Spatial scaling and multi-model inference in landscape genetics: Martes americana in northern Idaho

Treesearch

Tzeidle N. Wasserman; Samuel A. Cushman; Michael K. Schwartz; David O. Wallin

2010-01-01

Individual-based analyses relating landscape structure to genetic distances across complex landscapes enable rigorous evaluation of multiple alternative hypotheses linking landscape structure to gene flow. We utilize two extensions to increase the rigor of the individual-based causal modeling approach to inferring relationships between landscape patterns and gene flow...

Genetic evaluation of the evolutionary distinctness of a federally endangered butterfly, Lange's Metalmark.

PubMed

Proshek, Benjamin; Dupuis, Julian R; Engberg, Anna; Davenport, Ken; Opler, Paul A; Powell, Jerry A; Sperling, Felix A H

2015-04-25

The Mormon Metalmark (Apodemia mormo) species complex occurs as isolated and phenotypically variable colonies in dryland areas across western North America. Lange's Metalmark, A. m. langei, one of the 17 subspecies taxonomically recognized in the complex, is federally listed under the U.S. Endangered Species Act of 1973. Metalmark taxa have traditionally been described based on phenotypic and ecological characteristics, and it is unknown how well this nomenclature reflects their genetic and evolutionary distinctiveness. Genetic variation in six microsatellite loci and mitochondrial cytochrome oxidase subunit I sequence was used to assess the population structure of the A. mormo species complex across 69 localities, and to evaluate A. m. langei's qualifications as an Evolutionarily Significant Unit. We discovered substantial genetic divergence within the species complex, especially across the Continental Divide, with population genetic structure corresponding more closely with geographic proximity and local isolation than with taxonomic divisions originally based on wing color and pattern characters. Lange's Metalmark was as genetically divergent as several other locally isolated populations in California, and even the unique phenotype that warranted subspecific and conservation status is reminiscent of the morphological variation found in some other populations. This study is the first genetic treatment of the A. mormo complex across western North America and potentially provides a foundation for reassessing the taxonomy of the group. Furthermore, these results illustrate the utility of molecular markers to aid in demarcation of biological units below the species level. From a conservation point of view, Apodemia mormo langei's diagnostic taxonomic characteristics may, by themselves, not support its evolutionary significance, which has implications for its formal listing as an Endangered Species.

Direct protein-protein conjugation by genetically introducing bioorthogonal functional groups into proteins.

PubMed

Kim, Sanggil; Ko, Wooseok; Sung, Bong Hyun; Kim, Sun Chang; Lee, Hyun Soo

2016-11-15

Proteins often function as complex structures in conjunction with other proteins. Because these complex structures are essential for sophisticated functions, developing protein-protein conjugates has gained research interest. In this study, site-specific protein-protein conjugation was performed by genetically incorporating an azide-containing amino acid into one protein and a bicyclononyne (BCN)-containing amino acid into the other. Three to four sites in each of the proteins were tested for conjugation efficiency, and three combinations showed excellent conjugation efficiency. The genetic incorporation of unnatural amino acids (UAAs) is technically simple and produces the mutant protein in high yield. In addition, the conjugation reaction can be conducted by simple mixing, and does not require additional reagents or linker molecules. Therefore, this method may prove very useful for generating protein-protein conjugates and protein complexes of biochemical significance. Copyright © 2016. Published by Elsevier Ltd.

INTEGRATING GENETIC AND STRUCTURAL DATA ON HUMAN PROTEIN KINOME IN NETWORK-BASED MODELING OF KINASE SENSITIVITIES AND RESISTANCE TO TARGETED AND PERSONALIZED ANTICANCER DRUGS.

PubMed

Verkhivker, Gennady M

2016-01-01

The human protein kinome presents one of the largest protein families that orchestrate functional processes in complex cellular networks, and when perturbed, can cause various cancers. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Coupled with the evolution of system biology approaches, genomic and proteomic technologies are rapidly identifying and charactering novel resistance mechanisms with the goal to inform rationale design of personalized kinase drugs. Integration of experimental and computational approaches can help to bring these data into a unified conceptual framework and develop robust models for predicting the clinical drug resistance. In the current study, we employ a battery of synergistic computational approaches that integrate genetic, evolutionary, biochemical, and structural data to characterize the effect of cancer mutations in protein kinases. We provide a detailed structural classification and analysis of genetic signatures associated with oncogenic mutations. By integrating genetic and structural data, we employ network modeling to dissect mechanisms of kinase drug sensitivities to oncogenic EGFR mutations. Using biophysical simulations and analysis of protein structure networks, we show that conformational-specific drug binding of Lapatinib may elicit resistant mutations in the EGFR kinase that are linked with the ligand-mediated changes in the residue interaction networks and global network properties of key residues that are responsible for structural stability of specific functional states. A strong network dependency on high centrality residues in the conformation-specific Lapatinib-EGFR complex may explain vulnerability of drug binding to a broad spectrum of mutations and the emergence of drug resistance. Our study offers a systems-based perspective on drug design by unravelling complex relationships between robustness of targeted kinase genes and binding specificity of targeted kinase drugs. We discuss how these approaches can exploit advances in chemical biology and network science to develop novel strategies for rationally tailored and robust personalized drug therapies.

Dissecting genome-wide association signals for loss-of-function phenotypes in sorghum flavonoid pigmentation traits

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWAS) are a powerful method to dissect the genetic basis of traits, though in practice the effects of complex genetic architecture and population structure remain poorly understood. To compare mapping strategies we dissect the genetic control of flavonoid pigmentatio...

The role of self-defined race/ethnicity in population structure control.

PubMed

Liu, X-Q; Paterson, A D; John, E M; Knight, J A

2006-07-01

Population-based association studies are powerful tools for the genetic mapping of complex diseases. However, this method is sensitive to potential confounding by population structure. While statistical methods that use genetic markers to detect and control for population structure have been the focus of current literature, the utility of self-defined race/ethnicity in controlling for population structure has been controversial. In this study of 1334 individuals, who self-identified as either African American, European American or Hispanic, we demonstrated that when the true underlying genetic structure and the self-defined racial/ethnic groups were roughly in agreement with each other, the self-defined race/ethnicity information was useful in the control of population structure.

Testing the Structure of Hydrological Models using Genetic Programming

NASA Astrophysics Data System (ADS)

Selle, B.; Muttil, N.

2009-04-01

Genetic Programming is able to systematically explore many alternative model structures of different complexity from available input and response data. We hypothesised that genetic programming can be used to test the structure hydrological models and to identify dominant processes in hydrological systems. To test this, genetic programming was used to analyse a data set from a lysimeter experiment in southeastern Australia. The lysimeter experiment was conducted to quantify the deep percolation response under surface irrigated pasture to different soil types, water table depths and water ponding times during surface irrigation. Using genetic programming, a simple model of deep percolation was consistently evolved in multiple model runs. This simple and interpretable model confirmed the dominant process contributing to deep percolation represented in a conceptual model that was published earlier. Thus, this study shows that genetic programming can be used to evaluate the structure of hydrological models and to gain insight about the dominant processes in hydrological systems.

Pathogenesis of autism: a patchwork of genetic causes

PubMed Central

Grigorenko, Elena L

2009-01-01

Autism spectrum disorders (ASDs) are relatively infrequent but are devastating developmental conditions characterized by marked deficiencies in social, communicative and other behavioral domains. It has been known for a substantial period of time that these disorders are genetic in nature. However, elucidating the specific mechanisms of these disorders has been difficult. A major reason for such difficulty is the recognized genetic heterogeneity of ASDs. Specifically, many genetic mechanisms related to structural variations in the genome have been reported as possible genetic causes of these disorders. This review briefly exemplifies these genetic mechanisms, presents a concise overview of the evidence for the genetic basis of ASDs and provides an appraisal of the specific structural genetic variants thought to contribute to the pathogenesis of these complex disorders. PMID:19953194

The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia.

PubMed

Trifonova, E A; Eremina, E R; Urnov, F D; Stepanov, V A

2012-01-01

The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common "old" mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFRhaplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropicMTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics.

Genetic diversity based on 28S rDNA sequences among populations of Culex quinquefasciatus collected at different locations in Tamil Nadu, India.

PubMed

Sakthivelkumar, S; Ramaraj, P; Veeramani, V; Janarthanan, S

2015-09-01

The basis of the present study was to distinguish the existence of any genetic variability among populations of Culex quinquefasciatus which would be a valuable tool in the management of mosquito control programmes. In the present study, population of Cx. quinquefasciatus collected at different locations in Tamil Nadu were analyzed for their genetic variation based on 28S rDNA D2 region nucleotide sequences. A high degree of genetic polymorphism was detected in the sequences of D2 region of 28S rDNA on the predicted secondary structures in spite of high nucleotide sequence similarity. The findings based on secondary structure using rDNA sequences suggested the existence of a complex genotypic diversity of Cx. quinquefasciatus population collected at different locations of Tamil Nadu, India. This complexity in genetic diversity in a single mosquito population collected at different locations is considered an important issue towards their influence and nature of vector potential of these mosquitoes.

Testing the structure of a hydrological model using Genetic Programming

NASA Astrophysics Data System (ADS)

Selle, Benny; Muttil, Nitin

2011-01-01

SummaryGenetic Programming is able to systematically explore many alternative model structures of different complexity from available input and response data. We hypothesised that Genetic Programming can be used to test the structure of hydrological models and to identify dominant processes in hydrological systems. To test this, Genetic Programming was used to analyse a data set from a lysimeter experiment in southeastern Australia. The lysimeter experiment was conducted to quantify the deep percolation response under surface irrigated pasture to different soil types, watertable depths and water ponding times during surface irrigation. Using Genetic Programming, a simple model of deep percolation was recurrently evolved in multiple Genetic Programming runs. This simple and interpretable model supported the dominant process contributing to deep percolation represented in a conceptual model that was published earlier. Thus, this study shows that Genetic Programming can be used to evaluate the structure of hydrological models and to gain insight about the dominant processes in hydrological systems.

An evolutionary algorithm that constructs recurrent neural networks.

PubMed

Angeline, P J; Saunders, G M; Pollack, J B

1994-01-01

Standard methods for simultaneously inducing the structure and weights of recurrent neural networks limit every task to an assumed class of architectures. Such a simplification is necessary since the interactions between network structure and function are not well understood. Evolutionary computations, which include genetic algorithms and evolutionary programming, are population-based search methods that have shown promise in many similarly complex tasks. This paper argues that genetic algorithms are inappropriate for network acquisition and describes an evolutionary program, called GNARL, that simultaneously acquires both the structure and weights for recurrent networks. GNARL's empirical acquisition method allows for the emergence of complex behaviors and topologies that are potentially excluded by the artificial architectural constraints imposed in standard network induction methods.

Geographical genetic structuring and phenotypic variation in the Vellozia hirsuta (Velloziaceae) ochlospecies complex.

PubMed

Barbosa, Ariane R; Fiorini, Cecília F; Silva-Pereira, Viviane; Mello-Silva, Renato; Borba, Eduardo L

2012-09-01

Vellozia hirsuta forms a complex presenting wide morphological and anatomical variation, resulting in five specific names and 14 morpho-anatomical patterns occurring in disjunct populations. We carried out a phylogeographical study to investigate the existence of correlation among the genetic and morphological patterns within this complex, and to determine whether it is composed of various species or should be treated as an ochlospecies, a species having widely polymorphic and weakly polytypic complex variation, with morphological characteristics varying independently. We carried out phylogeographical analyses using cpDNA rpl32F-trnL intergenic region. We found 20 haplotypes in 23 populations sampled. The populations are genetically structured (Φ(ST) = 0.818) into four phylogeographical groups demonstrating geographical structuring but with no correlation with morpho-anatomical patterns. Our analyses do not support recognizing any of the species now synonymized under Vellozia hirsuta. The northern populations were the most genetically differentiated and could be considered a distinct taxon, as they are also morphologically different. It is recommended that Vellozia hirsuta be considered a single enormously variable species. The patterns of variation within V. hirsuta probably are related to climatic changes that occurred during the Pleistocene Epoch in tropical Brazil when reductions in forest cover favored the expansion of V. hirsuta populations into extensive lowland areas. The expansion of forest cover at the end of the glaciations would have again restricted the occurrence of campos rupestres vegetation to high elevations, which constitute the current centers of diversity of this species.

Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control

PubMed Central

Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram; Covelli, Antonio S.; Westler, William M.; Azadi, Parastoo; Nett, Jeniel

2018-01-01

ABSTRACT Candida biofilms resist the effects of available antifungal therapies. Prior studies with Candida albicans biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non-albicans Candida species (NAC). Our findings reveal that each Candida species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each Candida species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among Candida spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan-Candida species biofilm therapy. PMID:29615504

Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control.

PubMed

Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram; Covelli, Antonio S; Westler, William M; Azadi, Parastoo; Nett, Jeniel; Mitchell, Aaron P; Andes, David R

2018-04-03

Candida biofilms resist the effects of available antifungal therapies. Prior studies with Candida albicans biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non- albicans Candida species (NAC). Our findings reveal that each Candida species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each Candida species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among Candida spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan- Candida species biofilm therapy. IMPORTANCE Candida species, the most common fungal pathogens, frequently grow as a biofilm. These adherent communities tolerate extremely high concentrations of antifungal agents, due in large part, to a protective extracellular matrix. The present studies define the structural, functional, and genetic similarities and differences in the biofilm matrix from the four most common Candida species. Each species synthesizes an extracellular mannan-glucan complex (MGCx) which contributes to sequestration of antifungal drug, shielding the fungus from this external assault. Synthesis of a common polysaccharide backbone appears conserved. However, subtle structural differences in the branching side chains likely rely upon unique modification enzymes, which are species specific. Our findings identify MGCx backbone synthesis as a potential pan- Candida biofilm therapeutic target. Copyright © 2018 Dominguez et al.

Life history determines genetic structure and evolutionary potential of host–parasite interactions

PubMed Central

Barrett, Luke G.; Thrall, Peter H.; Burdon, Jeremy J.; Linde, Celeste C.

2009-01-01

Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns. PMID:18947899

Life history determines genetic structure and evolutionary potential of host-parasite interactions.

PubMed

Barrett, Luke G; Thrall, Peter H; Burdon, Jeremy J; Linde, Celeste C

2008-12-01

Measures of population genetic structure and diversity of disease-causing organisms are commonly used to draw inferences regarding their evolutionary history and potential to generate new variation in traits that determine interactions with their hosts. Parasite species exhibit a range of population structures and life-history strategies, including different transmission modes, life-cycle complexity, off-host survival mechanisms and dispersal ability. These are important determinants of the frequency and predictability of interactions with host species. Yet the complex causal relationships between spatial structure, life history and the evolutionary dynamics of parasite populations are not well understood. We demonstrate that a clear picture of the evolutionary potential of parasitic organisms and their demographic and evolutionary histories can only come from understanding the role of life history and spatial structure in influencing population dynamics and epidemiological patterns.

Complex Patterns of Local Adaptation in Teosinte

PubMed Central

Pyhäjärvi, Tanja; Hufford, Matthew B.; Mezmouk, Sofiane; Ross-Ibarra, Jeffrey

2013-01-01

Populations of widely distributed species encounter and must adapt to local environmental conditions. However, comprehensive characterization of the genetic basis of adaptation is demanding, requiring genome-wide genotype data, multiple sampled populations, and an understanding of population structure and potential selection pressures. Here, we used single-nucleotide polymorphism genotyping and data on numerous environmental variables to describe the genetic basis of local adaptation in 21 populations of teosinte, the wild ancestor of maize. We found complex hierarchical genetic structure created by altitude, dispersal events, and admixture among subspecies, which complicated identification of locally beneficial alleles. Patterns of linkage disequilibrium revealed four large putative inversion polymorphisms showing clinal patterns of frequency. Population differentiation and environmental correlations suggest that both inversions and intergenic polymorphisms are involved in local adaptation. PMID:23902747

Using Full Genomic Information to Predict Disease: Breaking Down the Barriers Between Complex and Mendelian Diseases.

PubMed

Jordan, Daniel M; Do, Ron

2018-04-11

While sequence-based genetic tests have long been available for specific loci, especially for Mendelian disease, the rapidly falling costs of genome-wide genotyping arrays, whole-exome sequencing, and whole-genome sequencing are moving us toward a future where full genomic information might inform the prognosis and treatment of a variety of diseases, including complex disease. Similarly, the availability of large populations with full genomic information has enabled new insights about the etiology and genetic architecture of complex disease. Insights from the latest generation of genomic studies suggest that our categorization of diseases as complex may conceal a wide spectrum of genetic architectures and causal mechanisms that ranges from Mendelian forms of complex disease to complex regulatory structures underlying Mendelian disease. Here, we review these insights, along with advances in the prediction of disease risk and outcomes from full genomic information. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 19 is August 31, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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, performs well under different simulated scenarios and with real data. Therefore, it could be a useful tool to determine genetically homogeneous groups, especially in those situations where the number of clusters is high, with complex population structure and where Hardy-Weinberg and/or linkage equilibrium are present. PMID:19900278

ViSEN: methodology and software for visualization of statistical epistasis networks

PubMed Central

Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W.; Moore, Jason H.

2013-01-01

The non-linear interaction effect among multiple genetic factors, i.e. epistasis, has been recognized as a key component in understanding the underlying genetic basis of complex human diseases and phenotypic traits. Due to the statistical and computational complexity, most epistasis studies are limited to interactions with an order of two. We developed ViSEN to analyze and visualize epistatic interactions of both two-way and three-way. ViSEN not only identifies strong interactions among pairs or trios of genetic attributes, but also provides a global interaction map that shows neighborhood and clustering structures. This visualized information could be very helpful to infer the underlying genetic architecture of complex diseases and to generate plausible hypotheses for further biological validations. ViSEN is implemented in Java and freely available at https://sourceforge.net/projects/visen/. PMID:23468157

Evaluation of the genetic structure present in natural populations of four subspecies of black cherry (Prunus serotina Ehrh.) from North America using SSR markers

USDA-ARS?s Scientific Manuscript database

Black cherry (Prunus serotina) is a fruit tree native to North America, and almost all parts of this plant have some use. This species is a complex of five subspecies with morphological differences and distinctive habitats. The genetic structure of 18 natural populations of black cherry was evaluate...

INNER EAR EMBRYOGENESIS: GENETIC AND ENVIRONMENTAL DETERMINANTS

EPA Science Inventory

The anatomy and developmental molecular genetics of the inner ear from establishment of the otic placode to formation of the definitive cochlea and vestibular apparatus will be reviewed and the complex 3-D structural changes that shape the developing inner ear will be illustrated...

[The muzzle and biochemical genetic markers as supplementary breed characteristics in cattle].

PubMed

Tarasiuk, S I; Glazko, V I; Trofimenko, A L

1997-01-01

The comparative analysis of characteristics of three different cattle breeds (Brown Carpathian, Pinzgauer, Red Polish) on the 5 molecular-genetic markers and 5 muzzle dermatoglyphic types was carried out. It was indicated, that one characteristic can not be use as a breed-specific one but only their complex. The main aspect of search of this complex is the use of characteristics which mark different structure-functional systems of whole organism.

A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

PubMed Central

Kijas, James W.; Townley, David; Dalrymple, Brian P.; Heaton, Michael P.; Maddox, Jillian F.; McGrath, Annette; Wilson, Peter; Ingersoll, Roxann G.; McCulloch, Russell; McWilliam, Sean; Tang, Dave; McEwan, John; Cockett, Noelle; Oddy, V. Hutton; Nicholas, Frank W.; Raadsma, Herman

2009-01-01

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 identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability. PMID:19270757

Islands within an island: Population genetic structure of the endemic Sardinian newt, Euproctus platycephalus.

PubMed

Ball, Sarah E; Bovero, Stefano; Sotgiu, Giuseppe; Tessa, Giulia; Angelini, Claudio; Bielby, Jon; Durrant, Christopher; Favelli, Marco; Gazzaniga, Enrico; Garner, Trenton W J

2017-02-01

The identification of historic and contemporary barriers to dispersal is central to the conservation of endangered amphibians, but may be hindered by their complex life history and elusive nature. The complementary information generated by mitochondrial (mtDNA) and microsatellite markers generates a valuable tool in elucidating population structure and the impact of habitat fragmentation. We applied this approach to the study of an endangered montane newt, Euproctus platycephalus . Endemic to the Mediterranean island of Sardinia, it is threatened by anthropogenic activity, disease, and climate change. We have demonstrated a clear hierarchy of structure across genetically divergent and spatially distinct subpopulations. Divergence between three main mountain regions dominated genetic partitioning with both markers. Mitochondrial phylogeography revealed a deep division dating to ca. 1 million years ago (Mya), isolating the northern region, and further differentiation between the central and southern regions ca. 0.5 Mya, suggesting an association with Pleistocene severe glacial oscillations. Our findings are consistent with a model of southward range expansion during glacial periods, with postglacial range retraction to montane habitat and subsequent genetic isolation. Microsatellite markers revealed further strong population structure, demonstrating significant divergence within the central region, and partial differentiation within the south. The northern population showed reduced genetic diversity. Discordance between mitochondrial and microsatellite markers at this scale indicated a further complexity of population structure, in keeping with male-biased dispersal and female philopatry. Our study underscores the need to elucidate cryptic population structure in the ecology and conservation strategies for endangered island-restricted amphibians, especially in the context of disease and climate change.

Genetic differentiation and phylogeographical structure of the Brachionus calyciflorus complex in eastern China.

PubMed

Xiang, Xian-Ling; Xi, Yi-Long; Wen, Xin-Li; Zhang, Gen; Wang, Jin-Xia; Hu, Ke

2011-07-01

Spatio-temporal patterns and processes of genetic differentiation in passively dispersing zooplankton are drawing much attention from both ecologists and evolutionary biologists. Two opposite phylogeographical scenarios have already been demonstrated in rotifers, which consist of high levels of genetic differentiation among populations even on small geographical scales on the one hand and the traditionally known cosmopolitanism that is associated with high levels of gene flow and long-distance dispersal via diapausing stages on the other hand. Here, we analysed the population genetic structure and the phylogeography of the Brachionus calyciflorus species complex in eastern China. By screening a total of 318 individuals from ten locations along a 2320-km gradient and analysing samples from two growing seasons, we aimed at focusing on both small- and large-scale patterns. We identified eight cryptic species and verified species status of two of these by sexual reproduction tests. Samples in summer and winter yielded different cryptic species. The distribution patterns of these genetically distinct cryptic species were diverse across eastern China, from full cosmopolitanism to local endemism. The two most abundant cryptic species BcWIII and BcSW showed a pattern of strong genetic differentiation among populations and no significant isolation by distance. Long-distance colonization, secondary contact and recent range expansion are probably responsible for the indistinct pattern of isolation by distance. Our results suggest that geographical distance is more important than temporal segregation across seasons in explaining population differentiation and the occurrence of cryptic species. We explain the current phylogeographical structure in the B. calyciflorus species complex by a combination of recent population expansion, restricted gene flow, priority effects and long-distance colonization. © 2011 Blackwell Publishing Ltd.

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.

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

PubMed Central

Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T.; Texier, Yves; van Beersum, Sylvia E. C.; Horn, Nicola; Willer, Jason R.; Mans, Dorus A.; Dougherty, Gerard; Lamers, Ideke J. C.; Coene, Karlien L. M.; Arts, Heleen H.; Betts, Matthew J.; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J. F.; Marcelis, Carlo L.; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M.; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A.; Toedt, Grischa; van Dam, Teunis J. P.; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L.; Blacque, Oliver E.; Gibson, Toby J.; Huynen, Martijn A.; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E.; Franco, Brunella; Giles, Rachel H.; Ueffing, Marius; Russell, Robert B.; Roepman, Ronald; Al-Turki, Saeed; Anderson, Carl; Antony, Dinu; Barroso, Inês; Bentham, Jamie; Bhattacharya, Shoumo; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Danecek, Petr; Durbin, Richard; Fitzpatrick, David; Floyd, Jamie; Reghan Foley, A.; Franklin, Chris; Futema, Marta; Humphries, Steve E.; Hurles, Matt; Joyce, Chris; McCarthy, Shane; Mitchison, Hannah M.; Muddyman, Dawn; Muntoni, Francesco; O'Rahilly, Stephen; Onoufriadis, Alexandros; Payne, Felicity; Plagnol, Vincent; Raymond, Lucy; Savage, David B.; Scambler, Peter; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert; Serra, Eva; Stalker, Jim; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Walter, Klaudia; Whittall, Ros; Williamson, Kathy

2016-01-01

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine. PMID:27173435

Adaptive major histocompatibility complex (MHC) and neutral genetic variation in two native Baltic Sea fishes (perch Perca fluviatilis and zander Sander lucioperca) with comparisons to an introduced and disease susceptible population in Australia (P. fluviatilis): assessing the risk of disease epidemics.

PubMed

Faulks, L K; Östman, Ö

2016-04-01

This study assessed the major histocompatibility complex (MHC) and neutral genetic variation and structure in two percid species, perch Perca fluviatilis and zander Sander lucioperca, in a unique brackish ecosystem, the Baltic Sea. In addition, to assess the importance of MHC diversity to disease susceptibility in these populations, comparisons were made to an introduced, disease susceptible, P. fluviatilis population in Australia. Eighty-three MHC class II B exon 2 variants were amplified: 71 variants from 92 P. fluviatilis samples, and 12 variants from 82 S. lucioperca samples. Microsatellite and MHC data revealed strong spatial genetic structure in S. lucioperca, but not P. fluviatilis, across the Baltic Sea. Both microsatellite and MHC data showed higher levels of genetic diversity in P. fluviatilis from the Baltic Sea compared to Australia, which may have facilitated the spread of an endemic virus, EHNV in the Australian population. The relatively high levels of genetic variation in the Baltic Sea populations, together with spatial genetic structure, however, suggest that there currently seems to be little risk of disease epidemics in this system. To ensure this remains the case in the face of ongoing environmental changes, fisheries and habitat disturbance, the conservation of local-scale genetic variation is recommended. © 2016 The Fisheries Society of the British Isles.

Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

PubMed

Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

2016-04-01

To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes.

Flying between sky islands: the effect of naturally fragmented habitat on butterfly population structure.

PubMed

Sekar, Sandhya; Karanth, Praveen

2013-01-01

High elevation montane areas are called "sky islands" when they occur as a series of high mountains separated by lowland valleys. Different climatic conditions at high elevations makes sky islands a specialized type of habitat, rendering them naturally fragmented compared to more continuous habitat at lower elevations. Species in sky islands face unsuitable climate in the intervening valleys when moving from one montane area to another. The high elevation shola-grassland mosaic in the Western Ghats of southern India form one such sky island complex. The fragmented patches make this area ideal to study the effect of the spatial orientation of suitable habitat patches on population genetic structure of species found in these areas. Past studies have suggested that sky islands tend to have genetically structured populations, possibly due to reduced gene flow between montane areas. To test this hypothesis, we adopted the comparative approach. Using Amplified Fragment Length Polymorphisms, we compared population genetic structures of two closely related, similar sized butterfly species: Heteropsis oculus, a high elevation shola-grassland specialist restricted to the southern Western Ghats, and Mycalesis patnia, found more continuously distributed in lower elevations. In all analyses, as per expectation the sky island specialist H. oculus exhibited a greater degree of population genetic structure than M. patnia, implying a difference in geneflow. This difference in geneflow in turn appears to be due to the natural fragmentation of the sky island complexes. Detailed analysis of a subset of H. oculus samples from one sky island complex (the Anamalais) showed a surprising genetic break. A possible reason for this break could be unsuitable conditions of higher temperature and lower rainfall in the intervening valley region. Thus, sky island species are not only restricted by lack of habitat continuity between montane areas, but also by the nature of the intervening habitat.

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.

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

A model for family-based case-control studies of genetic imprinting and epistasis.

PubMed

Li, Xin; Sui, Yihan; Liu, Tian; Wang, Jianxin; Li, Yongci; Lin, Zhenwu; Hegarty, John; Koltun, Walter A; Wang, Zuoheng; Wu, Rongling

2014-11-01

Genetic imprinting, or called the parent-of-origin effect, has been recognized to play an important role in the formation and pathogenesis of human diseases. Although the epigenetic mechanisms that establish genetic imprinting have been a focus of many genetic studies, our knowledge about the number of imprinting genes and their chromosomal locations and interactions with other genes is still scarce, limiting precise inference of the genetic architecture of complex diseases. In this article, we present a statistical model for testing and estimating the effects of genetic imprinting on complex diseases using a commonly used case-control design with family structure. For each subject sampled from a case and control population, we not only genotype its own single nucleotide polymorphisms (SNPs) but also collect its parents' genotypes. By tracing the transmission pattern of SNP alleles from parental to offspring generation, the model allows the characterization of genetic imprinting effects based on Pearson tests of a 2 × 2 contingency table. The model is expanded to test the interactions between imprinting effects and additive, dominant and epistatic effects in a complex web of genetic interactions. Statistical properties of the model are investigated, and its practical usefulness is validated by a real data analysis. The model will provide a useful tool for genome-wide association studies aimed to elucidate the picture of genetic control over complex human diseases. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neurogenetics of developmental dyslexia: from genes to behavior through brain neuroimaging and cognitive and sensorial mechanisms

PubMed Central

Mascheretti, S; De Luca, A; Trezzi, V; Peruzzo, D; Nordio, A; Marino, C; Arrigoni, F

2017-01-01

Developmental dyslexia (DD) is a complex neurodevelopmental deficit characterized by impaired reading acquisition, in spite of adequate neurological and sensorial conditions, educational opportunities and normal intelligence. Despite the successful characterization of DD-susceptibility genes, we are far from understanding the molecular etiological pathways underlying the development of reading (dis)ability. By focusing mainly on clinical phenotypes, the molecular genetics approach has yielded mixed results. More optimally reduced measures of functioning, that is, intermediate phenotypes (IPs), represent a target for researching disease-associated genetic variants and for elucidating the underlying mechanisms. Imaging data provide a viable IP for complex neurobehavioral disorders and have been extensively used to investigate both morphological, structural and functional brain abnormalities in DD. Performing joint genetic and neuroimaging studies in humans is an emerging strategy to link DD-candidate genes to the brain structure and function. A limited number of studies has already pursued the imaging–genetics integration in DD. However, the results are still not sufficient to unravel the complexity of the reading circuit due to heterogeneous study design and data processing. Here, we propose an interdisciplinary, multilevel, imaging–genetic approach to disentangle the pathways from genes to behavior. As the presence of putative functional genetic variants has been provided and as genetic associations with specific cognitive/sensorial mechanisms have been reported, new hypothesis-driven imaging–genetic studies must gain momentum. This approach would lead to the optimization of diagnostic criteria and to the early identification of ‘biologically at-risk’ children, supporting the definition of adequate and well-timed prevention strategies and the implementation of novel, specific remediation approach. PMID:28045463

A Multi-Faceted Approach to Analyse the Effects of Environmental Variables on Geographic Range and Genetic Structure of a Perennial Psammophilous Geophyte: The Case of the Sea Daffodil Pancratium maritimum L. in the Mediterranean Basin

PubMed Central

Di Febbraro, Mirko; Imparato, Gennaro; Innangi, Michele; Véla, Errol; Menale, Bruno

2016-01-01

The Mediterranean coastline is a dynamic and complex system which owes its complexity to its past and present vicissitudes, e.g. complex tectonic history, climatic fluctuations, and prolonged coexistence with human activities. A plant species that is widespread in this habitat is the sea daffodil, Pancratium maritimum (Amaryllidaceae), which is a perennial clonal geophyte of the coastal sands of the Mediterranean and neighbouring areas, well adapted to the stressful conditions of sand dune environments. In this study, an integrated approach was used, combining genetic and environmental data with a niche modelling approach, aimed to investigate: (1) the effect of climate change on the geographic range of this species at different times {past (last inter-glacial, LIG; and last glacial maximum, LGM), present (CURR), near-future (FUT)} and (2) the possible influence of environmental variables on the genetic structure of this species in the current period. The genetic results show that 48 sea daffodil populations (867 specimens) display a good genetic diversity in which the marginal populations (i.e. Atlantic Sea populations) present lower values. Recent genetic signature of bottleneck was detected in few populations (8%). The molecular variation was higher within the populations (77%) and two genetic pools were well represented. Comparing the different climatic simulations in time, the global range of this plant increased, and a further extension is foreseen in the near future thanks to projections on the climate of areas currently—more temperate, where our model suggested a forecast for a climate more similar to the Mediterranean coast. A significant positive correlation was observed between the genetic distance and Precipitation of Coldest Quarter variable in current periods. Our analyses support the hypothesis that geomorphology of the Mediterranean coasts, sea currents, and climate have played significant roles in shaping the current genetic structure of the sea daffodil especially during LGM because of strong variation in coastline caused by glaciations. PMID:27749920

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 (...

Multifaceted Population Structure and Reproductive Strategy in Leishmania donovani Complex in One Sudanese Village

PubMed Central

Hide, Mallorie; Le Falher, Georges; Bucheton, Bruno; Dereure, Jacques; El-Safi, Sayda H.; Dessein, Alain; Bañuls, Anne-Laure

2011-01-01

Leishmania species of the subgenus Leishmania and especially L. donovani are responsible for a large proportion of visceral leishmaniasis cases. The debate on the mode of reproduction and population structure of Leishmania parasites remains opened. It has been suggested that Leishmania parasites could alternate different modes of reproduction, more particularly clonality and frequent recombinations either between related individuals (endogamy) or between unrelated individuals (outcrossing) within strongly isolated subpopulations. To determine whether this assumption is generalized to other species, a population genetics analysis within Leishmania donovani complex strains was conducted within a single village. The results suggest that a mixed-mating reproduction system exists, an important heterogeneity of subsamples and the coexistence of several genetic entities in Sudanese L. donovani. Indeed, results showed significant genetic differentiation between the three taxa (L. donovani, L. infantum and L. archibaldi) and between the human or canine strains of such taxa, suggesting that there may be different imbricated transmission cycles involving either dogs or humans. Results also are in agreement with an almost strict specificity of L. donovani stricto sensu to human hosts. This empirical study demonstrates the complexity of population structure in the genus Leishmania and the need to pursue such kind of analyses at the smallest possible spatio-temporal and ecological scales. PMID:22206035

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

Impact of Geography and Climate on the Genetic Differentiation of the Subtropical Pine Pinus yunnanensis

PubMed Central

Zhao, Wei; Wang, Xiao-Ru

2013-01-01

Southwest China is a biodiversity hotspot characterized by complex topography, heterogeneous regional climates and rich flora. The processes and driving factors underlying this hotspot remain to be explicitly tested across taxa to gain a general understanding of the evolution of biodiversity and speciation in the region. In this study, we examined the role played by historically neutral processes, geography and environment in producing the current genetic diversity of the subtropical pine Pinus yunnanensis. We used genetic and ecological methods to investigate the patterns of genetic differentiation and ecological niche divergence across the distribution range of this species. We found both continuous genetic differentiation over the majority of its range, and discrete isolated local clusters. The discrete differentiation between two genetic groups in the west and east peripheries is consistent with niche divergence and geographical isolation of these groups. In the central area of the species’ range, population structure was shaped mainly by neutral processes and geography rather than by ecological selection. These results show that geographical and environmental factors together created stronger and more discrete genetic differentiation than isolation by distance alone, and illustrate the importance of ecological factors in forming or maintaining genetic divergence across a complex landscape. Our findings differ from other phylogenetic studies that identified the historical drainage system in the region as the primary factor shaping population structure, and highlight the heterogeneous contributions that geography and environment have made to genetic diversity among taxa in southwest China. PMID:23840668

Impact of Geography and Climate on the Genetic Differentiation of the Subtropical Pine Pinus yunnanensis.

PubMed

Wang, Baosheng; Mao, Jian-Feng; Zhao, Wei; Wang, Xiao-Ru

2013-01-01

Southwest China is a biodiversity hotspot characterized by complex topography, heterogeneous regional climates and rich flora. The processes and driving factors underlying this hotspot remain to be explicitly tested across taxa to gain a general understanding of the evolution of biodiversity and speciation in the region. In this study, we examined the role played by historically neutral processes, geography and environment in producing the current genetic diversity of the subtropical pine Pinus yunnanensis. We used genetic and ecological methods to investigate the patterns of genetic differentiation and ecological niche divergence across the distribution range of this species. We found both continuous genetic differentiation over the majority of its range, and discrete isolated local clusters. The discrete differentiation between two genetic groups in the west and east peripheries is consistent with niche divergence and geographical isolation of these groups. In the central area of the species' range, population structure was shaped mainly by neutral processes and geography rather than by ecological selection. These results show that geographical and environmental factors together created stronger and more discrete genetic differentiation than isolation by distance alone, and illustrate the importance of ecological factors in forming or maintaining genetic divergence across a complex landscape. Our findings differ from other phylogenetic studies that identified the historical drainage system in the region as the primary factor shaping population structure, and highlight the heterogeneous contributions that geography and environment have made to genetic diversity among taxa in southwest China.

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

PubMed Central

Archer, Trevor; Oscar-Berman, Marlene; Blum, Kenneth

2011-01-01

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring. PMID:22224195

The role of the Ord Arid Intrusion in the historical and contemporary genetic division of long-tailed finch subspecies in northern Australia

PubMed Central

Rollins, Lee Ann; Svedin, Nina; Pryke, Sarah R; Griffith, Simon C

2012-01-01

The effect of separation by biogeographic features followed by secondary contact can blur taxonomic boundaries and produce complex genetic signatures. We analyzed population structure and gene flow across the range of the long-tailed finch (Poephila acuticauda) in northern Australia (1) to test the hypothesis that Ord Arid Intrusion acted as the causative barrier that led to divergence of P. acuticauda subspecies, (2) to determine whether genetic data support the presence of a gradual cline across the range or a sudden shift, both of which have been suggested based on morphological data, and (3) to estimate levels of contemporary gene flow within this species complex. We collected samples from 302 individuals from 10 localities. Analyses of 12 microsatellite loci and sequence data from 333 base pairs of the mitochondrial control region were used to estimate population structure and gene flow, using analysis of molecular variance (AMOVA), haplotype network analysis, frequency statistics, and clustering methods. Mitochondrial sequence data indicated the presence of three genetic groups (regions) across the range of P. acuticauda. Genetic diversity was highest in the east and lowest in the west. The Ord Arid Intrusion appears to have functioned as a biogeographic barrier in the past, according to mtDNA evidence presented here and evidence from previous studies. The absence of isolation by distance between adjacent regions and the lack of population genetic structure of mtDNA within regions indicates that genetic changes across the range of P. acuticauda subspecies are characterized by discrete breaks between regions. While microsatellite data indicate a complete absence of genetic structure across this species’ range, it appears unlikely that this results from high levels of gene flow. Mitochondrial data do not support the presence of contemporary gene flow across the range of this species. PMID:22833795

Detection of expression quantitative trait Loci in complex mouse crosses: impact and alleviation of data quality and complex population substructure.

PubMed

Iancu, Ovidiu D; Darakjian, Priscila; Kawane, Sunita; Bottomly, Daniel; Hitzemann, Robert; McWeeney, Shannon

2012-01-01

Complex Mus musculus crosses, e.g., heterogeneous stock (HS), provide increased resolution for quantitative trait loci detection. However, increased genetic complexity challenges detection methods, with discordant results due to low data quality or complex genetic architecture. We quantified the impact of theses factors across three mouse crosses and two different detection methods, identifying procedures that greatly improve detection quality. Importantly, HS populations have complex genetic architectures not fully captured by the whole genome kinship matrix, calling for incorporating chromosome specific relatedness information. We analyze three increasingly complex crosses, using gene expression levels as quantitative traits. The three crosses were an F(2) intercross, a HS formed by crossing four inbred strains (HS4), and a HS (HS-CC) derived from the eight lines found in the collaborative cross. Brain (striatum) gene expression and genotype data were obtained using the Illumina platform. We found large disparities between methods, with concordance varying as genetic complexity increased; this problem was more acute for probes with distant regulatory elements (trans). A suite of data filtering steps resulted in substantial increases in reproducibility. Genetic relatedness between samples generated overabundance of detected eQTLs; an adjustment procedure that includes the kinship matrix attenuates this problem. However, we find that relatedness between individuals is not evenly distributed across the genome; information from distinct chromosomes results in relatedness structure different from the whole genome kinship matrix. Shared polymorphisms from distinct chromosomes collectively affect expression levels, confounding eQTL detection. We suggest that considering chromosome specific relatedness can result in improved eQTL detection.

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 solution to infer fine-scale genetic patterns. PMID:23077494

Sky island bird populations isolated by ancient genetic barriers are characterized by different song traits than those isolated by recent deforestation.

PubMed

Purushotham, Chetana B; Robin, V V

2016-10-01

Various mechanisms of isolation can structure populations and result in cultural and genetic differentiation. Similar to genetic markers, for songbirds, culturally transmitted sexual signals such as breeding song can be used as a measure of differentiation as songs can also be impacted by geographic isolation resulting in population-level differences in song structure. Several studies have found differences in song structure either across ancient geographic barriers or across contemporary habitat barriers owing to deforestation. However, very few studies have examined the effect of both ancient barriers and recent deforestation in the same system. In this study, we examined the geographic variation in song structure across six populations of the White-bellied Shortwing, a threatened and endemic songbird species complex found on isolated mountaintops or "sky islands" of the Western Ghats. While some sky islands in the system are isolated by ancient valleys, others are separated by deforestation. We examined 14 frequency and temporal spectral traits and two syntax traits from 835 songs of 38 individuals across the six populations. We identified three major song clusters based on a discriminant model of spectral traits, degree of similarity of syntax features, as well as responses of birds to opportunistic playback. However, some traits like complex vocal mechanisms (CVM), relating to the use of syrinxes, clearly differentiated both ancient and recently fragmented populations. We suggest that CVMs may have a cultural basis and can be used to identify culturally isolated populations that cannot be differentiated using genetic markers or commonly used frequency-based song traits. Our results demonstrate the use of bird songs to reconstruct phylogenetic groups and impacts of habitat fragmentation even in complex scenarios of historic and contemporary isolation.

Landscape genetics of Schistocephalus solidus parasites in threespine stickleback (Gasterosteus aculeatus) from Alaska.

PubMed

Sprehn, C Grace; Blum, Michael J; Quinn, Thomas P; Heins, David C

2015-01-01

The nature of gene flow in parasites with complex life cycles is poorly understood, particularly when intermediate and definitive hosts have contrasting movement potential. We examined whether the fine-scale population genetic structure of the diphyllobothriidean cestode Schistocephalus solidus reflects the habits of intermediate threespine stickleback hosts or those of its definitive hosts, semi-aquatic piscivorous birds, to better understand complex host-parasite interactions. Seventeen lakes in the Cook Inlet region of south-central Alaska were sampled, including ten in the Matanuska-Susitna Valley, five on the Kenai Peninsula, and two in the Bristol Bay drainage. We analyzed sequence variation across a 759 bp region of the mitochondrial DNA (mtDNA) cytochrome oxidase I region for 1,026 S. solidus individuals sampled from 2009-2012. We also analyzed allelic variation at 8 microsatellite loci for 1,243 individuals. Analysis of mtDNA haplotype and microsatellite genotype variation recovered evidence of significant population genetic structure within S. solidus. Host, location, and year were factors in structuring observed genetic variation. Pairwise measures revealed significant differentiation among lakes, including a pattern of isolation-by-distance. Bayesian analysis identified three distinct genotypic clusters in the study region, little admixture within hosts and lakes, and a shift in genotype frequencies over time. Evidence of fine-scale population structure in S. solidus indicates that movement of its vagile, definitive avian hosts has less influence on gene flow than expected based solely on movement potential. Observed patterns of genetic variation may reflect genetic drift, behaviors of definitive hosts that constrain dispersal, life history of intermediate hosts, and adaptive specificity of S. solidus to intermediate host genotype.

Up and down the blind alley: population divergence with scant gene flow in an endangered tropical lineage of Andean palms (Ceroxylon quindiuense clade: Ceroxyloideae).

PubMed

Sanín, María José; Zapata, Patricia; Pintaud, Jean-Christophe; Galeano, Gloria; Bohórquez, Adriana; Tohme, Joseph; Hansen, Michael Møller

2017-02-10

Given the geographical complexity of the Andes, species distributions hold interesting information regarding the history of isolation and gene flow across geographic barriers and ecological gradients. Moreover, current threats to the region’s enormous plant diversity pose an additional challenge to the understanding of these patterns. We explored the geographic structure of genetic diversity within the Ceroxylon quindiuense species complex (wax palms) at a regional scale, using a model-based approach to disentangle the historical mechanisms by which these species have dispersed over a range encompassing 17° of latitude in the tropical Andes. A total of 10 microsatellite loci were cross-amplified in 8 populations of the 3 species comprising the C. quindiuense complex. Analyses performed include estimates of molecular diversity and genetic structure, testing for genetic bottlenecks and an evaluation of the colonization scenario under approximate Bayesian computation. We showed that there was a geographical diversity gradient reflecting the orogenetic pattern of the northern Andes and its end at the cordilleras facing the Caribbean Sea. A general pattern of diversity suggests that the cordilleras of Colombia have served as historical recipients of gene flow occurring only scantly along the northern Andes. We provided evidence of important isolation between the largest populations of this complex, suggesting that both historical constraints to dispersal but also current anthropogenic effects might explain the high levels of population structuring. We provide a list of advisable measures for conservation stakeholders.

Associations between forest fragmentation patterns and geneticstructure in Pfrimer’s Parakeet (Pyrrhura pfrimeri), an endangered endemic to central Brazil’s dry forests

USGS Publications Warehouse

Haig, Susan M.; Miller, Leonard F.; Bianchi, Carlos; Mullins, Thomas D.

2012-01-01

When habitat becomes fragmented, populations of species may become increasingly isolated. In the absence of habitat corridors, genetic structure may develop and populations risk reductions in genetic diversity from increased genetic drift and inbreeding. Deforestation of the Cerrado biome of Brazil, particularly of the dry forests within the Parana˜ River Basin, has incrementally occurred since the 1970s and increased forest fragmentation within the region. We performed landscape genetic analyses of Pfrimer’s parakeet (Pyrrhura pfrimeri), a globally endangered endemic to the region, to determine if forest fragmentation patterns were associated with genetic structuring in this species. We used previously generated satellite imagery that identified the locations of Parana˜ River Basin forest fragments in 1977, 1993/94, and 2008. Behavioral data quantifying the affinity of Pfrimer’s parakeet for forest habitat was used to parameterize empirically derived landscape conductance surfaces. Though genetic structure was observed among Pfrimer’s parakeet populations, no association between genetic and geographic distance was detected. Likewise, least cost path lengths, circuit theorybased resistance distances, and a new measure of least cost path length complexity could not be conclusively associated with genetic structure patterns. Instead, a new quantity that encapsulated connection redundancy from the 1977 forest fragmentation data provided the clearest associations with pairwise genetic differentiation patterns (Jost’s D: r = 0.72, P = 0.006; FST: r = 0.741, P = 0.001). Our analyses suggest a 35-year or more lag between deforestation and its effect on genetic structure. Because 66 % of the Parana˜ River Basin has been deforested since 1977, we expect that genetic structure will increase substantially among Pfrimer’s Parakeet populations in the future, especially if fragmentation continues at its current pace.

Speciation in ancient cryptic species complexes: evidence from the molecular phylogeny of Brachionus plicatilis (Rotifera).

PubMed

Gómez, Africa; Serra, Manuel; Carvalho, Gary R; Lunt, David H

2002-07-01

Continental lake-dwelling zooplanktonic organisms have long been considered cosmopolitan species with little geographic variation in spite of the isolation of their habitats. Evidence of morphological cohesiveness and high dispersal capabilities support this interpretation. However, this view has been challenged recently as many such species have been shown either to comprise cryptic species complexes or to exhibit marked population genetic differentiation and strong phylogeographic structuring at a regional scale. Here we investigate the molecular phylogeny of the cosmopolitan passively dispersing rotifer Brachionus plicatilis (Rotifera: Monogononta) species complex using nucleotide sequence variation from both nuclear (ribosomal internal transcribed spacer 1, ITS1) and mitochondrial (cytochrome c oxidase subunit I, COI) genes. Analysis of rotifer resting eggs from 27 salt lakes in the Iberian Peninsula plus lakes from four continents revealed nine genetically divergent lineages. The high level of sequence divergence, absence of hybridization, and extensive sympatry observed support the specific status of these lineages. Sequence divergence estimates indicate that the B. plicatilis complex began diversifying many millions of years ago, yet has showed relatively high levels of morphological stasis. We discuss these results in relation to the ecology and genetics of aquatic invertebrates possessing dispersive resting propagules and address the apparent contradiction between zooplanktonic population structure and their morphological stasis.

Genetic differentiation and phylogeography of Mediterranean-North Eastern Atlantic blue shark (Prionace glauca, L. 1758) using mitochondrial DNA: panmixia or complex stock structure?

PubMed

Leone, Agostino; Urso, Ilenia; Damalas, Dimitrios; Martinsohn, Jann; Zanzi, Antonella; Mariani, Stefano; Sperone, Emilio; Micarelli, Primo; Garibaldi, Fulvio; Megalofonou, Persefoni; Bargelloni, Luca; Franch, Rafaella; Macias, David; Prodöhl, Paulo; Fitzpatrick, Séan; Stagioni, Marco; Tinti, Fausto; Cariani, Alessia

2017-01-01

The blue shark ( Prionace glauca , Linnaeus 1758) is one of the most abundant epipelagic shark inhabiting all the oceans except the poles, including the Mediterranean Sea, but its genetic structure has not been confirmed at basin and interoceanic distances. Past tagging programs in the Atlantic Ocean failed to find evidence of migration of blue sharks between the Mediterranean and the adjacent Atlantic, despite the extreme vagility of the species. Although the high rate of by-catch in the Mediterranean basin, to date no genetic study on Mediterranean blue shark was carried out, which constitutes a significant knowledge gap, considering that this population is classified as "Critically Endangered", unlike its open-ocean counterpart. Blue shark phylogeography and demography in the Mediterranean Sea and North-Eastern Atlantic Ocean were inferred using two mitochondrial genes (Cytb and control region) amplified from 207 and 170 individuals respectively, collected from six localities across the Mediterranean and two from the North-Eastern Atlantic. Although no obvious pattern of geographical differentiation was apparent from the haplotype network, Φst analyses indicated significant genetic structure among four geographical groups. Demographic analyses suggest that these populations have experienced a constant population expansion in the last 0.4-0.1 million of years. The weak, but significant, differences in Mediterranean and adjacent North-eastern Atlantic blue sharks revealed a complex phylogeographic structure, which appears to reject the assumption of panmixia across the study area, but also supports a certain degree of population connectivity across the Strait of Gibraltar, despite the lack of evidence of migratory movements observed by tagging data. Analyses of spatial genetic structure in relation to sex-ratio and size could indicate some level of sex/stage biased migratory behaviour.

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...

Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian.

PubMed

Griffiths, Sarah M; Harrison, Xavier A; Weldon, Ché; Wood, Michael D; Pretorius, Abigail; Hopkins, Kevin; Fox, Graeme; Preziosi, Richard F; Antwis, Rachael E

2018-06-25

Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases.

Series Hybrid Electric Vehicle Power System Optimization Based on Genetic Algorithm

NASA Astrophysics Data System (ADS)

Zhu, Tianjun; Li, Bin; Zong, Changfu; Wu, Yang

2017-09-01

Hybrid electric vehicles (HEV), compared with conventional vehicles, have complex structures and more component parameters. If variables optimization designs are carried on all these parameters, it will increase the difficulty and the convergence of algorithm program, so this paper chooses the parameters which has a major influence on the vehicle fuel consumption to make it all work at maximum efficiency. First, HEV powertrain components modelling are built. Second, taking a tandem hybrid structure as an example, genetic algorithm is used in this paper to optimize fuel consumption and emissions. Simulation results in ADVISOR verify the feasibility of the proposed genetic optimization algorithm.

Patterns and processes in the genetic differentiation of the Brachionus calyciflorus complex, a passively dispersing freshwater zooplankton.

PubMed

Xiang, Xian-ling; Xi, Yi-long; Wen, Xin-li; Zhang, Gen; Wang, Jin-xia; Hu, Ke

2011-05-01

Elucidating the evolutionary patterns and processes of extant species is an important objective of any research program that seeks to understand population divergence and, ultimately, speciation. The island-like nature and temporal fluctuation of limnetic habitats create opportunities for genetic differentiation in rotifers through space and time. To gain further understanding of spatio-temporal patterns of genetic differentiation in rotifers other than the well-studied Brachionus plicatilis complex in brackish water, a total of 318 nrDNA ITS sequences from the B. calyciflorus complex in freshwater were analysed using phylogenetic and phylogeographic methods. DNA taxonomy conducted by both the sequence divergence and the GMYC model suggested the occurrence of six potential cryptic species, supported also by reproductive isolation among the tested lineages. The significant genetic differentiation and non-significant correlation between geographic and genetic distances existed in the most abundant cryptic species, BcI-W and Bc-SW. The large proportion of genetic variability for cryptic species Bc-SW was due to differences between sampling localities within seasons, rather than between different seasons. Nested Clade Analysis suggested allopatric or past fragmentation, contiguous range expansion and long-distance colonization possibly coupled with subsequent fragmentation as the probable main forces shaping the present-day phylogeographic structure of the B. calyciflorus species complex. Copyright © 2011 Elsevier Inc. All rights reserved.

A novel structure-aware sparse learning algorithm for brain imaging genetics.

PubMed

Du, Lei; Jingwen, Yan; Kim, Sungeun; Risacher, Shannon L; Huang, Heng; Inlow, Mark; Moore, Jason H; Saykin, Andrew J; Shen, Li

2014-01-01

Brain imaging genetics is an emergent research field where the association between genetic variations such as single nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is evaluated. Sparse canonical correlation analysis (SCCA) is a bi-multivariate analysis method that has the potential to reveal complex multi-SNP-multi-QT associations. Most existing SCCA algorithms are designed using the soft threshold strategy, which assumes that the features in the data are independent from each other. This independence assumption usually does not hold in imaging genetic data, and thus inevitably limits the capability of yielding optimal solutions. We propose a novel structure-aware SCCA (denoted as S2CCA) algorithm to not only eliminate the independence assumption for the input data, but also incorporate group-like structure in the model. Empirical comparison with a widely used SCCA implementation, on both simulated and real imaging genetic data, demonstrated that S2CCA could yield improved prediction performance and biologically meaningful findings.

Distinct population structure for co-occurring Anopheles goeldii and Anopheles triannulatus in Amazonian Brazil

PubMed Central

McKeon, Sascha Naomi; Moreno, Marta; Sallum, Maria Anise; Povoa, Marinete Marins; Conn, Jan Evelyn

2013-01-01

To evaluate whether environmental heterogeneity contributes to the genetic heterogeneity in Anopheles triannulatus, larval habitat characteristics across the Brazilian states of Roraima and Pará and genetic sequences were examined. A comparison with Anopheles goeldii was utilised to determine whether high genetic diversity was unique to An. triannulatus. Student t test and analysis of variance found no differences in habitat characteristics between the species. Analysis of population structure of An. triannulatus and An. goeldii revealed distinct demographic histories in a largely overlapping geographic range. Cytochrome oxidase I sequence parsimony networks found geographic clustering for both species; however nuclear marker networks depicted An. triannulatus with a more complex history of fragmentation, secondary contact and recent divergence. Evidence of Pleistocene expansions suggests both species are more likely to be genetically structured by geographic and ecological barriers than demography. We hypothesise that niche partitioning is a driving force for diversity, particularly in An. triannulatus. PMID:23903977

Cellular automaton simulation examining progenitor hierarchy structure effects on mammary ductal carcinoma in situ.

PubMed

Bankhead, Armand; Magnuson, Nancy S; Heckendorn, Robert B

2007-06-07

A computer simulation is used to model ductal carcinoma in situ, a form of non-invasive breast cancer. The simulation uses known histological morphology, cell types, and stochastic cell proliferation to evolve tumorous growth within a duct. The ductal simulation is based on a hybrid cellular automaton design using genetic rules to determine each cell's behavior. The genetic rules are a mutable abstraction that demonstrate genetic heterogeneity in a population. Our goal was to examine the role (if any) that recently discovered mammary stem cell hierarchies play in genetic heterogeneity, DCIS initiation and aggressiveness. Results show that simpler progenitor hierarchies result in greater genetic heterogeneity and evolve DCIS significantly faster. However, the more complex progenitor hierarchy structure was able to sustain the rapid reproduction of a cancer cell population for longer periods of time.

Landscape-scale evaluation of genetic structure among barrier-isolated populations of coastal cutthroat trout, Oncorhynchus clarkii clarkii

USGS Publications Warehouse

Guy, T.J.; Gresswell, R.E.; Banks, M.A.

2008-01-01

Relationships among landscape structure, stochastic disturbance, and genetic diversity were assessed by examining interactions between watershed-scale environmental factors and genetic diversity of coastal cutthroat trout (Oncorhynchus clarkii clarkii) in 27 barrier-isolated watersheds from western Oregon, USA. Headwater populations of coastal cutthroat trout were genetically differentiated (mean FST = 0.33) using data from seven microsatellite loci (2232 individuals), but intrapopulation microsatellite genetic diversity (mean number of alleles per locus = 5, mean He = 0.60) was only moderate. Genetic diversity of coastal cutthroat trout was greater (P = 0.02) in the Coast Range ecoregion (mean alleles = 47) than in the Cascades ecoregion (mean alleles = 30), and differences coincided with indices of regional within-watershed complexity and connectivity. Furthermore, regional patterns of diversity evident from isolation-by-distance plots suggested that retention of within-population genetic diversity in the Coast Range ecoregion is higher than that in the Cascades, where genetic drift is the dominant factor influencing genetic patterns. Thus, it appears that physical landscape features have influenced genetic patterns in these populations isolated from short-term immigration. ?? 2008 NRC.

Genetic structure and invasion history of the house mouse (Mus musculus domesticus) in Senegal, West Africa: a legacy of colonial and contemporary times.

