabriel; Chapman, Timothy R; Barrera, Daniel J; Lin, Guan Ning; Malhotra, Dheeraj; Watts, Amanda C; Wong, Lawrence C; Estabillo, Jasper A; Gadomski, Therese E; Hong, Oanh; Fajardo, Karin V Fuentes; Bhandari, Abhishek; Owen, Renius; Baughn, Michael; Yuan, Jeffrey; Solomon, Terry; Moyzis, Alexandra G; Maile, Michelle S; Sanders, Stephan J; Reiner, Gail E; Vaux, Keith K; Strom, Charles M; Zhang, Kang; Muotri, Alysson R; Akshoomoff, Natacha; Leal, Suzanne M; Pierce, Karen; Courchesne, Eric; Iakoucheva, Lilia M; Corsello, Christina; Sebat, Jonathan

    2016-04-07

    Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.

  4. Frequency and Complexity of De Novo Structural Mutation in Autism

    PubMed Central

    Brandler, William M.; Antaki, Danny; Gujral, Madhusudan; Noor, Amina; Rosanio, Gabriel; Chapman, Timothy R.; Barrera, Daniel J.; Lin, Guan Ning; Malhotra, Dheeraj; Watts, Amanda C.; Wong, Lawrence C.; Estabillo, Jasper A.; Gadomski, Therese E.; Hong, Oanh; Fajardo, Karin V. Fuentes; Bhandari, Abhishek; Owen, Renius; Baughn, Michael; Yuan, Jeffrey; Solomon, Terry; Moyzis, Alexandra G.; Maile, Michelle S.; Sanders, Stephan J.; Reiner, Gail E.; Vaux, Keith K.; Strom, Charles M.; Zhang, Kang; Muotri, Alysson R.; Akshoomoff, Natacha; Leal, Suzanne M.; Pierce, Karen; Courchesne, Eric; Iakoucheva, Lilia M.; Corsello, Christina; Sebat, Jonathan

    2016-01-01

    Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement. PMID:27018473

  5. Variable Complexity Optimization of Composite Structures

    NASA Technical Reports Server (NTRS)

    Haftka, Raphael T.

    1999-01-01

    The use of several levels of modeling in design has been dubbed variable complexity modeling. The work under the grant focused on developing variable complexity modeling strategies with emphasis on response surface techniques. Applications included design of plates with discontinuities subject to uncertainty in material properties and geometry, design of stiffened composite plates for improved damage tolerance, and the use of response surfaces for fitting weights obtained by structural optimization.

  6. The Electronic Structure of Heavy Element Complexes

    SciTech Connect

    Bursten, Bruce E.

    2000-07-25

    The area of study is the bonding in heavy element complexes, and the application of more sophisticated electronic structure theories. Progress is recounted in several areas: (a) technological advances and current methodologies - Relativistic effects are extremely important in gaining an understanding of the electronic structure of compounds of the actinides, transactinides, and other heavy elements. Therefore, a major part of the continual benchmarking was the proper inclusion of the appropriate relativistic effects for the properties under study. (b) specific applications - These include organoactinide sandwich complexes, CO activation by actinide atoms, and theoretical studies of molecules of the transactinide elements. Finally, specific directions in proposed research are described.

  7. Structural polymorphism of DNA-dendrimer complexes

    NASA Astrophysics Data System (ADS)

    Evans, Heather M.; Ahmad, A.; Ewert, K.; Pfohl, T.; Martin-Herranz, A.; Bruinsma, R. F.; Safinya, C. R.

    2003-08-01

    DNA condensation in vivo relies on electrostatic complexation with small cations or large histones. We report a synchrotron x-ray study of the phase behavior of DNA complexed with synthetic cationic dendrimers of intermediate size and charge. We encounter unexpected structural transitions between columnar mesophases with in-plane square and hexagonal symmetries, as well as liquidlike disorder. The isoelectric point is a locus of structural instability. A simple model is proposed based on competing long-range electrostatic interactions and short-range entropic adhesion by counterion release.

  8. Genetic aspect of Alzheimer disease: Results of complex segregation analysis

    SciTech Connect

    Sadonvick, A.D.; Lee, I.M.L.; Bailey-Wilson, J.E.

    1994-09-01

    The study was designed to evaluate the possibility that a single major locus will explain the segregation of Alzheimer disease (AD). The data were from the population-based AD Genetic Database and consisted of 402 consecutive, unrelated probands, diagnosed to have either `probable` or `autopsy confirmed` AD and their 2,245 first-degree relatives. In this analysis, a relative was considered affected with AD only when there were sufficient medical/autopsy data to support diagnosis of AD being the most likely cause of the dementia. Transmission probability models allowing for a genotype-dependent and logistically distributed age-of-onset were used. The program REGTL in the S.A.G.E. computer program package was used for a complex segregation analysis. The models included correction for single ascertainment. Regressive familial effects were not estimated. The data were analyzed to test for single major locus (SML), random transmission and no transmission (environmental) hypotheses. The results of the complex segregation analysis showed that (1) the SML was the best fit, and (2) the non-genetic models could be rejected.

  9. Contribution of Large Region Joint Associations to Complex Traits Genetics

    PubMed Central

    Paré, Guillaume; Asma, Senay; Deng, Wei Q.

    2015-01-01

    A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

  10. The complex evolutionary history of big-eared horseshoe bats (Rhinolophus macrotis complex): insights from genetic, morphological and acoustic data

    PubMed Central

    Sun, Keping; Kimball, Rebecca T.; Liu, Tong; Wei, Xuewen; Jin, Longru; Jiang, Tinglei; Lin, Aiqing; Feng, Jiang

    2016-01-01

    Palaeoclimatic oscillations and different landscapes frequently result in complex population-level structure or the evolution of cryptic species. Elucidating the potential mechanisms is vital to understanding speciation events. However, such complex evolutionary patterns have rarely been reported in bats. In China, the Rhinolophus macrotis complex contains a large form and a small form, suggesting the existence of a cryptic bat species. Our field surveys found these two sibling species have a continuous and widespread distribution with partial sympatry. However, their evolutionary history has received little attention. Here, we used extensive sampling, morphological and acoustic data, as well as different genetic markers to investigate their evolutionary history. Genetic analyses revealed discordance between the mitochondrial and nuclear data. Mitochondrial data identified three reciprocally monophyletic lineages: one representing all small forms from Southwest China, and the other two containing all large forms from Central and Southeast China, respectively. The large form showed paraphyly with respect to the small form. However, clustering analyses of microsatellite and Chd1 gene sequences support two divergent clusters separating the large form and the small form. Moreover, morphological and acoustic analyses were consistent with nuclear data. This unusual pattern in the R. macrotis complex might be accounted for by palaeoclimatic oscillations, shared ancestral polymorphism and/or interspecific hybridization. PMID:27748429

  11. PEComa: morphology and genetics of a complex tumor family.

    PubMed

    Thway, Khin; Fisher, Cyril

    2015-10-01

    Perivascular epithelioid cell tumors, or PEComas, are mesenchymal neoplasms composed of histologically and immunohistochemically distinctive epithelioid or spindle cells, which are immunoreactive for both smooth muscle and melanocytic markers. The cells in PEComas are typically arranged around blood vessels and appear to form the vessel wall, often infiltrating the smooth muscle of small- to medium-sized vessels. Periluminal cells are usually epithelioid and the more peripheral cells are spindle shaped. The cells have small, round to oval nuclei, sometimes with focal nuclear atypia, and clear to eosinophilic cytoplasm, and no counterpart normal cell has been identified. The PEComa "family" now includes angiomyolipoma, pulmonary clear cell "sugar" tumor and lymphangioleiomyomatosis, primary extrapulmonary sugar tumor, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, and other tumors with similar features at various sites that are simply termed PEComa. Some PEComas occur in patients with tuberous sclerosis complex and share the genetic abnormalities. There is a behavioral spectrum from benign to frankly malignant, and histologic criteria have been proposed for assessing malignant potential. The differential diagnosis can include carcinomas, smooth muscle tumors, other clear cell neoplasms, and adipocytic tumors. PEComas constitute a genetically diverse group that includes neoplasms harboring TFE3 gene rearrangements and those with TSC2 mutations, indicating alternative tumorigenic pathways. Recent advances in therapy of malignant PEComas relate to increased knowledge of specific genetic changes and their effects on metabolic pathways that are susceptible to specific interventions. We review PEComas, emphasizing the diagnostic spectrum and recent immunohistochemical and genetic findings.

  12. Robustness and structure of complex networks

    NASA Astrophysics Data System (ADS)

    Shao, Shuai

    This dissertation covers the two major parts of my PhD research on statistical physics and complex networks: i) modeling a new type of attack -- localized attack, and investigating robustness of complex networks under this type of attack; ii) discovering the clustering structure in complex networks and its influence on the robustness of coupled networks. Complex networks appear in every aspect of our daily life and are widely studied in Physics, Mathematics, Biology, and Computer Science. One important property of complex networks is their robustness under attacks, which depends crucially on the nature of attacks and the structure of the networks themselves. Previous studies have focused on two types of attack: random attack and targeted attack, which, however, are insufficient to describe many real-world damages. Here we propose a new type of attack -- localized attack, and study the robustness of complex networks under this type of attack, both analytically and via simulation. On the other hand, we also study the clustering structure in the network, and its influence on the robustness of a complex network system. In the first part, we propose a theoretical framework to study the robustness of complex networks under localized attack based on percolation theory and generating function method. We investigate the percolation properties, including the critical threshold of the phase transition pc and the size of the giant component Pinfinity. We compare localized attack with random attack and find that while random regular (RR) networks are more robust against localized attack, Erdoḧs-Renyi (ER) networks are equally robust under both types of attacks. As for scale-free (SF) networks, their robustness depends crucially on the degree exponent lambda. The simulation results show perfect agreement with theoretical predictions. We also test our model on two real-world networks: a peer-to-peer computer network and an airline network, and find that the real-world networks

  13. Recent structural insights into transcription preinitiation complexes.

    PubMed

    Nogales, E

    2000-12-01

    Our understanding of the elaborate mechanism of gene transcription initiation in eukaryotes has been widened by recent structural information on some of the key components of the complex preinitiation transcriptional machinery. The high-resolution structures of both bacterial and eukaryotic polymerases are technical landmarks of great biological significance that have given us the first molecular insight into the mechanism of this large enzyme. While new atomic structures of different domains of general transcription factors, such as the double bromodomain of TAF250, have become available by means of X-ray crystallography and NMR studies, more global pictures of multisubunit transcription complexes, such as TFIID, TFIIH or the yeast mediator, have now been obtained by electron microscopy and image-reconstruction techniques. A combination of methodologies may prove essential for a complete structural description of the initial steps in the expression of eukaryotic genes.

  14. Structural genomic variation in childhood epilepsies with complex phenotypes

    PubMed Central

    Helbig, Ingo; Swinkels, Marielle E M; Aten, Emmelien; Caliebe, Almuth; van 't Slot, Ruben; Boor, Rainer; von Spiczak, Sarah; Muhle, Hiltrud; Jähn, Johanna A; van Binsbergen, Ellen; van Nieuwenhuizen, Onno; Jansen, Floor E; Braun, Kees P J; de Haan, Gerrit-Jan; Tommerup, Niels; Stephani, Ulrich; Hjalgrim, Helle; Poot, Martin; Lindhout, Dick; Brilstra, Eva H; Møller, Rikke S; Koeleman, Bobby PC

    2014-01-01

    A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. PMID:24281369

  15. Structural Changes in the Antennapedia Complex of Drosophila Pseudoobscura

    PubMed Central

    Randazzo, F. M.; Seeger, M. A.; Huss, C. A.; Sweeney, M. A.; Cecil, J. K.; Kaufman, T. C.

    1993-01-01

    The discovery of the striking positional conservation between the Antennapedia and Bithorax homeotic gene complexes (ANT-C and BX-C) in Drosophila melanogaster and the murine Hox and human HOX clusters has had a substantial impact on our understanding of the evolution of development and its genetic regulation. Structural differences do exist among the mammalian Hox complexes and the ANT-C in D. melanogaster. To gain further insight into the evolutionary changes among these complexes, the ANT-C was cloned in the closely related species, Drosophila pseudoobscura. The overall structure of the ANT-C in D. pseudoobscura is highly similar to its D. melanogaster counterpart; however, two differences in the organization of the ANT-C have been identified. First, the z2 gene, a member of the ANT-C in D. melanogaster, is not present in the D. pseudoobscura ANT-C and is possibly absent from the D. pseudoobscura genome. Second, the orientation of the Deformed gene is inverted in D. pseudoobscura, providing it with a 5' to 3' direction of transcription identical to the remaining ANT-C homeobox genes with the exception of fushi tarazu. These differences demonstrate that subtle changes can occur in ANT-C structure during relatively short periods of evolutionary divergence, although the fundamental organization of the complex is conserved. These observations and others suggest that the complex is not absolutely rigid but that selective pressures have maintained this organization of genes for some functional reason that remains elusive. PMID:8099892

  16. What's in a name; Genetic structure in Solanum section Petota studied using population-genetic tools

    PubMed Central

    2011-01-01

    Background The taxonomy and systematic relationships among species of Solanum section Petota are complicated and the section seems overclassified. Many of the presumed (sub)species from South America are very similar and they are able to exchange genetic material. We applied a population genetic approach to evaluate support for subgroups within this material, using AFLP data. Our approach is based on the following assumptions: (i) accessions that may exchange genetic material can be analyzed as if they are part of one gene pool, and (ii) genetic differentiation among species is expected to be higher than within species. Results A dataset of 566 South-American accessions (encompassing 89 species and subspecies) was analyzed in two steps. First, with the program STRUCTURE 2.2 in an 'unsupervised' procedure, individual accessions were assigned to inferred clusters based on genetic similarity. The results showed that the South American members of section Petota could be arranged in 16 clusters of various size and composition. Next, the accessions within the clusters were grouped by maximizing the partitioning of genetic diversity among subgroups (i.e., maximizing Fst values) for all available individuals of the accessions (2767 genotypes). This two-step approach produced an optimal partitioning into 44 groups. Some of the species clustered as genetically distinct groups, either on their own, or combined with one or more other species. However, accessions of other species were distributed over more than one cluster, and did not form genetically distinct units. Conclusions We could not find any support for 43 species (almost half of our dataset). For 28 species some level of support could be found varying from good to weak. For 18 species no conclusions could be drawn as the number of accessions included in our dataset was too low. These molecular data should be combined with data from morphological surveys, with geographical distribution data, and with information from

  17. Impulse Response Operators for Structural Complexes

    DTIC Science & Technology

    1990-05-12

    systems of the complex. The statistical energy analysis (SEA) is one such a device [ 13, 14]. The rendering of SEA from equation (21) and/or (25) lies...Propagation.] 13. L. Cremer, M. Heckl, and E.E. Ungar 1973 Structure-Borne Sound (Springer Verlag). 14. R. H. Lyon 1975 Statistical Energy Analysis of

  18. Structure of Complex Verb Forms in Meiteilon

    ERIC Educational Resources Information Center

    Singh, Lourembam Surjit

    2016-01-01

    This piece of work proposes to descriptively investigate the structures of complex verbs in Meiteilon. The categorization of such verbs is based on the nature of semantic and syntactic functions of a lexeme or verbal lexeme. A lexeme or verbal lexeme in Meiteilon may have multifunctional properties in the nature of occurrence. Such lexical items…

  19. Spatial and population genetic structure of microsatellites in white pine

    Treesearch

    Paula E. Marquardt; Bryan K. Epperson

    2004-01-01

    We evaluated the population genetic structure of seven microsatellite loci for old growth and second growth populations of eastern white pine (Pinus strobus). From each population, located within Hartwick Pines State Park, Grayling, Michigan, USA, 120-122 contiguous trees were sampled for genetic analysis. Within each population, genetic diversity...

  20. Fine-scale human genetic structure in Western France.

    PubMed

    Karakachoff, Matilde; Duforet-Frebourg, Nicolas; Simonet, Floriane; Le Scouarnec, Solena; Pellen, Nadine; Lecointe, Simon; Charpentier, Eric; Gros, Françoise; Cauchi, Stéphane; Froguel, Philippe; Copin, Nane; Le Tourneau, Thierry; Probst, Vincent; Le Marec, Hervé; Molinaro, Sabrina; Balkau, Beverley; Redon, Richard; Schott, Jean-Jacques; Blum, Michael Gb; Dina, Christian

    2015-06-01

    The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.

  1. Fine-scale human genetic structure in Western France

    PubMed Central

    Karakachoff, Matilde; Duforet-Frebourg, Nicolas; Simonet, Floriane; Le Scouarnec, Solena; Pellen, Nadine; Lecointe, Simon; Charpentier, Eric; Gros, Françoise; Cauchi, Stéphane; Froguel, Philippe; Copin, Nane; Balkau, B; Ducimetière, P; Eschwège;, E; Alhenc-Gelas, F; Girault, A; Fumeron, F; Marre, M; Roussel, R; Bonnet, F; Cauchi, S; Froguel, P; Cogneau, J; Born, C; Caces, E; Cailleau, M; Lantieri, O; Moreau, J G; Rakotozafy, F; Tichet, J; Le Tourneau, Thierry; Probst, Vincent; Le Marec, Hervé; Molinaro, Sabrina; Balkau, Beverley; Redon, Richard; Schott, Jean-Jacques; Blum, Michael GB; Dina, Christian

    2015-01-01

    The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses. PMID:25182131

  2. Dissecting the Genetics of Complex Inheritance: Linkage Disequilibrium Mapping Provides Insight into Crohn Disease

    PubMed Central

    Elding, Heather; Lau, Winston; Swallow, Dallas M.; Maniatis, Nikolas

    2011-01-01

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. PMID:22152681

  3. COMPLEX STRUCTURE IN CLASS 0 PROTOSTELLAR ENVELOPES

    SciTech Connect

    Tobin, John J.; Hartmann, Lee; Looney, Leslie W.; Chiang, Hsin-Fang

    2010-04-01

    We use archived Infrared Array Camera images from the Spitzer Space Telescope to show that many Class 0 protostars exhibit complex, irregular, and non-axisymmetric structure within their dusty envelopes. Our 8 {mu}m extinction maps probe some of the densest regions in these protostellar envelopes. Many of the systems are observed to have highly irregular and non-axisymmetric morphologies on scales {approx}>1000 AU, with a quarter of the sample exhibiting filamentary or flattened dense structures. Complex envelope structure is observed in regions spatially distinct from outflow cavities, and the densest structures often show no systematic alignment perpendicular to the cavities. These results indicate that mass ejection is not responsible for much of the irregular morphologies we detect; rather, we suggest that the observed envelope complexity is mostly the result of collapse from protostellar cores with initially non-equilibrium structures. The striking non-axisymmetry in many envelopes could provide favorable conditions for the formation of binary systems. We also note that protostars in the sample appear to be formed preferentially near the edges of clouds or bends in filaments, suggesting formation by gravitational focusing.

  4. Structural complexity of a composite amyloid fibril.

    PubMed

    Lewandowski, Józef R; van der Wel, Patrick C A; Rigney, Mike; Grigorieff, Nikolaus; Griffin, Robert G

    2011-09-21

    The molecular structure of amyloid fibrils and the mechanism of their formation are of substantial medical and biological importance, but present an ongoing experimental and computational challenge. An early high-resolution view of amyloid-like structure was obtained on amyloid-like crystals of a small fragment of the yeast prion protein Sup35p: the peptide GNNQQNY. As GNNQQNY also forms amyloid-like fibrils under similar conditions, it has been theorized that the crystal's structural features are shared by the fibrils. Here we apply magic-angle-spinning (MAS) NMR to examine the structure and dynamics of these fibrils. Previously multiple NMR signals were observed for such samples, seemingly consistent with the presence of polymorphic fibrils. Here we demonstrate that peptides with these three distinct conformations instead assemble together into composite protofilaments. Electron microscopy (EM) of the ribbon-like fibrils indicates that these protofilaments combine in differing ways to form striations of variable widths, presenting another level of structural complexity. Structural and dynamic NMR data reveal the presence of highly restricted side-chain conformations involved in interfaces between differently structured peptides, likely comprising interdigitated steric zippers. We outline molecular interfaces that are consistent with the observed EM and NMR data. The rigid and uniform structure of the GNNQQNY crystals is found to contrast distinctly with the more complex structural and dynamic nature of these "composite" amyloid fibrils. These results provide insight into the fibril-crystal distinction and also indicate a necessary caution with respect to the extrapolation of crystal structures to the study of fibril structure and formation.

  5. Solution Structures of PPARγ2/RXRα Complexes.

    PubMed

    Osz, Judit; Pethoukhov, Maxim V; Sirigu, Serena; Svergun, Dmitri I; Moras, Dino; Rochel, Natacha

    2012-01-01

    PPARγ is a key regulator of glucose homeostasis and insulin sensitization. PPARγ must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1α to regulate gene networks. To understand how coactivators are recognized by the functional heterodimer PPARγ/RXRα and to determine the topological organization of the complexes, we performed a structural study using small angle X-ray scattering of PPARγ/RXRα in complex with DNA from regulated gene and the TIF2 receptor interacting domain (RID). The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer.

  6. Solution Structures of PPARγ2/RXRα Complexes

    PubMed Central

    Osz, Judit; Pethoukhov, Maxim V.; Sirigu, Serena; Svergun, Dmitri I.; Moras, Dino; Rochel, Natacha

    2012-01-01

    PPARγ is a key regulator of glucose homeostasis and insulin sensitization. PPARγ must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1α to regulate gene networks. To understand how coactivators are recognized by the functional heterodimer PPARγ/RXRα and to determine the topological organization of the complexes, we performed a structural study using small angle X-ray scattering of PPARγ/RXRα in complex with DNA from regulated gene and the TIF2 receptor interacting domain (RID). The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer. PMID:23319938

  7. Structural Architecture of SNP Effects on Complex Traits

    PubMed Central

    Gamazon, Eric R.; Cox, Nancy J.; Davis, Lea K.

    2014-01-01

    Despite the discovery of copy-number variation (CNV) across the genome nearly 10 years ago, current SNP-based analysis methodologies continue to collapse the homozygous (i.e., A/A), hemizygous (i.e., A/0), and duplicative (i.e., A/A/A) genotype states, treating the genotype variable as irreducible or unaltered by other colocalizing forms of genetic (e.g., structural) variation. Our understanding of common, genome-wide CNVs suggests that the canonical genotype construct might belie the enormous complexity of the genome. Here we present multiple analyses of several phenotypes and provide methods supporting a conceptual shift that embraces the structural dimension of genotype. We comprehensively investigate the impact of the structural dimension of genotype on (1) GWAS methods, (2) interpretation of rare LOF variants, (3) characterization of genomic architecture, and (4) implications for mapping loci involved in complex disease. Taken together, these results argue for the inclusion of a structural dimension and suggest that some portion of the “missing” heritability might be recovered through integration of the structural dimension of SNP effects on complex traits. PMID:25307299

  8. Complex structures of dense lithium: Electronic origin

    NASA Astrophysics Data System (ADS)

    Degtyareva, V. F.

    2016-11-01

    Lithium—the lightest alkali metal exhibits unexpected structures and electronic behavior at high pressures. Like the heavier alkali metals, Li is bcc at ambient pressure and transforms first to fcc (at 7.5 GPa). The post-fcc high-pressure form Li-cI 16 (at 40-60 GPa) is similar to Na-cI 16 and related to more complex structures of heavy alkalis Rb-oC52 and Cs- oC84. The other high pressure phases for Li (oC88, oC40, oC24) observed at pressures up to 130 GPa are found only in Li. The different route of Li high-pressure structures correlates with its special electronic configuration containing the only 3 electrons (at 1s and 2s levels). Crystal structures for Li are analyzed within the model of Fermi sphere-Brillouin zone interactions. Stability of post-fcc structures for Li are supported by the Hume-Rothery arguments when new diffraction plains appear close to the Fermi level producing pseudogaps near the Fermi level and decreasing the crystal energy. The filling of Brillouin-Jones zones by electron states for a given structure defines the physical properties as optical reflectivity, electrical resistivity and superconductivity. To understand the complexity of structural and physical properties of Li above 60 GPa it is necessary to assume the valence electron band overlap with the core electrons and increase the valence electron count under compression.

  9. From genetics to structure to function: Exploring sleep in Drosophila

    PubMed Central

    Bushey, Daniel; Cirelli, Chiara

    2011-01-01

    Outline Sleep consists of quiescent periods with reduced responsiveness to external stimuli. Despite being maladaptive in that when asleep, animals are less able to respond to dangerous stimuli, sleep behavior is conserved in all animal species studied to date. Thus, sleep must be performing at least one fundamental, conserved function that is necessary, and/ or whose benefits outweigh its maladaptive consequences. Currently, there is no consensus on what that function might be. Over the last 10 years, multiple groups have started to characterize the molecular mechanisms and brain structures necessary for normal sleep in Drosophila melanogaster. These researchers are exploiting genetic tools developed in Drosophila over the past century to identify and manipulate gene expression. Forward genetic screens can identify molecular components in complex biological systems and once identified, these genes can be manipulated within specific brain areas to determine which neuronal groups are important to initiate and maintain sleep. Screening for mutations and brain regions necessary for normal sleep has revealed that several genes that affect sleep are involved in synaptic plasticity and have preferential expression in the mushroom bodies (MB). Moreover, altering MB neuronal activity alters sleep. Previous genetic screens found that the same genes enriched in MB are necessary for learning and memory. Increasing evidence in mammals, including humans, points to a beneficial role for sleep in synaptic plasticity, learning and memory. Thus, results from both flies and mammals suggest a strong link between sleep need and wake plasticity. PMID:21906542

  10. Empirical complexities in the genetic foundations of lethal mutagenesis.

    PubMed

    Bull, James J; Joyce, Paul; Gladstone, Eric; Molineux, Ian J

    2013-10-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias-mutagenesis of virions-but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

  11. Genetic differentiation and phylogeography of partially sympatric species complex Rhizophora mucronata Lam. and R. stylosa Griff. using SSR markers.

    PubMed

    Wee, Alison K S; Takayama, Koji; Chua, Jasher L; Asakawa, Takeshi; Meenakshisundaram, Sankararamasubramanian H; Onrizal; Adjie, Bayu; Ardli, Erwin Riyanto; Sungkaew, Sarawood; Malekal, Norhaslinda Binti; Tung, Nguyen Xuan; Salmo, Severino G; Yllano, Orlex Baylen; Saleh, M Nazre; Soe, Khin Khin; Tateishi, Yoichi; Watano, Yasuyuki; Baba, Shigeyuki; Webb, Edward L; Kajita, Tadashi

    2015-03-29

    Mangrove forests are ecologically important but globally threatened intertidal plant communities. Effective mangrove conservation requires the determination of species identity, management units, and genetic structure. Here, we investigate the genetic distinctiveness and genetic structure of an iconic but yet taxonomically confusing species complex Rhizophora mucronata and R. stylosa across their distributional range, by employing a suite of 20 informative nuclear SSR markers. Our results demonstrated the general genetic distinctiveness of R. mucronata and R. stylosa, and potential hybridization or introgression between them. We investigated the population genetics of each species without the putative hybrids, and found strong genetic structure between oceanic regions in both R. mucronata and R. stylosa. In R. mucronata, a strong divergence was detected between populations from the Indian Ocean region (Indian Ocean and Andaman Sea) and the Pacific Ocean region (Malacca Strait, South China Sea and Northwest Pacific Ocean). In R. stylosa, the genetic break was located more eastward, between populations from South and East China Sea and populations from the Southwest Pacific Ocean. The location of these genetic breaks coincided with the boundaries of oceanic currents, thus suggesting that oceanic circulation patterns might have acted as a cryptic barrier to gene flow. Our findings have important implications on the conservation of mangroves, especially relating to replanting efforts and the definition of evolutionary significant units in Rhizophora species. We outlined the genetic structure and identified geographical areas that require further investigations for both R. mucronata and R. stylosa. These results serve as the foundation for the conservation genetics of R. mucronata and R. stylosa and highlighted the need to recognize the genetic distinctiveness of closely-related species, determine their respective genetic structure, and avoid artificially promoting

  12. Imaging beneath complex structure: a case history

    SciTech Connect

    Gibson, B.; Larner, K.; Chambers, R.

    1983-08-01

    Migration is recognized as the essential step in converting seismic data into a representation of the earth's subsurface structure. Ironically, conventional migration often fails where migration is needed most - when the data are recorded over complex structures. In the Central American example, velocities increase nearly two-fold across an arched and thrust-faulted interface. Wave-front distortion introduced by this feature gives rise to distorted reflection from depth. Even with interval velocity known perfectly, no velocity is proper for time migrating the data here; time migration is the wrong process because it does not honor Snell's law. Depth migration of the stacked data, on the other hand, produces a reasonable image of the deeper section. The depth migration, however, leaves artifacts that could be attributed to problems that are common in structurally complicated areas: (1) departures of the stacked section from the ideal, a zero-offset section, (2) incorrect specification of velocities, and (3) loss of energy transmitted through the complex zone. For such an inhomogeneous velocity structure, shortcoming in CDP stacking are related directly to highly nonhyperbolic moveout. As with migration velocity, no proper stacking velocity can be developed for these data, even from the known interval-velocity model. Proper treatment of nonzero-offset reflection data could be accomplished by depth migration before stacking. Simple ray-theoretical correction of the complex moveouts, however, can produce a stack that is similar to the desired zero-offset section.

  13. Structure of bacterial respiratory complex I.

    PubMed

    Berrisford, John M; Baradaran, Rozbeh; Sazanov, Leonid A

    2016-07-01

    Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536 kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.

  14. Tetralogy of Fallot and Hypoplastic Left Heart Syndrome – Complex Clinical Phenotypes Meet Complex Genetic Networks

    PubMed Central

    Lahm, Harald; Schön, Patric; Doppler, Stefanie; Dreßen, Martina; Cleuziou, Julie; Deutsch, Marcus-André; Ewert, Peter; Lange, Rüdiger; Krane, Markus

    2015-01-01

    In many cases congenital heart disease (CHD) is represented by a complex phenotype and an array of several functional and morphological cardiac disorders. These malformations will be briefly summarized in the first part focusing on two severe CHD phenotypes, hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). In most cases of CHD the genetic origin remains largely unknown, though the complexity of the clinical picture strongly argues against a dysregulation which can be attributed to a single candidate gene but rather suggests a multifaceted polygenetic origin with elaborate interactions. Consistent with this idea, genome-wide approaches using whole exome sequencing, comparative sequence analysis of multiplex families to identify de novo mutations and global technologies to identify single nucleotide polymorphisms, copy number variants, dysregulation of the transcriptome and epigenetic variations have been conducted to obtain information about genetic alterations and potential predispositions possibly linked to the occurrence of a CHD phenotype. In the second part of this review we will summarize and discuss the available literature on identified genetic alterations linked to TOF and HLHS. PMID:26069455

  15. Environmental Variables Explain Genetic Structure in a Beetle-Associated Nematode

    PubMed Central

    McGaughran, Angela; Morgan, Katy; Sommer, Ralf J.

    2014-01-01

    The distribution of a species is a complex expression of its ecological and evolutionary history and integrating population genetic, environmental, and ecological data can provide new insights into the effects of the environment on the population structure of species. Previous work demonstrated strong patterns of genetic differentiation in natural populations of the hermaphroditic nematode Pristionchus pacificus in its La Réunion Island habitat, but gave no clear understanding of the role of the environment in structuring this variation. Here, we present what is to our knowledge the first study to statistically evaluate the role of the environment in shaping the structure and distribution of nematode populations. We test the hypothesis that genetic structure in P. pacificus is influenced by environmental variables, by combining population genetic analyses of microsatellite data from 18 populations and 370 strains, with multivariate statistics on environmental data, and species distribution modelling. We assess and quantify the relative importance of environmental factors (geographic distance, altitude, temperature, precipitation, and beetle host) on genetic variation among populations. Despite the fact that geographic populations of P. pacificus comprise vast genetic diversity sourced from multiple ancestral lineages, we find strong evidence for local associations between environment and genetic variation. Further, we show that significantly more genetic variation in P. pacificus populations is explained by environmental variation than by geographic distances. This supports a strong role for environmental heterogeneity vs. genetic drift in the divergence of populations, which we suggest may be influenced by adaptive forces. PMID:24498073

  16. [Researches on genetics and genetic epidemiology of common complex diseases: challenge and strategies].

    PubMed

    Gu, Dong-feng

    2006-04-01

    With the rapid development of human genome project, increased genetic and population-based association studies are focused on the identification of the underlying susceptibility genes and contributions from gene-environment interaction to common complex diseases. Whole-genome association study with high-density single nucleotide polymorphisms is one of the most important milestones in that process. However, problems still exist in study design, data processing, and results interpretation. Large-scale cohort study or population-based case-control design with sufficient statistical power, new approaches to assess the gene-gene and gene-environment interactions, as guarantee of the consistency and replicability of these researches are crucial in the exploration of the causes of these common complex diseases.