PubMed

Lippens, C; Estoup, A; Hima, M K; Loiseau, A; Tatard, C; Dalecky, A; Bâ, K; Kane, M; Diallo, M; Sow, A; Niang, Y; Piry, S; Berthier, K; Leblois, R; Duplantier, J-M; Brouat, C

2017-08-01

Knowledge of the genetic make-up and demographic history of invasive populations is critical to understand invasion mechanisms. Commensal rodents are ideal models to study whether complex invasion histories are typical of introductions involving human activities. The house mouse Mus musculus domesticus is a major invasive synanthropic rodent originating from South-West Asia. It has been largely studied in Europe and on several remote islands, but the genetic structure and invasion history of this taxon have been little investigated in several continental areas, including West Africa. In this study, we focussed on invasive populations of M. m. domesticus in Senegal. In this focal area for European settlers, the distribution area and invasion spread of the house mouse is documented by decades of data on commensal rodent communities. Genetic variation at one mitochondrial locus and 16 nuclear microsatellite markers was analysed from individuals sampled in 36 sites distributed across the country. A combination of phylogeographic and population genetics methods showed that there was a single introduction event on the northern coast of Senegal, from an exogenous (probably West European) source, followed by a secondary introduction from northern Senegal into a coastal site further south. The geographic locations of these introduction sites were consistent with the colonial history of Senegal. Overall, the marked microsatellite genetic structure observed in Senegal, even between sites located close together, revealed a complex interplay of different demographic processes occurring during house mouse spatial expansion, including sequential founder effects and stratified dispersal due to human transport along major roads.

Factors influencing organizational adoption and implementation of clinical genetic services.

PubMed

Hamilton, Alison B; Oishi, Sabine; Yano, Elizabeth M; Gammage, Cynthia E; Marshall, Nell J; Scheuner, Maren T

2014-03-01

We sought to identify characteristics of genetic services that facilitate or hinder adoption. We conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities. Genetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test-ordering processes. Adoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.

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

Phylogeography of the Rickett's big-footed bat, Myotis pilosus (Chiroptera: Vespertilionidae): a novel pattern of genetic structure of bats in China.

PubMed

Lu, Guanjun; Lin, Aiqing; Luo, Jinhong; Blondel, Dimitri V; Meiklejohn, Kelly A; Sun, Keping; Feng, Jiang

2013-11-05

China is characterized by complex topographic structure and dramatic palaeoclimatic changes, making species biogeography studies particularly interesting. Previous researchers have also demonstrated multiple species experienced complex population histories, meanwhile multiple shelters existed in Chinese mainland. Despite this, species phylogeography is still largely unexplored. In the present study, we used a combination of microsatellites and mitochondrial DNA (mtDNA) to investigate the phylogeography of the east Asian fish-eating bat (Myotis pilosus). Phylogenetic analyses showed that M. pilosus comprised three main lineages: A, B and C, which corresponded to distinct geographic populations of the Yangtze Plain (YTP), Sichuan Basin (SCB) and North and South of China (NSC), respectively. The most recent common ancestor of M. pilosus was dated as 0.25 million years before present (BP). Population expansion events were inferred for populations of Clade C, North China Plain region, Clade B and YunGui Plateau region at 38,700, 15,900, 4,520 and 4,520 years BP, respectively. Conflicting results were obtained from mtDNA and microsatellite analyses; strong population genetic structure was obtained from mtDNA data but not microsatellite data. The microsatellite data indicated that genetic subdivision fits an isolation-by-distance (IBD) model, but the mtDNA data failed to support this model. Our results suggested that Pleistocene climatic oscillations might have had a profound influence on the demographic history of M. pilosus. Spatial genetic structures of maternal lineages that are different from those observed in other sympatric bats species may be as a result of interactions among special population history and local environmental factors. There are at least three possible refugia for M. pilosus during glacial episodes. Apparently contradictory genetic structure patterns of mtDNA and microsatellite could be explained by male-mediated gene flow among populations. This study also provides insights on the necessity of conservation of M. pilosus populations to conserve this genetic biodiversity, especially in the areas of YTP, SCB and NSC regions.

Application of network methods for understanding evolutionary dynamics in discrete habitats.

PubMed

Greenbaum, Gili; Fefferman, Nina H

2017-06-01

In populations occupying discrete habitat patches, gene flow between habitat patches may form an intricate population structure. In such structures, the evolutionary dynamics resulting from interaction of gene-flow patterns with other evolutionary forces may be exceedingly complex. Several models describing gene flow between discrete habitat patches have been presented in the population-genetics literature; however, these models have usually addressed relatively simple settings of habitable patches and have stopped short of providing general methodologies for addressing nontrivial gene-flow patterns. In the last decades, network theory - a branch of discrete mathematics concerned with complex interactions between discrete elements - has been applied to address several problems in population genetics by modelling gene flow between habitat patches using networks. Here, we present the idea and concepts of modelling complex gene flows in discrete habitats using networks. Our goal is to raise awareness to existing network theory applications in molecular ecology studies, as well as to outline the current and potential contribution of network methods to the understanding of evolutionary dynamics in discrete habitats. We review the main branches of network theory that have been, or that we believe potentially could be, applied to population genetics and molecular ecology research. We address applications to theoretical modelling and to empirical population-genetic studies, and we highlight future directions for extending the integration of network science with molecular ecology. © 2017 John Wiley & Sons Ltd.

Complex spatial dynamics maintain northern leopard frog (Lithobates pipiens) genetic diversity in a temporally varying landscape

USGS Publications Warehouse

Mushet, David M.; Euliss, Ned H.; Chen, Yongjiu; Stockwell, Craig A.

2013-01-01

In contrast to most local amphibian populations, northeastern populations of the Northern Leopard Frog (Lithobates pipiens) have displayed uncharacteristically high levels of genetic diversity that have been attributed to large, stable populations. However, this widely distributed species also occurs in areas known for great climatic fluctuations that should be reflected in corresponding fluctuations in population sizes and reduced genetic diversity. To test our hypothesis that Northern Leopard Frog genetic diversity would be reduced in areas subjected to significant climate variability, we examined the genetic diversity of L. pipiens collected from 12 sites within the Prairie Pothole Region of North Dakota. Despite the region's fluctuating climate that includes periods of recurring drought and deluge, we found unexpectedly high levels of genetic diversity approaching that of northeastern populations. Further, genetic structure at a landscape scale was strikingly homogeneous; genetic differentiation estimates (Dest) averaged 0.10 (SD = 0.036) across the six microsatellite loci we studied, and two Bayesian assignment tests (STRUCTURE and BAPS) failed to reveal the development of significant population structure across the 68 km breadth of our study area. These results suggest that L. pipiens in the Prairie Pothole Region consists of a large, panmictic population capable of maintaining high genetic diversity in the face of marked climate variability.

Assessing the Genetic Influence of Ancient Sociopolitical Structure: Micro-differentiation Patterns in the Population of Asturias (Northern Spain)

PubMed Central

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

2012-01-01

The human populations of the Iberian Peninsula are the varied result of a complex mixture of cultures throughout history, and are separated by clear social, cultural, linguistic or geographic barriers. The stronger genetic differences between closely related populations occur in the northern third of Spain, a phenomenon commonly known as “micro-differentiation”. It has been argued and discussed how this form of genetic structuring can be related to both the rugged landscape and the ancient societies of Northern Iberia, but this is difficult to test in most regions due to the intense human mobility of previous centuries. Nevertheless, the Spanish autonomous community of Asturias shows a complex history which hints of a certain isolation of its population. This, joined together with a difficult terrain full of deep valleys and steep mountains, makes it suitable for performing a study of genetic structure, based on mitochondrial DNA and Y-Chromosome markers. Our analyses do not only show that there are micro-differentiation patterns inside the Asturian territory, but that these patterns are strikingly similar between both uniparental markers. The inference of barriers to gene flow also indicates that Asturian populations from the coastal north and the mountainous south seem to be relatively isolated from the rest of the territory. These findings are discussed in light of historic and geographic data and, coupled with previous evidence, show that the origin of the current genetic patterning might indeed lie in Roman and Pre-Roman sociopolitical divisions. PMID:23209673

Composite Structure Optimization with Genetic Algorithm

NASA Astrophysics Data System (ADS)

Deslandes, Olivier

2014-06-01

In the frame of optimization studies in CNES launcher directorate structure, thermic and material department, the need of an optimization tool based on metaheuristic and finite element models for composite structural dimensioning was underlined.Indeed, composite structures need complex optimization methodologies in order to be really compared to metallic structures with regard to mass, static strength and stiffness constraints (metallic structures using optimization methods better known).After some bibliography research, the use of a genetic algorithm coupled with design of experiment to generate the initial population was chosen. Academic functions were used to validate the optimization process and then it was applied to an industrial study aiming to optimize an interstage skirt with regard to its mass, stiffness and stability (global buckling).

A unified genetic association test robust to latent population structure for a count phenotype.

PubMed

Song, Minsun

2018-06-04

Confounding caused by latent population structure in genome-wide association studies has been a big concern despite the success of genome-wide association studies at identifying genetic variants associated with complex diseases. In particular, because of the growing interest in association mapping using count phenotype data, it would be interesting to develop a testing framework for genetic associations that is immune to population structure when phenotype data consist of count measurements. Here, I propose a solution for testing associations between single nucleotide polymorphisms and a count phenotype in the presence of an arbitrary population structure. I consider a classical range of models for count phenotype data. Under these models, a unified test for genetic associations that protects against confounding was derived. An algorithm was developed to efficiently estimate the parameters that are required to fit the proposed model. I illustrate the proposed approach using simulation studies and an empirical study. Both simulated and real-data examples suggest that the proposed method successfully corrects population structure. Copyright © 2018 John Wiley & Sons, Ltd.

Computational intelligence in bioinformatics: SNP/haplotype data in genetic association study for common diseases.

PubMed

Kelemen, Arpad; Vasilakos, Athanasios V; Liang, Yulan

2009-09-01

Comprehensive evaluation of common genetic variations through association of single-nucleotide polymorphism (SNP) structure with common complex disease in the genome-wide scale is currently a hot area in human genome research due to the recent development of the Human Genome Project and HapMap Project. Computational science, which includes computational intelligence (CI), has recently become the third method of scientific enquiry besides theory and experimentation. There have been fast growing interests in developing and applying CI in disease mapping using SNP and haplotype data. Some of the recent studies have demonstrated the promise and importance of CI for common complex diseases in genomic association study using SNP/haplotype data, especially for tackling challenges, such as gene-gene and gene-environment interactions, and the notorious "curse of dimensionality" problem. This review provides coverage of recent developments of CI approaches for complex diseases in genetic association study with SNP/haplotype data.

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.

Ontology driven modeling for the knowledge of genetic susceptibility to disease.

PubMed

Lin, Yu; Sakamoto, Norihiro

2009-05-12

For the machine helped exploring the relationships between genetic factors and complex diseases, a well-structured conceptual framework of the background knowledge is needed. However, because of the complexity of determining a genetic susceptibility factor, there is no formalization for the knowledge of genetic susceptibility to disease, which makes the interoperability between systems impossible. Thus, the ontology modeling language OWL was used for formalization in this paper. After introducing the Semantic Web and OWL language propagated by W3C, we applied text mining technology combined with competency questions to specify the classes of the ontology. Then, an N-ary pattern was adopted to describe the relationships among these defined classes. Based on the former work of OGSF-DM (Ontology of Genetic Susceptibility Factors to Diabetes Mellitus), we formalized the definition of "Genetic Susceptibility", "Genetic Susceptibility Factor" and other classes by using OWL-DL modeling language; and a reasoner automatically performed the classification of the class "Genetic Susceptibility Factor". The ontology driven modeling is used for formalization the knowledge of genetic susceptibility to complex diseases. More importantly, when a class has been completely formalized in an ontology, the OWL reasoning can automatically compute the classification of the class, in our case, the class of "Genetic Susceptibility Factors". With more types of genetic susceptibility factors obtained from the laboratory research, our ontologies always needs to be refined, and many new classes must be taken into account to harmonize with the ontologies. Using the ontologies to develop the semantic web needs to be applied in the future.

Genetic structure of seven Mexican indigenous populations based on five polymarker loci.

PubMed

Buentello-Malo, Leonora; Peñaloza-Espinosa, Rosenda I; Loeza, Francisco; Salamanca-Gomez, Fabio; Cerda-Flores, Ricardo M

2003-01-01

This descriptive study investigates the genetic structure of seven Mexican indigenous populations (Mixteca Alta, Mixteca Baja, Otomies, Purepecha, Nahuas-Guerrero, Nahuas-Xochimilco, and Tzeltales) on the basis of five PCR-based polymorphic DNA loci: LDLR, GYPA, HBGG, D7S8, and GC. Genetic distance and diversity analyses indicate that these Mexican indigenous are similar and that more than 96% of the total gene diversity (H(T)) can be attributed to individual variation within populations. Mixteca-Alta, Mixteca-Baja, and Nahuas-Xochimilco show indications of higher admixture with European-derived persons. The demonstration of a relative genetic homogeneity of Mexican Indians for the markers studied suggests that this population is suitable for studying disease-marker associations in the search for candidate genes of complex diseases. Copyright 2002 Wiley-Liss, Inc.

[Neuroanatomical, genetic and neurochemical aspects of infantile autism].

PubMed

Gerhant, Aneta; Olajossy, Marcin; Olajossy-Hilkesberger, Luiza

2013-01-01

Infantile autism is a neurodevelopmental disorder characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. The etiopathogenetic processes of autism are extremely complex, which is reflected in the varying course and its symptomatology. Trajectories of brain development and volumes of its structures are aberrant in autistic patients. It is suggested that disturbances in sertotoninergic, gabaergic, glutaminergic, cholinergic and dopaminergic neurotransmission can be responsible for symptoms of autism as well as can disturb the development of the young brain. The objective of this article is to present the results of reasearch on neuroanatomical, neurochemical and genetic aspects of autism.

Discovering Structure in High-Dimensional Data Through Correlation Explanation

DTIC Science & Technology

2014-12-08

transforming complex data into simpler, more meaningful forms goes under the rubric of representation learning [2] which shares many goals with...Zhivotovsky, and M.W. Feldman. Genetic structure of human populations. Science, 298(5602):2381–2385, 2002. [14] K. Bache and M. Lichman. UCI machine

Refining the structure and content of clinical genomic reports.

PubMed

Dorschner, Michael O; Amendola, Laura M; Shirts, Brian H; Kiedrowski, Lesli; Salama, Joseph; Gordon, Adam S; Fullerton, Stephanie M; Tarczy-Hornoch, Peter; Byers, Peter H; Jarvik, Gail P

2014-03-01

To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. © 2014 Wiley Periodicals, Inc.

Refining the Structure and Content of Clinical Genomic Reports

PubMed Central

DORSCHNER, MICHAEL O.; AMENDOLA, LAURA M.; SHIRTS, BRIAN H.; KIEDROWSKI, LESLI; SALAMA, JOSEPH; GORDON, ADAM S.; FULLERTON, STEPHANIE M.; TARCZY-HORNOCH, PETER; BYERS, PETER H.; JARVIK, GAIL P.

2014-01-01

To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. PMID:24616401

[New view on the population genetic structure of marine fish].

PubMed

Salmenkova, E A

2011-11-01

The view on homogeneous population genetic structure in many marine fish with high mobility has changed significantly during the last ten years. Molecular genetic population studies over the whole ranges of such species as Atlantic herring and Atlantic cod showed a complex picture of spatial differentiation both on the macrogeographic and, in many areas, on the microgeographic scale, although the differentiation for neutral molecular markers was low. It was established that the migration activity of such fish is constrained in many areas of the species range by hydrological and physicochemical transition zones (environmental gradients), as well as gyres in the spawning regions. Natal homing was recorded in a number of marine fish species. Existing in marine fish constraints of gene migration and a very high variance of reproductive success determine a significantly smaller proportion of effective reproductive size of their populations in the total population size, which generates more complex abundance dynamics than assumed earlier. The various constraints on gene migration and natal homing in marine fish promote the formation of local adaptations at ecologically important phenotypic traits. Effects of selection underlying adaptations are actively investigated in marine fish on the genomic level, using approaches of population genomics. The knowledge of adaptive intraspecific structure enables understanding the ecological and evolutionary processes, that influence biodiversity and providing spatial frames for conservation of genetic resources under commercial exploitation. Contemporary views on the population genetic and adaptive structures or biocomplexity in marine fish support and develop the main principles of the conception of systemic organization of the species and its regional populations, which were advanced by Yu.P. Altukhov and Yu.G. Rychkov.

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...

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 F ST = 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. © 2016 The Fisheries Society of the British Isles.

Spatial genetic analyses reveal cryptic population structure and migration patterns in a continuously harvested grey wolf (Canis lupus) population in north-eastern Europe.

PubMed

Hindrikson, Maris; Remm, Jaanus; Männil, Peep; Ozolins, Janis; Tammeleht, Egle; Saarma, Urmas

2013-01-01

Spatial genetics is a relatively new field in wildlife and conservation biology that is becoming an essential tool for unravelling the complexities of animal population processes, and for designing effective strategies for conservation and management. Conceptual and methodological developments in this field are therefore critical. Here we present two novel methodological approaches that further the analytical possibilities of STRUCTURE and DResD. Using these approaches we analyse structure and migrations in a grey wolf (Canislupus) population in north-eastern Europe. We genotyped 16 microsatellite loci in 166 individuals sampled from the wolf population in Estonia and Latvia that has been under strong and continuous hunting pressure for decades. Our analysis demonstrated that this relatively small wolf population is represented by four genetic groups. We also used a novel methodological approach that uses linear interpolation to statistically test the spatial separation of genetic groups. The new method, which is capable of using program STRUCTURE output, can be applied widely in population genetics to reveal both core areas and areas of low significance for genetic groups. We also used a recently developed spatially explicit individual-based method DResD, and applied it for the first time to microsatellite data, revealing a migration corridor and barriers, and several contact zones.

Genetics Home Reference: fibrochondrogenesis

MedlinePlus

... provide instructions for making components of type XI collagen, which is a complex molecule that gives structure ... the body's joints and organs. Specifically, type XI collagen is found in cartilage, a tough but flexible ...

Contrasting Effects of Historical Sea Level Rise and Contemporary Ocean Currents on Regional Gene Flow of Rhizophora racemosa in Eastern Atlantic Mangroves.

PubMed

Ngeve, Magdalene N; Van der Stocken, Tom; Menemenlis, Dimitris; Koedam, Nico; Triest, Ludwig

2016-01-01

Mangroves are seafaring taxa through their hydrochorous propagules that have the potential to disperse over long distances. Therefore, investigating their patterns of gene flow provides insights on the processes involved in the spatial genetic structuring of populations. The coastline of Cameroon has a particular geomorphological history and coastal hydrology with complex contemporary patterns of ocean currents, which we hypothesize to have effects on the spatial configuration and composition of present-day mangroves within its spans. A total of 982 trees were sampled from 33 transects (11 sites) in 4 estuaries. Using 11 polymorphic SSR markers, we investigated genetic diversity and structure of Rhizophora racemosa, a widespread species in the region. Genetic diversity was low to moderate and genetic differentiation between nearly all population pairs was significant. Bayesian clustering analysis, PCoA, estimates of contemporary migration rates and identification of barriers to gene flow were used and complemented with estimated dispersal trajectories of hourly released virtual propagules, using high-resolution surface current from a mesoscale and tide-resolving ocean simulation. These indicate that the Cameroon Volcanic Line (CVL) is not a present-day barrier to gene flow. Rather, the Inter-Bioko-Cameroon (IBC) corridor, formed due to sea level rise, allows for connectivity between two mangrove areas that were isolated during glacial times by the CVL. Genetic data and numerical ocean simulations indicated that an oceanic convergence zone near the Cameroon Estuary complex (CEC) presents a strong barrier to gene flow, resulting in genetic discontinuities between the mangrove areas on either side. This convergence did not result in higher genetic diversity at the CEC as we had hypothesized. In conclusion, the genetic structure of Rhizophora racemosa is maintained by the contrasting effects of the contemporary oceanic convergence and historical climate change-induced sea level rise.

Contrasting Effects of Historical Sea Level Rise and Contemporary Ocean Currents on Regional Gene Flow of Rhizophora racemosa in Eastern Atlantic Mangroves

PubMed Central

Ngeve, Magdalene N.; Van der Stocken, Tom; Menemenlis, Dimitris; Koedam, Nico; Triest, Ludwig

2016-01-01

Mangroves are seafaring taxa through their hydrochorous propagules that have the potential to disperse over long distances. Therefore, investigating their patterns of gene flow provides insights on the processes involved in the spatial genetic structuring of populations. The coastline of Cameroon has a particular geomorphological history and coastal hydrology with complex contemporary patterns of ocean currents, which we hypothesize to have effects on the spatial configuration and composition of present-day mangroves within its spans. A total of 982 trees were sampled from 33 transects (11 sites) in 4 estuaries. Using 11 polymorphic SSR markers, we investigated genetic diversity and structure of Rhizophora racemosa, a widespread species in the region. Genetic diversity was low to moderate and genetic differentiation between nearly all population pairs was significant. Bayesian clustering analysis, PCoA, estimates of contemporary migration rates and identification of barriers to gene flow were used and complemented with estimated dispersal trajectories of hourly released virtual propagules, using high-resolution surface current from a mesoscale and tide-resolving ocean simulation. These indicate that the Cameroon Volcanic Line (CVL) is not a present-day barrier to gene flow. Rather, the Inter-Bioko-Cameroon (IBC) corridor, formed due to sea level rise, allows for connectivity between two mangrove areas that were isolated during glacial times by the CVL. Genetic data and numerical ocean simulations indicated that an oceanic convergence zone near the Cameroon Estuary complex (CEC) presents a strong barrier to gene flow, resulting in genetic discontinuities between the mangrove areas on either side. This convergence did not result in higher genetic diversity at the CEC as we had hypothesized. In conclusion, the genetic structure of Rhizophora racemosa is maintained by the contrasting effects of the contemporary oceanic convergence and historical climate change-induced sea level rise. PMID:26964094

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.

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 the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress. PMID:16519816

The socio-genetics of a complex society: female gelada relatedness patterns mirror association patterns in a multilevel society.

PubMed

Snyder-Mackler, Noah; Alberts, Susan C; Bergman, Thore J

2014-12-01

Multilevel societies with fission-fusion dynamics--arguably the most complex animal societies--are defined by two or more nested levels of organization. The core of these societies are modular social units that regularly fission and fuse with one another. Despite convergent evolution in disparate taxa, we know strikingly little about how such societies form and how fitness benefits operate. Understanding the kinship structure of complex societies could inform us about the origins of the social structure as well as about the potential for individuals in these societies to accrue indirect fitness benefits. Here, we combined genetic and behavioural data on geladas (Theropithecus gelada), an Old World Monkey, to complete the most comprehensive socio-genetic analysis of a multilevel society to date. In geladas, individuals in the core social 'units', associate at different frequencies to form 'teams', 'bands' and, the largest aggregations, 'communities'. Units were composed of closely related females, and females remained with their close kin during permanent fissions of units. Interestingly, female-female relatedness also significantly predicted between-unit, between-team and between-band association patterns, while male-male relatedness did not. Thus, it is likely that the socio-genetic structure of gelada society results from females maintaining associations with their female relatives during successive unit fissions--possibly in an attempt to balance the direct and indirect fitness benefits of group living. Overall, the persistence of associations among related females across generations appears to drive the formation of higher levels of gelada society, suggesting that females seek kin for inclusive fitness benefits at multiple levels of gelada society. © 2014 John Wiley & Sons Ltd.

Genetic and Environmental Architecture of Changes in Episodic Memory from Middle to Late Middle Age

PubMed Central

Panizzon, Matthew S.; Neale, Michael C.; Docherty, Anna R.; Franz, Carol E.; Jacobson, Kristen C.; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K.; McKenzie, Ruth M.; Lyons, Michael J.; Kremen, William S.

2015-01-01

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined six measures from three episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints two of three test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for one test-specific factor (list learning). Mean change over time was nonsignificant for one test-level factor; one declined; one improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. PMID:25938244

Genetic and environmental architecture of changes in episodic memory from middle to late middle age.

PubMed

Panizzon, Matthew S; Neale, Michael C; Docherty, Anna R; Franz, Carol E; Jacobson, Kristen C; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K; McKenzie, Ruth; Lyons, Michael J; Kremen, William S

2015-06-01

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined 6 measures from 3 episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints 2 of 3 test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for 1 test-specific factor (list learning). Mean change over time was nonsignificant for 1 test-level factor; 1 declined; 1 improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. (c) 2015 APA, all rights reserved.

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.

Spatial and temporal patterns of neutral and adaptive genetic variation in the endangered African wild dog (Lycaon pictus).

PubMed

Marsden, Clare D; Woodroffe, Rosie; Mills, Michael G L; McNutt, J Weldon; Creel, Scott; Groom, Rosemary; Emmanuel, Masenga; Cleaveland, Sarah; Kat, Pieter; Rasmussen, Gregory S A; Ginsberg, Joshua; Lines, Robin; André, Jean-Marc; Begg, Colleen; Wayne, Robert K; Mable, Barbara K

2012-03-01

Deciphering patterns of genetic variation within a species is essential for understanding population structure, local adaptation and differences in diversity between populations. Whilst neutrally evolving genetic markers can be used to elucidate demographic processes and genetic structure, they are not subject to selection and therefore are not informative about patterns of adaptive variation. As such, assessments of pertinent adaptive loci, such as the immunity genes of the major histocompatibility complex (MHC), are increasingly being incorporated into genetic studies. In this study, we combined neutral (microsatellite, mtDNA) and adaptive (MHC class II DLA-DRB1 locus) markers to elucidate the factors influencing patterns of genetic variation in the African wild dog (Lycaon pictus); an endangered canid that has suffered extensive declines in distribution and abundance. Our genetic analyses found all extant wild dog populations to be relatively small (N(e)  < 30). Furthermore, through coalescent modelling, we detected a genetic signature of a recent and substantial demographic decline, which correlates with human expansion, but contrasts with findings in some other African mammals. We found strong structuring of wild dog populations, indicating the negative influence of extensive habitat fragmentation and loss of gene flow between habitat patches. Across populations, we found that the spatial and temporal structure of microsatellite diversity and MHC diversity were correlated and strongly influenced by demographic stability and population size, indicating the effects of genetic drift in these small populations. Despite this correlation, we detected signatures of selection at the MHC, implying that selection has not been completely overwhelmed by genetic drift. © 2012 Blackwell Publishing Ltd.

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.

Genetics Home Reference: otospondylomegaepiphyseal dysplasia

MedlinePlus

... instructions for making one component of type XI collagen, which is a complex molecule that gives structure ... support the body's joints and organs. Type XI collagen is found in cartilage, a tough but flexible ...

Genetics Home Reference: Stickler syndrome

MedlinePlus

... Stickler syndrome provide instructions for making components of collagens, which are complex molecules that give structure and ... genes impair the production, processing, or assembly of collagen molecules. Defective collagen molecules or reduced amounts of ...

Juxtaposed Polycomb complexes co-regulate vertebral identity.

PubMed

Kim, Se Young; Paylor, Suzanne W; Magnuson, Terry; Schumacher, Armin

2006-12-01

Best known as epigenetic repressors of developmental Hox gene transcription, Polycomb complexes alter chromatin structure by means of post-translational modification of histone tails. Depending on the cellular context, Polycomb complexes of diverse composition and function exhibit cooperative interaction or hierarchical interdependency at target loci. The present study interrogated the genetic, biochemical and molecular interaction of BMI1 and EED, pivotal constituents of heterologous Polycomb complexes, in the regulation of vertebral identity during mouse development. Despite a significant overlap in dosage-sensitive homeotic phenotypes and co-repression of a similar set of Hox genes, genetic analysis implicated eed and Bmi1 in parallel pathways, which converge at the level of Hox gene regulation. Whereas EED and BMI1 formed separate biochemical entities with EzH2 and Ring1B, respectively, in mid-gestation embryos, YY1 engaged in both Polycomb complexes. Strikingly, methylated lysine 27 of histone H3 (H3-K27), a mediator of Polycomb complex recruitment to target genes, stably associated with the EED complex during the maintenance phase of Hox gene repression. Juxtaposed EED and BMI1 complexes, along with YY1 and methylated H3-K27, were detected in upstream regulatory regions of Hoxc8 and Hoxa5. The combined data suggest a model wherein epigenetic and genetic elements cooperatively recruit and retain juxtaposed Polycomb complexes in mammalian Hox gene clusters toward co-regulation of vertebral identity.

Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis

DTIC Science & Technology

2007-04-01

for the subunits of this Complex responsible for the hereditary paraganglioma and pheochromocytoma (2- 4,12,13,30,31,32) suggest that Complex II...familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet. 2001, 69:49-54. 3. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC...Eng C. Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma . Cancer Res. 2000, 60

Allele frequency data for 15 autosomal STR loci in eight Indonesian subpopulations.

PubMed

Venables, Samantha J; Daniel, Runa; Sarre, Stephen D; Soedarsono, Nurtami; Sudoyo, Herawati; Suryadi, Helena; van Oorschot, Roland A H; Walsh, Simon J; Widodo, Putut T; McNevin, Dennis

2016-01-01

Evolutionary and cultural history can affect the genetic characteristics of a population and influences the frequency of different variants at a particular genetic marker (allele frequency). These characteristics directly influence the strength of forensic DNA evidence and make the availability of suitable allele frequency information for every discrete country or jurisdiction highly relevant. Population sub-structure within Indonesia has not been well characterised but should be expected given the complex geographical, linguistic and cultural architecture of the Indonesian population. Here we use forensic short tandem repeat (STR) markers to identify a number of distinct genetic subpopulations within Indonesia and calculate appropriate population sub-structure correction factors. This data represents the most comprehensive investigation of population sub-structure within Indonesia to date using these markers. The results demonstrate that significant sub-structure is present within the Indonesian population and must be accounted for using island specific allele frequencies and corresponding sub-structure correction factors in the calculation of forensic DNA match statistics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Bell miner provisioning calls are more similar among relatives and are used by helpers at the nest to bias their effort towards kin

PubMed Central

McDonald, Paul G.; Wright, Jonathan

2011-01-01

Kin selection predicts that helpers in cooperative systems should preferentially aid relatives to maximize fitness. In family-based groups, this can be accomplished simply by assisting all group members. In more complex societies, where large numbers of kin and non-kin regularly interact, more sophisticated kin-recognition mechanisms are needed. Bell miners (Manorina melanophrys) are just such a system where individuals regularly interact with both kin and non-kin within large colonies. Despite this complexity, individual helpers of both sexes facultatively work harder when provisioning the young of closer genetic relatedness. We investigated the mechanism by which such adaptive discrimination occurs by assessing genetic kinship influences on the structure of more than 1900 provisioning vocalizations of 185 miners. These ‘mew’ calls showed a significant, positive linear increase in call similarity with increasing genetic relatedness, most especially in comparisons between male helpers and the breeding male. Furthermore, individual helping effort was more heavily influenced by call similarity to breeding males than to genetic relatedness, as predicted if call similarity is indeed the rule-of-thumb used to discriminate kin in this system. Individual mew call structure appeared to be inflexible and innate, providing an effective mechanism by which helpers can assess their relatedness to any individual. This provides, to our knowledge, the first example of a mechanism for fine-scale kin discrimination in a complex avian society. PMID:21450738

The microgeographical patterns of morphological and molecular variation of a mixed ploidy population in the species complex Actinidia chinensis.

PubMed

Liu, Yifei; Li, Dawei; Yan, Ling; Huang, Hongwen

2015-01-01

Polyploidy and hybridization are thought to have significant impacts on both the evolution and diversification of the genus Actinidia, but the structure and patterns of morphology and molecular diversity relating to ploidy variation of wild Actinidia plants remain much less understood. Here, we examine the distribution of morphological variation and ploidy levels along geographic and environmental variables of a large mixed-ploidy population of the A. chinensis species complex. We then characterize the extent of both genetic and epigenetic diversity and differentiation exhibited between individuals of different ploidy levels. Our results showed that while there are three ploidy levels in this population, hexaploids were constituted the majority (70.3%). Individuals with different ploidy levels were microgeographically structured in relation to elevation and extent of niche disturbance. The morphological characters examined revealed clear difference between diploids and hexaploids, however tetraploids exhibited intermediate forms. Both genetic and epigenetic diversity were high but the differentiation among cytotypes was weak, suggesting extensive gene flow and/or shared ancestral variation occurred in this population even across ploidy levels. Epigenetic variation was clearly correlated with changes in altitudes, a trend of continuous genetic variation and gradual increase of epigenomic heterogeneities of individuals was also observed. Our results show that complex interactions between the locally microgeographical environment, ploidy and gene flow impact A. chinensis genetic and epigenetic variation. We posit that an increase in ploidy does not broaden the species habitat range, but rather permits A. chinensis adaptation to specific niches.

Red River barrier and Pleistocene climatic fluctuations shaped the genetic structure of Microhyla fissipes complex (Anura: Microhylidae) in southern China and Indochina

PubMed Central

Yuan, Zhi-Yong; Suwannapoom, Chatmongkon; Yan, Fang; Poyarkov, Nikolay A.; Nguyen, Sang Ngoc; Chen, Hong-man; Chomdej, Siriwadee; Murphy, Robert W.

2016-01-01

South China and Indochina host striking species diversity and endemism. Complex tectonic and climatic evolutions appear to be the main drivers of the biogeographic patterns. In this study, based on the geologic history of this region, we test 2 hypotheses using the evolutionary history of Microhyla fissipes species complex. Using DNA sequence data from both mitochondrial and nuclear genes, we first test the hypothesis that the Red River is a barrier to gene flow and dispersal. Second, we test the hypothesis that Pleistocene climatic cycling affected the genetic structure and population history of these frogs. We detect 2 major genetic splits that associate with the Red River. Time estimation suggests that late Miocene tectonic movement associated with the Red River drove their diversification. Species distribution modeling (SDM) resolves significant ecological differences between sides of the Red River. Thus, ecological divergence also probably promoted and maintained the diversification. Genogeography, historical demography, and SDM associate patterns in southern China with climate changes of the last glacial maximum (LGM), but not Indochina. Differences in geography and climate between the 2 areas best explain the discovery. Responses to the Pleistocene glacial–interglacial cycling vary among species and regions. PMID:29491943

A flexible model for multivariate interval-censored survival times with complex correlation structure.

PubMed

Falcaro, Milena; Pickles, Andrew

2007-02-10

We focus on the analysis of multivariate survival times with highly structured interdependency and subject to interval censoring. Such data are common in developmental genetics and genetic epidemiology. We propose a flexible mixed probit model that deals naturally with complex but uninformative censoring. The recorded ages of onset are treated as possibly censored ordinal outcomes with the interval censoring mechanism seen as arising from a coarsened measurement of a continuous variable observed as falling between subject-specific thresholds. This bypasses the requirement for the failure times to be observed as falling into non-overlapping intervals. The assumption of a normal age-of-onset distribution of the standard probit model is relaxed by embedding within it a multivariate Box-Cox transformation whose parameters are jointly estimated with the other parameters of the model. Complex decompositions of the underlying multivariate normal covariance matrix of the transformed ages of onset become possible. The new methodology is here applied to a multivariate study of the ages of first use of tobacco and first consumption of alcohol without parental permission in twins. The proposed model allows estimation of the genetic and environmental effects that are shared by both of these risk behaviours as well as those that are specific. 2006 John Wiley & Sons, Ltd.

Red River barrier and Pleistocene climatic fluctuations shaped the genetic structure of Microhyla fissipes complex (Anura: Microhylidae) in southern China and Indochina.

PubMed

Yuan, Zhi-Yong; Suwannapoom, Chatmongkon; Yan, Fang; Poyarkov, Nikolay A; Nguyen, Sang Ngoc; Chen, Hong-Man; Chomdej, Siriwadee; Murphy, Robert W; Che, Jing

2016-12-01

South China and Indochina host striking species diversity and endemism. Complex tectonic and climatic evolutions appear to be the main drivers of the biogeographic patterns. In this study, based on the geologic history of this region, we test 2 hypotheses using the evolutionary history of Microhyla fissipes species complex. Using DNA sequence data from both mitochondrial and nuclear genes, we first test the hypothesis that the Red River is a barrier to gene flow and dispersal. Second, we test the hypothesis that Pleistocene climatic cycling affected the genetic structure and population history of these frogs. We detect 2 major genetic splits that associate with the Red River. Time estimation suggests that late Miocene tectonic movement associated with the Red River drove their diversification. Species distribution modeling (SDM) resolves significant ecological differences between sides of the Red River. Thus, ecological divergence also probably promoted and maintained the diversification. Genogeography, historical demography, and SDM associate patterns in southern China with climate changes of the last glacial maximum (LGM), but not Indochina. Differences in geography and climate between the 2 areas best explain the discovery. Responses to the Pleistocene glacial-interglacial cycling vary among species and regions.

Genetic differentiation and phylogeography of Mediterranean-North Eastern Atlantic blue shark (Prionace glauca, L. 1758) using mitochondrial DNA: panmixia or complex stock structure?

PubMed Central

Damalas, Dimitrios; Martinsohn, Jann; Zanzi, Antonella; Mariani, Stefano; Sperone, Emilio; Micarelli, Primo; Garibaldi, Fulvio; Megalofonou, Persefoni; Bargelloni, Luca; Franch, Rafaella; Macias, David; Prodöhl, Paulo; Fitzpatrick, Séan; Stagioni, Marco; Tinti, Fausto; Cariani, Alessia

2017-01-01

Background The blue shark (Prionace glauca, Linnaeus 1758) is one of the most abundant epipelagic shark inhabiting all the oceans except the poles, including the Mediterranean Sea, but its genetic structure has not been confirmed at basin and interoceanic distances. Past tagging programs in the Atlantic Ocean failed to find evidence of migration of blue sharks between the Mediterranean and the adjacent Atlantic, despite the extreme vagility of the species. Although the high rate of by-catch in the Mediterranean basin, to date no genetic study on Mediterranean blue shark was carried out, which constitutes a significant knowledge gap, considering that this population is classified as “Critically Endangered”, unlike its open-ocean counterpart. Methods Blue shark phylogeography and demography in the Mediterranean Sea and North-Eastern Atlantic Ocean were inferred using two mitochondrial genes (Cytb and control region) amplified from 207 and 170 individuals respectively, collected from six localities across the Mediterranean and two from the North-Eastern Atlantic. Results Although no obvious pattern of geographical differentiation was apparent from the haplotype network, Φst analyses indicated significant genetic structure among four geographical groups. Demographic analyses suggest that these populations have experienced a constant population expansion in the last 0.4–0.1 million of years. Discussion The weak, but significant, differences in Mediterranean and adjacent North-eastern Atlantic blue sharks revealed a complex phylogeographic structure, which appears to reject the assumption of panmixia across the study area, but also supports a certain degree of population connectivity across the Strait of Gibraltar, despite the lack of evidence of migratory movements observed by tagging data. Analyses of spatial genetic structure in relation to sex-ratio and size could indicate some level of sex/stage biased migratory behaviour. PMID:29230359

Genet-specific DNA methylation probabilities detected in a spatial epigenetic analysis of a clonal plant population.

PubMed

Araki, Kiwako S; Kubo, Takuya; Kudoh, Hiroshi

2017-01-01

In sessile organisms such as plants, spatial genetic structures of populations show long-lasting patterns. These structures have been analyzed across diverse taxa to understand the processes that determine the genetic makeup of organismal populations. For many sessile organisms that mainly propagate via clonal spread, epigenetic status can vary between clonal individuals in the absence of genetic changes. However, fewer previous studies have explored the epigenetic properties in comparison to the genetic properties of natural plant populations. Here, we report the simultaneous evaluation of the spatial structure of genetic and epigenetic variation in a natural population of the clonal plant Cardamine leucantha. We applied a hierarchical Bayesian model to evaluate the effects of membership of a genet (a group of individuals clonally derived from a single seed) and vegetation cover on the epigenetic variation between ramets (clonal plants that are physiologically independent individuals). We sampled 332 ramets in a 20 m × 20 m study plot that contained 137 genets (identified using eight SSR markers). We detected epigenetic variation in DNA methylation at 24 methylation-sensitive amplified fragment length polymorphism (MS-AFLP) loci. There were significant genet effects at all 24 MS-AFLP loci in the distribution of subepiloci. Vegetation cover had no statistically significant effect on variation in the majority of MS-AFLP loci. The spatial aggregation of epigenetic variation is therefore largely explained by the aggregation of ramets that belong to the same genets. By applying hierarchical Bayesian analyses, we successfully identified a number of genet-specific changes in epigenetic status within a natural plant population in a complex context, where genotypes and environmental factors are unevenly distributed. This finding suggests that it requires further studies on the spatial epigenetic structure of natural populations of diverse organisms, particularly for sessile clonal species.

Connectivity in a pond system influences migration and genetic structure in threespine stickleback.

PubMed

Seymour, Mathew; Räsänen, Katja; Holderegger, Rolf; Kristjánsson, Bjarni K

2013-03-01

Neutral genetic structure of natural populations is primarily influenced by migration (the movement of individuals and, subsequently, their genes) and drift (the statistical chance of losing genetic diversity over time). Migration between populations is influenced by several factors, including individual behavior, physical barriers, and environmental heterogeneity among populations. However, drift is expected to be stronger in populations with low immigration rate and small effective population size. With the technological advancement in geological information systems and spatial analysis tools, landscape genetics now allows the development of realistic migration models and increased insight to important processes influencing diversity of natural populations. In this study, we investigated the relationship between landscape connectivity and genetic distance of threespine stickleback (Gasterosteus aculeatus) inhabiting a pond complex in Belgjarskógur, Northeast Iceland. We used two landscape genetic approaches (i.e., least-cost-path and isolation-by-resistance) and asked whether gene flow, as measured by genetic distance, was more strongly associated with Euclidean distance (isolation-by-distance) or with landscape connectivity provided by areas prone to flooding (as indicated by Carex sp. cover)? We found substantial genetic structure across the study area, with pairwise genetic distances among populations (DPS) ranging from 0.118 to 0.488. Genetic distances among populations were more strongly correlated with least-cost-path and isolation-by-resistance than with Euclidean distance, whereas the relative contribution of isolation-by-resistance and Euclidian distance could not be disentangled. These results indicate that migration among stickleback populations occurs via periodically flooded areas. Overall, this study highlights the importance of transient landscape elements influencing migration and genetic structure of populations at small spatial scales.

A weighted U statistic for association analyses considering genetic heterogeneity.

PubMed

Wei, Changshuai; Elston, Robert C; Lu, Qing

2016-07-20

Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Spatial genetic structure in wild cardoon, the ancestor of cultivated globe artichoke: Limited gene flow, fragmentation and population history.

PubMed

Rau, D; Rodriguez, M; Rapposelli, E; Murgia, M L; Papa, R; Brown, A H D; Attene, G

2016-12-01

Nuclear and chloroplast markers and phenotypic characters were integrated to analyse the population genetic structure of wild cardoon, Cynara cardunculus var. sylvestris, the ancestor of cultivated globe artichoke, Cynara cardunculus var. scolymus on the island of Sardinia, Italy. The spatial scale ranged from a few metres to ∼200km. Wild cardoon appears to be genetically fragmented, with significant genetic divergence at various scales, indicating that gene flow is insufficient to counterbalance the effects of genetic drift or founder effects. Divergence between populations was higher for chloroplast (40%) than for nuclear markers (15%), suggesting that gene flow via seed was lower than via pollen. Two main genetic groups were detected; these correlated with differences in flowering time, capitula size, glossiness, and anthocyanin pigmentation. A complex population structure of wild cardoon emerged over small spatial scales, likely resulting from the interplay between gene dispersal, colonisation history and selective forces. Indeed, Sardinia appears to be a 'hybrid zone' of different gene pools. The island has unique diverse germplasm that has originated from hybridisation among different gene pools. The sampling of seeds from a few plants but from many sites is suggested as the best strategy to harvest the genetic diversity of wild cardoon. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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"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.« less

Obstructive Sleep Apnea Syndrome: From Phenotype to Genetic Basis

PubMed Central

Casale, M; Pappacena, M; Rinaldi, V; Bressi, F; Baptista, P; Salvinelli, F

2009-01-01

Obstructive sleep apnea syndrome (OSAS) is a complex chronic clinical syndrome, characterized by snoring, periodic apnea, hypoxemia during sleep, and daytime hypersomnolence. It affects 4-5% of the general population. Racial studies and chromosomal mapping, familial studies and twin studies have provided evidence for the possible link between the OSAS and genetic factors and also most of the risk factors involved in the pathogenesis of OSAS are largely genetically determined. A percentage of 35-40% of its variance can be attributed to genetic factors. It is likely that genetic factors associated with craniofacial structure, body fat distribution and neural control of the upper airway muscles interact to produce the OSAS phenotype. Although the role of specific genes that influence the development of OSAS has not yet been identified, current researches, especially in animal model, suggest that several genetic systems may be important. In this chapter, we will first define the OSAS phenotype, the pathogenesis and the risk factors involved in the OSAS that may be inherited, then, we will review the current progress in the genetics of OSAS and suggest a few future perspectives in the development of therapeutic agents for this complex disease entity. PMID:19794884

Between (Racial) Groups and a Hard Place: An Exploration of Social Science Approaches to Race and Genetics, 2000-2014.

PubMed

Byrd, W Carson; Best, Latrica E

2016-01-01

As the social sciences expand their involvement in genetic and genomic research, more information is needed to understand how theoretical concepts are applied to genetic data found in social surveys. Given the layers of complexity of studying race in relation to genetics and genomics, it is important to identify the varying approaches used to discuss and operationalize race and identity by social scientists. The present study explores how social scientists have used race, ethnicity, and ancestry in studies published in four social science journals from 2000 to 2014. We identify not only how race, ethnicity, and ancestry are classified and conceptualized in this growing area of research, but also how these concepts are incorporated into the methodology and presentation of results, all of which structure the discussion of race, identity, and inequality. This research indicates the slippage between concepts, classifications, and their use by social scientists in their genetics-related research. The current study can assist social scientists with clarifying their use and interpretations of race and ethnicity with the incorporation of genetic data, while limiting possible misinterpretations of the complexities of the connection between genetics and the social world.

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

PubMed Central

Smoller, Jordan W

2016-01-01

Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories—posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders—for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene–environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research. PMID:26321314

Bio-Organic Nanotechnology: Using Proteins and Synthetic Polymers for Nanoscale Devices

NASA Technical Reports Server (NTRS)

Molnar, Linda K.; Xu, Ting; Trent, Jonathan D.; Russell, Thomas P.

2003-01-01

While the ability of proteins to self-assemble makes them powerful tools in nanotechnology, in biological systems protein-based structures ultimately depend on the context in which they form. We combine the self-assembling properties of synthetic diblock copolymers and proteins to construct intricately ordered, three-dimensional polymer protein structures with the ultimate goal of forming nano-scale devices. This hybrid approach takes advantage of the capabilities of organic polymer chemistry to build ordered structures and the capabilities of genetic engineering to create proteins that are selective for inorganic or organic substrates. Here, microphase-separated block copolymers coupled with genetically engineered heat shock proteins are used to produce nano-scale patterning that maximizes the potential for both increased structural complexity and integrity.

Population and genomic lessons from genetic analysis of two Indian populations.

PubMed

Juyal, Garima; Mondal, Mayukh; Luisi, Pierre; Laayouni, Hafid; Sood, Ajit; Midha, Vandana; Heutink, Peter; Bertranpetit, Jaume; Thelma, B K; Casals, Ferran

2014-10-01

Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.

A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria

PubMed Central

Hoppins, Suzanne; Collins, Sean R.; Cassidy-Stone, Ann; Hummel, Eric; DeVay, Rachel M.; Lackner, Laura L.; Westermann, Benedikt; Schuldiner, Maya

2011-01-01

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane–associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria. PMID:21987634

Evolution in Australia's mesic biome under past and future climates: Insights from a phylogenetic study of the Australian Rock Orchids (Dendrobium speciosum complex, Orchidaceae).

PubMed

Simpson, Lalita; Clements, Mark A; Crayn, Darren M; Nargar, Katharina

2018-01-01

The Australian mesic biome spans c. 33° of latitude along Australia's east coast and ranges and is dissected by historical and contemporary biogeographical barriers. To investigate the impact of these barriers on evolutionary diversification and to predict the impact of future climate change on the distribution of species and genetic diversity within this biome, we inferred phylogenetic relationships within the Dendrobium speciosum complex (Orchidaceae) across its distribution and undertook environmental niche modelling (ENM) under past, contemporary and projected future climates. Neighbor Joining tree inference, NeighborNet and Structure analyses of Amplified Fragment Length Polymorphism (AFLP) profiles for D. speciosum sampled from across its distribution showed that the complex consists of two highly supported main groups that are geographically separated by the St. Lawrence gap, an area of dry sclerophyll forest and woodland. The presence of several highly admixed individuals identified by the Structure analysis provided evidence of genetic exchange between the two groups across this gap. Whereas previous treatments have recognised between one to eleven species, the molecular results support the taxonomic treatment of the complex as a single species with two subspecies. The ENM analysis supported the hypothesis that lineage divergence within the complex was driven by past climatic changes. The St. Lawrence gap represented a stronger biogeographic barrier for the D. speciosum complex during the cool and dry glacial climatic conditions of the Pleistocene than under today's interglacial conditions. Shallow genetic divergence was found within the two lineages, which mainly corresponded to three other biogeographic barriers: the Black Mountain Corridor, Glass House Mountains and the Hunter Valley. Our ENM analyses provide further support for the hypothesis that biogeographic barriers along Australia's east coast were somewhat permeable to genetic exchange due to past episodic range expansions and contractions caused by climatic change resulting in recurrent contact between previously isolated populations. An overall southward shift in the distribution of the complex under future climate scenarios was predicted, with the strongest effects on the northern lineage. This study contributes to our understanding of the factors shaping biodiversity patterns in Australia's mesic biome. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovering Link Communities in Complex Networks by an Integer Programming Model and a Genetic Algorithm

PubMed Central

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. PMID:24386268

Genetics Home Reference: Weissenbacher-Zweymüller syndrome

MedlinePlus

... instructions for making one component of type XI collagen, which is a complex molecule that gives structure ... support the body's joints and organs. Type XI collagen is found in cartilage, a tough but flexible ...

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

The Case for Adopting the "Species Complex" Nomenclature for the Etiologic Agents of Cryptococcosis.

PubMed

Kwon-Chung, Kyung J; Bennett, John E; Wickes, Brian L; Meyer, Wieland; Cuomo, Christina A; Wollenburg, Kurt R; Bicanic, Tihana A; Castañeda, Elizabeth; Chang, Yun C; Chen, Jianghan; Cogliati, Massimo; Dromer, Françoise; Ellis, David; Filler, Scott G; Fisher, Matthew C; Harrison, Thomas S; Holland, Steven M; Kohno, Shigeru; Kronstad, James W; Lazera, Marcia; Levitz, Stuart M; Lionakis, Michail S; May, Robin C; Ngamskulrongroj, Popchai; Pappas, Peter G; Perfect, John R; Rickerts, Volker; Sorrell, Tania C; Walsh, Thomas J; Williamson, Peter R; Xu, Jianping; Zelazny, Adrian M; Casadevall, Arturo

2017-01-01

Cryptococcosis is a potentially lethal disease of humans/animals caused by Cryptococcus neoformans and Cryptococcus gattii . Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed that C. neoformans be divided into two species and C. gattii into five species based on a phylogenetic analysis of 115 isolates. While this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the published genotypes of 2,606 strains have already revealed more genetic diversity than is encompassed by seven species. Naming every clade as a separate species at this juncture will lead to continuing nomenclatural instability. In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, we recommend using " Cryptococcus neoformans species complex" and " C. gattii species complex" as a practical intermediate step, rather than creating more species. This strategy recognizes genetic diversity without creating confusion.

The walk is never random: subtle landscape effects shape gene flow in a continuous white-tailed deer population in the Midwestern United States

USGS Publications Warehouse

Robinson, Stacie J.; Samuel, Michael D.; Lopez, Davin L.; Shelton, Paul

2012-01-01

One of the pervasive challenges in landscape genetics is detecting gene flow patterns within continuous populations of highly mobile wildlife. Understanding population genetic structure within a continuous population can give insights into social structure, movement across the landscape and contact between populations, which influence ecological interactions, reproductive dynamics or pathogen transmission. We investigated the genetic structure of a large population of deer spanning the area of Wisconsin and Illinois, USA, affected by chronic wasting disease. We combined multiscale investigation, landscape genetic techniques and spatial statistical modelling to address the complex questions of landscape factors influencing population structure. We sampled over 2000 deer and used spatial autocorrelation and a spatial principal components analysis to describe the population genetic structure. We evaluated landscape effects on this pattern using a spatial autoregressive model within a model selection framework to test alternative hypotheses about gene flow. We found high levels of genetic connectivity, with gradients of variation across the large continuous population of white-tailed deer. At the fine scale, spatial clustering of related animals was correlated with the amount and arrangement of forested habitat. At the broader scale, impediments to dispersal were important to shaping genetic connectivity within the population. We found significant barrier effects of individual state and interstate highways and rivers. Our results offer an important understanding of deer biology and movement that will help inform the management of this species in an area where overabundance and disease spread are primary concerns.

Genetic Diversity and Population Structure of F3:6 Nebraska Winter Wheat Genotypes Using Genotyping-By-Sequencing.

PubMed

Eltaher, Shamseldeen; Sallam, Ahmed; Belamkar, Vikas; Emara, Hamdy A; Nower, Ahmed A; Salem, Khaled F M; Poland, Jesse; Baenziger, Peter S

2018-01-01

The availability of information on the genetic diversity and population structure in wheat ( Triticum aestivum L.) breeding lines will help wheat breeders to better use their genetic resources and manage genetic variation in their breeding program. The recent advances in sequencing technology provide the opportunity to identify tens or hundreds of thousands of single nucleotide polymorphism (SNPs) in large genome species (e.g., wheat). These SNPs can be utilized for understanding genetic diversity and performing genome wide association studies (GWAS) for complex traits. In this study, the genetic diversity and population structure were investigated in a set of 230 genotypes (F 3:6 ) derived from various crosses as a prerequisite for GWAS and genomic selection. Genotyping-by-sequencing provided 25,566 high-quality SNPs. The polymorphism information content (PIC) across chromosomes ranged from 0.09 to 0.37 with an average of 0.23. The distribution of SNPs markers on the 21 chromosomes ranged from 319 on chromosome 3D to 2,370 on chromosome 3B. The analysis of population structure revealed three subpopulations (G1, G2, and G3). Analysis of molecular variance identified 8% variance among and 92% within subpopulations. Of the three subpopulations, G2 had the highest level of genetic diversity based on three genetic diversity indices: Shannon's information index ( I ) = 0.494, diversity index ( h ) = 0.328 and unbiased diversity index (uh) = 0.331, while G3 had lowest level of genetic diversity ( I = 0.348, h = 0.226 and uh = 0.236). This high genetic diversity identified among the subpopulations can be used to develop new wheat cultivars.

Genetic Diversity and Population Structure of F3:6 Nebraska Winter Wheat Genotypes Using Genotyping-By-Sequencing

PubMed Central

Eltaher, Shamseldeen; Sallam, Ahmed; Belamkar, Vikas; Emara, Hamdy A.; Nower, Ahmed A.; Salem, Khaled F. M.; Poland, Jesse; Baenziger, Peter S.

2018-01-01

The availability of information on the genetic diversity and population structure in wheat (Triticum aestivum L.) breeding lines will help wheat breeders to better use their genetic resources and manage genetic variation in their breeding program. The recent advances in sequencing technology provide the opportunity to identify tens or hundreds of thousands of single nucleotide polymorphism (SNPs) in large genome species (e.g., wheat). These SNPs can be utilized for understanding genetic diversity and performing genome wide association studies (GWAS) for complex traits. In this study, the genetic diversity and population structure were investigated in a set of 230 genotypes (F3:6) derived from various crosses as a prerequisite for GWAS and genomic selection. Genotyping-by-sequencing provided 25,566 high-quality SNPs. The polymorphism information content (PIC) across chromosomes ranged from 0.09 to 0.37 with an average of 0.23. The distribution of SNPs markers on the 21 chromosomes ranged from 319 on chromosome 3D to 2,370 on chromosome 3B. The analysis of population structure revealed three subpopulations (G1, G2, and G3). Analysis of molecular variance identified 8% variance among and 92% within subpopulations. Of the three subpopulations, G2 had the highest level of genetic diversity based on three genetic diversity indices: Shannon’s information index (I) = 0.494, diversity index (h) = 0.328 and unbiased diversity index (uh) = 0.331, while G3 had lowest level of genetic diversity (I = 0.348, h = 0.226 and uh = 0.236). This high genetic diversity identified among the subpopulations can be used to develop new wheat cultivars. PMID:29593779

Beyond terrestrial biology: charting the chemical universe of α-amino acid structures.

PubMed

Meringer, Markus; Cleaves, H James; Freeland, Stephen J

2013-11-25

α-Amino acids are fundamental to biochemistry as the monomeric building blocks with which cells construct proteins according to genetic instructions. However, the 20 amino acids of the standard genetic code represent a tiny fraction of the number of α-amino acid chemical structures that could plausibly play such a role, both from the perspective of natural processes by which life emerged and evolved, and from the perspective of human-engineered genetically coded proteins. Until now, efforts to describe the structures comprising this broader set, or even estimate their number, have been hampered by the complex combinatorial properties of organic molecules. Here, we use computer software based on graph theory and constructive combinatorics in order to conduct an efficient and exhaustive search of the chemical structures implied by two careful and precise definitions of the α-amino acids relevant to coded biological proteins. Our results include two virtual libraries of α-amino acid structures corresponding to these different approaches, comprising 121 044 and 3 846 structures, respectively, and suggest a simple approach to exploring much larger, as yet uncomputed, libraries of interest.

Genetic diversity and structure related to expansion history and habitat isolation: stone marten populating rural-urban habitats.

PubMed

Wereszczuk, Anna; Leblois, Raphaël; Zalewski, Andrzej

2017-12-22

Population genetic diversity and structure are determined by past and current evolutionary processes, among which spatially limited dispersal, genetic drift, and shifts in species distribution boundaries have major effects. In most wildlife species, environmental modifications by humans often lead to contraction of species' ranges and/or limit their dispersal by acting as environmental barriers. However, in species well adapted to anthropogenic habitat or open landscapes, human induced environmental changes may facilitate dispersal and range expansions. In this study, we analysed whether isolation by distance and deforestation, among other environmental features, promotes or restricts dispersal and expansion in stone marten (Martes foina) populations. We genotyped 298 martens from eight sites at twenty-two microsatellite loci to characterize the genetic variability, population structure and demographic history of stone martens in Poland. At the landscape scale, limited genetic differentiation between sites in a mosaic of urban, rural and forest habitats was mostly influenced by isolation by distance. Statistical clustering and multivariate analyses showed weak genetic structuring with two to four clusters and a high rate of gene flow between them. Stronger genetic differentiation was detected for one stone marten population (NE1) located inside a large forest complex. Genetic differentiation between this site and all others was 20% higher than between other sites separated by similar distances. The genetic uniqueness index of NE1 was also twofold higher than in other sites. Past demographic history analyses showed recent expansion of this species in north-eastern Poland. A decrease in genetic diversity from south to north, and MIGRAINE analyses indicated the direction of expansion of stone marten. Our results showed that two processes, changes in species distribution boundaries and limited dispersal associated with landscape barriers, affect genetic diversity and structure in stone marten. Analysis of local barriers that reduced dispersal and large scale analyses of genetic structure and demographic history highlight the importance of isolation by distance and forest cover for the past colonization of central Europe by stone marten. This confirmed the hypothesis that human-landscape changes (deforestation) accelerated stone marten expansion, to which climate warming probably has also been contributing over the last few decades.

Self-Fertilization and Genetic Population Structure in a Colonizing Land Snail

PubMed Central

Selander, Robert K.; Kaufman, Donald W.

1973-01-01

The pulmonate land snail Rumina decollata in its native Mediterranean range is a complex of monogenic or weakly polygenic strains generated by a breeding system of facultative self-fertilization. One strain colonized North America and now occupies much of the southern United States and northern Mexico. No genetic variation within or among populations in the United States was detected in an electrophoretic analysis of proteins encoded by 25 loci. These findings emphasize the potential for adaptive convergence in the genetic systems of hermaphroditic animals and plants. PMID:16592078

The Meckel syndrome- associated protein MKS1 functionally interacts with components of the BBSome and IFT complexes to mediate ciliary trafficking and hedgehog signaling

PubMed Central

Barrington, Chloe L.; Katsanis, Nicholas

2017-01-01

The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins. To examine how ciliopathy protein complexes might function together, we have analyzed double mutants of an allele of the Meckel syndrome (MKS) complex protein MKS1 and the BBSome protein BBS4. We find that Mks1; Bbs4 double mutant mouse embryos exhibit exacerbated defects in Hedgehog (Hh) dependent patterning compared to either single mutant, and die by E14.5. Cells from double mutant embryos exhibit a defect in the trafficking of ARL13B, a ciliary membrane protein, resulting in disrupted ciliary structure and signaling. We also examined the relationship between the MKS complex and IFT proteins by analyzing double mutant between Mks1 and a hypomorphic allele of the IFTB component Ift172. Despite each single mutant surviving until around birth, Mks1; Ift172avc1 double mutants die at mid-gestation, and exhibit a dramatic failure of cilia formation. We also find that Mks1 interacts genetically with an allele of Dync2h1, the IFT retrograde motor. Thus, we have demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium. Moreover, the genetic interaction of Mks1 with components of IFT machinery suggests that the transition zone complex facilitates IFT to promote cilium assembly and structure. PMID:28291807

Unified framework to evaluate panmixia and migration direction among multiple sampling locations.

PubMed

Beerli, Peter; Palczewski, Michal

2010-05-01

For many biological investigations, groups of individuals are genetically sampled from several geographic locations. These sampling locations often do not reflect the genetic population structure. We describe a framework using marginal likelihoods to compare and order structured population models, such as testing whether the sampling locations belong to the same randomly mating population or comparing unidirectional and multidirectional gene flow models. In the context of inferences employing Markov chain Monte Carlo methods, the accuracy of the marginal likelihoods depends heavily on the approximation method used to calculate the marginal likelihood. Two methods, modified thermodynamic integration and a stabilized harmonic mean estimator, are compared. With finite Markov chain Monte Carlo run lengths, the harmonic mean estimator may not be consistent. Thermodynamic integration, in contrast, delivers considerably better estimates of the marginal likelihood. The choice of prior distributions does not influence the order and choice of the better models when the marginal likelihood is estimated using thermodynamic integration, whereas with the harmonic mean estimator the influence of the prior is pronounced and the order of the models changes. The approximation of marginal likelihood using thermodynamic integration in MIGRATE allows the evaluation of complex population genetic models, not only of whether sampling locations belong to a single panmictic population, but also of competing complex structured population models.

Distribution pattern and genetic structure of Aedes zammitii (Diptera: Culicidae) along the Mediterranean and Aegean coasts of Turkey.

PubMed

Yavasoglu, Sare Ilknur; Simsek, Fatih Mehmet; Ulger, Celal

2016-06-01

The Mariae species complex, consisting of Aedes mariae, Aedes phoeniciae, and Aedes zammitii, has a limited distribution worldwide. All three species are found in rocky habitats on the coastal areas of Mediterranean countries. Aedes phoeniciae and Ae. zammitii are two members of the Mariae complex that exist in Turkey. The aim of this study was to determine the distribution pattern and genetic structure of Ae. zammitii along the Mediterranean and Aegean regions. For this purpose, larval and adult samples of Ae. zammitii were collected from 19 different rocky habitats along the coastal regions of Antalya, Muğla, Aydın, İzmir, Balıkesir, and Çanakkale provinces. DNA isolation was performed primarily from collected samples, and mitochondrial NADH dehydrogenase 4 (ND4) gene was amplified by polymerase chain reaction. Based on ND4 sequence analyses, 21 haplotypes were detected along the distribution range of the species. Analyses of molecular variance (AMOVA) and spatial analyses of molecular variance (SAMOVA) indicated six groups, and most of the variation was among groups, demonstrating the population structuring at group level. Isolation by distance analyses (IBD) showed a correlation between geographic and genetic distances. © 2016 The Society for Vector Ecology.

Genotype-environment interaction and sociology: contributions and complexities.

PubMed

Seabrook, Jamie A; Avison, William R

2010-05-01

Genotype-environment interaction (G x E) refers to situations in which genetic effects connected to a phenotype are dependent upon variability in the environment, or when genes modify an organism's sensitivity to particular environmental features. Using a typology suggested in the G x E literature, we provide an overview of recent papers that show how social context can trigger a genetic vulnerability, compensate for a genetic vulnerability, control behaviors for which a genetic vulnerability exists, and improve adaptation via proximal causes. We argue that to improve their understanding of social structure, sociologists can take advantage of research in behavior genetics by assessing the impact of within-group variance of various health outcomes and complex human behaviors that are explainable by genotype, environment and their interaction. Insights from life course sociology can aid in ensuring that the dynamic nature of the environment in G x E has been accounted for. Identification of an appropriate entry point for sociologists interested in G x E research could begin with the choice of an environmental feature of interest, a genetic factor of interest, and/or behavior of interest. Optimizing measurement in order to capture the complexity of G x E is critical. Examining the interaction between poorly measured environmental factors and well measured genetic variables will overestimate the effects of genetic variables while underestimating the effect of environmental influences, thereby distorting the interaction between genotype and environment. Although the expense of collecting environmental data is very high, reliable and precise measurement of an environmental pathogen enhances a study's statistical power. Copyright 2010 Elsevier Ltd. All rights reserved.

Landscape determinants of fine-scale genetic structure of a small rodent in a heterogeneous landscape (Hluhluwe-iMfolozi Park, South Africa)

PubMed Central

Russo, Isa-Rita M.; Sole, Catherine L.; Barbato, Mario; von Bramann, Ullrich; Bruford, Michael W.

2016-01-01

Small mammals provide ecosystem services, acting, for example, as pollinators and seed dispersers. In addition, they are also disease reservoirs that can be detrimental to human health and they can also act as crop pests. Knowledge of their dispersal preferences is therefore useful for population management and landscape planning. Genetic data were used alongside landscape data to examine the influence of the landscape on the demographic connectedness of the Natal multimammate mouse (Mastomys natalensis) and to identify landscape characteristics that influence the genetic structure of this species across a spatially and temporally varying environment. The most significant landscape features shaping gene flow were aspect, vegetation cover, topographic complexity (TC) and rivers, with western facing slopes, topographic complexity and rivers restricting gene flow. In general, thicket vegetation was correlated with increased gene flow. Identifying features of the landscape that facilitate movement/dispersal in M. natalensis potentially has application for other small mammals in similar ecosystems. As the primary reservoir host of the zoonotic Lassa virus, a landscape genetics approach may have applications in determining areas of high disease risk to humans. Identifying these landscape features may also be important in crop management due to damage by rodent pests. PMID:27406468

Landscape determinants of fine-scale genetic structure of a small rodent in a heterogeneous landscape (Hluhluwe-iMfolozi Park, South Africa).

PubMed

Russo, Isa-Rita M; Sole, Catherine L; Barbato, Mario; von Bramann, Ullrich; Bruford, Michael W

2016-07-13

Small mammals provide ecosystem services, acting, for example, as pollinators and seed dispersers. In addition, they are also disease reservoirs that can be detrimental to human health and they can also act as crop pests. Knowledge of their dispersal preferences is therefore useful for population management and landscape planning. Genetic data were used alongside landscape data to examine the influence of the landscape on the demographic connectedness of the Natal multimammate mouse (Mastomys natalensis) and to identify landscape characteristics that influence the genetic structure of this species across a spatially and temporally varying environment. The most significant landscape features shaping gene flow were aspect, vegetation cover, topographic complexity (TC) and rivers, with western facing slopes, topographic complexity and rivers restricting gene flow. In general, thicket vegetation was correlated with increased gene flow. Identifying features of the landscape that facilitate movement/dispersal in M. natalensis potentially has application for other small mammals in similar ecosystems. As the primary reservoir host of the zoonotic Lassa virus, a landscape genetics approach may have applications in determining areas of high disease risk to humans. Identifying these landscape features may also be important in crop management due to damage by rodent pests.

Genetic structure in the European endemic seabird, Phalacrocorax aristotelis, shaped by a complex interaction of historical and contemporary, physical and nonphysical drivers.

PubMed

Thanou, Evanthia; Sponza, Stefano; Nelson, Emily J; Perry, Annika; Wanless, Sarah; Daunt, Francis; Cavers, Stephen

2017-05-01

Geographically separated populations tend to be less connected by gene flow, as a result of physical or nonphysical barriers preventing dispersal, and this can lead to genetic structure. In this context, highly mobile organisms such as seabirds are interesting because the small effect of physical barriers means nonphysical ones may be relatively more important. Here, we use microsatellite and mitochondrial data to explore the genetic structure and phylogeography of Atlantic and Mediterranean populations of a European endemic seabird, the European shag, Phalacrocorax aristotelis, and identify the primary drivers of their diversification. Analyses of mitochondrial markers revealed three phylogenetic lineages grouping the North Atlantic, Spanish/Corsican and eastern Mediterranean populations, apparently arising from fragmentation during the Pleistocene followed by range expansion. These traces of historical fragmentation were also evident in the genetic structure estimated by microsatellite markers, despite significant contemporary gene flow among adjacent populations. Stronger genetic structure, probably promoted by landscape, philopatry and local adaptation, was found among distant populations and those separated by physical and ecological barriers. This study highlights the enduring effect of Pleistocene climatic changes on shag populations, especially within the Mediterranean Basin, and suggests a role for cryptic northern refugia, as well as known southern refugia, on the genetic structure of European seabirds. Finally, it outlines how contemporary ecological barriers and behavioural traits may maintain population divergence, despite long-distance dispersal triggered by extreme environmental conditions (e.g. population crashes). © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Glycans – the third revolution in evolution

PubMed Central

Lauc, Gordan; Krištić, Jasminka; Zoldoš, Vlatka

2014-01-01

The development and maintenance of a complex organism composed of trillions of cells is an extremely complex task. At the molecular level every process requires a specific molecular structures to perform it, thus it is difficult to imagine how less than tenfold increase in the number of genes between simple bacteria and higher eukaryotes enabled this quantum leap in complexity. In this perspective article we present the hypothesis that the invention of glycans was the third revolution in evolution (the appearance of nucleic acids and proteins being the first two), which enabled the creation of novel molecular entities that do not require a direct genetic template. Contrary to proteins and nucleic acids, which are made from a direct DNA template, glycans are product of a complex biosynthetic pathway affected by hundreds of genetic and environmental factors. Therefore glycans enable adaptive response to environmental changes and, unlike other epiproteomic modifications, which act as off/on switches, glycosylation significantly contributes to protein structure and enables novel functions. The importance of glycosylation is evident from the fact that nearly all proteins invented after the appearance of multicellular life are composed of both polypeptide and glycan parts. PMID:24904645

NACSN, note 67--Application for revision of Articles 36 and 37, Lithodemic units of the North American stratigraphic code

USGS Publications Warehouse

Easton, Robert M.; Edwards, Lucy E.; Orndorff, Randall C.; Duguet, Manuel; Ferrusquia-Villafranca, Ismael

2015-01-01

Currently the North American Stratigraphic Code, (NACSN 2005, Article 37) sets restrictions on the use of the term “complex” for lithodemic units. With exceptions for “volcanic complex” and “structural complex,” a complex must consist of more than one genetic class of rock (i.e., sedimentary, igneous or metamorphic). Thus, the use of the term “complex” to describe masses of intrusive rocks is not allowed. Asimilar restriction is also included in a recent British Geological Survey proposal for using lithodemic units to classify igneous rocks (Gillespie et al. 2008).Currently the North American Stratigraphic Code, (NACSN 2005, Article 37) sets restrictions on the use of the term “complex” for lithodemic units. With exceptions for “volcanic complex” and “structural complex,” a complex must consist of more than one genetic class of rock (i.e., sedimentary, igneous or metamorphic). Thus, the use of the term “complex” to describe masses of intrusive rocks is not allowed. Asimilar restriction is also included in a recent British Geological Survey proposal for using lithodemic units to classify igneous rocks (Gillespie et al. 2008).

Admixture, Population Structure, and F-Statistics.

PubMed

Peter, Benjamin M

2016-04-01

Many questions about human genetic history can be addressed by examining the patterns of shared genetic variation between sets of populations. A useful methodological framework for this purpose isF-statistics that measure shared genetic drift between sets of two, three, and four populations and can be used to test simple and complex hypotheses about admixture between populations. This article provides context from phylogenetic and population genetic theory. I review how F-statistics can be interpreted as branch lengths or paths and derive new interpretations, using coalescent theory. I further show that the admixture tests can be interpreted as testing general properties of phylogenies, allowing extension of some ideas applications to arbitrary phylogenetic trees. The new results are used to investigate the behavior of the statistics under different models of population structure and show how population substructure complicates inference. The results lead to simplified estimators in many cases, and I recommend to replace F3 with the average number of pairwise differences for estimating population divergence. Copyright © 2016 by the Genetics Society of America.

Detecting a hierarchical genetic population structure via Multi-InDel markers on the X chromosome

PubMed Central

Fan, Guang Yao; Ye, Yi; Hou, Yi Ping

2016-01-01

Detecting population structure and estimating individual biogeographical ancestry are very important in population genetics studies, biomedical research and forensics. Single-nucleotide polymorphism (SNP) has long been considered to be a primary ancestry-informative marker (AIM), but it is constrained by complex and time-consuming genotyping protocols. Following up on our previous study, we propose that a multi-insertion-deletion polymorphism (Multi-InDel) with multiple haplotypes can be useful in ancestry inference and hierarchical genetic population structures. A validation study for the X chromosome Multi-InDel marker (X-Multi-InDel) as a novel AIM was conducted. Genetic polymorphisms and genetic distances among three Chinese populations and 14 worldwide populations obtained from the 1000 Genomes database were analyzed. A Bayesian clustering method (STRUCTURE) was used to discern the continental origins of Europe, East Asia, and Africa. A minimal panel of ten X-Multi-InDels was verified to be sufficient to distinguish human ancestries from three major continental regions with nearly the same efficiency of the earlier panel with 21 insertion-deletion AIMs. Along with the development of more X-Multi-InDels, an approach using this novel marker has the potential for broad applicability as a cost-effective tool toward more accurate determinations of individual biogeographical ancestry and population stratification. PMID:27535707

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.

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.; 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.

2015-01-01

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

Structural reducibility of multilayer networks

NASA Astrophysics Data System (ADS)

de Domenico, Manlio; Nicosia, Vincenzo; Arenas, Alexandre; Latora, Vito

2015-04-01

Many complex systems can be represented as networks consisting of distinct types of interactions, which can be categorized as links belonging to different layers. For example, a good description of the full protein-protein interactome requires, for some organisms, up to seven distinct network layers, accounting for different genetic and physical interactions, each containing thousands of protein-protein relationships. A fundamental open question is then how many layers are indeed necessary to accurately represent the structure of a multilayered complex system. Here we introduce a method based on quantum theory to reduce the number of layers to a minimum while maximizing the distinguishability between the multilayer network and the corresponding aggregated graph. We validate our approach on synthetic benchmarks and we show that the number of informative layers in some real multilayer networks of protein-genetic interactions, social, economical and transportation systems can be reduced by up to 75%.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia

PubMed Central

Lee, Phil H.; Baker, Justin T.; Holmes, Avram J.; Jahanshad, Neda; Ge, Tian; Jung, Jae-Yoon; Cruz, Yanela; Manoach, Dara S.; Hibar, Derrek P.; Faskowitz, Joshua; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicolas H.; Wright, Margaret J.; Öngür, Dost; Buckner, Randy; Roffman, Joshua; Thompson, Paul M.; Smoller, Jordan W.

2016-01-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide SNP and neuroimaging data from 1,750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (FDR=10%). In particular, intracranial volume (ICV) and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder. PMID:27725656

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

PubMed

Lee, P H; Baker, J T; Holmes, A J; Jahanshad, N; Ge, T; Jung, J-Y; Cruz, Y; Manoach, D S; Hibar, D P; Faskowitz, J; McMahon, K L; de Zubicaray, G I; Martin, N H; Wright, M J; Öngür, D; Buckner, R; Roffman, J; Thompson, P M; Smoller, J W

2016-12-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Optimizing multiple sequence alignments using a genetic algorithm based on three objectives: structural information, non-gaps percentage and totally conserved columns.

PubMed

Ortuño, Francisco M; Valenzuela, Olga; Rojas, Fernando; Pomares, Hector; Florido, Javier P; Urquiza, Jose M; Rojas, Ignacio

2013-09-01

Multiple sequence alignments (MSAs) are widely used approaches in bioinformatics to carry out other tasks such as structure predictions, biological function analyses or phylogenetic modeling. However, current tools usually provide partially optimal alignments, as each one is focused on specific biological features. Thus, the same set of sequences can produce different alignments, above all when sequences are less similar. Consequently, researchers and biologists do not agree about which is the most suitable way to evaluate MSAs. Recent evaluations tend to use more complex scores including further biological features. Among them, 3D structures are increasingly being used to evaluate alignments. Because structures are more conserved in proteins than sequences, scores with structural information are better suited to evaluate more distant relationships between sequences. The proposed multiobjective algorithm, based on the non-dominated sorting genetic algorithm, aims to jointly optimize three objectives: STRIKE score, non-gaps percentage and totally conserved columns. It was significantly assessed on the BAliBASE benchmark according to the Kruskal-Wallis test (P < 0.01). This algorithm also outperforms other aligners, such as ClustalW, Multiple Sequence Alignment Genetic Algorithm (MSA-GA), PRRP, DIALIGN, Hidden Markov Model Training (HMMT), Pattern-Induced Multi-sequence Alignment (PIMA), MULTIALIGN, Sequence Alignment Genetic Algorithm (SAGA), PILEUP, Rubber Band Technique Genetic Algorithm (RBT-GA) and Vertical Decomposition Genetic Algorithm (VDGA), according to the Wilcoxon signed-rank test (P < 0.05), whereas it shows results not significantly different to 3D-COFFEE (P > 0.05) with the advantage of being able to use less structures. Structural information is included within the objective function to evaluate more accurately the obtained alignments. The source code is available at http://www.ugr.es/~fortuno/MOSAStrE/MO-SAStrE.zip.

Chromosome organizaton in simple and complex unicellular organisms.

PubMed

O'Sullivan, Justin M

2011-01-01

The genomes of unicellular organisms form complex 3-dimensional structures. This spatial organization is hypothesized to have a significant role in genomic function. Spatial organization is not limited solely to the three-dimensional folding of the chromosome(s) in genomes but also includes genome positioning, and the folding and compartmentalization of any additional genetic material (e.g. episomes) present within complex genomes. In this comment, I will highlight similarities in the spatial organization of eukaryotic and prokaryotic unicellular genomes.

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

The crystal structure of DR6 in complex with the amyloid precursor protein provides insight into death receptor activation

DOE PAGES

Xu, Kai; Olsen, Olav; Tzvetkova-Robev, Dorothea; ...

2015-04-02

The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6 ectodomain in complex with the E2 domain of APP and show that it supports a model for APP-induced dimerization and activation of cell surface DR6.

Connectivity of the habitat-forming kelp, Ecklonia radiata within and among estuaries and open coast.

PubMed

Coleman, Melinda A

2013-01-01

With marine protected areas being established worldwide there is a pressing need to understand how the physical setting in which these areas are placed influences patterns of dispersal and connectivity of important marine organisms. This is particularly critical for dynamic and complex nearshore marine environments where patterns of genetic structure of organisms are often chaotic and uncoupled from broad scale physical processes. This study determines the influence of habitat heterogeneity (presence of estuaries) on patterns of genetic structure and connectivity of the common kelp, Ecklonia radiata. There was no genetic differentiation of kelp between estuaries and the open coast and the presence of estuaries did not increase genetic differentiation among open coast populations. Similarly, there were no differences in level of inbreeding or genetic diversity between estuarine and open coast populations. The presence of large estuaries along rocky coastlines does not appear to influence genetic structure of this kelp and factors other than physical heterogeneity of habitat are likely more important determinants of regional connectivity. Marine reserves are currently lacking in this bioregion and may be designated in the future. Knowledge of the factors that influence important habitat forming organisms such as kelp contribute to informed and effective marine protected area design and conservation initiatives to maintain resilience of important marine habitats.

Corallite skeletal morphological variation in Hawaiian Porites lobata

NASA Astrophysics Data System (ADS)

Tisthammer, Kaho H.; Richmond, Robert H.

2018-06-01

Due to their high morphological plasticity and complex evolutionary history, the species boundaries of many reef-building corals are poorly understood. The skeletal structures of corals have traditionally been used for species identification, but these structures can be highly variable, and currently we lack knowledge regarding the extent of morphological variation within species. Porites species are notorious for their taxonomic difficulties, both morphologically and genetically, and currently there are several unresolved species complexes in the Pacific. Despite its ubiquitous presence and broad use in coral research, Porites lobata belongs to one such unresolved species complex. To understand the degree of intraspecific variation in skeletal morphology, 120 corallites from the Hawaiian P. lobata were examined. A subset of samples from two genetically differentiated populations from contrasting high- and low-stress environments in Maunalua Bay, Hawaii, were then quantitatively analyzed using multivariate morphometrics. Our observations revealed high intraspecific variation in corallite morphology, as well as significant morphological differences between the two populations of P. lobata. Additionally, significant correlation was found between the morphological and genetic distances calculated from approximately 18,000 loci generated from restriction site-associated DNA sequencing. The unique morphological characters observed from the genetically differentiated population under environmental stress suggest that these characters may have adaptive values, but how such traits relate to fitness and how much plasticity they can exhibit remain to be determined by future studies. Relatively simple morphometric analyses used in our study can be useful in clarifying the existing ambiguity in skeletal architecture, thus contributing to resolving species issues in corals.

Role of evolutionary and ecological factors in the reproductive success and the spatial genetic structure of the temperate gorgonian Paramuricea clavata

PubMed Central

Mokhtar-Jamaï, Kenza; Coma, Rafel; Wang, Jinliang; Zuberer, Frederic; Féral, Jean-Pierre; Aurelle, Didier

2013-01-01

Dispersal and mating features strongly influence the evolutionary dynamics and the spatial genetic structure (SGS) of marine populations. For the first time in a marine invertebrate, we examined individual reproductive success, by conducting larval paternity assignments after a natural spawning event, combined with a small-scale SGS analysis within a population of the gorgonian Paramuricea clavata. Thirty four percent of the larvae were sired by male colonies surrounding the brooding female colonies, revealing that the bulk of the mating was accomplished by males from outside the studied area. Male success increased with male height and decreased with increasing male to female distance. The parentage analyses, with a strong level of self-recruitment (25%), unveiled the occurrence of a complex family structure at a small spatial scale, consistent with the limited larval dispersal of this species. However, no evidence of small scale SGS was revealed despite this family structure. Furthermore, temporal genetic structure was not observed, which appears to be related to the rather large effective population size. The low level of inbreeding found suggests a pattern of random mating in this species, which disagrees with expectations that limited larval dispersal should lead to biparental inbreeding. Surface brooding and investment in sexual reproduction in P. clavata contribute to multiple paternity (on average 6.4 fathers were assigned per brood), which enhance genetic diversity of the brood. Several factors may have contributed to the lack of biparental inbreeding in our study such as (i) the lack of sperm limitation at a small scale, (ii) multiple paternity, and (iii) the large effective population size. Thus, our results indicate that limited larval dispersal and complex family structure do not necessarily lead to biparental inbreeding and SGS. In the framework of conservation purposes, our results suggested that colony size, proximity among colonies and the population size should be taken into consideration for restoration projects. PMID:23789084

Crystal structure of RuvC resolvase in complex with Holliday junction substrate

PubMed Central

Górecka, Karolina M.; Komorowska, Weronika; Nowotny, Marcin

2013-01-01

The key intermediate in genetic recombination is the Holliday junction (HJ), a four-way DNA structure. At the end of recombination, HJs are cleaved by specific nucleases called resolvases. In Gram-negative bacteria, this cleavage is performed by RuvC, a dimeric endonuclease that belongs to the retroviral integrase superfamily. Here, we report the first crystal structure of RuvC in complex with a synthetic HJ solved at 3.75 Å resolution. The junction in the complex is in an unfolded 2-fold symmetrical conformation, in which the four arms point toward the vertices of a tetrahedron. The two scissile phosphates are located one nucleotide from the strand exchange point, and RuvC approaches them from the minor groove side. The key protein–DNA contacts observed in the structure were verified using a thiol-based site-specific cross-linking approach. Compared with known complex structures of the phage resolvases endonuclease I and endonuclease VII, the RuvC structure exhibits striking differences in the mode of substrate binding and location of the cleavage site. PMID:23980027

Genetic structure and evolution of the Leishmania genus in Africa and Eurasia: what does MLSA tell us.

PubMed

El Baidouri, Fouad; Diancourt, Laure; Berry, Vincent; Chevenet, François; Pratlong, Francine; Marty, Pierre; Ravel, Christophe

2013-01-01

Leishmaniasis is a complex parasitic disease from a taxonomic, clinical and epidemiological point of view. The role of genetic exchanges has been questioned for over twenty years and their recent experimental demonstration along with the identification of interspecific hybrids in natura has revived this debate. After arguing that genetic exchanges were exceptional and did not contribute to Leishmania evolution, it is currently proposed that interspecific exchanges could be a major driving force for rapid adaptation to new reservoirs and vectors, expansion into new parasitic cycles and adaptation to new life conditions. To assess the existence of gene flows between species during evolution we used MLSA-based (MultiLocus Sequence Analysis) approach to analyze 222 Leishmania strains from Africa and Eurasia to accurately represent the genetic diversity of this genus. We observed a remarkable congruence of the phylogenetic signal and identified seven genetic clusters that include mainly independent lineages which are accumulating divergences without any sign of recent interspecific recombination. From a taxonomic point of view, the strong genetic structuration of the different species does not question the current classification, except for species that cause visceral forms of leishmaniasis (L. donovani, L. infantum and L. archibaldi). Although these taxa cause specific clinical forms of the disease and are maintained through different parasitic cycles, they are not clearly distinct and form a continuum, in line with the concept of species complex already suggested for this group thirty years ago. These results should have practical consequences concerning the molecular identification of parasites and the subsequent therapeutic management of the disease.

Common Variants within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage

PubMed Central

Anderson, Christopher D.; Biffi, Alessandro; Nalls, Michael A.; Devan, William J.; Schwab, Kristin; Ayres, Alison M.; Valant, Valerie; Ross, Owen A.; Rost, Natalia S.; Saxena, Richa; Viswanathan, Anand; Worrall, Bradford B.; Brott, Thomas G.; Goldstein, Joshua N.; Brown, Devin; Broderick, Joseph P.; Norrving, Bo; Greenberg, Steven M.; Silliman, Scott L.; Hansen, Björn M.; Tirschwell, David L.; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Selim, Magdy; Roquer, Jaume; Montaner, Joan; Singleton, Andrew B.; Kidwell, Chelsea S.; Woo, Daniel; Furie, Karen L.; Meschia, James F.; Rosand, Jonathan

2013-01-01

Background and Purpose Prior studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods This association study employed a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis (GSEA) was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing GSEA were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio (OR)=1.17, p=0.008) and Complex I (OR=1.06, p=0.050). Among IS subtypes, small vessel (SV) stroke showed association with OXPHOS (OR=1.16, p=0.007), Complex I (OR=1.13, p=0.027) and Complex IV (OR 1.14, p=0.018). To further explore this SV association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and Complex IV (OR=1.08, p=0.008). Conclusions This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for SV stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. PMID:23362085

Genetic Structure and Gene Flows within Horses: A Genealogical Study at the French Population Scale

PubMed Central

Pirault, Pauline; Danvy, Sophy; Verrier, Etienne; Leroy, Grégoire

2013-01-01

Since horse breeds constitute populations submitted to variable and multiple outcrossing events, we analyzed the genetic structure and gene flows considering horses raised in France. We used genealogical data, with a reference population of 547,620 horses born in France between 2002 and 2011, grouped according to 55 breed origins. On average, individuals had 6.3 equivalent generations known. Considering different population levels, fixation index decreased from an overall species FIT of 1.37%, to an average of −0.07% when considering the 55 origins, showing that most horse breeds constitute populations without genetic structure. We illustrate the complexity of gene flows existing among horse breeds, a few populations being closed to foreign influence, most, however, being submitted to various levels of introgression. In particular, Thoroughbred and Arab breeds are largely used as introgression sources, since those two populations explain together 26% of founder origins within the overall horse population. When compared with molecular data, breeds with a small level of coancestry also showed low genetic distance; the gene pool of the breeds was probably impacted by their reproducer exchanges. PMID:23630596

What factors shape genetic diversity in cetaceans?

PubMed

Vachon, Felicia; Whitehead, Hal; Frasier, Timothy R

2018-02-01

Understanding what factors drive patterns of genetic diversity is a central aspect of many biological questions, ranging from the inference of historical demography to assessing the evolutionary potential of a species. However, as a larger number of datasets have become available, it is becoming clear that the relationship between the characteristics of a species and its genetic diversity is more complex than previously assumed. This may be particularly true for cetaceans, due to their relatively long lifespans, long generation times, complex social structures, and extensive ranges. In this study, we used microsatellite and mitochondrial DNA data from a systematic literature review to produce estimates of diversity for both markers across 42 cetacean species. Factors relating to demography, distribution, classification, biology, and behavior were then tested using phylogenetic methods and linear models to assess their relative influence on the genetic diversity of both marker types. The results show that while relative nuclear diversity is correlated with population size, mitochondrial diversity is not. This is particularly relevant given the widespread use of mitochondrial DNA to infer historical demography. Instead, mitochondrial diversity was mostly influenced by the range and social structure of the species. In addition to population size, habitat type (neritic vs. oceanic) had a significant correlation with relative nuclear diversity. Combined, these results show that many often-unconsidered factors are likely influencing patterns of genetic diversity in cetaceans, with implications regarding how to interpret, and what can be inferred from, existing patterns of diversity.

Crystal structure of the Csm3-Csm4 subcomplex in the type III-A CRISPR-Cas interference complex.

PubMed

Numata, Tomoyuki; Inanaga, Hideko; Sato, Chikara; Osawa, Takuo

2015-01-30

Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci play a pivotal role in the prokaryotic host defense system against invading genetic materials. The CRISPR loci are transcribed to produce CRISPR RNAs (crRNAs), which form interference complexes with CRISPR-associated (Cas) proteins to target the invading nucleic acid for degradation. The interference complex of the type III-A CRISPR-Cas system is composed of five Cas proteins (Csm1-Csm5) and a crRNA, and targets invading DNA. Here, we show that the Csm1, Csm3, and Csm4 proteins from Methanocaldococcus jannaschii form a stable subcomplex. We also report the crystal structure of the M. jannaschii Csm3-Csm4 subcomplex at 3.1Å resolution. The complex structure revealed the presence of a basic concave surface around their interface, suggesting the RNA and/or DNA binding ability of the complex. A gel retardation analysis showed that the Csm3-Csm4 complex binds single-stranded RNA in a non-sequence-specific manner. Csm4 structurally resembles Cmr3, a component of the type III-B CRISPR-Cas interference complex. Based on bioinformatics, we constructed a model structure of the Csm1-Csm4-Csm3 ternary complex, which provides insights into its role in the Csm interference complex. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic variations in the Dravidian population of South West coast of India: Implications in designing case-control studies.

PubMed

D'Cunha, Anitha; Pandit, Lekha; Malli, Chaithra

2017-06-01

Indian data have been largely missing from genome-wide databases that provide information on genetic variations in different populations. This hinders association studies for complex disorders in India. This study was aimed to determine whether the complex genetic structure and endogamy among Indians could potentially influence the design of case-control studies for autoimmune disorders in the south Indian population. A total of 12 single nucleotide variations (SNVs) related to genes associated with autoimmune disorders were genotyped in 370 healthy individuals belonging to six different caste groups in southern India. Allele frequencies were estimated; genetic divergence and phylogenetic relationship within the various caste groups and other HapMap populations were ascertained. Allele frequencies for all genotyped SNVs did not vary significantly among the different groups studied. Wright's FSTwas 0.001 per cent among study population and 0.38 per cent when compared with Gujarati in Houston (GIH) population on HapMap data. The analysis of molecular variance results showed a 97 per cent variation attributable to differences within the study population and <1 per cent variation due to differences between castes. Phylogenetic analysis showed a separation of Dravidian population from other HapMap populations and particularly from GIH population. Despite the complex genetic origins of the Indian population, our study indicated a low level of genetic differentiation among Dravidian language-speaking people of south India. Case-control studies of association among Dravidians of south India may not require stratification based on language and caste.

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

Population genetic structure of traditional populations in the Peruvian Central Andes and implications for South American population history.

PubMed

Cabana, Graciela S; Lewis, Cecil M; Tito, Raúl Y; Covey, R Alan; Cáceres, Angela M; Cruz, Augusto F De La; Durand, Diana; Housman, Genevieve; Hulsey, Brannon I; Iannacone, Gian Carlo; López, Paul W; Martínez, Rolando; Medina, Ángel; Dávila, Olimpio Ortega; Pinto, Karla Paloma Osorio; Santillán, Susan I Polo; Domínguez, Percy Rojas; Rubel, Meagan; Smith, Heather F; Smith, Silvia E; Massa, Verónica Rubín de Celis; Lizárraga, Beatriz; Stone, Anne C

2014-01-01

Molecular-based characterizations of Andean peoples are traditionally conducted in the service of elucidating continent-level evolutionary processes in South America. Consequently, genetic variation among "western" Andean populations is often represented in relation to variation among "eastern" Amazon and Orinoco River Basin populations. This west-east contrast in patterns of population genetic variation is typically attributed to large-scale phenomena, such as dual founder colonization events or differing long-term microevolutionary histories. However, alternative explanations that consider the nature and causes of population genetic diversity within the Andean region remain underexplored. Here we examine population genetic diversity in the Peruvian Central Andes using data from the mtDNA first hypervariable region and Y-chromosome short tandem repeats among 17 newly sampled populations and 15 published samples. Using this geographically comprehensive data set, we first reassessed the currently accepted pattern of western versus eastern population genetic structure, which our results ultimately reject: mtDNA population diversities were lower, rather than higher, within Andean versus eastern populations, and only highland Y-chromosomes exhibited significantly higher within-population diversities compared with eastern groups. Multiple populations, including several highland samples, exhibited low genetic diversities for both genetic systems. Second, we explored whether the implementation of Inca state and Spanish colonial policies starting at about ad 1400 could have substantially restructured population genetic variation and consequently constitute a primary explanation for the extant pattern of population diversity in the Peruvian Central Andes. Our results suggest that Peruvian Central Andean population structure cannot be parsimoniously explained as the sole outcome of combined Inca and Spanish policies on the region's population demography: highland populations differed from coastal and lowland populations in mtDNA genetic structure only; highland groups also showed strong evidence of female-biased gene flow and/or effective sizes relative to other Peruvian ecozones. Taken together, these findings indicate that population genetic structure in the Peruvian Central Andes is considerably more complex than previously reported and that characterizations of and explanations for genetic variation may be best pursued within more localized regions and defined time periods.

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.

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens. | Office of Cancer Genomics

Cancer.gov

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity.

Statistical Analysis of Big Data on Pharmacogenomics

PubMed Central

Fan, Jianqing; Liu, Han

2013-01-01

This paper discusses statistical methods for estimating complex correlation structure from large pharmacogenomic datasets. We selectively review several prominent statistical methods for estimating large covariance matrix for understanding correlation structure, inverse covariance matrix for network modeling, large-scale simultaneous tests for selecting significantly differently expressed genes and proteins and genetic markers for complex diseases, and high dimensional variable selection for identifying important molecules for understanding molecule mechanisms in pharmacogenomics. Their applications to gene network estimation and biomarker selection are used to illustrate the methodological power. Several new challenges of Big data analysis, including complex data distribution, missing data, measurement error, spurious correlation, endogeneity, and the need for robust statistical methods, are also discussed. PMID:23602905

Characterizing complex structural variation in germline and somatic genomes

PubMed Central

Quinlan, Aaron R.; Hall, Ira M.

2011-01-01

Genome structural variation (SV) is a major source of genetic diversity in mammals and a hallmark of cancer. While SV is typically defined by its canonical forms – duplication, deletion, insertion, inversion and translocation – recent breakpoint mapping studies have revealed a surprising number of “complex” variants that evade simple classification. Complex SVs are defined by clustered breakpoints that arose through a single mutation but cannot be explained by one simple end-joining or recombination event. Some complex variants exhibit profoundly complicated rearrangements between distinct loci from multiple chromosomes, while others involve more subtle alterations at a single locus. These diverse and unpredictable features present a challenge for SV mapping experiments. Here, we review current knowledge of complex SV in mammals, and outline techniques for identifying and characterizing complex variants using next-generation DNA sequencing. PMID:22094265

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 Mesoamerican Reef and is an important contribution toward improving the future management of this commercially protected species.

Evidence for progenitor–derivative speciation in sexually deceptive orchids

PubMed Central

Schlüter, Philipp M.; Ruas, Paulo M.; Kohl, Gudrun; Ruas, Claudete F.; Stuessy, Tod F.; Paulus, Hannes F.

2011-01-01

Background and Aims Sexually deceptive orchids of the genus Ophrys use mimicry of pollinator females to attract specific pollinators. Pollinator shifts may drive speciation in Ophrys, since novel pollinators may in principle act as isolating factors immediately. It is thus possible that evolution of novel species occurs rapidly and with a progenitor–derivative pattern. The aims of this study are to compare genetic structure and diversity among widespread and geographically restricted Ophrys taxa, to test whether genetic structure is associated with specific pollinators, and to investigate whether any widespread species may have acted as a progenitor for the evolution of more restricted taxa. Methods Genetic differentiation and diversity were investigated in O. leucadica and O. cinereophila, the two taxa of the Ophrys fusca sensu lato complex widespread in the Aegean, and three geographically restricted taxa from Rhodes, O. attaviria, O. parvula and O. persephonae, all differing in their specific pollinators. This was done using amplified fragment length polymorphism (AFLP) DNA fingerprinting, and sequencing of the low-copy nuclear gene LEAFY (LFY). Key Results All taxa were found to be separate genetic entities, with O. leucadica forming two geographic groups from the west and east of the Aegean. Genetic structure was significantly shaped by pollinators and geography, and comparison of sequence and AFLP data revealed ancestral polymorphisms shared among several taxa. Among the sampled taxa, O. leucadica harbours the greatest genetic differentiation and geographic structure, and the highest genetic diversity. Part of the genome of O. parvula, endemic to Rhodes, may be derived from O. leucadica. Conclusions Pollinators probably influence the genetic structure of the investigated Ophrys species. The genetic pattern identified is consistent with O. leucadica being the oldest of the sampled taxa, making O. leucadica a candidate progenitor species from which more restricted taxa such as O. parvula may have evolved. PMID:21890487

Structure of the CRISPR Interference Complex CSM Reveals Key Similarities with Cascade

PubMed Central

Rouillon, Christophe; Zhou, Min; Zhang, Jing; Politis, Argyris; Beilsten-Edmands, Victoria; Cannone, Giuseppe; Graham, Shirley; Robinson, Carol V.; Spagnolo, Laura; White, Malcolm F.

2013-01-01

Summary The Clustered Regularly Interspaced Palindromic Repeats (CRISPR) system is an adaptive immune system in prokaryotes. Interference complexes encoded by CRISPR-associated (cas) genes utilize small RNAs for homology-directed detection and subsequent degradation of invading genetic elements, and they have been classified into three main types (I–III). Type III complexes share the Cas10 subunit but are subclassifed as type IIIA (CSM) and type IIIB (CMR), depending on their specificity for DNA or RNA targets, respectively. The role of CSM in limiting the spread of conjugative plasmids in Staphylococcus epidermidis was first described in 2008. Here, we report a detailed investigation of the composition and structure of the CSM complex from the archaeon Sulfolobus solfataricus, using a combination of electron microscopy, mass spectrometry, and deep sequencing. This reveals a three-dimensional model for the CSM complex that includes a helical component strikingly reminiscent of the backbone structure of the type I (Cascade) family. PMID:24119402

Divergent population structure and climate associations of a chromosomal inversion polymorphism across the Mimulus guttatus species complex

PubMed Central

Oneal, Elen; Lowry, David B.; Wright, Kevin M.; Zhu, Zhirui; Willis, John H.

2014-01-01

Chromosomal rearrangement polymorphisms are common and increasingly found to be associated with adaptive ecological divergence and speciation. Rearrangements, such as inversions, reduce recombination in heterozygous individuals and thus can protect favourable allelic combinations at linked loci, facilitating their spread in the presence of gene flow. Recently, we identified a chromosomal inversion polymorphism that contributes to ecological adaptation and reproductive isolation between annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatus. Here we evaluate the population genetic structure of this inverted region in comparison with the collinear regions of the genome across the M. guttatus species complex. We tested whether annual and perennial M. guttatus exhibit different patterns of divergence for loci in the inverted and noninverted regions of the genome. We then evaluated whether there are contrasting climate associations with these genomic regions through redundancy analysis. We found that the inversion exhibits broadly different patterns of divergence among annual and perennial M. guttatus and is associated with environmental variation across population accessions. This study is the first widespread population genetic survey of the diversity of the M. guttatus species complex. Our findings contribute to a greater understanding of morphological, ecological, and genetic evolutionary divergence across this highly diverse group of closely related ecotypes and species. Finally, understanding species relationships among M. guttatus sp. has hitherto been stymied by accumulated evidence of substantial gene flow among populations as well as designated species. Nevertheless, our results shed light on these relationships and provide insight into adaptation in life history traits within the complex. PMID:24796267

2q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia

PubMed Central

Karayiorgou, Maria; Simon, Tony J.; Gogos, Joseph A.

2010-01-01

Recent studies are beginning to paint a clear and consistent picture of the impairments in psychological and cognitive competencies that are associated with microdeletions in chromosome 22q11.2. These studies have highlighted a strong link between this genetic lesion and schizophrenia. Parallel studies in humans and animal models are starting to uncover the complex genetic and neural substrates altered by the microdeletion. In addition to offering a deeper understanding of the effects of this genetic lesion, these findings may guide analysis of other copy-number variants associated with cognitive dysfunction and psychiatric disorders. PMID:20485365

Pleistocene and ecological effects on continental-scale genetic differentiation in the bobcat (Lynx rufus).

PubMed

Reding, Dawn M; Bronikowski, Anne M; Johnson, Warren E; Clark, William R

2012-06-01

The potential for widespread, mobile species to exhibit genetic structure without clear geographic barriers is a topic of growing interest. Yet the patterns and mechanisms of structure--particularly over broad spatial scales--remain largely unexplored for these species. Bobcats occur across North America and possess many characteristics expected to promote gene flow. To test whether historical, topographic or ecological factors have influenced genetic differentiation in this species, we analysed 1 kb mtDNA sequence and 15 microsatellite loci from over 1700 samples collected across its range. The primary signature in both marker types involved a longitudinal cline with a sharp transition, or suture zone, occurring along the Great Plains. Thus, the data distinguished bobcats in the eastern USA from those in the western half, with no obvious physical barrier to gene flow. Demographic analyses supported a scenario of expansion from separate Pleistocene refugia, with the Great Plains representing a zone of secondary contact. Substructure within the two main lineages likely reflected founder effects, ecological factors, anthropogenic/topographic effects or a combination of these forces. Two prominent topographic features, the Mississippi River and Rocky Mountains, were not supported as significant genetic barriers. Ecological regions and environmental correlates explained a small but significant proportion of genetic variation. Overall, results implicate historical processes as the primary cause of broad-scale genetic differentiation, but contemporary forces seem to also play a role in promoting and maintaining structure. Despite the bobcat's mobility and broad niche, large-scale landscape changes have contributed to significant and complex patterns of genetic structure. © 2012 Blackwell Publishing Ltd.

Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases

PubMed Central

Haan, Claude; Behrmann, Iris; Haan, Serge

2010-01-01

Abstract Gain-of-function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets. PMID:20132407

Direct introduction of gene constructs into the pronucleus-like structure of cloned embryos: a new strategy for the generation of genetically modified pigs.

PubMed

Kurome, Mayuko; Leuchs, Simon; Kessler, Barbara; Kemter, Elisabeth; Jemiller, Eva-Maria; Foerster, Beatrix; Klymiuk, Nikolai; Zakhartchenko, Valeri; Wolf, Eckhard

2017-04-01

Due to a rising demand of porcine models with complex genetic modifications for biomedical research, the approaches for their generation need to be adapted. In this study we describe the direct introduction of a gene construct into the pronucleus (PN)-like structure of cloned embryos as a novel strategy for the generation of genetically modified pigs, termed "nuclear injection". To evaluate the reliability of this new strategy, the developmental ability of embryos in vitro and in vivo as well as the integration and expression efficiency of a transgene carrying green fluorescence protein (GFP) were examined. Eighty percent of the cloned pig embryos (633/787) exhibited a PN-like structure, which met the prerequisite to technically perform the new method. GFP fluorescence was observed in about half of the total blastocysts (21/40, 52.5%), which was comparable to classical zygote PN injection (28/41, 68.3%). In total, 478 cloned embryos injected with the GFP construct were transferred into 4 recipients and from one recipient 4 fetuses (day 68) were collected. In one of the fetuses which showed normal development, the integration of the transgene was confirmed by PCR in different tissues and organs from all three primary germ layers and placenta. The integration pattern of the transgene was mosaic (48 out of 84 single-cell colonies established from a kidney were positive for GFP DNA by PCR). Direct GFP fluorescence was observed macro- and microscopically in the fetus. Our novel strategy could be useful particularly for the generation of pigs with complex genetic modifications.

Ancient trade routes shaped the genetic structure of horses in eastern Eurasia.

PubMed

Warmuth, Vera M; Campana, Michael G; Eriksson, Anders; Bower, Mim; Barker, Graeme; Manica, Andrea

2013-11-01

Animal exchange networks have been shown to play an important role in determining gene flow among domestic animal populations. The Silk Road is one of the oldest continuous exchange networks in human history, yet its effectiveness in facilitating animal exchange across large geographical distances and topographically challenging landscapes has never been explicitly studied. Horses are known to have been traded along the Silk Roads; however, extensive movement of horses in connection with other human activities may have obscured the genetic signature of the Silk Roads. To investigate the role of the Silk Roads in shaping the genetic structure of horses in eastern Eurasia, we analysed microsatellite genotyping data from 455 village horses sampled from 17 locations. Using least-cost path methods, we compared the performance of models containing the Silk Roads as corridors for gene flow with models containing single landscape features. We also determined whether the recent isolation of former Soviet Union countries from the rest of Eurasia has affected the genetic structure of our samples. The overall level of genetic differentiation was low, consistent with historically high levels of gene flow across the study region. The spatial genetic structure was characterized by a significant, albeit weak, pattern of isolation by distance across the continent with no evidence for the presence of distinct genetic clusters. Incorporating landscape features considerably improved the fit of the data; however, when we controlled for geographical distance, only the correlation between genetic differentiation and the Silk Roads remained significant, supporting the effectiveness of this ancient trade network in facilitating gene flow across large geographical distances in a topographically complex landscape. © 2013 John Wiley & Sons Ltd.

Tracking climate change in a dispersal-limited species: reduced spatial and genetic connectivity in a montane salamander.

PubMed

Velo-Antón, G; Parra, J L; Parra-Olea, G; Zamudio, K R

2013-06-01

Tropical montane taxa are often locally adapted to very specific climatic conditions, contributing to their lower dispersal potential across complex landscapes. Climate and landscape features in montane regions affect population genetic structure in predictable ways, yet few empirical studies quantify the effects of both factors in shaping genetic structure of montane-adapted taxa. Here, we considered temporal and spatial variability in climate to explain contemporary genetic differentiation between populations of the montane salamander, Pseudoeurycea leprosa. Specifically, we used ecological niche modelling (ENM) and measured spatial connectivity and gene flow (using both mtDNA and microsatellite markers) across extant populations of P. leprosa in the Trans-Mexican Volcanic Belt (TVB). Our results indicate significant spatial and genetic isolation among populations, but we cannot distinguish between isolation by distance over time or current landscape barriers as mechanisms shaping population genetic divergences. Combining ecological niche modelling, spatial connectivity analyses, and historical and contemporary genetic signatures from different classes of genetic markers allows for inference of historical evolutionary processes and predictions of the impacts future climate change will have on the genetic diversity of montane taxa with low dispersal rates. Pseudoeurycea leprosa is one montane species among many endemic to this region and thus is a case study for the continued persistence of spatially and genetically isolated populations in the highly biodiverse TVB of central Mexico. © 2013 John Wiley & Sons Ltd.

Possible implication of the genetic composition of the Lutzomyia longipalpis (Diptera: Psychodidae) populations in the epidemiology of the visceral leishmaniasis.

PubMed

Rocha, Leonardo de Souza; Falqueto, Aloisio; Dos Santos, Claudiney Biral; Grimaldi, Gabriel Júnior; Cupolillo, Elisa

2011-09-01

Lutzomyia longipalpis (Diptera: Psychodidae) is the principal vector of American visceral leishmaniasis. Several studies have indicated that the Lu. longipalpis population structure is complex. It has been suggested that genetic divergence caused by genetic drift, selection, or both may affect the vectorial capacity of Lu. longipalpis. However, it remains unclear whether genetic differences among Lu. longipalpis populations are directly implicated in the transmission features of visceral leishmaniasis. We evaluated the genetic composition and the patterns of genetic differentiation among Lu. longipalpis populations collected from regions with different patterns of transmission of visceral leishmaniasis by analyzing the sequence variation in the mitochondrial cytochrome b gene. Furthermore, we investigated the temporal distribution of haplotypes and compared our results with those obtained in a previous study. Our data indicate that there are differences in the haplotype composition and that there has been significant differentiation between the analyzed populations. Our results reveal that measures used to control visceral leishmaniasis might have influenced the genetic composition of the vector population. This finding raises important questions concerning the epidemiology of visceral leishmaniasis, because these differences in the genetic structures among populations of Lu. longipalpis may have implications with respect to their efficiency as vectors for visceral leishmaniasis.

Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.

PubMed

Wilbe, Maria; Jokinen, Päivi; Truvé, Katarina; Seppala, Eija H; Karlsson, Elinor K; Biagi, Tara; Hughes, Angela; Bannasch, Danika; Andersson, Göran; Hansson-Hamlin, Helene; Lohi, Hannes; Lindblad-Toh, Kerstin

2010-03-01

The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.

A genetic algorithm for solving supply chain network design model

NASA Astrophysics Data System (ADS)

Firoozi, Z.; Ismail, N.; Ariafar, S. H.; Tang, S. H.; Ariffin, M. K. M. A.

2013-09-01

Network design is by nature costly and optimization models play significant role in reducing the unnecessary cost components of a distribution network. This study proposes a genetic algorithm to solve a distribution network design model. The structure of the chromosome in the proposed algorithm is defined in a novel way that in addition to producing feasible solutions, it also reduces the computational complexity of the algorithm. Computational results are presented to show the algorithm performance.

Parana Basin Structure from Multi-Objective Inversion of Surface Wave and Receiver Function by Competent Genetic Algorithm

NASA Astrophysics Data System (ADS)

An, M.; Assumpcao, M.

2003-12-01

The joint inversion of receiver function and surface wave is an effective way to diminish the influences of the strong tradeoff among parameters and the different sensitivity to the model parameters in their respective inversions, but the inversion problem becomes more complex. Multi-objective problems can be much more complicated than single-objective inversion in the model selection and optimization. If objectives are involved and conflicting, models can be ordered only partially. In this case, Pareto-optimal preference should be used to select solutions. On the other hand, the inversion to get only a few optimal solutions can not deal properly with the strong tradeoff between parameters, the uncertainties in the observation, the geophysical complexities and even the incompetency of the inversion technique. The effective way is to retrieve the geophysical information statistically from many acceptable solutions, which requires more competent global algorithms. Competent genetic algorithms recently proposed are far superior to the conventional genetic algorithm and can solve hard problems quickly, reliably and accurately. In this work we used one of competent genetic algorithms, Bayesian Optimization Algorithm as the main inverse procedure. This algorithm uses Bayesian networks to draw out inherited information and can use Pareto-optimal preference in the inversion. With this algorithm, the lithospheric structure of Paran"› basin is inverted to fit both the observations of inter-station surface wave dispersion and receiver function.

Environmental Complexity and Biodiversity: The Multi-Layered Evolutionary History of a Log-Dwelling Velvet Worm in Montane Temperate Australia

PubMed Central

Garrick, Ryan C.; Gardner, Michael G.; Tait, Noel N.; Briscoe, David A.; Rowell, David M.; Sunnucks, Paul

2013-01-01

Phylogeographic studies provide a framework for understanding the importance of intrinsic versus extrinsic factors in shaping patterns of biodiversity through identifying past and present microevolutionary processes that contributed to lineage divergence. Here we investigate population structure and diversity of the Onychophoran (velvet worm) Euperipatoides rowelli in southeastern Australian montane forests that were not subject to Pleistocene glaciations, and thus likely retained more forest cover than systems under glaciation. Over a ~100 km transect of structurally-connected forest, we found marked nuclear and mitochondrial (mt) DNA genetic structuring, with spatially-localised groups. Patterns from mtDNA and nuclear data broadly corresponded with previously defined geographic regions, consistent with repeated isolation in refuges during Pleistocene climatic cycling. Nevertheless, some E. rowelli genetic contact zones were displaced relative to hypothesized influential landscape structures, implying more recent processes overlying impacts of past environmental history. Major impacts at different timescales were seen in the phylogenetic relationships among mtDNA sequences, which matched geographic relationships and nuclear data only at recent timescales, indicating historical gene flow and/or incomplete lineage sorting. Five major E. rowelli phylogeographic groups were identified, showing substantial but incomplete reproductive isolation despite continuous habitat. Regional distinctiveness, in the face of lineages abutting within forest habitat, could indicate pre- and/or postzygotic gene flow limitation. A potentially functional phenotypic character, colour pattern variation, reflected the geographic patterns in the molecular data. Spatial-genetic patterns broadly match those in previously-studied, co-occurring low-mobility organisms, despite a variety of life histories. We suggest that for E. rowelli, the complex topography and history of the region has led to interplay among limited dispersal ability, historical responses to environmental change, local adaptation, and some resistance to free admixture at geographic secondary contact, leading to strong genetic structuring at fine spatial scale. PMID:24358365

Prioritisation of associations between protein domains and complex diseases using domain-domain interaction networks.

PubMed

Wang, W; Zhang, W; Jiang, R; Luan, Y

2010-05-01

It is of vital importance to find genetic variants that underlie human complex diseases and locate genes that are responsible for these diseases. Since proteins are typically composed of several structural domains, it is reasonable to assume that harmful genetic variants may alter structures of protein domains, affect functions of proteins and eventually cause disorders. With this understanding, the authors explore the possibility of recovering associations between protein domains and complex diseases. The authors define associations between protein domains and disease families on the basis of associations between non-synonymous single nucleotide polymorphisms (nsSNPs) and complex diseases, similarities between diseases, and relations between proteins and domains. Based on a domain-domain interaction network, the authors propose a 'guilt-by-proximity' principle to rank candidate domains according to their average distance to a set of seed domains in the domain-domain interaction network. The authors validate the method through large-scale cross-validation experiments on simulated linkage intervals, random controls and the whole genome. Results show that areas under receiver operating characteristic curves (AUC scores) can be as high as 77.90%, and the mean rank ratios can be as low as 21.82%. The authors further offer a freely accessible web interface for a genome-wide landscape of associations between domains and disease families.

Wheat landraces: A mini review

USDA-ARS?s Scientific Manuscript database

Farmers developed and utilized diverse wheat landraces to meet the complexity of a multitude of spatio-temporal, agro-ecological systems and to provide reliable sustenance and a sustainable food source to local communities. The genetic structure of wheat landraces is an evolutionary approach to surv...

Mothers’ perspectives on their child’s mental illness as compared to other complex disorders in their family: Insights to inform genetic counseling practice

PubMed Central

Lautenbach, Denise M.; Hiraki, Susan; Campion, MaryAnn W.; Austin, Jehannine C.