  17. New knowledge-based genetic algorithm for excavator boom structural optimization

    NASA Astrophysics Data System (ADS)

    Hua, Haiyan; Lin, Shuwen

    2014-03-01

    Due to the insufficiency of utilizing knowledge to guide the complex optimal searching, existing genetic algorithms fail to effectively solve excavator boom structural optimization problem. To improve the optimization efficiency and quality, a new knowledge-based real-coded genetic algorithm is proposed. A dual evolution mechanism combining knowledge evolution with genetic algorithm is established to extract, handle and utilize the shallow and deep implicit constraint knowledge to guide the optimal searching of genetic algorithm circularly. Based on this dual evolution mechanism, knowledge evolution and population evolution can be connected by knowledge influence operators to improve the configurability of knowledge and genetic operators. Then, the new knowledge-based selection operator, crossover operator and mutation operator are proposed to integrate the optimal process knowledge and domain culture to guide the excavator boom structural optimization. Eight kinds of testing algorithms, which include different genetic operators, are taken as examples to solve the structural optimization of a medium-sized excavator boom. By comparing the results of optimization, it is shown that the algorithm including all the new knowledge-based genetic operators can more remarkably improve the evolutionary rate and searching ability than other testing algorithms, which demonstrates the effectiveness of knowledge for guiding optimal searching. The proposed knowledge-based genetic algorithm by combining multi-level knowledge evolution with numerical optimization provides a new effective method for solving the complex engineering optimization problem.

  18. The Knowledge Structure of Mendelian Genetics.

    ERIC Educational Resources Information Center

    Collins, Angelo; Stewart, James H.

    1989-01-01

    Examines the content knowledge of genetics as it is organized for solving effect-to-cause problems. Reviews proposed reasons explaining why students find genetics difficult to learn. Explains dominant and codominant inheritance patterns, multiple alleles, and X-linkage. (RT)

  19. Dilated cardiomyopathy: the complexity of a diverse genetic architecture.

    PubMed

    Hershberger, Ray E; Hedges, Dale J; Morales, Ana

    2013-09-01

    Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in >30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype. Large, publicly available datasets have provided the opportunity to evaluate previously identified DCM-causing mutations, and to examine the population frequency of sequence variants similar to those that have been observed to cause DCM. The frequency of these variants, whether associated with dilated or hypertrophic cardiomyopathy, is greater than estimates of disease prevalence. This mismatch might be explained by one or more of the following possibilities: that the penetrance of DCM-causing mutations is lower than previously thought, that some variants are noncausal, that DCM prevalence is higher than previously estimated, or that other more-complex genomics underlie DCM. Reassessment of our assumptions about the complexity of the genomic and phenomic architecture of DCM is warranted. Much about the genomic basis of DCM remains to be investigated, which will require comprehensive genomic studies in much larger cohorts of rigorously phenotyped probands and family members than previously examined.

  20. On some genetic consequences of social structure, mating systems, dispersal, and sampling

    PubMed Central

    Parreira, Bárbara R.; Chikhi, Lounès

    2015-01-01

    Many species are spatially and socially organized, with complex social organizations and dispersal patterns that are increasingly documented. Social species typically consist of small age-structured units, where a limited number of individuals monopolize reproduction and exhibit complex mating strategies. Here, we model social groups as age-structured units and investigate the genetic consequences of social structure under distinct mating strategies commonly found in mammals. Our results show that sociality maximizes genotypic diversity, which contradicts the belief that social groups are necessarily subject to strong genetic drift and at high risk of inbreeding depression. Social structure generates an excess of genotypic diversity. This is commonly observed in ecological studies but rarely reported in population genetic studies that ignore social structure. This heterozygosity excess, when detected, is often interpreted as a consequence of inbreeding avoidance mechanisms, but we show that it can occur even in the absence of such mechanisms. Many seemly contradictory results from ecology and population genetics can be reconciled by genetic models that include the complexities of social species. We find that such discrepancies can be explained by the intrinsic properties of social groups and by the sampling strategies of real populations. In particular, the number of social groups and the nature of the individuals that compose samples (e.g., nonreproductive and reproductive individuals) are key factors in generating outbreeding signatures. Sociality is an important component of population structure that needs to be revisited by ecologists and population geneticists alike. PMID:26080393

  1. Variable Complexity Structural Optimization of Shells

    NASA Technical Reports Server (NTRS)

    Haftka, Raphael T.; Venkataraman, Satchi

    1999-01-01

    Structural designers today face both opportunities and challenges in a vast array of available analysis and optimization programs. Some programs such as NASTRAN, are very general, permitting the designer to model any structure, to any degree of accuracy, but often at a higher computational cost. Additionally, such general procedures often do not allow easy implementation of all constraints of interest to the designer. Other programs, based on algebraic expressions used by designers one generation ago, have limited applicability for general structures with modem materials. However, when applicable, they provide easy understanding of design decisions trade-off. Finally, designers can also use specialized programs suitable for designing efficiently a subset of structural problems. For example, PASCO and PANDA2 are panel design codes, which calculate response and estimate failure much more efficiently than general-purpose codes, but are narrowly applicable in terms of geometry and loading. Therefore, the problem of optimizing structures based on simultaneous use of several models and computer programs is a subject of considerable interest. The problem of using several levels of models in optimization has been dubbed variable complexity modeling. Work under NASA grant NAG1-2110 has been concerned with the development of variable complexity modeling strategies with special emphasis on response surface techniques. In addition, several modeling issues for the design of shells of revolution were studied.

  2. Variable Complexity Structural Optimization of Shells

    NASA Technical Reports Server (NTRS)

    Haftka, Raphael T.; Venkataraman, Satchi

    1998-01-01

    Structural designers today face both opportunities and challenges in a vast array of available analysis and optimization programs. Some programs such as NASTRAN, are very general, permitting the designer to model any structure, to any degree of accuracy, but often at a higher computational cost. Additionally, such general procedures often do not allow easy implementation of all constraints of interest to the designer. Other programs, based on algebraic expressions used by designers one generation ago, have limited applicability for general structures with modem materials. However, when applicable, they provide easy understanding of design decisions trade-off. Finally, designers can also use specialized programs suitable for designing efficiently a subset of structural problems. For example, PASCO and PANDA2 are panel design codes, which calculate response and estimate failure much more efficiently than general-purpose codes, but are narrowly applicable in terms of geometry and loading. Therefore, the problem of optimizing structures based on simultaneous use of several models and computer programs is a subject of considerable interest. The problem of using several levels of models in optimization has been dubbed variable complexity modeling. Work under NASA grant NAG1-1808 has been concerned with the development of variable complexity modeling strategies with special emphasis on response surface techniques. In addition several modeling issues for the design of shells of revolution were studied.

  3. Inter-annual maintenance of the fine-scale genetic structure in a biennial plant

    PubMed Central

    Valverde, Javier; Gómez, José María; García, Cristina; Sharbel, Timothy F.; Jiménez, María Noelia; Perfectti, Francisco

    2016-01-01

    Within plant populations, space-restricted gene movement, together with environmental heterogeneity, can result in a spatial variation in gene frequencies. In biennial plants, inter-annual flowering migrants can homogenize gene frequencies between consecutive cohorts. However, the actual impact of these migrants on spatial genetic variation remains unexplored. Here, we used 10 nuclear microsatellite and one plastid genetic marker to characterize the spatial genetic structure within two consecutive cohorts in a population of the biennial plant Erysimum mediohispanicum (Brassicaceae). We explored the maintenance of this structure between consecutive flowering cohorts at different levels of complexity, and investigated landscape effects on gene flow. We found that cohorts were not genetically differentiated and showed a spatial genetic structure defined by a negative genetic-spatial correlation at fine scale that varied in intensity with compass directions. This spatial genetic structure was maintained when comparing plants from different cohorts. Additionally, genotypes were consistently associated with environmental factors such as light availability and soil composition, but to a lesser extent compared with the spatial autocorrelation. We conclude that inter-annual migrants, in combination with limited seed dispersal and environmental heterogeneity, play a major role in shaping and maintaining the spatial genetic structure among cohorts in this biennial plant. PMID:27883087

  4. Genetic structure of Mesoamerican populations of Big-leaf mahogany (Swietenia macrophylla) inferred from microsatellite analysis.

    PubMed

    Novick, Rachel Roth; Dick, Christopher W; Lemes, Maristerra R; Navarro, Carlos; Caccone, Adalgisa; Bermingham, Eldredge

    2003-11-01

    While microsatellites have been used to examine genetic structure in local populations of Neotropical trees, genetic studies based on such high-resolution markers have not been carried out for Mesoamerica as a whole. Here we assess the genetic structure of the Mesoamerican mahogany Swietenia macrophylla King (big-leaf mahogany), a Neotropical tree species recently listed as endangered in CITES which is commercially extinct through much of its native range. We used seven variable microsatellite loci to assess genetic diversity and population structure in eight naturally established mahogany populations from six Mesoamerican countries. Measures of genetic differentiation (FST and RST) indicated significant differences between most populations. Unrooted dendrograms based on genetic distances between populations provide evidence of strong phylogeographic structure in Mesoamerican mahogany. The two populations on the Pacific coasts of Costa Rica and Panama were genetically distant from all the others, and from one another. The remaining populations formed two clusters, one comprised of the northern populations of Mexico, Belize and Guatemala and the other containing the southern Atlantic populations of Nicaragua and Costa Rica. Significant correlation was found between geographical distance and all pairwise measures of genetic divergence, suggesting the importance of regional biogeography and isolation by distance in Mesoamerican mahogany. The results of this study demonstrate greater phylogeographic structure than has been found across Amazon basin S. macrophylla. Our findings suggest a relatively complex Mesoamerican biogeographic history and lead to the prediction that other Central American trees will show similar patterns of regional differentiation.

  5. Inter-annual maintenance of the fine-scale genetic structure in a biennial plant.

    PubMed

    Valverde, Javier; Gómez, José María; García, Cristina; Sharbel, Timothy F; Jiménez, María Noelia; Perfectti, Francisco

    2016-11-24

    Within plant populations, space-restricted gene movement, together with environmental heterogeneity, can result in a spatial variation in gene frequencies. In biennial plants, inter-annual flowering migrants can homogenize gene frequencies between consecutive cohorts. However, the actual impact of these migrants on spatial genetic variation remains unexplored. Here, we used 10 nuclear microsatellite and one plastid genetic marker to characterize the spatial genetic structure within two consecutive cohorts in a population of the biennial plant Erysimum mediohispanicum (Brassicaceae). We explored the maintenance of this structure between consecutive flowering cohorts at different levels of complexity, and investigated landscape effects on gene flow. We found that cohorts were not genetically differentiated and showed a spatial genetic structure defined by a negative genetic-spatial correlation at fine scale that varied in intensity with compass directions. This spatial genetic structure was maintained when comparing plants from different cohorts. Additionally, genotypes were consistently associated with environmental factors such as light availability and soil composition, but to a lesser extent compared with the spatial autocorrelation. We conclude that inter-annual migrants, in combination with limited seed dispersal and environmental heterogeneity, play a major role in shaping and maintaining the spatial genetic structure among cohorts in this biennial plant.

  6. A genetic similarity rule determines arthropod community structure.

    PubMed

    Bangert, R K; Turek, R J; Rehill, B; Wimp, G M; Schweitzer, J A; Allan, G J; Bailey, J K; Martinsen, G D; Keim, P; Lindroth, R L; Whitham, T G

    2006-04-01

    We define a genetic similarity rule that predicts how genetic variation in a dominant plant affects the structure of an arthropod community. This rule applies to hybridizing cottonwood species where plant genetic variation determines plant-animal interactions and structures a dependent community of leaf-modifying arthropods. Because the associated arthropod community is expected to respond to important plant traits, we also tested whether plant chemical composition is one potential intermediate link between plant genes and arthropod community composition. Two lines of evidence support our genetic similarity rule. First, in a common garden experiment we found that trees with similar genetic compositions had similar chemical compositions and similar arthropod compositions. Second, in a wild population, we found a similar relationship between genetic similarity in cottonwoods and the dependent arthropod community. Field data demonstrate that the relationship between genes and arthropods was also significant when the hybrids were analysed alone, i.e. the pattern is not dependent upon the inclusion of both parental species. Because plant-animal interactions and natural hybridization are common to diverse plant taxa, we suggest that a genetic similarity rule is potentially applicable, and may be extended, to other systems and ecological processes. For example, plants with similar genetic compositions may exhibit similar litter decomposition rates. A corollary to this genetic similarity rule predicts that in systems with low plant genetic variability, the environment will be a stronger factor structuring the dependent community. Our findings argue that the genetic composition of a dominant plant can structure higher order ecological processes, thus placing community and ecosystem ecology within a genetic and evolutionary framework. A genetic similarity rule also has important conservation implications because the loss of genetic diversity in one species, especially

  7. Ocean circulation model predicts high genetic structure observed in a long-lived pelagic developer.

    PubMed

    Sunday, J M; Popovic, I; Palen, W J; Foreman, M G G; Hart, M W

    2014-10-01

    Understanding the movement of genes and individuals across marine seascapes is a long-standing challenge in marine ecology and can inform our understanding of local adaptation, the persistence and movement of populations, and the spatial scale of effective management. Patterns of gene flow in the ocean are often inferred based on population genetic analyses coupled with knowledge of species' dispersive life histories. However, genetic structure is the result of time-integrated processes and may not capture present-day connectivity between populations. Here, we use a high-resolution oceanographic circulation model to predict larval dispersal along the complex coastline of western Canada that includes the transition between two well-studied zoogeographic provinces. We simulate dispersal in a benthic sea star with a 6-10 week pelagic larval phase and test predictions of this model against previously observed genetic structure including a strong phylogeographic break within the zoogeographical transition zone. We also test predictions with new genetic sampling in a site within the phylogeographic break. We find that the coupled genetic and circulation model predicts the high degree of genetic structure observed in this species, despite its long pelagic duration. High genetic structure on this complex coastline can thus be explained through ocean circulation patterns, which tend to retain passive larvae within 20-50 km of their parents, suggesting a necessity for close-knit design of Marine Protected Area networks.

  8. Genetic algorithms applied to nonlinear and complex domains

    SciTech Connect

    Barash, D; Woodin, A E

    1999-06-01

    The dissertation, titled ''Genetic Algorithms Applied to Nonlinear and Complex Domains'', describes and then applies a new class of powerful search algorithms (GAS) to certain domains. GAS are capable of solving complex and nonlinear problems where many parameters interact to produce a ''final'' result such as the optimization of the laser pulse in the interaction of an atom with an intense laser field. GAS can very efficiently locate the global maximum by searching parameter space in problems which are unsuitable for a search using traditional methods. In particular, the dissertation contains new scientific findings in two areas. First, the dissertation examines the interaction of an ultra-intense short laser pulse with atoms. GAS are used to find the optimal frequency for stabilizing atoms in the ionization process. This leads to a new theoretical formulation, to explain what is happening during the ionization process and how the electron is responding to finite (real-life) laser pulse shapes. It is shown that the dynamics of the process can be very sensitive to the ramp of the pulse at high frequencies. The new theory which is formulated, also uses a novel concept (known as the (t,t') method) to numerically solve the time-dependent Schrodinger equation Second, the dissertation also examines the use of GAS in modeling decision making problems. It compares GAS with traditional techniques to solve a class of problems known as Markov Decision Processes. The conclusion of the dissertation should give a clear idea of where GAS are applicable, especially in the physical sciences, in problems which are nonlinear and complex, i.e. difficult to analyze by other means.

  9. Genetic algorithms applied to nonlinear and complex domains

    SciTech Connect

    Barash, Danny

    1999-06-01

    The dissertation, titled ''Genetic Algorithms Applied to Nonlinear and Complex Domains'', describes and then applies a new class of powerful search algorithms (GAS) to certain domains. GAS are capable of solving complex and nonlinear problems where many parameters interact to produce a ''final'' result such as the optimization of the laser pulse in the interaction of an atom with an intense laser field. GAS can very efficiently locate the global maximum by searching parameter space in problems which are unsuitable for a search using traditional methods. In particular, the dissertation contains new scientific findings in two areas. First, the dissertation examines the interaction of an ultra-intense short laser pulse with atoms. GAS are used to find the optimal frequency for stabilizing atoms in the ionization process. This leads to a new theoretical formulation, to explain what is happening during the ionization process and how the electron is responding to finite (real-life) laser pulse shapes. It is shown that the dynamics of the process can be very sensitive to the ramp of the pulse at high frequencies. The new theory which is formulated, also uses a novel concept (known as the (t,t') method) to numerically solve the time-dependent Schrodinger equation Second, the dissertation also examines the use of GAS in modeling decision making problems. It compares GAS with traditional techniques to solve a class of problems known as Markov Decision Processes. The conclusion of the dissertation should give a clear idea of where GAS are applicable, especially in the physical sciences, in problems which are nonlinear and complex, i.e. difficult to analyze by other means.

  10. Genetic algorithms applied to nonlinear and complex domains

    SciTech Connect

    Barash, Danny

    1999-06-01

    The dissertation, titled ''Genetic Algorithms Applied to Nonlinear and Complex Domains'', describes and then applies a new class of powerful search algorithms (GAS) to certain domains. GAS are capable of solving complex and nonlinear problems where many parameters interact to produce a final result such as the optimization of the laser pulse in the interaction of an atom with an intense laser field. GAS can very efficiently locate the global maximum by searching parameter space in problems which are unsuitable for a search using traditional methods. In particular, the dissertation contains new scientific findings in two areas. First, the dissertation examines the interaction of an ultra-intense short laser pulse with atoms. GAS are used to find the optimal frequency for stabilizing atoms in the ionization process. This leads to a new theoretical formulation, to explain what is happening during the ionization process and how the electron is responding to finite (real-life) laser pulse shapes. It is shown that the dynamics of the process can be very sensitive to the ramp of the pulse at high frequencies. The new theory which is formulated, also uses a novel concept (known as the (t,t') method) to numerically solve the time-dependent Schrodinger equation Second, the dissertation also examines the use of GAS in modeling decision making problems. It compares GAS with traditional techniques to solve a class of problems known as Markov Decision Processes. The conclusion of the dissertation should give a clear idea of where GAS are applicable, especially in the physical sciences, in problems which are nonlinear and complex, i.e. difficult to analyze by other means.

  11. Genetic evidence of peripheral isolation and low diversity in marginal populations of the Acropora hyacinthus complex

    NASA Astrophysics Data System (ADS)

    Suzuki, Go; Keshavmurthy, Shashank; Hayashibara, Takeshi; Wallace, Carden C.; Shirayama, Yoshihisa; Chen, Chaolun Allen; Fukami, Hironobu

    2016-12-01

    Zooxanthellate corals are found throughout the tropics, but also extend into subtropical and marginal locations due to the presence of warm ocean currents. The population history of corals in marginal locations is of great interest in relation to changing global climatic conditions, as species edge zones might play an important role in evolutionary innovation. Here, we examine the genetic structure of a widely distributed coral species complex, Acropora hyacinthus, from tropical to high subtropical regions along the Kuroshio Current in Taiwan and Japan. Population genetic analysis of 307 specimens from 18 locations (7 reefal and 11 marginal) identified at least four genetic lineages within the A. hyacinthus complex: HyaA, HyaB, HyaC (dominating reefal locations) and HyaD dominating marginal locations in mainland Japan and Taiwan, except the upper Penghu Islands, which were dominated by HyaC. Crossing experiments suggested semi-incompatibility and hybridization between HyaC and D from reefal locations, implying that the existence of hybridization partners enhances diversification and genetic diversity. An incomplete barrier between the HyaC and HyaD dominations was found along the two straits in the Ryukyu Islands, where Kuroshio Current flows constantly. Despite geographical distance, the genetic composition of populations in mainland Japan was comparable to that in mainland Taiwan, which may reflect a region-specific connectivity around the northern limit of A. hyacinthus in the Pacific. In contrast, populations in the Ryukyu Islands were not significantly different from those of Palau and the Great Barrier Reef. While the precise taxonomic nature of the lineages found around the Kuroshio Current remains to be elucidated, these results indicate that, despite the presence of four lineages in the Kuroshio triangle, low genetic diversity populations of the two main lines might be isolating and differentiating in the marginal region.

  12. Genetic variation of major histocompatibility complex genes in the endangered red-crowned crane.

    PubMed

    Akiyama, Takuya; Kohyama, Tetsuo I; Nishida, Chizuko; Onuma, Manabu; Momose, Kunikazu; Masuda, Ryuichi

    2017-07-01

    Populations that have drastically decreased in the past often have low genetic variation, which may increase the risk of extinction. The genes of major histocompatibility complex (MHC) play an important role in the adaptive immune response of jawed vertebrates. Maintenance of adaptive genetic diversity such as that of MHC genes is important for wildlife conservation. Here, we determined genotypes of exon 3 of MHC class IA genes (MHCIA) and exon 2 of MHC class IIB genes (MHCIIB) to evaluate genetic variation of the endangered red-crowned crane population on Hokkaido Island, Japan, which experienced severe population decline in the past. We identified 16 and 6 alleles of MHCIA and MHCIIB, respectively, from 152 individuals. We found evidence of a positive selection at the antigen-binding sites in MHCIA exon 3 and MHCIIB exon 2. The phylogenetic analyses indicated evidence of trans-species polymorphism among the crane MHC genes. The genetic variability in both classes of MHC genes at the population level was low. No geographic structure was found based on the genetic diversity of microsatellite and MHC genes. Our study provides useful data for the optimal management of the red-crowned crane population in Hokkaido and can contribute to future studies on MHC genes of the continental populations of the red-crowned crane and other crane species.

  13. Aedes aegypti in Senegal: genetic diversity and genetic structure of domestic and sylvatic populations.

    PubMed

    Huber, Karine; Ba, Yamar; Dia, Ibrahima; Mathiot, Christian; Sall, Amadou A; Diallo, Mawlouth

    2008-08-01

    Aedes aegypti is the main vector of dengue viruses. The epidemiology of dengue fever remains poorly understood in Senegal. A sylvatic transmission seems to predominate. However, despite the sylvatic circulation of the dengue virus and the presence of vectors in urban areas, only sporadic cases have been reported. Ae. aegypti is a polytypic species. In Senegal, a purely sylvatic form is found in the forest gallery areas and a domestic form is found in the villages in savannah and sahelian areas and in urban areas. Using allozymes, we analyzed the genetic diversity and the genetic structure of Ae. aegypti populations differing in their ecological characteristics. Populations from Senegal were significantly structured but with a low level of genetic differentiation. Ae. aegypti from the "domestic" populations show a decreased genetic diversity and a lower genetic differentiation compared with "sylvatic" populations. These findings suggest that environmental conditions, ecological factors, and human activities may impact the genetic structure of Ae. aegypti populations in Senegal.

  14. Characterization of large structural genetic mosaicism in human autosomes.

    PubMed

    Machiela, Mitchell J; Zhou, Weiyin; Sampson, Joshua N; Dean, Michael C; Jacobs, Kevin B; Black, Amanda; Brinton, Louise A; Chang, I-Shou; Chen, Chu; Chen, Constance; Chen, Kexin; Cook, Linda S; Crous Bou, Marta; De Vivo, Immaculata; Doherty, Jennifer; Friedenreich, Christine M; Gaudet, Mia M; Haiman, Christopher A; Hankinson, Susan E; Hartge, Patricia; Henderson, Brian E; Hong, Yun-Chul; Hosgood, H Dean; Hsiung, Chao A; Hu, Wei; Hunter, David J; Jessop, Lea; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Robert; Kraft, Peter; Lan, Qing; Lin, Dongxin; Liu, Jianjun; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M; Matsuo, Keitaro; Olson, Sara H; Orlow, Irene; Park, Jae Yong; Pooler, Loreall; Prescott, Jennifer; Rastogi, Radhai; Risch, Harvey A; Schumacher, Fredrick; Seow, Adeline; Setiawan, Veronica Wendy; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; VanDen Berg, David; Wang, Jiu-Cun; Wentzensen, Nicolas; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Yi-Long; Xia, Lucy; Yang, Hannah P; Yang, Pan-Chyr; Zheng, Wei; Zhou, Baosen; Abnet, Christian C; Albanes, Demetrius; Aldrich, Melinda C; Amos, Christopher; Amundadottir, Laufey T; Berndt, Sonja I; Blot, William J; Bock, Cathryn H; Bracci, Paige M; Burdett, Laurie; Buring, Julie E; Butler, Mary A; Carreón, Tania; Chatterjee, Nilanjan; Chung, Charles C; Cook, Michael B; Cullen, Michael; Davis, Faith G; Ding, Ti; Duell, Eric J; Epstein, Caroline G; Fan, Jin-Hu; Figueroa, Jonine D; Fraumeni, Joseph F; Freedman, Neal D; Fuchs, Charles S; Gao, Yu-Tang; Gapstur, Susan M; Patiño-Garcia, Ana; Garcia-Closas, Montserrat; Gaziano, J Michael; Giles, Graham G; Gillanders, Elizabeth M; Giovannucci, Edward L; Goldin, Lynn; Goldstein, Alisa M; Greene, Mark H; Hallmans, Goran; Harris, Curtis C; Henriksson, Roger; Holly, Elizabeth A; Hoover, Robert N; Hu, Nan; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Koh, Woon-Puay; Kolonel, Laurence N; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C; LaCroix, Andrea; Landgren, Annelie; Landi, Maria Teresa; Li, Donghui; Liao, Linda M; Malats, Nuria; McGlynn, Katherine A; McNeill, Lorna H; McWilliams, Robert R; Melin, Beatrice S; Mirabello, Lisa; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M; Prokunina-Olsson, Ludmila; Purdue, Mark; Qiao, You-Lin; Rabe, Kari G; Rajaraman, Preetha; Real, Francisco X; Riboli, Elio; Rodríguez-Santiago, Benjamín; Rothman, Nathaniel; Ruder, Avima M; Savage, Sharon A; Schwartz, Ann G; Schwartz, Kendra L; Sesso, Howard D; Severi, Gianluca; Silverman, Debra T; Spitz, Margaret R; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R; Teras, Lauren R; Tobias, Geoffrey S; Viswanathan, Kala; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J; Wheeler, William; White, Emily; Wiencke, John K; Wolpin, Brian M; Wu, Xifeng; Wunder, Jay S; Yu, Kai; Zanetti, Krista A; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G; de Andrade, Mariza; Barnes, Kathleen C; Beaty, Terri H; Bierut, Laura J; Desch, Karl C; Doheny, Kimberly F; Feenstra, Bjarke; Ginsburg, David; Heit, John A; Kang, Jae H; Laurie, Cecilia A; Li, Jun Z; Lowe, William L; Marazita, Mary L; Melbye, Mads; Mirel, Daniel B; Murray, Jeffrey C; Nelson, Sarah C; Pasquale, Louis R; Rice, Kenneth; Wiggs, Janey L; Wise, Anastasia; Tucker, Margaret; Pérez-Jurado, Luis A; Laurie, Cathy C; Caporaso, Neil E; Yeager, Meredith; Chanock, Stephen J

    2015-03-05

    Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. Structural investigations into microtubule-MAP complexes.

    PubMed

    Hoenger, Andreas; Gross, Heinz

    2008-01-01

    Microtubules interact with a large variety of factors commonly referred to as either molecular motors (kinesins, dyneins) or structural microtubule-associated proteins (MAPs). MAPs do not exhibit motor activity, but regulate microtubule dynamics and their interactions with molecular motors, and organelles such as kinetochores or centrosomes. Structural investigations into microtubule-kinesin motor complexes are quite advanced today and by helical three-dimensional (3-D) analysis reveal a resolution of the motor-tubulin interface at <1.0 nm. However, due to their flexible structure MAPs like tau or MAP2C cannot be visualized in the same straightforward manner. Helical averaging usually reveals only the location of strong binding sites while the overall structure of the MAP remains unsolved. Other MAPs such as EB1 bind very selectively only to some parts of the microtubule lattice such as the lattice seam. Thus, they do not reveal a stoichiometric tubulin:MAP-binding ratio that would allow for a quantitative helical 3-D analysis. Therefore, to get a better view on the structure of microtubule-MAP complexes we often used a strategy that combined cryo-electron microscopy and helical or tomographic 3-D analysis with freeze-drying and high-resolution unidirectional surface shadowing. 3-D analysis of ice-embedded specimens reveals their full 3-D volume. This relies either on a repetitive structure following a helical symmetry that can be used for averaging or suffers from the limited resolution that is currently achievable with cryotomography. Surface metal shadowing exclusively images surface-exposed features at very high contrast, adding highly valuable information to 2-D or 3-D data of vitrified structures.

  16. Fine-scale genetic structure among greater sage-grouse leks in central Nevada.

    PubMed

    Jahner, Joshua P; Gibson, Daniel; Weitzman, Chava L; Blomberg, Erik J; Sedinger, James S; Parchman, Thomas L

    2016-06-14

    Mating systems that reduce dispersal and lead to non-random mating might increase the potential for genetic structure to arise at fine geographic scales. Greater sage-grouse (Centrocercus urophasianus) have a lek-based mating system and exhibit high site fidelity and skewed mating ratios. We quantified population structure by analyzing variation at 27,866 single-nucleotide polymorphisms in 140 males from ten leks (within five lek complexes) occurring in a small geographic region in central Nevada. Lek complexes, and to a lesser extent individual leks, formed statistically identifiable clusters in ordination analyses, providing evidence for fine-scale geographic genetic differentiation. Lek geography predicted genetic differentiation even at a small geographic scale, which could be sharpened by strong site fidelity. Relatedness was also higher among individuals within lek complexes (and leks), suggesting that reproductive skew, where few males participate in most of the successful matings, could also potentially contribute to genetic differentiation. Models incorporating a habitat resistance surface as a proxy for potentially reduced movement due to landscape features indicated that both geographic distance and habitat suitability (i.e. preferred habitat) predicted genetic structure, with no significant effect of man-made barriers to movement (i.e. power lines and roads). Finally, we illustrate how data sets containing fewer loci (<4000) had less statistical precision and failed to detect the full degree of genetic structure. Our results suggest that habitat features and lek site geography of sage-grouse shape fine scale genetic structure, and highlight how larger data sets can have increased precision and accuracy for quantifying ecologically relevant genetic structure over small geographic scales.

  17. Exploring the catalytic core of complex I by Yarrowia lipolytica yeast genetics.

    PubMed

    Kerscher, S; Kashani-Poor, N; Zwicker, K; Zickermann, V; Brandt, U

    2001-06-01

    We have developed Yarrowia lipolytica as a model system to study mitochondrial complex I that combines the application of fast and convenient yeast genetics with efficient structural and functional analysis of its very stable complex I isolated by his-tag affinity purification with high yield. Guided by a structural model based on homologies between complex I and [NiFe] hydrogenases mutational analysis revealed that the 49 kDa subunit plays a central functional role in complex I. We propose that critical parts of the catalytic core of complex I have evolved from the hydrogen reactive site of [NiFe] hydrogenases and that iron-sulfur cluster N2 resides at the interface between the 49 kDa and PSST subunits. These findings are in full agreement with the "semiquinone switch" mechanism according to which coupling of electron and proton transfer in complex I is achieved by a single integrated pump comprising cluster N2, the binding site for substrate ubiquinone, and a tightly bound quinone or quinoid group.

  18. Structures of the CRISPR genome integration complex.

    PubMed

    Wright, Addison V; Liu, Jun-Jie; Knott, Gavin J; Doxzen, Kevin W; Nogales, Eva; Doudna, Jennifer A

    2017-09-15

    CRISPR-Cas systems depend on the Cas1-Cas2 integrase to capture and integrate short foreign DNA fragments into the CRISPR locus, enabling adaptation to new viruses. We present crystal structures of Cas1-Cas2 bound to both donor and target DNA in intermediate and product integration complexes, as well as a cryo-electron microscopy structure of the full CRISPR locus integration complex, including the accessory protein IHF (integration host factor). The structures show unexpectedly that indirect sequence recognition dictates integration site selection by favoring deformation of the repeat and the flanking sequences. IHF binding bends the DNA sharply, bringing an upstream recognition motif into contact with Cas1 to increase both the specificity and efficiency of integration. These results explain how the Cas1-Cas2 CRISPR integrase recognizes a sequence-dependent DNA structure to ensure site-selective CRISPR array expansion during the initial step of bacterial adaptive immunity. Copyright © 2017, American Association for the Advancement of Science.

  19. Ethical and legal issues arising from complex genetic disorders. DOE final report

    SciTech Connect

    Andrews, Lori

    2002-10-09

    The project analyzed the challenges raised by complex genetic disorders in genetic counselling, for clinical practice, for public health, for quality assurance, and for protection against discrimination. The research found that, in some settings, solutions created in the context of single gene disorders are more difficult to apply to complex disorders. In other settings, the single gene solutions actually backfired and created additional problems when applied to complex genetic disorders. The literature of five common, complex genetic disorders--Alzheimer's, asthma, coronary heart disease, diabetes, and psychiatric illnesses--was evaluated in depth.

  20. Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis

    PubMed Central

    Bull, James J.; Joyce, Paul; Gladstone, Eric; Molineux, Ian J.