2013-01-01

To facilitate the development of a therapeutic alliance in genetic counseling, it is important that the counselor understands how families might perceive the condition that constitutes the reason for the referral. Through training and professional practice, genetic counselors develop a thorough understanding of families’ perceptions of the conditions that are common indications for genetic counseling. But, for referral indications that are less frequent, like serious mental illnesses, genetic counselors may feel less confident in their understanding of the family’s experience, or in their ability to provide psychosocial support when serious mental illness is reported in a family history. This may impede the establishment of a therapeutic alliance. As research shows that most referrals for genetic counseling related to serious mental illness are for female first-degree family members of affected individuals, we sought to explore how this group perceives serious mental illness. To provide a frame of reference with which genetic counselors may be more familiar, we explored how women perceived serious mental illness compared to other common complex disorders in their family. We conducted semi-structured interviews with women who had a child with a serious mental illness (schizophrenia, schizoaffective disorder, bipolar disorder) and a first-degree relative with another common complex disorder (diabetes, heart disease, cancer). Interviews were transcribed and subjected to thematic analysis. Saturation was reached when nine women had participated. Serious mental illness was perceived as being more severe and as having a greater impact on the family than diabetes, heart disease, or cancer. Themes identified included guilt, stigma, and loss. Some of the most important issues that contribute to mothers’ perceptions that serious mental illness is more severe than other common complex disorders could be effectively addressed in genetic counseling. Developing a heightened awareness of how family members experience a relative’s mental illness may help genetic counselors to be better able to provide psychosocial support to this group, whether serious mental illness constitutes the primary reason for referral or appears in the family history during counseling for a different referral reason. PMID:22089936

Ancient deuterostome origins of vertebrate brain signalling centres.

PubMed

Pani, Ariel M; Mullarkey, Erin E; Aronowicz, Jochanan; Assimacopoulos, Stavroula; Grove, Elizabeth A; Lowe, Christopher J

2012-03-14

Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates. © 2012 Macmillan Publishers Limited. All rights reserved

Analysis of Population Substructure in Two Sympatric Populations of Gran Chaco, Argentina

PubMed Central

Sevini, Federica; Yao, Daniele Yang; Lomartire, Laura; Barbieri, Annalaura; Vianello, Dario; Ferri, Gianmarco; Moretti, Edgardo; Dasso, Maria Cristina; Garagnani, Paolo; Pettener, Davide; Franceschi, Claudio; Luiselli, Donata; Franceschi, Zelda Alice

2013-01-01

Sub-population structure and intricate kinship dynamics might introduce biases in molecular anthropology studies and could invalidate the efforts to understand diseases in highly admixed populations. In order to clarify the previously observed distribution pattern and morbidity of Chagas disease in Gran Chaco, Argentina, we studied two populations (Wichí and Criollos) recruited following an innovative bio-cultural model considering their complex cultural interactions. By reconstructing the genetic background and the structure of these two culturally different populations, the pattern of admixture, the correspondence between genealogical and genetic relationships, this integrated perspective had the power to validate data and to link the gap usually relying on a singular discipline. Although Wichí and Criollos share the same area, these sympatric populations are differentiated from the genetic point of view as revealed by Non Recombinant Y Chromosome genotyping resulting in significantly high Fst values and in a lower genetic variability in the Wichí population. Surprisingly, the Amerindian and the European components emerged with comparable amounts (20%) among Criollos and Wichí respectively. The detailed analysis of mitochondrial DNA showed that the two populations have as much as 87% of private haplotypes. Moreover, from the maternal perspective, despite a common Amerindian origin, an Andean and an Amazonian component emerged in Criollos and in Wichí respectively. Our approach allowed us to highlight that quite frequently there is a discrepancy between self-reported and genetic kinship. Indeed, if self-reported identity and kinship are usually utilized in population genetics as a reliable proxy for genetic identity and parental relationship, in our model populations appear to be the result not only and not simply of the genetic background but also of complex cultural determinants. This integrated approach paves the way to a rigorous reconstruction of demographic and cultural history as well as of bioancestry and propensity to diseases of Wichí and Criollos. PMID:23717528

IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina.

PubMed

Lalucque, Hervé; Malagnac, Fabienne; Green, Kimberly; Gautier, Valérie; Grognet, Pierre; Chan Ho Tong, Laetitia; Scott, Barry; Silar, Philippe

2017-01-15

Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures. Copyright © 2016 Elsevier Inc. All rights reserved.

World without borders-genetic population structure of a highly migratory marine predator, the blue shark (Prionace glauca).

PubMed

Veríssimo, Ana; Sampaio, Íris; McDowell, Jan R; Alexandrino, Paulo; Mucientes, Gonzalo; Queiroz, Nuno; da Silva, Charlene; Jones, Catherine S; Noble, Leslie R

2017-07-01

Highly migratory, cosmopolitan oceanic sharks often exhibit complex movement patterns influenced by ontogeny, reproduction, and feeding. These elusive species are particularly challenging to population genetic studies, as representative samples suitable for inferring genetic structure are difficult to obtain. Our study provides insights into the genetic population structure one of the most abundant and wide-ranging oceanic shark species, the blue shark Prionace glauca, by sampling the least mobile component of the populations, i.e., young-of-year and small juveniles (<2 year; N  = 348 individuals), at three reported nursery areas, namely, western Iberia, Azores, and South Africa. Samples were collected in two different time periods (2002-2008 and 2012-2015) and were screened at 12 nuclear microsatellites and at a 899-bp fragment of the mitochondrial control region. Our results show temporally stable genetic homogeneity among the three Atlantic nurseries at both nuclear and mitochondrial markers, suggesting basin-wide panmixia. In addition, comparison of mtDNA CR sequences from Atlantic and Indo-Pacific locations also indicated genetic homogeneity and unrestricted female-mediated gene flow between ocean basins. These results are discussed in light of the species' life history and ecology, but suggest that blue shark populations may be connected by gene flow at the global scale. The implications of the present findings to the management of this important fisheries resource are also discussed.

Demographic modelling reveals a history of divergence with gene flow for a glacially tied stonefly in a changing post-Pleistocene landscape

USGS Publications Warehouse

Hotaling, Scott; Muhlfeld, Clint C.; Giersch, J. Joseph; Ali, Omar; Jordan, Steve; Miller, Michael R.; Luikart, Gordon; Weisrock, David W.

2018-01-01

AimClimate warming is causing extensive loss of glaciers in mountainous regions, yet our understanding of how glacial recession influences evolutionary processes and genetic diversity is limited. Linking genetic structure with the influences shaping it can improve understanding of how species respond to environmental change. Here, we used genome-scale data and demographic modelling to resolve the evolutionary history of Lednia tumana, a rare, aquatic insect endemic to alpine streams. We also employed a range of widely used data filtering approaches to quantify how they influenced population structure results.LocationAlpine streams in the Rocky Mountains of Glacier National Park, Montana, USA.TaxonLednia tumana, a stonefly (Order Plecoptera) in the family Nemouridae.MethodsWe generated single nucleotide polymorphism data through restriction-site associated DNA sequencing to assess contemporary patterns of genetic structure for 11 L. tumana populations. Using identified clusters, we assessed demographic history through model selection and parameter estimation in a coalescent framework. During population structure analyses, we filtered our data to assess the influence of singletons, missing data and total number of markers on results.ResultsContemporary patterns of population structure indicate that L. tumana exhibits a pattern of isolation-by-distance among populations within three genetic clusters that align with geography. Mean pairwise genetic differentiation (FST) among populations was 0.033. Coalescent-based demographic modelling supported divergence with gene flow among genetic clusters since the end of the Pleistocene (~13-17 kya), likely reflecting the south-to-north recession of ice sheets that accumulated during the Wisconsin glaciation.Main conclusionsWe identified a link between glacial retreat, evolutionary history and patterns of genetic diversity for a range-restricted stonefly imperiled by climate change. This finding included a history of divergence with gene flow, an unexpected conclusion for a mountaintop species. Beyond L. tumana, this study demonstrates the complexity of assessing genetic structure for weakly differentiated species, shows the degree to which rare alleles and missing data may influence results, and highlights the usefulness of genome-scale data to extend population genetic inquiry in non-model species.

Structural genomic variations and Parkinson's disease.

PubMed

Bandrés-Ciga, Sara; Ruz, Clara; Barrero, Francisco J; Escamilla-Sevilla, Francisco; Pelegrina, Javier; Vives, Francisco; Duran, Raquel

2017-10-01

Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "non-genetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD. Also, variants with incomplete penetrance in the genes LRRK2 and GBA are considered to be strong risk factors for PD worldwide. Although genetic studies have provided valuable insights into the pathogenic mechanisms underlying PD, the role of structural variation in PD has been understudied in comparison with other genomic variations. Structural genomic variations might substantially account for such genetic substrates yet to be discovered. The present review aims to provide an overview of the structural genomic variants implicated in the pathogenesis of PD.

Biomimetic self-templating optical structures fabricated by genetically engineered M13 bacteriophage.

PubMed

Kim, Won-Geun; Song, Hyerin; Kim, Chuntae; Moon, Jong-Sik; Kim, Kyujung; Lee, Seung-Wuk; Oh, Jin-Woo

2016-11-15

Here, we describe a highly sensitive and selective surface plasmon resonance sensor system by utilizing self-assembly of genetically engineered M13 bacteriophage. About 2700 copies of genetically expressed peptide copies give superior selectivity and sensitivity to M13 phage-based SPR sensor. Furthermore, the sensitivity of the M13 phage-based SPR sensor was enhanced due to the aligning of receptor matrix in specific direction. Incorporation of specific binding peptide (His Pro Gln: HPQ) gives M13 bacteriophage high selectivity for the streptavidin. Our M13 phage-based SPR sensor takes advantage of simplicity of self-assembly compared with relatively complex photolithography techniques or chemical conjugations. Additionally, designed structure which is composed of functionalized M13 bacteriophage can simultaneously improve the sensitivity and selectivity of SPR sensor evidently. By taking advantages of the genetic engineering and self-assembly, we propose the simple method for fabricating novel M13 phage-based SPR sensor system which has a high sensitivity and high selectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

A planktonic diatom displays genetic structure over small spatial scales.

PubMed

Sefbom, Josefin; Kremp, Anke; Rengefors, Karin; Jonsson, Per R; Sjöqvist, Conny; Godhe, Anna

2018-04-03

Marine planktonic microalgae have potentially global dispersal, yet reduced gene flow has been confirmed repeatedly for several species. Over larger distances (>200 km) geographic isolation and restricted oceanographic connectivity have been recognized as instrumental in driving population divergence. Here we investigated whether similar patterns, that is, structured populations governed by geographic isolation and/or oceanographic connectivity, can be observed at smaller (6-152 km) geographic scales. To test this we established 425 clonal cultures of the planktonic diatom Skeletonema marinoi collected from 11 locations in the Archipelago Sea (northern Baltic Sea). The region is characterized by a complex topography, entailing several mixing regions of which four were included in the sampling area. Using eight microsatellite markers and conventional F-statistics, significant genetic differentiation was observed between several sites. Moreover, Bayesian cluster analysis revealed the co-occurrence of two genetic groups spread throughout the area. However, geographic isolation and oceanographic connectivity could not explain the genetic patterns observed. Our data reveal hierarchical genetic structuring whereby despite high dispersal potential, significantly diverged populations have developed over small spatial scales. Our results suggest that biological characteristics and historical events may be more important in generating barriers to gene flow than physical barriers at small spatial scales. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Clinical exome sequencing reports: current informatics practice and future opportunities.

PubMed

Swaminathan, Rajeswari; Huang, Yungui; Astbury, Caroline; Fitzgerald-Butt, Sara; Miller, Katherine; Cole, Justin; Bartlett, Christopher; Lin, Simon

2017-11-01

The increased adoption of clinical whole exome sequencing (WES) has improved the diagnostic yield for patients with complex genetic conditions. However, the informatics practice for handling information contained in whole exome reports is still in its infancy, as evidenced by the lack of a common vocabulary within clinical sequencing reports generated across genetic laboratories. Genetic testing results are mostly transmitted using portable document format, which can make secondary analysis and data extraction challenging. This paper reviews a sample of clinical exome reports generated by Clinical Laboratory Improvement Amendments-certified genetic testing laboratories at tertiary-care facilities to assess and identify common data elements. Like structured radiology reports, which enable faster information retrieval and reuse, structuring genetic information within clinical WES reports would help facilitate integration of genetic information into electronic health records and enable retrospective research on the clinical utility of WES. We identify elements listed as mandatory according to practice guidelines but are currently missing from some of the clinical reports, which might help to organize the data when stored within structured databases. We also highlight elements, such as patient consent, that, although they do not appear within any of the current reports, may help in interpreting some of the information within the reports. Integrating genetic and clinical information would assist the adoption of personalized medicine for improved patient care and outcomes. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Urban population genetics of slum-dwelling rats (Rattus norvegicus) in Salvador, Brazil

PubMed Central

Kajdacsi, Brittney; Costa, Federico; Hyseni, Chaz; Porter, Fleur; Brown, Julia; Rodrigues, Gorete; Farias, Helena; Reis, Mitermeyer G.; Childs, James E.; Ko, Albert I.; Caccone, Adalgisa

2013-01-01

Throughout the developing world, urban centers with sprawling slum settlements are rapidly expanding and invading previously forested ecosystems. Slum communities are characterized by untended refuse, open sewers, and overgrown vegetation, which promote rodent infestation. Norway rats (Rattus norvegicus), are reservoirs for epidemic transmission of many zoonotic pathogens of public health importance. Understanding the population ecology of R. norvegicus is essential to formulate effective rodent control strategies, as this knowledge aids estimation of the temporal stability and spatial connectivity of populations. We screened for genetic variation, characterized the population genetic structure, and evaluated the extent and patterns of gene flow in the urban landscape using 17 microsatellite loci in 146 rats from 9 sites in the city of Salvador, Brazil. These sites were divided between three neighborhoods within the city spaced an average of 2.7 km apart. Surprisingly, we detected very little relatedness among animals trapped at the same site and found high levels of genetic diversity, as well as structuring across small geographic distances. Most FST comparisons among sites were statistically significant, including sites <400 m apart. Bayesian analyses grouped the samples in three genetic clusters, each associated with distinct sampling sites from different neighborhoods or valleys within neighborhoods. These data indicate the existence of complex genetic structure in R. norvegicus in Salvador, linked to the heterogeneous urban landscape. Future rodent control measures need to take into account the spatial and temporal linkage of rat populations in Salvador, as revealed by genetic data, to develop informed eradication strategies. PMID:24118116

Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study

PubMed Central

Kendler, K. S.; Myers, J.; Reichborn-Kjennerud, T.

2011-01-01

Objective To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality. Method A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory. Results A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative. Conclusion In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation. PMID:21198457

Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study.

PubMed

Kendler, K S; Myers, J; Reichborn-Kjennerud, T

2011-05-01

To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality. A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory. A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative. In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation. © 2010 John Wiley & Sons A/S.

A phylogeographic study of the endemic rodent Eliurus carletoni (Rodentia: Nesomyinae) in an ecological transition zone of Northern Madagascar.

PubMed

Rakotoarisoa, Jean-Eric; Raheriarisena, Martin; Goodman, Steven M

2013-01-01

We conducted a mitochondrial phylogeographic study of the endemic dry forest rodent Eliurus carletoni (Rodentia: Nesomyinae) in an ecological transition zone of northern Madagascar (Loky-Manambato) and 2 surrounding regions (Ankarana and Analamerana). The main goal was to assess the evolutionary consequences on this taxon of the complex landscape features and Quaternary ecological vicissitudes. Three haplogroups were identified from the 215 specimens obtained from 15 populations. High levels of genetic diversity and significant genetic differentiation among populations were observed. The different geographical subdivisions of the study area by regions, by river catchment zones, and the physical distance between populations are not correlated with genetic patterns. In contrast, population structure is mostly explained by the geographic distribution of the samples among existing forest blocks. E. carletoni experienced a genetic bottleneck between 18 750 and 7500 years BP, which correlates with periods when moister climates existed on the island. Overall, our data suggest that the complex genetic patterns of E. carletoni can be explained by Quaternary climatic vicissitudes that resulted in habitat fluctuations between dry and humid forests, as well as subsequent human-induced fragmentation of forest habitat.

Genetic and biochemical findings in Chinese children with Leigh syndrome.

PubMed

Ma, Yan-Yan; Wu, Tong-Fei; Liu, Yu-Peng; Wang, Qiao; Song, Jin-Qing; Li, Xi-Yuan; Shi, Xiu-Yu; Zhang, Wei-Na; Zhao, Meng; Hu, Lin-Yan; Yang, Yan-Ling; Zou, Li-Ping

2013-11-01

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Patterns of Post-Glacial Genetic Differentiation in Marginal Populations of a Marine Microalga

PubMed Central

Tahvanainen, Pia; Alpermann, Tilman J.; Figueroa, Rosa Isabel; John, Uwe; Hakanen, Päivi; Nagai, Satoshi; Blomster, Jaanika; Kremp, Anke

2012-01-01

This study investigates the genetic structure of an eukaryotic microorganism, the toxic dinoflagellate Alexandrium ostenfeldii, from the Baltic Sea, a geologically young and ecologically marginal brackish water estuary which is predicted to support evolution of distinct, genetically impoverished lineages of marine macroorganisms. Analyses of the internal transcribed spacer (ITS) sequences and Amplified Fragment Length Polymorphism (AFLP) of 84 A. ostenfeldii isolates from five different Baltic locations and multiple external sites revealed that Baltic A. ostenfeldii is phylogenetically differentiated from other lineages of the species and micro-geographically fragmented within the Baltic Sea. Significant genetic differentiation (F ST) between northern and southern locations was correlated to geographical distance. However, instead of discrete genetic units or continuous genetic differentiation, the analysis of population structure suggests a complex and partially hierarchic pattern of genetic differentiation. The observed pattern suggests that initial colonization was followed by local differentiation and varying degrees of dispersal, most likely depending on local habitat conditions and prevailing current systems separating the Baltic Sea populations. Local subpopulations generally exhibited low levels of overall gene diversity. Association analysis suggests predominately asexual reproduction most likely accompanied by frequency shifts of clonal lineages during planktonic growth. Our results indicate that the general pattern of genetic differentiation and reduced genetic diversity of Baltic populations found in large organisms also applies to microscopic eukaryotic organisms. PMID:23300940

Patterns of post-glacial genetic differentiation in marginal populations of a marine microalga.

PubMed

Tahvanainen, Pia; Alpermann, Tilman J; Figueroa, Rosa Isabel; John, Uwe; Hakanen, Päivi; Nagai, Satoshi; Blomster, Jaanika; Kremp, Anke

2012-01-01

This study investigates the genetic structure of an eukaryotic microorganism, the toxic dinoflagellate Alexandrium ostenfeldii, from the Baltic Sea, a geologically young and ecologically marginal brackish water estuary which is predicted to support evolution of distinct, genetically impoverished lineages of marine macroorganisms. Analyses of the internal transcribed spacer (ITS) sequences and Amplified Fragment Length Polymorphism (AFLP) of 84 A. ostenfeldii isolates from five different Baltic locations and multiple external sites revealed that Baltic A. ostenfeldii is phylogenetically differentiated from other lineages of the species and micro-geographically fragmented within the Baltic Sea. Significant genetic differentiation (F(ST)) between northern and southern locations was correlated to geographical distance. However, instead of discrete genetic units or continuous genetic differentiation, the analysis of population structure suggests a complex and partially hierarchic pattern of genetic differentiation. The observed pattern suggests that initial colonization was followed by local differentiation and varying degrees of dispersal, most likely depending on local habitat conditions and prevailing current systems separating the Baltic Sea populations. Local subpopulations generally exhibited low levels of overall gene diversity. Association analysis suggests predominately asexual reproduction most likely accompanied by frequency shifts of clonal lineages during planktonic growth. Our results indicate that the general pattern of genetic differentiation and reduced genetic diversity of Baltic populations found in large organisms also applies to microscopic eukaryotic organisms.

On the Structural Plasticity of the Human Genome: Chromosomal Inversions Revisited

PubMed Central

Alves, Joao M; Lopes, Alexandra M; Chikhi, Lounès; Amorim, António

2012-01-01

With the aid of novel and powerful molecular biology techniques, recent years have witnessed a dramatic increase in the number of studies reporting the involvement of complex structural variants in several genomic disorders. In fact, with the discovery of Copy Number Variants (CNVs) and other forms of unbalanced structural variation, much attention has been directed to the detection and characterization of such rearrangements, as well as the identification of the mechanisms involved in their formation. However, it has long been appreciated that chromosomes can undergo other forms of structural changes - balanced rearrangements - that do not involve quantitative variation of genetic material. Indeed, a particular subtype of balanced rearrangement – inversions – was recently found to be far more common than had been predicted from traditional cytogenetics. Chromosomal inversions alter the orientation of a specific genomic sequence and, unless involving breaks in coding or regulatory regions (and, disregarding complex trans effects, in their close vicinity), appear to be phenotypically silent. Such a surprising finding, which is difficult to reconcile with the classical interpretation of inversions as a mechanism causing subfertility (and ultimately reproductive isolation), motivated a new series of theoretical and empirical studies dedicated to understand their role in human genome evolution and to explore their possible association to complex genetic disorders. With this review, we attempt to describe the latest methodological improvements to inversions detection at a genome wide level, while exploring some of the possible implications of inversion rearrangements on the evolution of the human genome. PMID:23730202

Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology.

PubMed Central

Garattini, Enrico; Mendel, Ralf; Romão, Maria João; Wright, Richard; Terao, Mineko

2003-01-01

The molybdo-flavoenzymes are structurally related proteins that require a molybdopterin cofactor and FAD for their catalytic activity. In mammals, four enzymes are known: xanthine oxidoreductase, aldehyde oxidase and two recently described mouse proteins known as aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2. The present review article summarizes current knowledge on the structure, enzymology, genetics, regulation and pathophysiology of mammalian molybdo-flavoenzymes. Molybdo-flavoenzymes are structurally complex oxidoreductases with an equally complex mechanism of catalysis. Our knowledge has greatly increased due to the recent crystallization of two xanthine oxidoreductases and the determination of the amino acid sequences of many members of the family. The evolution of molybdo-flavoenzymes can now be traced, given the availability of the structures of the corresponding genes in many organisms. The genes coding for molybdo-flavoenzymes are expressed in a cell-specific fashion and are controlled by endogenous and exogenous stimuli. The recent cloning of the genes involved in the biosynthesis of the molybdenum cofactor has increased our knowledge on the assembly of the apo-forms of molybdo-flavoproteins into the corresponding holo-forms. Xanthine oxidoreductase is the key enzyme in the catabolism of purines, although recent data suggest that the physiological function of this enzyme is more complex than previously assumed. The enzyme has been implicated in such diverse pathological situations as organ ischaemia, inflammation and infection. At present, very little is known about the pathophysiological relevance of aldehyde oxidase, aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2, which do not as yet have an accepted endogenous substrate. PMID:12578558

Retinal dystrophies, genomic applications in diagnosis and prospects for therapy

PubMed Central

Nash, Benjamin M.; Wright, Dale C.; Grigg, John R.; Bennetts, Bruce

2015-01-01

Retinal dystrophies (RDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. This review aims to demonstrate the high degree of genetic complexity in both the causative disease genes and their associated phenotypes, highlighting the more common clinical manifestation of retinitis pigmentosa (RP). The review also provides insight to recent advances in genomic molecular diagnosis and gene and cell-based therapies for the RDs. PMID:26835369

Decoding Mechanisms by which Silent Codon Changes Influence Protein Biogenesis and Function

PubMed Central

Bali, Vedrana; Bebok, Zsuzsanna

2015-01-01

Scope Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health. Purpose This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics. Physiological and medical relevance Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies. PMID:25817479

A genetic-algorithm approach for assessing the liquefaction potential of sandy soils

NASA Astrophysics Data System (ADS)

Sen, G.; Akyol, E.

2010-04-01

The determination of liquefaction potential is required to take into account a large number of parameters, which creates a complex nonlinear structure of the liquefaction phenomenon. The conventional methods rely on simple statistical and empirical relations or charts. However, they cannot characterise these complexities. Genetic algorithms are suited to solve these types of problems. A genetic algorithm-based model has been developed to determine the liquefaction potential by confirming Cone Penetration Test datasets derived from case studies of sandy soils. Software has been developed that uses genetic algorithms for the parameter selection and assessment of liquefaction potential. Then several estimation functions for the assessment of a Liquefaction Index have been generated from the dataset. The generated Liquefaction Index estimation functions were evaluated by assessing the training and test data. The suggested formulation estimates the liquefaction occurrence with significant accuracy. Besides, the parametric study on the liquefaction index curves shows a good relation with the physical behaviour. The total number of misestimated cases was only 7.8% for the proposed method, which is quite low when compared to another commonly used method.

Molecular Imprint of Exposure to Naturally Occurring Genetic Variants of Human Cytomegalovirus on the T cell Repertoire

NASA Astrophysics Data System (ADS)

Smith, Corey; Gras, Stephanie; Brennan, Rebekah M.; Bird, Nicola L.; Valkenburg, Sophie A.; Twist, Kelly-Anne; Burrows, Jacqueline M.; Miles, John J.; Chambers, Daniel; Bell, Scott; Campbell, Scott; Kedzierska, Katherine; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv

2014-02-01

Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.

New approaches to optimization in aerospace conceptual design

NASA Technical Reports Server (NTRS)

Gage, Peter J.

1995-01-01

Aerospace design can be viewed as an optimization process, but conceptual studies are rarely performed using formal search algorithms. Three issues that restrict the success of automatic search are identified in this work. New approaches are introduced to address the integration of analyses and optimizers, to avoid the need for accurate gradient information and a smooth search space (required for calculus-based optimization), and to remove the restrictions imposed by fixed complexity problem formulations. (1) Optimization should be performed in a flexible environment. A quasi-procedural architecture is used to conveniently link analysis modules and automatically coordinate their execution. It efficiently controls a large-scale design tasks. (2) Genetic algorithms provide a search method for discontinuous or noisy domains. The utility of genetic optimization is demonstrated here, but parameter encodings and constraint-handling schemes must be carefully chosen to avoid premature convergence to suboptimal designs. The relationship between genetic and calculus-based methods is explored. (3) A variable-complexity genetic algorithm is created to permit flexible parameterization, so that the level of description can change during optimization. This new optimizer automatically discovers novel designs in structural and aerodynamic tasks.

Systems Engineering Design Via Experimental Operation Research: Complex Organizational Metric for Programmatic Risk Environments (COMPRE)

NASA Technical Reports Server (NTRS)

Mog, Robert A.

1999-01-01

Unique and innovative graph theory, neural network, organizational modeling, and genetic algorithms are applied to the design and evolution of programmatic and organizational architectures. Graph theory representations of programs and organizations increase modeling capabilities and flexibility, while illuminating preferable programmatic/organizational design features. Treating programs and organizations as neural networks results in better system synthesis, and more robust data modeling. Organizational modeling using covariance structures enhances the determination of organizational risk factors. Genetic algorithms improve programmatic evolution characteristics, while shedding light on rulebase requirements for achieving specified technological readiness levels, given budget and schedule resources. This program of research improves the robustness and verifiability of systems synthesis tools, including the Complex Organizational Metric for Programmatic Risk Environments (COMPRE).

Admixture in Latin America.

PubMed

Adhikari, Kaustubh; Mendoza-Revilla, Javier; Chacón-Duque, Juan Camilo; Fuentes-Guajardo, Macarena; Ruiz-Linares, Andrés

2016-12-01

Latin Americans arguably represent the largest recently admixed populations in the world. This reflects a history of massive settlement by immigrants (mostly Europeans and Africans) and their variable admixture with Natives, starting in 1492. This process resulted in the population of Latin America showing an extensive genetic and phenotypic diversity. Here we review how genetic analyses are being applied to examine the demographic history of this population, including patterns of mating, population structure and ancestry. The admixture history of Latin America, and the resulting extensive diversity of the region, represents a natural experiment offering an advantageous setting for genetic association studies. We review how recent analyses in Latin Americans are contributing to elucidating the genetic architecture of human complex traits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structure and function of the homeotic gene complex (HOM-C) in the beetle, Tribolium castaneum

NASA Technical Reports Server (NTRS)

Beeman, R. W.; Stuart, J. J.; Brown, S. J.; Denell, R. E.; Spooner, B. S. (Principal Investigator)

1993-01-01

The powerful combination of genetic, developmental and molecular approaches possible with the fruit fly, Drosophila melanogaster, has led to a profound understanding of the genetic control of early developmental events. However, Drosophila is a highly specialized long germ insect, and the mechanisms controlling its early development may not be typical of insects or Arthropods in general. The beetle, Tribolium castaneum, offers a similar opportunity to integrate high resolution genetic analysis with the developmental/molecular approaches currently used in other organisms. Early results document significant differences between insect orders in the functions of genes responsible for establishing developmental commitments.

Structure and function of the homeotic gene complex (HOM-C) in the beetle, Tribolium castaneum.

PubMed

Beeman, R W; Stuart, J J; Brown, S J; Denell, R E

1993-07-01

The powerful combination of genetic, developmental and molecular approaches possible with the fruit fly, Drosophila melanogaster, has led to a profound understanding of the genetic control of early developmental events. However, Drosophila is a highly specialized long germ insect, and the mechanisms controlling its early development may not be typical of insects or Arthropods in general. The beetle, Tribolium castaneum, offers a similar opportunity to integrate high resolution genetic analysis with the developmental/molecular approaches currently used in other organisms. Early results document significant differences between insect orders in the functions of genes responsible for establishing developmental commitments.

Prediction and Biochemical Demonstration of a Catabolic Pathway for the Osmoprotectant Proline Betaine

PubMed Central

Kumar, Ritesh; Zhao, Suwen; Vetting, Matthew W.; Wood, B. McKay; Sakai, Ayano; Cho, Kyuil; Solbiati, José; Almo, Steven C.; Sweedler, Jonathan V.; Jacobson, Matthew P.; Gerlt, John A.; Cronan, John E.

2014-01-01

ABSTRACT Through the use of genetic, enzymatic, metabolomic, and structural analyses, we have discovered the catabolic pathway for proline betaine, an osmoprotectant, in Paracoccus denitrificans and Rhodobacter sphaeroides. Genetic and enzymatic analyses showed that several of the key enzymes of the hydroxyproline betaine degradation pathway also function in proline betaine degradation. Metabolomic analyses detected each of the metabolic intermediates of the pathway. The proline betaine catabolic pathway was repressed by osmotic stress and cold stress, and a regulatory transcription factor was identified. We also report crystal structure complexes of the P. denitrificans HpbD hydroxyproline betaine epimerase/proline betaine racemase with l-proline betaine and cis-hydroxyproline betaine. PMID:24520058

Flexible ligand docking using a genetic algorithm

NASA Astrophysics Data System (ADS)

Oshiro, C. M.; Kuntz, I. D.; Dixon, J. Scott

1995-04-01

Two computational techniques have been developed to explore the orientational and conformational space of a flexible ligand within an enzyme. Both methods use the Genetic Algorithm (GA) to generate conformationally flexible ligands in conjunction with algorithms from the DOCK suite of programs to characterize the receptor site. The methods are applied to three enzyme-ligand complexes: dihydrofolate reductase-methotrexate, thymidylate synthase-phenolpthalein and HIV protease-thioketal haloperidol. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. The potential for the GA method to screen a database of compounds is also examined. A collection of ligands is evaluated simultaneously, rather than docking the ligands individually into the enzyme.

Recent Advances in Algal Genetic Tool Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

R. Dahlin, Lukas; T. Guarnieri, Michael

The goal of achieving cost-effective biofuels and bioproducts derived from algal biomass will require improvements along the entire value chain, including identification of robust, high-productivity strains and development of advanced genetic tools. Though there have been modest advances in development of genetic systems for the model alga Chlamydomonas reinhardtii, progress in development of algal genetic tools, especially as applied to non-model algae, has generally lagged behind that of more commonly utilized laboratory and industrial microbes. This is in part due to the complex organellar structure of algae, including robust cell walls and intricate compartmentalization of target loci, as well asmore » prevalent gene silencing mechanisms, which hinder facile utilization of conventional genetic engineering tools and methodologies. However, recent progress in global tool development has opened the door for implementation of strain-engineering strategies in industrially-relevant algal strains. Here, we review recent advances in algal genetic tool development and applications in eukaryotic microalgae.« less

Recent Advances in Algal Genetic Tool Development

DOE PAGES

R. Dahlin, Lukas; T. Guarnieri, Michael

2016-06-24

The goal of achieving cost-effective biofuels and bioproducts derived from algal biomass will require improvements along the entire value chain, including identification of robust, high-productivity strains and development of advanced genetic tools. Though there have been modest advances in development of genetic systems for the model alga Chlamydomonas reinhardtii, progress in development of algal genetic tools, especially as applied to non-model algae, has generally lagged behind that of more commonly utilized laboratory and industrial microbes. This is in part due to the complex organellar structure of algae, including robust cell walls and intricate compartmentalization of target loci, as well asmore » prevalent gene silencing mechanisms, which hinder facile utilization of conventional genetic engineering tools and methodologies. However, recent progress in global tool development has opened the door for implementation of strain-engineering strategies in industrially-relevant algal strains. Here, we review recent advances in algal genetic tool development and applications in eukaryotic microalgae.« less

The genetic landscape of a physical interaction

PubMed Central

Diss, Guillaume

2018-01-01

A key question in human genetics and evolutionary biology is how mutations in different genes combine to alter phenotypes. Efforts to systematically map genetic interactions have mostly made use of gene deletions. However, most genetic variation consists of point mutations of diverse and difficult to predict effects. Here, by developing a new sequencing-based protein interaction assay – deepPCA – we quantified the effects of >120,000 pairs of point mutations on the formation of the AP-1 transcription factor complex between the products of the FOS and JUN proto-oncogenes. Genetic interactions are abundant both in cis (within one protein) and trans (between the two molecules) and consist of two classes – interactions driven by thermodynamics that can be predicted using a three-parameter global model, and structural interactions between proximally located residues. These results reveal how physical interactions generate quantitatively predictable genetic interactions. PMID:29638215

Under the Influence of Genetics: How Transdisciplinarity Leads Us to Rethink Social Pathways to Illness

PubMed Central

Pescosolido, Bernice A.; Perry, Brea L.; Long, J. Scott; Martin, Jack K.; Nurnberger, John I.; Hesselbrock, Victor

2015-01-01

To extend our understanding of how social structures and social processes impact behavior, sociologists have been challenged to incorporate the potential explanatory role of genetics in their models. Here, we draw propositions from three major understandings of illness causation offered by social theory – fundamental causes, social stress processes, and social safety net theories. We tailor hypotheses to the case of alcohol dependence, long considered a multifaceted problem, defying simple explanation and having both biological and social roots. After briefly reviewing current appeals for transdisciplinary research, we describe both sociological and genetic theories, and derive propositions expected under each and under a transdisciplinary theoretical frame. Analyses of a later wave of the preeminent medical science study, the Collaborative Study on the Genetics of Alcoholism (COGA), reveals a complex interplay of how the GABRA2 gene works with and against social structural factors to produce cases meeting DSM/ICD diagnoses. When both genetic and social factors are controlled, virtually equivalent effects of each remain; and, only modest evidence suggests that genetic influence works through social structural conditions and experiences. Further exploratory analyses using multiplicative terms reveal enhanced gene-environment interactions: 1) women are largely unaffected in their risk for alcohol dependence by allele status at this candidate gene; 2) family support attenuates genetic influence; 3) childhood deprivation exacerbates genetic predispositions. We discuss how these findings lead us to consider the essential intradisciplinary tension in sociological theories (i.e., the role of proximal and distal influences in social processes). Overall, our findings point to the promise of theories blending social and genetic influences by focusing directly on dynamic, networked sequences that produce different pathways to health and illness. PMID:19569404

Dissection of complex adult traits in a mouse synthetic population.

PubMed

Burke, David T; Kozloff, Kenneth M; Chen, Shu; West, Joshua L; Wilkowski, Jodi M; Goldstein, Steven A; Miller, Richard A; Galecki, Andrzej T

2012-08-01

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology.

Assessment of Genetic Diversity and Structure of Large Garlic (Allium sativum) Germplasm Bank, by Diversity Arrays Technology “Genotyping-by-Sequencing” Platform (DArTseq)

PubMed Central

Egea, Leticia A.; Mérida-García, Rosa; Kilian, Andrzej; Hernandez, Pilar; Dorado, Gabriel

2017-01-01

Garlic (Allium sativum) is used worldwide in cooking and industry, including pharmacology/medicine and cosmetics, for its interesting properties. Identifying redundancies in germplasm blanks to generate core collections is a major concern, mostly in large stocks, in order to reduce space and maintenance costs. Yet, similar appearance and phenotypic plasticity of garlic varieties hinder their morphological classification. Molecular studies are challenging, due to the large and expected complex genome of this species, with asexual reproduction. Classical molecular markers, like isozymes, RAPD, SSR, or AFLP, are not convenient to generate germplasm core-collections for this species. The recent emergence of high-throughput genotyping-by-sequencing (GBS) approaches, like DArTseq, allow to overcome such limitations to characterize and protect genetic diversity. Therefore, such technology was used in this work to: (i) assess genetic diversity and structure of a large garlic-germplasm bank (417 accessions); (ii) create a core collection; (iii) relate genotype to agronomical features; and (iv) describe a cost-effective method to manage genetic diversity in garlic-germplasm banks. Hierarchical-cluster analysis, principal-coordinates analysis and STRUCTURE showed general consistency, generating three main garlic-groups, mostly determined by variety and geographical origin. In addition, high-resolution genotyping identified 286 unique and 131 redundant accessions, used to select a reduced size germplasm-bank core collection. This demonstrates that DArTseq is a cost-effective method to analyze species with large and expected complex genomes, like garlic. To the best of our knowledge, this is the first report of high-throughput genotyping of a large garlic germplasm. This is particularly interesting for garlic adaptation and improvement, to fight biotic and abiotic stresses, in the current context of climate change and global warming. PMID:28775737

Assessment of Genetic Diversity and Structure of Large Garlic (Allium sativum) Germplasm Bank, by Diversity Arrays Technology "Genotyping-by-Sequencing" Platform (DArTseq).

PubMed

Egea, Leticia A; Mérida-García, Rosa; Kilian, Andrzej; Hernandez, Pilar; Dorado, Gabriel

2017-01-01

Garlic ( Allium sativum ) is used worldwide in cooking and industry, including pharmacology/medicine and cosmetics, for its interesting properties. Identifying redundancies in germplasm blanks to generate core collections is a major concern, mostly in large stocks, in order to reduce space and maintenance costs. Yet, similar appearance and phenotypic plasticity of garlic varieties hinder their morphological classification. Molecular studies are challenging, due to the large and expected complex genome of this species, with asexual reproduction. Classical molecular markers, like isozymes, RAPD, SSR, or AFLP, are not convenient to generate germplasm core-collections for this species. The recent emergence of high-throughput genotyping-by-sequencing (GBS) approaches, like DArTseq, allow to overcome such limitations to characterize and protect genetic diversity. Therefore, such technology was used in this work to: (i) assess genetic diversity and structure of a large garlic-germplasm bank (417 accessions); (ii) create a core collection; (iii) relate genotype to agronomical features; and (iv) describe a cost-effective method to manage genetic diversity in garlic-germplasm banks. Hierarchical-cluster analysis, principal-coordinates analysis and STRUCTURE showed general consistency, generating three main garlic-groups, mostly determined by variety and geographical origin. In addition, high-resolution genotyping identified 286 unique and 131 redundant accessions, used to select a reduced size germplasm-bank core collection. This demonstrates that DArTseq is a cost-effective method to analyze species with large and expected complex genomes, like garlic. To the best of our knowledge, this is the first report of high-throughput genotyping of a large garlic germplasm. This is particularly interesting for garlic adaptation and improvement, to fight biotic and abiotic stresses, in the current context of climate change and global warming.

The "chicken-and-egg" development of political opinions.

PubMed

Beattie, Peter

2017-01-01

Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a "chicken-and-egg" question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.

Genetics objective structured clinical exams at the Maimonides Infants & Children's Hospital of Brooklyn, New York.

PubMed

Altshuler, Lisa; Kachur, Elizabeth; Krinshpun, Shifra; Sullivan, Deborah

2008-11-01

In 2003, the Maimonides Infants & Children's Hospital received a Title VII Residency Training in Primary Care grant to integrate genetic-specific competencies into postgraduate pediatrics education. As part of that endeavor, mandatory yearly genetics objective structured clinical exams (OSCEs) were instituted for third-year residents. This article reports on the first three years of experience with this innovative educational tool.After an overview of genetic concepts, dysmorphology, and communication styles, residents complete a five-station OSCE and receive feedback from standardized patients and from the faculty who observe them. After this clinical exercise, the residents participate in a small-group debriefing session to share strategies for effective communication and clinical case management and to discuss the ethical issues that arise with these genetic cases.In three years, 60 residents have completed the genetics OSCE program. Evaluation data demonstrate that the program has been effective in both introducing genetic-specific challenges and assessing residents' clinical skills. It has helped trainees self-identify both strengths and further training needs. Pre- and postsurveys among the trainees show increased comfort levels in performing 5 of 12 genetic-related clinical tasks.We conclude that genetics OSCEs are an enriching educational tool. Merely providing trainees and practicing physicians with the latest scientific information is unlikely to prepare them for counseling patients about complex genetic issues. Developing proficiency requires focused practice and effective feedback.This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.

Broad Bandwidth or High Fidelity? Evidence from the Structure of Genetic and Environmental Effects on the Facets of the Five Factor Model

PubMed Central

Briley, Daniel A.; Tucker-Drob, Elliot M.

2017-01-01

The Five Factor Model (FFM) of personality is well-established at the phenotypic level, but much less is known about the coherence of the genetic and environmental influences within each personality domain. Univariate behavioral genetic analyses have consistently found the influence of additive genes and nonshared environment on multiple personality facets, but the extent to which genetic and environmental influences on specific facets reflect more general influences on higher order factors is less clear. We applied a multivariate quantitative-genetic approach to scores on the CPI-Big Five facets for 490 monozygotic and 317 dizygotic twins who took part in the National Merit Twin Study. Our results revealed a complex genetic structure for facets composing all five factors, with both domain-general and facet-specific genetic and environmental influences. Models that required common genetic and environmental influences on each facet to occur by way of effects on a higher order trait did not fit as well as models allowing for common genetic and environmental effects to act directly on the facets for three of the Big Five domains. These results add to the growing body of literature indicating that important variation in personality occurs at the facet level which may be overshadowed by aggregating to the trait level. Research at the facet level, rather than the factor level, is likely to have pragmatic advantages in future research on the genetics of personality. PMID:22695681

Contrasting patterns of population history and seed-mediated gene flow in two endemic Costa Rican oak species.

PubMed

Rodríguez-Correa, Hernando; Oyama, Ken; Quesada, Mauricio; Fuchs, Eric J; González-Rodríguez, Antonio

2018-03-02

Lower Central America is an important area to study recent population history and diversification of Neotropical species due to its complex and dynamic geology and climate. Phylogeographic studies in this region are few in comparison with other regions and even less for tree species. The aim of the present study was to characterize the phylogeographic structure in two partially co-distributed endemic oak species (Quercus costaricensis and Q. bumelioides) of the Costa Rican mountains using chloroplast short sequence repeats (cpSSRs), and to test for the effect of geological and palaeoclimatic processes on their population history. Genetic diversity and structure, haplotype networks, patterns of seed-mediated gene flow and historical demography were estimated for both species. Results suggested contrasting patterns. Quercus costaricensis exhibited high values of genetic diversity, a marked phylogeographic structure, a north-to-south genetic diversity gradient and evidence of a demographic expansion during the Quaternary. Quercus bumelioides did not show significant genetic structure and the haplotype network and historical demography estimates suggested a recent population expansion probably during the Pleistocene-Holocene transition. Phylogeographic structure of Q. costaricensis seems to be related to Pleistocene altitudinal migration due to its higher altitudinal distribution. Meanwhile, historical seed-mediated gene flow through the lower altitudinal distribution of Q. bumelioides may have promoted the homogenization of genetic variation. Population expansion and stable availability of suitable climatic areas in both species probably indicate that palaeoclimatic changes promoted downwards altitudinal migration and formation of continuous forests allowing oak species to expand their distribution into the Panamanian mountains during glacial stages.

Sexual recombination is a signature of a persisting malaria epidemic in Peru

PubMed Central

2011-01-01

Background The aim of this study was to consider the impact that multi-clone, complex infections have on a parasite population structure in a low transmission setting. In general, complexity of infection (minimum number of clones within an infection) and the overall population level diversity is expected to be minimal in low transmission settings. Additionally, the parasite population structure is predicted to be clonal, rather than sexual due to infrequent parasite inoculation and lack of recombination between genetically distinct clones. However, in this low transmission of the Peruvian Amazon, complex infections are becoming more frequent, in spite of decreasing infection prevalence. In this study, it was hypothesized that sexual recombination between distinct clonal lineages of Plasmodium falciparum parasites were altering the subpopulation structure and effectively maintaining the population-level diversity. Methods Fourteen microsatellite markers were chosen to describe the genetic diversity in 313 naturally occurring P. falciparum infections from Peruvian Amazon. The population and subpopulation structure was characterized by measuring: clusteredness, expected heterozygosity (He), allelic richness, private allelic richness, and linkage disequilibrium. Next, microsatellite haplotypes and alleles were correlated with P. falciparum merozoite surface protein 1 Block 2 (Pfmsp1-B2) to examine the presence of recombinant microsatellite haplotypes. Results The parasite population structure consists of six genetically diverse subpopulations of clones, called "clusters". Clusters 1, 3, 4, and 6 have unique haplotypes that exceed 70% of the total number of clones within each cluster, while Clusters 2 and 5 have a lower proportion of unique haplotypes, but still exceed 46%. By measuring the He, allelic richness, and private allelic richness within each of the six subpopulations, relatively low levels of genetic diversity within each subpopulation (except Cluster 4) are observed. This indicated that the number of alleles, and not the combination of alleles, are limited. Next, the standard index of association (IAS) was measured, which revealed a significant decay in linkage disequilibrium (LD) associated with Cluster 6, which is indicative of independent assortment of alleles. This decay in LD is a signature of this subpopulation approaching linkage equilibrium by undergoing sexual recombination. To trace possible recombination events, the two most frequent microsatellite haplotypes observed over time (defined by either a K1 or Mad20) were selected as the progenitors and then potential recombinants were identified in within the natural population. Conclusions Contrary to conventional low transmission models, this study provides evidence of a parasite population structure that is superficially defined by a clonal backbone. Sexual recombination does occur and even arguably is responsible for maintaining the substructure of this population. PMID:22039962

Pharmacologic Effects on Mitochondrial Function

ERIC Educational Resources Information Center

Cohen, Bruce H.

2010-01-01

The vast majority of energy necessary for cellular function is produced in mitochondria. Free-radical production and apoptosis are other critical mitochondrial functions. The complex structure, electrochemical properties of the inner mitochondrial membrane (IMM), and genetic control from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) are…

Structural and functional impacts of copy number variations on the cattle genome

USDA-ARS?s Scientific Manuscript database

Although there have been significant advances in resolving the pattern and nature of single nucleotide polymorphisms (SNPs), similar realizations for larger, more complex forms of genetic variation have just emerged. Several recent publications reveal that copy number variations (CNVs) are common an...

Independently segregating simple sequence repeats (SSR) alleles in polyploid sugarcane

USDA-ARS?s Scientific Manuscript database

The complex nuclear genomic and flower structures of sugarcane cultivars (Saccharum hybrids spp., 2n = 10x = 100 – 130) render sugarcane a difficult subject for genetics research. Using a capillary electrophoresis- and fluorescence-labeling-based SSR genotyping platform, the segregation of a multi-a...

Quantitative genetics of immunity and life history under different photoperiods.

PubMed

Hammerschmidt, K; Deines, P; Wilson, A J; Rolff, J

2012-05-01

Insects with complex life-cycles should optimize age and size at maturity during larval development. When inhabiting seasonal environments, organisms have limited reproductive periods and face fundamental decisions: individuals that reach maturity late in season have to either reproduce at a small size or increase their growth rates. Increasing growth rates is costly in insects because of higher juvenile mortality, decreased adult survival or increased susceptibility to parasitism by bacteria and viruses via compromised immune function. Environmental changes such as seasonality can also alter the quantitative genetic architecture. Here, we explore the quantitative genetics of life history and immunity traits under two experimentally induced seasonal environments in the cricket Gryllus bimaculatus. Seasonality affected the life history but not the immune phenotypes. Individuals under decreasing day length developed slower and grew to a bigger size. We found ample additive genetic variance and heritability for components of immunity (haemocyte densities, proPhenoloxidase activity, resistance against Serratia marcescens), and for the life history traits, age and size at maturity. Despite genetic covariance among traits, the structure of G was inconsistent with genetically based trade-off between life history and immune traits (for example, a strong positive genetic correlation between growth rate and haemocyte density was estimated). However, conditional evolvabilities support the idea that genetic covariance structure limits the capacity of individual traits to evolve independently. We found no evidence for G × E interactions arising from the experimentally induced seasonality.

Sea surface currents and geographic isolation shape the genetic population structure of a coral reef fish in the Indian Ocean.

PubMed

Huyghe, Filip; Kochzius, Marc

2018-01-01

In this contribution, we determine the genetic population structure in the Skunk Clownfish (Amphiprion akallopsisos) across the Indian Ocean, and on a smaller geographic scale in the Western Indian Ocean (WIO). Highly restricted gene flow was discovered between populations on either side of the Indian Ocean using the control region as a mitochondrial marker (mtDNA). We verify this conclusion using 13 microsatellite markers and infer fine scale genetic structuring within the WIO. In total 387 samples from 21 sites were analysed using mtDNA and 13 microsatellite loci. Analysis included estimation of genetic diversity and population differentiation. A haplotype network was inferred using mtDNA. Nuclear markers were used in Bayesian clustering and a principal component analysis. Both markers confirmed strong genetic differentiation between WIO and Eastern Indian Ocean (EIO) populations, and a shallower population structure among Malagasy and East African mainland populations. Limited gene flow across the Mozambique Channel may be explained by its complex oceanography, which could cause local retention of larvae, limiting dispersal between Madagascar and the East African coast. Two other potential current-mediated barriers to larval dispersal suggested in the WIO, the split of the SEC at approximately 10° S and the convergence of the Somali Current with the East African Coast Current at approximately 3° S, were not found to form a barrier to gene flow in this species.

Sea surface currents and geographic isolation shape the genetic population structure of a coral reef fish in the Indian Ocean

PubMed Central

Kochzius, Marc

2018-01-01

In this contribution, we determine the genetic population structure in the Skunk Clownfish (Amphiprion akallopsisos) across the Indian Ocean, and on a smaller geographic scale in the Western Indian Ocean (WIO). Highly restricted gene flow was discovered between populations on either side of the Indian Ocean using the control region as a mitochondrial marker (mtDNA). We verify this conclusion using 13 microsatellite markers and infer fine scale genetic structuring within the WIO. In total 387 samples from 21 sites were analysed using mtDNA and 13 microsatellite loci. Analysis included estimation of genetic diversity and population differentiation. A haplotype network was inferred using mtDNA. Nuclear markers were used in Bayesian clustering and a principal component analysis. Both markers confirmed strong genetic differentiation between WIO and Eastern Indian Ocean (EIO) populations, and a shallower population structure among Malagasy and East African mainland populations. Limited gene flow across the Mozambique Channel may be explained by its complex oceanography, which could cause local retention of larvae, limiting dispersal between Madagascar and the East African coast. Two other potential current-mediated barriers to larval dispersal suggested in the WIO, the split of the SEC at approximately 10° S and the convergence of the Somali Current with the East African Coast Current at approximately 3° S, were not found to form a barrier to gene flow in this species. PMID:29522547

Fine-scale genetic population structure in a mobile marine mammal: inshore bottlenose dolphins in Moreton Bay, Australia.

PubMed

Ansmann, Ina C; Parra, Guido J; Lanyon, Janet M; Seddon, Jennifer M

2012-09-01

Highly mobile marine species in areas with no obvious geographic barriers are expected to show low levels of genetic differentiation. However, small-scale variation in habitat may lead to resource polymorphisms and drive local differentiation by adaptive divergence. Using nuclear microsatellite genotyping at 20 loci, and mitochondrial control region sequencing, we investigated fine-scale population structuring of inshore bottlenose dolphins (Tursiops aduncus) inhabiting a range of habitats in and around Moreton Bay, Australia. Bayesian structure analysis identified two genetic clusters within Moreton Bay, with evidence of admixture between them (F(ST) = 0.05, P = 0.001). There was only weak isolation by distance but one cluster of dolphins was more likely to be found in shallow southern areas and the other in the deeper waters of the central northern bay. In further analysis removing admixed individuals, southern dolphins appeared genetically restricted with lower levels of variation (AR = 3.252, π = 0.003) and high mean relatedness (r = 0.239) between individuals. In contrast, northern dolphins were more diverse (AR = 4.850, π = 0.009) and were mixing with a group of dolphins outside the bay (microsatellite-based STRUCTURE analysis), which appears to have historically been distinct from the bay dolphins (mtDNA Φ(ST) = 0.272, P < 0.001). This study demonstrates the ability of genetic techniques to expose fine-scale patterns of population structure and explore their origins and mechanisms. A complex variety of inter-related factors including local habitat variation, differential resource use, social behaviour and learning, and anthropogenic disturbances are likely to have played a role in driving fine-scale population structure among bottlenose dolphins in Moreton Bay. © 2012 Blackwell Publishing Ltd.

Swept away: ocean currents and seascape features influence genetic structure across the 18,000 Km Indo-Pacific distribution of a marine invertebrate, the black-lip pearl oyster Pinctada margaritifera.

PubMed

Lal, Monal M; Southgate, Paul C; Jerry, Dean R; Bosserelle, Cyprien; Zenger, Kyall R

2017-01-10

Genetic structure in many widely-distributed broadcast spawning marine invertebrates remains poorly understood, posing substantial challenges for their fishery management, conservation and aquaculture. Under the Core-Periphery Hypothesis (CPH), genetic diversity is expected to be highest at the centre of a species' distribution, progressively decreasing with increased differentiation towards outer range limits, as populations become increasingly isolated, fragmented and locally adapted. The unique life history characteristics of many marine invertebrates such as high dispersal rates, stochastic survival and variable recruitment are also likely to influence how populations are organised. To examine the microevolutionary forces influencing population structure, connectivity and adaptive variation in a highly-dispersive bivalve, populations of the black-lip pearl oyster Pinctada margaritifera were examined across its ~18,000 km Indo-Pacific distribution. Analyses utilising 9,624 genome-wide SNPs and 580 oysters, discovered differing patterns of significant and substantial broad-scale genetic structure between the Indian and Pacific Ocean basins. Indian Ocean populations were markedly divergent (F st  = 0.2534-0.4177, p < 0.001), compared to Pacific Ocean oysters, where basin-wide gene flow was much higher (F st  = 0.0007-0.1090, p < 0.001). Partitioning of genetic diversity (hierarchical AMOVA) attributed 18.1% of variance between ocean basins, whereas greater proportions were resolved within samples and populations (45.8% and 35.7% respectively). Visualisation of population structure at selectively neutral loci resolved three and five discrete genetic clusters for the Indian and Pacific Oceans respectively. Evaluation of genetic structure at adaptive loci for Pacific populations (89 SNPs under directional selection; F st  = 0.1012-0.4371, FDR = 0.05), revealed five clusters identical to those detected at neutral SNPs, suggesting environmental heterogeneity within the Pacific. Patterns of structure and connectivity were supported by Mantel tests of isolation by distance (IBD) and independent hydrodynamic particle dispersal simulations. It is evident that genetic structure and connectivity across the natural range of P. margaritifera is highly complex, and produced by the interaction of ocean currents, IBD and seascape features at a broad scale, together with habitat geomorphology and local adaptation at regional levels. Overall population organisation is far more elaborate than generalised CPH predictions, however valuable insights for regional fishery management, and a greater understanding of range-wide genetic structure in a highly-dispersive marine invertebrate have been gained.

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

PubMed Central

Robinson, Elise B.; Kirby, Andrew; Ruparel, Kosha; Yang, Jian; McGrath, Lauren; Anttila, Verneri; Neale, Benjamin M.; Merikangas, Kathleen; Lehner, Thomas; Sleiman, Patrick M.A.; Daly, Mark J.; Gur, Ruben; Gur, Raquel; Hakonarson, Hakon

2014-01-01

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3,689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample of ages 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis (GCTA) to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (e.g. reading ability, h2g=0.43, p=4e-06; emotion identification, h2g=0.36, p=1e-05; verbal memory, h2g=0.24, p=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (e.g. language reasoning and spatial reasoning, r(g)=0.72, p=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities. PMID:25023143

Evolution of the Plant Reproduction Master Regulators LFY and the MADS Transcription Factors: The Role of Protein Structure in the Evolutionary Development of the Flower.

PubMed

Silva, Catarina S; Puranik, Sriharsha; Round, Adam; Brennich, Martha; Jourdain, Agnès; Parcy, François; Hugouvieux, Veronique; Zubieta, Chloe

2015-01-01

Understanding the evolutionary leap from non-flowering (gymnosperms) to flowering (angiosperms) plants and the origin and vast diversification of the floral form has been one of the focuses of plant evolutionary developmental biology. The evolving diversity and increasing complexity of organisms is often due to relatively small changes in genes that direct development. These "developmental control genes" and the transcription factors (TFs) they encode, are at the origin of most morphological changes. TFs such as LEAFY (LFY) and the MADS-domain TFs act as central regulators in key developmental processes of plant reproduction including the floral transition in angiosperms and the specification of the male and female organs in both gymnosperms and angiosperms. In addition to advances in genome wide profiling and forward and reverse genetic screening, structural techniques are becoming important tools in unraveling TF function by providing atomic and molecular level information that was lacking in purely genetic approaches. Here, we summarize previous structural work and present additional biophysical and biochemical studies of the key master regulators of plant reproduction - LEAFY and the MADS-domain TFs SEPALLATA3 and AGAMOUS. We discuss the impact of structural biology on our understanding of the complex evolutionary process leading to the development of the bisexual flower.

A tale of two seas: contrasting patterns of population structure in the small-spotted catshark across Europe

PubMed Central

Gubili, Chrysoula; Sims, David W.; Veríssimo, Ana; Domenici, Paolo; Ellis, Jim; Grigoriou, Panagiotis; Johnson, Andrew F.; McHugh, Matthew; Neat, Francis; Satta, Andrea; Scarcella, Giuseppe; Serra-Pereira, Bárbara; Soldo, Alen; Genner, Martin J.; Griffiths, Andrew M.

2014-01-01

Elasmobranchs represent important components of marine ecosystems, but they can be vulnerable to overexploitation. This has driven investigations into the population genetic structure of large-bodied pelagic sharks, but relatively little is known of population structure in smaller demersal taxa, which are perhaps more representative of the biodiversity of the group. This study explores spatial population genetic structure of the small-spotted catshark (Scyliorhinus canicula), across European seas. The results show significant genetic differences among most of the Mediterranean sample collections, but no significant structure among Atlantic shelf areas. The data suggest the Mediterranean populations are likely to have persisted in a stable and structured environment during Pleistocene sea-level changes. Conversely, the Northeast Atlantic populations would have experienced major changes in habitat availability during glacial cycles, driving patterns of population reduction and expansion. The data also provide evidence of male-biased dispersal and female philopatry over large spatial scales, implying complex sex-determined differences in the behaviour of elasmobranchs. On the basis of this evidence, we suggest that patterns of connectivity are determined by trends of past habitat stability that provides opportunity for local adaptation in species exhibiting philopatric behaviour, implying that resilience of populations to fisheries and other stressors may differ across the range of species. PMID:26064555

Molecular genetic analysis of two native desert palm genera, Washingtonia and Brahea, from the Baja California Peninsula and Guadalupe Island.

PubMed

Klimova, Anastasia; Hoffman, Joseph I; Gutierrez-Rivera, Jesus N; Leon de la Luz, Jose; Ortega-Rubio, Alfredo

2017-07-01

The complex geological and ecological processes that have generated high levels of biodiversity and endemism in the Baja California Peninsula have been the subject of intensive study. However, relatively little is known about phylogeography of the iconic endemic palm species of this region. We therefore analyzed a total of 2,294 bp of chloroplast and 738 bp of nuclear sequence data in 169 samples of five native palm species from Baja California, Sonora and Guadalupe Island. We found that Washingtonia and Brahea palms had low levels of genetic diversity and were highly structured, with the majority of species and major geographic regions being characterized by distinct haplotypes. We also found strong support for currently recognized species in Washingtonia , but our results were less clear cut for Brahea due to haplotype sharing. Furthermore, patterns of population structure were broadly consistent with historical vicariant events such as the inundation of the Isthmus of La Paz, the formation of the Sea of Cortez, and the more recent colonization and isolation of Guadalupe Island's palms. Our findings contribute toward a growing appreciation of the complexity of plant responses to past geological changes and also provide valuable baseline genetic data on relict American palm species.

Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands-Relation to Rheumatoid Arthritis.

PubMed

Trier, Nicole; Izarzugaza, Jose; Chailyan, Anna; Marcatili, Paolo; Houen, Gunnar

2018-01-21

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50-60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex.

Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

PubMed Central

Trier, Nicole; Izarzugaza, Jose; Chailyan, Anna; Marcatili, Paolo; Houen, Gunnar

2018-01-01

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex. PMID:29361739

Population structure of the Yersinia pseudotuberculosis complex according to multilocus sequence typing

PubMed Central

Laukkanen-Ninios, Riikka; Didelot, Xavier; Jolley, Keith A.; Morelli, Giovanna; Sangal, Vartul; Kristo, Paula; Imori, Priscilla F. M.; Fukushima, Hiroshi; Siitonen, Anja; Tseneva, Galina; Voskressenskaya, Ekaterina; Falcao, Juliana P.; Korkeala, Hannu; Maiden, Martin C. J.; Mazzoni, Camila; Carniel, Elisabeth; Skurnik, Mikael; Achtman, Mark

2014-01-01

Summary Multilocus sequence analysis of 417 strains of Yersinia pseudotuberculosis revealed that it is a complex of four populations, three of which have been previously assigned species status [Y. pseudotuberculosis sensu stricto (s.s.), Yersinia pestis and Yersinia similis] and a fourth population, which we refer to as the Korean group, which may be in the process of speciation. We detected clear signs of recombination within Y. pseudotuberculosis s.s. as well as imports from Y. similis and the Korean group. The sources of genetic diversification within Y. pseudotuberculosis s.s. were approximately equally divided between recombination and mutation, whereas recombination has not yet been demonstrated in Y. pestis, which is also much more genetically monomorphic than is Y. pseudotuberculosis s.s. Most Y. pseudotuberculosis s.s. belong to a diffuse group of sequence types lacking clear population structure, although this species contains a melibiose-negative clade that is present globally in domesticated animals. Yersinia similis corresponds to the previously identified Y. pseudotuberculosis genetic type G4, which is probably not pathogenic because it lacks the virulence factors that are typical for Y. pseudotuberculosis s.s. In contrast, Y. pseudotuberculosis s.s., the Korean group and Y. pestis can all cause disease in humans. PMID:21951486

Restricted gene flow and fine-scale population structuring in tool using New Caledonian crows

NASA Astrophysics Data System (ADS)

Rutz, C.; Ryder, T. B.; Fleischer, R. C.

2012-04-01

New Caledonian crows Corvus moneduloides are the most prolific avian tool users. It has been suggested that some aspects of their complex tool use behaviour are under the influence of cultural processes, involving the social transmission—and perhaps even progressive refinement—of tool designs. Using microsatellite and mt-haplotype profiling of crows from three distinct habitats (dry forest, farmland and beachside habitat), we show that New Caledonian crow populations can exhibit significant fine-scale genetic structuring. Our finding that some sites of <10 km apart were highly differentiated demonstrates considerable potential for genetic and/or cultural isolation of crow groups. Restricted movement of birds between local populations at such small spatial scales, especially across habitat boundaries, illustrates how specific tool designs could be preserved over time, and how tool technologies of different crow groups could diverge due to drift and local selection pressures. Young New Caledonian crows have an unusually long juvenile dependency period, during which they acquire complex tool-related foraging skills. We suggest that the resulting delayed natal dispersal drives population-divergence patterns in this species. Our work provides essential context for future studies that examine the genetic makeup of crow populations across larger geographic areas, including localities with suspected cultural differences in crow tool technologies.

Positional cloning in mice and its use for molecular dissection of inflammatory arthritis.

PubMed

Abe, Koichiro; Yu, Philipp

2009-02-01

One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this review, first, we describe a general scheme of positional cloning in mice. Next, recent accomplishments on the patho-mechanisms of inflammatory arthritis by forward genetics approaches are introduced; Positional cloning effort for skg, Ali5, Ali18, cmo, and lupo mutants are provided as examples for the application to human complex diseases. As seen in the examples, the identification of genetic factors by positional cloning in the mouse have potential in solving molecular complexity of gene-environment interactions in human complex diseases.

Genealogical information and the structure of rural Latin-American populations: reality and fantasy.

PubMed

Castilla, E E; Adams, J

1996-01-01

Genetic data organized in the form of genealogies can provide much information regarding the history and genetic structure of human populations. A large proportion of the population of Latin America is organized in small rural semi-isolated communities, with little immigration, and until the last 50-100 years, little emigration. These communities have a strong sense of their genealogical history, and this "genealogical conscience' is a frequent leitmotif in modern Latin-American literature. In this communication, we compare the characteristics of fictitious genealogies described in two masterpieces of Latin-American literature, García Márquez' Cien Años de Soledad (A Hundred Years of Solitude), and Verissimo's O Tempo e o Vento (Time and the Wind), with one existing well-studied population in Argentina, Aicuña. All three populations exhibit a number of common characteristics, such as histories of long periods of civil war, and large pedigrees with complex paths of inheritance resulting in complex patterns of inbreeding. Genetic themes common to all three are: (1) the use of genealogical records to substantiate the property of the land or the political power of a kinship; (2) the genealogical registry of biological descendants, independent of their legal or marital status in the clan; (3) the existence of pedigrees of the aristocratic branches in the same kindreds, which illustrate the legal principle of primogeniture; (4) the value of last names as indicators of kinships and the extent of genetic isolation, and (5) the awareness of the deleterious consequences of consanguinity.

Genomic diversity and introgression in O. sativa reveal the impact of domestication and breeding on the rice genome.

PubMed

Zhao, Keyan; Wright, Mark; Kimball, Jennifer; Eizenga, Georgia; McClung, Anna; Kovach, Michael; Tyagi, Wricha; Ali, Md Liakat; Tung, Chih-Wei; Reynolds, Andy; Bustamante, Carlos D; McCouch, Susan R

2010-05-24

The domestication of Asian rice (Oryza sativa) was a complex process punctuated by episodes of introgressive hybridization among and between subpopulations. Deep genetic divergence between the two main varietal groups (Indica and Japonica) suggests domestication from at least two distinct wild populations. However, genetic uniformity surrounding key domestication genes across divergent subpopulations suggests cultural exchange of genetic material among ancient farmers. In this study, we utilize a novel 1,536 SNP panel genotyped across 395 diverse accessions of O. sativa to study genome-wide patterns of polymorphism, to characterize population structure, and to infer the introgression history of domesticated Asian rice. Our population structure analyses support the existence of five major subpopulations (indica, aus, tropical japonica, temperate japonica and GroupV) consistent with previous analyses. Our introgression analysis shows that most accessions exhibit some degree of admixture, with many individuals within a population sharing the same introgressed segment due to artificial selection. Admixture mapping and association analysis of amylose content and grain length illustrate the potential for dissecting the genetic basis of complex traits in domesticated plant populations. Genes in these regions control a myriad of traits including plant stature, blast resistance, and amylose content. These analyses highlight the power of population genomics in agricultural systems to identify functionally important regions of the genome and to decipher the role of human-directed breeding in refashioning the genomes of a domesticated species.

Biogenic manganese oxide nanoparticle formation by a multimeric multicopper oxidase Mnx

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romano, Christine A.; Zhou, Mowei; Song, Yang

Bacteria that produce Mn oxides are extraordinarily skilled engineers of nanomaterials that contribute significantly to global biogeochemical cycles. Their enzyme-based reaction mechanisms may be genetically tailored for environmental remediation applications or bioenergy production. However, significant challenges exist for structural characterization of the enzymes responsible for biomineralization. The active Mn oxidase, Mnx, in Bacillus sp. PL-12 is a complex composed of a multicopper oxidase (MCO), MnxG, and two accessory proteins MnxE and MnxF. MnxG shares sequence similarity with other, structurally characterized MCOs. However, MnxE and MnxF have no similarity to any characterized proteins. The ~200 kDa complex has been recalcitrant tomore » crystallization, so its structure is unknown. In this study, native mass spectrometry defines the subunit topology and copper binding of the Mnx complex, while high resolution electron microscopy visualizes the protein and nascent Mn oxide minerals. These data provide critical structural information for conceptualizing how Mnx produces nanoparticulate Mn oxides.« less

The Evolution of Campylobacter jejuni and Campylobacter coli

PubMed Central

Sheppard, Samuel K.; Maiden, Martin C.J.

2015-01-01

The global significance of Campylobacter jejuni and Campylobacter coli as gastrointestinal human pathogens has motivated numerous studies to characterize their population biology and evolution. These bacteria are a common component of the intestinal microbiota of numerous bird and mammal species and cause disease in humans, typically via consumption of contaminated meat products, especially poultry meat. Sequence-based molecular typing methods, such as multilocus sequence typing (MLST) and whole genome sequencing (WGS), have been instructive for understanding the epidemiology and evolution of these bacteria and how phenotypic variation relates to the high degree of genetic structuring in C. coli and C. jejuni populations. Here, we describe aspects of the relatively short history of coevolution between humans and pathogenic Campylobacter, by reviewing research investigating how mutation and lateral or horizontal gene transfer (LGT or HGT, respectively) interact to create the observed population structure. These genetic changes occur in a complex fitness landscape with divergent ecologies, including multiple host species, which can lead to rapid adaptation, for example, through frame-shift mutations that alter gene expression or the acquisition of novel genetic elements by HGT. Recombination is a particularly strong evolutionary force in Campylobacter, leading to the emergence of new lineages and even large-scale genome-wide interspecies introgression between C. jejuni and C. coli. The increasing availability of large genome datasets is enhancing understanding of Campylobacter evolution through the application of methods, such as genome-wide association studies, but MLST-derived clonal complex designations remain a useful method for describing population structure. PMID:26101080

The benefits of analysing complete mitochondrial genomes: Deep insights into the phylogeny and population structure of Echinococcus granulosus sensu lato genotypes G6 and G7.

PubMed

Laurimäe, Teivi; Kinkar, Liina; Romig, Thomas; Omer, Rihab A; Casulli, Adriano; Umhang, Gérald; Gasser, Robin B; Jabbar, Abdul; Sharbatkhori, Mitra; Mirhendi, Hossein; Ponce-Gordo, Francisco; Lazzarini, Lorena E; Soriano, Silvia V; Varcasia, Antonio; Nejad, Mohammad Rostami; Andresiuk, Vanessa; Maravilla, Pablo; González, Luis Miguel; Dybicz, Monika; Gawor, Jakub; Šarkūnas, Mindaugas; Šnábel, Viliam; Kuzmina, Tetiana; Saarma, Urmas

2018-06-12

Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the species complex Echinococcus granulosus sensu lato. Within this complex, genotypes G6 and G7 have been frequently associated with human CE worldwide. Previous studies exploring the genetic variability and phylogeography of genotypes G6 and G7 have been based on relatively short mtDNA sequences, and the resolution of these studies has often been low. Moreover, using short sequences, the distinction between G6 and G7 has in some cases remained challenging. The aim here was to sequence complete mitochondrial genomes (mitogenomes) to obtain deeper insight into the genetic diversity, phylogeny and population structure of genotypes G6 and G7. We sequenced complete mitogenomes of 94 samples collected from 15 different countries worldwide. The results demonstrated that (i) genotypes G6 and G7 can be clearly distinguished when mitogenome sequences are used; (ii) G7 is represented by two major haplogroups, G7a and G7b, the latter being specific to islands of Corsica and Sardinia; (iii) intensive animal trade, but also geographical isolation, have likely had the largest impact on shaping the genetic structure and distribution of genotypes G6 and G7. In addition, we found phylogenetically highly divergent haplotype from Mongolia (Gmon), which had a higher affinity to G6. Copyright © 2017. Published by Elsevier B.V.

Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

PubMed Central

Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

2012-01-01

Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

Pronounced fixation, strong population differentiation and complex population history in the Canary Islands blue tit subspecies complex.

PubMed

Hansson, Bengt; Ljungqvist, Marcus; Illera, Juan-Carlos; Kvist, Laura

2014-01-01

Evolutionary molecular studies of island radiations may lead to insights in the role of vicariance, founder events, population size and drift in the processes of population differentiation. We evaluate the degree of population genetic differentiation and fixation of the Canary Islands blue tit subspecies complex using microsatellite markers and aim to get insights in the population history using coalescence based methods. The Canary Island populations were strongly genetically differentiated and had reduced diversity with pronounced fixation including many private alleles. In population structure models, the relationship between the central island populations (La Gomera, Tenerife and Gran Canaria) and El Hierro was difficult to disentangle whereas the two European populations showed consistent clustering, the two eastern islands (Fuerteventura and Lanzarote) and Morocco weak clustering, and La Palma a consistent unique lineage. Coalescence based models suggested that the European mainland forms an outgroup to the Afrocanarian population, a split between the western island group (La Palma and El Hierro) and the central island group, and recent splits between the three central islands, and between the two eastern islands and Morocco, respectively. It is clear that strong genetic drift and low level of concurrent gene flow among populations have shaped complex allelic patterns of fixation and skewed frequencies over the archipelago. However, understanding the population history remains challenging; in particular, the pattern of extreme divergence with low genetic diversity and yet unique genetic material in the Canary Island system requires an explanation. A potential scenario is population contractions of a historically large and genetically variable Afrocanarian population, with vicariance and drift following in the wake. The suggestion from sequence-based analyses of a Pleistocene extinction of a substantial part of North Africa and a Pleistocene/Holocene eastward re-colonisation of western North Africa from the Canaries remains possible.

Pronounced Fixation, Strong Population Differentiation and Complex Population History in the Canary Islands Blue Tit Subspecies Complex

PubMed Central

Hansson, Bengt; Ljungqvist, Marcus; Illera, Juan-Carlos; Kvist, Laura

2014-01-01

Evolutionary molecular studies of island radiations may lead to insights in the role of vicariance, founder events, population size and drift in the processes of population differentiation. We evaluate the degree of population genetic differentiation and fixation of the Canary Islands blue tit subspecies complex using microsatellite markers and aim to get insights in the population history using coalescence based methods. The Canary Island populations were strongly genetically differentiated and had reduced diversity with pronounced fixation including many private alleles. In population structure models, the relationship between the central island populations (La Gomera, Tenerife and Gran Canaria) and El Hierro was difficult to disentangle whereas the two European populations showed consistent clustering, the two eastern islands (Fuerteventura and Lanzarote) and Morocco weak clustering, and La Palma a consistent unique lineage. Coalescence based models suggested that the European mainland forms an outgroup to the Afrocanarian population, a split between the western island group (La Palma and El Hierro) and the central island group, and recent splits between the three central islands, and between the two eastern islands and Morocco, respectively. It is clear that strong genetic drift and low level of concurrent gene flow among populations have shaped complex allelic patterns of fixation and skewed frequencies over the archipelago. However, understanding the population history remains challenging; in particular, the pattern of extreme divergence with low genetic diversity and yet unique genetic material in the Canary Island system requires an explanation. A potential scenario is population contractions of a historically large and genetically variable Afrocanarian population, with vicariance and drift following in the wake. The suggestion from sequence-based analyses of a Pleistocene extinction of a substantial part of North Africa and a Pleistocene/Holocene eastward re-colonisation of western North Africa from the Canaries remains possible. PMID:24587269

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-climbing capability in the conventional genetic algorithm by using the flexible memory functions of TS. Compared with some previous algorithms, GATS algorithm has better performance in global optimization and can predict 3D protein structure more effectively. PMID:20522256

Urban population genetics of slum-dwelling rats (Rattus norvegicus) in Salvador, Brazil.

PubMed

Kajdacsi, Brittney; Costa, Federico; Hyseni, Chaz; Porter, Fleur; Brown, Julia; Rodrigues, Gorete; Farias, Helena; Reis, Mitermayer G; Childs, James E; Ko, Albert I; Caccone, Adalgisa

2013-10-01

Throughout the developing world, urban centres with sprawling slum settlements are rapidly expanding and invading previously forested ecosystems. Slum communities are characterized by untended refuse, open sewers and overgrown vegetation, which promote rodent infestation. Norway rats (Rattus norvegicus) are reservoirs for epidemic transmission of many zoonotic pathogens of public health importance. Understanding the population ecology of R. norvegicus is essential to formulate effective rodent control strategies, as this knowledge aids estimation of the temporal stability and spatial connectivity of populations. We screened for genetic variation, characterized the population genetic structure and evaluated the extent and patterns of gene flow in the urban landscape using 17 microsatellite loci in 146 rats from nine sites in the city of Salvador, Brazil. These sites were divided between three neighbourhoods within the city spaced an average of 2.7 km apart. Surprisingly, we detected very little relatedness among animals trapped at the same site and found high levels of genetic diversity, as well as structuring across small geographical distances. Most F(ST) comparisons among sites were statistically significant, including sites <400 m apart. Bayesian analyses grouped the samples in three genetic clusters, each associated with distinct sampling sites from different neighbourhoods or valleys within neighbourhoods. These data indicate the existence of complex genetic structure in R. norvegicus in Salvador, linked to the heterogeneous urban landscape. Future rodent control measures need to take into account the spatial and temporal linkage of rat populations in Salvador, as revealed by genetic data, to develop informed eradication strategies. © 2013 John Wiley & Sons Ltd.

Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function

PubMed Central

Ungar, Daniel; Oka, Toshihiko; Brittle, Elizabeth E.; Vasile, Eliza; Lupashin, Vladimir V.; Chatterton, Jon E.; Heuser, John E.; Krieger, Monty; Waters, M. Gerard

2002-01-01

Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Three complexes that have previously been partially characterized include (a) the Golgi transport complex (GTC), identified in an in vitro membrane transport assay, (b) the ldlCp complex, identified in analyses of CHO cell mutants with defects in Golgi-associated glycosylation reactions, and (c) the mammalian Sec34 complex, identified by homology to yeast Sec34p, implicated in vesicular transport. We show that these three complexes are identical and rename them the conserved oligomeric Golgi (COG) complex. The COG complex comprises four previously characterized proteins (Cog1/ldlBp, Cog2/ldlCp, Cog3/Sec34, and Cog5/GTC-90), three homologues of yeast Sec34/35 complex subunits (Cog4, -6, and -8), and a previously unidentified Golgi-associated protein (Cog7). EM of ldlB and ldlC mutants established that COG is required for normal Golgi morphology. “Deep etch” EM of purified COG revealed an ∼37-nm-long structure comprised of two similarly sized globular domains connected by smaller extensions. Consideration of biochemical and genetic data for mammalian COG and its yeast homologue suggests a model for the subunit distribution within this complex, which plays critical roles in Golgi structure and function. PMID:11980916

Mitochondrial disease associated with complex I (NADH-CoQ oxidoreductase) deficiency.

PubMed

Scheffler, Immo E

2015-05-01

Mitochondrial diseases due to a reduced capacity for oxidative phosphorylation were first identified more than 20 years ago, and their incidence is now recognized to be quite significant. In a large proportion of cases the problem can be traced to a complex I (NADH-CoQ oxidoreductase) deficiency (Phenotype MIM #252010). Because the complex consists of 44 subunits, there are many potential targets for pathogenic mutations, both on the nuclear and mitochondrial genomes. Surprisingly, however, almost half of the complex I deficiencies are due to defects in as yet unidentified genes that encode proteins other than the structural proteins of the complex. This review attempts to summarize what we know about the molecular basis of complex I deficiencies: mutations in the known structural genes, and mutations in an increasing number of genes encoding "assembly factors", that is, proteins required for the biogenesis of a functional complex I that are not found in the final complex I. More such genes must be identified before definitive genetic counselling can be applied in all cases of affected families.

Revolting Developments in Our Understanding of the Organization of the Eukaryotic Genome.

ERIC Educational Resources Information Center

Krider, Hallie M.

1984-01-01

Various typs of DNA are discussed. Areas considered include highly repetitive and satellite sequences, genes encoding, ribosomal RNA, histone protein genes, and dispersed repeated genes that jump. Regulated genetic misbehavior, structure and use of unique genes, and higher order complexities of chromosomes are also discussed. (JN)

Modeling Molecular Machinery

ERIC Educational Resources Information Center

Hunter, Christine

2015-01-01

Imagine a microscopic world filled with tiny motors, ratchets, switches, and pumps controlled by complex signaling and feedback systems. Now imagine that these parts can assemble themselves. This is the world presented to students in the protein structure unit of a genetic engineering course. Students learn how protein folding gives rise to the…

Genetic diversity of Flavobacterium psychrophilum isolates from three Oncorhynchus spp. in the United States, as revealed by multilocus sequence typing

USDA-ARS?s Scientific Manuscript database

Flavobacterium psychrophilum is an important pathogen of salmonids worldwide. Multilocus sequence typing (MLST) has identified a recombinogenic population structure from which emerged a few epidemic clonal complexes particularly threatening for salmonid aquaculture. To date, MLST genotypes for this ...

Unveiling the complexity of the maize transcriptome by single-molecule long-read sequencing

USDA-ARS?s Scientific Manuscript database

Zea mays is an important crop species and genetic model for elucidating transcriptional networks in plants. Uncertainties about the complete structure of mRNA transcripts, particularly with respect to alternatively spliced isoforms, limit the progress of research in this system. In this study, we us...

Genetics, systems, and alcohol.

PubMed

McClearn, G E

1993-03-01

Under a variety of rubrics (e.g., complexity, self-constructing systems, dissipative structures), interest has recently burgeoned in applying principles of complex systems to a wide variety of scientific issues. A major concern is with emergent properties of systems not derivable from the properties of components of the systems. In this paper, some elementary aspects of "systems" considerations are applied to phenomena of alcohol pharmacogenetics. It is likely that whole new families of informative phenotypes can be generated by this approach.

GENOME-WIDE GENETIC INTERACTION ANALYSIS OF GLAUCOMA USING EXPERT KNOWLEDGE DERIVED FROM HUMAN PHENOTYPE NETWORKS

PubMed Central

HU, TING; DARABOS, CHRISTIAN; CRICCO, MARIA E.; KONG, EMILY; MOORE, JASON H.

2014-01-01

The large volume of GWAS data poses great computational challenges for analyzing genetic interactions associated with common human diseases. We propose a computational framework for characterizing epistatic interactions among large sets of genetic attributes in GWAS data. We build the human phenotype network (HPN) and focus around a disease of interest. In this study, we use the GLAUGEN glaucoma GWAS dataset and apply the HPN as a biological knowledge-based filter to prioritize genetic variants. Then, we use the statistical epistasis network (SEN) to identify a significant connected network of pairwise epistatic interactions among the prioritized SNPs. These clearly highlight the complex genetic basis of glaucoma. Furthermore, we identify key SNPs by quantifying structural network characteristics. Through functional annotation of these key SNPs using Biofilter, a software accessing multiple publicly available human genetic data sources, we find supporting biomedical evidences linking glaucoma to an array of genetic diseases, proving our concept. We conclude by suggesting hypotheses for a better understanding of the disease. PMID:25592582

Ancient DNA reveals that the genetic structure of the northern Han Chinese was shaped prior to 3,000 years ago.

PubMed

Zhao, Yong-Bin; Zhang, Ye; Zhang, Quan-Chao; Li, Hong-Jie; Cui, Ying-Qiu; Xu, Zhi; Jin, Li; Zhou, Hui; Zhu, Hong

2015-01-01

The Han Chinese are the largest ethnic group in the world, and their origins, development, and expansion are complex. Many genetic studies have shown that Han Chinese can be divided into two distinct groups: northern Han Chinese and southern Han Chinese. The genetic history of the southern Han Chinese has been well studied. However, the genetic history of the northern Han Chinese is still obscure. In order to gain insight into the genetic history of the northern Han Chinese, 89 human remains were sampled from the Hengbei site which is located in the Central Plain and dates back to a key transitional period during the rise of the Han Chinese (approximately 3,000 years ago). We used 64 authentic mtDNA data obtained in this study, 27 Y chromosome SNP data profiles from previously studied Hengbei samples, and genetic datasets of the current Chinese populations and two ancient northern Chinese populations to analyze the relationship between the ancient people of Hengbei and present-day northern Han Chinese. We used a wide range of population genetic analyses, including principal component analyses, shared mtDNA haplotype analyses, and geographic mapping of maternal genetic distances. The results show that the ancient people of Hengbei bore a strong genetic resemblance to present-day northern Han Chinese and were genetically distinct from other present-day Chinese populations and two ancient populations. These findings suggest that the genetic structure of northern Han Chinese was already shaped 3,000 years ago in the Central Plain area.

Ancient DNA Reveals That the Genetic Structure of the Northern Han Chinese Was Shaped Prior to 3,000 Years Ago

PubMed Central

Zhang, Quan-Chao; Li, Hong-Jie; Cui, Ying-Qiu; Xu, Zhi; Jin, Li; Zhou, Hui; Zhu, Hong

2015-01-01

The Han Chinese are the largest ethnic group in the world, and their origins, development, and expansion are complex. Many genetic studies have shown that Han Chinese can be divided into two distinct groups: northern Han Chinese and southern Han Chinese. The genetic history of the southern Han Chinese has been well studied. However, the genetic history of the northern Han Chinese is still obscure. In order to gain insight into the genetic history of the northern Han Chinese, 89 human remains were sampled from the Hengbei site which is located in the Central Plain and dates back to a key transitional period during the rise of the Han Chinese (approximately 3,000 years ago). We used 64 authentic mtDNA data obtained in this study, 27 Y chromosome SNP data profiles from previously studied Hengbei samples, and genetic datasets of the current Chinese populations and two ancient northern Chinese populations to analyze the relationship between the ancient people of Hengbei and present-day northern Han Chinese. We used a wide range of population genetic analyses, including principal component analyses, shared mtDNA haplotype analyses, and geographic mapping of maternal genetic distances. The results show that the ancient people of Hengbei bore a strong genetic resemblance to present-day northern Han Chinese and were genetically distinct from other present-day Chinese populations and two ancient populations. These findings suggest that the genetic structure of northern Han Chinese was already shaped 3,000 years ago in the Central Plain area. PMID:25938511

The functional consequences of non-genetic diversity in cellular navigation

NASA Astrophysics Data System (ADS)

Emonet, Thierry; Waite, Adam J.; Frankel, Nicholas W.; Dufour, Yann; Johnston, Jessica F.

Substantial non-genetic diversity in complex behaviors, such as chemotaxis in E. coli, has been observed for decades, but the relevance of this diversity for the population is not well understood. Here, we use microfluidics to show that non-genetic diversity leads to significant structuring of the population in space and time, which confirms predictions made by our detailed mathematical model of chemotaxis. We then use genetic tools to show that altering the expression level of a single chemotaxis protein is sufficient to alter the distribution of swimming behaviors, which directly determines the performance of a population in a gradient of attractant, a result also predicted by our model. Supported by NIH 1R01GM106189, the James S McDonnell Foundation, and the Paul Allen foundation.

Genetic diversity in populations of Isatis glauca Aucher ex Boiss. ssp. from Central Anatolia in Turkey, as revealed by AFLP analysis.

PubMed

Özbek, Özlem; Görgülü, Elçin; Yıldırımlı, Şinasi

2013-12-01

Isatidae L. is a complex and systematically difficult genus in Brassicaceae. The genus displays great morphological polymorphism, which makes the classification of species and subspecies difficult as it is observed in Isatis glauca Aucher ex Boiss. The aim of this study is characterization of the genetic diversity in subspecies of Isatis glauca Aucher ex Boiss. distributed widely in Central Anatolia, in Turkey by using Amplified Fragment Length Polymorphism (AFLP) technique. Eight different Eco RI-Mse I primer combinations produced 805 AFLP loci, 793 (98.5%) of which were polymorphic in 67 accessions representing nine different populations. The data obtained by AFLP was computed with using GDA (Genetic Data Analysis) and STRUCTURE (version 2.3.3) software programs for population genetics. The mean proportion of the polymorphic locus (P), the mean number of alleles (A), the number of unique alleles (U) and the mean value of gene diversity (He) were 0.59, 1.59, 20, and 0.23 respectively. The coancestry coefficient (ϴ) was 0.24. The optimal number of K was identified as seven. The principal component analysis (PCA) explained 85.61% of the total genetic variation. Isatis glauca ssp. populations showed a high level of genetic diversity, and the AFLP analysis revealed that high polymorphism and differentiated subspecies could be used conveniently for population genetic studies. The principal coordinate analysis (PCoA) based on the dissimilarity matrix, the dendrogram drawn with UPGMA method and STRUCTURE cluster analysis distinguished the accessions successfully. The accessions formed distinctive population structures for populations AA, AB, E, K, and S. Populations AG1 and AG2 seemed to have similar genetic content, in addition, in both populations several hybrid individuals were observed. The accessions did not formed distinctive population structures for both populations AI and ANP. Consequently, Ankara province might be the area, where species Isatis glauca Aucher ex Boiss. originated.

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

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

PubMed

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

2006-09-01

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

Stocking activities for the Arctic charr in Lake Geneva: Genetic effects in space and time.

PubMed

Savary, Romain; Dufresnes, Christophe; Champigneulle, Alexis; Caudron, Arnaud; Dubey, Sylvain; Perrin, Nicolas; Fumagalli, Luca

2017-07-01

Artificial stocking practices are widely used by resource managers worldwide, in order to sustain fish populations exploited by both recreational and commercial activities, but their benefits are controversial. Former practices involved exotic strains, although current programs rather consider artificial breeding of local fishes (supportive breeding). Understanding the complex genetic effects of these management strategies is an important challenge with economic and conservation implications, especially in the context of population declines. In this study, we focus on the declining Arctic charr ( Salvelinus alpinus ) population from Lake Geneva (Switzerland and France), which has initially been restocked with allochtonous fishes in the early eighties, followed by supportive breeding. In this context, we conducted a genetic survey to document the evolution of the genetic diversity and structure throughout the last 50 years, before and after the initiation of hatchery supplementation, using contemporary and historical samples. We show that the introduction of exotic fishes was associated with a genetic bottleneck in the 1980-1990s, a break of Hardy-Weinberg Equilibrium (HWE), a reduction in genetic diversity, an increase in genetic structure among spawning sites, and a change in their genetic composition. Together with better environmental conditions, three decades of subsequent supportive breeding using local fishes allowed to re-establish HWE and the initial levels of genetic variation. However, current spawning sites have not fully recovered their original genetic composition and were extensively homogenized across the lake. Our study demonstrates the drastic genetic consequences of different restocking tactics in a comprehensive spatiotemporal framework and suggests that genetic alteration by nonlocal stocking may be partly reversible through supportive breeding. We recommend that conservation-based programs consider local diversity and implement adequate protocols to limit the genetic homogenization of this Arctic charr population.

Structure of Peptide Sex Pheromone Receptor PrgX and PrgX/Pheromone Complexes and Regulation of Conjugation in Enterococcus faecalis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi,K.; Brown, C.; Gu, Z.

2005-01-01

Many bacterial activities, including expression of virulence factors, horizontal genetic transfer, and production of antibiotics, are controlled by intercellular signaling using small molecules. To date, understanding of the molecular mechanisms of peptide-mediated cell-cell signaling has been limited by a dearth of published information about the molecular structures of the signaling components. Here, we present the molecular structure of PrgX, a DNA- and peptide-binding protein that regulates expression of the conjugative transfer genes of the Enterococcus faecalis plasmid pCF10 in response to an intercellular peptide pheromone signal. Comparison of the structures of PrgX and the PrgX/pheromone complex suggests that pheromone bindingmore » destabilizes PrgX tetramers, opening a 70-bp pCF10 DNA loop required for conjugation repression.« less

Genetics Home Reference: mitochondrial complex III deficiency

MedlinePlus

... DNA packaged in chromosomes within the cell nucleus (nuclear DNA). It is not clear why the severity ... deficiency Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 2 Genetic Testing Registry: Mitochondrial complex III ...

Multiscale structure in eco-evolutionary dynamics

NASA Astrophysics Data System (ADS)

Stacey, Blake C.

In a complex system, the individual components are neither so tightly coupled or correlated that they can all be treated as a single unit, nor so uncorrelated that they can be approximated as independent entities. Instead, patterns of interdependency lead to structure at multiple scales of organization. Evolution excels at producing such complex structures. In turn, the existence of these complex interrelationships within a biological system affects the evolutionary dynamics of that system. I present a mathematical formalism for multiscale structure, grounded in information theory, which makes these intuitions quantitative, and I show how dynamics defined in terms of population genetics or evolutionary game theory can lead to multiscale organization. For complex systems, "more is different," and I address this from several perspectives. Spatial host--consumer models demonstrate the importance of the structures which can arise due to dynamical pattern formation. Evolutionary game theory reveals the novel effects which can result from multiplayer games, nonlinear payoffs and ecological stochasticity. Replicator dynamics in an environment with mesoscale structure relates to generalized conditionalization rules in probability theory. The idea of natural selection "acting at multiple levels" has been mathematized in a variety of ways, not all of which are equivalent. We will face down the confusion, using the experience developed over the course of this thesis to clarify the situation.

A case of isolation by distance and short-term temporal stability of population structure in brown trout (Salmo trutta) within the River Dart, southwest England

PubMed Central

Griffiths, Andrew M; Koizumi, Itsuro; Bright, Dylan; Stevens, Jamie R

2009-01-01

Salmonid fishes exhibit high levels of population differentiation. In particular, the brown trout (Salmo trutta L.) demonstrates complex within river drainage genetic structure. Increasingly, these patterns can be related to the underlying evolutionary models, of which three scenarios (member-vagrant hypothesis, metapopulation model and panmixia) facilitate testable predictions for investigations into population structure. We analysed 1225 trout collected from the River Dart, a 75 km long river located in southwest England. Specimens were collected from 22 sample sites across three consecutive summers (2001–2003) and genetic variation was examined at nine microsatellite loci. A hierarchical analysis of molecular variance revealed that negligible genetic variation was attributed among temporal samples. The highest levels of differentiation occurred among samples isolated above barriers to fish movement, and once these samples were removed, a significant effect of isolation-by-distance was observed. These results suggest that, at least in the short-term, ecological events are more important in shaping the population structure of Dart trout than stochastic extinction events, and certainly do not contradict the expectations of a member-vagrant hypothesis. Furthermore, individual-level spatial autocorrelation analyses support previous recommendations for the preservation of a number of spawning sites spaced throughout the tributary system to conserve the high levels of genetic variation identified in salmonid species. PMID:25567897

Diverse Supramolecular Nanofiber Networks Assembled by Functional Low-Complexity Domains.

PubMed

An, Bolin; Wang, Xinyu; Cui, Mengkui; Gui, Xinrui; Mao, Xiuhai; Liu, Yan; Li, Ke; Chu, Cenfeng; Pu, Jiahua; Ren, Susu; Wang, Yanyi; Zhong, Guisheng; Lu, Timothy K; Liu, Cong; Zhong, Chao

2017-07-25

Self-assembling supramolecular nanofibers, common in the natural world, are of fundamental interest and technical importance to both nanotechnology and materials science. Despite important advances, synthetic nanofibers still lack the structural and functional diversity of biological molecules, and the controlled assembly of one type of molecule into a variety of fibrous structures with wide-ranging functional attributes remains challenging. Here, we harness the low-complexity (LC) sequence domain of fused in sarcoma (FUS) protein, an essential cellular nuclear protein with slow kinetics of amyloid fiber assembly, to construct random copolymer-like, multiblock, and self-sorted supramolecular fibrous networks with distinct structural features and fluorescent functionalities. We demonstrate the utilities of these networks in the templated, spatially controlled assembly of ligand-decorated gold nanoparticles, quantum dots, nanorods, DNA origami, and hybrid structures. Owing to the distinguishable nanoarchitectures of these nanofibers, this assembly is structure-dependent. By coupling a modular genetic strategy with kinetically controlled complex supramolecular self-assembly, we demonstrate that a single type of protein molecule can be used to engineer diverse one-dimensional supramolecular nanostructures with distinct functionalities.

Strong incidence of Pseudomonas aeruginosa on bacterial rrs and ITS genetic structures of cystic fibrosis sputa

PubMed Central

Pages-Monteiro, Laurence; Marti, Romain; Commun, Carine; Alliot, Nolwenn; Bardel, Claire; Meugnier, Helene; Perouse-de-Montclos, Michele; Reix, Philippe; Durieu, Isabelle; Durupt, Stephane; Vandenesch, Francois; Freney, Jean; Cournoyer, Benoit; Doleans-Jordheim, Anne

2017-01-01

Cystic fibrosis (CF) lungs harbor a complex community of interacting microbes, including pathogens like Pseudomonas aeruginosa. Meta-taxogenomic analysis based on V5-V6 rrs PCR products of 52 P. aeruginosa-positive (Pp) and 52 P. aeruginosa-negative (Pn) pooled DNA extracts from CF sputa suggested positive associations between P. aeruginosa and Stenotrophomonas and Prevotella, but negative ones with Haemophilus, Neisseria and Burkholderia. Internal Transcribed Spacer analyses (RISA) from individual DNA extracts identified three significant genetic structures within the CF cohorts, and indicated an impact of P. aeruginosa. RISA clusters Ip and IIIp contained CF sputa with a P. aeruginosa prevalence above 93%, and of 24.2% in cluster IIp. Clusters Ip and IIIp showed lower RISA genetic diversity and richness than IIp. Highly similar cluster IIp RISA profiles were obtained from two patients harboring isolates of a same P. aeruginosa clone, suggesting convergent evolution in the structure of their microbiota. CF patients of cluster IIp had received significantly less antibiotics than patients of clusters Ip and IIIp but harbored the most resistant P. aeruginosa strains. Patients of cluster IIIp were older than those of Ip. The effects of P. aeruginosa on the RISA structures could not be fully dissociated from the above two confounding factors but several trends in these datasets support the conclusion of a strong incidence of P. aeruginosa on the genetic structure of CF lung microbiota. PMID:28282386

A comparative phylogenetic study of genetics and folk music.

PubMed

Pamjav, Horolma; Juhász, Zoltán; Zalán, Andrea; Németh, Endre; Damdin, Bayarlkhagva

2012-04-01

Computer-aided comparison of folk music from different nations is one of the newest research areas. We were intrigued to have identified some important similarities between phylogenetic studies and modern folk music. First of all, both of them use similar concepts and representation tools such as multidimensional scaling for modelling relationship between populations. This gave us the idea to investigate whether these connections are merely accidental or if they mirror population migrations from the past. We raised the question; does the complex structure of musical connections display a clear picture and can this system be interpreted by the genetic analysis? This study is the first to systematically investigate the incidental genetic background of the folk music context between different populations. Paternal (42 populations) and maternal lineages (56 populations) were compared based on Fst genetic distances of the Y chromosomal and mtDNA haplogroup frequencies. To test this hypothesis, the corresponding musical cultures were also compared using an automatic overlap analysis of parallel melody styles for 31 Eurasian nations. We found that close musical relations of populations indicate close genetic distances (<0.05) with a probability of 82%. It was observed that there is a significant correlation between population genetics and folk music; maternal lineages have a more important role in folk music traditions than paternal lineages. Furthermore, the combination of these disciplines establishing a new interdisciplinary research field of "music-genetics" can be an efficient tool to get a more comprehensive picture on the complex behaviour of populations in prehistoric time.

Should I Perform Genetic Testing? A Qualitative Look into the Decision Making Considerations of Religious Israeli Undergraduate Students.

PubMed

Siani, Merav; Assaraf, Orit Ben-Zvi

2016-10-01

The aim of this study is to draw a picture of the concerns that guide the decision making of Israeli religious undergraduate students and the complex considerations they take into account while facing the need to have genetic testing or to attend a genetic counseling session. We examined how the religious affiliation of the students influences their perceptions toward genetics and how these are expressed. Qualitative data were collected from 51 semi-structured interviews with students, in which recurring themes were identified using 'thematic analysis.' The codes from the thematic analysis were obtained according to 'grounded theory'. Our results show that religious undergraduate students' decision making in these issues is influenced by factors that fall under three main categories: knowledge and perceptions, values, and norms. In order to include all the components of influence, we created the Triple C model: "Culture influences Choices towards genetic Counseling" which aims to generalize the complex decision making considerations that we detected. Our model places religion, as part of culture, as its central point of influence that impacts all three of the main categories we detected. It also traces the bidirectional influences that each of these main categories have on one another. Using this model may help identify the sociocultural differences between different types of patients, helping genetic counselors to better assist them in addressing their genetic status by tailoring the counseling more specifically to the patient's cultural uniqueness.

Dealing with AFLP genotyping errors to reveal genetic structure in Plukenetia volubilis (Euphorbiaceae) in the Peruvian Amazon

PubMed Central

Vašek, Jakub; Viehmannová, Iva; Ocelák, Martin; Cachique Huansi, Danter; Vejl, Pavel

2017-01-01

An analysis of the population structure and genetic diversity for any organism often depends on one or more molecular marker techniques. Nonetheless, these techniques are not absolutely reliable because of various sources of errors arising during the genotyping process. Thus, a complex analysis of genotyping error was carried out with the AFLP method in 169 samples of the oil seed plant Plukenetia volubilis L. from small isolated subpopulations in the Peruvian Amazon. Samples were collected in nine localities from the region of San Martin. Analysis was done in eight datasets with a genotyping error from 0 to 5%. Using eleven primer combinations, 102 to 275 markers were obtained according to the dataset. It was found that it is only possible to obtain the most reliable and robust results through a multiple-level filtering process. Genotyping error and software set up influence both the estimation of population structure and genetic diversity, where in our case population number (K) varied between 2–9 depending on the dataset and statistical method used. Surprisingly, discrepancies in K number were caused more by statistical approaches than by genotyping errors themselves. However, for estimation of genetic diversity, the degree of genotyping error was critical because descriptive parameters (He, FST, PLP 5%) varied substantially (by at least 25%). Due to low gene flow, P. volubilis mostly consists of small isolated subpopulations (ΦPT = 0.252–0.323) with some degree of admixture given by socio-economic connectivity among the sites; a direct link between the genetic and geographic distances was not confirmed. The study illustrates the successful application of AFLP to infer genetic structure in non-model plants. PMID:28910307

Potential of SNP markers for the characterization of Brazilian cassava germplasm.

PubMed

de Oliveira, Eder Jorge; Ferreira, Cláudia Fortes; da Silva Santos, Vanderlei; de Jesus, Onildo Nunes; Oliveira, Gilmara Alvarenga Fachardo; da Silva, Maiane Suzarte

2014-06-01

High-throughput markers, such as SNPs, along with different methodologies were used to evaluate the applicability of the Bayesian approach and the multivariate analysis in structuring the genetic diversity in cassavas. The objective of the present work was to evaluate the diversity and genetic structure of the largest cassava germplasm bank in Brazil. Complementary methodological approaches such as discriminant analysis of principal components (DAPC), Bayesian analysis and molecular analysis of variance (AMOVA) were used to understand the structure and diversity of 1,280 accessions genotyped using 402 single nucleotide polymorphism markers. The genetic diversity (0.327) and the average observed heterozygosity (0.322) were high considering the bi-allelic markers. In terms of population, the presence of a complex genetic structure was observed indicating the formation of 30 clusters by DAPC and 34 clusters by Bayesian analysis. Both methodologies presented difficulties and controversies in terms of the allocation of some accessions to specific clusters. However, the clusters suggested by the DAPC analysis seemed to be more consistent for presenting higher probability of allocation of the accessions within the clusters. Prior information related to breeding patterns and geographic origins of the accessions were not sufficient for providing clear differentiation between the clusters according to the AMOVA analysis. In contrast, the F ST was maximized when considering the clusters suggested by the Bayesian and DAPC analyses. The high frequency of germplasm exchange between producers and the subsequent alteration of the name of the same material may be one of the causes of the low association between genetic diversity and geographic origin. The results of this study may benefit cassava germplasm conservation programs, and contribute to the maximization of genetic gains in breeding programs.

Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes

PubMed Central

Froese, D. Sean; Gravel, Roy A.

2010-01-01

Vitamin B12 (cobalamin, Cbl) is an essential nutrient in human metabolism. Genetic diseases of vitamin B12 utilisation constitute an important fraction of inherited newborn disease. Functionally, B12 is the cofactor for methionine synthase and methylmalonyl CoA mutase. To function as a cofactor, B12 must be metabolised through a complex pathway that modifies its structure and takes it through subcellular compartments of the cell. Through the study of inherited disorders of vitamin B12 utilisation, the genes for eight complementation groups have been identified, leading to the determination of the general structure of vitamin B12 processing and providing methods for carrier testing, prenatal diagnosis and approaches to treatment. PMID:21114891

The Rise of Complexity: Do the Pavilion Lake Microbialites Suggest a Way to Build a Macroorganism?

NASA Astrophysics Data System (ADS)

Schulze-Makuch, D.; Laval, B.; Lim, D. S.; Irwin, L. N.

2005-12-01

The distinctive assemblage of freshwater calcite microbialites discovered at Pavilion Lake, BC, has been associated with organisms such as Epiphyton and Girvanella, fossils from just before the Cambrian explosion about 550 million years ago (Laval et al., 2000). The presence of the microbialite structures in a dimictic mid-latitude lake and their establishment after the last ice age about 10,000 years ago is puzzling. Their distinctive morphologies include cone-shaped seepage structures 2 m or more in height with hollow internal conduits that open at the top of the cones, and dense artichoke-like structures with calcite "leaves" greater than 1 m in height. These structures are astounding as they imply functional properties. In principle, this is not unlike the interaction of individual cells in a macroorganism, in which many different types of specialized cells interact with each other to the benefit of the whole organism (e.g. interaction of blood, integument, and organ cells within animals). Certainly, the complex interaction of these microbial cells is not equivalent to the collaboration of cells within an individual multicellular organism, where each cell has the same genetic information but differential gene expression provides well-defined cellular specializations. However, the microbialites raise the question of how much complexity and structure can be achieved by a high degree of communication within a multitude of microbial cells. Our findings indicate a complex and interacting microbial consortium associated with the structures at Pavilion Lake, and revealed biomarkers for proteobacteria, sulphur reducing bacteria, and firmicutes (possibly photosynthetic heliobacteria), among others. Types of genetic exchange among these microbial cells may include lateral gene transfer via conjugation, transformation, and transduction, or other mechanisms. This finding may have significant implications for the evolution of life on Earth and possible life on other planets. References: Laval, B., Cady, S.L., Pollack, J.C., McKay, C.P., Bird, J.S., Grotzinger, J.P., Ford, D.C., and Bohm, H.R. (2000) Modern freshwater microbialite analogues for ancient dendritic reef structures. Nature 407, 626-629.

Phytomonas: analysis of polymorphism and genetic relatedness between isolates from plants and phytophagous insects from different geographic regions by RAPD fingerprints and synapomorphic markers.

PubMed

Serrano, M G; Camargo, E P; Teixeira, M M

1999-01-01

The random amplification of polymorphic DNA was used for easy, quick and sensitive assessment of genetic polymorphism within Phytomonas to discriminate isolates and determine genetic relationships within the genus. We examined 48 Phytomonas spp., 31 isolates from plants and 17 from insects, from different geographic regions. Topology of the dendrogram based on randomly amplified polymorphic DNA fingerprints segregated the Phytomonas spp. into 5 main clusters, despite the high genetic variability within this genus. Similar clustering could also be obtained by both visual and cross-hybridization analysis of randomly amplified synapomorphic DNA fragments. There was some concordance between the genetic relationship of isolates and their plant tissue tropism. Moreover, Phytomonas spp. from plants and insects were grouped according to geographic origin, thus revealing a complex structure of this taxon comprising several clusters of very closely related organisms.

Genetic perspectives on northern population cycles: bridging the gap between theory and empirical studies.

PubMed

Norén, Karin; Angerbjörn, Anders

2014-05-01

Many key species in northern ecosystems are characterised by high-amplitude cyclic population demography. In 1924, Charles Elton described the ecology and evolution of cyclic populations in a classic paper and, since then, a major focus has been the underlying causes of population cycles. Elton hypothesised that fluctuations reduced population genetic variation and influenced the direction of selection pressures. In concordance with Elton, present theories concern the direct consequences of population cycles for genetic structure due to the processes of genetic drift and selection, but also include feedback models of genetic composition on population dynamics. Most of these theories gained mathematical support during the 1970s and onwards, but due to methodological drawbacks, difficulties in long-term sampling and a complex interplay between microevolutionary processes, clear empirical data allowing the testing of these predictions are still scarce. Current genetic tools allow for estimates of genetic variation and identification of adaptive genomic regions, making this an ideal time to revisit this subject. Herein, we attempt to contribute towards a consensus regarding the enigma described by Elton almost 90 years ago. We present nine predictions covering the direct and genetic feedback consequences of population cycles on genetic variation and population structure, and review the empirical evidence. Generally, empirical support for the predictions was low and scattered, with obvious gaps in the understanding of basic population processes. We conclude that genetic variation in northern cyclic populations generally is high and that the geographic distribution and amount of diversity are usually suggested to be determined by various forms of context- and density-dependent dispersal exceeding the impact of genetic drift. Furthermore, we found few clear signatures of selection determining genetic composition in cyclic populations. Dispersal is assumed to have a strong impact on genetic structuring and we suggest that the signatures of other microevolutionary processes such as genetic drift and selection are weaker and have been over-shadowed by density-dependent dispersal. We emphasise that basic biological and demographical questions still need to be answered and stress the importance of extensive sampling, appropriate choice of tools and the value of standardised protocols. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

Ancient connections among the European rivers and watersheds revealed from the evolutionary history of the genus Telestes (Actinopterygii; Cypriniformes).

PubMed

Buj, Ivana; Marčić, Zoran; Ćaleta, Marko; Šanda, Radek; Geiger, Matthias F; Freyhof, Jörg; Machordom, Annie; Vukić, Jasna

2017-01-01

In order to better understand the complex geologic history of the Mediterranean area, we have analysed evolutionary history, phylogeographic structure and molecular diversity of freshwater fishes belonging to the genus Telestes. As primary freshwater fishes distributed largely in the Mediterranean basin, this genus represents a suitable model system for investigating the historical biogeography of freshwater drainage systems in southern Europe. In this investigation we have included samples representing all Telestes species and based our analyses on one mitochondrial and one nuclear gene. We have investigated phylogenetic structure inside the genus Telestes, estimated divergence times, reconstructed ancestral distribution ranges and described intraspecific molecular diversity. Diversification of Telestes started in the Early Miocene, when the ancestors of T. souffia, lineage comprising T. croaticus and T. fontinalis, and the one comprising T. pleurobipunctatus and T. beoticus got isolated. The remaining species are genetically more closely related and form a common cluster in the recovered phylogenetic trees. Complex geological history of southern Europe, including formation of continental bridges, fragmentation of landmass, closing of the sea corridor, local tectonic activities, led to complicated biogeographical pattern of this genus, caused by multiple colonization events and passovers between ancient rivers and water basins. Especially pronounced diversity of Telestes found in the Adriatic watershed in Croatia and Bosnia and Herzegovina is a consequence of a triple colonization of this area by different lineages, which led to an existence of genetically distinct species in neighboring areas. Significant intraspecific structuring is present in T. souffia, T. muticellus, T. croaticus and T. pleurobipunctatus. Besides in well-structured species, elevated levels of genetic polymorphism were found inside T. turskyi and T. ukliva, as a consequence of their old origin and unconstrained evolutionary history.

Microsatellite Marker Analysis Reveals the Complex Phylogeographic History of Rhododendron ferrugineum (Ericaceae) in the Pyrenees

PubMed Central

Charrier, Olivia; Dupont, Pierre; Pornon, André; Escaravage, Nathalie

2014-01-01

Genetic variation within plant species is determined by a number of factors such as reproductive mode, breeding system, life history traits and climatic events. In alpine regions, plants experience heterogenic abiotic conditions that influence the population's genetic structure. The aim of this study was to investigate the genetic structure and phylogeographic history of the subalpine shrub Rhododendron ferrugineum across the Pyrenees and the links between the populations in the Pyrenees, the Alps and Jura Mountains. We used 27 microsatellite markers to genotype 645 samples from 29 Pyrenean populations, three from the Alps and one from the Jura Mountains. These data were used to estimate population genetics statistics such as allelic richness, observed heterozygosity, expected heterozygosity, fixation index, inbreeding coefficient and number of migrants. Genetic diversity was found to be higher in the Alps than in the Pyrenees suggesting colonization waves from the Alps to the Pyrenees. Two separate genetic lineages were found in both the Alps and Pyrenees, with a substructure of five genetic clusters in the Pyrenees where a loss of genetic diversity was noted. The strong differentiation among clusters is maintained by low gene flow across populations. Moreover, some populations showed higher genetic diversity than others and presented rare alleles that may indicate the presence of alpine refugia. Two lineages of R. ferrugineum have colonized the Pyrenees from the Alps. Then, during glaciation events R. ferrugineum survived in the Pyrenees in different refugia such as lowland refugia at the eastern part of the chain and nunataks at high elevations leading to a clustered genetic pattern. PMID:24667824

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

PubMed Central

Kendler, Kenneth S.; Hitzemann, Robert J.

2012-01-01

A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data. PMID:21910077

Population structure and landscape genetics of two endangered frog species of genus Odorrana: different scenarios on two islands

PubMed Central

Igawa, T; Oumi, S; Katsuren, S; Sumida, M

2013-01-01

Isolation by distance and landscape connectivity are fundamental factors underlying speciation and evolution. To understand how landscapes affect gene flow and shape population structures, island species provide intrinsic study objects. We investigated the effects of landscapes on the population structure of the endangered frog species, Odorrana ishikawae and O. splendida, which each inhabit an island in southwest Japan. This was done by examining population structure, gene flow and demographic history of each species by analyzing 12 microsatellite loci and exploring causal environmental factors through ecological niche modeling (ENM) and the cost-distance approach. Our results revealed that the limited gene flow and multiple-population structure in O. splendida and the single-population structure in O. ishikawae were maintained after divergence of the species through ancient vicariance between islands. We found that genetic distance correlated with geographic distance between populations of both species. Our landscape genetic analysis revealed that the connectivity of suitable habitats influences gene flow and leads to the formation of specific population structures. In particular, different degrees of topographical complexity between islands are the major determining factor for shaping contrasting population structures of two species. In conclusion, our results illustrate the diversification mechanism of organisms through the interaction with space and environment. Our results also present an ENM approach for identifying the key factors affecting demographic history and population structures of target species, especially endangered species. PMID:22990312

Hybridization and differential introgression associated with environmental shifts in a mistletoe species complex.

PubMed

Baena-Díaz, Fernanda; Ramírez-Barahona, Santiago; Ornelas, Juan Francisco

2018-04-03

Host specialization after host shifting is traditionally viewed as the pathway to speciation in parasitic plants. However, geographical and environmental changes can also influence parasite speciation, through hybridization processes. Here we investigated the impact of past climatic fluctuations, environment, and host shifts on the genetic structure and patterns of hybridization and gene flow between Psittacanthus calyculatus and P. schiedeanus, a Mesoamerican species complex. Using microsatellites (408 individuals), we document moderate genetic diversity but high genetic differentiation between widespread parental clusters, calyculatus in dry pine-oak forests and schiedeanus in cloud forests. Bayesian analyses identified a third cluster, with admixture between parental clusters in areas of xeric and tropical dry forests and high levels of migration rates following secondary contact. Coincidently host associations in these areas differ from those in areas of parental species, suggesting that past hybridization played a role in environmental and host shifts. Overall, the observed genetic and geographic patterns suggest that these Psittacanthus populations could have entered a distinct evolutionary pathway. The results provide evidence for highlights on the importance of the Pleistocene climate changes, habitat differences, and potential host shifts in the evolutionary history of Neotropical mistletoes.

Looking Beyond the Genes: The Interplay Between Signaling Pathways and Mechanics in the Shaping and Diversification of Epithelial Tissues.

PubMed

Urdy, S; Goudemand, N; Pantalacci, S

2016-01-01

The core of Evo-Devo lies in the intuition that the way tissues grow during embryonic development, the way they sustain their structure and function throughout lifetime, and the way they evolve are closely linked. Epithelial tissues are ubiquitous in metazoans, covering the gut and internal branched organs, as well as the skin and its derivatives (ie, teeth). Here, we discuss in vitro, in vivo, and in silico studies on epithelial tissues to illustrate the conserved, dynamical, and complex aspects of their development. We then explore the implications of the dynamical and nonlinear nature of development on the evolution of their size and shape at the phenotypic and genetic levels. In rare cases, when the interplay between signaling and mechanics is well understood at the cell level, it is becoming clear that the structure of development leads to covariation of characters, an integration which in turn provides some predictable structure to evolutionary changes. We suggest that such nonlinear systems are prone to genetic drift, cryptic genetic variation, and context-dependent mutational effects. We argue that experimental and theoretical studies at the cell level are critical to our understanding of the phenotypic and genetic evolution of epithelial tissues, including carcinomas. © 2016 Elsevier Inc. All rights reserved.