    2013-01-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias—mutagenesis of virions—but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it. PMID:23934886

  1. Structure of the haptoglobin-haemoglobin complex.

    PubMed

    Andersen, Christian Brix Folsted; Torvund-Jensen, Morten; Nielsen, Marianne Jensby; de Oliveira, Cristiano Luis Pinto; Hersleth, Hans-Petter; Andersen, Niels Højmark; Pedersen, Jan Skov; Andersen, Gregers Rom; Moestrup, Søren Kragh

    2012-09-20

    Red cell haemoglobin is the fundamental oxygen-transporting molecule in blood, but also a potentially tissue-damaging compound owing to its highly reactive haem groups. During intravascular haemolysis, such as in malaria and haemoglobinopathies, haemoglobin is released into the plasma, where it is captured by the protective acute-phase protein haptoglobin. This leads to formation of the haptoglobin-haemoglobin complex, which represents a virtually irreversible non-covalent protein-protein interaction. Here we present the crystal structure of the dimeric porcine haptoglobin-haemoglobin complex determined at 2.9 Å resolution. This structure reveals that haptoglobin molecules dimerize through an unexpected β-strand swap between two complement control protein (CCP) domains, defining a new fusion CCP domain structure. The haptoglobin serine protease domain forms extensive interactions with both the α- and β-subunits of haemoglobin, explaining the tight binding between haptoglobin and haemoglobin. The haemoglobin-interacting region in the αβ dimer is highly overlapping with the interface between the two αβ dimers that constitute the native haemoglobin tetramer. Several haemoglobin residues prone to oxidative modification after exposure to haem-induced reactive oxygen species are buried in the haptoglobin-haemoglobin interface, thus showing a direct protective role of haptoglobin. The haptoglobin loop previously shown to be essential for binding of haptoglobin-haemoglobin to the macrophage scavenger receptor CD163 (ref. 3) protrudes from the surface of the distal end of the complex, adjacent to the associated haemoglobin α-subunit. Small-angle X-ray scattering measurements of human haptoglobin-haemoglobin bound to the ligand-binding fragment of CD163 confirm receptor binding in this area, and show that the rigid dimeric complex can bind two receptors. Such receptor cross-linkage may facilitate scavenging and explain the increased functional affinity of

  2. Structural alignment of RNA with complex pseudoknot structure.

    PubMed

    Wong, Thomas K F; Lam, T W; Sung, Wing-Kin; Cheung, Brenda W Y; Yiu, S M

    2011-01-01

    The secondary structure of an ncRNA molecule is known to play an important role in its biological functions. Aligning a known ncRNA to a target candidate to determine the sequence and structural similarity helps in identifying de novo ncRNA molecules that are in the same family of the known ncRNA. However, existing algorithms cannot handle complex pseudoknot structures which are found in nature. In this article, we propose algorithms to handle two types of complex pseudoknots: simple non-standard pseudoknots and recursive pseudoknots. Although our methods are not designed for general pseudoknots, it already covers all known ncRNAs in both Rfam and PseudoBase databases. An evaluation of our algorithms shows that it is useful to identify ncRNA molecules in other species which are in the same family of a known ncRNA.

  3. Genetic and environmental influences on the longitudinal structure of neuroticism: a trait-state approach.

    PubMed

    Laceulle, Odilia M; Ormel, Johan; Aggen, Steven H; Neale, Michael C; Kendler, Kenneth S

    2013-09-01

    In this study, we sought to elucidate both stable and changing factors in the longitudinal structure of neuroticism using a behavioral genetic twin design. We tested whether this structure is best accounted for by a trait-state, a trait-only, or a state-only model. In line with classic views on personality, our results revealed substantial trait and state components. The contributions of genetic and environmental influences on the trait component were nearly equal, whereas environmental influences on the state component were much stronger than genetic influences. Although the overall findings were similar for older and younger twins, genetic influences on the trait component were stronger than environmental influences in younger twins, whereas the opposite was found for older twins. The current findings help to elucidate how the complex interplay between genetic and environmental factors contributes to both stability and change in neuroticism.

  4. Population genetic structure of Aphis glycines.

    PubMed

    Michel, Andrew P; Zhang, Wei; Kyo Jung, Jin; Kang, Sung-Taeg; Mian, M A Rouf

    2009-08-01

    The soybean aphid (Aphis glycines Matsumura) is an invasive pest of cultivated soybean (Glycine max L.) in North America. After the initial invasion in 2000, the aphid has quickly spread across most of the United States and Canada, suggesting large-scale dispersal and rapid adaptation to new environments. Using microsatellite markers from closely related species, we compared the genetic diversity and the amount of genetic differentiation within and among 2 South Korean and 10 North American populations. Overall allelic polymorphism was low, never exceeding four alleles per locus. However, differences in genetic diversity were seen among South Korean and North American populations in terms of heterozygote excesses and genotypic richness. Within North America, two populations (Michigan and Ontario), had lower genetic diversities and exhibited high genetic differentiation compared with the remaining eight populations. The earlier collection time of Michigan and Ontario samples explained the genetic differences better than geographic subdivisions. These data indicate a pattern of small colonizing populations on soybeans, followed by rapid clonal amplification and subsequent large-scale dispersal across North America.

  5. Solution structure of the core SMN–Gemin2 complex

    SciTech Connect

    Sarachan, Kathryn L.; Valentine, Kathleen G.; Gupta, Kushol; Moorman, Veronica R.; Gledhill, John M.; Bernens, Matthew; Tommos, Cecilia; Wand, A.  Joshua; Van Duyne, Gregory D.

    2012-08-01

    In humans, assembly of spliceosomal snRNPs (small nuclear ribonucleoproteins) begins in the cytoplasm where the multi-protein SMN (survival of motor neuron) complex mediates the formation of a seven-membered ring of Sm proteins on to a conserved site of the snRNA (small nuclear RNA). The SMN complex contains the SMN protein Gemin2 and several additional Gemins that participate in snRNP biosynthesis. SMN was first identified as the product of a gene found to be deleted or mutated in patients with the neurodegenerative disease SMA (spinal muscular atrophy), the leading genetic cause of infant mortality. In the present study, we report the solution structure of Gemin2 bound to the Gemin2-binding domain of SMN determined by NMR spectroscopy. This complex reveals the structure of Gemin2, how Gemin2 binds to SMN and the roles of conserved SMN residues near the binding interface. Surprisingly, several conserved SMN residues, including the sites of two SMA patient mutations, are not required for binding to Gemin2. Instead, they form a conserved SMN/Gemin2 surface that may be functionally important for snRNP assembly. The SMN–Gemin2 structure explains how Gemin2 is stabilized by SMN and establishes a framework for structure–function studies to investigate snRNP biogenesis as well as biological processes involving Gemin2 that do not involve snRNP assembly.

  6. Structure of a human translation termination complex

    PubMed Central

    Matheisl, Sarah; Berninghausen, Otto; Becker, Thomas; Beckmann, Roland

    2015-01-01

    In contrast to bacteria that have two release factors, RF1 and RF2, eukaryotes only possess one unrelated release factor eRF1, which recognizes all three stop codons of the mRNA and hydrolyses the peptidyl-tRNA bond. While the molecular basis for bacterial termination has been elucidated, high-resolution structures of eukaryotic termination complexes have been lacking. Here we present a 3.8 Å structure of a human translation termination complex with eRF1 decoding a UAA(A) stop codon. The complex was formed using the human cytomegalovirus (hCMV) stalling peptide, which perturbs the peptidyltransferase center (PTC) to silence the hydrolysis activity of eRF1. Moreover, unlike sense codons or bacterial stop codons, the UAA stop codon adopts a U-turn-like conformation within a pocket formed by eRF1 and the ribosome. Inducing the U-turn conformation for stop codon recognition rationalizes how decoding by eRF1 includes monitoring geometry in order to discriminate against sense codons. PMID:26384426

  7. Structurally robust control of complex networks

    NASA Astrophysics Data System (ADS)

    Nacher, Jose C.; Akutsu, Tatsuya

    2015-01-01

    Robust control theory has been successfully applied to numerous real-world problems using a small set of devices called controllers. However, the real systems represented by networks contain unreliable components and modern robust control engineering has not addressed the problem of structural changes on complex networks including scale-free topologies. Here, we introduce the concept of structurally robust control of complex networks and provide a concrete example using an algorithmic framework that is widely applied in engineering. The developed analytical tools, computer simulations, and real network analyses lead herein to the discovery that robust control can be achieved in scale-free networks with exactly the same order of controllers required in a standard nonrobust configuration by adjusting only the minimum degree. The presented methodology also addresses the probabilistic failure of links in real systems, such as neural synaptic unreliability in Caenorhabditis elegans, and suggests a new direction to pursue in studies of complex networks in which control theory has a role.

  8. Extreme genetic structure in a social bird species despite high dispersal capacity.

    PubMed

    Morinha, Francisco; Dávila, José A; Bastos, Estela; Cabral, João A; Frías, Óscar; González, José L; Travassos, Paulo; Carvalho, Diogo; Milá, Borja; Blanco, Guillermo

    2017-02-21

    Social barriers have been shown to reduce gene flow and contribute to genetic structure among populations in species with high cognitive capacity and complex societies, such as cetaceans, apes and humans. In birds, high dispersal capacity is thought to prevent population divergence unless major geographical or habitat barriers induce isolation patterns by dispersal, colonization or adaptation limitation. We report that Iberian populations of the red-billed chough, a social, gregarious corvid with high dispersal capacity, show a striking degree of genetic structure composed of at least 15 distinct genetic units. Monitoring of marked individuals over 30 years revealed that long-distance movements over hundreds of kilometres are common, yet recruitment into breeding populations is infrequent and highly philopatric. Genetic differentiation is weakly related to geographical distance, and habitat types used are overall qualitatively similar among regions and regularly shared by individuals of different populations, so that genetic structure is unlikely to be due solely to isolation by distance or isolation by adaptation. Moreover, most population nuclei showed relatively high levels of genetic diversity, suggesting a limited role for genetic drift in significantly differentiating populations. We propose that social mechanisms may underlie this unprecedented level of genetic structure in birds through a pattern of isolation by social barriers not yet described, which may have driven this remarkable population divergence in the absence of geographical and environmental barriers.

  9. Morphologically complex protostellar envelopes : structure and kinematics

    NASA Astrophysics Data System (ADS)

    Tobin, John J.

    I present an in-depth study of protostars and their surrounding envelopes of dense gas and dust, using a multitude of observational methods to reveal new details of the star formation process. I use mid-infrared imaging from the Spitzer Space Telescope, combined with photometry spanning the near-infrared to millimeter wavelengths, to construct a model of the L1527 protostellar system. I modeled both the spectral energy distribution and resolved scattered light images to determine physical properties of the protostellar system. The nature of the apparent central point source in the Spitzer images was uncertain until high-resolution L-band imaging from the Gemini observatory resolved the point source into a disk in scattered light, having a radius of 200 AU. Protostellar envelopes are also often found to cast shadows against the 8 micron Galactic background in Spitzer imaging, enabling direct probes of envelope structure. The shadow images show that the dense envelopes around twenty-two Class 0 protostars are generally morphologically complex from 0.1 pc scales down to ˜1000 AU; they are often filamentary, and frequently non-axisymmetric. The observed envelope structure indicates a likely origin in turbulent cloud structure rather than a quasi-static/equilibrium formation. The complex envelope structure also may indicate an increased likelihood of fragmentation during collapse, forming close binaries. To further characterize these envelopes, I have observed them in the dense molecular gas tracers nthp and nht, both of which closely follow the 8 micron extinction morphology. The magnitude of the velocity gradients and envelope complexity on ˜10000 AU scales indicates that the velocity structure may reflect large-scale infall in addition to the often assumed rotation. Comparisons with three-dimensional filamentary and symmetric rotating collapse models reinforce the interpretation of velocities reflecting large-scale infall, showing that the structure of the envelope

  10. The Structure and Dynamics of Economic Complexity

    NASA Astrophysics Data System (ADS)

    Hidalgo, Cesar A.

    2011-03-01

    Can network science help us understand the structure and evolution of the global economy? In this talk I summarize recent research that uses networks and complexity science to describe and explain the evolution of the mix of products that countries, and cities, produce and export. First, I show how to use information on the network connecting industries to locations to measure the complexity of an economy. Using these measures I demonstrate that countries tend to approach a level of income that is dictated by the complexity of their economies. Next, I study the evolution of economic complexity by showing that it is constrained by a coordination problem that countries, and cities, deal with using three different channels: First, they move to products that are close by, in the Product Space, to the products that they already do. Second, they are more likely to develop a product if a geographical neighbor has already developed it. And third, they follow the nestedness of the network connecting industries to locations. Finally, I introduce a simple model to account for the stylized facts uncovered in the previous sections.

  11. Structural mapping: how to study the genetic architecture of a phenotypic trait through its formation mechanism.

    PubMed

    Tong, Chunfa; Shen, Lianying; Lv, Yafei; Wang, Zhong; Wang, Xiaoling; Feng, Sisi; Li, Xin; Sui, Yihan; Pang, Xiaoming; Wu, Rongling

    2014-01-01

    Traditional approaches for genetic mapping are to simply associate the genotypes of a quantitative trait locus (QTL) with the phenotypic variation of a complex trait. A more mechanistic strategy has emerged to dissect the trait phenotype into its structural components and map specific QTLs that control the mechanistic and structural formation of a complex trait. We describe and assess such a strategy, called structural mapping, by integrating the internal structural basis of trait formation into a QTL mapping framework. Electrical impedance spectroscopy (EIS) has been instrumental for describing the structural components of a phenotypic trait and their interactions. By building robust mathematical models on circuit EIS data and embedding these models within a mixture model-based likelihood for QTL mapping, structural mapping implements the EM algorithm to obtain maximum likelihood estimates of QTL genotype-specific EIS parameters. The uniqueness of structural mapping is to make it possible to test a number of hypotheses about the pattern of the genetic control of structural components. We validated structural mapping by analyzing an EIS data collected for QTL mapping of frost hardiness in a controlled cross of jujube trees. The statistical properties of parameter estimates were examined by simulation studies. Structural mapping can be a powerful alternative for genetic mapping of complex traits by taking account into the biological and physical mechanisms underlying their formation.

  12. Population genetic structure of Aedes albopictus in Penang, Malaysia.

    PubMed

    Zawani, M K N; Abu, H A; Sazaly, A B; Zary, S Y; Darlina, M N

    2014-10-07

    The mosquito Aedes albopictus is indigenous to Southeast Asian and is a vector for arbovirus diseases. Studies examining the population genetics structure of A. albopictus have been conducted worldwide; however, there are no documented reports on the population genetic structure of A. albopictus in Malaysia, particularly in Penang. We examined the population genetics of A. albopictus based on a 445-base pair segment of the mitochondrial DNA cytochrome oxidase 1 gene among 77 individuals from 9 localities representing 4 regions (Seberang Perai Utara, Seberang Perai Tengah, Northeast, and Southwest) of Penang. A total of 37 haplotypes were detected, including 28 unique haplotypes. The other 9 haplotypes were shared among various populations. These shared haplotypes reflect the weak population genetic structure of A. albopictus. The phylogenetic tree showed a low bootstrap value with no genetic structure, which was supported by minimum spanning network analysis. Analysis of mismatch distribution showed poor fit of equilibrium distribution. The genetic distance showed low genetic variation, while pairwise FST values showed no significant difference between all regions in Penang except for some localities. High haplotype diversity and low nucleotide diversity was observed for cytochrome oxidase 1 mtDNA. We conclude that there is no population genetic structure of A. albopictus mosquitoes in the Penang area.

  13. Structured analysis and modeling of complex systems

    NASA Technical Reports Server (NTRS)

    Strome, David R.; Dalrymple, Mathieu A.

    1992-01-01

    The Aircrew Evaluation Sustained Operations Performance (AESOP) facility at Brooks AFB, Texas, combines the realism of an operational environment with the control of a research laboratory. In recent studies we collected extensive data from the Airborne Warning and Control Systems (AWACS) Weapons Directors subjected to high and low workload Defensive Counter Air Scenarios. A critical and complex task in this environment involves committing a friendly fighter against a hostile fighter. Structured Analysis and Design techniques and computer modeling systems were applied to this task as tools for analyzing subject performance and workload. This technology is being transferred to the Man-Systems Division of NASA Johnson Space Center for application to complex mission related tasks, such as manipulating the Shuttle grappler arm.

  14. Topological structural classes of complex networks

    NASA Astrophysics Data System (ADS)

    Estrada, Ernesto

    2007-01-01

    We use theoretical principles to study how complex networks are topologically organized at large scale. Using spectral graph theory we predict the existence of four different topological structural classes of networks. These classes correspond, respectively, to highly homogenous networks lacking structural bottlenecks, networks organized into highly interconnected modules with low inter-community connectivity, networks with a highly connected central core surrounded by a sparser periphery, and networks displaying a combination of highly connected groups (quasicliques) and groups of nodes partitioned into disjoint subsets (quasibipartites). Here we show by means of the spectral scaling method that these classes really exist in real-world ecological, biological, informational, technological, and social networks. We show that neither of three network growth mechanisms—random with uniform distribution, preferential attachment, and random with the same degree sequence as real network—is able to reproduce the four structural classes of complex networks. These models reproduce two of the network classes as a function of the average degree but completely fail in reproducing the other two classes of networks.

  15. Parallel Structural Evolution of Mitochondrial Ribosomes and OXPHOS Complexes

    PubMed Central

    van der Sluis, Eli O.; Bauerschmitt, Heike; Becker, Thomas; Mielke, Thorsten; Frauenfeld, Jens; Berninghausen, Otto; Neupert, Walter; Herrmann, Johannes M.; Beckmann, Roland

    2015-01-01

    The five macromolecular complexes that jointly mediate oxidative phosphorylation (OXPHOS) in mitochondria consist of many more subunits than those of bacteria, yet, it remains unclear by which evolutionary mechanism(s) these novel subunits were recruited. Even less well understood is the structural evolution of mitochondrial ribosomes (mitoribosomes): while it was long thought that their exceptionally high protein content would physically compensate for their uniquely low amount of ribosomal RNA (rRNA), this hypothesis has been refuted by structural studies. Here, we present a cryo-electron microscopy structure of the 73S mitoribosome from Neurospora crassa, together with genomic and proteomic analyses of mitoribosome composition across the eukaryotic domain. Surprisingly, our findings reveal that both structurally and compositionally, mitoribosomes have evolved very similarly to mitochondrial OXPHOS complexes via two distinct phases: A constructive phase that mainly acted early in eukaryote evolution, resulting in the recruitment of altogether approximately 75 novel subunits, and a reductive phase that acted during metazoan evolution, resulting in gradual length-reduction of mitochondrially encoded rRNAs and OXPHOS proteins. Both phases can be well explained by the accumulation of (slightly) deleterious mutations and deletions, respectively, in mitochondrially encoded rRNAs and OXPHOS proteins. We argue that the main role of the newly recruited (nuclear encoded) ribosomal- and OXPHOS proteins is to provide structural compensation to the mutationally destabilized mitochondrially encoded components. While the newly recruited proteins probably provide a selective advantage owing to their compensatory nature, and while their presence may have opened evolutionary pathways toward novel mitochondrion-specific functions, we emphasize that the initial events that resulted in their recruitment was nonadaptive in nature. Our framework is supported by population genetic

  16. Parallel Structural Evolution of Mitochondrial Ribosomes and OXPHOS Complexes.

    PubMed

    van der Sluis, Eli O; Bauerschmitt, Heike; Becker, Thomas; Mielke, Thorsten; Frauenfeld, Jens; Berninghausen, Otto; Neupert, Walter; Herrmann, Johannes M; Beckmann, Roland

    2015-04-09

    The five macromolecular complexes that jointly mediate oxidative phosphorylation (OXPHOS) in mitochondria consist of many more subunits than those of bacteria, yet, it remains unclear by which evolutionary mechanism(s) these novel subunits were recruited. Even less well understood is the structural evolution of mitochondrial ribosomes (mitoribosomes): while it was long thought that their exceptionally high protein content would physically compensate for their uniquely low amount of ribosomal RNA (rRNA), this hypothesis has been refuted by structural studies. Here, we present a cryo-electron microscopy structure of the 73S mitoribosome from Neurospora crassa, together with genomic and proteomic analyses of mitoribosome composition across the eukaryotic domain. Surprisingly, our findings reveal that both structurally and compositionally, mitoribosomes have evolved very similarly to mitochondrial OXPHOS complexes via two distinct phases: A constructive phase that mainly acted early in eukaryote evolution, resulting in the recruitment of altogether approximately 75 novel subunits, and a reductive phase that acted during metazoan evolution, resulting in gradual length-reduction of mitochondrially encoded rRNAs and OXPHOS proteins. Both phases can be well explained by the accumulation of (slightly) deleterious mutations and deletions, respectively, in mitochondrially encoded rRNAs and OXPHOS proteins. We argue that the main role of the newly recruited (nuclear encoded) ribosomal- and OXPHOS proteins is to provide structural compensation to the mutationally destabilized mitochondrially encoded components. While the newly recruited proteins probably provide a selective advantage owing to their compensatory nature, and while their presence may have opened evolutionary pathways toward novel mitochondrion-specific functions, we emphasize that the initial events that resulted in their recruitment was nonadaptive in nature. Our framework is supported by population genetic

  17. Genetic structure and extinction of the woolly mammoth, Mammuthus primigenius.

    PubMed

    Barnes, Ian; Shapiro, Beth; Lister, Adrian; Kuznetsova, Tatiana; Sher, Andrei; Guthrie, Dale; Thomas, Mark G

    2007-06-19

    The interval since circa 50 Ka has been a period of significant species extinctions among the large mammal fauna. However, the relative roles of an increasing human presence and a synchronous series of complex environmental changes in these extinctions have yet to be fully resolved. Recent analyses of fossil material from Beringia have clarified our understanding of the spatiotemporal pattern of Late Pleistocene extinctions, identifying periods of population turnover well before the last glacial maximum (LGM: circa 21 Ka) or subsequent human expansion. To examine the role of pre-LGM population changes in shaping the genetic structure of an extinct species, we analyzed the mitochondrial DNA of woolly mammoths in western Beringia and across its range. We identify genetic signatures of a range expansion of mammoths, from eastern to western Beringia, after the last interglacial (circa 125 Ka), and then an extended period during which demographic inference indicates no population-size increase. The most marked change in diversity at this time is the loss of one of two major mitochondrial lineages.

  18. Population Genetic Structure of the People of Qatar

    PubMed Central

    Hunter-Zinck, Haley; Musharoff, Shaila; Salit, Jacqueline; Al-Ali, Khalid A.; Chouchane, Lotfi; Gohar, Abeer; Matthews, Rebecca; Butler, Marcus W.; Fuller, Jennifer; Hackett, Neil R.; Crystal, Ronald G.; Clark, Andrew G.

    2010-01-01

    People of the Qatar peninsula represent a relatively recent founding by a small number of families from three tribes of the Arabian Peninsula, Persia, and Oman, with indications of African admixture. To assess the roles of both this founding effect and the customary first-cousin marriages among the ancestral Islamic populations in Qatar's population genetic structure, we obtained and genotyped with Affymetrix 500k SNP arrays DNA samples from 168 self-reported Qatari nationals sampled from Doha, Qatar. Principal components analysis was performed along with samples from the Human Genetic Diversity Project data set, revealing three clear clusters of genotypes whose proximity to other human population samples is consistent with Arabian origin, a more eastern or Persian origin, and individuals with African admixture. The extent of linkage disequilibrium (LD) is greater than that of African populations, and runs of homozygosity in some individuals reflect substantial consanguinity. However, the variance in runs of homozygosity is exceptionally high, and the degree of identity-by-descent sharing generally appears to be lower than expected for a population in which nearly half of marriages are between first cousins. Despite the fact that the SNPs of the Affymetrix 500k chip were ascertained with a bias toward SNPs common in Europeans, the data strongly support the notion that the Qatari population could provide a valuable resource for the mapping of genes associated with complex disorders and that tests of pairwise interactions are particularly empowered by populations with elevated LD like the Qatari. PMID:20579625

  19. Simulating Vibrations in a Complex Loaded Structure

    NASA Technical Reports Server (NTRS)

    Cao, Tim T.

    2005-01-01

    The Dynamic Response Computation (DIRECT) computer program simulates vibrations induced in a complex structure by applied dynamic loads. Developed to enable rapid analysis of launch- and landing- induced vibrations and stresses in a space shuttle, DIRECT also can be used to analyze dynamic responses of other structures - for example, the response of a building to an earthquake, or the response of an oil-drilling platform and attached tanks to large ocean waves. For a space-shuttle simulation, the required input to DIRECT includes mathematical models of the space shuttle and its payloads, and a set of forcing functions that simulates launch and landing loads. DIRECT can accommodate multiple levels of payload attachment and substructure as well as nonlinear dynamic responses of structural interfaces. DIRECT combines the shuttle and payload models into a single structural model, to which the forcing functions are then applied. The resulting equations of motion are reduced to an optimum set and decoupled into a unique format for simulating dynamics. During the simulation, maximum vibrations, loads, and stresses are monitored and recorded for subsequent analysis to identify structural deficiencies in the shuttle and/or payloads.

  20. Complexity and the relaxation of hierarchical structures

    NASA Astrophysics Data System (ADS)

    Bachas, Constantin P.; Huberman, Bernardo A.

    1986-10-01

    We solve exactly the problem of diffusion in an arbitrary hierarchical space. We prove that for a given ``tree silhouette'' 0complexity. We conclude that uniform trees are optimal for information diffusion, that in thermally activated processes the temperature dependence of ν varies with the underlying tree structure, and that thin elongated trees are the only ones capable of producing a 1/f spectrum.

  1. Genome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa

    PubMed Central

    Zhao, Keyan; Tung, Chih-Wei; Eizenga, Georgia C.; Wright, Mark H.; Ali, M. Liakat; Price, Adam H.; Norton, Gareth J.; Islam, M. Rafiqul; Reynolds, Andy; Mezey, Jason; McClung, Anna M.; Bustamante, Carlos D.; McCouch, Susan R.

    2011-01-01

    Asian rice, Oryza sativa is a cultivated, inbreeding species that feeds over half of the world's population. Understanding the genetic basis of diverse physiological, developmental, and morphological traits provides the basis for improving yield, quality and sustainability of rice. Here we show the results of a genome-wide association study based on genotyping 44,100 SNP variants across 413 diverse accessions of O. sativa collected from 82 countries that were systematically phenotyped for 34 traits. Using cross-population-based mapping strategies, we identified dozens of common variants influencing numerous complex traits. Significant heterogeneity was observed in the genetic architecture associated with subpopulation structure and response to environment. This work establishes an open-source translational research platform for genome-wide association studies in rice that directly links molecular variation in genes and metabolic pathways with the germplasm resources needed to accelerate varietal development and crop improvement. PMID:21915109

  2. Genome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa.

    PubMed

    Zhao, Keyan; Tung, Chih-Wei; Eizenga, Georgia C; Wright, Mark H; Ali, M Liakat; Price, Adam H; Norton, Gareth J; Islam, M Rafiqul; Reynolds, Andy; Mezey, Jason; McClung, Anna M; Bustamante, Carlos D; McCouch, Susan R

    2011-09-13

    Asian rice, Oryza sativa is a cultivated, inbreeding species that feeds over half of the world's population. Understanding the genetic basis of diverse physiological, developmental, and morphological traits provides the basis for improving yield, quality and sustainability of rice. Here we show the results of a genome-wide association study based on genotyping 44,100 SNP variants across 413 diverse accessions of O. sativa collected from 82 countries that were systematically phenotyped for 34 traits. Using cross-population-based mapping strategies, we identified dozens of common variants influencing numerous complex traits. Significant heterogeneity was observed in the genetic architecture associated with subpopulation structure and response to environment. This work establishes an open-source translational research platform for genome-wide association studies in rice that directly links molecular variation in genes and metabolic pathways with the germplasm resources needed to accelerate varietal development and crop improvement.

  3. Aphid-parasitoid community structure on genetically modified wheat.

    PubMed

    von Burg, Simone; van Veen, Frank J F; Álvarez-Alfageme, Fernando; Romeis, Jörg

    2011-06-23

    Since the introduction of genetically modified (GM) plants, one of the main concerns has been their potential effect on non-target insects. Many studies have looked at GM plant effects on single non-target herbivore species or on simple herbivore-natural enemy food chains. Agro-ecosystems, however, are characterized by numerous insect species which are involved in complex interactions, forming food webs. In this study, we looked at transgenic disease-resistant wheat (Triticum aestivum) and its effect on aphid-parasitoid food webs. We hypothesized that the GM of the wheat lines directly or indirectly affect aphids and that these effects cascade up to change the structure of the associated food webs. Over 2 years, we studied different experimental wheat lines under semi-field conditions. We constructed quantitative food webs to compare their properties on GM lines with the properties on corresponding non-transgenic controls. We found significant effects of the different wheat lines on insect community structure up to the fourth trophic level. However, the observed effects were inconsistent between study years and the variation between wheat varieties was as big as between GM plants and their controls. This suggests that the impact of our powdery mildew-resistant GM wheat plants on food web structure may be negligible and potential ecological effects on non-target insects limited.

  4. An efficient genetic algorithm for structure prediction at the nanoscale.

    PubMed

    Lazauskas, Tomas; Sokol, Alexey A; Woodley, Scott M

    2017-03-17

    We have developed and implemented a new global optimization technique based on a Lamarckian genetic algorithm with the focus on structure diversity. The key process in the efficient search on a given complex energy landscape proves to be the removal of duplicates that is achieved using a topological analysis of candidate structures. The careful geometrical prescreening of newly formed structures and the introduction of new mutation move classes improve the rate of success further. The power of the developed technique, implemented in the Knowledge Led Master Code, or KLMC, is demonstrated by its ability to locate and explore a challenging double funnel landscape of a Lennard-Jones 38 atom system (LJ38). We apply the redeveloped KLMC to investigate three chemically different systems: ionic semiconductor (ZnO)1-32, metallic Ni13 and covalently bonded C60. All four systems have been systematically explored on the energy landscape defined using interatomic potentials. The new developments allowed us to successfully locate the double funnels of LJ38, find new local and global minima for ZnO clusters, extensively explore the Ni13 and C60 (the buckminsterfullerene, or buckyball) potential energy surfaces.

  5. Landscape-level spatial genetic structure in Quercus acutissima (Fagaceae).

    PubMed

    Chung, Mi Yoon; Nason, John; Chung, Myong Gi; Kim, Ki-Joong; Park, Chong-Wook; Sun, Byung-Yun; Pak, Jae-Hong

    2002-08-01

    Quercus acutissima (Fagaceae), a deciduous broad-leaved tree, is an important forest element in hillsides of South Korea. We used allozyme loci, Wright's F statistics, and multilocus spatial autocorrelation statistics to examine the distribution of genetic diversity within and among three local populations and the spatial genetic structure at a landscape scale (15 ha, 250 × 600 m) on Oenaro Island, South Korea. Levels of genetic diversity in Q. acutissima populations were comparable to mean values for other oak species. A moderate but significant deficit of heterozygotes (mean F(IS) = 0.069) was detected within local populations and low but significant differentiation was observed among populations (F(ST) = 0.010). Spatial autocorrelation analyses revealed little evidence of significant genetic structure at spatial scales of 100-120 m. The failure to detect genetic structure within populations may be due to intraspecific competition or random mortality among saplings, resulting in extensive thinning within maternal half-sib groups. Alternatively, low genetic differentiation at the landscape scale indicates substantial gene flow among local populations. Although wind-borne pollen may be the primary source of gene flow in Q. acutissima, these results suggest that acorn movement by animals may be more extensive than previously anticipated. Comparison of these genetic data for Oenaro Island with a disturbed isolated inland population suggests that population-to-population differences in internal genetic structure may be influenced by local variation in regeneration environment (e.g., disturbance).

  6. Temporal Stability of Genetic Structure in a Mesopelagic Copepod.

    PubMed

    Goetze, Erica; Andrews, Kimberly R; Peijnenburg, Katja T C A; Portner, Elan; Norton, Emily L

    2015-01-01

    Although stochasticity in oceanographic conditions is known to be an important driver of temporal genetic change in many marine species, little is known about whether genetically distinct plankton populations can persist in open ocean habitats. A prior study demonstrated significant population genetic structure among oceanic gyres in the mesopelagic copepod Haloptilus longicornis in both the Atlantic and Pacific Oceans, and we hypothesized that populations within each gyre represent distinct gene pools that persist over time. We tested this expectation through basin-scale sampling across the Atlantic Ocean in 2010 and 2012. Using both mitochondrial (mtCOII) and microsatellite markers (7 loci), we show that the genetic composition of populations was stable across two years in both the northern and southern subtropical gyres. Genetic variation in this species was partitioned among ocean gyres (FCT = 0.285, P < 0.0001 for mtCOII, FCT = 0.013, P < 0.0001 for microsatellites), suggesting strong spatial population structure, but no significant partitioning was found among sampling years. This temporal persistence of population structure across a large geographic scale was coupled with chaotic genetic patchiness at smaller spatial scales, but the magnitude of genetic differentiation was an order of magnitude lower at these smaller scales. Our results demonstrate that genetically distinct plankton populations persist over time in highly-dispersive open ocean habitats, and this is the first study to rigorously test for temporal stability of large scale population structure in the plankton.