Phylogeography of the reticulated python (Malayopython reticulatus ssp.): Conservation implications for the worlds' most traded snake species.

PubMed

Murray-Dickson, Gillian; Ghazali, Muhammad; Ogden, Rob; Brown, Rafe; Auliya, Mark

2017-01-01

As an important economic natural resource in Southeast Asia, reticulated pythons (Malayopython reticulatus ssp.) are primarily harvested from the wild for their skins-which are prized in the luxury leather goods industry. Trade dynamics of this CITES Appendix II listed species are complex and management approaches on the country or regional level appear obscure. Little is known about the actual geographic point-of-harvest of snakes, how genetic diversity is partitioned across the species range, how current harvest levels may affect the genetic viability of populations, and whether genetic structure could (or should) be accounted for when managing harvest quotas. As an initial survey, we use mitochondrial sequence data to define the broad-scale geographic structure of genetic diversity across a significant portion of the reticulated python's native range. Preliminary results reveal: (1) prominent phylogenetic structure across populations east and west of Huxley's modification of Wallace's line. Thirty-four haplotypes were apportioned across two geographically distinct groups, estimated to be moderately (5.2%); (2) Philippine, Bornean and Sulawesian populations appear to cluster distinctly; (3) individuals from Ambon Island suggest recent human introduction. Malayopython reticulatus is currently managed as a single taxonomic unit across Southeast Asia yet these initial results may justify special management considerations of the Philippine populations as a phylogenetically distinct unit, that warrants further examination. In Indonesia, genetic structure does not conform tightly to political boundaries and therefore we advocate the precautionary designation and use of Evolutionary Significant Units within Malayopython reticulatus, to inform and guide regional adaptive management plans.

Phylogeography of the reticulated python (Malayopython reticulatus ssp.): Conservation implications for the worlds’ most traded snake species

PubMed Central

Ghazali, Muhammad; Ogden, Rob; Brown, Rafe; Auliya, Mark

2017-01-01

As an important economic natural resource in Southeast Asia, reticulated pythons (Malayopython reticulatus ssp.) are primarily harvested from the wild for their skins—which are prized in the luxury leather goods industry. Trade dynamics of this CITES Appendix II listed species are complex and management approaches on the country or regional level appear obscure. Little is known about the actual geographic point-of-harvest of snakes, how genetic diversity is partitioned across the species range, how current harvest levels may affect the genetic viability of populations, and whether genetic structure could (or should) be accounted for when managing harvest quotas. As an initial survey, we use mitochondrial sequence data to define the broad-scale geographic structure of genetic diversity across a significant portion of the reticulated python’s native range. Preliminary results reveal: (1) prominent phylogenetic structure across populations east and west of Huxley’s modification of Wallace’s line. Thirty-four haplotypes were apportioned across two geographically distinct groups, estimated to be moderately (5.2%); (2) Philippine, Bornean and Sulawesian populations appear to cluster distinctly; (3) individuals from Ambon Island suggest recent human introduction. Malayopython reticulatus is currently managed as a single taxonomic unit across Southeast Asia yet these initial results may justify special management considerations of the Philippine populations as a phylogenetically distinct unit, that warrants further examination. In Indonesia, genetic structure does not conform tightly to political boundaries and therefore we advocate the precautionary designation and use of Evolutionary Significant Units within Malayopython reticulatus, to inform and guide regional adaptive management plans. PMID:28817588

Why genes don't count (for racial differences in health).

PubMed Central

Goodman, A H

2000-01-01

There is a paradoxical relationship between "race" and genetics. Whereas genetic data were first used to prove the validity of race, since the early 1970s they have been used to illustrate the invalidity of biological races. Indeed, race does not account for human genetic variation, which is continuous, complexly structured, constantly changing, and predominantly within "races." Despite the disproof of race-as-biology, genetic variation continues to be used to explain racial differences. Such explanations require the acceptance of 2 disproved assumptions: that genetic variation explains variation in disease and that genetic variation explains racial variation in disease. While the former is a form of geneticization, the notion that genes are the primary determinants of biology and behavior, the latter represents a form of racialization, an exaggeration of the salience of race. Using race as a proxy for genetic differences limits understandings of the complex interactions among political-economic processes, lived experiences, and human biologies. By moving beyond studies of racialized genetics, we can clarify the processes by which varied and interwoven forms of racialization and racism affect individuals "under the skin." PMID:11076233

Why genes don't count (for racial differences in health).

PubMed

Goodman, A H

2000-11-01

There is a paradoxical relationship between "race" and genetics. Whereas genetic data were first used to prove the validity of race, since the early 1970s they have been used to illustrate the invalidity of biological races. Indeed, race does not account for human genetic variation, which is continuous, complexly structured, constantly changing, and predominantly within "races." Despite the disproof of race-as-biology, genetic variation continues to be used to explain racial differences. Such explanations require the acceptance of 2 disproved assumptions: that genetic variation explains variation in disease and that genetic variation explains racial variation in disease. While the former is a form of geneticization, the notion that genes are the primary determinants of biology and behavior, the latter represents a form of racialization, an exaggeration of the salience of race. Using race as a proxy for genetic differences limits understandings of the complex interactions among political-economic processes, lived experiences, and human biologies. By moving beyond studies of racialized genetics, we can clarify the processes by which varied and interwoven forms of racialization and racism affect individuals "under the skin."

Biomechanical cell regulatory networks as complex adaptive systems in relation to cancer.

PubMed

Feller, Liviu; Khammissa, Razia Abdool Gafaar; Lemmer, Johan

2017-01-01

Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis. Some of the non-genetic factors that may also favour cancerization are dysregulation in epithelial-mesenchymal interactions, in cell-to-cell communication, in extracellular matrix turnover, in extracellular matrix-to-cell interactions and in mechanotransduction pathways. Persistent increase in extracellular matrix stiffness, for whatever reason, has been shown to play an important role in cell transformation, and later in cancer cell invasion. In this article we review certain cell regulatory networks driving carcinogenesis, focussing on the role of mechanical stresses modulating structure and function of cells and their extracellular matrices.

The Major Histocompatibility Complex and Autism Spectrum Disorder

PubMed Central

Needleman, Leigh A.; McAllister, A. Kimberley

2015-01-01

Autism spectrum disorder (ASD) is a complex disorder that appears to be caused by interactions between genetic changes and environmental insults during early development. A wide range of factors have been linked to the onset of ASD, but recently both genetic associations and environmental factors point to a central role for immune- related genes and immune responses to environmental stimuli. Specifically, many of the proteins encoded by the major histocompatibility complex (MHC) play a vital role in the formation, refinement, maintenance, and plasticity of the brain. Manipulations of levels of MHC molecules have illustrated how disrupted MHC signaling can significantly alter brain connectivity and function. Thus, an emerging hypothesis in our field is that disruptions in MHC expression in the developing brain caused by mutations and/or immune dysregulation may contribute to the altered brain connectivity and function characteristic of ASD. This review provides an overview of the structure and function of the three classes of MHC molecules in the immune system, healthy brain, and their possible involvement in ASD. PMID:22760919

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.

Phenotypic Variation among Culex pipiens Complex (Diptera: Culicidae) Populations from the Sacramento Valley, California: Horizontal and Vertical Transmission of West Nile Virus, Diapause Potential, Autogeny, and Host Selection

PubMed Central

Nelms, Brittany M.; Kothera, Linda; Thiemann, Tara; Macedo, Paula A.; Savage, Harry M.; Reisen, William K.

2013-01-01

The vector competence and bionomics of Culex pipiens form pipiens L. and Cx. pipiens f. molestus Forskäl were evaluated for populations from the Sacramento Valley. Both f. pipiens and f. molestus females became infected, produced disseminated infections, and were able to transmit West Nile virus. Form molestus females also transmitted West Nile virus vertically to egg rafts and F1 progeny, whereas f. pipiens females only transmitted to egg rafts. Culex pipiens complex from urban Sacramento blood-fed on seven different avian species and two mammalian species. Structure analysis of blood-fed mosquitoes identified K = 4 genetic clusters: f. molestus, f. pipiens, a group of genetically similar hybrids (Cluster X), and admixed individuals. When females were exposed as larvae to midwinter conditions in bioenvironmental chambers, 85% (N = 79) of aboveground Cx. pipiens complex females and 100% (N = 34) of underground f. molestus females did not enter reproductive diapause. PMID:24043690

Genetic variability in the Guahibo population from Venezuela.

PubMed

Moral, Pedro; Marini, Elisabetta; Esteban, Esther; Mameli, Giuseppa Elisa; Succa, Valeria; Vona, Giuseppe

2002-01-01

Four communities from Guahibo of Venezuela were analyzed for the genetic variants of nine erythrocyte enzymes and five serum proteins. Of the 14 loci determined, four were monomorphic. Significant frequency differentiation among communities, was present for ESD and TF markers. In general, Guahibo allele frequencies are in the variation ranges described for South American groups. The analysis indicates a relatively higher affinity of Guahibos with other Venezuelan groups within an irregular pattern of genetic distances that are likely related to the complex demographic history of the South American groups. Genetic diversity estimates reveal a moderate degree of genetic structure between the four Guahibo communities. This intra-tribal variability in Guahibo appears to be lower than in Venezuelan Piaroa but higher than in other Amerindians and could be attributed to a combined effect of low population size and relative isolation of communities. At a continental level, the distribution of genetic diversity is consistent with preferential population movements along the eastern and western coastal areas.

Domestication to Crop Improvement: Genetic Resources for Sorghum and Saccharum (Andropogoneae)

PubMed Central

Dillon, Sally L.; Shapter, Frances M.; Henry, Robert J.; Cordeiro, Giovanni; Izquierdo, Liz; Lee, L. Slade

2007-01-01

Background Both sorghum (Sorghum bicolor) and sugarcane (Saccharum officinarum) are members of the Andropogoneae tribe in the Poaceae and are each other's closest relatives amongst cultivated plants. Both are relatively recent domesticates and comparatively little of the genetic potential of these taxa and their wild relatives has been captured by breeding programmes to date. This review assesses the genetic gains made by plant breeders since domestication and the progress in the characterization of genetic resources and their utilization in crop improvement for these two related species. Genetic Resources The genome of sorghum has recently been sequenced providing a great boost to our knowledge of the evolution of grass genomes and the wealth of diversity within S. bicolor taxa. Molecular analysis of the Sorghum genus has identified close relatives of S. bicolor with novel traits, endosperm structure and composition that may be used to expand the cultivated gene pool. Mutant populations (including TILLING populations) provide a useful addition to genetic resources for this species. Sugarcane is a complex polyploid with a large and variable number of copies of each gene. The wild relatives of sugarcane represent a reservoir of genetic diversity for use in sugarcane improvement. Techniques for quantitative molecular analysis of gene or allele copy number in this genetically complex crop have been developed. SNP discovery and mapping in sugarcane has been advanced by the development of high-throughput techniques for ecoTILLING in sugarcane. Genetic linkage maps of the sugarcane genome are being improved for use in breeding selection. The improvement of both sorghum and sugarcane will be accelerated by the incorporation of more diverse germplasm into the domesticated gene pools using molecular tools and the improved knowledge of these genomes. PMID:17766842

Evolution of complex dynamics

NASA Astrophysics Data System (ADS)

Wilds, Roy; Kauffman, Stuart A.; Glass, Leon

2008-09-01

We study the evolution of complex dynamics in a model of a genetic regulatory network. The fitness is associated with the topological entropy in a class of piecewise linear equations, and the mutations are associated with changes in the logical structure of the network. We compare hill climbing evolution, in which only mutations that increase the fitness are allowed, with neutral evolution, in which mutations that leave the fitness unchanged are allowed. The simple structure of the fitness landscape enables us to estimate analytically the rates of hill climbing and neutral evolution. In this model, allowing neutral mutations accelerates the rate of evolutionary advancement for low mutation frequencies. These results are applicable to evolution in natural and technological systems.

Global search in photoelectron diffraction structure determination using genetic algorithms

NASA Astrophysics Data System (ADS)

Viana, M. L.; Díez Muiño, R.; Soares, E. A.; Van Hove, M. A.; de Carvalho, V. E.

2007-11-01

Photoelectron diffraction (PED) is an experimental technique widely used to perform structural determinations of solid surfaces. Similarly to low-energy electron diffraction (LEED), structural determination by PED requires a fitting procedure between the experimental intensities and theoretical results obtained through simulations. Multiple scattering has been shown to be an effective approach for making such simulations. The quality of the fit can be quantified through the so-called R-factor. Therefore, the fitting procedure is, indeed, an R-factor minimization problem. However, the topography of the R-factor as a function of the structural and non-structural surface parameters to be determined is complex, and the task of finding the global minimum becomes tough, particularly for complex structures in which many parameters have to be adjusted. In this work we investigate the applicability of the genetic algorithm (GA) global optimization method to this problem. The GA is based on the evolution of species, and makes use of concepts such as crossover, elitism and mutation to perform the search. We show results of its application in the structural determination of three different systems: the Cu(111) surface through the use of energy-scanned experimental curves; the Ag(110)-c(2 × 2)-Sb system, in which a theory-theory fit was performed; and the Ag(111) surface for which angle-scanned experimental curves were used. We conclude that the GA is a highly efficient method to search for global minima in the optimization of the parameters that best fit the experimental photoelectron diffraction intensities to the theoretical ones.

DXS10011: studies on structure, allele distribution in three populations and genetic linkage to further q-telomeric chromosome X markers.

PubMed

Hering, Sandra; Brundirs, Nicola; Kuhlisch, Eberhard; Edelmann, Jeanett; Plate, Ines; Benecke, Mark; Van, Pham Hung; Michael, Matthias; Szibor, Reinhard

2004-12-01

The hypervariable tetranucleotide STR polymorphism DXS10011 is a powerful marker for forensic purposes. Investigation of this STR led to an allele nomenclature which is in consensus with the ISFG recommendations. DXS10011 is located at Xq28 and genetically closely linked to DXS7423 and DXS8377 but is unlinked to HPRTB and more distant X-chromosomal STRs. DXS10011 is a very complex marker exhibiting some structural variants within alleles of identical length. Two types of repeat structure (regular and inter-alleles) are known and described as types A and B. Two SNPs which are in strong linkage disequilibrium to the different sequence types were found in the repeat flanking region. The type A sequence consists of a long stretch of uninterrupted homogenous repeats which is highly susceptible to slippage mutation during male meiosis.

Use of modern tomato breeding germplasm for deciphering the genetic control of agronomical traits by Genome Wide Association study.

PubMed

Bauchet, Guillaume; Grenier, Stéphane; Samson, Nicolas; Bonnet, Julien; Grivet, Laurent; Causse, Mathilde

2017-05-01

A panel of 300 tomato accessions including breeding materials was built and characterized with >11,000 SNP. A population structure in six subgroups was identified. Strong heterogeneity in linkage disequilibrium and recombination landscape among groups and chromosomes was shown. GWAS identified several associations for fruit weight, earliness and plant growth. Genome-wide association studies (GWAS) have become a method of choice in quantitative trait dissection. First limited to highly polymorphic and outcrossing species, it is now applied in horticultural crops, notably in tomato. Until now GWAS in tomato has been performed on panels of heirloom and wild accessions. Using modern breeding materials would be of direct interest for breeding purpose. To implement GWAS on a large panel of 300 tomato accessions including 168 breeding lines, this study assessed the genetic diversity and linkage disequilibrium decay and revealed the population structure and performed GWA experiment. Genetic diversity and population structure analyses were based on molecular markers (>11,000 SNP) covering the whole genome. Six genetic subgroups were revealed and associated to traits of agronomical interest, such as fruit weight and disease resistance. Estimates of linkage disequilibrium highlighted the heterogeneity of its decay among genetic subgroups. Haplotype definition allowed a fine characterization of the groups and their recombination landscape revealing the patterns of admixture along the genome. Selection footprints showed results in congruence with introgressions. Taken together, all these elements refined our knowledge of the genetic material included in this panel and allowed the identification of several associations for fruit weight, plant growth and earliness, deciphering the genetic architecture of these complex traits and identifying several new loci useful for tomato breeding.

Genetic structuring, dispersal and taxonomy of the high-alpine populations of the Geranium arabicum/kilimandscharicum complex in tropical eastern Africa

PubMed Central

Gizaw, Abel; Tusiime, Felly M.; Masao, Catherine A.; Abdi, Ahmed A.; Hou, Yan; Nemomissa, Sileshi; Brochmann, Christian

2017-01-01

The scattered eastern African high mountains harbor a renowned and highly endemic flora, but the taxonomy and phylogeographic history of many plant groups are still insufficiently known. The high-alpine populations of the Geranium arabicum/kilimandscharicum complex present intricate morphological variation and have recently been suggested to comprise two new endemic taxa. Here we aim to contribute to a clarification of the taxonomy of these populations by analyzing genetic (AFLP) variation in range-wide high-alpine samples, and we address whether hybridization has contributed to taxonomic problems. We identified only two genetic groups. One corresponded to G. kilimandscharicum, which has been reported as exclusively high-alpine and confined to the eastern Rift mountains in East Africa. The other corresponded to G. arabicum, reported from lower altitudes on the same mountains as well as from a wide altitudinal span in Ethiopia and on the western Rift mountains in East Africa. The four populations analyzed of a recently described species from the Bale Mts in Ethiopia were admixed, indicating that they result from recent long-distance dispersal of G. kilimandscharicum from East Africa followed by hybridization with local G. arabicum in naturally disturbed habitats. Some admixture between the two genetic groups was also inferred on other mountains, supporting earlier suggestions of introgression based on morphology. We did not find support for recognition of the recently suggested new subspecies of G. arabicum in Ethiopia. Interestingly, the high-alpine G. kilimandscharicum lacked clear geographic structuring, suggesting a recent history of colonization of the different mountains or extensive intermountain gene flow. PMID:28552970

The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

PubMed Central

Magalhães da Silva, Thiago; Sandhya Rani, M R; de Oliveira Costa, Gustavo Nunes; Figueiredo, Maria A; Melo, Paulo S; Nascimento, João F; Molyneaux, Neil D; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória; Blanton, Ronald E

2015-01-01

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry. PMID:25293718

Genetic structure of Micromeria (Lamiaceae) in Tenerife, the imprint of geological history and hybridization on within-island diversification.

PubMed

Puppo, Pamela; Curto, Manuel; Meimberg, Harald

2016-06-01

Geological history of oceanic islands can have a profound effect on the evolutionary history of insular flora, especially in complex islands such as Tenerife in the Canary Islands. Tenerife results from the secondary connection of three paleo-islands by a central volcano, and other geological events that further shaped it. This geological history has been shown to influence the phylogenetic history of several taxa, including genus Micromeria (Lamiaceae). Screening 15 microsatellite markers in 289 individuals representing the eight species of Micromeria present in Tenerife, this study aims to assess the genetic diversity and structure of these species and its relation with the geological events on the island. In addition, we evaluate the extent of hybridization among species and discuss its influence on the speciation process. We found that the species restricted to the paleo-islands present lower levels of genetic diversity but the highest levels of genetic differentiation suggesting that their ranges might have contracted over time. The two most widespread species in the island, M. hyssopifolia and M. varia , present the highest genetic diversity levels and a genetic structure that seems correlated with the geological composition of the island. Samples from M. hyssopifolia from the oldest paleo-island, Adeje, appear as distinct while samples from M. varia segregate into two main clusters corresponding to the paleo-islands of Anaga and Teno. Evidence of hybridization and intraspecific migration between species was found. We argue that species boundaries would be retained despite hybridization in response to the habitat's specific conditions causing postzygotic isolation and preserving morphological differentiation.

Anonymous nuclear markers reveal taxonomic incongruence and long-term disjunction in a cactus species complex with continental-island distribution in South America.

PubMed

Perez, Manolo F; Carstens, Bryan C; Rodrigues, Gustavo L; Moraes, Evandro M

2016-02-01

The Pilosocereus aurisetus complex consists of eight cactus species with a fragmented distribution associated to xeric enclaves within the Cerrado biome in eastern South America. The phylogeny of these species is incompletely resolved, and this instability complicates evolutionary analyses. Previous analyses based on both plastid and microsatellite markers suggested that this complex contained species with inherent phylogeographic structure, which was attributed to recent diversification and recurring range shifts. However, limitations of the molecular markers used in these analyses prevented some questions from being properly addressed. In order to better understand the relationship among these species and make a preliminary assessment of the genetic structure within them, we developed anonymous nuclear loci from pyrosequencing data of 40 individuals from four species in the P. aurisetus complex. The data obtained from these loci were used to identify genetic clusters within species, and to investigate the phylogenetic relationship among these inferred clusters using a species tree methodology. Coupled with a palaeodistributional modelling, our results reveal a deep phylogenetic and climatic disjunction between two geographic lineages. Our results highlight the importance of sampling more regions from the genome to gain better insights on the evolution of species with an intricate evolutionary history. The methodology used here provides a feasible approach to develop numerous genealogical molecular markers throughout the genome for non-model species. These data provide a more robust hypothesis for the relationship among the lineages of the P. aurisetus complex. Copyright © 2015 Elsevier Inc. All rights reserved.

Complete nucleotide sequence of the Oenothera elata plastid chromosome, representing plastome I of the five distinguishable euoenothera plastomes.

PubMed

Hupfer, H; Swiatek, M; Hornung, S; Herrmann, R G; Maier, R M; Chiu, W L; Sears, B

2000-05-01

We describe the 159,443-bp [corrected] sequence of the plastid chromosome of Oenothera elata (evening primrose). The Oe. elata plastid chromosome represents type I of the five genetically distinguishable basic plastomes found in the subsection Euoenothera. The genus Oenothera provides an ideal system in which to address fundamental questions regarding the functional integration of the compartmentalised genetic system characteristic of the eukaryotic cell. Its highly developed taxonomy and genetics, together with a favourable combination of features in its genetic structure (interspecific fertility, stable heterozygous progeny, biparental transmission of organelles, and the phenomenon of complex heterozygosity), allow facile exchanges of nuclei, plastids and mitochondria, as well as individual chromosome pairs, between species. The resulting hybrids or cybrids are usually viable and fertile, but can display various forms of developmental disturbance.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structure solution of DNA-binding proteins and complexes with ARCIMBOLDO libraries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pröpper, Kevin; Instituto de Biologia Molecular de Barcelona; Meindl, Kathrin

2014-06-01

The structure solution of DNA-binding protein structures and complexes based on the combination of location of DNA-binding protein motif fragments with density modification in a multi-solution frame is described. Protein–DNA interactions play a major role in all aspects of genetic activity within an organism, such as transcription, packaging, rearrangement, replication and repair. The molecular detail of protein–DNA interactions can be best visualized through crystallography, and structures emphasizing insight into the principles of binding and base-sequence recognition are essential to understanding the subtleties of the underlying mechanisms. An increasing number of high-quality DNA-binding protein structure determinations have been witnessed despite themore » fact that the crystallographic particularities of nucleic acids tend to pose specific challenges to methods primarily developed for proteins. Crystallographic structure solution of protein–DNA complexes therefore remains a challenging area that is in need of optimized experimental and computational methods. The potential of the structure-solution program ARCIMBOLDO for the solution of protein–DNA complexes has therefore been assessed. The method is based on the combination of locating small, very accurate fragments using the program Phaser and density modification with the program SHELXE. Whereas for typical proteins main-chain α-helices provide the ideal, almost ubiquitous, small fragments to start searches, in the case of DNA complexes the binding motifs and DNA double helix constitute suitable search fragments. The aim of this work is to provide an effective library of search fragments as well as to determine the optimal ARCIMBOLDO strategy for the solution of this class of structures.« less

Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

PubMed

Sithaldeen, Riashna; Ackermann, Rebecca Rogers; Bishop, Jacqueline M

2015-01-01

Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp.) supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef) through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

Evolution of the Plant Reproduction Master Regulators LFY and the MADS Transcription Factors: The Role of Protein Structure in the Evolutionary Development of the Flower

PubMed Central

Silva, Catarina S.; Puranik, Sriharsha; Round, Adam; Brennich, Martha; Jourdain, Agnès; Parcy, François; Hugouvieux, Veronique; Zubieta, Chloe

2016-01-01

Understanding the evolutionary leap from non-flowering (gymnosperms) to flowering (angiosperms) plants and the origin and vast diversification of the floral form has been one of the focuses of plant evolutionary developmental biology. The evolving diversity and increasing complexity of organisms is often due to relatively small changes in genes that direct development. These “developmental control genes” and the transcription factors (TFs) they encode, are at the origin of most morphological changes. TFs such as LEAFY (LFY) and the MADS-domain TFs act as central regulators in key developmental processes of plant reproduction including the floral transition in angiosperms and the specification of the male and female organs in both gymnosperms and angiosperms. In addition to advances in genome wide profiling and forward and reverse genetic screening, structural techniques are becoming important tools in unraveling TF function by providing atomic and molecular level information that was lacking in purely genetic approaches. Here, we summarize previous structural work and present additional biophysical and biochemical studies of the key master regulators of plant reproduction – LEAFY and the MADS-domain TFs SEPALLATA3 and AGAMOUS. We discuss the impact of structural biology on our understanding of the complex evolutionary process leading to the development of the bisexual flower. PMID:26779227

Capturing neutral and adaptive genetic diversity for conservation in a highly structured tree species.

PubMed

Rodríguez-Quilón, Isabel; Santos-Del-Blanco, Luis; Serra-Varela, María Jesús; Koskela, Jarkko; González-Martínez, Santiago C; Alía, Ricardo

2016-10-01

Preserving intraspecific genetic diversity is essential for long-term forest sustainability in a climate change scenario. Despite that, genetic information is largely neglected in conservation planning, and how conservation units should be defined is still heatedly debated. Here, we use maritime pine (Pinus pinaster Ait.), an outcrossing long-lived tree with a highly fragmented distribution in the Mediterranean biodiversity hotspot, to prove the importance of accounting for genetic variation, of both neutral molecular markers and quantitative traits, to define useful conservation units. Six gene pools associated to distinct evolutionary histories were identified within the species using 12 microsatellites and 266 single nucleotide polymorphisms (SNPs). In addition, height and survival standing variation, their genetic control, and plasticity were assessed in a multisite clonal common garden experiment (16 544 trees). We found high levels of quantitative genetic differentiation within previously defined neutral gene pools. Subsequent cluster analysis and post hoc trait distribution comparisons allowed us to define 10 genetically homogeneous population groups with high evolutionary potential. They constitute the minimum number of units to be represented in a maritime pine dynamic conservation program. Our results uphold that the identification of conservation units below the species level should account for key neutral and adaptive components of genetic diversity, especially in species with strong population structure and complex evolutionary histories. The environmental zonation approach currently used by the pan-European genetic conservation strategy for forest trees would be largely improved by gradually integrating molecular and quantitative trait information, as data become available. © 2016 by the Ecological Society of America.

The group II intron maturase: a reverse transcriptase and splicing factor go hand in hand.

PubMed

Zhao, Chen; Pyle, Anna Marie

2017-12-01

The splicing of group II introns in vivo requires the assistance of a multifunctional intron encoded protein (IEP, or maturase). Each IEP is also a reverse-transcriptase enzyme that enables group II introns to behave as mobile genetic elements. During splicing or retro-transposition, each group II intron forms a tight, specific complex with its own encoded IEP, resulting in a highly reactive holoenzyme. This review focuses on the structural basis for IEP function, as revealed by recent crystal structures of an IEP reverse transcriptase domain and cryo-EM structures of an IEP-intron complex. These structures explain how the same IEP scaffold is utilized for intron recognition, splicing and reverse transcription, while providing a physical basis for understanding the evolutionary transformation of the IEP into the eukaryotic splicing factor Prp8. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario

PubMed Central

Gunz, Philipp; Bookstein, Fred L.; Mitteroecker, Philipp; Stadlmayr, Andrea; Seidler, Horst; Weber, Gerhard W.

2009-01-01

The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa. PMID:19307568

Postnatal brain development: Structural imaging of dynamic neurodevelopmental processes

PubMed Central

Jernigan, Terry L.; Baaré, William F. C.; Stiles, Joan; Madsen, Kathrine Skak

2013-01-01

After birth, there is striking biological and functional development of the brain’s fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain–behavior associations in children, including genetic variation, behavioral interventions, and hormonal variation associated with puberty. At present longitudinal studies are few, and we do not yet know how variability in individual trajectories of biological development in specific neural systems map onto similar variability in behavioral trajectories. PMID:21489384

Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

PubMed Central

Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

2015-01-01

Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

The "chicken-and-egg" development of political opinionsThe roles of genes, social status, ideology, and information.

PubMed

Peter, Beattie J D

2017-01-01

Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a "chicken-and-egg" question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.

Temporal genetic structure of a drone congregation area of the giant Asian honeybee ( Apis dorsata)

NASA Astrophysics Data System (ADS)

Kraus, F. B.; Koeniger, N.; Tingek, S.; Moritz, R. F. A.

2005-12-01

The giant Asian honeybee ( Apis dorsata), like all other members of the genus Apis, has a complex mating system in which the queens and males (drones) mate at spatially defined drone congregation areas (DCAs). Here, we studied the temporal genetic structure of a DCA of A. dorsata over an 8-day time window by the genotyping of sampled drones with microsatellite markers. Analysis of the genotypic data revealed a significant genetic differentiation between 3 sampling days and indicated that the DCA was used by at least two subpopulations at all days in varying proportions. The estimation of the number of colonies which used the DCA ranged between 20 and 40 colonies per subpopulation, depending on the estimation procedure and population. The overall effective population size was estimated as high as N e=140. The DCA seems to counteract known tendencies of A. dorsata for inbreeding within colony aggregations by facilitating gene flow among subpopulations and increasing the effective population size.

Consumers' Kansei Needs Clustering Method for Product Emotional Design Based on Numerical Design Structure Matrix and Genetic Algorithms.

PubMed

Yang, Yan-Pu; Chen, Deng-Kai; Gu, Rong; Gu, Yu-Feng; Yu, Sui-Huai

2016-01-01

Consumers' Kansei needs reflect their perception about a product and always consist of a large number of adjectives. Reducing the dimension complexity of these needs to extract primary words not only enables the target product to be explicitly positioned, but also provides a convenient design basis for designers engaging in design work. Accordingly, this study employs a numerical design structure matrix (NDSM) by parameterizing a conventional DSM and integrating genetic algorithms to find optimum Kansei clusters. A four-point scale method is applied to assign link weights of every two Kansei adjectives as values of cells when constructing an NDSM. Genetic algorithms are used to cluster the Kansei NDSM and find optimum clusters. Furthermore, the process of the proposed method is presented. The details of the proposed approach are illustrated using an example of electronic scooter for Kansei needs clustering. The case study reveals that the proposed method is promising for clustering Kansei needs adjectives in product emotional design.

Consumers' Kansei Needs Clustering Method for Product Emotional Design Based on Numerical Design Structure Matrix and Genetic Algorithms

PubMed Central

Chen, Deng-kai; Gu, Rong; Gu, Yu-feng; Yu, Sui-huai

2016-01-01

Consumers' Kansei needs reflect their perception about a product and always consist of a large number of adjectives. Reducing the dimension complexity of these needs to extract primary words not only enables the target product to be explicitly positioned, but also provides a convenient design basis for designers engaging in design work. Accordingly, this study employs a numerical design structure matrix (NDSM) by parameterizing a conventional DSM and integrating genetic algorithms to find optimum Kansei clusters. A four-point scale method is applied to assign link weights of every two Kansei adjectives as values of cells when constructing an NDSM. Genetic algorithms are used to cluster the Kansei NDSM and find optimum clusters. Furthermore, the process of the proposed method is presented. The details of the proposed approach are illustrated using an example of electronic scooter for Kansei needs clustering. The case study reveals that the proposed method is promising for clustering Kansei needs adjectives in product emotional design. PMID:27630709

Structure of the Cmr2 Subunit of the CRISPR-Cas RNA Silencing Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cocozaki, Alexis I.; Ramia, Nancy F.; Shao, Yaming

Cmr2 is the largest and an essential subunit of a CRISPR RNA-Cas protein complex (the Cmr complex) that cleaves foreign RNA to protect prokaryotes from invading genetic elements. Cmr2 is thought to be the catalytic subunit of the effector complex because of its N-terminal HD nuclease domain. Here, however, we report that the HD domain of Cmr2 is not required for cleavage by the complex in vitro. The 2.3 {angstrom} crystal structure of Pyrococcus furiosus Cmr2 (lacking the HD domain) reveals two adenylyl cyclase-like and two {alpha}-helical domains. The adenylyl cyclase-like domains are arranged as in homodimeric adenylyl cyclases andmore » bind ADP and divalent metals. However, mutagenesis studies show that the metal- and ADP-coordinating residues of Cmr2 are also not critical for cleavage by the complex. Our findings suggest that another component provides the catalytic function and that the essential role by Cmr2 does not require the identified ADP- or metal-binding or HD domains in vitro.« less

Population Genetics of Two Key Mosquito Vectors of Rift Valley Fever Virus Reveals New Insights into the Changing Disease Outbreak Patterns in Kenya

PubMed Central

Tchouassi, David P.; Bastos, Armanda D. S.; Sole, Catherine L.; Diallo, Mawlouth; Lutomiah, Joel; Mutisya, James; Mulwa, Francis; Borgemeister, Christian; Sang, Rosemary; Torto, Baldwyn

2014-01-01

Rift Valley fever (RVF) outbreaks in Kenya have increased in frequency and range to include northeastern Kenya where viruses are increasingly being isolated from known (Aedes mcintoshi) and newly-associated (Ae. ochraceus) vectors. The factors contributing to these changing outbreak patterns are unclear and the population genetic structure of key vectors and/or specific virus-vector associations, in particular, are under-studied. By conducting mitochondrial and nuclear DNA analyses on >220 Kenyan specimens of Ae. mcintoshi and Ae. ochraceus, we uncovered high levels of vector complexity which may partly explain the disease outbreak pattern. Results indicate that Ae. mcintoshi consists of a species complex with one of the member species being unique to the newly-established RVF outbreak-prone northeastern region of Kenya, whereas Ae. ochraceus is a homogeneous population that appears to be undergoing expansion. Characterization of specimens from a RVF-prone site in Senegal, where Ae. ochraceus is a primary vector, revealed direct genetic links between the two Ae. ochraceus populations from both countries. Our data strongly suggest that unlike Ae. mcintoshi, Ae. ochraceus appears to be a relatively recent, single 'introduction' into Kenya. These results, together with increasing isolations from this vector, indicate that Ae. ochraceus will likely be of greater epidemiological importance in future RVF outbreaks in Kenya. Furthermore, the overall vector complexity calls into question the feasibility of mosquito population control approaches reliant on genetic modification. PMID:25474018

Genetic tests in major psychiatric disorders-integrating molecular medicine with clinical psychiatry-why is it so difficult?

PubMed

Demkow, U; Wolańczyk, T

2017-06-13

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays' medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease.

Genetic tests in major psychiatric disorders—integrating molecular medicine with clinical psychiatry—why is it so difficult?

PubMed Central

Demkow, U; Wolańczyk, T

2017-01-01

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays’ medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease. PMID:28608853

Conservation and Divergence of Mediator Structure and Function: Insights from Plants.

PubMed

Dolan, Whitney L; Chapple, Clint

2017-01-01

The Mediator complex is a large, multisubunit, transcription co-regulator that is conserved across eukaryotes. Studies of the Arabidopsis Mediator complex and its subunits have shown that it functions in nearly every aspect of plant development and fitness. In addition to revealing mechanisms of regulation of plant-specific pathways, studies of plant Mediator complexes have the potential to shed light on the conservation and divergence of Mediator structure and function across Kingdoms and plant lineages. The majority of insights into plant Mediator function have come from Arabidopsis because it is the only plant from which Mediator has been purified and from which an array of Mediator mutants have been isolated by forward and reverse genetics. So far, these studies indicate that, despite low sequence similarity between many orthologous subunits, the overall structure and function of Mediator is well conserved between Kingdoms. Several studies have also expanded our knowledge of Mediator to other plant species, opening avenues of investigation into the role of Mediator in plant adaptation and fitness.

Pelagic Life and Depth: Coastal Physical Features in West Africa Shape the Genetic Structure of the Bonga Shad, Ethmalosa fimbriata

PubMed Central

Durand, Jean-Dominique; Guinand, Bruno; Dodson, Julian J.; Lecomte, Frédéric

2013-01-01

The bonga shad, Ethmalosa fimbriata, is a West African pelagic species still abundant in most habitats of its distribution range and thought to be only recently affected by anthropogenic pressure (habitat destruction or fishing pressure). Its presence in a wide range of coastal habitats characterised by different hydrodynamic processes, represents a case study useful for evaluating the importance of physical structure of the west African shoreline on the genetic structure of a small pelagic species. To investigate this question, the genetic diversity of E. fimbriata was assessed at both regional and species range scales, using mitochondrial (mt) and nuclear DNA markers. Whereas only three panmictic units were identified with mtDNA at the large spatial scale, nuclear genetic markers (EPIC: exon-primed intron-crossing) indicated a more complex genetic pattern at the regional scale. In the northern-most section of shad’s distribution range, up to 4 distinct units were identified. Bayesian inference as well as spatial autocorrelation methods provided evidence that gene flow is impeded by the presence of deep-water areas near the coastline (restricting the width of the coastal shelf), such as the Cap Timiris and the Kayar canyons in Mauritania and Senegal, respectively. The added discriminatory power provided by the use of EPIC markers proved to be essential to detect the influence of more subtle, contemporary processes (e.g. gene flow, barriers, etc.) acting within the glacial refuges identified previously by mtDNA. PMID:24130890

Genetic analysis across different spatial scales reveals multiple dispersal mechanisms for the invasive hydrozoan Cordylophora in the Great Lakes.

PubMed

Darling, John A; Folino-Rorem, Nadine C

2009-12-01

Discerning patterns of post-establishment spread by invasive species is critically important for the design of effective management strategies and the development of appropriate theoretical models predicting spatial expansion of introduced populations. The globally invasive colonial hydrozoan Cordylophora produces propagules both sexually and vegetatively and is associated with multiple potential dispersal mechanisms, making it a promising system to investigate complex patterns of population structure generated throughout the course of rapid range expansion. Here, we explore genetic patterns associated with the spread of this taxon within the North American Great Lakes basin. We collected intensively from eight harbours in the Chicago area in order to conduct detailed investigation of local population expansion. In addition, we collected from Lakes Michigan, Erie, and Ontario, as well as Lake Cayuga in the Finger Lakes of upstate New York in order to assess genetic structure on a regional scale. Based on data from eight highly polymorphic microsatellite loci we examined the spatial extent of clonal genotypes, assessed levels of neutral genetic diversity, and explored patterns of migration and dispersal at multiple spatial scales through assessment of population level genetic differentiation (pairwise F(ST) and factorial correspondence analysis), Bayesian inference of population structure, and assignment tests on individual genotypes. Results of these analyses indicate that Cordylophora populations in this region spread predominantly through sexually produced propagules, and that while limited natural larval dispersal can drive expansion locally, regional expansion likely relies on anthropogenic dispersal vectors.

Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen.

PubMed

Nir, Oaz; Bakal, Chris; Perrimon, Norbert; Berger, Bonnie

2010-03-01

Biological networks are highly complex systems, consisting largely of enzymes that act as molecular switches to activate/inhibit downstream targets via post-translational modification. Computational techniques have been developed to perform signaling network inference using some high-throughput data sources, such as those generated from transcriptional and proteomic studies, but comparable methods have not been developed to use high-content morphological data, which are emerging principally from large-scale RNAi screens, to these ends. Here, we describe a systematic computational framework based on a classification model for identifying genetic interactions using high-dimensional single-cell morphological data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila, and evaluate its efficacy. Augmented by knowledge of the basic structure of RhoGAP/GTPase signaling, namely, that GAPs act directly upstream of GTPases, we apply our framework for identifying genetic interactions to predict signaling relationships between these proteins. We find that our method makes mediocre predictions using only RhoGAP single-knockdown morphological data, yet achieves vastly improved accuracy by including original data from a double-knockdown RhoGAP genetic screen, which likely reflects the redundant network structure of RhoGAP/GTPase signaling. We consider other possible methods for inference and show that our primary model outperforms the alternatives. This work demonstrates the fundamental fact that high-throughput morphological data can be used in a systematic, successful fashion to identify genetic interactions and, using additional elementary knowledge of network structure, to infer signaling relations.

A quadratically regularized functional canonical correlation analysis for identifying the global structure of pleiotropy with NGS data

PubMed Central

Zhu, Yun; Fan, Ruzong; Xiong, Momiao

2017-01-01

Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore correlation information of genetic variants, effectively reduce data dimensions, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new statistic method referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the ten competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and ten other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the ten other statistics. PMID:29040274

Resolving complex phylogeographic patterns in the Balkan Peninsula using closely related wall-lizard species as a model system.

PubMed

Psonis, Nikolaos; Antoniou, Aglaia; Karameta, Emmanouela; Leaché, Adam D; Kotsakiozi, Panayiota; Darriba, Diego; Kozlov, Alexey; Stamatakis, Alexandros; Poursanidis, Dimitris; Kukushkin, Oleg; Jablonski, Daniel; Crnobrnja-Isailović, Jelka; Gherghel, Iulian; Lymberakis, Petros; Poulakakis, Nikos

2018-08-01

The Balkan Peninsula constitutes a biodiversity hotspot with high levels of species richness and endemism. The complex geological history of the Balkans in conjunction with the climate evolution are hypothesized as the main drivers generating this biodiversity. We investigated the phylogeography, historical demography, and population structure of closely related wall-lizard species from the Balkan Peninsula and southeastern Europe to better understand diversification processes of species with limited dispersal ability, from Late Miocene to the Holocene. We used several analytical methods integrating genome-wide SNPs (ddRADseq), microsatellites, mitochondrial and nuclear DNA data, as well as species distribution modelling. Phylogenomic analysis resulted in a completely resolved species level phylogeny, population level analyses confirmed the existence of at least two cryptic evolutionary lineages and extensive within species genetic structuring. Divergence time estimations indicated that the Messinian Salinity Crisis played a key role in shaping patterns of species divergence, whereas intraspecific genetic structuring was mainly driven by Pliocene tectonic events and Quaternary climatic oscillations. The present work highlights the effectiveness of utilizing multiple methods and data types coupled with extensive geographic sampling to uncover the evolutionary processes that shaped the species over space and time. Copyright © 2018 Elsevier Inc. All rights reserved.

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity

PubMed Central

Dendrou, Calliope A.; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G.; Attfield, Kathrine E.; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A.; Desel, Christiane; Faergeman, Soren L.; Cheeseman, Jane; Neville, Matt J.; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R.; Everett, Christine; Bell, John I.; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2017-01-01

Thousands of genetic variants have been identified that contribute to the development of complex diseases, but determining how to fully elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders, subsequent molecular, cellular, in vivo and structural functional follow-up and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for multiple autoimmune disorders. PMID:27807284

Advances in asthma and allergy genetics in 2007.

PubMed

Vercelli, Donata

2008-08-01

This review discusses the main advances in the genetics of asthma and allergy published in the Journal in 2007. The association studies discussed herein addressed 3 main topics: the effect of the environment and gene-environment interactions on asthma/allergy susceptibility, the contribution of T(H)2 immunity gene variants to allergic inflammation, and the role of filaggrin mutations in atopic dermatitis and associated phenotypes. Other articles revealed novel, potentially important candidate genes or confirmed known ones. Collectively, the works published in 2007 reiterate that allergy and asthma are typical complex diseases; that is, they are disorders in which intricate interactions among environmental and genetic factors modify disease susceptibility by altering the fundamental structural and functional properties of target organs at critical developmental windows.

Genetic Diversity of Human Pathogenic Members of the Fusarium oxysporum Complex Inferred from Multilocus DNA Sequence Data and Amplified Fragment Length Polymorphism Analyses: Evidence for the Recent Dispersion of a Geographically Widespread Clonal Lineage and Nosocomial Origin

PubMed Central

O'Donnell, Kerry; Sutton, Deanna A.; Rinaldi, Michael G.; Magnon, Karen C.; Cox, Patricia A.; Revankar, Sanjay G.; Sanche, Stephen; Geiser, David M.; Juba, Jean H.; van Burik, Jo-Anne H.; Padhye, Arvind; Anaissie, Elias J.; Francesconi, Andrea; Walsh, Thomas J.; Robinson, Jody S.

2004-01-01

Fusarium oxysporum is a phylogenetically diverse monophyletic complex of filamentous ascomycetous fungi that are responsible for localized and disseminated life-threatening opportunistic infections in immunocompetent and severely neutropenic patients, respectively. Although members of this complex were isolated from patients during a pseudoepidemic in San Antonio, Tex., and from patients and the water system in a Houston, Tex., hospital during the 1990s, little is known about their genetic relatedness and population structure. This study was conducted to investigate the global genetic diversity and population biology of a comprehensive set of clinically important members of the F. oxysporum complex, focusing on the 33 isolates from patients at the San Antonio hospital and on strains isolated in the United States from the water systems of geographically distant hospitals in Texas, Maryland, and Washington, which were suspected as reservoirs of nosocomial fusariosis. In all, 18 environmental isolates and 88 isolates from patients spanning four continents were genotyped. The major finding of this study, based on concordant results from phylogenetic analyses of multilocus DNA sequence data and amplified fragment length polymorphisms, is that a recently dispersed, geographically widespread clonal lineage is responsible for over 70% of all clinical isolates investigated, including all of those associated with the pseudoepidemic in San Antonio. Moreover, strains of the clonal lineage recovered from patients were conclusively shown to genetically match those isolated from the hospital water systems of three U.S. hospitals, providing support for the hypothesis that hospitals may serve as a reservoir for nosocomial fusarial infections. PMID:15528703

Advances in the genetically complex autoinflammatory diseases.

PubMed

Ombrello, Michael J

2015-07-01

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.

Speciation on the Rocks: Integrated Systematics of the Heteronotia spelea Species Complex (Gekkota; Reptilia) from Western and Central Australia

PubMed Central

Pepper, Mitzy; Doughty, Paul; Fujita, Matthew K.; Moritz, Craig; Keogh, J. Scott

2013-01-01

The isolated uplands of the Australian arid zone are known to provide mesic refuges in an otherwise xeric landscape, and divergent lineages of largely arid zone taxa have persisted in these regions following the onset of Miocene aridification. Geckos of the genus Heteronotia are one such group, and have been the subject of many genetic studies, including H. spelea, a strongly banded form that occurs in the uplands of the Pilbara and Central Ranges regions of the Australian arid zone. Here we assess the systematics of these geckos based on detailed examination of morphological and genetic variation. The H. spelea species complex is a monophyletic lineage to the exclusion of the H. binoei and H. planiceps species complexes. Within the H. spelea complex, our previous studies based on mtDNA and nine nDNA loci found populations from the Central Ranges to be genetically divergent from Pilbara populations. Here we supplement our published molecular data with additional data gathered from central Australian samples. In the spirit of integrative species delimitation, we combine multi-locus, coalescent-based lineage delimitation with extensive morphological analyses to test species boundaries, and we describe the central populations as a new species, H. fasciolatus sp. nov. In addition, within the Pilbara there is strong genetic evidence for three lineages corresponding to northeastern (type), southern, and a large-bodied melanic population isolated in the northwest. Due to its genetic distinctiveness and extreme morphological divergence from all other Heteronotia, we describe the melanic form as a new species, H. atra sp. nov. The northeastern and southern Pilbara populations are morphologically indistinguishable with the exception of a morpho-type in the southeast that has a banding pattern resembling H. planiceps from the northern monsoonal tropics. Pending more extensive analyses, we therefore treat Pilbara H. spelea as a single species with phylogenetic structure and morphological heterogeneity. PMID:24244289

Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

PubMed Central

2018-01-01

Schizophrenia (SZ) is a heritable brain disease originating from a complex interaction of genetic and environmental factors. The genes underpinning the neurobiology of SZ are largely unknown but recent data suggest strong evidence for genetic variations, such as single nucleotide polymorphisms, making the brain vulnerable to the risk of SZ. Structural and functional brain mapping of these genetic variations are essential for the development of agents and tools for better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging methods in combination with genetic analysis have been increasingly used for almost 20 years. So-called imaging genetics, the opportunities of this approach along with its limitations for SZ research will be outlined in this invited paper. While the problems such as reproducibility, genetic effect size, specificity and sensitivity exist, opportunities such as multivariate analysis, development of multisite consortia for large-scale data collection, emergence of non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely to contribute to a rapid progress for gene discovery besides to gene validation studies that are related to SZ. PMID:29324666

Multilocus Phylogeography and Species Delimitation in the Cumberland Plateau Salamander, Plethodon kentucki: Incongruence among Data Sets and Methods

PubMed Central

Kuchta, Shawn R.; Brown, Ashley D.; Converse, Paul E.; Highton, Richard

2016-01-01

Species are a fundamental unit of biodiversity, yet can be challenging to delimit objectively. This is particularly true of species complexes characterized by high levels of population genetic structure, hybridization between genetic groups, isolation by distance, and limited phenotypic variation. Previous work on the Cumberland Plateau Salamander, Plethodon kentucki, suggested that it might constitute a species complex despite occupying a relatively small geographic range. To examine this hypothesis, we sampled 135 individuals from 43 populations, and used four mitochondrial loci and five nuclear loci (5693 base pairs) to quantify phylogeographic structure and probe for cryptic species diversity. Rates of evolution for each locus were inferred using the multidistribute package, and time calibrated gene trees and species trees were inferred using BEAST 2 and *BEAST 2, respectively. Because the parameter space relevant for species delimitation is large and complex, and all methods make simplifying assumptions that may lead them to fail, we conducted an array of analyses. Our assumption was that strongly supported species would be congruent across methods. Putative species were first delimited using a Bayesian implementation of the GMYC model (bGMYC), Geneland, and Brownie. We then validated these species using the genealogical sorting index and BPP. We found substantial phylogeographic diversity using mtDNA, including four divergent clades and an inferred common ancestor at 14.9 myr (95% HPD: 10.8–19.7 myr). By contrast, this diversity was not corroborated by nuclear sequence data, which exhibited low levels of variation and weak phylogeographic structure. Species trees estimated a far younger root than did the mtDNA data, closer to 1.0 myr old. Mutually exclusive putative species were identified by the different approaches. Possible causes of data set discordance, and the problem of species delimitation in complexes with high levels of population structure and introgressive hybridization, are discussed. PMID:26974148

Research advances on microbial genetics in China in 2015.

PubMed

Xie, Jian-ping; Han, Yu-bo; Liu, Gang; Bai, Lin-quan

2016-09-01

In 2015, there are significant progresses in many aspects of the microbial genetics in China. To showcase the contribution of Chinese scientists in microbial genetics, this review surveys several notable progresses in microbial genetics made largely by Chinese scientists, and some key findings are highlighted. For the basic microbial genetics, the components, structures and functions of many macromolecule complexes involved in gene expression regulation have been elucidated. Moreover, the molecular basis underlying the recognition of foreign nucleic acids by microbial immune systems was unveiled. We also illustrated the biosynthetic pathways and regulators of multiple microbial compounds, novel enzyme reactions, and new mechanisms regulating microbial gene expression. And new findings were obtained in the microbial development, evolution and population genetics. For the industrial microbiology, more understanding on the molecular basis of the microbial factory has been gained. For the pathogenic microbiology, the genetic circuits of several pathogens were depicted, and significant progresses were achieved for understanding the pathogen-host interaction and revealing the genetic mechanisms underlying antimicrobial resistance, emerging pathogens and environmental microorganisms at the genomic level. In future, the genetic diversity of microbes can be used to obtain specific products, while gut microbiome is gathering momentum.

The influence of gene flow and drift on genetic and phenotypic divergence in two species of Zosterops in Vanuatu

PubMed Central

Clegg, Sonya M.; Phillimore, Albert B.

2010-01-01

Colonization of an archipelago sets the stage for adaptive radiation. However, some archipelagos are home to spectacular radiations, while others have much lower levels of diversification. The amount of gene flow among allopatric populations is one factor proposed to contribute to this variation. In island colonizing birds, selection for reduced dispersal ability is predicted to produce changing patterns of regional population genetic structure as gene flow-dominated systems give way to drift-mediated divergence. If this transition is important in facilitating phenotypic divergence, levels of genetic and phenotypic divergence should be associated. We consider population genetic structure and phenotypic divergence among two co-distributed, congeneric (Genus: Zosterops) bird species inhabiting the Vanuatu archipelago. The more recent colonist, Z. lateralis, exhibits genetic patterns consistent with a strong influence of distance-mediated gene flow. However, complex patterns of asymmetrical gene flow indicate variation in dispersal ability or inclination among populations. The endemic species, Z. flavifrons, shows only a partial transition towards a drift-mediated system, despite a long evolutionary history on the archipelago. We find no strong evidence that gene flow constrains phenotypic divergence in either species, suggesting that levels of inter-island gene flow do not explain the absence of a radiation across this archipelago. PMID:20194170

Rotation is visualisation, 3D is 2D: using a novel measure to investigate the genetics of spatial ability

PubMed Central

Shakeshaft, Nicholas G.; Rimfeld, Kaili; Schofield, Kerry L.; Selzam, Saskia; Malanchini, Margherita; Rodic, Maja; Kovas, Yulia; Plomin, Robert

2016-01-01

Spatial abilities–defined broadly as the capacity to manipulate mental representations of objects and the relations between them–have been studied widely, but with little agreement reached concerning their nature or structure. Two major putative spatial abilities are “mental rotation” (rotating mental models) and “visualisation” (complex manipulations, such as identifying objects from incomplete information), but inconsistent findings have been presented regarding their relationship to one another. Similarly inconsistent findings have been reported for the relationship between two- and three-dimensional stimuli. Behavioural genetic methods offer a largely untapped means to investigate such relationships. 1,265 twin pairs from the Twins Early Development Study completed the novel “Bricks” test battery, designed to tap these abilities in isolation. The results suggest substantial genetic influence unique to spatial ability as a whole, but indicate that dissociations between the more specific constructs (rotation and visualisation, in 2D and 3D) disappear when tested under identical conditions: they are highly correlated phenotypically, perfectly correlated genetically (indicating that the same genetic influences underpin performance), and are related similarly to other abilities. This has important implications for the structure of spatial ability, suggesting that the proliferation of apparent sub-domains may sometimes reflect idiosyncratic tasks rather than meaningful dissociations. PMID:27476554

The systematics and population genetics of Opisthorchis viverrini sensu lato: implications in parasite epidemiology and bile duct cancer.

PubMed

Sithithaworn, Paiboon; Andrews, Ross H; Petney, Trevor N; Saijuntha, Weerachai; Laoprom, Nonglak

2012-03-01

Together with host and environmental factors, the systematics and population genetic variation of Opisthorchis viverrini may contribute to recorded local and regional differences in epidemiology and host morbidity in opisthorchiasis and cholangiocarcinoma (CCA). In this review, we address recent findings that O. viverrini comprises a species complex with varying degrees of population genetic variation which are associated with specific river wetland systems within Thailand as well as the Lao PDR. Having an accurate understanding of systematics is a prerequisite for a meaningful assessment of the population structure of each species within the O. viverrini complex in nature, as well as a better understanding of the magnitude of genetic variation that occurs within different species of hosts in its life cycle. Whether specific genotypes are related to habitat type(s) and/or specific intermediate host species are discussed based on current available data. Most importantly, we focus on whether there is a correlation between incidence of CCA and genotype(s) of O. viverrini. This will provide a solid basis for further comprehensive investigations of the role of genetic variation within each species of O. viverrini sensu lato in human epidemiology and genotype related morbidity as well as co-evolution of parasites with primary and secondary intermediate species of host. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Forward genetics in Candida albicans that reveals the Arp2/3 complex is required for hyphal formation, but not endocytosis

PubMed Central

Epp, Elias; Walther, Andrea; Guylaine, Lépine; Leon, Zully; Mullick, Alaka; Raymond, Martine; Wendland, Jürgen; Whiteway, Malcolm

2014-01-01

Summary Candida albicans is a diploid fungal pathogen lacking a defined complete sexual cycle, and thus has been refractory to standard forward genetic analysis. Instead, transcription profiling and reverse genetic strategies based on Saccharomyces cerevisiae have typically been used to link genes to functions. To overcome restrictions inherent in such indirect approaches, we have investigated a forward genetic mutagenesis strategy based on the UAU1 technology. We screened 4700 random insertion mutants for defects in hyphal development and linked two new genes (ARP2 and VPS52) to hyphal growth. Deleting ARP2 abolished hyphal formation, generated round and swollen yeast phase cells, disrupted cortical actin patches and blocked virulence in mice. The mutants also showed a global lack of induction of hyphae-specific genes upon the yeast-to-hyphae switch. Surprisingly, both arp2Δ/Δ and arp2Δ/Δarp3Δ/Δ mutants were still able to endocytose FM4-64 and Lucifer Yellow, although as shown by time-lapse movies internalization of FM4-64 was somewhat delayed in mutant cells. Thus the non-essential role of the Arp2/3 complex discovered by forward genetic screening in C. albicans showed that uptake of membrane components from the plasma membrane to vacuolar structures is not dependent on this actin nucleating machinery. PMID:20141603

Phylogenetic relationships within the Opisthorchis viverrini species complex with specific analysis of O. viverrini sensu lato from Sakon Nakhon, Thailand by mitochondrial and nuclear DNA sequencing.

PubMed

Pitaksakulrat, Opal; Webster, Bonnie L; Webster, Joanne P; Laha, Thewarach; Saijuntha, Weerachai; Lamberton, Poppy H L; Kiatsopit, Nadda; Andrews, Ross H; Petney, Trevor N; Sithithaworn, Paiboon

2018-04-19

The liver fluke Opisthorchis viverrini sensu lato causes serious public-health problems in Northeast Thailand and Southeast Asian countries. A hypothesis has been proposed that O. viverrini represents a species complex with varying levels of genetic differentiation in Thailand and Lao PDR. This study aimed to clarify whether O. viverrini populations can be genetically divided into separate taxa. We collected O. viverrini s.l. from eight different locations in Lao PDR and Thailand. The results of nad1, cox1, CF-int6, Pm-int9, ITS2 and 28S rDNA sequence analysis revealed that sub-structuring occurred between the eight populations. We found that O. viverrini s.l. from Sakon Nakhon (SK), Thailand, shows significant genetic differentiation (P < .05) from all other isolates from different localities in Thailand and Lao PDR. This was supported by haplotype and phylogenetic tree analyses in which the SK isolate was separated from all other isolates. This suggests that O. viverrini s.l. from SK is a cryptic species. The data, however, also confirm the association between genetic groups of O. viverrini s.l. and specific wetland systems, and raise important questions regarding the epidemiological significance of these genetic differences. Copyright © 2018 Elsevier B.V. All rights reserved.