  7. Genetic structure and differentiation in cultivated fig (Ficus carica L.)

    USDA-ARS?s Scientific Manuscript database

    One hundred ninety-four germplasm accessions of fig representing the four fig types, Common, Smyrna, San Pedro, and Caprifig were analyzed for genetic diversity, structure, and differentiation using genetic polymorphism at 17 microsatellite loci. The collection showed considerable polymorphism with ...

  8. Genetic structure of populations and differentiation in forest trees

    Treesearch

    Raymond P. Guries; F. Thomas Ledig

    1981-01-01

    Electrophoretic techniques permit population biologists to analyze genetic structure of natural populations by using large numbers of allozyme loci. Several methods of analysis have been applied to allozyme data, including chi-square contingency tests, F-statistics, and genetic distance. This paper compares such statistics for pitch pine (Pinus rigida...

  9. Temporal Stability of Genetic Structure in a Mesopelagic Copepod

    PubMed Central

    Goetze, Erica; Andrews, Kimberly R.; Peijnenburg, Katja T. C. A.; Portner, Elan; Norton, Emily L.

    2015-01-01

    Although stochasticity in oceanographic conditions is known to be an important driver of temporal genetic change in many marine species, little is known about whether genetically distinct plankton populations can persist in open ocean habitats. A prior study demonstrated significant population genetic structure among oceanic gyres in the mesopelagic copepod Haloptilus longicornis in both the Atlantic and Pacific Oceans, and we hypothesized that populations within each gyre represent distinct gene pools that persist over time. We tested this expectation through basin-scale sampling across the Atlantic Ocean in 2010 and 2012. Using both mitochondrial (mtCOII) and microsatellite markers (7 loci), we show that the genetic composition of populations was stable across two years in both the northern and southern subtropical gyres. Genetic variation in this species was partitioned among ocean gyres (FCT = 0.285, P < 0.0001 for mtCOII, FCT = 0.013, P < 0.0001 for microsatellites), suggesting strong spatial population structure, but no significant partitioning was found among sampling years. This temporal persistence of population structure across a large geographic scale was coupled with chaotic genetic patchiness at smaller spatial scales, but the magnitude of genetic differentiation was an order of magnitude lower at these smaller scales. Our results demonstrate that genetically distinct plankton populations persist over time in highly-dispersive open ocean habitats, and this is the first study to rigorously test for temporal stability of large scale population structure in the plankton. PMID:26302332

  10. Higher-order genetic interactions and their contribution to complex traits

    PubMed Central

    Taylor, Matthew B.; Ehrenreich, Ian M.

    2014-01-01

    The contribution of genetic interactions involving three or more loci to complex traits is poorly understood. Because these higher-order genetic interactions (HGIs) are difficult to detect in genetic mapping studies, very few examples of them have been described. However, the lack of data on HGIs should not be misconstrued as proof that this class of genetic effect is unimportant. To the contrary, evidence from model organisms suggests that HGIs frequently influence genetic studies and contribute to many complex traits. Here, we review the growing literature on HGIs and discuss the future of research on this topic. PMID:25284288

  11. Microsatellite variation reveals weak genetic structure and retention of genetic variability in threatened Chinook salmon (Oncorhynchus tshawytscha) within a Snake River watershed

    USGS Publications Warehouse

    Neville, Helen; Issacs, Frank B.; Thurow, Russel; Dunham, J.B.; Rieman, B.

    2007-01-01

    Pacific salmon (Oncorhynchus spp.) have been central to the development of management concepts associated with evolutionarily significant units (ESUs), yet there are still relatively few studies of genetic diversity within threatened and endangered ESUs for salmon or other species. We analyzed genetic variation at 10 microsatellite loci to evaluate spatial population structure and genetic variability in indigenous Chinook salmon (Oncorhynchus tshawytscha) across a large wilderness basin within a Snake River ESU. Despite dramatic 20th century declines in abundance, these populations retained robust levels of genetic variability. No significant genetic bottlenecks were found, although the bottleneck metric (M ratio) was significantly correlated with average population size and variability. Weak but significant genetic structure existed among tributaries despite evidence of high levels of gene flow, with the strongest genetic differentiation mirroring the physical segregation of fish from two sub-basins. Despite the more recent colonization of one sub-basin and differences between sub-basins in the natural level of fragmentation, gene diversity and genetic differentiation were similar between sub-basins. Various factors, such as the (unknown) genetic contribution of precocial males, genetic compensation, lack of hatchery influence, and high levels of current gene flow may have contributed to the persistence of genetic variability in this system in spite of historical declines. This unique study of indigenous Chinook salmon underscores the importance of maintaining natural populations in interconnected and complex habitats to minimize losses of genetic diversity within ESUs.

  12. Effects of kin-structured seed dispersal on the genetic structure of the clonal dioecious shrub ilex leucoclada.

    PubMed

    Torimaru, T; Tani, N; Tsumura, Y; Nishimura, N; Tomaru, N

    2007-06-01

    Nonrandom patterns of gene dispersal have been identified as possible causes of genetic structuring within populations. Attempts to model these patterns have generally focused solely on the effects of isolation by distance, but the processes involved are more complex than such modeling suggests. Here, we extend considerations of gene dispersal processes beyond simple isolation by distance effects by directly evaluating the effects of kin-structured gene dispersal mediated by the group dispersal of related seeds within fruits (i.e., kin-structured seed dispersal) by birds on genetic structure in Ilex leucoclada, a clonal dioecious shrub. To examine the genetic structure patterns, we established two 30x30 m plots (one with immature soils in old-growth forest and one in secondary forest, designated IM and SC, respectively) with different I. leucoclada stem densities. In these two plots 145 and 510 stems were found, representing 78 and 85 genets, respectively, identified by analyzing their genotypes at eight microsatellite loci. The clonal structure was stronger in the SC plot than in the IM plot. Correlograms of coancestry for genets in both plots exhibited significant, positive, high values in the shortest distance class, indicating the presence of strong genetic structure. However, Sp statistics revealed that the pattern of the genetic structure differed between the plots. In addition, to estimate the family structure within fruits, we sampled forty fruits, in total, from 15 randomly selected plants in the area around the IM and SC plots, and found that 80% of the fruits were multiseeded and 42-100% of the multiseeded fruits contained at least one pair of full sibs. Simulations based on these estimates demonstrated that the group dispersal of related seeds produced through correlated mating both within and across fruits, but not unstructured half-sib dispersal, could generate the observed magnitude and trends of genetic structure found in the IM plot. Furthermore

  13. Electronic Structure and Bonding in Complex Biomolecule

    NASA Astrophysics Data System (ADS)

    Ouyang, Lizhi

    2005-03-01

    For over a century vitamin B12 and its enzyme cofactor derivates have persistently attracted research efforts for their vital biological role, unique Co-C bonding, rich red-ox chemistry, and recently their candidacies as drug delivery vehicles etc. However, our understanding of this complex metalorganic molecule's efficient enzyme activated catalytic power is still controversial. We have for the first time calculated the electronic structure, Mulliken effective charge and bonding of a whole Vitamin B12 molecule without any structural simplification by first- principles approaches based on density functional theory using structures determined by high resolution X-ray diffraction. A partial density of states analysis shows excellent agreement with X-ray absorption data and has been used successfully to interpret measured optical absorption spectra. Mulliken bonding analysis of B12 and its derivatives reveal noticeable correlations between the two axial ligands which could be exploited by the enzyme to control the catalytic process. Our calculated X-ray near edge structure of B12 and its derivates using Slater's transition state theory are also in good agreement with experiments. The same approach has been applied to other B12 derivatives, ferrocene peptides, and recently DNA molecules.

  14. The Structure and Function of the Rh antigen Complex

    PubMed Central

    Westhoff, Connie M.

    2007-01-01

    The Rh system is one of the most important and complex blood group systems because of the large number of antigens and the serious complications for the fetus of a woman sensitized by transfusion or pregnancy. Major advances in our understanding of the Rh system have occurred with the cloning of the genes and with functional evidence that the Rh blood group proteins belong to an ancient family of membrane proteins involved in ammonia transport. The arrangement and configuration of the genes at the RH locus promotes genetic exchange, generating new antigens. Importantly, RH genetic testing can now be applied to clinical transfusion medicine and prenatal practice. This includes testing for RHD zygosity, confirmation or resolution of D antigen status, and detection of altered RHD and RHCE genes in individuals at risk for producing antibodies to high incidence Rh antigens, particularly sickle cell disease patients. The Rh proteins form a core complex that is critical to the structure of the erythrocyte membrane, and may play a physiologically role in the sequestration of blood ammonia. The Rh family of proteins now includes non-erythroid Rh homologs present in many other tissues, and comparative genomics reveals Rh homologs in all domains of life. PMID:17198846

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

    PubMed Central

    Saeb, Amr T. M.; Al-Naqeb, Dhekra

    2016-01-01

    Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases. PMID:27313952

  16. Phylogeography and Population Genetic Structure of the Ornate Dragon Lizard, Ctenophorus ornatus

    PubMed Central

    Levy, Esther; Kennington, W. Jason; Tomkins, Joseph L.; LeBas, Natasha R.

    2012-01-01

    Species inhabiting ancient, geologically stable landscapes that have been impacted by agriculture and urbanisation are expected to have complex patterns of genetic subdivision due to the influence of both historical and contemporary gene flow. Here, we investigate genetic differences among populations of the granite outcrop-dwelling lizard Ctenophorus ornatus, a phenotypically variable species with a wide geographical distribution across the south-west of Western Australia. Phylogenetic analysis of mitochondrial DNA sequence data revealed two distinct evolutionary lineages that have been isolated for more than four million years within the C. ornatus complex. This evolutionary split is associated with a change in dorsal colouration of the lizards from deep brown or black to reddish-pink. In addition, analysis of microsatellite data revealed high levels of genetic structuring within each lineage, as well as strong isolation by distance at multiple spatial scales. Among the 50 outcrop populations’ analysed, non-hierarchical Bayesian clustering analysis revealed the presence of 23 distinct genetic groups, with outcrop populations less than 4 km apart usually forming a single genetic group. When a hierarchical analysis was carried out, almost every outcrop was assigned to a different genetic group. Our results show there are multiple levels of genetic structuring in C. ornatus, reflecting the influence of both historical and contemporary evolutionary processes. They also highlight the need to recognise the presence of two evolutionarily distinct lineages when making conservation management decisions on this species. PMID:23049697

  17. Genetic structure of the world's polar bear populations

    USGS Publications Warehouse

    Paetkau, David; Amstrup, Steven C.; Born, E.W.; Calvert, W.; Derocher, A.E.; Garner, G.W.; Messier, F.; Stirling, I.; Taylor, M.K.; Wiig, O.; Strobeck, C.

    1999-01-01

    We studied genetic structure in polar bear (Ursus maritimus) populations by typing a sample of 473 individuals spanning the species distribution at 16 highly variable microsatellite loci. No genetic discontinuities were found that would be consistent with evolutionarily significant periods of isolation between groups. Direct comparison of movement data and genetic data from the Canadian Arctic revealed a highly significant correlation. Genetic data generally supported existing population (management unit) designations, although there were two cases where genetic data failed to differentiate between pairs of populations previously resolved by movement data. A sharp contrast was found between the minimal genetic structure observed among populations surrounding the polar basin and the presence of several marked genetic discontinuities in the Canadian Arctic. The discontinuities in the Canadian Arctic caused the appearance of four genetic clusters of polar bear populations. These clusters vary in total estimated population size from 100 to over 10 000, and the smallest may merit a relatively conservative management strategy in consideration of its apparent isolation. We suggest that the observed pattern of genetic discontinuities has developed in response to differences in the seasonal distribution and pattern of sea ice habitat and the effects of these differences on the distribution and abundance of seals.

  18. A genetic algorithm approach in interface and surface structure optimization

    SciTech Connect

    Zhang, Jian

    2010-01-01

    The thesis is divided into two parts. In the first part a global optimization method is developed for the interface and surface structures optimization. Two prototype systems are chosen to be studied. One is Si[001] symmetric tilted grain boundaries and the other is Ag/Au induced Si(111) surface. It is found that Genetic Algorithm is very efficient in finding lowest energy structures in both cases. Not only existing structures in the experiments can be reproduced, but also many new structures can be predicted using Genetic Algorithm. Thus it is shown that Genetic Algorithm is a extremely powerful tool for the material structures predictions. The second part of the thesis is devoted to the explanation of an experimental observation of thermal radiation from three-dimensional tungsten photonic crystal structures. The experimental results seems astounding and confusing, yet the theoretical models in the paper revealed the physics insight behind the phenomena and can well reproduced the experimental results.

  19. Genetic Structure and Potential Environmental Determinants of Local Genetic Diversity in Japanese Honeybees (Apis cerana japonica)

    PubMed Central

    Nagamitsu, Teruyoshi; Yasuda, Mika; Saito-Morooka, Fuki; Inoue, Maki N.; Nishiyama, Mio; Goka, Koichi; Sugiura, Shinji; Maeto, Kaoru; Okabe, Kimiko; Taki, Hisatomo

    2016-01-01

    Declines in honeybee populations have been a recent concern. Although causes of the declines remain unclear, environmental factors may be responsible. We focused on the potential environmental determinants of local populations of wild honeybees, Apis cerana japonica, in Japan. This subspecies has little genetic variation in terms of its mitochondrial DNA sequences, and genetic variations at nuclear loci are as yet unknown. We estimated the genetic structure and environmental determinants of local genetic diversity in nuclear microsatellite genotypes of fathers and mothers, inferred from workers collected at 139 sites. The genotypes of fathers and mothers showed weak isolation by distance and negligible genetic structure. The local genetic diversity was high in central Japan, decreasing toward the peripheries, and depended on the climate and land use characteristics of the sites. The local genetic diversity decreased as the annual precipitation increased, and increased as the proportion of urban and paddy field areas increased. Positive effects of natural forest area, which have also been observed in terms of forager abundance in farms, were not detected with respect to the local genetic diversity. The findings suggest that A. cerana japonica forms a single population connected by gene flow in its main distributional range, and that climate and landscape properties potentially affect its local genetic diversity. PMID:27898704

  20. Characterization of Large Structural Genetic Mosaicism in Human Autosomes

    PubMed Central

    Machiela, Mitchell J.; Zhou, Weiyin; Sampson, Joshua N.; Dean, Michael C.; Jacobs, Kevin B.; Black, Amanda; Brinton, Louise A.; Chang, I-Shou; Chen, Chu; Chen, Constance; Chen, Kexin; Cook, Linda S.; Crous Bou, Marta; De Vivo, Immaculata; Doherty, Jennifer; Friedenreich, Christine M.; Gaudet, Mia M.; Haiman, Christopher A.; Hankinson, Susan E.; Hartge, Patricia; Henderson, Brian E.; Hong, Yun-Chul; Hosgood, H. Dean; Hsiung, Chao A.; Hu, Wei; Hunter, David J.; Jessop, Lea; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Robert; Kraft, Peter; Lan, Qing; Lin, Dongxin; Liu, Jianjun; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Matsuo, Keitaro; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Pooler, Loreall; Prescott, Jennifer; Rastogi, Radhai; Risch, Harvey A.; Schumacher, Fredrick; Seow, Adeline; Setiawan, Veronica Wendy; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; VanDen Berg, David; Wang, Jiu-Cun; Wentzensen, Nicolas; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Yi-Long; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Zheng, Wei; Zhou, Baosen; Abnet, Christian C.; Albanes, Demetrius; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Berndt, Sonja I.; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Carreón, Tania; Chatterjee, Nilanjan; Chung, Charles C.; Cook, Michael B.; Cullen, Michael; Davis, Faith G.; Ding, Ti; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Freedman, Neal D.; Fuchs, Charles S.; Gao, Yu-Tang; Gapstur, Susan M.; Patiño-Garcia, Ana; Garcia-Closas, Montserrat; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Greene, Mark H.; Hallmans, Goran; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hoover, Robert N.; Hu, Nan; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Landgren, Annelie; Landi, Maria Teresa; Li, Donghui; Liao, Linda M.; Malats, Nuria; McGlynn, Katherine A.; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Prokunina-Olsson, Ludmila; Purdue, Mark; Qiao, You-Lin; Rabe, Kari G.; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Rodríguez-Santiago, Benjamín; Rothman, Nathaniel; Ruder, Avima M.; Savage, Sharon A.; Schwartz, Ann G.; Schwartz, Kendra L.; Sesso, Howard D.; Severi, Gianluca; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Viswanathan, Kala; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J.; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wu, Xifeng; Wunder, Jay S.; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G.; de Andrade, Mariza; Barnes, Kathleen C.; Beaty, Terri H.; Bierut, Laura J.; Desch, Karl C.; Doheny, Kimberly F.; Feenstra, Bjarke; Ginsburg, David; Heit, John A.; Kang, Jae H.; Laurie, Cecilia A.; Li, Jun Z.; Lowe, William L.; Marazita, Mary L.; Melbye, Mads; Mirel, Daniel B.; Murray, Jeffrey C.; Nelson, Sarah C.; Pasquale, Louis R.; Rice, Kenneth; Wiggs, Janey L.; Wise, Anastasia; Tucker, Margaret; Pérez-Jurado, Luis A.; Laurie, Cathy C.; Caporaso, Neil E.; Yeager, Meredith; Chanock, Stephen J.

    2015-01-01

    Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10−31) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. PMID:25748358

  1. Complex Genetics Control Natural Variation in Arabidopsis thaliana Resistance to Botrytis cinerea

    PubMed Central

    Rowe, Heather C.; Kliebenstein, Daniel J.

    2008-01-01

    The genetic architecture of plant defense against microbial pathogens may be influenced by pathogen lifestyle. While plant interactions with biotrophic pathogens are frequently controlled by the action of large-effect resistance genes that follow classic Mendelian inheritance, our study suggests that plant defense against the necrotrophic pathogen Botrytis cinerea is primarily quantitative and genetically complex. Few studies of quantitative resistance to necrotrophic pathogens have used large plant mapping populations to dissect the genetic structure of resistance. Using a large structured mapping population of Arabidopsis thaliana, we identified quantitative trait loci influencing plant response to B. cinerea, measured as expansion of necrotic lesions on leaves and accumulation of the antimicrobial compound camalexin. Testing multiple B. cinerea isolates, we identified 23 separate QTL in this population, ranging in isolate-specificity from being identified with a single isolate to controlling resistance against all isolates tested. We identified a set of QTL controlling accumulation of camalexin in response to pathogen infection that largely colocalized with lesion QTL. The identified resistance QTL appear to function in epistatic networks involving three or more loci. Detection of multilocus connections suggests that natural variation in specific signaling or response networks may control A. thaliana–B. cinerea interaction in this population. PMID:18845849

  2. Dispersal and genetic structure in the American marten, Martes americana.

    PubMed

    Broquet, T; Johnson, C A; Petit, E; Thompson, I; Burel, F; Fryxell, J M

    2006-05-01

    Natal dispersal in a vagile carnivore, the American marten (Martes americana), was studied by comparing radio-tracking data and microsatellite genetic structure in two populations occupying contrasting habitats. The genetic differentiation determined among groups of individuals using F(ST) indices appeared to be weak in both landscapes, and showed no increase with geographical distance. Genetic structure investigated using pairwise genetic distances between individuals conversely showed a pattern of isolation by distance (IBD), but only in the population occurring in a homogeneous high-quality habitat, therefore showing the advantage of individual-based analyses in detecting within-population processes and local landscape effects. The telemetry study of juveniles revealed a leptokurtic distribution of dispersal distances in both populations, and estimates of the mean squared parent-offspring axial distance (sigma2) inferred both from the genetic pattern of IBD and from the radio-tracking survey showed that most juveniles make little contribution to gene flow.

  3. Extensive population genetic structure in the giraffe

    PubMed Central

    Brown, David M; Brenneman, Rick A; Koepfli, Klaus-Peter; Pollinger, John P; Milá, Borja; Georgiadis, Nicholas J; Louis, Edward E; Grether, Gregory F; Jacobs, David K; Wayne, Robert K

    2007-01-01

    Background A central question in the evolutionary diversification of large, widespread, mobile mammals is how substantial differentiation can arise, particularly in the absence of topographic or habitat barriers to dispersal. All extant giraffes (Giraffa camelopardalis) are currently considered to represent a single species classified into multiple subspecies. However, geographic variation in traits such as pelage pattern is clearly evident across the range in sub-Saharan Africa and abrupt transition zones between different pelage types are typically not associated with extrinsic barriers to gene flow, suggesting reproductive isolation. Results By analyzing mitochondrial DNA sequences and nuclear microsatellite loci, we show that there are at least six genealogically distinct lineages of giraffe in Africa, with little evidence of interbreeding between them. Some of these lineages appear to be maintained in the absence of contemporary barriers to gene flow, possibly by differences in reproductive timing or pelage-based assortative mating, suggesting that populations usually recognized as subspecies have a long history of reproductive isolation. Further, five of the six putative lineages also contain genetically discrete populations, yielding at least 11 genetically distinct populations. Conclusion Such extreme genetic subdivision within a large vertebrate with high dispersal capabilities is unprecedented and exceeds that of any other large African mammal. Our results have significant implications for giraffe conservation, and imply separate in situ and ex situ management, not only of pelage morphs, but also of local populations. PMID:18154651

  4. The Spectrum of Pyruvate Dehydrogenase Complex Deficiency: Clinical, Biochemical and Genetic Features in 371 Patients

    PubMed Central

    Patel, Kavi P.; O'Brien, Thomas W.; Subramony, Sankarasubramon H.; Shuster, Jonathan; Stacpoole, Peter W.

    2013-01-01

    Context Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, death during childhood. There has been no recent comprehensive analysis of the natural history and clinical course of this disease. Objective We reviewed 371 cases of PDC deficiency, published between 1970-2010, that involved defects in subunits E1α and E1β and components E1, E2, E3 and the E3 Binding Protein of the complex. Data Sources and Extraction English language peer-reviewed publications were identified, primarily by using PubMed and Google Scholar search engines. Results Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency. Structural brain abnormalities frequently included ventriculomegaly, dysgenesis of the corpus callosum and neuroimaging findings typical of Leigh syndrome. Neither gender nor any clinical or neuroimaging feature differentiated the various biochemical etiologies of the disease. Patients who died were younger, presented clinically earlier and had higher blood lactate levels and lower residual enzyme activities than subjects who were still alive at the time of reporting. Survival bore no relationship to the underlying biochemical or genetic abnormality or to gender. Conclusions Although the clinical spectrum of PDC deficiency is broad, the dominant clinical phenotype includes presentation during the first year of life; neurological and neuromuscular degeneration; structural lesions revealed by neuroimaging; lactic acidosis and a blood lactate:pyruvate ratio ≤20. PMID:22079328

  5. The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients

    PubMed Central

    Patel, Kavi P.; O’Brien, Thomas W.; Subramony, Sankarasubramon H.; Shuster, Jonathan; Stacpoole, Peter W.

    2014-01-01

    Context Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, death during childhood. There has been no recent comprehensive analysis of the natural history and clinical course of this disease. Objective We reviewed 371 cases of PDC deficiency, published between 1970 and 2010, that involved defects in subunits E1α and E1β and components E1, E2, E3 and the E3 binding protein of the complex. Data sources and extraction English language peer-reviewed publications were identified, primarily by using PubMed and Google Scholar search engines. Results Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency. Structural brain abnormalities frequently included ventriculomegaly, dysgenesis of the corpus callosum and neuroimaging findings typical of Leigh syndrome. Neither gender nor any clinical or neuroimaging feature differentiated the various biochemical etiologies of the disease. Patients who died were younger, presented clinically earlier and had higher blood lactate levels and lower residual enzyme activities than subjects who were still alive at the time of reporting. Survival bore no relationship to the underlying biochemical or genetic abnormality or to gender. Conclusions Although the clinical spectrum of PDC deficiency is broad, the dominant clinical phenotype includes presentation during the first year of life; neurological and neuromuscular degeneration; structural lesions revealed by neuroimaging; lactic acidosis and a blood lactate:pyruvate ratio≤20. PMID:22896851

  6. Assessment of Genetic Diversity and Population Genetic Structure of Corylus mandshurica in China Using SSR Markers

    PubMed Central

    Zong, Jian-Wei; Zhao, Tian-Tian; Ma, Qing-Hua; Liang, Li-Song; Wang, Gui-Xi

    2015-01-01

    Corylus mandshurica, also known as pilose hazelnut, is an economically and ecologically important species in China. In this study, ten polymorphic simple sequence repeat (SSR) markers were applied to evaluate the genetic diversity and population structure of 348 C. mandshurica individuals among 12 populations in China. The SSR markers expressed a relatively high level of genetic diversity (Na = 15.3, Ne = 5.6604, I = 1.8853, Ho = 0.6668, and He = 0.7777). According to the coefficient of genetic differentiation (Fst = 0.1215), genetic variation within the populations (87.85%) were remarkably higher than among populations (12.15%). The average gene flow (Nm = 1.8080) significantly impacts the genetic structure of C. mandshurica populations. The relatively high gene flow (Nm = 1.8080) among wild C. mandshurica may be caused by wind-pollinated flowers, highly nutritious seeds and self-incompatible mating system. The UPGMA (unweighted pair group method of arithmetic averages) dendrogram was divided into two main clusters. Moreover, the results of STRUCTURE analysis suggested that C. mandshurica populations fell into two main clusters. Comparison of the UPGMA dendrogram and the Bayesian STRUCTURE analysis showed general agreement between the population subdivisions and the genetic relationships among populations of C. mandshurica. Group I accessions were located in Northeast China, while Group II accessions were in North China. It is worth noting that a number of genetically similar populations were located in the same geographic region. The results further showed that there was obvious genetic differentiation among populations from Northeast China to North China. Results from the Mantel test showed a weak but still significant positive correlation between Nei’s genetic distance and geographic distance (km) among populations (r = 0.419, P = 0.005), suggesting that genetic differentiation in the 12 C. mandshurica populations might be related to geographic distance

  7. Assessment of Genetic Diversity and Population Genetic Structure of Corylus mandshurica in China Using SSR Markers.

    PubMed

    Zong, Jian-Wei; Zhao, Tian-Tian; Ma, Qing-Hua; Liang, Li-Song; Wang, Gui-Xi

    2015-01-01

    Corylus mandshurica, also known as pilose hazelnut, is an economically and ecologically important species in China. In this study, ten polymorphic simple sequence repeat (SSR) markers were applied to evaluate the genetic diversity and population structure of 348 C. mandshurica individuals among 12 populations in China. The SSR markers expressed a relatively high level of genetic diversity (Na = 15.3, Ne = 5.6604, I = 1.8853, Ho = 0.6668, and He = 0.7777). According to the coefficient of genetic differentiation (Fst = 0.1215), genetic variation within the populations (87.85%) were remarkably higher than among populations (12.15%). The average gene flow (Nm = 1.8080) significantly impacts the genetic structure of C. mandshurica populations. The relatively high gene flow (Nm = 1.8080) among wild C. mandshurica may be caused by wind-pollinated flowers, highly nutritious seeds and self-incompatible mating system. The UPGMA (unweighted pair group method of arithmetic averages) dendrogram was divided into two main clusters. Moreover, the results of STRUCTURE analysis suggested that C. mandshurica populations fell into two main clusters. Comparison of the UPGMA dendrogram and the Bayesian STRUCTURE analysis showed general agreement between the population subdivisions and the genetic relationships among populations of C. mandshurica. Group I accessions were located in Northeast China, while Group II accessions were in North China. It is worth noting that a number of genetically similar populations were located in the same geographic region. The results further showed that there was obvious genetic differentiation among populations from Northeast China to North China. Results from the Mantel test showed a weak but still significant positive correlation between Nei's genetic distance and geographic distance (km) among populations (r = 0.419, P = 0.005), suggesting that genetic differentiation in the 12 C. mandshurica populations might be related to geographic distance. These

  8. Energy-Complexity Relations by Structural Complexity Methods

    NASA Astrophysics Data System (ADS)

    Ricca, Renzo L.

    2011-09-01

    In this paper we shall review some of the most recent developments and results on work on energy-complexity relations and, if time will allow it, we shall provide an analytical proof of eq. (3) below, a fundamental relation between energy and complexity established by numerical experiments.

  9. Does the genetic type of collagen determine fibril structure

    SciTech Connect

    Eikenberry, E.; Brodsky, B.; Cassidy, K.

    1980-10-01

    A number of genetic types of collagen, all triple-helical but with significant variations in their amino acid sequences, have been found and the distribution of these genetic types is tissue specific. For example, tendon is composed only of type I collagen, while cartilage contains largely type II collagen. Skin contains a large amount of type I, but has a significant fraction, approx. 15%, of type III. Each of these types can form fibrils, but it is not known whether they form distinctive fibril structures that are important in determining tissue organization. We are using x-ray diffraction to analyze a variety of tissues with different collagen genetic types to compare the fibril structures and thus investigate whether genetic type is an important determinant of this structure.

  10. Geomechanical numerical simulations of complex geologic structures

    SciTech Connect

    Arguello, J.G.; Stone, C.M.; Lorenz, J.C.

    1996-05-01

    Ability to predict mechanical response of rock in three dimensions over the spatial and time scales of geologic interest would give the oil and gas industry the ability to reduce risk on prospects, improve pre-project initial reserve estimates, and lower operating costs. A program has recently been initiated, under the auspices of the Advanced Computational Technology Initiative (ACTI), to achieve such a computational technology breakthrough by adapting the unique advanced quasistatic finite element technology developed by Sandia to the mechanics applications important to exploration and production activities within the oil and gas industry. As a precursor to that program, in an effort to evaluate the feasibility of the approach, several complex geologic structures of interest were analyzed with the existing two-dimensional quasistatic finite element code, SANTOS, developed at Sandia. Examples are presented and discussed.

  11. Identifying community structure in complex networks

    NASA Astrophysics Data System (ADS)

    Shao, Chenxi; Duan, Yubing

    2015-07-01

    A wide variety of applications could be formulated to resolve the problem of finding all communities from a given network, ranging from social and biological network analysis to web mining and searching. In this study, we propose the concept of virtual attractive strength between each pair of node in networks, and then give the definition of community structure based on the proposed attractive strength. Furthermore, we present a community detection method by moving vertices to the clusters that produce the largest attractive strengths to them until the division of network reaches unchanged. Experimental results on synthetic and real networks indicate that the proposed approach has favorite effectiveness and fast convergence speed, which provides an efficient method for exploring and analyzing complex systems.

  12. Transcription initiation complex structures elucidate DNA opening.

    PubMed

    Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

    2016-05-19

    Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

  13. Electronic structures of ytterbocene-imine complexes

    SciTech Connect

    Da Re, R. E.; Kuehl, C. J.; John, K. D.; Morris, D. E.

    2004-01-01

    The electronic structures of complexes of the form [(C{sub 5}Me{sub 5}){sub 2}Yb(L)]{sup +/0} (L = bipyridine, phenanthroline, terpyridine) have been probed using cyclic voltammetry and electronic spectroscopy. Remarkably, the voltammetric data reveal that the imine-based LUMO is stabilized and the redox-active metal f orbital is destabilized by ca. 1 V each upon formation of the ytterbocene-imine adduct, which is presumably responsible for the [(f){sup 13}({pi}*(L)){sup 1}] charge-transfer ground state characteristic of these complexes. The ca. 0.8 V separation between ligand-based oxidation and metal-based reduction waves for each ytterbocene adduct correlates with the energy of its optically promoted {pi}*(L)-f(Yb) charge transfer (LMCT) transition (ca. 5000 cm{sup -1}). The coupling between this LMCT excited state and the {sup 2}F{sub 7/2} ground and {sup 2}F{sub 5/2} excited states of Yb(III) leads to unusually large intensities ({var_epsilon} {approx} 1000) for the metal-localized f-f bands, which will be discussed in the context of an intensity borrowing mechanism that invokes exchange between the ligand-based {sup 2}S and metal-based {sup 2}F spin states.

  14. Discovering link communities in complex networks by an integer programming model and a genetic algorithm.

    PubMed

    Li, Zhenping; Zhang, Xiang-Sun; Wang, Rui-Sheng; Liu, Hongwei; Zhang, Shihua

    2013-01-01

    Identification of communities in complex networks is an important topic and issue in many fields such as sociology, biology, and computer science. Communities are often defined as groups of related nodes or links that correspond to functional subunits in the corresponding complex systems. While most conventional approaches have focused on discovering communities of nodes, some recent studies start partitioning links to find overlapping communities straightforwardly. In this paper, we propose a new quantity function for link community identification in complex networks. Based on this quantity function we formulate the link community partition problem into an integer programming model which allows us to partition a complex network into overlapping communities. We further propose a genetic algorithm for link community detection which can partition a network into overlapping communities without knowing the number of communities. We test our model and algorithm on both artificial networks and real-world networks. The results demonstrate that the model and algorithm are efficient in detecting overlapping community structure in complex networks.

  15. Refined Genetic Algorithms for Polypeptide Structure Prediction.

    DTIC Science & Technology

    1996-12-01

    fo cused ev olution program. 2.5 Parallel Genetic Algorithms General information ab out parallel computing is a v ailable in App endix C. There are t w...to generate a more t \\feasible" candidate, and th us, escap e the lo cal minim a. T able 14. Final minim um energies (k cal/mol) for [Met]-enk...prop osed the tec hnique kno wn as ev olutionary programming. Ev olu- tionary programmi ng tries to generate computational biological ev olution

  16. Enhanced Bayesian modelling in BAPS software for learning genetic structures of populations.

    PubMed

    Corander, Jukka; Marttinen, Pekka; Sirén, Jukka; Tang, Jing

    2008-12-16

    During the most recent decade many Bayesian statistical models and software for answering questions related to the genetic structure underlying population samples have appeared in the scientific literature. Most of these methods utilize molecular markers for the inferences, while some are also capable of handling DNA sequence data. In a number of earlier works, we have introduced an array of statistical methods for population genetic inference that are implemented in the software BAPS. However, the complexity of biological problems related to genetic structure analysis keeps increasing such that in many cases the current methods may provide either inappropriate or insufficient solutions. We discuss the necessity of enhancing the statistical approaches to face the challenges posed by the ever-increasing amounts of molecular data generated by scientists over a wide range of research areas and introduce an array of new statistical tools implemented in the most recent version of BAPS. With these methods it is possible, e.g., to fit genetic mixture models using user-specified numbers of clusters and to estimate levels of admixture under a genetic linkage model. Also, alleles representing a different ancestry compared to the average observed genomic positions can be tracked for the sampled individuals, and a priori specified hypotheses about genetic population structure can be directly compared using Bayes' theorem. In general, we have improved further the computational characteristics of the algorithms behind the methods implemented in BAPS facilitating the analyses of large and complex datasets. In particular, analysis of a single dataset can now be spread over multiple computers using a script interface to the software. The Bayesian modelling methods introduced in this article represent an array of enhanced tools for learning the genetic structure of populations. Their implementations in the BAPS software are designed to meet the increasing need for analyzing large

  17. GENETIC CONSEQUENCES OF SEED DISPERSAL IN THREE SYMPATRIC FOREST HERBS. I. HIERARCHICAL POPULATION-GENETIC STRUCTURE.

    PubMed

    Williams, Charles F; Guries, Raymond P

    1994-06-01

    To examine the effects of seed dispersal on spatial genetic structure, we compare three sympatric species of forest herbs in the family Apiaceae whose fruits differ widely in morphological adaptations for animal-attached dispersal. Cryptotaenia canadensis has smooth fruits that are gravity dispersed, whereas Osmorhiza claytonii and Sanicula odorata fruits have appendages that facilitate their attachment to animals. The relative seed-dispersal ability among species, measured as their ability to remain attached to mammal fur, is ranked Sanicula > Osmorhiza > Cryptotaenia. We use a nested hierarchical sampling design to analyze genetic structure at spatial scales ranging from a few meters to hundreds of kilometers. Genetic differentiation among population subdivisions, estimated by average genetic distance and hierarchical F-statistics, has an inverse relationship with dispersal ability such that Cryptotaenia > Osmorhiza > Sanicula. In each species, genetic differentiation increases with distance among population subdivisions. Stochastic variation in gene flow, arising from seed dispersal by attachment to animals, may partly explain the weak relationship between pairwise spatial and genetic distance among populations and heterogeneity in estimates of single locus F-statistics. A hierarchical island model of gene flow is invoked to describe the effects of seed dispersal on population genetic structure. Seed dispersal is the predominant factor affecting variation in gene flow among these ecologically similar, taxonomically related species. © 1994 The Society for the Study of Evolution.

  18. Genetic Diversity and Population Structure of Teosinte

    PubMed Central

    Fukunaga, Kenji; Hill, Jason; Vigouroux, Yves; Matsuoka, Yoshihiro; Sanchez G., Jesus; Liu, Kejun; Buckler, Edward S.; Doebley, John

    2005-01-01

    The teosintes, the closest wild relatives of maize, are important resources for the study of maize genetics and evolution and for plant breeding. We genotyped 237 individual teosinte plants for 93 microsatellites. Phylogenetic relationships among species and subspecific taxa were largely consistent with prior analyses for other types of molecular markers. Plants of all species formed monophyletic clades, although relationships among species were not fully resolved. Phylogenetic analysis indicated that the Mexican annual teosintes divide into two clusters that largely correspond to the previously defined subspecies, Z. mays ssp. parviglumis and ssp. mexicana, although there are a few samples that represent either evolutionary intermediates or hybrids between these two subspecies. The Mexican annual teosintes show genetic substructuring along geographic lines. Hybridization or introgression between some teosintes and maize occurs at a low level and appears most common with Z. mays ssp. mexicana. Phylogeographic and phylogenetic analyses of the Mexican annual teosintes indicated that ssp. parviglumis diversified in the eastern part of its distribution and spread from east to west and that ssp. mexicana diversified in the Central Plateau of Mexico and spread along multiple paths to the north and east. We defined core sets of collections of Z. mays ssp. mexicana and ssp. parviglumis that attempt to capture the maximum number of microsatellite alleles for given sample sizes. PMID:15687282

  19. Coherent structures in a supersonic complex nozzle

    NASA Astrophysics Data System (ADS)

    Magstadt, Andrew; Berry, Matthew; Glauser, Mark

    2016-11-01

    The jet flow from a complex supersonic nozzle is studied through experimental measurements. The nozzle's geometry is motivated by future engine designs for high-performance civilian and military aircraft. This rectangular jet has a single plane of symmetry, an additional shear layer (referred to as a wall jet), and an aft deck representative of airframe integration. The core flow operates at a Mach number of Mj , c = 1 . 6 , and the wall jet is choked (Mj , w = 1 . 0). This high Reynolds number jet flow is comprised of intense turbulence levels, an intricate shock structure, shear and boundary layers, and powerful corner vortices. In the present study, stereo PIV measurements are simultaneously sampled with high-speed pressure measurements, which are embedded in the aft deck, and far-field acoustics in the anechoic chamber at Syracuse University. Time-resolved schlieren measurements have indicated the existence of strong flow events at high frequencies, at a Strouhal number of St = 3 . 4 . These appear to result from von Kàrmàn vortex shedding within the nozzle and pervade the entire flow and acoustic domain. Proper orthogonal decomposition is applied on the current data to identify coherent structures in the jet and study the influence of this vortex street. AFOSR Turbulence and Transition Program (Grant No. FA9550-15-1-0435) with program managers Dr. I. Leyva and Dr. R. Ponnappan.

  20. Characterizing the Community Structure of Complex Networks

    PubMed Central

    Lancichinetti, Andrea; Kivelä, Mikko; Saramäki, Jari; Fortunato, Santo

    2010-01-01

    Background Community structure is one of the key properties of complex networks and plays a crucial role in their topology and function. While an impressive amount of work has been done on the issue of community detection, very little attention has been so far devoted to the investigation of communities in real networks. Methodology/Principal Findings We present a systematic empirical analysis of the statistical properties of communities in large information, communication, technological, biological, and social networks. We find that the mesoscopic organization of networks of the same category is remarkably similar. This is reflected in several characteristics of community structure, which can be used as “fingerprints” of specific network categories. While community size distributions are always broad, certain categories of networks consist mainly of tree-like communities, while others have denser modules. Average path lengths within communities initially grow logarithmically with community size, but the growth saturates or slows down for communities larger than a characteristic size. This behaviour is related to the presence of hubs within communities, whose roles differ across categories. Also the community embeddedness of nodes, measured in terms of the fraction of links within their communities, has a characteristic distribution for each category. Conclusions/Significance Our findings, verified by the use of two fundamentally different community detection methods, allow for a classification of real networks and pave the way to a realistic modelling of networks' evolution. PMID:20711338

  1. The Kuroshio current influences genetic diversity and population genetic structure of a tropical seagrass, Enhalus acoroides.

    PubMed

    Nakajima, Yuichi; Matsuki, Yu; Lian, Chunlan; Fortes, Miguel D; Uy, Wilfredo H; Campos, Wilfredo L; Nakaoka, Masahiro; Nadaoka, Kazuo

    2014-12-01

    Information on genetic diversity and differentiation of seagrass populations is essential for the conservation of coastal ecosystems. However, little is known about the seagrasses in the Indo-West Pacific Ocean, where the world's highest diversity of seagrasses occurs. The influence of sea currents on these populations is also unknown. We estimated the genetic diversity and population genetic structure and identified reproductive features in Enhalus acoroides populations from the Yaeyama Islands, Hainan Island and the Philippines. The Philippines are situated at the centre of the E. acoroides range, Yaeyama and Hainan are peripheral populations, and the Yaeyama population is at the northern limit of the species range. The powerful Kuroshio Current flows from the Philippines to Yaeyama. Genetic analyses using nine microsatellite markers indicated that reproduction of E. acoroides is mostly sexual. Clonal diversity does not decrease in northern populations, although genetic diversity does. However, the genetic diversity of the Yaeyama populations is greater than that of the Hainan populations. Significant genetic differentiation among most populations was evident; however, the Yaeyama and north-east Philippines populations were genetically similar, despite being separated by ~1100 km. An assignment test suggested that recruitment occurs from the north-east Philippines to Yaeyama. The strong current in this region is probably responsible for the extant genetic diversity and recruitment patterns. © 2014 John Wiley & Sons Ltd.

  2. Genetic Diversity and Spatial Genetic Structure of the Grassland Perennial Saxifraga granulata along Two River Systems

    PubMed Central

    van der Meer, Sascha; Jacquemyn, Hans

    2015-01-01

    Due to changes in land use, the natural habitats of an increasing number of plant species have become more and more fragmented. In landscapes that consist of patches of suitable habitat, the frequency and extent of long-distance seed dispersal can be expected to be an important factor determining local genetic diversity and regional population structure of the remaining populations. In plant species that are restricted to riparian habitats, rivers can be expected to have a strong impact on the dynamics and spatial genetic structure of populations as they may enable long-distance seed dispersal and thus maintain gene flow between fragmented populations. In this study, we used polymorphic microsatellite markers to investigate the genetic diversity and the spatial genetic structure of 28 populations of Saxifraga granulata along two rivers in central Belgium. We hypothesized that rivers might be essential for gene flow among increasingly isolated populations of this species. Genetic diversity was high (HS = 0.68), which to a certain extent can be explained by the octoploid nature of S. granulata in the study area. Populations along the Dijle and Demer rivers were also highly differentiated (G”ST = 0.269 and 0.164 and DEST = 0.190 and 0.124, respectively) and showed significant isolation-by-distance, indicating moderate levels of gene flow primarily between populations that are geographically close to each other. Along the river Demer population genetic diversity was higher upstream than downstream, suggesting that seed dispersal via the water was not the primary mode of dispersal. Overall, these results indicate that despite increasing fragmentation populations along both rivers were highly genetically diverse. The high ploidy level and longevity of S. granulata have most likely buffered negative effects of fragmentation on genetic diversity and the spatial genetic structure of populations in riparian grasslands. PMID:26079603

  3. Genetic Diversity and Spatial Genetic Structure of the Grassland Perennial Saxifraga granulata along Two River Systems.

    PubMed

    van der Meer, Sascha; Jacquemyn, Hans

    2015-01-01

    Due to changes in land use, the natural habitats of an increasing number of plant species have become more and more fragmented. In landscapes that consist of patches of suitable habitat, the frequency and extent of long-distance seed dispersal can be expected to be an important factor determining local genetic diversity and regional population structure of the remaining populations. In plant species that are restricted to riparian habitats, rivers can be expected to have a strong impact on the dynamics and spatial genetic structure of populations as they may enable long-distance seed dispersal and thus maintain gene flow between fragmented populations. In this study, we used polymorphic microsatellite markers to investigate the genetic diversity and the spatial genetic structure of 28 populations of Saxifraga granulata along two rivers in central Belgium. We hypothesized that rivers might be essential for gene flow among increasingly isolated populations of this species. Genetic diversity was high (HS = 0.68), which to a certain extent can be explained by the octoploid nature of S. granulata in the study area. Populations along the Dijle and Demer rivers were also highly differentiated (G"ST = 0.269 and 0.164 and DEST = 0.190 and 0.124, respectively) and showed significant isolation-by-distance, indicating moderate levels of gene flow primarily between populations that are geographically close to each other. Along the river Demer population genetic diversity was higher upstream than downstream, suggesting that seed dispersal via the water was not the primary mode of dispersal. Overall, these results indicate that despite increasing fragmentation populations along both rivers were highly genetically diverse. The high ploidy level and longevity of S. granulata have most likely buffered negative effects of fragmentation on genetic diversity and the spatial genetic structure of populations in riparian grasslands.

  4. Functional Dissection of the NuA4 Histone Acetyltransferase Reveals Its Role as a Genetic Hub and that Eaf1 Is Essential for Complex Integrity▿

    PubMed Central

    Mitchell, Leslie; Lambert, Jean-Philippe; Gerdes, Maria; Al-Madhoun, Ashraf S.; Skerjanc, Ilona S.; Figeys, Daniel; Baetz, Kristin

    2008-01-01

    The Saccharomyces cerevisiae NuA4 histone acetyltransferase complex catalyzes the acetylation of histone H4 and the histone variant Htz1 to regulate key cellular events, including transcription, DNA repair, and faithful chromosome segregation. To further investigate the cellular processes impacted by NuA4, we exploited the nonessential subunits of the complex to build an extensive NuA4 genetic-interaction network map. The map reveals that NuA4 is a genetic hub whose function buffers a diverse range of cellular processes, many not previously linked to the complex, including Golgi complex-to-vacuole vesicle-mediated transport. Further, we probe the role that nonessential subunits play in NuA4 complex integrity. We find that most nonessential subunits have little impact on NuA4 complex integrity and display between 12 and 42 genetic interactions. In contrast, the deletion of EAF1 causes the collapse of the NuA4 complex and displays 148 genetic interactions. Our study indicates that Eaf1 plays a crucial function in NuA4 complex integrity. Further, we determine that Eaf5 and Eaf7 form a subcomplex, which reflects their similar genetic interaction profiles and phenotypes. Our integrative study demonstrates that genetic interaction maps are valuable in dissecting complex structure and provides insight into why the human NuA4 complex, Tip60, has been associated with a diverse range of pathologies. PMID:18212056

  5. Complex Host Genetics Influence the Microbiome in Inflammatory Bowel Disease

    DTIC Science & Technology

    2016-09-09

    SECURITY CLASSIFICATION OF: Human genetics and host- associated microbial communities have been associated independently with a wide range of chronic...diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor...when the dysbiosis was initially genetically derived. Although there have been several tests for association of 1. REPORT DATE (DD-MM-YYYY) 4

  6. AFRICAN GENETIC DIVERSITY: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

    PubMed Central

    Campbell, Michael C.; Tishkoff, Sarah A.

    2010-01-01

    Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility. PMID:18593304

  7. Spatial and temporal determinants of genetic structure in Gentianella bohemica

    PubMed Central

    Königer, Julia; Rebernig, Carolin A; Brabec, Jiří; Kiehl, Kathrin; Greimler, Josef

    2012-01-01

    The biennial plant Gentianella bohemica is a subendemic of the Bohemian Massif, where it occurs in seminatural grasslands. It has become rare in recent decades as a result of profound changes in land use. Using amplified fragment length polymorphisms (AFLP) fingerprint data, we investigated the genetic structure within and among populations of G. bohemica in Bavaria, the Czech Republic, and the Austrian border region. The aim of our study was (1) to analyze the genetic structure among populations and to discuss these findings in the context of present and historical patterns of connectivity and isolation of populations, (2) to analyze genetic structure among consecutive generations (cohorts of two consecutive years), and (3) to investigate relationships between intrapopulational diversity and effective population size (Ne) as well as plant traits. (1) The German populations were strongly isolated from each other (pairwise FST= 0.29–0.60) and from all other populations (FST= 0.24–0.49). We found a pattern of near panmixis among the latter (FST= 0.15–0.35) with geographical distance explaining only 8% of the genetic variance. These results were congruent with a principal coordinate analysis (PCoA) and analysis using STRUCTURE to identify genetically coherent groups. These findings are in line with the strong physical barrier and historical constraints, resulting in separation of the German populations from the others. (2) We found pronounced genetic differences between consecutive cohorts of the German populations (pairwise FST= 0.23 and 0.31), which can be explained by local population history (land use, disturbance). (3) Genetic diversity within populations (Shannon index, HSh) was significantly correlated with Ne (RS= 0.733) and reflected a loss of diversity due to several demographic bottlenecks. Overall, we found that the genetic structure in G. bohemica is strongly influenced by historical periods of high connectivity and isolation as well as by marked

  8. Intraspecific Genetic Admixture and the Morphological Diversification of an Estuarine Fish Population Complex

    PubMed Central

    Legault, Michel

    2015-01-01

    The North-east American Rainbow smelt (Osmerus mordax) is composed of two glacial races first identified through the spatial distribution of two distinct mtDNA lineages. Contemporary breeding populations of smelt in the St. Lawrence estuary comprise contrasting mixtures of both lineages, suggesting that the two races came into secondary contact in this estuary. The overall objective of this study was to assess the role of intraspecific genetic admixture in the morphological diversification of the estuarine rainbow smelt population complex. The morphology of mixed-ancestry populations varied as a function of the relative contribution of the two races to estuarine populations, supporting the hypothesis of genetic admixture. Populations comprising both ancestral mtDNA races did not exhibit intermediate morphologies relative to pure populations but rather exhibited many traits that exceeded the parental trait values, consistent with the hypothesis of transgressive segregation. Evidence for genetic admixture at the level of the nuclear gene pool, however, provided only partial support for this hypothesis. Variation at nuclear AFLP markers revealed clear evidence of the two corresponding mtDNA glacial races. The admixture of the two races at the nuclear level is only pronounced in mixed-ancestry populations dominated by one of the mtDNA lineages, the same populations showing the greatest degree of morphological diversification and population structure. In contrast, mixed-ancestry populations dominated by the alternate mtDNA lineage showed little evidence of introgression of the nuclear genome, little morphological diversification and little contemporary population genetic structure. These results only partially support the hypothesis of transgressive segregation and may be the result of the differential effects of natural selection acting on admixed genomes from different sources. PMID:25856193

  9. Intraspecific genetic admixture and the morphological diversification of an estuarine fish population complex.

    PubMed

    Dodson, Julian J; Bourret, Audrey; Barrette, Marie France; Turgeon, Julie; Daigle, Gaétan; Legault, Michel; Lecomte, Frédéric

    2015-01-01

    The North-east American Rainbow smelt (Osmerus mordax) is composed of two glacial races first identified through the spatial distribution of two distinct mtDNA lineages. Contemporary breeding populations of smelt in the St. Lawrence estuary comprise contrasting mixtures of both lineages, suggesting that the two races came into secondary contact in this estuary. The overall objective of this study was to assess the role of intraspecific genetic admixture in the morphological diversification of the estuarine rainbow smelt population complex. The morphology of mixed-ancestry populations varied as a function of the relative contribution of the two races to estuarine populations, supporting the hypothesis of genetic admixture. Populations comprising both ancestral mtDNA races did not exhibit intermediate morphologies relative to pure populations but rather exhibited many traits that exceeded the parental trait values, consistent with the hypothesis of transgressive segregation. Evidence for genetic admixture at the level of the nuclear gene pool, however, provided only partial support for this hypothesis. Variation at nuclear AFLP markers revealed clear evidence of the two corresponding mtDNA glacial races. The admixture of the two races at the nuclear level is only pronounced in mixed-ancestry populations dominated by one of the mtDNA lineages, the same populations showing the greatest degree of morphological diversification and population structure. In contrast, mixed-ancestry populations dominated by the alternate mtDNA lineage showed little evidence of introgression of the nuclear genome, little morphological diversification and little contemporary population genetic structure. These results only partially support the hypothesis of transgressive segregation and may be the result of the differential effects of natural selection acting on admixed genomes from different sources.

  10. Ecological factors influence population genetic structure of European grey wolves.

    PubMed

    Pilot, Malgorzata; Jedrzejewski, Wlodzimierz; Branicki, Wojciech; Sidorovich, Vadim E; Jedrzejewska, Bogumila; Stachura, Krystyna; Funk, Stephan M

    2006-12-01

    Although the mechanisms controlling gene flow among populations are particularly important for evolutionary processes, they are still poorly understood, especially in the case of large carnivoran mammals with extensive continuous distributions. We studied the question of factors affecting population genetic structure in the grey wolf, Canis lupus, one of the most mobile terrestrial carnivores. We analysed variability in mitochondrial DNA and 14 microsatellite loci for a sample of 643 individuals from 59 localities representing most of the continuous wolf range in Eastern Europe. We tested an array of geographical, historical and ecological factors to check whether they may explain genetic differentiation among local wolf populations. We showed that wolf populations in Eastern Europe displayed nonrandom spatial genetic structure in the absence of obvious physical barriers to movement. Neither topographic barriers nor past fragmentation could explain spatial genetic structure. However, we found that the genetic differentiation among local populations was correlated with climate, habitat types, and wolf diet composition. This result shows that ecological processes may strongly influence the amount of gene flow among populations. We suggest natal-habitat-biased dispersal as an underlying mechanism linking population ecology with population genetic structure.

  11. Missing heritability of complex diseases: Enlightenment by genetic variants from intermediate phenotypes

    PubMed Central

    Blanco-Gómez, Adrián; Castillo-Lluva, Sonia; del Mar Sáez-Freire, María; Hontecillas-Prieto, Lourdes; Mao, Jian Hua; Castellanos-Martín, Andrés; Pérez-Losada, Jesus

    2016-01-01

    Diseases of complex origin have a component of quantitative genetics that contributes to their susceptibility and phenotypic variability. However, after several studies, a major part of the genetic component of complex phenotypes has still not been found, a situation known as “missing heritability”. Although there have been many hypotheses put forward to explain the reasons for the missing heritability, its definitive causes remain unknown. Complex diseases are caused by multiple intermediate phenotypes involved in their pathogenesis and, very often, each one of these intermediate phenotypes also has a component of quantitative inheritance. Here we propose that at least part of the missing heritability can be explained by the genetic component of intermediate phenotypes that is not detectable at the level of the main complex trait. At the same time, the identification of the genetic component of intermediate phenotypes provides an opportunity to identify part of the missing heritability of complex diseases. PMID:27241833

  12. Population genetic structure, genetic diversity, and natural history of the South American species of Nothofagus subgenus Lophozonia (Nothofagaceae) inferred from nuclear microsatellite data.

    PubMed

    Vergara, Rodrigo; Gitzendanner, Matthew A; Soltis, Douglas E; Soltis, Pamela S

    2014-06-01

    The effect of glaciation on the levels and patterns of genetic variation has been well studied in the Northern Hemisphere. However, although glaciation has undoubtedly shaped the genetic structure of plants in the Southern Hemisphere, fewer studies have characterized the effect, and almost none of them using microsatellites. Particularly, complex patterns of genetic structure might be expected in areas such as the Andes, where both latitudinal and altitudinal glacial advance and retreat have molded modern plant communities. We therefore studied the population genetics of three closely related, hybridizing species of Nothofagus (N. obliqua, N. alpina, and N. glauca, all of subgenus Lophozonia; Nothofagaceae) from Chile. To estimate population genetic parameters and infer the influence of the last ice age on the spatial and genetic distribution of these species, we examined and analyzed genetic variability at seven polymorphic microsatellite DNA loci in 640 individuals from 40 populations covering most of the ranges of these species in Chile. Populations showed no significant inbreeding and exhibited relatively high levels of genetic diversity (H E = 0.502-0.662) and slight, but significant, genetic structure (R ST = 8.7-16.0%). However, in N. obliqua, the small amount of genetic structure was spatially organized into three well-defined latitudinal groups. Our data may also suggest some introgression of N. alpina genes into N. obliqua in the northern populations. These results allowed us to reconstruct the influence of the last ice age on the genetic structure of these species, suggesting several centers of genetic diversity for N. obliqua and N. alpina, in agreement with the multiple refugia hypothesis.

  13. Population genetic structure, genetic diversity, and natural history of the South American species of Nothofagus subgenus Lophozonia (Nothofagaceae) inferred from nuclear microsatellite data

    PubMed Central

    Vergara, Rodrigo; Gitzendanner, Matthew A; Soltis, Douglas E; Soltis, Pamela S

    2014-01-01

    The effect of glaciation on the levels and patterns of genetic variation has been well studied in the Northern Hemisphere. However, although glaciation has undoubtedly shaped the genetic structure of plants in the Southern Hemisphere, fewer studies have characterized the effect, and almost none of them using microsatellites. Particularly, complex patterns of genetic structure might be expected in areas such as the Andes, where both latitudinal and altitudinal glacial advance and retreat have molded modern plant communities. We therefore studied the population genetics of three closely related, hybridizing species of Nothofagus (N. obliqua, N. alpina, and N. glauca, all of subgenus Lophozonia; Nothofagaceae) from Chile. To estimate population genetic parameters and infer the influence of the last ice age on the spatial and genetic distribution of these species, we examined and analyzed genetic variability at seven polymorphic microsatellite DNA loci in 640 individuals from 40 populations covering most of the ranges of these species in Chile. Populations showed no significant inbreeding and exhibited relatively high levels of genetic diversity (HE = 0.502–0.662) and slight, but significant, genetic structure (RST = 8.7–16.0%). However, in N. obliqua, the small amount of genetic structure was spatially organized into three well-defined latitudinal groups. Our data may also suggest some introgression of N. alpina genes into N. obliqua in the northern populations. These results allowed us to reconstruct the influence of the last ice age on the genetic structure of these species, suggesting several centers of genetic diversity for N. obliqua and N. alpina, in agreement with the multiple refugia hypothesis. PMID:25360279

  14. Fine-Scale Genetic Structure and Reproductive Biology of the Blueberry Pathogen Monilinia vaccinii-corymbosi.

    PubMed

    Burchhardt, Kathleen M; Miller, Megan E; Cline, William O; Cubeta, Marc A

    2017-02-01

    The fungus Monilinia vaccinii-corymbosi, a pathogen of Vaccinium spp., requires asexual and sexual spore production to complete its life cycle. A recent study found population structuring of M. vaccinii-corymbosi over a broad spatial scale in the United States. In this study, we examined fine-scale genetic structuring, temporal dynamics, and reproductive biology within a 125-by-132-m blueberry plot from 2010 to 2012. In total, 395 isolates of M. vaccinii-corymbosi were sampled from infected shoots and fruit to examine their multilocus haplotype (MLH) using microsatellite markers. The MLH of 190 single-ascospore isolates from 21 apothecia was also determined. Little to no genetic differentiation and unrestricted gene flow were detected among four sampled time points and between infected tissue types. Discriminant analysis of principal components suggested genetic structuring within the field, with at least K = 3 genetically distinct clusters maintained over four sampled time points. Single-ascospore progeny from eight apothecia had identical MLH and at least two distinct MLH were detected from 13 apothecia. Tests for linkage disequilibrium suggested that genetically diverse ascospore progeny were the product of recombination. This study supports the idea that the fine-scale dynamics of M. vaccinii-corymbosi may be complex, with genetic structuring, inbreeding, and outcrossing detected in the study area.

  15. Genetic diversity and genetic structure of the Siberian roe deer (Capreolus pygargus) populations from Asia.

    PubMed

    Lee, Yun Sun; Markov, Nickolay; Voloshina, Inna; Argunov, Alexander; Bayarlkhagva, Damdingiin; Oh, Jang Geun; Park, Yong-Su; Min, Mi-Sook; Lee, Hang; Kim, Kyung Seok

    2015-08-18

    The roe deer, Capreolus sp., is one of the most widespread meso-mammals of Palearctic distribution, and includes two species, the European roe deer, C. capreolus inhabiting mainly Europe, and the Siberian roe deer, C. pygargus, distributed throughout continental Asia. Although there are a number of genetic studies concerning European roe deer, the Siberian roe deer has been studied less, and none of these studies use microsatellite markers. Natural processes have led to genetic structuring in wild populations. To understand how these factors have affected genetic structure and connectivity of Siberian roe deer, we investigated variability at 12 microsatellite loci for Siberian roe deer from ten localities in Asia. Moderate levels of genetic diversity (H(E) = 0.522 to 0.628) were found in all populations except in Jeju Island, South Korea, where the diversity was lowest (H(E) = 0.386). Western populations showed relatively low genetic diversity and higher degrees of genetic differentiation compared with eastern populations (mean Ar = 3.54 (east), 2.81 (west), mean F(ST) = 0.122). Bayesian-based clustering analysis revealed the existence of three genetically distinct groups (clusters) for Siberian roe deer, which comprise of the Southeastern group (Mainland Korea, Russian Far East, Trans-Baikal region and Northern part of Mongolia), Northwestern group (Western Siberia and Ural in Russia) and Jeju Island population. Genetic analyses including AMOVA (F(RT) = 0.200), Barrier and PCA also supported genetic differentiation among regions separated primarily by major mountain ridges, suggesting that mountains played a role in the genetic differentiation of Siberian roe deer. On the other hand, genetic evidence also suggests an ongoing migration that may facilitate genetic admixture at the border areas between two groups. Our results reveal an apparent pattern of genetic differentiation among populations inhabiting Asia, showing moderate levels of genetic diversity with an

  16. Genetic variability and relationships for populations of Cerastoderma edule and of the C. Glaucum complex

    NASA Astrophysics Data System (ADS)

    Hummel, H.; Wolowicz, M.; Bogaards, R. H.

    Genetic variability and relationships of populations of the cockles Cerastoderma edule and of the C. glaucum complex in Europe were determined by means of isoenzyme electrophoresis. Distinct isoenzyme markers allowed a clear distinction between these two taxa. C edule showed a higher genetic intra-population variability than the other cockle species. The imbalance of the genotypes within popuulation and the inter-population differentiation of the C. glaucum complex are stronger than in C. edule. The genetic variability is related to the different habitats of the species, the members of the C. glaucum complex living in more isolated areas and having more limited gene flow.

  17. Genetic Complexity in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin

    PubMed Central

    Park, Soo-Young; Ludwig, Michael Z.; Tamarina, Natalia A.; He, Bin Z.; Carl, Sarah H.; Dickerson, Desiree A.; Barse, Levi; Arun, Bharath; Williams, Calvin L.; Miles, Cecelia M.; Philipson, Louis H.; Steiner, Donald F.; Bell, Graeme I.; Kreitman, Martin

    2014-01-01

    Drosophila melanogaster has been widely used as a model of human Mendelian disease, but its value in modeling complex disease has received little attention. Fly models of complex disease would enable high-resolution mapping of disease-modifying loci and the identification of novel targets for therapeutic intervention. Here, we describe a fly model of permanent neonatal diabetes mellitus and explore the complexity of this model. The approach involves the transgenic expression of a misfolded mutant of human preproinsulin, hINSC96Y, which is a cause of permanent neonatal diabetes. When expressed in fly imaginal discs, hINSC96Y causes a reduction of adult structures, including the eye, wing, and notum. Eye imaginal discs exhibit defects in both the structure and the arrangement of ommatidia. In the wing, expression of hINSC96Y leads to ectopic expression of veins and mechano-sensory organs, indicating disruption of wild-type signaling processes regulating cell fates. These readily measurable “disease” phenotypes are sensitive to temperature, gene dose, and sex. Mutant (but not wild-type) proinsulin expression in the eye imaginal disc induces IRE1-mediated XBP1 alternative splicing, a signal for endoplasmic reticulum stress response activation, and produces global change in gene expression. Mutant hINS transgene tester strains, when crossed to stocks from the Drosophila Genetic Reference Panel, produce F1 adults with a continuous range of disease phenotypes and large broad-sense heritability. Surprisingly, the severity of mutant hINS-induced disease in the eye is not correlated with that in the notum in these crosses, nor with eye reduction phenotypes caused by the expression of two dominant eye mutants acting in two different eye development pathways, Drop (Dr) or Lobe (L), when crossed into the same genetic backgrounds. The tissue specificity of genetic variability for mutant hINS-induced disease has, therefore, its own distinct signature. The genetic dominance of

  18. Population genetic structure of Meccus longipennis (Hemiptera, Reduviidae, Triatominae), vector of Chagas disease in West Mexico.