HLA-C molecular characterization of a Lebanese population and genetic structure of 39 populations from Europe to India-Pakistan.

PubMed

Buhler, S; Megarbane, A; Lefranc, G; Tiercy, J-M; Sanchez-Mazas, A

2006-07-01

Lebanon is located at a continental crossroad between Europe, Africa, and Asia. This region has been the center of wide-scale movements of populations as well as the theater of genetic and cultural trade off among neighboring populations. In this study, HLA-C alleles were characterized by a PCR-SSOP (sequence-specific oligonucleotide probes) hybridization protocol in a sample of 97 Lebanese. A total of 23 alleles were identified with four predominant, Cw*0401, Cw*0602, Cw*0701/06, and Cw*1203, accounting for almost 60% of HLA-C allele frequencies. We included the Lebanese data into a broad analysis of the HLA-C genetic structure of a large set of populations located in Europe, the Middle East, and the Indian subcontinent. Our results indicate that Lebanese exhibit an intermediate genetic profile among the populations from the Middle East, which constitute a rather homogeneous genetic group. In Europe, a high correlation coefficient is found between genetic and geographic distances. In this continent, we also identified a significant genetic frontier following a north-east to south-west axis. This frontier cuts through the Alps and the Pyrenees, thus separating the north-western European populations from those located in the eastern and Mediterranean areas. Finally, the populations from India - Pakistan are very heterogeneous, particularly the Dravidians. Their differentiation has probably been caused by rapid genetic drift under complex influences of cultural, linguistic, and/or religious barriers. Overall, the results show that the HLA-C genetic patterns of these three geographic regions, i.e., the Middle East, Europe, and India-Pakistan, have been shaped by very different genetic histories.

The Generalized Higher Criticism for Testing SNP-Set Effects in Genetic Association Studies

PubMed Central

Barnett, Ian; Mukherjee, Rajarshi; Lin, Xihong

2017-01-01

It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online. PMID:28736464

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.

Differential Roles of the Fan-Shaped Body and the Ellipsoid Body in "Drosophila" Visual Pattern Memory

ERIC Educational Resources Information Center

Pan, Yufeng; Zhou, Yanqiong; Guo, Chao; Gong, Haiyun; Gong, Zhefeng; Liu, Li

2009-01-01

The central complex is a prominent structure in the "Drosophila" brain. Visual learning experiments in the flight simulator, with flies with genetically altered brains, revealed that two groups of horizontal neurons in one of its substructures, the fan-shaped body, were required for "Drosophila" visual pattern memory. However,…

Changing Places: A Cross-Language Perspective on Frequency and Family Size in Dutch and Hebrew

ERIC Educational Resources Information Center

Moscoso del Prado Martin, Fermin; Deutsch, Avital; Frost, Ram; Schreuder, Robert; De Jong, Nivja H.; Baayen, R. Harald

2005-01-01

This study uses the morphological family size effect as a tool for exploring the degree of isomorphism in the networks of morphologically related words in the Hebrew and Dutch mental lexicon. Hebrew and Dutch are genetically unrelated, and they structure their morphologically complex words in very different ways. Two visual lexical decision…

LONI visualization environment.

PubMed

Dinov, Ivo D; Valentino, Daniel; Shin, Bae Cheol; Konstantinidis, Fotios; Hu, Guogang; MacKenzie-Graham, Allan; Lee, Erh-Fang; Shattuck, David; Ma, Jeff; Schwartz, Craig; Toga, Arthur W

2006-06-01

Over the past decade, the use of informatics to solve complex neuroscientific problems has increased dramatically. Many of these research endeavors involve examining large amounts of imaging, behavioral, genetic, neurobiological, and neuropsychiatric data. Superimposing, processing, visualizing, or interpreting such a complex cohort of datasets frequently becomes a challenge. We developed a new software environment that allows investigators to integrate multimodal imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic databases, and 3D virtual data reconstruction models. The Laboratory of Neuro Imaging visualization environment (LONI Viz) consists of the following components: a sectional viewer for imaging data, an interactive 3D display for surface and volume rendering of imaging data, a brain ontology viewer, and an external database query system. The synchronization of all components according to stereotaxic coordinates, region name, hierarchical ontology, and genetic labels is achieved via a comprehensive BrainMapper functionality, which directly maps between position, structure name, database, and functional connectivity information. This environment is freely available, portable, and extensible, and may prove very useful for neurobiologists, neurogenetisists, brain mappers, and for other clinical, pedagogical, and research endeavors.

The Complexity of Clinical Huntington's Disease: Developments in Molecular Genetics, Neuropathology and Neuroimaging Biomarkers.

PubMed

Tippett, Lynette J; Waldvogel, Henry J; Snell, Russell G; Vonsattel, Jean-Paul; Young, Anne B; Faull, Richard L M

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.

Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

PubMed

Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

2015-04-01

Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

Between “design” and “bricolage”: Genetic networks, levels of selection, and adaptive evolution

PubMed Central

Wilkins, Adam S.

2007-01-01

The extent to which “developmental constraints” in complex organisms restrict evolutionary directions remains contentious. Yet, other forms of internal constraint, which have received less attention, may also exist. It will be argued here that a set of partial constraints below the level of phenotypes, those involving genes and molecules, influences and channels the set of possible evolutionary trajectories. At the top-most organizational level there are the genetic network modules, whose operations directly underlie complex morphological traits. The properties of these network modules, however, have themselves been set by the evolutionary history of the component genes and their interactions. Characterization of the components, structures, and operational dynamics of specific genetic networks should lead to a better understanding not only of the morphological traits they underlie but of the biases that influence the directions of evolutionary change. Furthermore, such knowledge may permit assessment of the relative degrees of probability of short evolutionary trajectories, those on the microevolutionary scale. In effect, a “network perspective” may help transform evolutionary biology into a scientific enterprise with greater predictive capability than it has hitherto possessed. PMID:17494754

Between "design" and "bricolage": genetic networks, levels of selection, and adaptive evolution.

PubMed

Wilkins, Adam S

2007-05-15

The extent to which "developmental constraints" in complex organisms restrict evolutionary directions remains contentious. Yet, other forms of internal constraint, which have received less attention, may also exist. It will be argued here that a set of partial constraints below the level of phenotypes, those involving genes and molecules, influences and channels the set of possible evolutionary trajectories. At the top-most organizational level there are the genetic network modules, whose operations directly underlie complex morphological traits. The properties of these network modules, however, have themselves been set by the evolutionary history of the component genes and their interactions. Characterization of the components, structures, and operational dynamics of specific genetic networks should lead to a better understanding not only of the morphological traits they underlie but of the biases that influence the directions of evolutionary change. Furthermore, such knowledge may permit assessment of the relative degrees of probability of short evolutionary trajectories, those on the microevolutionary scale. In effect, a "network perspective" may help transform evolutionary biology into a scientific enterprise with greater predictive capability than it has hitherto possessed.

Genetic Diversity of Anopheles triannulatus s.l. (Diptera: Culicidae) from Northwestern and Southeastern Colombia

PubMed Central

Rosero, Doris A.; Jaramillo, Luz M.; Gutiérrez, Lina A.; Conn, Jan E.; Correa, Margarita M.

2012-01-01

Anopheles triannulatus s.l. is a species complex, however in Colombia its taxonomic status is unclear. This study was conducted to understand the level of genetic differentiation or population structure of specimens of An. triannulatus s.l. from northwestern and southeastern Colombia. Cytochrome oxidase subunit I (COI) and internal transcribed spacer (ITS2) sequence analyses suggested high genetic differentiation between the NW and SE populations. A TCS network and Bayesian inference analysis based on 814 bp of COI showed two main groups: group I included samples from the NW and group II samples from the SE. Two main ITS2-polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) patterns were found. Pattern I is present in both the NW and SE, and pattern II is found in the SE specimens. To further elucidate the taxonomic status of An. triannulatus s.l. in Colombia and how these COI lineages are related to the Triannulatus Complex species, the evaluation of immature stages, male genitalia, and additional mitochondrial and nuclear markers will be needed. PMID:22949519

Genetic diversity of Anopheles triannulatus s.l. (Diptera: Culicidae) from northwestern and southeastern Colombia.

PubMed

Rosero, Doris A; Jaramillo, Luz M; Gutiérrez, Lina A; Conn, Jan E; Correa, Margarita M

2012-11-01

Anopheles triannulatus s.l. is a species complex, however in Colombia its taxonomic status is unclear. This study was conducted to understand the level of genetic differentiation or population structure of specimens of An. triannulatus s.l. from northwestern and southeastern Colombia. Cytochrome oxidase subunit I (COI) and internal transcribed spacer (ITS2) sequence analyses suggested high genetic differentiation between the NW and SE populations. A TCS network and Bayesian inference analysis based on 814 bp of COI showed two main groups: group I included samples from the NW and group II samples from the SE. Two main ITS2-polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) patterns were found. Pattern I is present in both the NW and SE, and pattern II is found in the SE specimens. To further elucidate the taxonomic status of An. triannulatus s.l. in Colombia and how these COI lineages are related to the Triannulatus Complex species, the evaluation of immature stages, male genitalia, and additional mitochondrial and nuclear markers will be needed.

Bacterial Population Genetics in a Forensic Context

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velsko, S P

This report addresses the recent Department of Homeland Security (DHS) call for a Phase I study to (1) assess gaps in the forensically relevant knowledge about the population genetics of eight bacterial agents of concern, (2) formulate a technical roadmap to address those gaps, and (3) identify new bioinformatics tools that would be necessary to analyze and interpret population genetic data in a forensic context. The eight organisms that were studied are B. anthracis, Y. pestis, F. tularensis, Brucella spp., E. coli O157/H7, Burkholderia mallei, Burkholderia pseudomallei, and C. botulinum. Our study focused on the use of bacterial population geneticsmore » by forensic investigators to test hypotheses about the possible provenance of an agent that was used in a crime or act of terrorism. Just as human population genetics underpins the calculations of match probabilities for human DNA evidence, bacterial population genetics determines the level of support that microbial DNA evidence provides for or against certain well-defined hypotheses about the origins of an infecting strain. Our key findings are: (1) Bacterial population genetics is critical for answering certain types of questions in a probabilistic manner, akin (but not identical) to 'match probabilities' in DNA forensics. (2) A basic theoretical framework for calculating likelihood ratios or posterior probabilities for forensic hypotheses based on microbial genetic comparisons has been formulated. This 'inference-on-networks' framework has deep but simple connections to the population genetics of mtDNA and Y-STRs in human DNA forensics. (3) The 'phylogeographic' approach to identifying microbial sources is not an adequate basis for understanding bacterial population genetics in a forensic context, and has limited utility, even for generating 'leads' with respect to strain origin. (4) A collection of genotyped isolates obtained opportunistically from international locations augmented by phylogenetic representations of relatedness will not and enzootic outbreaks noted through international outbreak surveillance systems, and 'representative' genetic sequences from each outbreak. (5) Interpretation of genetic comparisons between an attack strain and reference strains requires a model for the network structure of maintenance foci, enzootic outbreaks, and human outbreaks of that disease, coupled with estimates of mutational rate constants. Validation of the model requires a set of sequences from exemplary outbreaks and laboratory data on mutation rates during animal passage. The necessary number of isolates in each validation set is determined by disease transmission network theory, and is based on the 'network diameter' of the outbreak. (6) The 8 bacteria in this study can be classified into 4 categories based on the complexity of the transmission network structure of their natural maintenance foci and their outbreaks, both enzootic and zoonotic. (7) For B. anthracis, Y. pestis, E. coli O157, and Brucella melitensis, and their primary natural animal hosts, most of the fundamental parameters needed for modeling genetic change within natural host or human transmission networks have been determined or can be estimated from existing field and laboratory studies. (8) For Burkholderia mallei, plausible approaches to transmission network models exist, but much of the fundamental parameterization does not. In addition, a validated high-resolution typing system for characterizing genetic change within outbreaks or foci has not yet been demonstrated, although a candidate system exists. (9) For Francisella tularensis, the increased complexity of the transmission network and unresolved questions about maintenance and transmission suggest that it will be more complex and difficult to develop useful models based on currently available data. (10) For Burkholderia pseudomallei and Clostridium botulinum, the transmission and maintenance networks involve complex soil communities and metapopulations about which very little is known. It is not clear that these pathogens can be brought into the inference-on-networks framework without additional conceptual advances. (11) For all 8 bacteria some combination of field studies, computational modeling, and laboratory experiments are needed to provide a useful forensic capability for bacterial genetic inference.« less

Routine Discovery of Complex Genetic Models using Genetic Algorithms

PubMed Central

Moore, Jason H.; Hahn, Lance W.; Ritchie, Marylyn D.; Thornton, Tricia A.; White, Bill C.

2010-01-01

Simulation studies are useful in various disciplines for a number of reasons including the development and evaluation of new computational and statistical methods. This is particularly true in human genetics and genetic epidemiology where new analytical methods are needed for the detection and characterization of disease susceptibility genes whose effects are complex, nonlinear, and partially or solely dependent on the effects of other genes (i.e. epistasis or gene-gene interaction). Despite this need, the development of complex genetic models that can be used to simulate data is not always intuitive. In fact, only a few such models have been published. We have previously developed a genetic algorithm approach to discovering complex genetic models in which two single nucleotide polymorphisms (SNPs) influence disease risk solely through nonlinear interactions. In this paper, we extend this approach for the discovery of high-order epistasis models involving three to five SNPs. We demonstrate that the genetic algorithm is capable of routinely discovering interesting high-order epistasis models in which each SNP influences risk of disease only through interactions with the other SNPs in the model. This study opens the door for routine simulation of complex gene-gene interactions among SNPs for the development and evaluation of new statistical and computational approaches for identifying common, complex multifactorial disease susceptibility genes. PMID:20948983

Biogenic manganese oxide nanoparticle formation by a multimeric multicopper oxidase Mnx.

PubMed

Romano, Christine A; Zhou, Mowei; Song, Yang; Wysocki, Vicki H; Dohnalkova, Alice C; Kovarik, Libor; Paša-Tolić, Ljiljana; Tebo, Bradley M

2017-09-29

Bacteria that produce Mn oxides are extraordinarily skilled engineers of nanomaterials that contribute significantly to global biogeochemical cycles. Their enzyme-based reaction mechanisms may be genetically tailored for environmental remediation applications or bioenergy production. However, significant challenges exist for structural characterization of the enzymes responsible for biomineralization. The active Mn oxidase in Bacillus sp. PL-12, Mnx, is a complex composed of a multicopper oxidase (MCO), MnxG, and two accessory proteins, MnxE and MnxF. MnxG shares sequence similarity with other, structurally characterized MCOs. MnxE and MnxF have no similarity to any characterized proteins. The ~200 kDa complex has been recalcitrant to crystallization, so its structure is unknown. Here, we show that native mass spectrometry defines the subunit topology and copper binding of Mnx, while high-resolution electron microscopy visualizes the protein and nascent Mn oxide minerals. These data provide critical structural information for understanding Mn biomineralization by such unexplored enzymes.Significant challenges exist for structural characterization of enzymes responsible for biomineralization. Here the authors show that native mass spectrometry and high resolution electron microscopy can define the subunit topology and copper binding of a manganese oxidizing complex, and describe early stage formation of its mineral products.

State of the APC/C: Organization, function, and structure

PubMed Central

McLean, Janel R.; Chaix, Denis; Ohi, Melanie D.; Gould, Kathleen L.

2016-01-01

The ubiquitin-proteasome protein degradation system is involved in many essential cellular processes including cell cycle regulation, cell differentiation, and the unfolded protein response.The anaphase-promoting complex/cyclosome (APC/C), an evolutionary conserved E3 ubiquitin ligase, was discovered 15 years ago because of its pivotal role in cyclin degradation and mitotic progression. Since then, we have learned that the APC/C is a very large, complex E3 ligase composed of 13 subunits, yielding a molecular machine of approximately 1 MDa. The intricate regulation of the APC/C is mediated by the Cdc20 family of activators, pseudosubstrate inhibitors, protein kinases and phosphatases and the spindle assembly checkpoint. The large size, complexity, and dynamic nature of the APC/C represent significant obstacles toward high-resolution structural techniques; however, over the last decade, there have been a number of lower resolution APC/C structures determined using single particle electron microscopy. These structures, when combined with data generated from numerous genetic and biochemical studies, have begun to shed light on how APC/C activity is regulated. Here, we discuss the most recent developments in the APC/C field concerning structure, substrate recognition, and catalysis. PMID:21261459

Intervarietal and intravarietal genetic structure in Douglas-fir: nuclear SSRs bring novel insights into past population demographic processes, phylogeography, and intervarietal hybridization

PubMed Central

van Loo, Marcela; Hintsteiner, Wolfgang; Pötzelsberger, Elisabeth; Schüler, Silvio; Hasenauer, Hubert

2015-01-01

Douglas-fir (Pseudotsuga menziesii) is one of numerous wide-range forest tree species represented by subspecies/varieties, which hybridize in contact zones. This study examined the genetic structure of this North American conifer and its two hybridizing varieties, coastal and Rocky Mountain, at intervarietal and intravarietal level. The genetic structure was subsequently associated with the Pleistocene refugial history, postglacial migration and intervarietal hybridization/introgression. Thirty-eight populations from the USA and Canada were genotyped for 13 nuclear SSRs and analyzed with simulations and traditional population genetic structuring methods. Eight genetic clusters were identified. The coastal clusters embodied five refugial populations originating from five distinct refugia. Four coastal refugial populations, three from California and one from western Canada, diverged during the Pleistocene (56.9–40.1 ka). The three Rocky Mountain clusters reflected distinct refugial populations of three glacial refugia. For Canada, ice covered during the Last Glacial Maximum, we present the following three findings. (1) One refugial population of each variety was revealed in the north of the distribution range. Additional research including paleodata is required to support and determine whether both northern populations originated from cryptic refugia situated south or north of the ice-covered area. (2) An interplay between intravarietal gene flow of different refugial populations and intervarietal gene flow by hybridization and introgression was identified. (3) The Canadian hybrid zone displayed predominantly introgressants of the Rocky Mountain into the coastal variety. This study provides new insights into the complex Quaternary dynamics of this conifer essential for understanding its evolution (outside and inside the native range), adaptation to future climates and for forest management. PMID:26140197

Genetic landscape of populations along the Silk Road: admixture and migration patterns.

PubMed

Mezzavilla, Massimo; Vozzi, Diego; Pirastu, Nicola; Girotto, Giorgia; d'Adamo, Pio; Gasparini, Paolo; Colonna, Vincenza

2014-12-05

The ancient Silk Road has been a trading route between Europe and Central Asia from the 2(nd) century BCE to the 15(th) century CE. While most populations on this route have been characterized, the genetic background of others remains poorly understood, and little is known about past migration patterns. The scientific expedition "Marco Polo" has recently collected genetic and phenotypic data in six regions (Georgia, Armenia, Azerbaijan, Uzbekistan, Kazakhstan, Tajikistan) along the Silk Road to study the genetics of a number of phenotypes. We characterized the genetic structure of these populations within a worldwide context. We observed a West-East subdivision albeit the existence of a genetic component shared within Central Asia and nearby populations from Europe and Near East. We observed a contribution of up to 50% from Europe and Asia to most of the populations that have been analyzed. The contribution from Asia dates back to ~25 generations and is limited to the Eastern Silk Road. Time and direction of this contribution are consistent with the Mongolian expansion era. We clarified the genetic structure of six populations from Central Asia and suggested a complex pattern of gene flow among them. We provided a map of migration events in time and space and we quantified exchanges among populations. Altogether these novel findings will support the future studies aimed at understanding the genetics of the phenotypes that have been collected during the Marco Polo campaign, they will provide insights into the history of these populations, and they will be useful to reconstruct the developments and events that have shaped modern Eurasians genomes.

Assessing genetic structure and diversity of airborne bacterial communities by DNA fingerprinting and 16S rDNA clone library

NASA Astrophysics Data System (ADS)

Maron, Pierre-Alain; Lejon, David P. H.; Carvalho, Esmeralda; Bizet, Karine; Lemanceau, Philippe; Ranjard, Lionel; Mougel, Christophe

The density, genetic structure and diversity of airborne bacterial communities were assessed in the outdoor atmosphere. Two air samples were collected on the same location (north of France) at two dates (March 2003 (sample1) and May 2003 (sample 2)). Molecular culture -independent methods were used to characterise airborne bacterial communities regardless of the cell culturability. The automated-ribosomal intergenic spacer analysis (A-RISA) was performed to characterise the community structure in each sample. For both sampling dates, complex A-RISA patterns were observed suggesting a highly diverse community structure, comparable to those found in soil, water or sediment environments. Furthermore, differences in the genetic structure of airborne bacterial communities were observed between samples 1 and 2 suggesting an important variability in time. A clone library of 16S rDNA directly amplified from air DNA of sample 1 was constructed and sequenced to analyse the community composition and diversity. The Proteobacteria group had the greatest representation (60%), with bacteria belonging to the different subdivisions α- (19%), β-(21%), γ-(12%) and δ-(8%). Firmicute and Actinobacteria were also well represented with 14% and 12%, respectively. Most of the identified bacteria are known to be commonly associated with soil or plant environments suggesting that the atmosphere is mainly colonised transiently by microorganisms from local sources, depending on air fluxes.

The genetic basis of developmental abnormalities in interpopulation hybrids of the moss Ceratodon purpureus.

PubMed

McDaniel, Stuart F; Willis, John H; Shaw, A Jonathan

2008-07-01

Divergent populations are intrinsically reproductively isolated when hybrids between them either fail to develop properly or do not produce viable offspring. Intrinsic isolation may result from Dobzhansky-Muller (DM) incompatibilities, in which deleterious interactions among genes or gene products lead to developmental problems or underdominant chromosome structure differences between the parents. These mechanisms can be tested by studying marker segregation patterns in a hybrid mapping population. Here we examine the genetic basis of abnormal development in hybrids between two geographically distant populations of the moss Ceratodon purpureus. Approximately half of the hybrid progeny exhibited a severely reduced growth rate in early gametophyte development. We identified four unlinked quantitative trait loci (QTL) that interacted asymmetrically to cause the abnormal development phenotype. This pattern is consistent with DM interactions. We also found an excess of recombination between three marker pairs in the abnormally developing progeny, relative to that estimated in the normal progeny. This suggests that structural differences in these regions contribute to hybrid breakdown. Two QTL coincided with inferred structural differences, consistent with recent theory suggesting that rearrangements may harbor population divergence alleles. These observations suggest that multiple complex genetic factors contribute to divergence among populations of C. purpureus.

Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks

PubMed Central

Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

2016-01-01

The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains. Here we review phylogenomic analyses that reconstruct the early history of the synthetase enzymes and the ribosome, their interactions with RNA, and the inception of amino acid charging and codon specificities in tRNA that are responsible for the genetic code. We also trace the age of domains and tRNA onto ancient tRNA homologies that were recently identified in rRNA. Our findings reveal a timeline of recruitment of tRNA building blocks for the formation of a functional ribosome, which holds both the biocatalytic functions of protein biosynthesis and the ability to store genetic memory in primordial RNA genomic templates. PMID:27918435

Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks.

PubMed

Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

2016-12-02

The origin of biomolecular machinery likely centered around an ancient and central molecule capable of interacting with emergent macromolecular complexity. tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation. Phylogenetic approaches that focus on molecular structure allow reconstruction of evolutionary timelines that describe the history of RNA and protein structural domains. Here we review phylogenomic analyses that reconstruct the early history of the synthetase enzymes and the ribosome, their interactions with RNA, and the inception of amino acid charging and codon specificities in tRNA that are responsible for the genetic code. We also trace the age of domains and tRNA onto ancient tRNA homologies that were recently identified in rRNA. Our findings reveal a timeline of recruitment of tRNA building blocks for the formation of a functional ribosome, which holds both the biocatalytic functions of protein biosynthesis and the ability to store genetic memory in primordial RNA genomic templates.

[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.

Kinetics of the LOV domain of ZEITLUPE determine its circadian function in Arabidopsis

PubMed Central

Pudasaini, Ashutosh; Shim, Jae Sung; Song, Young Hun; Shi, Hua; Kiba, Takatoshi; Somers, David E; Imaizumi, Takato; Zoltowski, Brian D

2017-01-01

A LOV (Light, Oxygen, or Voltage) domain containing blue-light photoreceptor ZEITLUPE (ZTL) directs circadian timing by degrading clock proteins in plants. Functions hinge upon allosteric differences coupled to the ZTL photocycle; however, structural and kinetic information was unavailable. Herein, we tune the ZTL photocycle over two orders of magnitude. These variants reveal that ZTL complexes with targets independent of light, but dictates enhanced protein degradation in the dark. In vivo experiments definitively show photocycle kinetics dictate the rate of clock component degradation, thereby impacting circadian period. Structural studies demonstrate that photocycle dependent activation of ZTL depends on an unusual dark-state conformation of ZTL. Crystal structures of ZTL LOV domain confirm delineation of structural and kinetic mechanisms and identify an evolutionarily selected allosteric hinge differentiating modes of PAS/LOV signal transduction. The combined biochemical, genetic and structural studies provide new mechanisms indicating how PAS/LOV proteins integrate environmental variables in complex networks. DOI: http://dx.doi.org/10.7554/eLife.21646.001 PMID:28244872

Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution

NASA Astrophysics Data System (ADS)

Quade, Nick; Boehringer, Daniel; Leibundgut, Marc; van den Heuvel, Joop; Ban, Nenad

2015-07-01

Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 Å resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs.

Molecular mechanisms of inner ear development.

PubMed

Wu, Doris K; Kelley, Matthew W

2012-08-01

The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms.

Two-level optimization of composite wing structures based on panel genetic optimization

NASA Astrophysics Data System (ADS)

Liu, Boyang

The design of complex composite structures used in aerospace or automotive vehicles presents a major challenge in terms of computational cost. Discrete choices for ply thicknesses and ply angles leads to a combinatorial optimization problem that is too expensive to solve with presently available computational resources. We developed the following methodology for handling this problem for wing structural design: we used a two-level optimization approach with response-surface approximations to optimize panel failure loads for the upper-level wing optimization. We tailored efficient permutation genetic algorithms to the panel stacking sequence design on the lower level. We also developed approach for improving continuity of ply stacking sequences among adjacent panels. The decomposition approach led to a lower-level optimization of stacking sequence with a given number of plies in each orientation. An efficient permutation genetic algorithm (GA) was developed for handling this problem. We demonstrated through examples that the permutation GAs are more efficient for stacking sequence optimization than a standard GA. Repair strategies for standard GA and the permutation GAs for dealing with constraints were also developed. The repair strategies can significantly reduce computation costs for both standard GA and permutation GA. A two-level optimization procedure for composite wing design subject to strength and buckling constraints is presented. At wing-level design, continuous optimization of ply thicknesses with orientations of 0°, 90°, and +/-45° is performed to minimize weight. At the panel level, the number of plies of each orientation (rounded to integers) and inplane loads are specified, and a permutation genetic algorithm is used to optimize the stacking sequence. The process begins with many panel genetic optimizations for a range of loads and numbers of plies of each orientation. Next, a cubic polynomial response surface is fitted to the optimum buckling load. The resulting response surface is used for wing-level optimization. In general, complex composite structures consist of several laminates. A common problem in the design of such structures is that some plies in the adjacent laminates terminate in the boundary between the laminates. These discontinuities may cause stress concentrations and may increase manufacturing difficulty and cost. We developed measures of continuity of two adjacent laminates. We studied tradeoffs between weight and continuity through a simple composite wing design. Finally, we compared the two-level optimization to a single-level optimization based on flexural lamination parameters. The single-level optimization is efficient and feasible for a wing consisting of unstiffened panels.

Population Structure of the Coral-eating Fireworm Hermodice carunculata in the Wider Caribbean, Atlantic and Mediterranean Sea

NASA Astrophysics Data System (ADS)

Cruz, M.; Schizas, N. V.

2016-02-01

The bearded fireworm Hermodice carunculata is an important benthic invertebrate scavenger distributed in reefs worldwide. Fireworms are facultative corallivores and have been shown to transfer pathogenic agents between coral colonies. The effects of predation on coral species can be substantial. There is limited data on the genetic population structure of H. carunculata because of its cryptic nature and past studies resulted in ambiguous findings. Both morphological and molecular data suggest the presence of multiple fireworm sibling species but the morphological differences do not reflect the phylogeographic patterns of the species complex. Hermodice carunculata is an ideal species to use for genetic analysis to infer patterns of population structure and gene flow because of its biphasic life style with planktonic larvae and benthic adults. We collected 412 H. carunculata samples from over 20 locations in the Caribbean, Mediterranean Sea, Gulf of Mexico, Western and Eastern Atlantic Ocean. We sequenced two mitochondrial markers: Cytochrome C Oxidase subunit I (COI) and Cytochrome b (Cytb) from each specimen to examine the genetic diversity of H. carunculata. There is substantial genetic diversity within H. carunculata and preliminary evidence suggests the presence of at least two cryptic species in multiple locations. The presence of multiple species in bearded fireworms indicates our incomplete knowledge in one of the most important invertebrate scavengers in tropical and subtropical reefs.

Convenient QSAR model for predicting the complexation of structurally diverse compounds with beta-cyclodextrins.

PubMed

Pérez-Garrido, Alfonso; Morales Helguera, Aliuska; Abellán Guillén, Adela; Cordeiro, M Natália D S; Garrido Escudero, Amalio

2009-01-15

This paper reports a QSAR study for predicting the complexation of a large and heterogeneous variety of substances (233 organic compounds) with beta-cyclodextrins (beta-CDs). Several different theoretical molecular descriptors, calculated solely from the molecular structure of the compounds under investigation, and an efficient variable selection procedure, like the Genetic Algorithm, led to models with satisfactory global accuracy and predictivity. But the best-final QSAR model is based on Topological descriptors meanwhile offering a reasonable interpretation. This QSAR model was able to explain ca. 84% of the variance in the experimental activity, and displayed very good internal cross-validation statistics and predictivity on external data. It shows that the driving forces for CD complexation are mainly hydrophobic and steric (van der Waals) interactions. Thus, the results of our study provide a valuable tool for future screening and priority testing of beta-CDs guest molecules.

Porcine colonization of the Americas: a 60k SNP story

PubMed Central

Burgos-Paz, W; Souza, C A; Megens, H J; Ramayo-Caldas, Y; Melo, M; Lemús-Flores, C; Caal, E; Soto, H W; Martínez, R; Álvarez, L A; Aguirre, L; Iñiguez, V; Revidatti, M A; Martínez-López, O R; Llambi, S; Esteve-Codina, A; Rodríguez, M C; Crooijmans, R P M A; Paiva, S R; Schook, L B; Groenen, M A M; Pérez-Enciso, M

2013-01-01

The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level. PMID:23250008

Failure of replicating the association between hippocampal volume and 3 single-nucleotide polymorphisms identified from the European genome-wide association study in Asian populations.

PubMed

Li, Ming; Ohi, Kazutaka; Chen, Chunhui; He, Qinghua; Liu, Jie-Wei; Chen, Chuansheng; Luo, Xiong-Jian; Dong, Qi; Hashimoto, Ryota; Su, Bing

2014-12-01

Hippocampal volume is a key brain structure for learning ability and memory process, and hippocampal atrophy is a recognized biological marker of Alzheimer's disease. However, the genetic bases of hippocampal volume are still unclear although it is a heritable trait. Genome-wide association studies (GWASs) on hippocampal volume have implicated several significantly associated genetic variants in Europeans. Here, to test the contributions of these GWASs identified genetic variants to hippocampal volume in different ethnic populations, we screened the GWAS-identified candidate single-nucleotide polymorphisms in 3 independent healthy Asian brain imaging samples (a total of 990 subjects). The results showed that none of these single-nucleotide polymorphisms were associated with hippocampal volume in either individual or combined Asian samples. The replication results suggested a complexity of genetic architecture for hippocampal volume and potential genetic heterogeneity between different ethnic populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Theodosius Dobzhansky and the genetic race concept.

PubMed

Gannett, Lisa

2013-09-01

The use of 'race' as a proxy for population structure in the genetic mapping of complex traits has provoked controversy about its legitimacy as a category for biomedical research, given its social and political connotations. The controversy has reignited debates among scientists and philosophers of science about whether there is a legitimate biological concept of race. This paper examines the genetic race concept as it developed historically in the work of Theodosius Dobzhansky from the 1930s to 1950s. Dobzhansky's definitions of race changed over this time from races as 'arrays of forms' or 'clusters' in 1933-1939, to races as genetically distinct geographical populations in 1940-1946, to races as genetically distinct 'Mendelian populations' in 1947-1955. Dobzhansky responded to nominalist challenges by appealing to the biological reality of race as a process. This response came into tension with the object ontology of race that was implied by Dobzhansky's increasingly holistic treatment of Mendelian populations, a tension, the paper argues, he failed to appreciate or resolve. Copyright © 2013 Elsevier Ltd. All rights reserved.

Psychosocial aspects of genetic testing.

PubMed

Cameron, Linda D; Muller, Cecile

2009-03-01

With rapid advances in genetic testing for disease susceptibility, behavioral medicine faces significant challenges in identifying likely patterns of use, how individuals interpret test results, and psychosocial and health impacts of testing. We review recent research on these psychosocial aspects of genetic testing for disease risk. Individuals exhibit limited sensitivity in their perceptions of genetic risk information, and mental representations of disease risk appear to guide testing perceptions and behavioral responses. Motivations to undergo testing are complex, and efforts to develop decision aids are underway. Findings on psychological and behavioral impacts of genetic testing vary markedly, with some evidence of minimal or positive effects and other evidence indicating negative consequences that may be undetectable using common measures of general well being. Recent evidence suggests that genetic risk information can motivate health behavior change. Research demonstrates wide-ranging influences of testing on family dynamics, and use of genetic testing with children is of increasing concern. More research is needed to determine how to structure health communications and counseling to motivate informed use, promote positive responses, and optimize behavior change. Given the ramifications of genetic information for families, personalized genomics will demand a shift toward a family-based healthcare model.

Genetic diversity and sex ratio of naked mole rat, Heterocephalus glaber, zoo populations.

PubMed

Chau, Linh M; Groh, Amy M; Anderson, Emily C; Alcala, Micaela O; Mendelson, Joseph R; Slade, Stephanie B; Kerns, Kenton; Sarro, Steve; Lusardi, Clinton; Goodisman, Michael A D

2018-05-01

The naked mole rat, Heterocephalus glaber, is a highly unusual mammal that displays a complex social system similar to that found in eusocial insects. Colonies of H. glaber are commonly maintained in zoo collections because they represent fascinating educational exhibits for the public. However, little is known about the genetic structure or sex ratio of captive populations of H. glaber. In this study, we developed a set of microsatellite markers to examine genetic variation in three captive zoo populations of H. glaber. We also studied sex ratio of these captive populations. Our goal was to determine levels of genetic variation within, and genetic differences between, captive populations of H. glaber. Overall, we found modest levels of genetic variation in zoo populations. We also uncovered little evidence for inbreeding within the captive populations. However, zoo populations did differ genetically, which may reflect the isolation of captive naked mole rat colonies. Finally, we found no evidence of biased sex ratios within colonies. Overall, our study documents levels of genetic variation and sex ratios in a captive eusocial mammalian population. Our results may provide insight into how to manage captive populations of H. glaber. © 2018 Wiley Periodicals, Inc.

Phylogeographic Insights into a Peripheral Refugium: The Importance of Cumulative Effect of Glaciation on the Genetic Structure of Two Endemic Plants

PubMed Central

Zecca, Giovanni; Minuto, Luigi

2016-01-01

Quaternary glaciations and mostly last glacial maximum have shaped the contemporary distribution of many species in the Alps. However, in the Maritime and Ligurian Alps a more complex picture is suggested by the presence of many Tertiary paleoendemisms and by the divergence time between lineages in one endemic species predating the Late Pleistocene glaciation. The low number of endemic species studied limits the understanding of the processes that took place within this region. We used species distribution models and phylogeographical methods to infer glacial refugia and to reconstruct the phylogeographical pattern of Silene cordifolia All. and Viola argenteria Moraldo & Forneris. The predicted suitable area for last glacial maximum roughly fitted current known distribution. Our results suggest that separation of the major clades predates the last glacial maximum and the following repeated glacial and interglacial periods probably drove differentiations. The complex phylogeographical pattern observed in the study species suggests that both populations and genotypes extinction was minimal during the last glacial maximum, probably due to the low impact of glaciations and to topographic complexity in this area. This study underlines the importance of cumulative effect of previous glacial cycles in shaping the genetic structure of plant species in Maritime and Ligurian Alps, as expected for a Mediterranean mountain region more than for an Alpine region. PMID:27870888

Epigenetic Modifications in Essential Hypertension

PubMed Central

Wise, Ingrid A.; Charchar, Fadi J.

2016-01-01

Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. PMID:27023534

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 for this species. PMID:25435649

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

PubMed

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

2014-03-01

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. Ireland, Britain and continental Europe. 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. 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. 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 for this species.

Persistent genetic signatures of historic climatic events in an Antarctic octopus.

PubMed

Strugnell, J M; Watts, P C; Smith, P J; Allcock, A L

2012-06-01

Repeated cycles of glaciation have had major impacts on the distribution of genetic diversity of the Antarctic marine fauna. During glacial periods, ice cover limited the amount of benthic habitat on the continental shelf. Conversely, more habitat and possibly altered seaways were available during interglacials when the ice receded and the sea level was higher. We used microsatellites and partial sequences of the mitochondrial cytochrome oxidase 1 gene to examine genetic structure in the direct-developing, endemic Southern Ocean octopod Pareledone turqueti sampled from a broad range of areas that circumvent Antarctica. We find that, unusually for a species with poor dispersal potential, P. turqueti has a circumpolar distribution and is also found off the islands of South Georgia and Shag Rocks. The overriding pattern of spatial genetic structure can be explained by hydrographic (with ocean currents both facilitating and hindering gene flow) and bathymetric features. The Antarctic Peninsula region displays a complex population structure, consistent with its varied topographic and oceanographic influences. Genetic similarities between the Ross and Weddell Seas, however, are interpreted as a persistent historic genetic signature of connectivity during the hypothesized Pleistocene West Antarctic Ice Sheet collapses. A calibrated molecular clock indicates two major lineages within P. turqueti, a continental lineage and a sub-Antarctic lineage, that diverged in the mid-Pliocene with no subsequent gene flow. Both lineages survived subsequent major glacial cycles. Our data are indicative of potential refugia at Shag Rocks and South Georgia and also around the Antarctic continent within the Ross Sea, Weddell Sea and off Adélie Land. The mean age of mtDNA diversity within these main continental lineages coincides with Pleistocene glacial cycles. © 2012 Blackwell Publishing Ltd.

Genetic diversity of drug and multidrug-resistant Mycobacterium tuberculosis circulating in Veracruz, Mexico

PubMed Central

Munro-Rojas, Daniela; Fernandez-Morales, Esdras; Zarrabal-Meza, José; Martínez-Cazares, Ma. Teresa; Parissi-Crivelli, Aurora; Fuentes-Domínguez, Javier; Séraphin, Marie Nancy; Lauzardo, Michael; González-y-Merchand, Jorge Alberto; Rivera-Gutierrez, Sandra

2018-01-01

Background Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. Methods In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. Findings The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%). A total of 29 (25%) isolates were identified as orphan. The most abundant SITs were SIT53/T1 and SIT42/LAM9 with 10 isolates each and SIT50/H3 with eight isolates. Fifty-two spoligotype patterns, twenty-seven clusters and ten clonal complexes were observed, demonstrating an important genetic diversity of drug and multidrug-resistant tuberculosis isolates in circulation and transmission level of these aggravated forms of tuberculosis. Being defined as orphan or as part of an orphan cluster, was a risk factor for multidrug resistant-tuberculosis (OR 2.5, IC 1.05–5.86 and OR 3.3, IC 1–11.03, respectively). Multiple correspondence analyses showed association of some clusters and SITs with specific geographical locations. Conclusions Our study provides one of the most detailed description of the genetic structure of drug and multidrug-resistant tuberculosis strains in southeast Mexico, establishing for the first time a baseline of the genotypes observed in resistant isolates circulating, however further studies are required to better elucidate the genetic structure of tuberculosis in region and the factors that could be participating in their dispersion. PMID:29543819

Graph theoretical analysis of complex networks in the brain

PubMed Central

Stam, Cornelis J; Reijneveld, Jaap C

2007-01-01

Since the discovery of small-world and scale-free networks the study of complex systems from a network perspective has taken an enormous flight. In recent years many important properties of complex networks have been delineated. In particular, significant progress has been made in understanding the relationship between the structural properties of networks and the nature of dynamics taking place on these networks. For instance, the 'synchronizability' of complex networks of coupled oscillators can be determined by graph spectral analysis. These developments in the theory of complex networks have inspired new applications in the field of neuroscience. Graph analysis has been used in the study of models of neural networks, anatomical connectivity, and functional connectivity based upon fMRI, EEG and MEG. These studies suggest that the human brain can be modelled as a complex network, and may have a small-world structure both at the level of anatomical as well as functional connectivity. This small-world structure is hypothesized to reflect an optimal situation associated with rapid synchronization and information transfer, minimal wiring costs, as well as a balance between local processing and global integration. The topological structure of functional networks is probably restrained by genetic and anatomical factors, but can be modified during tasks. There is also increasing evidence that various types of brain disease such as Alzheimer's disease, schizophrenia, brain tumours and epilepsy may be associated with deviations of the functional network topology from the optimal small-world pattern. PMID:17908336

Evolutionary diversification of protein-protein interactions by interface add-ons.

PubMed

Plach, Maximilian G; Semmelmann, Florian; Busch, Florian; Busch, Markus; Heizinger, Leonhard; Wysocki, Vicki H; Merkl, Rainer; Sterner, Reinhard

2017-10-03

Cells contain a multitude of protein complexes whose subunits interact with high specificity. However, the number of different protein folds and interface geometries found in nature is limited. This raises the question of how protein-protein interaction specificity is achieved on the structural level and how the formation of nonphysiological complexes is avoided. Here, we describe structural elements called interface add-ons that fulfill this function and elucidate their role for the diversification of protein-protein interactions during evolution. We identified interface add-ons in 10% of a representative set of bacterial, heteromeric protein complexes. The importance of interface add-ons for protein-protein interaction specificity is demonstrated by an exemplary experimental characterization of over 30 cognate and hybrid glutamine amidotransferase complexes in combination with comprehensive genetic profiling and protein design. Moreover, growth experiments showed that the lack of interface add-ons can lead to physiologically harmful cross-talk between essential biosynthetic pathways. In sum, our complementary in silico, in vitro, and in vivo analysis argues that interface add-ons are a practical and widespread evolutionary strategy to prevent the formation of nonphysiological complexes by specializing protein-protein interactions.

Flexible social organization and high incidence of drifting in the sweat bee, Halictus scabiosae.

PubMed

Ulrich, Yuko; Perrin, Nicolas; Chapuisat, Michel

2009-04-01

The very diverse social systems of sweat bees make them interesting models to study social evolution. Here we focus on the dispersal behaviour and social organization of Halictus scabiosae, a common yet poorly known species of Europe. By combining field observations and genetic data, we show that females have multiple reproductive strategies, which generates a large diversity in the social structure of nests. A detailed microsatellite analysis of 60 nests revealed that 55% of the nests contained the offspring of a single female, whereas the rest had more complex social structures, with three clear cases of multiple females reproducing in the same nest and frequent occurrence of unrelated individuals. Drifting among nests was surprisingly common, as 16% of the 122 nests in the overall sample and 44% of the nests with complex social structure contained females that had genotypes consistent with being full-sisters of females sampled in other nests of the population. Drifters originated from nests with an above-average productivity and were unrelated to their nestmates, suggesting that drifting might be a strategy to avoid competition among related females. The sex-specific comparison of genetic differentiation indicated that dispersal was male-biased, which would reinforce local resource competition among females. The pattern of genetic differentiation among populations was consistent with a dynamic process of patch colonization and extinction, as expected from the unstable, anthropogenic habitat of this species. Overall, our data show that H. scabiosae varies greatly in dispersal behaviour and social organization. The surprisingly high frequency of drifters echoes recent findings in wasps and bees, calling for further investigation of the adaptive basis of drifting in the social insects.

Genetic Diversity and Population Structure of Rice Varieties Cultivated in Temperate Regions.

PubMed

Reig-Valiente, Juan L; Viruel, Juan; Sales, Ester; Marqués, Luis; Terol, Javier; Gut, Marta; Derdak, Sophia; Talón, Manuel; Domingo, Concha

2016-12-01

After its domestication, rice cultivation expanded from tropical regions towards northern latitudes with temperate climate in a progressive process to overcome limiting photoperiod and temperature conditions. This process has originated a wide range of diversity that can be regarded as a valuable resource for crop improvement. In general, current rice breeding programs have to deal with a lack of both germplasm accessions specifically adapted to local agro-environmental conditions and adapted donors carrying desired agronomical traits. Comprehensive maps of genome variability and population structure would facilitate genome-wide association studies of complex traits, functional gene investigations and the selection of appropriate donors for breeding purposes. A collection of 217 rice varieties mainly cultivated in temperate regions was generated. The collection encompasses modern elite and old cultivars, as well as traditional landraces covering a wide genetic diversity available for rice breeders. Whole Genome Sequencing was performed on 14 cultivars representative of the collection and the genomic profiles of all cultivars were constructed using a panel of 2697 SNPs with wide coverage throughout the rice genome, obtained from the sequencing data. The population structure and genetic relationship analyses showed a strong substructure in the temperate rice population, predominantly based on grain type and the origin of the cultivars. Dendrogram also agrees population structure results. Based on SNP markers, we have elucidated the genetic relationship and the degree of genetic diversity among a collection of 217 temperate rice varieties possessing an enormous variety of agromorphological and physiological characters. Taken together, the data indicated the occurrence of relatively high gene flow and elevated rates of admixture between cultivars grown in remote regions, probably favoured by local breeding activities. The results of this study significantly expand the current genetic resources available for temperate varieties of rice, providing a valuable tool for future association mapping studies.

Spatial genetic and morphologic structure of wolves and coyotes in relation to environmental heterogeneity in a Canis hybrid zone.

PubMed

Benson, John F; Patterson, Brent R; Wheeldon, Tyler J

2012-12-01

Eastern wolves have hybridized extensively with coyotes and gray wolves and are listed as a 'species of special concern' in Canada. However, a distinct population of eastern wolves has been identified in Algonquin Provincial Park (APP) in Ontario. Previous studies of the diverse Canis hybrid zone adjacent to APP have not linked genetic analysis with field data to investigate genotype-specific morphology or determine how resident animals of different ancestry are distributed across the landscape in relation to heterogeneous environmental conditions. Accordingly, we studied resident wolves and coyotes in and adjacent to APP to identify distinct Canis types, clarify the extent of the APP eastern wolf population beyond the park boundaries and investigate fine-scale spatial genetic structure and landscape-genotype associations in the hybrid zone. We documented three genetically distinct Canis types within the APP region that also differed morphologically, corresponding to putative gray wolves, eastern wolves and coyotes. We also documented a substantial number of hybrid individuals (36%) that were admixed between 2 or 3 of the Canis types. Breeding eastern wolves were less common outside of APP, but occurred in some unprotected areas where they were sympatric with a diverse combination of coyotes, gray wolves and hybrids. We found significant spatial genetic structure and identified a steep cline extending west from APP where the dominant genotype shifted abruptly from eastern wolves to coyotes and hybrids. The genotypic pattern to the south and northwest was a more complex mosaic of alternating genotypes. We modelled genetic ancestry in response to prey availability and human disturbance and found that individuals with greater wolf ancestry occupied areas of higher moose density and fewer roads. Our results clarify the structure of the Canis hybrid zone adjacent to APP and provide unique insight into environmental conditions influencing hybridization dynamics between wolves and coyotes. © 2012 Blackwell Publishing Ltd.

Meeting Report: Structural Determination of Environmentally Responsive Proteins

PubMed Central

Reinlib, Leslie

2005-01-01

The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein–protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health. PMID:16263521

Utility of computer simulations in landscape genetics

Treesearch

Bryan K. Epperson; Brad H. McRae; Kim Scribner; Samuel A. Cushman; Michael S. Rosenberg; Marie-Josee Fortin; Patrick M. A. James; Melanie Murphy; Stephanie Manel; Pierre Legendre; Mark R. T. Dale

2010-01-01

Population genetics theory is primarily based on mathematical models in which spatial complexity and temporal variability are largely ignored. In contrast, the field of landscape genetics expressly focuses on how population genetic processes are affected by complex spatial and temporal environmental heterogeneity. It is spatially explicit and relates patterns to...

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

PubMed

Dendrou, Calliope A; Cortes, Adrian; Shipman, Lydia; Evans, Hayley G; Attfield, Kathrine E; Jostins, Luke; Barber, Thomas; Kaur, Gurman; Kuttikkatte, Subita Balaram; Leach, Oliver A; Desel, Christiane; Faergeman, Soren L; Cheeseman, Jane; Neville, Matt J; Sawcer, Stephen; Compston, Alastair; Johnson, Adam R; Everett, Christine; Bell, John I; Karpe, Fredrik; Ultsch, Mark; Eigenbrot, Charles; McVean, Gil; Fugger, Lars

2016-11-02

Thousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders. Copyright © 2016, American Association for the Advancement of Science.

Study of genetic direct search algorithms for function optimization

NASA Technical Reports Server (NTRS)

Zeigler, B. P.

1974-01-01

The results are presented of a study to determine the performance of genetic direct search algorithms in solving function optimization problems arising in the optimal and adaptive control areas. The findings indicate that: (1) genetic algorithms can outperform standard algorithms in multimodal and/or noisy optimization situations, but suffer from lack of gradient exploitation facilities when gradient information can be utilized to guide the search. (2) For large populations, or low dimensional function spaces, mutation is a sufficient operator. However for small populations or high dimensional functions, crossover applied in about equal frequency with mutation is an optimum combination. (3) Complexity, in terms of storage space and running time, is significantly increased when population size is increased or the inversion operator, or the second level adaptation routine is added to the basic structure.

An Adaptive Immune Genetic Algorithm for Edge Detection

NASA Astrophysics Data System (ADS)

Li, Ying; Bai, Bendu; Zhang, Yanning

An adaptive immune genetic algorithm (AIGA) based on cost minimization technique method for edge detection is proposed. The proposed AIGA recommends the use of adaptive probabilities of crossover, mutation and immune operation, and a geometric annealing schedule in immune operator to realize the twin goals of maintaining diversity in the population and sustaining the fast convergence rate in solving the complex problems such as edge detection. Furthermore, AIGA can effectively exploit some prior knowledge and information of the local edge structure in the edge image to make vaccines, which results in much better local search ability of AIGA than that of the canonical genetic algorithm. Experimental results on gray-scale images show the proposed algorithm perform well in terms of quality of the final edge image, rate of convergence and robustness to noise.

Using Multi-Objective Genetic Programming to Synthesize Stochastic Processes

NASA Astrophysics Data System (ADS)

Ross, Brian; Imada, Janine

Genetic programming is used to automatically construct stochastic processes written in the stochastic π-calculus. Grammar-guided genetic programming constrains search to useful process algebra structures. The time-series behaviour of a target process is denoted with a suitable selection of statistical feature tests. Feature tests can permit complex process behaviours to be effectively evaluated. However, they must be selected with care, in order to accurately characterize the desired process behaviour. Multi-objective evaluation is shown to be appropriate for this application, since it permits heterogeneous statistical feature tests to reside as independent objectives. Multiple undominated solutions can be saved and evaluated after a run, for determination of those that are most appropriate. Since there can be a vast number of candidate solutions, however, strategies for filtering and analyzing this set are required.

Saturation of recognition elements blocks evolution of new tRNA identities

PubMed Central

Saint-Léger, Adélaïde; Bello, Carla; Dans, Pablo D.; Torres, Adrian Gabriel; Novoa, Eva Maria; Camacho, Noelia; Orozco, Modesto; Kondrashov, Fyodor A.; Ribas de Pouplana, Lluís

2016-01-01

Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure. PMID:27386510

Preliminary results on the genetic structure of Heterobasidion annosum white fir (Abies concolor) root decay centers

Treesearch

M. Garbelotto; F. Cobb; T. Bruns; W. Otrosina; Garey Slaughter; T. Popenuck

1994-01-01

It is known that Heterobasidion annosum is a complex species comprised of at least three biological species, more precisely defined as intersterility groups (ISGs). The S ISG is widely diffused in North America, Europe, and probably Asia. Although with regional variations, S ISG isolates are commonly found associated with Picea spp., Abies spp., Tsuga spp.,...

Influence of host resistance on the genetic structure of the white pine blister rust fungus in the western United States

Treesearch

B. A. Richardson; N. B. Klopfenstein; P. J. Zambino; G. I. McDonald; B. W. Geils; L. M. Carris

2008-01-01

Cronartium ribicola, the causal agent of white pine blister rust, has been devastating to five-needled white pines in North America since its introduction nearly a century ago. However, dynamic and complex interactions occur among C. ribicola, five-needled white pines, and the environment. To examine potential evolutionary...

Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold

PubMed Central

Ribardo, Deborah A.; Brennan, Caitlin A.; Ruby, Edward G.; Jensen, Grant J.; Hendrixson, David R.

2016-01-01

Although it is known that diverse bacterial flagellar motors produce different torques, the mechanism underlying torque variation is unknown. To understand this difference better, we combined genetic analyses with electron cryo-tomography subtomogram averaging to determine in situ structures of flagellar motors that produce different torques, from Campylobacter and Vibrio species. For the first time, to our knowledge, our results unambiguously locate the torque-generating stator complexes and show that diverse high-torque motors use variants of an ancestrally related family of structures to scaffold incorporation of additional stator complexes at wider radii from the axial driveshaft than in the model enteric motor. We identify the protein components of these additional scaffold structures and elucidate their sequential assembly, demonstrating that they are required for stator-complex incorporation. These proteins are widespread, suggesting that different bacteria have tailored torques to specific environments by scaffolding alternative stator placement and number. Our results quantitatively account for different motor torques, complete the assignment of the locations of the major flagellar components, and provide crucial constraints for understanding mechanisms of torque generation and the evolution of multiprotein complexes. PMID:26976588

From population connectivity to the art of striping Russian dolls: the lessons from Pocillopora corals.

PubMed

Gélin, Pauline; Fauvelot, Cécile; Bigot, Lionel; Baly, Joseph; Magalon, Hélène

2018-01-01

Here, we examined the genetic variability in the coral genus Pocillopora , in particular within the Primary Species Hypothesis PSH09, identified by Gélin, Postaire, Fauvelot and Magalon (2017) using species delimitation methods [also named Pocillopora eydouxi/meandrina complex sensu , Schmidt-Roach, Miller, Lundgren, & Andreakis (2014)] and which was found to split into three secondary species hypotheses (SSH09a, SSH09b, and SSH09c) according to assignment tests using multi-locus genotypes (13 microsatellites). From a large sampling (2,507 colonies) achieved in three marine provinces [Western Indian Ocean (WIO), Tropical Southwestern Pacific (TSP), and Southeast Polynesia (SEP)], genetic structuring analysis conducted with two clustering analyses (structure and DAPC) using 13 microsatellites revealed that SSH09a was restricted to the WIO while SSH09b and SSH09c were almost exclusively in the TSP and SEP. More surprisingly, each SSH split into two to three genetically differentiated clusters, found in sympatry at the reef scale, leading to a pattern of nested hierarchical levels (PSH > SSH > cluster), each level hiding highly differentiated genetic groups. Thus, rather than structured populations within a single species, these three SSHs, and even the eight clusters, likely represent distinct genetic lineages engaged in a speciation process or real species. The issue is now to understand which hierarchical level (SSH, cluster, or even below) corresponds to the species one. Several hypotheses are discussed on the processes leading to this pattern of mixed clusters in sympatry, evoking formation of reproductive barriers, either by allopatric speciation or habitat selection.

The role of protein structural analysis in the next generation sequencing era.

PubMed

Yue, Wyatt W; Froese, D Sean; Brennan, Paul E

2014-01-01

Proteins are macromolecules that serve a cell's myriad processes and functions in all living organisms via dynamic interactions with other proteins, small molecules and cellular components. Genetic variations in the protein-encoding regions of the human genome account for >85% of all known Mendelian diseases, and play an influential role in shaping complex polygenic diseases. Proteins also serve as the predominant target class for the design of small molecule drugs to modulate their activity. Knowledge of the shape and form of proteins, by means of their three-dimensional structures, is therefore instrumental to understanding their roles in disease and their potentials for drug development. In this chapter we outline, with the wide readership of non-structural biologists in mind, the various experimental and computational methods available for protein structure determination. We summarize how the wealth of structure information, contributed to a large extent by the technological advances in structure determination to date, serves as a useful tool to decipher the molecular basis of genetic variations for disease characterization and diagnosis, particularly in the emerging era of genomic medicine, and becomes an integral component in the modern day approach towards rational drug development.

Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor

PubMed Central

Evans, Nicholas J.; Harrison, Odile B.; Clow, Kirsten; Derrick, Jeremy P.; Feavers, Ian M.; Maiden, Martin C. J.