    PubMed

    Brenière, Simone Frédérique; Waleckx, Etienne; Magallón-Gastélum, Ezequiel; Bosseno, Marie-France; Hardy, Xavier; Ndo, Cyrille; Lozano-Kasten, Felipe; Barnabé, Christian; Kengne, Pierre

    2012-03-01

    The originally wild species of the Meccus complex are important vectors of Chagas disease in Mexico. In West Mexico, Meccus longipennis plays an important epidemiological role. To understand the genetic structure of the domestic and wild populations of this species, a preliminary study with five polymorphic microsatellite loci was conducted. The population genetics analysis showed high structuring between peridomestic biotopes, with breeding subunits detected in a single peridomestic structure. In the wild environment, two genetic patterns were observed according to the biotope, possible breeding subunits in large rocky formations and a larger panmictic unit in agropastoral areas, suggesting considerable dispersal of bugs in this biotope. Moreover, the discovery of two foci of wild populations at the edge of Guadalajara city raises the question of new urban areas where the phenomenon of bug incursions into households could constitute a risk of transmission of Chagas disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. The genetic structure of a relict population of wood frogs

    USGS Publications Warehouse

    Scherer, Rick; Muths, Erin; Noon, Barry; Oyler-McCance, Sara

    2012-01-01

    Habitat fragmentation and the associated reduction in connectivity between habitat patches are commonly cited causes of genetic differentiation and reduced genetic variation in animal populations. We used eight microsatellite markers to investigate genetic structure and levels of genetic diversity in a relict population of wood frogs (Lithobates sylvatica) in Rocky Mountain National Park, Colorado, where recent disturbances have altered hydrologic processes and fragmented amphibian habitat. We also estimated migration rates among subpopulations, tested for a pattern of isolation-by-distance, and looked for evidence of a recent population bottleneck. The results from the clustering algorithm in Program STRUCTURE indicated the population is partitioned into two genetic clusters (subpopulations), and this result was further supported by factorial component analysis. In addition, an estimate of FST (FST = 0.0675, P value \\0.0001) supported the genetic differentiation of the two clusters. Estimates of migration rates among the two subpopulations were low, as were estimates of genetic variability. Conservation of the population of wood frogs may be improved by increasing the spatial distribution of the population and improving gene flow between the subpopulations. Construction or restoration of wetlands in the landscape between the clusters has the potential to address each of these objectives.

  20. Mitochondrial DNA analysis of Tunisians reveals a mosaic genetic structure with recent population expansion.

    PubMed

    Frigi, S; Mota-Vieira, L; Cherni, L; van Oven, M; Pires, R; Boussetta, S; El-Gaaied, A Ben Ammar

    2017-05-19

    Tunisia is a country of great interest for human population genetics due to its strategic geographic position and rich human settlement history. These factors significantly contributed to the genetic makeup of present-day Tunisians harbouring components of diverse geographic origins. Here, we investigated the genetic structure of Tunisians by performing a mitochondrial DNA (mtDNA) comparison of 15 Tunisian population groups, in order to explore their complex genetic landscape. All Tunisian data were also analysed against 40 worldwide populations. Statistical results (Tajima's D and Fu's FS tests) suggested recent population expansion for the majority of studied populations, as well as showed (AMOVA test) that all populations were significantly different from each other, which is evidence of population structure even if it is not guided by geographic and ethnic effects. Gene flow analysis revealed the assignment of Tunisians to multiple ancestries, which agrees with their genetic heterogeneity. The resulting picture for the mtDNA pool confirms the evidence of a recent expansion of the Tunisian population and is in accordance with a mosaic structure, composed by North African, Middle Easterner, European and Sub-Saharan lineages, resulting from a complex settlement history. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Genetic covariance structure of incisor crown size in twins.

    PubMed

    Dempsey, P J; Townsend, G C; Martin, N G; Neale, M C

    1995-07-01

    Previous studies of tooth size in twins and their families have suggested a high degree of genetic control, although there have been difficulties separating the various genetic and environmental effects. A genetic analysis of variation in crown size of the permanent incisors of South Australian twins was carried out, with structural equation modeling used to determine the relative contributions of genetic and environmental factors. Maximum mesiodistal crown dimensions of maxillary and mandibular permanent incisors were recorded from dental models of 298 pairs of twins, including 149 monozygous (MZ) and 149 dizygous (DZ) pairs. The analysis revealed that: (i) an adequate fit required additive genetic and unique environmental components; (ii) augmenting the model with non-additive genetic variation did not lead to a significant improvement in fit; (iii) there was evidence of shared environmental influences in the upper central incisors of males; (iv) the additive genetic component constituted a general factor loading on all eight teeth, with group factors loading on antimeric pairs of teeth; (v) unique environmental effects were mostly variable-specific; (vi) most factor loadings on antimeric tooth pairs could be constrained to be equal, indicating a symmetry of genetic and environmental influences between left and right sides; and (vii) estimated heritability of the incisor mesiodistal dimensions varied from 0.81 to 0.91.

  2. Genetic Structure of First Nation Communities in the Pacific Northwest.

    PubMed

    Hughes, Cris E; Rogers, Mary P; Owings, Amanda C; Petzelt, Barbara; Mitchell, Joycelynn; Harry, Harold; Williams, Theresa; Goldberg, Dena; Labuda, Damian; Smith, David Glenn; Cybulski, Jerome S; Malhi, Ripan S

    2016-10-01

    This study presents genetic data for nine Native American populations from northern North America. Analyses of genetic variation focus on the Pacific Northwest (PNW). Using mitochondrial, Y chromosomal, and autosomal DNA variants, we aimed to more closely address the relationships of geography and language with present genetic diversity among the regional PNW Native American populations. Patterns of genetic diversity exhibited by the three genetic systems were consistent with our hypotheses: genetic variation was more strongly explained by geographic proximity than by linguistic structure. Our findings were corroborated through a variety on analytic approaches, with the unrooted trees for the three genetic systems consistently separating inland from coastal PNW populations. Furthermore, analyses of molecular variance support the trends exhibited by the unrooted trees, with geographic partitioning of PNW populations (FCT = 19.43%, p = 0.010 ± 0.009) accounting for over twice as much of the observed genetic variation as linguistic partitioning of the same populations (FCT = 9.15%, p = 0.193 ± 0.013). These findings demonstrate a consensus with previous PNW population studies examining the relationships of genome-wide variation, mitochondrial haplogroup frequencies, and skeletal morphology with geography and language.

  3. Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India

    PubMed Central

    Gautam, Vikas; Patil, Prashant P.; Kumar, Sunil; Midha, Samriti; Kaur, Mandeep; Kaur, Satinder; Singh, Meenu; Mali, Swapna; Shastri, Jayanthi; Arora, Anita; Ray, Pallab; Patil, Prabhu B.

    2016-01-01

    Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005–2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient’s isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen. PMID:27767197

  4. Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India.

    PubMed

    Gautam, Vikas; Patil, Prashant P; Kumar, Sunil; Midha, Samriti; Kaur, Mandeep; Kaur, Satinder; Singh, Meenu; Mali, Swapna; Shastri, Jayanthi; Arora, Anita; Ray, Pallab; Patil, Prabhu B

    2016-10-21

    Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005-2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient's isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen.

  5. Phenotypic differentiation of the Solidago virgaurea complex along an elevational gradient: Insights from a common garden experiment and population genetics.

    PubMed

    Hirano, Masaaki; Sakaguchi, Shota; Takahashi, Koichi

    2017-09-01

    Plant species distributed along wide elevational or latitudinal gradients show phenotypic variation due to their heterogeneous habitats. This study investigated whether phenotypic variation in populations of the Solidago virgaurea complex along an elevational gradient is caused by genetic differentiation. A common garden experiment was based on seeds collected from nine populations of the S. virgaurea complex growing at elevations from 1,597 m to 2,779 m a.s.l. on Mt. Norikura in central Japan. Population genetic analyses with microsatellite markers were used to infer the genetic structure and levels of gene flow between populations. Leaf mass per area was lower, while leaf nitrogen and chlorophyll concentrations were greater for higher elevations at which seeds were originally collected. For reproductive traits, plants derived from higher elevations had larger flower heads on shorter stems and flowering started earlier. These elevational changes in morphology were consistent with the clines in the field, indicating that phenotypic variation along the elevational gradient would have been caused by genetic differentiation. However, population genetic analysis using 16 microsatellite loci suggested an extremely low level of genetic differentiation of neutral genes among the nine populations. Analysis of molecular variance also indicated that most genetic variation was partitioned into individuals within a population, and the genetic differentiation among the populations was not significant. This study suggests that genome regions responsible for adaptive traits may differ among the populations despite the existence of gene flow and that phenotypic variation of the S. virgaurea complex along the elevational gradient is maintained by strong selection pressure.

  6. Genetic structuring across marine biogeographic boundaries in rocky shore invertebrates.

    PubMed

    Villamor, Adriana; Costantini, Federica; Abbiati, Marco

    2014-01-01

    Biogeography investigates spatial patterns of species distribution. Discontinuities in species distribution are identified as boundaries between biogeographic areas. Do these boundaries affect genetic connectivity? To address this question, a multifactorial hierarchical sampling design, across three of the major marine biogeographic boundaries in the central Mediterranean Sea (Ligurian-Tyrrhenian, Tyrrhenian-Ionian and Ionian-Adriatic) was carried out. Mitochondrial COI sequence polymorphism of seven species of Mediterranean benthic invertebrates was analysed. Two species showed significant genetic structure across the Tyrrhenian-Ionian boundary, as well as two other species across the Ionian Sea, a previously unknown phylogeographic barrier. The hypothesized barrier in the Ligurian-Tyrrhenian cannot be detected in the genetic structure of the investigated species. Connectivity patterns across species at distances up to 800 km apart confirmed that estimates of pelagic larval dispersal were poor predictors of the genetic structure. The detected genetic discontinuities seem more related to the effect of past historical events, though maintained by present day oceanographic processes. Multivariate statistical tools were used to test the consistency of the patterns across species, providing a conceptual framework for across-species barrier locations and strengths. Additional sequences retrieved from public databases supported our findings. Heterogeneity of phylogeographic patterns shown by the 7 investigated species is relevant to the understanding of the genetic diversity, and carry implications for conservation biology.

  7. Genetic diversity and population structure of cucumber (Cucumis sativus L.).

    PubMed

    Lv, Jing; Qi, Jianjian; Shi, Qiuxiang; Shen, Di; Zhang, Shengping; Shao, Guangjin; Li, Hang; Sun, Zhanyong; Weng, Yiqun; Shang, Yi; Gu, Xingfang; Li, Xixiang; Zhu, Xiaoguo; Zhang, Jinzhe; van Treuren, Robbert; van Dooijeweert, Willem; Zhang, Zhonghua; Huang, Sanwen

    2012-01-01

    Knowing the extent and structure of genetic variation in germplasm collections is essential for the conservation and utilization of biodiversity in cultivated plants. Cucumber is the fourth most important vegetable crop worldwide and is a model system for other Cucurbitaceae, a family that also includes melon, watermelon, pumpkin and squash. Previous isozyme studies revealed a low genetic diversity in cucumber, but detailed insights into the crop's genetic structure and diversity are largely missing. We have fingerprinted 3,342 accessions from the Chinese, Dutch and U.S. cucumber collections with 23 highly polymorphic Simple Sequence Repeat (SSR) markers evenly distributed in the genome. The data reveal three distinct populations, largely corresponding to three geographic regions. Population 1 corresponds to germplasm from China, except for the unique semi-wild landraces found in Xishuangbanna in Southwest China and East Asia; population 2 to Europe, America, and Central and West Asia; and population 3 to India and Xishuangbanna. Admixtures were also detected, reflecting hybridization and migration events between the populations. The genetic background of the Indian germplasm is heterogeneous, indicating that the Indian cucumbers maintain a large proportion of the genetic diversity and that only a small fraction was introduced to other parts of the world. Subsequently, we defined a core collection consisting of 115 accessions and capturing over 77% of the SSR alleles. Insight into the genetic structure of cucumber will help developing appropriate conservation strategies and provides a basis for population-level genome sequencing in cucumber.

  8. Genetic Diversity and Population Structure of Cucumber (Cucumis sativus L.)

    PubMed Central

    Shao, Guangjin; Li, Hang; Sun, Zhanyong; Weng, Yiqun; Shang, Yi; Gu, Xingfang; Li, Xixiang; Zhu, Xiaoguo; Zhang, Jinzhe; van Treuren, Robbert; van Dooijeweert, Willem; Zhang, Zhonghua; Huang, Sanwen

    2012-01-01

    Knowing the extent and structure of genetic variation in germplasm collections is essential for the conservation and utilization of biodiversity in cultivated plants. Cucumber is the fourth most important vegetable crop worldwide and is a model system for other Cucurbitaceae, a family that also includes melon, watermelon, pumpkin and squash. Previous isozyme studies revealed a low genetic diversity in cucumber, but detailed insights into the crop's genetic structure and diversity are largely missing. We have fingerprinted 3,342 accessions from the Chinese, Dutch and U.S. cucumber collections with 23 highly polymorphic Simple Sequence Repeat (SSR) markers evenly distributed in the genome. The data reveal three distinct populations, largely corresponding to three geographic regions. Population 1 corresponds to germplasm from China, except for the unique semi-wild landraces found in Xishuangbanna in Southwest China and East Asia; population 2 to Europe, America, and Central and West Asia; and population 3 to India and Xishuangbanna. Admixtures were also detected, reflecting hybridization and migration events between the populations. The genetic background of the Indian germplasm is heterogeneous, indicating that the Indian cucumbers maintain a large proportion of the genetic diversity and that only a small fraction was introduced to other parts of the world. Subsequently, we defined a core collection consisting of 115 accessions and capturing over 77% of the SSR alleles. Insight into the genetic structure of cucumber will help developing appropriate conservation strategies and provides a basis for population-level genome sequencing in cucumber. PMID:23071663

  9. Genetic Structuring across Marine Biogeographic Boundaries in Rocky Shore Invertebrates

    PubMed Central

    Villamor, Adriana; Costantini, Federica; Abbiati, Marco

    2014-01-01

    Biogeography investigates spatial patterns of species distribution. Discontinuities in species distribution are identified as boundaries between biogeographic areas. Do these boundaries affect genetic connectivity? To address this question, a multifactorial hierarchical sampling design, across three of the major marine biogeographic boundaries in the central Mediterranean Sea (Ligurian-Tyrrhenian, Tyrrhenian-Ionian and Ionian-Adriatic) was carried out. Mitochondrial COI sequence polymorphism of seven species of Mediterranean benthic invertebrates was analysed. Two species showed significant genetic structure across the Tyrrhenian-Ionian boundary, as well as two other species across the Ionian Sea, a previously unknown phylogeographic barrier. The hypothesized barrier in the Ligurian-Tyrrhenian cannot be detected in the genetic structure of the investigated species. Connectivity patterns across species at distances up to 800 km apart confirmed that estimates of pelagic larval dispersal were poor predictors of the genetic structure. The detected genetic discontinuities seem more related to the effect of past historical events, though maintained by present day oceanographic processes. Multivariate statistical tools were used to test the consistency of the patterns across species, providing a conceptual framework for across-species barrier locations and strengths. Additional sequences retrieved from public databases supported our findings. Heterogeneity of phylogeographic patterns shown by the 7 investigated species is relevant to the understanding of the genetic diversity, and carry implications for conservation biology. PMID:24983738

  10. A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

    USDA-ARS?s Scientific Manuscript database

    The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identi...

  11. Genetic diversity of Saccharum complex using ISSR markers.

    PubMed

    Oliveira, L A R; Machado, C A; Cardoso, M N; Oliveira, A C A; Amaral, A L; Rabbani, A R C; Silva, A V C; Ledo, A S

    2017-09-21

    Sugarcane (Saccharum sp, Poaceae) is native to Southeast Asia, and due to growing demand as raw material, its cultivation recently expanded to new frontiers. The genetic diversity analysis is essential for targeting strategies in the formation and maintenance of a germplasm. This study aimed to assess the genetic diversity of 26 accessions of sugarcane from the Active Germplasm Bank of Embrapa Coastal Tablelands, using inter-simple sequence repeat (ISSR) molecular markers. Sixteen primers were used, resulting in 87 fragments with 91.13% of polymorphism. The similarity of the individuals ranged between 0.22 and 0.87. Individuals RB867515 and RB92579 were closer genetically, and the most distant ones were PI240785 and NSL 291970. Four distinct clusters were formed, using UPGMA. This information can be used to prioritize the selection of accessions for the conduction of hybridization in breeding and germplasm exchange actions.

  12. The psoriasis genetics as a model of complex disease.

    PubMed

    Giardina, Emiliano; Sinibaldi, Cecilia; Novelli, Giuseppe

    2004-06-01

    Psoriasis [OMIM*177900] is a common, chronic and papulosquamous inflammatory skin disease affecting approximately 2% of Caucasian. However, this disorder is rare among Japanese, Eskimos, West Africans and North American blacks and very uncommon in North American and South American natives. The causes for these variations are likely to be both genetic and environmental. Population-based studies and twin studies indicate that psoriasis is a heritable disease with a polygenic mode of inheritance with variable penetrance. Independent genome-wide scans have suggested the involvement of a large number of chromosomal regions (loci), and many candidate genes have been proposed. We discuss genetic approaches to the disease, results and interpretations of relevant studies, as well as future perspectives. Understanding the genetic basis of psoriasis will represent a major advance in our understanding of the disease and will reveal novel disease-specific biologic pathways.

  13. Dominant Genetic Variation and Missing Heritability for Human Complex Traits: Insights from Twin versus Genome-wide Common SNP Models.

    PubMed

    Chen, Xu; Kuja-Halkola, Ralf; Rahman, Iffat; Arpegård, Johannes; Viktorin, Alexander; Karlsson, Robert; Hägg, Sara; Svensson, Per; Pedersen, Nancy L; Magnusson, Patrik K E

    2015-11-05

    In order to further illuminate the potential role of dominant genetic variation in the "missing heritability" debate, we investigated the additive (narrow-sense heritability, h(2)) and dominant (δ(2)) genetic variance for 18 human complex traits. Within the same study base (10,682 Swedish twins), we calculated and compared the estimates from classic twin-based structural equation model with SNP-based genomic-relatedness-matrix restricted maximum likelihood [GREML(d)] method. Contributions of δ(2) were evident for 14 traits in twin models (average δ(2)twin = 0.25, range 0.14-0.49), two of which also displayed significant δ(2) in the GREMLd analyses (triglycerides δ(2)SNP = 0.28 and waist circumference δ(2)SNP = 0.19). On average, the proportion of h(2)SNP/h(2)twin was 70% for ADE-fitted traits (for which the best-fitting model included additive and dominant genetic and unique environmental components) and 31% for AE-fitted traits (for which the best-fitting model included additive genetic and unique environmental components). Independent evidence for contribution from shared environment, also in ADE-fitted traits, was obtained from self-reported within-pair contact frequency and age at separation. We conclude that despite the fact that additive genetics appear to constitute the bulk of genetic influences for most complex traits, dominant genetic variation might often be masked by shared environment in twin and family studies and might therefore have a more prominent role than what family-based estimates often suggest. The risk of erroneously attributing all inherited genetic influences (additive and dominant) to the h(2) in too-small twin studies might also lead to exaggerated "missing heritability" (the proportion of h(2) that remains unexplained by SNPs). Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  14. Genetic structure in four West African population groups.

    PubMed

    Adeyemo, Adebowale A; Chen, Guanjie; Chen, Yuanxiu; Rotimi, Charles

    2005-06-24

    Africa contains the most genetically divergent group of continental populations and several studies have reported that African populations show a high degree of population stratification. In this regard, it is important to investigate the potential for population genetic structure or stratification in genetic epidemiology studies involving multiple African populations. The presences of genetic sub-structure, if not properly accounted for, have been reported to lead to spurious association between a putative risk allele and a disease. Within the context of the Africa America Diabetes Mellitus (AADM) Study (a genetic epidemiologic study of type 2 diabetes mellitus in West Africa), we have investigated population structure or stratification in four ethnic groups in two countries (Akan and Gaa-Adangbe from Ghana, Yoruba and Igbo from Nigeria) using data from 372 autosomal microsatellite loci typed in 493 unrelated persons (986 chromosomes). There was no significant population genetic structure in the overall sample. The smallest probability is associated with an inferred cluster of 1 and little of the posterior probability is associated with a higher number of inferred clusters. The distribution of members of the sample to inferred clusters is consistent with this finding; roughly the same proportion of individuals from each group is assigned to each cluster with little variation between the ethnic groups. Analysis of molecular variance (AMOVA) showed that the between-population component of genetic variance is less than 0.1% in contrast to 99.91% for the within population component. Pair-wise genetic distances between the four ethnic groups were also very similar. Nonetheless, the small between-population genetic variance was sufficient to distinguish the two Ghanaian groups from the two Nigerian groups. There was little evidence for significant population substructure in the four major West African ethnic groups represented in the AADM study sample. Ethnicity

  15. Structure and genetics of circular bacteriocins.

    PubMed

    van Belkum, Marco J; Martin-Visscher, Leah A; Vederas, John C

    2011-08-01

    Circular bacteriocins are antimicrobial peptides produced by a variety of Gram-positive bacteria. They are part of a growing family of ribosomally synthesized peptides with a head-to-tail cyclization of their backbone that are found in mammals, plants, fungi and bacteria and are exceptionally stable. These bacteriocins permeabilize the membrane of sensitive bacteria, causing loss of ions and dissipation of the membrane potential. Most circular bacteriocins probably adopt a common 3D structure consisting of four or five α-helices encompassing a hydrophobic core. This review compares the various structures, as well as the gene clusters that encode circular bacteriocins, and discusses the biogenesis of this unique class of bacteriocins.

  16. Evolutionary genetics: inheritance of a complex pollination syndrome.

    PubMed

    Wright, Kevin M; Bomblies, Kirsten

    2013-06-17

    How adaptive traits that are controlled by multiple genes evolve is an intriguing question in evolutionary genetics. A recent study shows that tight linkage allows genes that contribute to a multitrait pollination syndrome to be inherited together as a unit. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Evaluating empirical bounds on complex disease genetic architecture

    PubMed Central

    Agarwala, Vineeta; Flannick, Jason; Sunyaev, Shamil; Altshuler, David

    2014-01-01

    The genetic architecture of human diseases governs the success of genetic mapping and the future of personalized medicine. Although numerous studies have queried the genetic basis of common disease, contradictory hypotheses have been advocated about features of genetic architecture (e.g., the contribution of rare vs. common variants). We developed an integrated simulation framework, calibrated to empirical data, to enable systematic evaluation of such hypotheses. For type 2 diabetes (T2D), two simple parameters – (a) the target size for causal mutation and (b) the coupling between selection and phenotypic effect – define a broad space of architectures. While extreme models are excluded, many models remain consistent with epidemiology, linkage, and genome-wide association studies for T2D, including those where rare variants explain little (<25%) or most (>80%) of heritability. Ongoing sequencing and genotyping studies will further constrain architecture, but very large samples (e.g., >250K unselected individuals) will be required to localize most of the heritability underlying traits like T2D. PMID:24141362

  18. Population genetic structure in a social landscape: barley in a traditional Ethiopian agricultural system

    PubMed Central

    Samberg, Leah H; Fishman, Lila; Allendorf, Fred W

    2013-01-01

    Conservation strategies are increasingly driven by our understanding of the processes and patterns of gene flow across complex landscapes. The expansion of population genetic approaches into traditional agricultural systems requires understanding how social factors contribute to that landscape, and thus to gene flow. This study incorporates extensive farmer interviews and population genetic analysis of barley landraces (Hordeum vulgare) to build a holistic picture of farmer-mediated geneflow in an ancient, traditional agricultural system in the highlands of Ethiopia. We analyze barley samples at 14 microsatellite loci across sites at varying elevations and locations across a contiguous mountain range, and across farmer-identified barley types and management strategies. Genetic structure is analyzed using population-based and individual-based methods, including measures of population differentiation and genetic distance, multivariate Principal Coordinate Analysis, and Bayesian assignment tests. Phenotypic analysis links genetic patterns to traits identified by farmers. We find that differential farmer management strategies lead to markedly different patterns of population structure across elevation classes and barley types. The extent to which farmer seed management appears as a stronger determinant of spatial structure than the physical landscape highlights the need for incorporation of social, landscape, and genetic data for the design of conservation strategies in human-influenced landscapes. PMID:24478796

  19. Genome evolution predicts genetic interactions in protein complexes and reveals cancer drug targets

    PubMed Central

    Lu, Xiaowen; Kensche, Philip R.; Huynen, Martijn A.; Notebaart, Richard A.

    2013-01-01

    Genetic interactions reveal insights into cellular function and can be used to identify drug targets. Here we construct a new model to predict negative genetic interactions in protein complexes by exploiting the evolutionary history of genes in parallel converging pathways in metabolism. We evaluate our model with protein complexes of Saccharomyces cerevisiae and show that the predicted protein pairs more frequently have a negative genetic interaction than random proteins from the same complex. Furthermore, we apply our model to human protein complexes to predict novel cancer drug targets, and identify 20 candidate targets with empirical support and 10 novel targets amenable to further experimental validation. Our study illustrates that negative genetic interactions can be predicted by systematically exploring genome evolution, and that this is useful to identify novel anti-cancer drug targets. PMID:23851603

  20. Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

    PubMed Central

    Yadav, Anupama; Dhole, Kaustubh

    2016-01-01

    Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets. PMID:28172852

  1. Spatial and temporal genetic structure in a hybrid cordgrass invasion.

    PubMed

    Sloop, C M; Ayres, D R; Strong, D R

    2011-04-01

    Invasive hybrids and their spread dynamics pose unique opportunities to study evolutionary processes. Invasive hybrids of native Spartina foliosa and introduced S. alterniflora have expanded throughout San Francisco Bay intertidal habitats within the past 35 years by deliberate plantation and seeds floating on the tide. Our goals were to assess spatial and temporal scales of genetic structure in Spartina hybrid populations within the context of colonization history. We genotyped adult and seedling Spartina using 17 microsatellite loci and mapped their locations in three populations. All sampled seedlings were hybrids. Bayesian ordination analysis distinguished hybrid populations from parent species, clearly separated the population that originated by plantation from populations that originated naturally by seed and aligned most seedlings within each population. Population genetic structure estimated by analysis of molecular variance was substantial (F(ST)=0.21). Temporal genetic structure among age classes varied highly between populations. At one population, the divergence between adults and 2004 seedlings was low (F(ST)=0.02) whereas at another population this divergence was high (F(ST)=0.26). This latter result was consistent with local recruitment of self-fertilized seed produced by only a few parental plants. We found fine-scale spatial genetic structure at distances less than ∼200 m, further supporting local seed and/or pollen dispersal. We posit a few self-fertile plants dominating local recruitment created substantial spatial genetic structure despite initial long-distance, human dispersal of hybrid Spartina through San Francisco Bay. Fine-scale genetic structure may more strongly develop when local recruits are dominated by the offspring of a few self-fertile plants.

  2. Structural analysis of DNA complexation with cationic lipids

    PubMed Central

    Marty, Regis; N'soukpoé-Kossi, Christophe N.; Charbonneau, David; Weinert, Carl Maximilian; Kreplak, Laurent; Tajmir-Riahi, Heidar-Ali

    2009-01-01

    Complexes of cationic liposomes with DNA are promising tools to deliver genetic information into cells for gene therapy and vaccines. Electrostatic interaction is thought to be the major force in lipid–DNA interaction, while lipid-base binding and the stability of cationic lipid–DNA complexes have been the subject of more debate in recent years. The aim of this study was to examine the complexation of calf-thymus DNA with cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioctadecyldimethylammoniumbromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE), at physiological condition, using constant DNA concentration and various lipid contents. Fourier transform infrared (FTIR), UV-visible, circular dichroism spectroscopic methods and atomic force microscopy were used to analyse lipid-binding site, the binding constant and the effects of lipid interaction on DNA stability and conformation. Structural analysis showed a strong lipid–DNA interaction via major and minor grooves and the backbone phosphate group with overall binding constants of KChol = 1.4 (±0.5) × 104 M−1, KDDAB = 2.4 (±0.80) × 104 M−1, KDOTAP = 3.1 (±0.90) × 104 M−1 and KDOPE = 1.45 (± 0.60) × 104 M−1. The order of stability of lipid–DNA complexation is DOTAP>DDAB>DOPE>Chol. Hydrophobic interactions between lipid aliphatic tails and DNA were observed. Chol and DOPE induced a partial B to A-DNA conformational transition, while a partial B to C-DNA alteration occurred for DDAB and DOTAP at high lipid concentrations. DNA aggregation was observed at high lipid content. PMID:19103664

  3. Is there a genetic solution to bovine respiratory disease complex?

    USDA-ARS?s Scientific Manuscript database

    Bovine respiratory disease complex (BRDC) is a complex multi-factor disease, which increases costs and reduces revenue from feedlot cattle. Multiple stressors and pathogens (viral and bacterial) have been implicated in the etiology of BRDC, therefore multiple approaches will be needed to evaluate a...

  4. Genetic simulation tools for post-genome wide association studies of complex diseases.

    PubMed

    Chen, Huann-Sheng; Hutter, Carolyn M; Mechanic, Leah E; Amos, Christopher I; Bafna, Vineet; Hauser, Elizabeth R; Hernandez, Ryan D; Li, Chun; Liberles, David A; McAllister, Kimberly; Moore, Jason H; Paltoo, Dina N; Papanicolaou, George J; Peng, Bo; Ritchie, Marylyn D; Rosenfeld, Gabriel; Witte, John S; Gillanders, Elizabeth M; Feuer, Eric J

    2015-01-01

    Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high-throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled "Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases" at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were to (1) identify opportunities, challenges, and resource needs for the development and application of genetic simulation models; (2) improve the integration of tools for modeling and analysis of simulated data; and (3) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting, the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation. © 2014 WILEY PERIODICALS, INC.

  5. Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases

    PubMed Central

    Amos, Christopher I.; Bafna, Vineet; Hauser, Elizabeth R.; Hernandez, Ryan D.; Li, Chun; Liberles, David A.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Papanicolaou, George J.; Peng, Bo; Ritchie, Marylyn D.; Rosenfeld, Gabriel; Witte, John S.

    2014-01-01

    Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high-throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled “Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases” at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were to: (i) identify opportunities, challenges and resource needs for the development and application of genetic simulation models; (ii) improve the integration of tools for modeling and analysis of simulated data; and (iii) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation. PMID:25371374

  6. Immune allied genetic algorithm for Bayesian network structure learning

    NASA Astrophysics Data System (ADS)

    Song, Qin; Lin, Feng; Sun, Wei; Chang, KC

    2012-06-01

    Bayesian network (BN) structure learning is a NP-hard problem. In this paper, we present an improved approach to enhance efficiency of BN structure learning. To avoid premature convergence in traditional single-group genetic algorithm (GA), we propose an immune allied genetic algorithm (IAGA) in which the multiple-population and allied strategy are introduced. Moreover, in the algorithm, we apply prior knowledge by injecting immune operator to individuals which can effectively prevent degeneration. To illustrate the effectiveness of the proposed technique, we present some experimental results.

  7. Understanding macroalgal dispersal in a complex hydrodynamic environment: a combined population genetic and physical modelling approach

    PubMed Central

    Brennan, Georgina; Kregting, Louise; Beatty, Gemma E.; Cole, Claudia; Elsäßer, Björn; Savidge, Graham; Provan, Jim

    2014-01-01

    Gene flow in macroalgal populations can be strongly influenced by spore or gamete dispersal. This, in turn, is influenced by a convolution of the effects of current flow and specific plant reproductive strategies. Although several studies have demonstrated genetic variability in macroalgal populations over a wide range of spatial scales, the associated current data have generally been poorly resolved spatially and temporally. In this study, we used a combination of population genetic analyses and high-resolution hydrodynamic modelling to investigate potential connectivity between populations of the kelp Laminaria digitata in the Strangford Narrows, a narrow channel characterized by strong currents linking the large semi-enclosed sea lough, Strangford Lough, to the Irish Sea. Levels of genetic structuring based on six microsatellite markers were very low, indicating high levels of gene flow and a pattern of isolation-by-distance, where populations are more likely to exchange migrants with geographically proximal populations, but with occasional long-distance dispersal. This was confirmed by the particle tracking model, which showed that, while the majority of spores settle near the release site, there is potential for dispersal over several kilometres. This combined population genetic and modelling approach suggests that the complex hydrodynamic environment at the entrance to Strangford Lough can facilitate dispersal on a scale exceeding that proposed for L. digitata in particular, and the majority of macroalgae in general. The study demonstrates the potential of integrated physical–biological approaches for the prediction of ecological changes resulting from factors such as anthropogenically induced coastal zone changes. PMID:24671941

  8. Genetic architecture of cancer and other complex diseases: lessons learned and future directions

    PubMed Central

    Hindorff, Lucia A.; Gillanders, Elizabeth M.; Manolio, Teri A.

    2011-01-01

    Genome-wide association studies have broadened our understanding of the genetic architecture of cancer to include common variants, in addition to the rare variants previously identified by linkage analysis. We review current knowledge on the genetic architecture of four cancers—breast, lung, prostate and colorectal—for which the balance of common and rare alleles identified ranges from fewer common alleles (lung cancer) to more common alleles (prostate cancer). Although most variants are cancer specific, pleiotropy has been observed for several variants, for example, variants at the 8q24 locus and breast, ovarian and prostate cancers or variants in KITLG in relation to hair color and testicular cancer. Although few studies have been adequately powered to investigate heterogeneity among ancestry groups, effect sizes associated with common variants have been reported to be fairly homogenous among ethnic groups. Some associations appear to be ancestry specific, such as HNF1B, which is associated with prostate cancer in European Americans and Latinos but not in African-Americans. Studies of cancer and other complex diseases suggest that a simple dichotomy between rare and common allelic architectures may be too simplistic and that future research is needed to characterize a fuller spectrum of allele frequency (common (>5%), uncommon (1–5%) and rare (<<1%) alleles) and effect size. In addition, a broadening of the concept of genetic architecture to encompass both population architecture, which reflects differences in exposures, genetic factors and population level risk among diverse groups of people, and genomic architecture, which includes structural, epigenomic and somatic variation, is envisioned. PMID:21459759

  9. Invasion genetics of the Ciona intestinalis species complex: from regional endemism to global homogeneity.

    PubMed

    Zhan, Aibin; Macisaac, Hugh J; Cristescu, Melania E

    2010-11-01

    Determining the degree of population connectivity and investigating factors driving genetic exchange at various geographical scales are essential to understanding population dynamics and spread potential of invasive species. Here, we explore these issues in the highly invasive vase tunicate, Ciona intestinalis, a species whose invasion history has been obscured by its poorly understood taxonomy and population genetics. Recent phylogenetic and comparative genomic studies suggest that C. intestinalis is a cryptic species complex consisting of at least three species. We reconstructed phylogenies based on both mitochondrial (cytochrome c oxidase subunit 3--NADH dehydrogenase subunit 1 region and NADH dehydrogenase subunit 4 gene) and nuclear (internal transcribed spacer 1) sequences, results of which support four major phylogroups corresponding to the previously reported spA, spB and Ciona spp. (spC) as well as an undescribed cryptic species (spD). While spC and spD remain restricted to their native ranges in the Mediterranean Sea and Black Sea, respectively, the highly invasive species (spA and spB) have disjunct global distributions. Despite extensive interspecific divergences, we identified low phylogeographical structure within these two invasive species. Haplotype network analyses revealed comparatively limited mutation steps among haplotypes within each species. Population genetic analyses based on two mtDNA fragments and eight unlinked microsatellites illustrated relatively low population differentiation and high population connectivity at both regional and continental scales in the two invasive species. Human-mediated dispersal coupled with a high potential for natural dispersal is probably responsible for the observed genetic homogeneity.

  10. The importance of structural complexity in coral reef ecosystems

    NASA Astrophysics Data System (ADS)

    Graham, N. A. J.; Nash, K. L.

    2013-06-01

    The importance of structural complexity in coral reefs has come to the fore with the global degradation of reef condition; however, the limited scale and replication of many studies have restricted our understanding of the role of complexity in the ecosystem. We qualitatively and quantitatively (where sufficient standardised data were available) assess the literature regarding the role of structural complexity in coral reef ecosystems. A rapidly increasing number of publications have studied the role of complexity in reef ecosystems over the past four decades, with a concomitant increase in the diversity of methods used to quantify structure. Quantitative analyses of existing data indicate a strong negative relationship between structural complexity and algal cover, which may reflect the important role complexity plays in enhancing herbivory by reef fishes. The cover of total live coral and branching coral was positively correlated with structural complexity. These habitat attributes may be creating much of the structure, resulting in a collinear relationship; however, there is also evidence of enhanced coral recovery from disturbances where structural complexity is high. Urchin densities were negatively correlated with structural complexity; a relationship that may be driven by urchins eroding reef structure or by their gregarious behaviour when in open space. There was a strong positive relationship between structural complexity and fish density and biomass, likely mediated through density-dependent competition and refuge from predation. More variable responses were found when assessing individual fish families, with all families examined displaying a positive relationship to structural complexity, but only half of these relationships were significant. Although only corroborated with qualitative data, structural complexity also seems to have a positive effect on two ecosystem services: tourism and shoreline protection. Clearly, structural complexity is an

  11. Landscape genetics, adaptive diversity and population structure in Phaseolus vulgaris.

    PubMed

    Rodriguez, Monica; Rau, Domenico; Bitocchi, Elena; Bellucci, Elisa; Biagetti, Eleonora; Carboni, Andrea; Gepts, Paul; Nanni, Laura; Papa, Roberto; Attene, Giovanna

    2016-03-01

    Here we studied the organization of genetic variation of the common bean (Phaseolus vulgaris) in its centres of domestication. We used 131 single nucleotide polymorphisms to investigate 417 wild common bean accessions and a representative sample of 160 domesticated genotypes, including Mesoamerican and Andean genotypes, for a total of 577 accessions. By analysing the genetic spatial patterns of the wild common bean, we documented the existence of several genetic groups and the occurrence of variable degrees of diversity in Mesoamerica and the Andes. Moreover, using a landscape genetics approach, we demonstrated that both demographic processes and selection for adaptation were responsible for the observed genetic structure. We showed that the study of correlations between markers and ecological variables at a continental scale can help in identifying local adaptation genes. We also located putative areas of common bean domestication in Mesoamerica, in the Oaxaca Valley, and the Andes, in southern Bolivia-northern Argentina. These observations are of paramount importance for the conservation and exploitation of the genetic diversity preserved within this species and other plant genetic resources. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  12. Connectivity and genetic structure of the queen conch on the Mesoamerican Reef

    NASA Astrophysics Data System (ADS)

    Machkour-M'Rabet, Salima; Cruz-Medina, Jorge; García-De León, Francisco J.; De Jesús-Navarrete, Alberto; Hénaut, Yann

    2017-06-01

    The queen conch ( Strombus gigas) is a commercially important marine invertebrate that is widely distributed throughout the western Atlantic, from Bermuda to Brazil. Intense exploitation has resulted in a decrease in population numbers of this species, which is listed as protected from commercial exploitation under IUCN and CITES. Previous studies on population genetics have demonstrated contrasting results in terms of the population structure of S. gigas. This research analyzed the genetic connectivity of the queen conch over a wide area of the Mesoamerican Reef System to determine whether S. gigas presents one panmictic population or a more complex structure. Furthermore, we evaluated the risk of local extinction by establishing the genetic diversity of the studied populations. High resolution was obtained for the five ISSR markers used for a total of 190 individuals, from seven localities along the Mesoamerican Reef. Our results reject the panmictic structure hypothesis for the queen conch in the study area and demonstrate genetic patchiness, indicating general homogeneity among localities that present an isolation-by-distance pattern. However, some genetic temporal variation was confirmed for the Cozumel locality. Furthermore, our results reveal self-recruitment for the Alacranes Reef aggregation and suggest sufficient connectivity with localities on the Caribbean coast to maintain high genetic diversity. With regard to genetic diversity, the results demonstrate that the queen conch is not genetically threatened in the study area. This is probably due to high annual recruitment within Caribbean queen conch aggregations, and suggests that S. gigas is a highly resilient organism. We advocate that the appropriate management of S. gigas (fishing quota and/or closed season) must be followed to attain a rapid recovery of queen conch populations. This study represents a fundamental step in the understanding of the dynamic population structure of S. gigas in the

  13. A new conceptual framework for investigating complex genetic disease

    PubMed Central

    Hussain, Shobbir

    2015-01-01

    Some common diseases are known to have an inherited component, however, their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. Studies that have attempted to identify the causative genetic factors have been designed on this polygenic framework, but so far the yield has been largely unsatisfactory. Based on accumulating recent observations concerning the roles of somatic mosaicism in disease, in this article a second framework which posits a single gene-two hit model which can be modulated by a mutator/anti-mutator genetic background is suggested. I discuss whether such a model can be considered a viable alternative based on current knowledge, its advantages over the current polygenic framework, and describe practical routes via which the new framework can be investigated. PMID:26583033

  14. Evolving complex dynamics in electronic models of genetic networks

    NASA Astrophysics Data System (ADS)

    Mason, Jonathan; Linsay, Paul S.; Collins, J. J.; Glass, Leon

    2004-09-01

    Ordinary differential equations are often used to model the dynamics and interactions in genetic networks. In one particularly simple class of models, the model genes control the production rates of products of other genes by a logical function, resulting in piecewise linear differential equations. In this article, we construct and analyze an electronic circuit that models this class of piecewise linear equations. This circuit combines CMOS logic and RC circuits to model the logical control of the increase and decay of protein concentrations in genetic networks. We use these electronic networks to study the evolution of limit cycle dynamics. By mutating the truth tables giving the logical functions for these networks, we evolve the networks to obtain limit cycle oscillations of desired period. We also investigate the fitness landscapes of our networks to determine the optimal mutation rate for evolution.

  15. Genomic patterns in Acropora cervicornis show extensive population structure and variable genetic diversity.

    PubMed

    Drury, Crawford; Schopmeyer, Stephanie; Goergen, Elizabeth; Bartels, Erich; Nedimyer, Ken; Johnson, Meaghan; Maxwell, Kerry; Galvan, Victor; Manfrino, Carrie; Lirman, Diego

    2017-08-01

    Threatened Caribbean coral communities can benefit from high-resolution genetic data used to inform management and conservation action. We use Genotyping by Sequencing (GBS) to investigate genetic patterns in the threatened coral, Acropora cervicornis, across the Florida Reef Tract (FRT) and the western Caribbean. Results show extensive population structure at regional scales and resolve previously unknown structure within the FRT. Different regions also exhibit up to threefold differences in genetic diversity (He), suggesting targeted management based on the goals and resources of each population is needed. Patterns of genetic diversity have a strong spatial component, and our results show Broward and the Lower Keys are among the most diverse populations in Florida. The genetic diversity of Caribbean staghorn coral is concentrated within populations and within individual reefs (AMOVA), highlighting the complex mosaic of population structure. This variance structure is similar over regional and local scales, which suggests that in situ nurseries are adequately capturing natural patterns of diversity, representing a resource that can replicate the average diversity of wild assemblages, serving to increase intraspecific diversity and potentially leading to improved biodiversity and ecosystem function. Results presented here can be translated into specific goals for the recovery of A. cervicornis, including active focus on low diversity areas, protection of high diversity and connectivity, and practical thresholds for responsible restoration.

  16. Population genetic analysis and sub-structuring in Babesia bovis.

    PubMed

    Simuunza, Martin; Bilgic, Huseyin; Karagenc, Tulin; Syakalima, Michelo; Shiels, Brian; Tait, Andy; Weir, William

    2011-06-01

    The tick-borne protozoan parasite, Babesia bovis is one of the causes of bovine babesiosis, an economically important disease of cattle in tropical and sub-tropical countries. Using the recently published genome sequence of the parasite, we developed a panel of eight mini- and micro-satellite markers and used these to investigate the role of genetic exchange in the population structure and diversity of the parasite using isolates from Zambia and Turkey. This population genetic analysis showed that genetic exchange occurs and that there are high levels of genetic diversity, with geographical sub-structuring quantified using Wright's F Index. Linkage disequilibrium was observed when isolates from both countries were treated as one population, but when isolates from Zambia were analysed separately linkage equilibrium was observed. The Turkish isolates were sub-structured, containing two genetically distinct sub-groups, both of which appeared to be in linkage equilibrium. The results of the Zambian study suggest that a sub-set of the parasite population is responsible for the westward spread of babesiosis into the previously disease-free central region of the country. The Zambian isolates had a significantly higher number of genotypes per sample than those from Turkey and age was found to be a significant predictor of the multiplicity of infection. The high levels of diversity seen in the Zambian and Turkish B. bovis populations have implications in the development of subunit vaccines against the disease and the spread of drug resistance.

  17. Genetic structure of whitefish (Coregonus maraena) in the Baltic Sea

    NASA Astrophysics Data System (ADS)

    Olsson, Jens; Florin, Ann-Britt; Mo, Kerstin; Aho, Teija; Ryman, Nils

    2012-01-01

    Stocks of whitefish ( Coregonus maraena) in the northern part of the Baltic Sea have in many areas declined drastically during recent years. Causes for the decline are yet not fully understood, but knowledge on the genetic population structure of the species is pivotal for future conservation measures. In this study we analyse the genetic variation at seven microsatellite loci for whitefish from 18 different sites along the Swedish coast of the Baltic Sea. We found a strong dependence of isolation by distance ( R = 0.73), and a week but rather fine scaled genetic structure. In addition, there were differences between more northern and southern sites in the population genetic structure, where the degree of differentiation appears to be stronger in the north compared to the south. The results suggest that whitefish is a species suitable for local management with a regional context of the management strategy. In addition, the findings corroborate what is previously known for other coastal fish species in the Baltic Sea, such as perch and pike, suggesting that the majority of gene flow occurs between adjacent areas. Finally, our results highlight the potential for genetic subdivision even when the dependence of isolation by distance is strong.

  18. Complex Convective Thermal Fluxes and Vorticity Structure

    NASA Astrophysics Data System (ADS)

    Redondo, Jose M.; Tellez, Jackson; Sotillos, Laura; Lopez Gonzalez-Nieto, Pilar; Sanchez, Jesus M.; Furmanek, Petr; Diez, Margarita

    2015-04-01

    Local Diffusion and the topological structure of vorticity and velocity fields is measured in the transition from a homogeneous linearly stratified fluid to a cellular or layered structure by means of convective cooling and/or heating[1,2]. Patterns arise by setting up a convective flow generated by an array of Thermoelectric devices (Peltier/Seebeck cells) these are controlled by thermal PID generating a buoyant heat flux [2]. The experiments described here investigate high Prandtl number mixing using brine and fresh water in order to form density interfaces and low Prandtl number mixing with temperature gradients. The set of dimensionless parameters define conditions of numeric and small scale laboratory modeling of environmental flows. Fields of velocity, density and their gradients were computed and visualized [3,4]. When convective heating and cooling takes place the combination of internal waves and buoyant turbulence is much more complicated if the Rayleigh and Reynolds numbers are high in order to study entrainment and mixing. Using ESS and selfsimilarity structures in the velocity and vorticity fieds and intermittency [3,5] that forms in the non-homogeneous flow is related to mixing and stiring. The evolution of the mixing fronts are compared and the topological characteristics of the merging of plumes and jets in different configurations presenting detailed comparison of the evolution of RM and RT, Jets and Plumes in overall mixing. The relation between structure functions, fractal analysis and spectral analysis can be very useful to determine the evolution of scales. Experimental and numerical results on the advance of a mixing or nonmixing front occurring at a density interface due to body forces [6]and gravitational acceleration are analyzed considering the fractal and spectral structure of the fronts like in removable plate experiments for Rayleigh-Taylor flows. The evolution of the turbulent mixing layer and its complex configuration is studied

  19. Complex genetic diseases: controversy over the Croesus code.

    PubMed

    Wright, A F; Hastie, N D

    2001-01-01

    The polarization of views on how best to exploit new information from the Human Genome Project for medicine reflects our ignorance of the genetic architecture underlying common diseases: are susceptibility alleles common or rare, neutral or deleterious, few or many? Single-nucleotide polymorphism (SNP) technology is almost in place to dissect such diseases and to create a personalized medicine, but success is critically dependent on the biology and "Nature to be commanded must be obeyed" (Francis Bacon, 1620, Novum Organum).

  20. Genetic diversity, structure and differentiation in cultivate walnut (Juglans regia L.)

    Treesearch

    M. Aradhya; K. Woeste; D. Velasco

    2012-01-01

    An analysis of genetic structure and differentiation in cultivated walnut (Juglans regia) using 15 microsatellite loci revealed a considerable amount of genetic variation with a mild genetic structure indicating five genetic groups corresponding to the centers of diversity within the home range of walnut in Eurasia. Despite the narrow genetic...

  1. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology

    PubMed Central

    Brudey, Karine; Driscoll, Jeffrey R; Rigouts, Leen; Prodinger, Wolfgang M; Gori, Andrea; Al-Hajoj, Sahal A; Allix, Caroline; Aristimuño, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T; Fauville-Dufaux, Maryse; Ferdinand, Séverine; de Viedma, Dario Garcia; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M; Guttierez, M Cristina; Hawkey, Peter M; van Helden, Paul D; Kadival, Gurujaj V; Kreiswirth, Barry N; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaïa, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Zeaur; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M Lucia; Rüsch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor G; Singh, Urvashi B; Somoskovi, Akos; Skuce, Robin A; van Soolingen, Dick; Streicher, Elisabeth M; Suffys, Philip N; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Véronique; Victor, Tommie C; Warren, Robin M; Yap, Sook Fan; Zaman, Khadiza; Portaels, Françoise; Rastogi, Nalin; Sola, Christophe

    2006-01-01

    Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests

  2. Structure, dynamics, assembly, and evolution of protein complexes.

    PubMed

    Marsh, Joseph A; Teichmann, Sarah A

    2015-01-01

    The assembly of individual proteins into functional complexes is fundamental to nearly all biological processes. In recent decades, many thousands of homomeric and heteromeric protein complex structures have been determined, greatly improving our understanding of the fundamental principles that control symmetric and asymmetric quaternary structure organization. Furthermore, our conception of protein complexes has moved beyond static representations to include dynamic aspects of quaternary structure, including conformational changes upon binding, multistep ordered assembly pathways, and structural fluctuations occurring within fully assembled complexes. Finally, major advances have been made in our understanding of protein complex evolution, both in reconstructing evolutionary histories of specific complexes and in elucidating general mechanisms that explain how quaternary structure tends to evolve. The evolution of quaternary structure occurs via changes in self-assembly state or through the gain or loss of protein subunits, and these processes can be driven by both adaptive and nonadaptive influences.

  3. Capacitating epistasis--detection and role in the genetic architecture of complex traits.

    PubMed

    Pettersson, Mats E; Carlborg, Orjan

    2015-01-01

    Here, we discuss the potential role of capacitating epistasis in the genetic architecture of complex traits. Two alternative methods for identifying such gene-gene interactions in genetic association studies-mapping of variance controlling loci and the variance plane ratio (VPR) method-are introduced. An overview of the theoretical foundation of the methods is presented together with a discussion on their implementation and available software for performing these analyses. We conclude by highlighting a few examples of capacitating epistasis described in the literature and its potential impacts on the genetics of complex traits.

  4. Genetic Networks of Complex Disorders: from a Novel Search Engine for PubMed Article Database.

    PubMed

    Jung, Jae-Yoon; Wall, Dennis Paul

    2013-01-01

    Finding genetic risk factors of complex disorders may involve reviewing hundreds of genes or thousands of research articles iteratively, but few tools have been available to facilitate this procedure. In this work, we built a novel publication search engine that can identify target-disorder specific, genetics-oriented research articles and extract the genes with significant results. Preliminary test results showed that the output of this engine has better coverage in terms of genes or publications, than other existing applications. We consider it as an essential tool for understanding genetic networks of complex disorders.

  5. Genetic Networking of the Bemisia tabaci Cryptic Species Complex Reveals Pattern of Biological Invasions

    PubMed Central

    De Barro, Paul; Ahmed, Muhammad Z.

    2011-01-01

    Background A challenge within the context of cryptic species is the delimitation of individual species within the complex. Statistical parsimony network analytics offers the opportunity to explore limits in situations where there are insufficient species-specific morphological characters to separate taxa. The results also enable us to explore the spread in taxa that have invaded globally. Methodology/Principal Findings Using a 657 bp portion of mitochondrial cytochrome oxidase 1 from 352 unique haplotypes belonging to the Bemisia tabaci cryptic species complex, the analysis revealed 28 networks plus 7 unconnected individual haplotypes. Of the networks, 24 corresponded to the putative species identified using the rule set devised by Dinsdale et al. (2010). Only two species proposed in Dinsdale et al. (2010) departed substantially from the structure suggested by the analysis. The analysis of the two invasive members of the complex, Mediterranean (MED) and Middle East – Asia Minor 1 (MEAM1), showed that in both cases only a small number of haplotypes represent the majority that have spread beyond the home range; one MEAM1 and three MED haplotypes account for >80% of the GenBank records. Israel is a possible source of the globally invasive MEAM1 whereas MED has two possible sources. The first is the eastern Mediterranean which has invaded only the USA, primarily Florida and to a lesser extent California. The second are western Mediterranean haplotypes that have spread to the USA, Asia and South America. The structure for MED supports two home range distributions, a Sub-Saharan range and a Mediterranean range. The MEAM1 network supports the Middle East - Asia Minor region. Conclusion/Significance The network analyses show a high level of congruence with the species identified in a previous phylogenetic analysis. The analysis of the two globally invasive members of the complex support the view that global invasion often involve very small portions of the available

  6. Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure

    SciTech Connect

    Wang, Jing; Dye, Billy T; Rajashankar, Kanagalaghatta R; Kurinov, Igor; Schulman, Brenda A

    2009-12-01

    The multisubunit anaphase promoting complex (APC) is an essential cell-cycle regulator. Although CDC26 is known to have a role in APC assembly, its molecular function has remained unclear. Biophysical, structural and genetic studies presented here reveal that CDC26 stabilizes the structure of APC6, a core TPR protein required for APC integrity. Notably, CDC26-APC6 association involves an intermolecular TPR mimic composed of one helix from each protein.

  7. Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.

    PubMed

    Yan, Jingwen; Du, Lei; Kim, Sungeun; Risacher, Shannon L; Huang, Heng; Moore, Jason H; Saykin, Andrew J; Shen, Li

    2014-09-01

    Imaging genetics is an emerging field that studies the influence of genetic variation on brain structure and function. The major task is to examine the association between genetic markers such as single-nucleotide polymorphisms (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. The complexity of these datasets has presented critical bioinformatics challenges that require new enabling tools. Sparse canonical correlation analysis (SCCA) is a bi-multivariate technique used in imaging genetics to identify complex multi-SNP-multi-QT associations. However, most of the existing SCCA algorithms are designed using the soft thresholding method, which assumes that the input features are independent from one another. This assumption clearly does not hold for the imaging genetic data. In this article, we propose a new knowledge-guided SCCA algorithm (KG-SCCA) to overcome this limitation as well as improve learning results by incorporating valuable prior knowledge. The proposed KG-SCCA method is able to model two types of prior knowledge: one as a group structure (e.g. linkage disequilibrium blocks among SNPs) and the other as a network structure (e.g. gene co-expression network among brain regions). The new model incorporates these prior structures by introducing new regularization terms to encourage weight similarity between grouped or connected features. A new algorithm is designed to solve the KG-SCCA model without imposing the independence constraint on the input features. We demonstrate the effectiveness of our algorithm with both synthetic and real data. For real data, using an Alzheimer's disease (AD) cohort, we examine the imaging genetic associations between all SNPs in the APOE gene (i.e. top AD gene) and amyloid deposition measures among cortical regions (i.e. a major AD hallmark). In comparison with a widely used SCCA implementation, our KG-SCCA algorithm produces not only improved cross-validation performances but also biologically meaningful

  8. A multi-agent genetic algorithm for community detection in complex networks

    NASA Astrophysics Data System (ADS)

    Li, Zhangtao; Liu, Jing

    2016-05-01

    Complex networks are popularly used to represent a lot of practical systems in the domains of biology and sociology, and the structure of community is one of the most important network attributes which has received an enormous amount of attention. Community detection is the process of discovering the community structure hidden in complex networks, and modularity Q is one of the best known quality functions measuring the quality of communities of networks. In this paper, a multi-agent genetic algorithm, named as MAGA-Net, is proposed to optimize modularity value for the community detection. An agent, coded by a division of a network, represents a candidate solution. All agents live in a lattice-like environment, with each agent fixed on a lattice point. A series of operators are designed, namely split and merging based neighborhood competition operator, hybrid neighborhood crossover, adaptive mutation and self-learning operator, to increase modularity value. In the experiments, the performance of MAGA-Net is validated on both well-known real-world benchmark networks and large-scale synthetic LFR networks with 5000 nodes. The systematic comparisons with GA-Net and Meme-Net show that MAGA-Net outperforms these two algorithms, and can detect communities with high speed, accuracy and stability.

  9. Aging and Heterogeneity: Genetics, Social Structure, and Personality.

    ERIC Educational Resources Information Center

    Light, John M.; And Others

    1996-01-01

    Suggests that the heterogeneity of human personality characteristics increases with age. Examines reasons for this phenomenon in terms of individual differentiation, social structure/allocation, and behavioral genetics. Develops a model synthesizing various study designs that prevent variation and covariation errors from occurring in life course…

  10. Population Genetic Structure of Aedes fluviatilis (Diptera: Culicidae).

    PubMed

    Multini, Laura Cristina; Wilke, André Barretto Bruno; Suesdek, Lincoln; Marrelli, Mauro Toledo

    2016-01-01

    Although Aedes fluviatilis is an anthropophilic mosquito found abundantly in urban environments, its biology, epidemiological potential and genetic characteristics are poorly understood. Climate change and urbanization processes that result in environmental modifications benefit certain anthropophilic mosquito species such as Ae. fluviatilis, greatly increasing their abundance in urban areas. To gain a better understanding of whether urbanization processes modulate the genetic structure of this species in the city of São Paulo, we used eight microsatellite loci to genetically characterize Ae. fluviatilis populations collected in nine urban parks in the city of São Paulo. Our results show that there is high gene flow among the populations of this species, heterozygosity deficiency and low genetic structure and that the species may have undergone a recent population expansion. There are two main hypotheses to explain these findings: (i) Ae. fluviatilis populations have undergone a population expansion as a result of urbanization; and (ii) as urbanization of the city of São Paulo occurred recently and was quite intense, the structuring of these populations cannot be observed yet, apart from in the populations of Ibirapuera and Piqueri parks, where the first signs of structuring have appeared. We believe that the expansion found in Ae. fluviatilis populations is probably correlated with the unplanned urbanization of the city of São Paulo, which transformed green areas into urbanized areas, as well as the increasing population density in the city.

  11. Population genetic structure of a colonising, triploid weed, Hieracium lepidulum.

    PubMed

    Chapman, H; Robson, B; Pearson, M L

    2004-03-01

    Understanding the breeding system and population genetic structure of invasive weed species is important for biocontrol, and contributes to our understanding of the evolutionary processes associated with invasions. Hieracium lepidulum is an invasive weed in New Zealand, colonising a diverse range of habitats including native Nothofagus forest, pine plantations, scrubland and tussock grassland. It is competing with native subalpine and alpine grassland and herbfield vegetation. H. lepidulum is a triploid, diplosporous apomict, so theoretically all seed is clonal, and there is limited potential for the creation of variation through recombination. We used intersimple sequence repeats (ISSRs) to determine the population genetic structure of New Zealand populations of H. lepidulum. ISSR analysis of five populations from two regions in the South Island demonstrated high intrapopulation genotypic diversity, and high interpopulation genetic structuring; PhiST = 0.54 over all five populations. No private alleles were found in any of the five populations, and allelic differentiation was correlated to geographic distance. Cladistic compatibility analysis indicated that both recombination and mutation were important in the creation of genotypic diversity. Our data will contribute to any biocontrol program developed for H. lepidulum. It will also be a baseline data set for future comparisons of genetic structure during the course of H. lepidulum invasions.

  12. Population Genetic Structure of Aedes fluviatilis (Diptera: Culicidae)

    PubMed Central

    Multini, Laura Cristina; Suesdek, Lincoln; Marrelli, Mauro Toledo

    2016-01-01

    Although Aedes fluviatilis is an anthropophilic mosquito found abundantly in urban environments, its biology, epidemiological potential and genetic characteristics are poorly understood. Climate change and urbanization processes that result in environmental modifications benefit certain anthropophilic mosquito species such as Ae. fluviatilis, greatly increasing their abundance in urban areas. To gain a better understanding of whether urbanization processes modulate the genetic structure of this species in the city of São Paulo, we used eight microsatellite loci to genetically characterize Ae. fluviatilis populations collected in nine urban parks in the city of São Paulo. Our results show that there is high gene flow among the populations of this species, heterozygosity deficiency and low genetic structure and that the species may have undergone a recent population expansion. There are two main hypotheses to explain these findings: (i) Ae. fluviatilis populations have undergone a population expansion as a result of urbanization; and (ii) as urbanization of the city of São Paulo occurred recently and was quite intense, the structuring of these populations cannot be observed yet, apart from in the populations of Ibirapuera and Piqueri parks, where the first signs of structuring have appeared. We believe that the expansion found in Ae. fluviatilis populations is probably correlated with the unplanned urbanization of the city of São Paulo, which transformed green areas into urbanized areas, as well as the increasing population density in the city. PMID:27598889

  13. Host genetics and population structure effects on parasitic disease.

    PubMed

    Williams-Blangero, Sarah; Criscione, Charles D; VandeBerg, John L; Correa-Oliveira, Rodrigo; Williams, Kimberly D; Subedi, Janardan; Kent, Jack W; Williams, Jeff; Kumar, Satish; Blangero, John

    2012-03-19

    Host genetic factors exert significant influences on differential susceptibility to many infectious diseases. In addition, population structure of both host and parasite may influence disease distribution patterns. In this study, we assess the effects of population structure on infectious disease in two populations in which host genetic factors influencing susceptibility to parasitic disease have been extensively studied. The first population is the Jirel population of eastern Nepal that has been the subject of research on the determinants of differential susceptibility to soil-transmitted helminth infections. The second group is a Brazilian population residing in an area endemic for Trypanosoma cruzi infection that has been assessed for genetic influences on differential disease progression in Chagas disease. For measures of Ascaris worm burden, within-population host genetic effects are generally more important than host population structure factors in determining patterns of infectious disease. No significant influences of population structure on measures associated with progression of cardiac disease in individuals who were seropositive for T. cruzi infection were found.

  14. Genetic Differentiation and Relationships of Populations in the Cycas balansae Complex (Cycadaceae) and its Conservation Implications

    PubMed Central

    XIAO, LONG-QIAN; GONG, XUN

    2006-01-01

    • Background and Aims The Cycas balansae complex is arguably a controversial group with regard to species delineation. Some taxonomists recognize a single polymorphic species while others distinguish five narrowly defined ones. The unresolved taxonomy has the potential to bring about significant problems for species conservation. Thus, an investigation to examine the genetic diversity and differentiation in the C. balansae complex was performed to determine the relationship of populations and to test whether the morphologically defined segregations represent genetically distinct units. • Methods Inter-simple sequence repeat (ISSR) markers were employed to assess the genetic diversity in the C. balansae complex with a sample of 158 individuals from all extant populations in China. • Key Results ISSR markers revealed low genetic diversity in all populations studied (HE and HO averaged 0·0639 and 0·0798 at the population level, respectively). Phenetic analysis showed that the C. balansae complex grouped into five clusters closely corresponding to the narrowly defined C. balansae, C. parvula, C. shiwandashanica, C. tanqingii and C. simplicipinna. • Conclusions ISSR data suggest that the C. balansae complex has evolved into five genetically distinct units. These might be derived from a relatively widespread common ancestor through multiple vicariant events including geographical isolation resulting from the collision of the Indian plate with the Eurasian plate and from Pleistocene glaciations. In conservation, attention should be paid to each genetic unit. PMID:16517547

  15. Genetics, mental illness, and complex disease: development and distribution of an interactive CD-ROM for genetic counselors. Final report for period 15 August 2000 - 31 December 2002

    SciTech Connect

    McInerney, Joseph D.

    2003-03-31

    "Genetics and Major Psychiatric Disorders: A Program for Genetic Counselors" provides an introduction to psychiatric genetics, with a focus on the genetics of common complex disease, for genetics professionals. The program is available as a CD-ROM and an online educational resource. The on-line version requires a direct internet connection. Each educational module begins with an interactive case study that raises significant issues addressed in each module. In addition, case studies provided throughout the educational materials support teaching of major concepts. Incorporated throughout the content are expert video clips, video clips from individuals affected by psychiatric illness, and optional "learn more" materials that offer greater depth about a particular topic. The structure of the CD-ROM permits self-navigation, but we have suggested a sequence that allows materials to build upon each other. At any point in the materials, users may pause and look up terms in the glossary or review the DSM-IV criteria for selected psychiatric disorders. A detailed site map is available for those who choose to self navigate through the content.

  16. Contrasting genetic architectures in different mouse reference populations used for studying complex traits

    PubMed Central

    Buchner, David A.; Nadeau, Joseph H.

    2015-01-01

    Quantitative trait loci (QTLs) are being used to study genetic networks, protein functions, and systems properties that underlie phenotypic variation and disease risk in humans, model organisms, agricultural species, and natural populations. The challenges are many, beginning with the seemingly simple tasks of mapping QTLs and identifying their underlying genetic determinants. Various specialized resources have been developed to study complex traits in many model organisms. In the mouse, remarkably different pictures of genetic architectures are emerging. Chromosome Substitution Strains (CSSs) reveal many QTLs, large phenotypic effects, pervasive epistasis, and readily identified genetic variants. In contrast, other resources as well as genome-wide association studies (GWAS) in humans and other species reveal genetic architectures dominated with a relatively modest number of QTLs that have small individual and combined phenotypic effects. These contrasting architectures are the result of intrinsic differences in the study designs underlying different resources. The CSSs examine context-dependent phenotypic effects independently among individual genotypes, whereas with GWAS and other mouse resources, the average effect of each QTL is assessed among many individuals with heterogeneous genetic backgrounds. We argue that variation of genetic architectures among individuals is as important as population averages. Each of these important resources has particular merits and specific applications for these individual and population perspectives. Collectively, these resources together with high-throughput genotyping, sequencing and genetic engineering technologies, and information repositories highlight the power of the mouse for genetic, functional, and systems studies of complex traits and disease models. PMID:25953951

  17. Biological pattern formation: from basic mechanisms to complex structures

    SciTech Connect

    Koch, A.J.; Meinhardt, H. )

    1994-10-01

    The reliable development of highly complex organisms is an intriguing and fascinating problem. The genetic material is, as a rule, the same in each cell of an organism. How then do cells, under the influence of their common genes, produce spatial patterns Simple models are discussed that describe the generation of patterns out of an initially nearly homogeneous state. They are based on nonlinear interactions of at least two chemicals and on their diffusion. The concepts of local autocatalysis and of long-range inhibition play a fundamental role. Numerical simulations show that the models account for many basic biological observations such as the regeneration of a pattern after excision of tissue or the production of regular (or nearly regular) arrays of organs during (or after) completion of growth. Very complex patterns can be generated in a reproducible way by hierarchical coupling of several such elementary reactions. Applications to animal coats and to the generation of polygonally shaped patterns are provided. It is further shown how to generate a strictly periodic pattern of units that themselves exhibit a complex and polar fine structure. This is illustrated by two examples: the assembly of photoreceptor cells in the eye of [ital Drosophila] and the positioning of leaves and axillary buds in a growing shoot. In both cases, the substructures have to achieve an internal polarity under the influence of some primary pattern-forming system existing in the fly's eye or in the plant. The fact that similar models can describe essential steps in organisms as distantly related as animals and plants suggests that they reveal some universal mechanisms.

  18. Biological pattern formation: from basic mechanisms to complex structures

    NASA Astrophysics Data System (ADS)

    Koch, A. J.; Meinhardt, H.

    1994-10-01

    The reliable development of highly complex organisms is an intriguing and fascinating problem. The genetic material is, as a rule, the same in each cell of an organism. How then do cells, under the influence of their common genes, produce spatial patterns? Simple models are discussed that describe the generation of patterns out of an initially nearly homogeneous state. They are based on nonlinear interactions of at least two chemicals and on their diffusion. The concepts of local autocatalysis and of long-range inhibition play a fundamental role. Numerical simulations show that the models account for many basic biological observations such as the regeneration of a pattern after excision of tissue or the production of regular (or nearly regular) arrays of organs during (or after) completion of growth. Very complex patterns can be generated in a reproducible way by hierarchical coupling of several such elementary reactions. Applications to animal coats and to the generation of polygonally shaped patterns are provided. It is further shown how to generate a strictly periodic pattern of units that themselves exhibit a complex and polar fine structure. This is illustrated by two examples: the assembly of photoreceptor cells in the eye of Drosophila and the positioning of leaves and axillary buds in a growing shoot. In both cases, the substructures have to achieve an internal polarity under the influence of some primary pattern-forming system existing in the fly's eye or in the plant. The fact that similar models can describe essential steps in organisms as distantly related as animals and plants suggests that they reveal some universal mechanisms.

  19. Genetic relatedness among Mycobacterium paratuberculosis and M. avium complex.

    PubMed

    Labidi, A; Thoen, C O

    1989-01-01

    Total DNA was extracted from M. paratuberculosis (ATCC 19698) and from M. avium complex (ATCC 25291) cultivated on RVB-10 enriched liquid media. Restriction endonuclease analysis of total DNA was performed with 34 enzymes and DNA digestion profiles were compared. Fifteen enzymes revealed important differences between the two species. Two pairs of enzymes (EcoRII, BstNI) and (MboI, Sau3AI) provide evidence for the presence of dcmI and dam methylation in DNA of M. avium complex and M. paratuberculosis. The differences in DNA fragments of these two species could be of potential value in differentiating these clinically significant mycobacteria.

  20. Functional significance of genetic variation underlying limb bone diaphyseal structure

    PubMed Central

    Wallace, Ian J.; Middleton, Kevin M.; Lublinsky, Svetlana; Kelly, Scott A.; Judex, Stefan; Garland, Theodore; Demes, Brigitte

    2010-01-01

    Limb bone diaphyseal structure is frequently used to infer hominin activity levels from skeletal remains, an approach based on the well-documented ability of bone to adjust to its loading environment during life. However, diaphyseal structure is also determined in part by genetic factors. This study investigates the possibility that genetic variation underlying diaphyseal structure is influenced by the activity levels of ancestral populations and might also have functional significance in an evolutionary context. We adopted an experimental evolution approach and tested for differences in femoral diaphyseal structure in one-week-old mice from a line that had been artificially selected (45 generations) for high voluntary wheel running and unselected controls. As adults, selected mice are significantly more active on wheels and in home cages, and have thicker diaphyses. Structural differences at one week can be assumed to primarily reflect the effects of selective breeding rather than direct mechanical stimuli, given that the onset of locomotion in mice is shortly after day seven. We hypothesized that if genetically determined diaphyseal structure reflects the activity patterns of members of a lineage, then selected animals will have relatively larger diaphyseal dimensions at one week compared to controls. The results provide strong support for this hypothesis and suggest that limb bone cross sections may not always only reflect the activity levels of particular fossil individuals, but also convey an evolutionary signal providing information about hominin activity in the past. PMID:20310061

  1. Fine-scaled human genetic structure revealed by SNP microarrays.

    PubMed

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure.

  2. Genetic structure of spatial and verbal working memory.

    PubMed

    Ando, J; Ono, Y; Wright, M J

    2001-11-01

    Working memory (WM) encompasses both short-term memory (storage) and executive functions that play an essential role in all forms of cognition. In this study, the genetic structure of storage and executive functions engaged in both a spatial and verbal WM span task is investigated using a twin sample. The sample consists of 143 monozygotic (MZ) and 93 dizygotic (DZ) Japanese twin pairs, ages 16 to 29 years. In 155 (87 MZ, 62 DZ) of these pairs, cognitive ability scores from the Kyodai Japanese IQ test are also obtained. The phenotypic relationship between WM and cognitive ability is confirmed (r = 0.26-0.44). Individual differences in WM storage and executive functions are found to be significantly influenced by genes, with heritability estimates all moderately high (43%-49%), and estimates for cognitive ability comparable to previous studies (65%). A large part of the genetic variance in storage and executive functions in both spatial and verbal modalities is due to a common genetic factor that accounts for 11% to 43% of the variance. In the reduced sample, this common genetic factor accounts for 64% and 26% of the variance in spatial and verbal cognitive ability, respectively. Additional genetic variance in WM (7%-30%) is due to modality specific factors (spatial and verbal) and a storage specific factor that may be particularly important for the verbal modality. None of the variance in cognitive ability is accounted for by the modality and storage genetic factors, suggesting these may be specific to WM.

  3. Structurally simple complexes of CO2.

    PubMed

    Murphy, Luke J; Robertson, Katherine N; Kemp, Richard A; Tuononen, Heikki M; Clyburne, Jason A C

    2015-03-07

    The ability to bind CO2 through the formation of low-energy, easily-broken, bonds could prove invaluable in a variety of chemical contexts. For example, weak bonds to CO2 would greatly decrease the cost of the energy-intensive sorbent-regeneration step common to most carbon capture technologies. Furthermore, exploration of this field could lead to the discovery of novel CO2 chemistry. Reduction of complexed carbon dioxide might generate chemical feedstocks for the preparation of value-added products, particularly transportation fuels or fuel precursors. Implementation on a large scale could help to drastically reduce CO2 concentrations in the atmosphere. However, literature examples of weakly bonded complexes of CO2 are relatively few and true coordination complexes to a 'naked' CO2 fragment are nearly unheard of. In this review article, a variety of complexes of CO2 featuring diverse binding modes and reactivity will be examined. Topics covered include: (A) inclusion complexes of CO2 in porous materials. (B) Zwitterionic carbamates produced from the reaction of CO2 with polyamines. (C) Carbamate salts produced from reaction of CO2 with two equivalents of an amine. (D) Insertion products of CO2 into acid-base adducts (e.g., metal complexes). (E) Lewis acid-base activated CO2, such as frustrated Lewis pair complexes. (F) Simple base-CO2 adducts, wherein the base-CO2 bond is the only interaction formed. Complexes in the last category are of particular interest, and include imidazol-2-carboxylates (N-heterocyclic carbene adducts of CO2) as well as a few other examples that lie outside NHC chemistry.

  4. Understanding the Etiology of Complex Traits: Symbiotic Relationships between Psychology and Genetics

    ERIC Educational Resources Information Center

    Grigorenko, Elena L.

    2007-01-01

    The present article offers comments on the infusion of methodologies, approaches, reasoning strategies, and findings from the fields of genetics and genomics into studies of complex human behaviors (hereafter, complex phenotypes). Specifically, I discuss issues of generality and specificity, causality, and replicability as they pertain to…

  5. Understanding the Etiology of Complex Traits: Symbiotic Relationships between Psychology and Genetics

    ERIC Educational Resources Information Center

    Grigorenko, Elena L.

    2007-01-01

    The present article offers comments on the infusion of methodologies, approaches, reasoning strategies, and findings from the fields of genetics and genomics into studies of complex human behaviors (hereafter, complex phenotypes). Specifically, I discuss issues of generality and specificity, causality, and replicability as they pertain to…

  6. Mapping of Genetic Factors That Elicit Intermale Aggressive Behavior on Mouse Chromosome 15: Intruder Effects and the Complex Genetic Basis

    PubMed Central

    Takahashi, Aki; Sugimoto, Hiroki; Kato, Shogo; Shiroishi, Toshihiko; Koide, Tsuyoshi

    2015-01-01

    Despite high estimates of the heritability of aggressiveness, the genetic basis for individual differences in aggression remains unclear. Previously, we showed that the wild-derived mouse strain MSM/Ms (MSM) exhibits highly aggressive behaviors, and identified chromosome 15 (Chr 15) as the location of one of the genetic factors behind this escalated aggression by using a panel of consomic strains of MSM in a C57BL/6J (B6) background. To understand the genetic effect of Chr 15 derived from MSM in detail, this study examined the aggressive behavior of a Chr 15 consomic strain towards different types of opponent. Our results showed that both resident and intruder animals had to have the same MSM Chr 15 genotype in order for attack bites to increase and attack latency to be reduced, whereas there was an intruder effect of MSM Chr 15 on tail rattle behavior. To narrow down the region that contains the genetic loci involved in the aggression-eliciting effects on Chr 15, we established a panel of subconsomic strains of MSM Chr 15. Analysis of these strains suggested the existence of multiple genes that enhance and suppress aggressive behavior on Chr 15, and these loci interact in a complex way. Regression analysis successfully identified four genetic loci on Chr 15 that influence attack latency, and one genetic locus that partially elicits aggressive behaviors was narrowed down to a 4.1-Mbp region (from 68.40 Mb to 72.50 Mb) on Chr 15. PMID:26389588

  7. Genetic Variation and Population Structure in Native Americans

    PubMed Central

    Ramachandran, Sohini; Ray, Nicolas; Bedoya, Gabriel; Rojas, Winston; Parra, Maria V; Molina, Julio A; Gallo, Carla; Mazzotti, Guido; Poletti, Giovanni; Hill, Kim; Hurtado, Ana M; Labuda, Damian; Klitz, William; Barrantes, Ramiro; Bortolini, Maria Cátira; Salzano, Francisco M; Petzl-Erler, Maria Luiza; Tsuneto, Luiza T; Llop, Elena; Rothhammer, Francisco; Excoffier, Laurent; Feldman, Marcus W; Rosenberg, Noah A; Ruiz-Linares, Andrés

    2007-01-01

    We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians—signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas. PMID:18039031

  8. Molecular Population Genetic Structure in the Piping Plover

    USGS Publications Warehouse

    Miller, Mark P.; Haig, Susan M.; Gratto-Trevor, Cheri L.; Mullins, Thomas D.

    2009-01-01

    The Piping Plover (Charadrius melodus) is a migratory shorebird currently listed as Endangered in Canada and the U.S. Great Lakes, and threatened throughout the remainder of its U.S. breeding and winter range. In this study, we undertook the first comprehensive molecular genetic-based investigation of Piping Plovers. Our primary goals were to (1) address higher level subspecific taxonomic issues, (2) characterize population genetic structure, and (3) make inferences regarding past bottlenecks or population expansions that have occurred within this species. Our analyses included samples of individuals from 23 U.S. States and Canadian Provinces, and were based on mitochondrial DNA sequences (580 bp, n = 245 individuals) and eight nuclear microsatellite loci (n = 229 individuals). Our findings illustrate strong support for separate Atlantic and Interior Piping Plover subspecies (C. m. melodus and C. m. circumcinctus, respectively). Birds from the Great Lakes region were allied with the Interior subspecies group and should be taxonomically referred to as C. m. circumcinctus. Population genetic analyses suggested that genetic structure was stronger among Atlantic birds relative to the Interior group. This pattern indicates that natal and breeding site fidelity may be reduced among Interior birds. Furthermore, analyses suggested that Interior birds have previously experienced genetic bottlenecks, whereas no evidence for such patterns existed among the Atlantic subspecies. Likewise, genetic analyses indicated that the Great Lakes region has experienced a population expansion. This finding may be interpreted as population growth following a previous bottleneck event. No genetic evidence for population expansions was found for Atlantic, Prairie Canada, or U.S. Northern Great Plains individuals. We interpret our population history insights in light of 25 years of Piping Plover census data. Overall, differences observed between Interior and Atlantic birds may reflect

  9. HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology.

    PubMed

    Rosenson, Robert S; Brewer, H Bryan; Barter, Philip J; Björkegren, Johan L M; Chapman, M John; Gaudet, Daniel; Kim, Daniel Seung; Niesor, Eric; Rye, Kerry-Anne; Sacks, Frank M; Tardif, Jean-Claude; Hegele, Robert A

    2017-08-10

    Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants. Furthermore, only a fraction of HDL-C variation has been explained by known loci from genome-wide association studies (GWAS), suggesting the existence of additional pathways and targets. Systems genetics can enhance our understanding of the spectrum of HDL pathways, particularly those pathways that involve new and non-obvious GWAS loci. Bioinformatic approaches can also define new molecular interactions inferred from both large-scale genotypic data and RNA sequencing data to reveal biologically meaningful gene modules and networks governing HDL metabolism with direct relevance to disease end points. Targeting these newly recognized causal networks might inform the development of novel therapeutic strategies to reduce the risk of cardiovascular disease.

  10. Complexity of Infection and Genetic Diversity in Cambodian Plasmodium vivax

    PubMed Central

    Friedrich, Lindsey R.; Popovici, Jean; Kim, Saorin; Dysoley, Lek; Zimmerman, Peter A.; Menard, Didier; Serre, David

    2016-01-01

    Background Plasmodium vivax is the most widely distributed human malaria parasite with 2.9 billion people living in endemic areas. Despite intensive malaria control efforts, the proportion of cases attributed to P. vivax is increasing in many countries. Genetic analyses of the parasite population and its dynamics could provide an assessment of the efficacy of control efforts, but, unfortunately, these studies are limited in P. vivax by the lack of informative markers and high-throughput genotyping methods. Methodology/Principal Findings We developed a sequencing-based assay to simultaneously genotype more than 100 SNPs and applied this approach to ~500 P. vivax-infected individuals recruited across nine locations in Cambodia between 2004 and 2013. Our analyses showed that the vast majority of infections are polyclonal (92%) and that P. vivax displays high genetic diversity in Cambodia without apparent geographic stratification. Interestingly, our analyses also revealed that the proportion of monoclonal infections significantly increased between 2004 and 2013, possibly suggesting that malaria control strategies in Cambodia may be successfully affecting the parasite population. Conclusions/Significance Our findings demonstrate that this high-throughput genotyping assay is efficient in characterizing P. vivax diversity and can provide valuable insights to assess the efficacy of malaria elimination programs or to monitor the spread of specific parasites. PMID:27018585

  11. A structural snapshot of the rhodopsin–arrestin complex

    PubMed Central

    Kang, Yanyong; Gao, Xiang; Zhou, X. Edward; He, Yuanzheng; Melcher, Karsten; Xu, H. Eric

    2015-01-01

    The crystal structure of the rhodopsin–arrestin complex provides important insights into how G protein–coupled receptor signaling is terminated by arrestin and a structural basis for understanding the mechanism of arrestin-biased signaling. PMID:26467309

  12. Dispersal differences predict population genetic structure in Mormon crickets.

    PubMed

    Bailey, Nathan W; Gwynne, Darryl T; Ritchie, Michael G

    2007-05-01

    Research investigating the geographical context of speciation has primarily focused on abiotic factors such as the role of Pleistocene glacial cycles, or geotectonic events. Few study systems allow a direct comparison of how biological differences, such as dispersal behaviour, affect population genetic structure of organisms that were subdivided during the Pleistocene. Mormon crickets exist in solitary and gregarious 'phases', which broadly correspond with an east-west mtDNA division across the Rocky Mountains. Gregarious individuals form bands that can move up to 2 km daily. This study assessed whether population genetic structure results mainly from deep Pleistocene vicariance or if we can also detect more recent genetic patterns due to phase and dispersal differences superimposed on the older, deeper divisions. We found that separation in refugia was a more important influence on genetic divergence than phase, with the Rockies acting as a barrier that separated Mormon cricket populations into eastern and western refugia during Pleistocene glacial cycles. However, patterns of isolation by distance differ between eastern and western clades for both mitochondrial and nuclear DNA, with greater divergence within the eastern, solitary clade. An mtDNA haplotype mismatch distribution is compatible with historical population expansion in the western clade but not in the eastern clade. A persistent (and possibly sex-biased) difference in dispersal ability has most likely influenced the greater population genetic structure seen in the eastern clade, emphasizing the importance of the interaction of Quaternary climate fluctuations and geography with biotic factors in producing the patterns of genetic subdivision observed today.

  13. The geography of malaria genetics in the Democratic Republic of Congo: A complex and fragmented landscape

    PubMed Central

    Carrel, Margaret; Patel, Jaymin; Taylor, Steve M.; Janko, Mark; Mwandagalirwa, Melchior Kashamuka; Tshefu, Antoinette K.; Escalante, Ananias A.; McCollum, Andrea; Alam, Md Tauqeer; Udhayakumar, Venkatachalam; Meshnick, Steven; Emch, Michael

    2014-01-01

    Understanding how malaria parasites move between populations is important, particularly given the potential for malaria to be reintroduced into areas where it was previously eliminated. We examine the distribution of malaria genetics across seven sites within the Democratic Republic of Congo (DRC) and two nearby countries, Ghana and Kenya, in order to understand how the relatedness of malaria parasites varies across space, and whether there are barriers to the flow of malaria parasites within the DRC or across borders. Parasite DNA was retrieved from dried blood spots from 7 Demographic and Health Survey sample clusters in the DRC. Malaria genetic characteristics of parasites from Ghana and Kenya were also obtained. For each of 9 geographic sites (7 DRC, 1 Ghana and 1 Kenya), a pair-wise RST statistic was calculated, indicating the genetic distance between malaria parasites found in those locations. Mapping genetics across the spatial extent of the study area indicates a complex genetic landscape, where relatedness between two proximal sites may be relatively high (RST > 0.64) or low (RST < 0.05), and where distal sites also exhibit both high and low genetic similarity. Mantel’s tests suggest that malaria genetics differ as geographic distances increase. Principal Coordinate Analysis suggests that genetically related samples are not co-located. Barrier analysis reveals no significant barriers to gene flow between locations. Malaria genetics in the DRC have a complex and fragmented landscape. Limited exchange of genes across space is reflected in greater genetic distance between malaria parasites isolated at greater geographic distances. There is, however, evidence for close genetic ties between distally located sample locations, indicating that movement of malaria parasites and flow of genes is being driven by factors other than distance decay. This research demonstrates the contributions that spatial disease ecology and landscape genetics can make to

  14. Finding friends and enemies in an enemies-only network: A graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions

    PubMed Central

    Qi, Yan; Suhail, Yasir; Lin, Yu-yi; Boeke, Jef D.; Bader, Joel S.

    2008-01-01

    The yeast synthetic lethal genetic interaction network contains rich information about underlying pathways and protein complexes as well as new genetic interactions yet to be discovered. We have developed a graph diffusion kernel as a unified framework for inferring complex/pathway membership analogous to “friends” and genetic interactions analogous to “enemies” from the genetic interaction network. When applied to the Saccharomyces cerevisiae synthetic lethal genetic interaction network, we can achieve a precision around 50% with 20% to 50% recall in the genome-wide prediction of new genetic interactions, supported by experimental validation. The kernels show significant improvement over previous best methods for predicting genetic interactions and protein co-complex membership from genetic interaction data. PMID:18832443

  15. [Genetic structure of the Pinzgauer breed in the Carpathian region].

    PubMed

    Glazko, V I; Stolpovskiĭ, Iu A; Tarasiuk, S I; Bukarov, N G; Popov, N A

    1996-05-01

    Phenotypic and genotypic characteristics of groups of Pinzgauer cattle bred at lowland, highland, and alpine farms in the Carpathian Mountains were studied. A high variation of the cattle with respect to blood groups was revealed. It was found that the genetic structure of the highland group of Pinzagauer cattle was somewhat similar to that of Brown Carpathian cattle with respect to biochemical genetic systems, mainly transferrin and amylase-I loci. It is thought that the similarity found may be accounted for by close ecological and geographical breeding conditions of the groups of cattle studied.

  16. Population genetic structure of mussels from the Baltic Sea

    NASA Astrophysics Data System (ADS)

    Bulnheim, H.-P.; Gosling, E.

    1988-03-01

    In a macrogeographic survey, the population genetic structure of mussels from various regions of the Baltic Sea, a large semi-enclosed brackish-water basin, was examined with reference to Mytilus edulis and M. galloprovincialis samples from the North Sea, Irish coast and southern Portugal. Electrophoretically detectable variation was analysed at 6 polymorphic enzyme loci ( Ap, Est-D, Lap-2, Odh, Pgi and Pgm). Evidence was provided of a remarkably large amount of biochemical genetic differentiation among ecologically and morphologically divergent mussel populations in the Baltic. Patterns of allele frequencies in low-salinity populations from the area of the Baltic Proper were demonstrated to be widely homogeneous but contrast strongly with those of the western Baltic, the latter resembling populations from marine habitats of the North Sea. Associated with a pronounced salinity gradient, the spatial heterogeneity in gene-pool structure is indicated by steep clines of allele frequency changes in the area of the eastern Danish isles. The adaptive significance of the observed allozymic variation is suggested. From genetic distance estimates, the subdivision of population structure is discussed in relation to the significant amount of differentiation detected within Mytilus populations to date and to the evolutionary time required for the divergence of Baltic mussel populations. The allozymic data provide evidence for the genetic distinctiveness of mussels from the low-salinity areas of the Baltic. Their position at the specific or subspecific level of classification requires further consideration.

  17. Genetic structure of North American wolverine (Gulo gulo) populations.

    PubMed

    Kyle, C J; Strobeck, C

    2001-02-01

    Wolverines (Gulo gulo) are found in low densities throughout their circumpolar distribution. They are also potentially susceptible to human-caused population fragmentation (development, recreation and fur harvesting). The combination of these factors has contributed to this species being listed as having either vulnerable or endangered status across much of its current range. The effects of inherently low densities and anthropogenic pressures on the genetic structure and variation of wolverine populations are, as yet, unknown. In this study, 461 individuals were typed at 12 microsatellite loci to investigate the population genetic structure of wolverines from north-western Alaska to eastern Manitoba. Levels of gene flow and population differentiation among the sampled regions were estimated via a genotype assignment test, pairwise F(ST), and two genetic distance measures. Our results suggest that wolverine populations from southernmost regions, in which anthropogenic factors are strongest, revealed more genetic structuring than did northern populations. Furthermore, these results suggest that reductions in this species' range may have led to population fragmentation in the extreme reaches of its southern distribution. The continued reduction of suitable habitat for this species may lead to more populations becoming isolated remnants of a larger distribution of northern wolverines, as documented in other North American carnivore species.

  18. SHIPS: Spectral Hierarchical clustering for the Inference of Population Structure in genetic studies.

    PubMed

    Bouaziz, Matthieu; Paccard, Caroline; Guedj, Mickael; Ambroise, Christophe

    2012-01-01

    Inferring the structure of populations has many applications for genetic research. In addition to providing information for evolutionary studies, it can be used to account for the bias induced by population stratification in association studies. To this end, many algorithms have been proposed to cluster individuals into genetically homogeneous sub-populations. The parametric algorithms, such as Structure, are very popular but their underlying complexity and their high computational cost led to the development of faster parametric alternatives such as Admixture. Alternatives to these methods are the non-parametric approaches. Among this category, AWclust has proven efficient but fails to properly identify population structure for complex datasets. We present in this article a new clustering algorithm called Spectral Hierarchical clustering for the Inference of Population Structure (SHIPS), based on a divisive hierarchical clustering strategy, allowing a progressive investigation of population structure. This method takes genetic data as input to cluster individuals into homogeneous sub-populations and with the use of the gap statistic estimates the optimal number of such sub-populations. SHIPS was applied to a set of simulated discrete and admixed datasets and to real SNP datasets, that are data from the HapMap and Pan-Asian SNP consortium. The programs Structure, Admixture, AWclust and PCAclust were also investigated in a comparison study. SHIPS and the parametric approach Structure were the most accurate when applied to simulated datasets both in terms of individual assignments and estimation of the correct number of clusters. The analysis of the results on the real datasets highlighted that the clusterings of SHIPS were the more consistent with the population labels or those produced by the Admixture program. The performances of SHIPS when applied to SNP data, along with its relatively low computational cost and its ease of use make this method a promising

  19. SHIPS: Spectral Hierarchical Clustering for the Inference of Population Structure in Genetic Studies

    PubMed Central

    Bouaziz, Matthieu; Paccard, Caroline; Guedj, Mickael; Ambroise, Christophe

    2012-01-01

    Inferring the structure of populations has many applications for genetic research. In addition to providing information for evolutionary studies, it can be used to account for the bias induced by population stratification in association studies. To this end, many algorithms have been proposed to cluster individuals into genetically homogeneous sub-populations. The parametric algorithms, such as Structure, are very popular but their underlying complexity and their high computational cost led to the development of faster parametric alternatives such as Admixture. Alternatives to these methods are the non-parametric approaches. Among this category, AWclust has proven efficient but fails to properly identify population structure for complex datasets. We present in this article a new clustering algorithm called Spectral Hierarchical clustering for the Inference of Population Structure (SHIPS), based on a divisive hierarchical clustering strategy, allowing a progressive investigation of population structure. This method takes genetic data as input to cluster individuals into homogeneous sub-populations and with the use of the gap statistic estimates the optimal number of such sub-populations. SHIPS was applied to a set of simulated discrete and admixed datasets and to real SNP datasets, that are data from the HapMap and Pan-Asian SNP consortium. The programs Structure, Admixture, AWclust and PCAclust were also investigated in a comparison study. SHIPS and the parametric approach Structure were the most accurate when applied to simulated datasets both in terms of individual assignments and estimation of the correct number of clusters. The analysis of the results on the real datasets highlighted that the clusterings of SHIPS were the more consistent with the population labels or those produced by the Admixture program. The performances of SHIPS when applied to SNP data, along with its relatively low computational cost and its ease of use make this method a promising

  20. Spatial Genetic Structure of a Symbiotic Beetle-Fungal System: Toward Multi-Taxa Integrated Landscape Genetics

    PubMed Central

    James, Patrick M. A.; Coltman, Dave W.; Murray, Brent W.; Hamelin, Richard C.; Sperling, Felix A. H.

    2011-01-01

    Spatial patterns of genetic variation in interacting species can identify shared features that are important to gene flow and can elucidate co-evolutionary relationships. We assessed concordance in spatial genetic variation between the mountain pine beetle (Dendroctonus ponderosae) and one of its fungal symbionts, Grosmanniaclavigera, in western Canada using neutral genetic markers. We examined how spatial heterogeneity affects genetic variation within beetles and fungi and developed a novel integrated landscape genetics approach to assess reciprocal genetic influences between species using constrained ordination. We also compared landscape genetic models built using Euclidean distances based on allele frequencies to traditional pair-wise Fst. Both beetles and fungi exhibited moderate levels of genetic structure over the total study area, low levels of structure in the south, and more pronounced fungal structure in the north. Beetle genetic variation was associated with geographic location while that of the fungus was not. Pinevolume and climate explained beetle genetic variation in the northern region of recent outbreak expansion. Reciprocal genetic relationships were only detectedin the south where there has been alonger history of beetle infestations. The Euclidean distance and Fst-based analyses resulted in similar models in the north and over the entire study area, but differences between methods in the south suggest that genetic distances measures should be selected based on ecological and evolutionary contexts. The integrated landscape genetics framework we present is powerful, general, and can be applied to other systems to quantify the biotic and abiotic determinants of spatial genetic variation within and among taxa. PMID:21991309

  1. Spatial genetic structure of a symbiotic beetle-fungal system: toward multi-taxa integrated landscape genetics.

    PubMed

    James, Patrick M A; Coltman, Dave W; Murray, Brent W; Hamelin, Richard C; Sperling, Felix A H

    2011-01-01

    Spatial patterns of genetic variation in interacting species can identify shared features that are important to gene flow and can elucidate co-evolutionary relationships. We assessed concordance in spatial genetic variation between the mountain pine beetle (Dendroctonus ponderosae) and one of its fungal symbionts, Grosmanniaclavigera, in western Canada using neutral genetic markers. We examined how spatial heterogeneity affects genetic variation within beetles and fungi and developed a novel integrated landscape genetics approach to assess reciprocal genetic influences between species using constrained ordination. We also compared landscape genetic models built using Euclidean distances based on allele frequencies to traditional pair-wise Fst. Both beetles and fungi exhibited moderate levels of genetic structure over the total study area, low levels of structure in the south, and more pronounced fungal structure in the north. Beetle genetic variation was associated with geographic location while that of the fungus was not. Pinevolume and climate explained beetle genetic variation in the northern region of recent outbreak expansion. Reciprocal genetic relationships were only detectedin the south where there has been alonger history of beetle infestations. The Euclidean distance and Fst-based analyses resulted in similar models in the north and over the entire study area, but differences between methods in the south suggest that genetic distances measures should be selected based on ecological and evolutionary contexts. The integrated landscape genetics framework we present is powerful, general, and can be applied to other systems to quantify the biotic and abiotic determinants of spatial genetic variation within and among taxa.

  2. Precision genetics for complex objectives in animal agriculture.

    PubMed

    Fahrenkrug, S C; Blake, A; Carlson, D F; Doran, T; Van Eenennaam, A; Faber, D; Galli, C; Gao, Q; Hackett, P B; Li, N; Maga, E A; Muir, W M; Murray, J D; Shi, D; Stotish, R; Sullivan, E; Taylor, J F; Walton, M; Wheeler, M; Whitelaw, B; Glenn, B P

    2010-07-01

    Indirect modification of animal genomes by interspecific hybridization, cross-breeding, and selection has produced an enormous spectrum of phenotypic diversity over more than 10,000 yr of animal domestication. Using these established technologies, the farming community has successfully increased the yield and efficiency of production in most agricultural species while utilizing land resources that are often unsuitable for other agricultural purposes. Moving forward, animal well-being and agricultural sustainability are moral and economic priorities of consumers and producers alike. Therefore, these considerations will be included in any strategy designed to meet the challenges produced by global climate change and an expanding world population. Improvements in the efficiency and precision of genetic technologies will enable a timely response to meet the multifaceted food requirements of a rapidly increasing world population.

  3. Structural Evidence for Common Ancestry of the Nuclear Pore Complex and Vesicle Coats

    SciTech Connect

    Brohawn, S.; Leksa, N; Spear, E; Rajashankar, K; Schwartz, T

    2008-01-01

    Nuclear pore complexes (NPCs) facilitate nucleocytoplasmic transport. These massive assemblies comprise an eightfold symmetric scaffold of architectural proteins and central-channel phenylalanine-glycine-repeat proteins forming the transport barrier. We determined the nucleoporin 85 (Nup85)bulletSeh1 structure, a module in the heptameric Nup84 complex, at 3.5 angstroms resolution. Structural, biochemical, and genetic analyses position the Nup84 complex in two peripheral NPC rings. We establish a conserved tripartite element, the ancestral coatomer element ACE1, that reoccurs in several nucleoporins and vesicle coat proteins, providing structural evidence of coevolution from a common ancestor. We identified interactions that define the organization of the Nup84 complex on the basis of comparison with vesicle coats and confirmed the sites by mutagenesis. We propose that the NPC scaffold, like vesicle coats, is composed of polygons with vertices and edges forming a membrane-proximal lattice that provides docking sites for additional nucleoporins.

  4. Brain imaging genetics in ADHD and beyond - mapping pathways from gene to disorder at different levels of complexity.

    PubMed

    Klein, Marieke; Onnink, Marten; van Donkelaar, Marjolein; Wolfers, Thomas; Harich, Benjamin; Shi, Yan; Dammers, Janneke; Arias-Va Squez, Alejandro; Hoogman, Martine; Franke, Barbara

    2017-01-31

    Attention-deficit/hyperactivity disorder (ADHD) is a common and often persistent neurodevelopmental disorder. Beyond gene-finding, neurobiological parameters, such as brain structure, connectivity, and function, have been used to link genetic variation to ADHD symptomatology. We performed a systematic review of brain imaging genetics studies involving 62 ADHD candidate genes in childhood and adult ADHD cohorts. Fifty-one eligible research articles described studies of 13 ADHD candidate genes. Almost exclusively, single genetic variants were studied, mostly focussing on dopamine-related genes. While promising results have been reported, imaging genetics studies are thus f