2010-01-01

Meningococcal disease caused by serogroup B Neisseria meningitidis remains an important health problem in many parts of the world, and there are currently no comprehensive vaccines. Poor immunogenicity, combined with immunological identity to human sialic acids, have hindered the development of a serogroup B conjugate vaccine, resulting in the development of alternative vaccine candidates, including many outer-membrane protein (OMP)-based formulations. However, the design of protein-based meningococcal vaccines is complicated by the high level of genetic and antigenic diversity of the meningococcus. Knowledge of the extent and structuring of this diversity can have implications for the use of particular proteins as potential vaccine candidates. With this in mind, the diversity of the meningococcal OMP HmbR was investigated among N. meningitidis isolates representative of major hyper-invasive lineages. In common with other meningococcal antigens, the genetic diversity of hmbR resulted from a combination of intraspecies horizontal genetic exchange and de novo mutation. Furthermore, genealogical analysis showed an association of hmbR genes with clonal complexes and the occurrence of two hmbR families, A and B. Three variable regions (VR1–VR3), located in loops 2, 3 and 4, were observed with clonal complex structuring of VR types. A minority of codons (3.9 %), located within putative surface-exposed loop regions of a 2D model, were under diversifying selection, indicating regions of the protein likely to be subject to immune attack. PMID:20150237

Identification of metapopulation dynamics among Northern Goshawks of the Alexander Archipelago, Alaska, and Coastal British Columbia

USGS Publications Warehouse

Sonsthagen, Sarah A.; McClaren, Erica L.; Doyle, Frank I.; Titus, K.; Sage, George K.; Wilson, Robert E.; Gust, Judy R.; Talbot, Sandra L.

2012-01-01

Northern Goshawks occupying the Alexander Archipelago, Alaska, and coastal British Columbia nest primarily in old-growth and mature forest, which results in spatial heterogeneity in the distribution of individuals across the landscape. We used microsatellite and mitochondrial data to infer genetic structure, gene flow, and fluctuations in population demography through evolutionary time. Patterns in the genetic signatures were used to assess predictions associated with the three population models: panmixia, metapopulation, and isolated populations. Population genetic structure was observed along with asymmetry in gene flow estimates that changed directionality at different temporal scales, consistent with metapopulation model predictions. Therefore, Northern Goshawk assemblages located in the Alexander Archipelago and coastal British Columbia interact through a metapopulation framework, though they may not fit the classic model of a metapopulation. Long-term population sources (coastal mainland British Columbia) and sinks (Revillagigedo and Vancouver islands) were identified. However, there was no trend through evolutionary time in the directionality of dispersal among the remaining assemblages, suggestive of a rescue-effect dynamic. Admiralty, Douglas, and Chichagof island complex appears to be an evolutionarily recent source population in the Alexander Archipelago. In addition, Kupreanof island complex and Kispiox Forest District populations have high dispersal rates to populations in close geographic proximity and potentially serve as local source populations. Metapopulation dynamics occurring in the Alexander Archipelago and coastal British Columbia by Northern Goshawks highlight the importance of both occupied and unoccupied habitats to long-term population persistence of goshawks in this region.

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background.

PubMed

Miguéns, Miguel; Kastanauskaite, Asta; Coria, Santiago M; Selvas, Abraham; Ballesteros-Yañez, Inmaculada; DeFelipe, Javier; Ambrosio, Emilio

2015-01-01

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optimisation of Fabric Reinforced Polymer Composites Using a Variant of Genetic Algorithm

NASA Astrophysics Data System (ADS)

Axinte, Andrei; Taranu, Nicolae; Bejan, Liliana; Hudisteanu, Iuliana

2017-12-01

Fabric reinforced polymeric composites are high performance materials with a rather complex fabric geometry. Therefore, modelling this type of material is a cumbersome task, especially when an efficient use is targeted. One of the most important issue of its design process is the optimisation of the individual laminae and of the laminated structure as a whole. In order to do that, a parametric model of the material has been defined, emphasising the many geometric variables needed to be correlated in the complex process of optimisation. The input parameters involved in this work, include: widths or heights of the tows and the laminate stacking sequence, which are discrete variables, while the gaps between adjacent tows and the height of the neat matrix are continuous variables. This work is one of the first attempts of using a Genetic Algorithm ( GA) to optimise the geometrical parameters of satin reinforced multi-layer composites. Given the mixed type of the input parameters involved, an original software called SOMGA (Satin Optimisation with a Modified Genetic Algorithm) has been conceived and utilised in this work. The main goal is to find the best possible solution to the problem of designing a composite material which is able to withstand to a given set of external, in-plane, loads. The optimisation process has been performed using a fitness function which can analyse and compare mechanical behaviour of different fabric reinforced composites, the results being correlated with the ultimate strains, which demonstrate the efficiency of the composite structure.

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.

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

Duplication and population dynamics shape historic patterns of selection and genetic variation at the major histocompatibility complex in rodents

PubMed Central

Winternitz, Jamie C; Wares, John P

2013-01-01

Genetic variation at the major histocompatibility complex (MHC) is vitally important for wildlife populations to respond to pathogen threats. As natural populations can fluctuate greatly in size, a key issue concerns how population cycles and bottlenecks that could reduce genetic diversity will influence MHC genes. Using 454 sequencing, we characterized genetic diversity at the DRB Class II locus in montane voles (Microtus montanus), a North American rodent that regularly undergoes high-amplitude fluctuations in population size. We tested for evidence of historic balancing selection, recombination, and gene duplication to identify mechanisms maintaining allelic diversity. Counter to our expectations, we found strong evidence of purifying selection acting on the DRB locus in montane voles. We speculate that the interplay between population fluctuations and gene duplication might be responsible for the weak evidence of historic balancing selection and strong evidence of purifying selection detected. To further explore this idea, we conducted a phylogenetically controlled comparative analysis across 16 rodent species with varying demographic histories and MHC duplication events (based on the maximum number of alleles detected per individual). On the basis of phylogenetic generalized linear model-averaging, we found evidence that the estimated number of duplicated loci was positively related to allelic diversity and, surprisingly, to the strength of purifying selection at the DRB locus. Our analyses also revealed that species that had undergone population bottlenecks had lower allelic richness than stable species. This study highlights the need to consider demographic history and genetic structure alongside patterns of natural selection to understand resulting patterns of genetic variation at the MHC. PMID:23789067

Genetic studies of the Roma (Gypsies): a review

PubMed Central

Kalaydjieva, Luba; Gresham, David; Calafell, Francesc

2001-01-01

Background Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups. Conclusion Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma. PMID:11299048

Morphology delimits more species than molecular genetic clusters of invasive Pilosella.

PubMed

Moffat, Chandra E; Ensing, David J; Gaskin, John F; De Clerck-Floate, Rosemarie A; Pither, Jason

2015-07-01

• Accurate assessments of biodiversity are paramount for understanding ecosystem processes and adaptation to change. Invasive species often contribute substantially to local biodiversity; correctly identifying and distinguishing invaders is thus necessary to assess their potential impacts. We compared the reliability of morphology and molecular sequences to discriminate six putative species of invasive Pilosella hawkweeds (syn. Hieracium, Asteraceae), known for unreliable identifications and historical introgression. We asked (1) which morphological traits dependably discriminate putative species, (2) if genetic clusters supported morphological species, and (3) if novel hybridizations occur in the invaded range.• We assessed 33 morphometric characters for their discriminatory power using the randomForest classifier and, using AFLPs, evaluated genetic clustering with the program structure and subsequently with an AMOVA. The strength of the association between morphological and genotypic dissimilarity was assessed with a Mantel test.• Morphometric analyses delimited six species while genetic analyses defined only four clusters. Specifically, we found (1) eight morphological traits could reliably distinguish species, (2) structure suggested strong genetic differentiation but for only four putative species clusters, and (3) genetic data suggest both novel hybridizations and multiple introductions have occurred.• (1) Traditional floristic techniques may resolve more species than molecular analyses in taxonomic groups subject to introgression. (2) Even within complexes of closely related species, relatively few but highly discerning morphological characters can reliably discriminate species. (3) By clarifying patterns of morphological and genotypic variation of invasive Pilosella, we lay foundations for further ecological study and mitigation. © 2015 Botanical Society of America, Inc.

Genetic structure of the Newfoundland and Labrador population: founder effects modulate variability.

PubMed

Zhai, Guangju; Zhou, Jiayi; Woods, Michael O; Green, Jane S; Parfrey, Patrick; Rahman, Proton; Green, Roger C

2016-07-01

The population of the province of Newfoundland and Labrador (NL) has been a resource for genetic studies because of its historical isolation and increased prevalence of several monogenic disorders. Controversy remains regarding the genetic substructure and the extent of genetic homogeneity, which have implications for disease gene mapping. Population substructure has been reported from other isolated populations such as Iceland, Finland and Sardinia. We undertook this study to further our understanding of the genetic architecture of the NL population. We enrolled 494 individuals randomly selected from NL. Genome-wide SNP data were analyzed together with that from 14 other populations including HapMap3, Ireland, Britain and Native American samples from the Human Genome Diversity Project. Using multidimensional scaling and admixture analysis, we observed that the genetic structure of the NL population resembles that of the British population but can be divided into three clusters that correspond to religious/ethnic origins: Protestant English, Roman Catholic Irish and North American aboriginals. We observed reduced heterozygosity and an increased inbreeding coefficient (mean=0.005), which corresponds to that expected in the offspring of third-cousin marriages. We also found that the NL population has a significantly higher number of runs of homozygosity (ROH) and longer lengths of ROH segments. These results are consistent with our understanding of the population history and indicate that the NL population may be ideal for identifying recessive variants for complex diseases that affect populations of European origin.

Estimation of the genetic diversity in tetraploid alfalfa populations based on RAPD markers for breeding purposes.

PubMed

Nagl, Nevena; Taski-Ajdukovic, Ksenija; Barac, Goran; Baburski, Aleksandar; Seccareccia, Ivana; Milic, Dragan; Katic, Slobodan

2011-01-01

Alfalfa is an autotetraploid, allogamous and heterozygous forage legume, whose varieties are synthetic populations. Due to the complex nature of the species, information about genetic diversity of germplasm used in any alfalfa breeding program is most beneficial. The genetic diversity of five alfalfa varieties, involved in progeny tests at Institute of Field and Vegetable Crops, was characterized based on RAPD markers. A total of 60 primers were screened, out of which 17 were selected for the analysis of genetic diversity. A total of 156 polymorphic bands were generated, with 10.6 bands per primer. Number and percentage of polymorphic loci, effective number of alleles, expected heterozygosity and Shannon's information index were used to estimate genetic variation. Variety Zuzana had the highest values for all tested parameters, exhibiting the highest level of variation, whereas variety RSI 20 exhibited the lowest. Analysis of molecular variance (AMOVA) showed that 88.39% of the total genetic variation was attributed to intra-varietal variance. The cluster analysis for individual samples and varieties revealed differences in their population structures: variety Zuzana showed a very high level of genetic variation, Banat and Ghareh were divided in subpopulations, while Pecy and RSI 20 were relatively uniform. Ways of exploiting the investigated germplasm in the breeding programs are suggested in this paper, depending on their population structure and diversity. The RAPD analysis shows potential to be applied in analysis of parental populations in semi-hybrid alfalfa breeding program in both, development of new homogenous germplasm, and identification of promising, complementary germplasm.

Genetic Drift Linked to Heterogeneous Landscape and Ecological Specialization Drives Diversification in the Alpine Endemic Columbine Aquilegia thalictrifolia.

PubMed

Lega, Margherita; Fior, Simone; Li, Mingai; Leonardi, Stefano; Varotto, Claudio

2014-01-01

The European Alpine system is an extensive mountain range, whose heterogeneous landscape together with Quaternary climatic oscillations significantly affected organismal diversity and distribution in Europe. The model genus Aquilegia represents a textbook example of a rapid and recent radiation through the Northern hemisphere, with the majority of the European taxa occuring in the Alpine system. However, the processes governing genetic differentiation of the genus in this complex geographic area are still widely unexplored. In this work, we used 9 microsatellite loci to study the genetic structure and diversity of 11 populations of Aquilegia thalictrifolia Schott & Kotschy, an alpine taxon characterized by a marked ecological specificity. We found that, despite the endemic and fragmented distribution, A. thalictrifolia has overall high levels of heterozygosity, which is consistent to the substantial inbreeding depression that characterizes the genus. Strong spatial genetic structuring of populations suggests a historical prevalence of genetic drift over gene flow, with natural barriers and ecological niche hindering migration. An analytical comparison of fixation and population differentiation indexes allowed us to infer hypotheses of the postglacial history and more recent demographic events that have influenced the genetics of the species. Overall, our results indicate allopatry as a major force of differentiation in the European scenario, likely to underlie the development of taxonomic boundaries in a broader geographic context. This adds to previous notions on the primary evolutionary forces shaping the Aquilegia radiation in Europe. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cryptic or pseudocryptic: can morphological methods inform copepod taxonomy? An analysis of publications and a case study of the Eurytemora affinis species complex

PubMed Central

Lajus, Dmitry; Sukhikh, Natalia; Alekseev, Victor

2015-01-01

Interest in cryptic species has increased significantly with current progress in genetic methods. The large number of cryptic species suggests that the resolution of traditional morphological techniques may be insufficient for taxonomical research. However, some species now considered to be cryptic may, in fact, be designated pseudocryptic after close morphological examination. Thus the “cryptic or pseudocryptic” dilemma speaks to the resolution of morphological analysis and its utility for identifying species. We address this dilemma first by systematically reviewing data published from 1980 to 2013 on cryptic species of Copepoda and then by performing an in-depth morphological study of the former Eurytemora affinis complex of cryptic species. Analyzing the published data showed that, in 5 of 24 revisions eligible for systematic review, cryptic species assignment was based solely on the genetic variation of forms without detailed morphological analysis to confirm the assignment. Therefore, some newly described cryptic species might be designated pseudocryptic under more detailed morphological analysis as happened with Eurytemora affinis complex. Recent genetic analyses of the complex found high levels of heterogeneity without morphological differences; it is argued to be cryptic. However, next detailed morphological analyses allowed to describe a number of valid species. Our study, using deep statistical analyses usually not applied for new species describing, of this species complex confirmed considerable differences between former cryptic species. In particular, fluctuating asymmetry (FA), the random variation of left and right structures, was significantly different between forms and provided independent information about their status. Our work showed that multivariate statistical approaches, such as principal component analysis, can be powerful techniques for the morphological discrimination of cryptic taxons. Despite increasing cryptic species designations, morphological techniques have great potential in determining copepod taxonomy. PMID:26120427

MHC class II is an important genetic risk factor for canine systemic lupus erythematosus (SLE)-related disease: implications for reproductive success.

PubMed

Wilbe, M; Andersson, G

2012-01-01

Major histocompatibility complex (MHC) class II genes are important genetic risk factors for development of immune-mediated diseases in mammals. Recently, the dog (Canis lupus familiaris) has emerged as a useful model organism to identify critical MHC class II genotypes that contribute to development of these diseases. Therefore, a study aimed to evaluate a potential genetic association between the dog leukocyte antigen (DLA) class II region and an immune-mediated disease complex in dogs of the Nova Scotia duck tolling retriever breed was performed. We show that DLA is one of several genetic risk factors for this disease complex and that homozygosity of the risk haplotype is disadvantageous. Importantly, the disease is complex and has many genetic risk factors and therefore we cannot provide recommendations for breeders exclusively on the basis of genetic testing for DLA class II genotype. © 2012 Blackwell Verlag GmbH.

Genome Structure of the Legume, Lotus japonicus

PubMed Central

Sato, Shusei; Nakamura, Yasukazu; Kaneko, Takakazu; Asamizu, Erika; Kato, Tomohiko; Nakao, Mitsuteru; Sasamoto, Shigemi; Watanabe, Akiko; Ono, Akiko; Kawashima, Kumiko; Fujishiro, Tsunakazu; Katoh, Midori; Kohara, Mitsuyo; Kishida, Yoshie; Minami, Chiharu; Nakayama, Shinobu; Nakazaki, Naomi; Shimizu, Yoshimi; Shinpo, Sayaka; Takahashi, Chika; Wada, Tsuyuko; Yamada, Manabu; Ohmido, Nobuko; Hayashi, Makoto; Fukui, Kiichi; Baba, Tomoya; Nakamichi, Tomoko; Mori, Hirotada; Tabata, Satoshi

2008-01-01

The legume Lotus japonicus has been widely used as a model system to investigate the genetic background of legume-specific phenomena such as symbiotic nitrogen fixation. Here, we report structural features of the L. japonicus genome. The 315.1-Mb sequences determined in this and previous studies correspond to 67% of the genome (472 Mb), and are likely to cover 91.3% of the gene space. Linkage mapping anchored 130-Mb sequences onto the six linkage groups. A total of 10 951 complete and 19 848 partial structures of protein-encoding genes were assigned to the genome. Comparative analysis of these genes revealed the expansion of several functional domains and gene families that are characteristic of L. japonicus. Synteny analysis detected traces of whole-genome duplication and the presence of synteny blocks with other plant genomes to various degrees. This study provides the first opportunity to look into the complex and unique genetic system of legumes. PMID:18511435

Conformational changes in the expression domain of the Escherichia coli thiM riboswitch

PubMed Central

Rentmeister, Andrea; Mayer, Günter; Kuhn, Nicole; Famulok, Michael

2007-01-01

The thiM riboswitch contains an aptamer domain that adaptively binds the coenzyme thiamine pyrophosphate (TPP). The binding of TPP to the aptamer domain induces structural rearrangements that are relayed to a second domain, the so-called expression domain, thereby interfering with gene expression. The recently solved crystal structures of the aptamer domains of the thiM riboswitches in complex with TPP revealed how TPP stabilizes secondary and tertiary structures in the RNA ligand complex. To understand the global modes of reorganization between the two domains upon metabolite binding the structure of the entire riboswitch in presence and absence of TPP needs to be determined. Here we report the secondary structure of the entire thiM riboswitch from Escherichia coli in its TPP-free form and its transition into the TPP-bound variant, thereby depicting domains of the riboswitch that serve as communication links between the aptamer and the expression domain. Furthermore, structural probing provides an explanation for the lack of genetic control exerted by a riboswitch variant with mutations in the expression domain that still binds TPP. PMID:17517779

Data Mining and Complex Problems: Case Study in Composite Materials

NASA Technical Reports Server (NTRS)

Rabelo, Luis; Marin, Mario

2009-01-01

Data mining is defined as the discovery of useful, possibly unexpected, patterns and relationships in data using statistical and non-statistical techniques in order to develop schemes for decision and policy making. Data mining can be used to discover the sources and causes of problems in complex systems. In addition, data mining can support simulation strategies by finding the different constants and parameters to be used in the development of simulation models. This paper introduces a framework for data mining and its application to complex problems. To further explain some of the concepts outlined in this paper, the potential application to the NASA Shuttle Reinforced Carbon-Carbon structures and genetic programming is used as an illustration.

State of the art in forensic investigation of sudden cardiac death.

PubMed

Oliva, Antonio; Brugada, Ramon; D'Aloja, Ernesto; Boschi, Ilaria; Partemi, Sara; Brugada, Josep; Pascali, Vincenzo L

2011-03-01

The sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death. Many of the causes of sudden death are due to genetic heart disorders, which can lead to both structural (eg, hypertrophic cardiomyopathy) and arrhythmogenic abnormalities (eg, familial long QT syndrome, Brugada syndrome). Most commonly, sudden cardiac death can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a great challenge to the forensic pathologist involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counselor, and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological, and social complexities observed in families in which there has been a young sudden cardiac death. The present study will address the spectrum of structural substrates of cardiac sudden death with particular emphasis given to the possible role of forensic molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability.

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 years, although the majority of invasive infections was associated with MSSA strains. Moreover, an association between age group of children from the study population and a specific strain genotype (spa type, clonal complex or genetic content) was observed among the patients. PMID:26992009

Distribution and Polymorphism of the Flagellin Genes from Isolates of Campylobacter coli and Campylobacter jejuni

DTIC Science & Technology

1993-05-01

R. M . Barker, P. B. 51. Whitians, T. S., and R. A. Wilson. 1988. Genetic relationships Crichton , D. C. Old, 3. M . Musser, and T. S. Whittam. 1990...a, y and iden{ify •)y Mock • J" -- "--"/’•" i l i • • ELECTEI Iq S*/, o.o a•l "(3 ! : .• m -..- ,.,. • ! Ir,,Ji-- = •, / !.9 • > ,•=’:I-; / o•/ t...siderable genetic diversity among the fin genes in Campylo- structural diversity of flagellins which form complex flagella. acter spp. A ithough a m o f th

'Battling my biology': psychological effects of genetic testing for risk of weight gain.

PubMed

Meisel, S F; Wardle, J

2014-04-01

The availability of genetic tests for multifactorial conditions such as obesity raises concerns that higher-risk results could lead to fatalistic reactions or lower-risk results to complacency. No study has investigated the effects of genetic test feedback for the risk of obesity in non-clinical samples. The present study explored psychological and behavioral reactions to genetic test feedback for a weight related gene (FTO) in a volunteer sample (n = 18) using semi-structured interviews. Respondents perceived the gene test result as scientifically objective; removing some of the emotion attached to the issue of weight control. Those who were struggling with weight control reported relief of self-blame. There was no evidence for either complacency or fatalism; all respondents emphasized the importance of lifestyle choices in long-term weight management, although they recognized the role of both genes and environment. Regardless of the test result, respondents evaluated the testing positively and found it motivating and informative. Genetic test feedback for risk of weight gain may offer psychological benefits beyond its objectively limited clinical utility. As the role of genetic counselors is likely to expand, awareness of reasons for genetic testing for common, complex conditions and reactions to the test result is important.

Introduction to focus issue: quantitative approaches to genetic networks.

PubMed

Albert, Réka; Collins, James J; Glass, Leon

2013-06-01

All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

Balancing selection and genetic drift at major histocompatibility complex class II genes in isolated populations of golden snub-nosed monkey (Rhinopithecus roxellana)

PubMed Central

2012-01-01

Background Small, isolated populations often experience loss of genetic variation due to random genetic drift. Unlike neutral or nearly neutral markers (such as mitochondrial genes or microsatellites), major histocompatibility complex (MHC) genes in these populations may retain high levels of polymorphism due to balancing selection. The relative roles of balancing selection and genetic drift in either small isolated or bottlenecked populations remain controversial. In this study, we examined the mechanisms maintaining polymorphisms of MHC genes in small isolated populations of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) by comparing genetic variation found in MHC and microsatellite loci. There are few studies of this kind conducted on highly endangered primate species. Results Two MHC genes were sequenced and sixteen microsatellite loci were genotyped from samples representing three isolated populations. We isolated nine DQA1 alleles and sixteen DQB1 alleles and validated expression of the alleles. Lowest genetic variation for both MHC and microsatellites was found in the Shennongjia (SNJ) population. Historical balancing selection was revealed at both the DQA1 and DQB1 loci, as revealed by excess non-synonymous substitutions at antigen binding sites (ABS) and maximum-likelihood-based random-site models. Patterns of microsatellite variation revealed population structure. FST outlier analysis showed that population differentiation at the two MHC loci was similar to the microsatellite loci. Conclusions MHC genes and microsatellite loci showed the same allelic richness pattern with the lowest genetic variation occurring in SNJ, suggesting that genetic drift played a prominent role in these isolated populations. As MHC genes are subject to selective pressures, the maintenance of genetic variation is of particular interest in small, long-isolated populations. The results of this study may contribute to captive breeding and translocation programs for endangered species. PMID:23083308

Introduction to Focus Issue: Quantitative Approaches to Genetic Networks

NASA Astrophysics Data System (ADS)

Albert, Réka; Collins, James J.; Glass, Leon

2013-06-01

All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

The structure of people's hair.

PubMed

Yang, Fei-Chi; Zhang, Yuchen; Rheinstädter, Maikel C

2014-01-01

Hair is a filamentous biomaterial consisting mainly of proteins in particular keratin. The structure of human hair is well known: the medulla is a loosely packed, disordered region near the centre of the hair surrounded by the cortex, which contains the major part of the fibre mass, mainly consisting of keratin proteins and structural lipids. The cortex is surrounded by the cuticle, a layer of dead, overlapping cells forming a protective layer around the hair. The corresponding structures have been studied extensively using a variety of different techniques, such as light, electron and atomic force microscopes, and also X-ray diffraction. We were interested in the question how much the molecular hair structure differs from person to person, between male and female hair, hair of different appearances such as colour and waviness. We included hair from parent and child, identical and fraternal twins in the study to see if genetically similar hair would show similar structural features. The molecular structure of the hair samples was studied using high-resolution X-ray diffraction, which covers length scales from molecules up to the organization of secondary structures. Signals due to the coiled-coil phase of α-helical keratin proteins, intermediate keratin filaments in the cortex and from the lipid layers in the cell membrane complex were observed in the specimen of all individuals, with very small deviations. Despite the relatively small number of individuals (12) included in this study, some conclusions can be drawn. While the general features were observed in all individuals and the corresponding molecular structures were almost identical, additional signals were observed in some specimen and assigned to different types of lipids in the cell membrane complex. Genetics seem to play a role in this composition as identical patterns were observed in hair from father and daughter and identical twins, however, not for fraternal twins. Identification and characterization of these features is an important step towards the detection of abnormalities in the molecular structure of hair as a potential diagnostic tool for certain diseases.

Genetic variations in the serotonergic system contribute to amygdala volume in humans.

PubMed

Li, Jin; Chen, Chunhui; Wu, Karen; Zhang, Mingxia; Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K; Dong, Qi

2015-01-01

The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1%) and the reported 63-65% heritability of amygdala structure. To understand the "missing heritability," we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p = 0.043, permuted for 1000 times). Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure.

Historical and current introgression in a Mesoamerican hummingbird species complex: a biogeographic perspective

PubMed Central

Jiménez, Rosa Alicia

2016-01-01

The influence of geologic and Pleistocene glacial cycles might result in morphological and genetic complex scenarios in the biota of the Mesoamerican region. We tested whether berylline, blue-tailed and steely-blue hummingbirds, Amazilia beryllina, Amazilia cyanura and Amazilia saucerottei, show evidence of historical or current introgression as their plumage colour variation might suggest. We also analysed the role of past and present climatic events in promoting genetic introgression and species diversification. We collected mitochondrial DNA (mtDNA) sequence data and microsatellite loci scores for populations throughout the range of the three Amazilia species, as well as morphological and ecological data. Haplotype network, Bayesian phylogenetic and divergence time inference, historical demography, palaeodistribution modelling, and niche divergence tests were used to reconstruct the evolutionary history of this Amazilia species complex. An isolation-with-migration coalescent model and Bayesian assignment analysis were assessed to determine historical introgression and current genetic admixture. mtDNA haplotypes were geographically unstructured, with haplotypes from disparate areas interdispersed on a shallow tree and an unresolved haplotype network. Assignment analysis of the nuclear genome (nuDNA) supported three genetic groups with signs of genetic admixture, corresponding to: (1) A. beryllina populations located west of the Isthmus of Tehuantepec; (2) A. cyanura populations between the Isthmus of Tehuantepec and the Nicaraguan Depression (Nuclear Central America); and (3) A. saucerottei populations southeast of the Nicaraguan Depression. Gene flow and divergence time estimates, and demographic and palaeodistribution patterns suggest an evolutionary history of introgression mediated by Quaternary climatic fluctuations. High levels of gene flow were indicated by mtDNA and asymmetrical isolation-with-migration, whereas the microsatellite analyses found evidence for three genetic clusters with distributions corresponding to isolation by the Isthmus of Tehuantepec and the Nicaraguan Depression and signs of admixture. Historical levels of migration between genetically distinct groups estimated using microsatellites were higher than contemporary levels of migration. These results support the scenario of secondary contact and range contact during the glacial periods of the Pleistocene and strongly imply that the high levels of structure currently observed are a consequence of the limited dispersal of these hummingbirds across the isthmus and depression barriers. PMID:26788433

Genetic relatedness of previously Plant-Variety-Protected commercial maize inbreds.

PubMed

Beckett, Travis J; Morales, A Jason; Koehler, Klaus L; Rocheford, Torbert R

2017-01-01

The emergence of high-throughput, high-density genotyping methods combined with increasingly powerful computing systems has created opportunities to further discover and exploit the genes controlling agronomic performance in elite maize breeding populations. Understanding the genetic basis of population structure in an elite set of materials is an essential step in this genetic discovery process. This paper presents a genotype-based population analysis of all maize inbreds whose Plant Variety Protection certificates had expired as of the end of 2013 (283 inbreds) as well as 66 public founder inbreds. The results provide accurate population structure information and allow for important inferences in context of the historical development of North American elite commercial maize germplasm. Genotypic data was obtained via genotyping-by-sequencing on 349 inbreds. After filtering for missing data, 77,314 high-quality markers remained. The remaining missing data (average per individual was 6.22 percent) was fully imputed at an accuracy of 83 percent. Calculation of linkage disequilibrium revealed that the average r2 of 0.20 occurs at approximately 1.1 Kb. Results of population genetics analyses agree with previously published studies that divide North American maize germplasm into three heterotic groups: Stiff Stalk, Non-Stiff Stalk, and Iodent. Principal component analysis shows that population differentiation is indeed very complex and present at many levels, yet confirms that division into three main sub-groups is optimal for population description. Clustering based on Nei's genetic distance provides an additional empirical representation of the three main heterotic groups. Overall fixation index (FST), indicating the degree of genetic divergence between the three main heterotic groups, was 0.1361. Understanding the genetic relationships and population differentiation of elite germplasm may help breeders to maintain and potentially increase the rate of genetic gain, resulting in higher overall agronomic performance.

Epigenetics and Epigenomics of Plants.

PubMed

Yadav, Chandra Bhan; Pandey, Garima; Muthamilarasan, Mehanathan; Prasad, Manoj

2018-01-23

The genetic material DNA in association with histone proteins forms the complex structure called chromatin, which is prone to undergo modification through certain epigenetic mechanisms including cytosine DNA methylation, histone modifications, and small RNA-mediated methylation. Alterations in chromatin structure lead to inaccessibility of genomic DNA to various regulatory proteins such as transcription factors, which eventually modulates gene expression. Advancements in high-throughput sequencing technologies have provided the opportunity to study the epigenetic mechanisms at genome-wide levels. Epigenomic studies using high-throughput technologies will widen the understanding of mechanisms as well as functions of regulatory pathways in plant genomes, which will further help in manipulating these pathways using genetic and biochemical approaches. This technology could be a potential research tool for displaying the systematic associations of genetic and epigenetic variations, especially in terms of cytosine methylation onto the genomic region in a specific cell or tissue. A comprehensive study of plant populations to correlate genotype to epigenotype and to phenotype, and also the study of methyl quantitative trait loci (QTL) or epiGWAS, is possible by using high-throughput sequencing methods, which will further accelerate molecular breeding programs for crop improvement. Graphical Abstract.

Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.

PubMed

Morello, Roy; Lee, Brendan

2002-05-01

In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity

NASA Astrophysics Data System (ADS)

Simon, Joseph R.; Carroll, Nick J.; Rubinstein, Michael; Chilkoti, Ashutosh; López, Gabriel P.

2017-06-01

Dynamic protein-rich intracellular structures that contain phase-separated intrinsically disordered proteins (IDPs) composed of sequences of low complexity (SLC) have been shown to serve a variety of important cellular functions, which include signalling, compartmentalization and stabilization. However, our understanding of these structures and our ability to synthesize models of them have been limited. We present design rules for IDPs possessing SLCs that phase separate into diverse assemblies within droplet microenvironments. Using theoretical analyses, we interpret the phase behaviour of archetypal IDP sequences and demonstrate the rational design of a vast library of multicomponent protein-rich structures that ranges from uniform nano-, meso- and microscale puncta (distinct protein droplets) to multilayered orthogonally phase-separated granular structures. The ability to predict and program IDP-rich assemblies in this fashion offers new insights into (1) genetic-to-molecular-to-macroscale relationships that encode hierarchical IDP assemblies, (2) design rules of such assemblies in cell biology and (3) molecular-level engineering of self-assembled recombinant IDP-rich materials.

SM2PH-db: an interactive system for the integrated analysis of phenotypic consequences of missense mutations in proteins involved in human genetic diseases.

PubMed

Friedrich, Anne; Garnier, Nicolas; Gagnière, Nicolas; Nguyen, Hoan; Albou, Laurent-Philippe; Biancalana, Valérie; Bettler, Emmanuel; Deléage, Gilbert; Lecompte, Odile; Muller, Jean; Moras, Dino; Mandel, Jean-Louis; Toursel, Thierry; Moulinier, Luc; Poch, Olivier

2010-02-01

Understanding how genetic alterations affect gene products at the molecular level represents a first step in the elucidation of the complex relationships between genotypic and phenotypic variations, and is thus a major challenge in the postgenomic era. Here, we present SM2PH-db (http://decrypthon.igbmc.fr/sm2ph), a new database designed to investigate structural and functional impacts of missense mutations and their phenotypic effects in the context of human genetic diseases. A wealth of up-to-date interconnected information is provided for each of the 2,249 disease-related entry proteins (August 2009), including data retrieved from biological databases and data generated from a Sequence-Structure-Evolution Inference in Systems-based approach, such as multiple alignments, three-dimensional structural models, and multidimensional (physicochemical, functional, structural, and evolutionary) characterizations of mutations. SM2PH-db provides a robust infrastructure associated with interactive analysis tools supporting in-depth study and interpretation of the molecular consequences of mutations, with the more long-term goal of elucidating the chain of events leading from a molecular defect to its pathology. The entire content of SM2PH-db is regularly and automatically updated thanks to a computational grid data federation facilities provided in the context of the Decrypthon program. (c) 2009 Wiley-Liss, Inc.

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.

Cortical complexity in bipolar disorder applying a spherical harmonics approach.

PubMed

Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

2017-05-30

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Enantioselective synthesis of pactamycin, a complex antitumor antibiotic.

PubMed

Malinowski, Justin T; Sharpe, Robert J; Johnson, Jeffrey S

2013-04-12

Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties across multiple phylogenetic domains, but it is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.

Visualizing Viral Protein Structures in Cells Using Genetic Probes for Correlated Light and Electron Microscopy

PubMed Central

Ou, Horng D.; Deerinck, Thomas J.; Bushong, Eric; Ellisman, Mark H.; O’Shea, Clodagh C.

2015-01-01

Structural studies of viral proteins most often use high-resolution techniques such as X-ray crystallography, nuclear magnetic resonance, single particle negative stain, or cryo-electron microscopy (EM) to reveal atomic interactions of soluble, homogeneous viral proteins or viral protein complexes. Once viral proteins or complexes are separated from their host’s cellular environment, their natural in-situ structure and details of how they interact with other cellular components may be lost. EM has been an invaluable tool in virology since its introduction in the late 1940’s and subsequent application to cells in the 1950’s. EM studies have expanded our knowledge of viral entry, viral replication, alteration of cellular components, and viral lysis. Most of these early studies were focused on conspicuous morphological cellular changes, because classic EM metal stains were designed to highlight classes of cellular structures rather than specific molecular structures. Much later, to identify viral proteins inducing specific structural configurations at the cellular level, immunostaining with a primary antibody followed by colloidal gold secondary antibody was employed to mark the location of specific viral proteins. This technique can suffer from artifacts in cellular ultrastructure due to compromises required to provide access to the immuno-reagents. Immunolocalization methods also require the generation of highly specific antibodies, which may not be available for every viral protein. Here we discuss new methods to visualize viral proteins and structures at high resolutions in-situ using correlated light and electron microscopy (CLEM). We discuss the use of genetically encoded protein fusions that oxidize diaminobenzidine (DAB) into an osmiophilic polymer that can be visualized by EM. Detailed protocols for applying the genetically encoded photo-oxidizing protein MiniSOG to a viral protein, photo-oxidation of the fusion protein to yield DAB polymer staining, and preparation of photo-oxidized samples for TEM and serial block-face scanning EM (SBEM) for large-scale volume EM data acquisition are also presented. As an example, we discuss the recent multi-scale analysis of Adenoviral protein E4-ORF3 that reveals a new type of multi-functional polymer that disrupts multiple cellular proteins. This new capability to visualize unambiguously specific viral protein structures at high resolutions in the native cellular environment is revealing new insights into how they usurp host proteins and functions to drive pathological viral replication. PMID:26066760

Visualizing viral protein structures in cells using genetic probes for correlated light and electron microscopy.

PubMed

Ou, Horng D; Deerinck, Thomas J; Bushong, Eric; Ellisman, Mark H; O'Shea, Clodagh C

2015-11-15

Structural studies of viral proteins most often use high-resolution techniques such as X-ray crystallography, nuclear magnetic resonance, single particle negative stain, or cryo-electron microscopy (EM) to reveal atomic interactions of soluble, homogeneous viral proteins or viral protein complexes. Once viral proteins or complexes are separated from their host's cellular environment, their natural in situ structure and details of how they interact with other cellular components may be lost. EM has been an invaluable tool in virology since its introduction in the late 1940's and subsequent application to cells in the 1950's. EM studies have expanded our knowledge of viral entry, viral replication, alteration of cellular components, and viral lysis. Most of these early studies were focused on conspicuous morphological cellular changes, because classic EM metal stains were designed to highlight classes of cellular structures rather than specific molecular structures. Much later, to identify viral proteins inducing specific structural configurations at the cellular level, immunostaining with a primary antibody followed by colloidal gold secondary antibody was employed to mark the location of specific viral proteins. This technique can suffer from artifacts in cellular ultrastructure due to compromises required to provide access to the immuno-reagents. Immunolocalization methods also require the generation of highly specific antibodies, which may not be available for every viral protein. Here we discuss new methods to visualize viral proteins and structures at high resolutions in situ using correlated light and electron microscopy (CLEM). We discuss the use of genetically encoded protein fusions that oxidize diaminobenzidine (DAB) into an osmiophilic polymer that can be visualized by EM. Detailed protocols for applying the genetically encoded photo-oxidizing protein MiniSOG to a viral protein, photo-oxidation of the fusion protein to yield DAB polymer staining, and preparation of photo-oxidized samples for TEM and serial block-face scanning EM (SBEM) for large-scale volume EM data acquisition are also presented. As an example, we discuss the recent multi-scale analysis of Adenoviral protein E4-ORF3 that reveals a new type of multi-functional polymer that disrupts multiple cellular proteins. This new capability to visualize unambiguously specific viral protein structures at high resolutions in the native cellular environment is revealing new insights into how they usurp host proteins and functions to drive pathological viral replication. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Centrioles, centrosomes, and cilia in health and disease.

PubMed

Nigg, Erich A; Raff, Jordan W

2009-11-13

Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia.

Mate choice for major histocompatibility complex genetic divergence as a bet-hedging strategy in the Atlantic salmon (Salmo salar).

PubMed

Evans, Melissa L; Dionne, Mélanie; Miller, Kristina M; Bernatchez, Louis

2012-01-22

Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (Salmo salar) in Québec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0+ and 1+, and 1+ and 2+ and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHC-dependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures.

Population and allelic variation of A-to-I RNA editing in human transcriptomes.

PubMed

Park, Eddie; Guo, Jiguang; Shen, Shihao; Demirdjian, Levon; Wu, Ying Nian; Lin, Lan; Xing, Yi

2017-07-28

A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of RNA editing. In order to determine the influence of genetic variation on A-to-I RNA editing, we integrate genomic and transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis. We identify 1054 RNA editing events associated with cis genetic polymorphisms. Additionally, we find that a subset of these polymorphisms is linked to genome-wide association study signals of complex traits or diseases. Finally, compared to random cis polymorphisms, polymorphisms associated with RNA editing variation are located closer spatially to their respective editing sites and have a more pronounced impact on RNA secondary structure. Our study reveals widespread cis variation in RNA editing among genetically distinct individuals and sheds light on possible phenotypic consequences of such variation on complex traits and diseases.

Mate choice for major histocompatibility complex genetic divergence as a bet-hedging strategy in the Atlantic salmon (Salmo salar)

PubMed Central

Evans, Melissa L.; Dionne, Mélanie; Miller, Kristina M.; Bernatchez, Louis

2012-01-01

Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (Salmo salar) in Québec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0+ and 1+, and 1+ and 2+ and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHC-dependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures. PMID:21697172

Proteome complexity and the forces that drive proteome imbalance.

PubMed

Harper, J Wade; Bennett, Eric J

2016-09-15

The cellular proteome is a complex microcosm of structural and regulatory networks that requires continuous surveillance and modification to meet the dynamic needs of the cell. It is therefore crucial that the protein flux of the cell remains in balance to ensure proper cell function. Genetic alterations that range from chromosome imbalance to oncogene activation can affect the speed, fidelity and capacity of protein biogenesis and degradation systems, which often results in proteome imbalance. An improved understanding of the causes and consequences of proteome imbalance is helping to reveal how these systems can be targeted to treat diseases such as cancer.

Molecular Mechanisms of Inner Ear Development

PubMed Central

Wu, Doris K.; Kelley, Matthew W.

2012-01-01

The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms. PMID:22855724

Suppressor Analysis of the Fusogenic Lambda Spanins.

PubMed

Cahill, Jesse; Rajaure, Manoj; Holt, Ashley; Moreland, Russell; O'Leary, Chandler; Kulkarni, Aneesha; Sloan, Jordan; Young, Ry

2017-07-15

The final step of lysis in phage λ infections of Escherichia coli is mediated by the spanins Rz and Rz1. These proteins form a complex that bridges the cell envelope and that has been proposed to cause fusion of the inner and outer membranes. Accordingly, mutations that block spanin function are found within coiled-coil domains and the proline-rich region, motifs essential in other fusion systems. To gain insight into spanin function, pseudorevertant alleles that restored plaque formation for lysis-defective mutants of Rz and Rz1 were selected. Most second-site suppressors clustered within a coiled-coil domain of Rz near the outer leaflet of the cytoplasmic membrane and were not allele specific. Suppressors largely encoded polar insertions within the hydrophobic core of the coiled-coil interface. Such suppressor changes resulted in decreased proteolytic stability of the Rz double mutants in vivo Unlike the wild type, in which lysis occurs while the cells retain a rod shape, revertant alleles with second-site suppressor mutations supported lysis events that were preceded by spherical cell formation. This suggests that destabilization of the membrane-proximal coiled coil restores function for defective spanin alleles by increasing the conformational freedom of the complex at the cost of its normal, all-or-nothing functionality. IMPORTANCE Caudovirales encode cell envelope-spanning proteins called spanins, which are thought to fuse the inner and outer membranes during phage lysis. Recent genetic analysis identified the functional domains of the lambda spanins, which are similar to class I viral fusion proteins. While the pre- and postfusion structures of model fusion systems have been well characterized, the intermediate structure(s) formed during the fusion reaction remains elusive. Genetic analysis would be expected to identify functional connections between intermediates. Since most membrane fusion systems are not genetically tractable, only few such investigations have been reported. Here, we report a suppressor analysis of lambda spanin function. To our knowledge this is the first suppression analysis of a class I-like complex and also the first such analysis of a prokaryote membrane fusion system. Copyright © 2017 American Society for Microbiology.

Circumpolar Genetic Structure and Recent Gene Flow of Polar Bears: A Reanalysis.

PubMed

Malenfant, René M; Davis, Corey S; Cullingham, Catherine I; Coltman, David W

2016-01-01

Recently, an extensive study of 2,748 polar bears (Ursus maritimus) from across their circumpolar range was published in PLOS ONE, which used microsatellites and mitochondrial haplotypes to apparently show altered population structure and a dramatic change in directional gene flow towards the Canadian Archipelago-an area believed to be a future refugium for polar bears as their southernmost habitats decline under climate change. Although this study represents a major international collaborative effort and promised to be a baseline for future genetics work, methodological shortcomings and errors of interpretation undermine some of the study's main conclusions. Here, we present a reanalysis of this data in which we address some of these issues, including: (1) highly unbalanced sample sizes and large amounts of systematically missing data; (2) incorrect calculation of FST and of significance levels; (3) misleading estimates of recent gene flow resulting from non-convergence of the program BayesAss. In contrast to the original findings, in our reanalysis we find six genetic clusters of polar bears worldwide: the Hudson Bay Complex, the Western and Eastern Canadian Arctic Archipelago, the Western and Eastern Polar Basin, and-importantly-we reconfirm the presence of a unique and possibly endangered cluster of bears in Norwegian Bay near Canada's expected last sea-ice refugium. Although polar bears' abundance, distribution, and population structure will certainly be negatively affected by ongoing-and increasingly rapid-loss of Arctic sea ice, these genetic data provide no evidence of strong directional gene flow in response to recent climate change.

The Population Origins and Expansion of Feral Cats in Australia.

PubMed

Spencer, Peter B S; Yurchenko, Andrey A; David, Victor A; Scott, Rachael; Koepfli, Klaus-Peter; Driscoll, Carlos; O'Brien, Stephen J; Menotti-Raymond, Marilyn

2016-03-01

The historical literature suggests that in Australia, the domestic cat (Felis catus) had a European origin [~200 years before present (ybp)], but it is unclear if cats arrived from across the Asian land bridge contemporaneously with the dingo (4000 ybp), or perhaps immigrated ~40000 ybp in association with Aboriginal settlement from Asia. The origin of cats in Australia is important because the continent has a complex and ancient faunal assemblage that is dominated by endemic rodents and marsupials and lacks the large placental carnivores found on other large continents. Cats are now ubiquitous across the entire Australian continent and have been implicit in the range contraction or extinction of its small to medium sized (<3.5kg) mammals. We analyzed the population structure of 830 cats using 15 short tandem repeat (STR) genomic markers. Their origin appears to come exclusively from European founders. Feral cats in continental Australia exhibit high genetic diversity in comparison with the low diversity found in populations of feral cats living on islands. The genetic structure is consistent with a rapid westerly expansion from eastern Australia and a limited expansion in coastal Western Australia. Australian cats show modest if any population structure and a close genetic alignment with European feral cats as compared to cats from Asia, the Christmas and Cocos (Keeling) Islands (Indian Ocean), and European wildcats (F. silvestris silvestris). © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Environmental Sensing of Expert Knowledge in a Computational Evolution System for Complex Problem Solving in Human Genetics

NASA Astrophysics Data System (ADS)

Greene, Casey S.; Hill, Douglas P.; Moore, Jason H.

The relationship between interindividual variation in our genomes and variation in our susceptibility to common diseases is expected to be complex with multiple interacting genetic factors. A central goal of human genetics is to identify which DNA sequence variations predict disease risk in human populations. Our success in this endeavour will depend critically on the development and implementation of computational intelligence methods that are able to embrace, rather than ignore, the complexity of the genotype to phenotype relationship. To this end, we have developed a computational evolution system (CES) to discover genetic models of disease susceptibility involving complex relationships between DNA sequence variations. The CES approach is hierarchically organized and is capable of evolving operators of any arbitrary complexity. The ability to evolve operators distinguishes this approach from artificial evolution approaches using fixed operators such as mutation and recombination. Our previous studies have shown that a CES that can utilize expert knowledge about the problem in evolved operators significantly outperforms a CES unable to use this knowledge. This environmental sensing of external sources of biological or statistical knowledge is important when the search space is both rugged and large as in the genetic analysis of complex diseases. We show here that the CES is also capable of evolving operators which exploit one of several sources of expert knowledge to solve the problem. This is important for both the discovery of highly fit genetic models and because the particular source of expert knowledge used by evolved operators may provide additional information about the problem itself. This study brings us a step closer to a CES that can solve complex problems in human genetics in addition to discovering genetic models of disease.

Genetically encoded photocross-linkers determine the biological binding site of exendin-4 peptide in the N-terminal domain of the intact human glucagon-like peptide-1 receptor (GLP-1R)

PubMed Central

Koole, Cassandra; Reynolds, Christopher A.; Mobarec, Juan C.; Hick, Caroline; Sexton, Patrick M.; Sakmar, Thomas P.

2017-01-01

The glucagon-like peptide-1 receptor (GLP-1R) is a key therapeutic target in the management of type II diabetes mellitus, with actions including regulation of insulin biosynthesis and secretion, promotion of satiety, and preservation of β-cell mass. Like most class B G protein-coupled receptors (GPCRs), there is limited knowledge linking biological activity of the GLP-1R with the molecular structure of an intact, full-length, and functional receptor·ligand complex. In this study, we have utilized genetic code expansion to site-specifically incorporate the photoactive amino acid p-azido-l-phenylalanine (azF) into N-terminal residues of a full-length functional human GLP-1R in mammalian cells. UV-mediated photolysis of azF was then carried out to induce targeted photocross-linking to determine the proximity of the azido group in the mutant receptor with the peptide exendin-4. Cross-linking data were compared directly with the crystal structure of the isolated N-terminal extracellular domain of the GLP-1R in complex with exendin(9–39), revealing both similarities as well as distinct differences in the mode of interaction. Generation of a molecular model to accommodate the photocross-linking constraints highlights the potential influence of environmental conditions on the conformation of the receptor·peptide complex, including folding dynamics of the peptide and formation of dimeric and higher order oligomeric receptor multimers. These data demonstrate that crystal structures of isolated receptor regions may not give a complete reflection of peptide/receptor interactions and should be combined with additional experimental constraints to reveal peptide/receptor interactions occurring in the dynamic, native, and full-length receptor state. PMID:28283573

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

PubMed Central

Markus, B; Alshafee, I; Birk, O S

2014-01-01

The Bedouin Israeli population is highly inbred and structured with a very high prevalence of recessive diseases. Many studies in the past two decades focused on linkage analysis in large, multiple consanguineous pedigrees of this population. The advent of high-throughput technologies motivated researchers to search for rare variants shared between smaller pedigrees, integrating data from clinically similar yet seemingly non-related sporadic cases. However, such analyses are challenging because, without pedigree data, there is no prior knowledge regarding possible relatedness between the sporadic cases. Here, we describe models and techniques for the study of relationships between pedigrees and use them for the inference of tribal co-ancestry, delineating the complex social interactions between different tribes in the Negev Bedouins of southern Israel. Through our analysis, we differentiate between tribes that share many yet small genomic segments because of co-ancestry versus tribes that share larger segments because of recent admixture. The emergent pattern is well correlated with the prevalence of rare mutations in the different tribes. Tribes that do not intermarry, mostly because of social restrictions, hold private mutations, whereas tribes that do intermarry demonstrate a genetic flow of mutations between them. Thus, social structure within an inbred community can be delineated through genomic data, with implications to genetic counseling and genetic mapping. PMID:24084643

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data.

PubMed

Markus, B; Alshafee, I; Birk, O S

2014-02-01

The Bedouin Israeli population is highly inbred and structured with a very high prevalence of recessive diseases. Many studies in the past two decades focused on linkage analysis in large, multiple consanguineous pedigrees of this population. The advent of high-throughput technologies motivated researchers to search for rare variants shared between smaller pedigrees, integrating data from clinically similar yet seemingly non-related sporadic cases. However, such analyses are challenging because, without pedigree data, there is no prior knowledge regarding possible relatedness between the sporadic cases. Here, we describe models and techniques for the study of relationships between pedigrees and use them for the inference of tribal co-ancestry, delineating the complex social interactions between different tribes in the Negev Bedouins of southern Israel. Through our analysis, we differentiate between tribes that share many yet small genomic segments because of co-ancestry versus tribes that share larger segments because of recent admixture. The emergent pattern is well correlated with the prevalence of rare mutations in the different tribes. Tribes that do not intermarry, mostly because of social restrictions, hold private mutations, whereas tribes that do intermarry demonstrate a genetic flow of mutations between them. Thus, social structure within an inbred community can be delineated through genomic data, with implications to genetic counseling and genetic mapping.

Coexistence of the social types: genetic population structure in the ant Formica exsecta.

PubMed

Seppä, Perttu; Gyllenstrand, Niclas; Corander, Jukka; Pamilo, Pekka

2004-11-01

The ant Formica exsecta has two types of colonies that exist in sympatry but usually as separate subpopulations: colonies with simple social organization and single queens (M type) or colonial networks with multiple queens (P type). We used both nuclear (DNA microsatellites) and mitochondrial markers to study the transition between the social types, and the contribution of males and females in gene flow within and between the types. Our results showed that the social types had different spatial genetic structures. The M subpopulations formed a fairly uniform population, whereas the P subpopulations were, on average, more differentiated from each other than from the nearby M subpopulations and could have been locally established from the M-type colonies, followed by philopatric behavior and restricted emigration of females. Thus, the relationship between the two social types resembles that of source (M type) and sink (P type) populations. The comparison of mitochondrial (phiST) and nuclear (FST) differentiation indicates that the dispersal rate of males is four to five times larger than that of females both among the P-type subpopulations and between the social types. Our results suggest that evolution toward complex social organization can have an important effect on genetic population structure through changes in dispersal behavior associated with different sociogenetic organizations.

Developing approaches for linear mixed modeling in landscape genetics through landscape-directed dispersal simulations

USGS Publications Warehouse

Row, Jeffrey R.; Knick, Steven T.; Oyler-McCance, Sara J.; Lougheed, Stephen C.; Fedy, Bradley C.

2017-01-01

Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R2 values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.

Gene flow and genetic structure of Bactrocera carambolae (Diptera, Tephritidae) among geographical differences and sister species, B. dorsalis, inferred from microsatellite DNA data.

PubMed

Aketarawong, Nidchaya; Isasawin, Siriwan; Sojikul, Punchapat; Thanaphum, Sujinda

2015-01-01

The Carambola fruit fly, Bactrocera carambolae, is an invasive pest in Southeast Asia. It has been introduced into areas in South America such as Suriname and Brazil. Bactrocera carambolae belongs to the Bactrocera dorsalis species complex, and seems to be separated from Bactrocera dorsalis based on morphological and multilocus phylogenetic studies. Even though the Carambola fruit fly is an important quarantine species and has an impact on international trade, knowledge of the molecular ecology of Bactrocera carambolae, concerning species status and pest management aspects, is lacking. Seven populations sampled from the known geographical areas of Bactrocera carambolae including Southeast Asia (i.e., Indonesia, Malaysia, Thailand) and South America (i.e., Suriname), were genotyped using eight microsatellite DNA markers. Genetic variation, genetic structure, and genetic network among populations illustrated that the Suriname samples were genetically differentiated from Southeast Asian populations. The genetic network revealed that samples from West Sumatra (Pekanbaru, PK) and Java (Jakarta, JK) were presumably the source populations of Bactrocera carambolae in Suriname, which was congruent with human migration records between the two continents. Additionally, three populations of Bactrocera dorsalis were included to better understand the species boundary. The genetic structure between the two species was significantly separated and approximately 11% of total individuals were detected as admixed (0.100 ≤ Q ≤ 0.900). The genetic network showed connections between Bactrocera carambolae and Bactrocera dorsalis groups throughout Depok (DP), JK, and Nakhon Sri Thammarat (NT) populations. These data supported the hypothesis that the reproductive isolation between the two species may be leaky. Although the morphology and monophyly of nuclear and mitochondrial DNA sequences in previous studies showed discrete entities, the hypothesis of semipermeable boundaries may not be rejected. Alleles at microsatellite loci could be introgressed rather than other nuclear and mitochondrial DNA. Bactrocera carambolae may be an incipient rather than a distinct species of Bactrocera dorsalis. Regarding the pest management aspect, the genetic sexing Salaya5 strain (SY5) was included for comparison with wild populations. The SY5 strain was genetically assigned to the Bactrocera carambolae cluster. Likewise, the genetic network showed that the strain shared greatest genetic similarity to JK, suggesting that SY5 did not divert away from its original genetic makeup. Under laboratory conditions, at least 12 generations apart, selection did not strongly affect genetic compatibility between the strain and wild populations. This knowledge further confirms the potential utilization of the Salaya5 strain in regional programs of area-wide integrated pest management using SIT.

Gene flow and genetic structure of Bactrocera carambolae (Diptera, Tephritidae) among geographical differences and sister species, B. dorsalis, inferred from microsatellite DNA data

PubMed Central

Aketarawong, Nidchaya; Isasawin, Siriwan; Sojikul, Punchapat; Thanaphum, Sujinda

2015-01-01

Abstract The Carambola fruit fly, Bactrocera carambolae, is an invasive pest in Southeast Asia. It has been introduced into areas in South America such as Suriname and Brazil. Bactrocera carambolae belongs to the Bactrocera dorsalis species complex, and seems to be separated from Bactrocera dorsalis based on morphological and multilocus phylogenetic studies. Even though the Carambola fruit fly is an important quarantine species and has an impact on international trade, knowledge of the molecular ecology of Bactrocera carambolae, concerning species status and pest management aspects, is lacking. Seven populations sampled from the known geographical areas of Bactrocera carambolae including Southeast Asia (i.e., Indonesia, Malaysia, Thailand) and South America (i.e., Suriname), were genotyped using eight microsatellite DNA markers. Genetic variation, genetic structure, and genetic network among populations illustrated that the Suriname samples were genetically differentiated from Southeast Asian populations. The genetic network revealed that samples from West Sumatra (Pekanbaru, PK) and Java (Jakarta, JK) were presumably the source populations of Bactrocera carambolae in Suriname, which was congruent with human migration records between the two continents. Additionally, three populations of Bactrocera dorsalis were included to better understand the species boundary. The genetic structure between the two species was significantly separated and approximately 11% of total individuals were detected as admixed (0.100 ≤ Q ≤ 0.900). The genetic network showed connections between Bactrocera carambolae and Bactrocera dorsalis groups throughout Depok (DP), JK, and Nakhon Sri Thammarat (NT) populations. These data supported the hypothesis that the reproductive isolation between the two species may be leaky. Although the morphology and monophyly of nuclear and mitochondrial DNA sequences in previous studies showed discrete entities, the hypothesis of semipermeable boundaries may not be rejected. Alleles at microsatellite loci could be introgressed rather than other nuclear and mitochondrial DNA. Bactrocera carambolae may be an incipient rather than a distinct species of Bactrocera dorsalis. Regarding the pest management aspect, the genetic sexing Salaya5 strain (SY5) was included for comparison with wild populations. The SY5 strain was genetically assigned to the Bactrocera carambolae cluster. Likewise, the genetic network showed that the strain shared greatest genetic similarity to JK, suggesting that SY5 did not divert away from its original genetic makeup. Under laboratory conditions, at least 12 generations apart, selection did not strongly affect genetic compatibility between the strain and wild populations. This knowledge further confirms the potential utilization of the Salaya5 strain in regional programs of area-wide integrated pest management using SIT. PMID:26798262

Fine-scale population structure in a desert amphibian: landscape genetics of the black toad (Bufo exsul).

PubMed

Wang, Ian J

2009-09-01

Environmental variables can strongly influence a variety of intra- and inter-population processes, including demography, population structure and gene flow. When environmental conditions are particularly harsh for a certain species, investigating these effects is important to understanding how populations persist under difficult conditions. Furthermore, species inhabiting challenging environments present excellent opportunities to examine the effects of complex landscapes on population processes because these effects will often be more pronounced. In this study, I use 16 microsatellite loci to examine population structure, gene flow and demographic history in the black toad, Bufo exsul, which has one of the most restricted natural ranges of any amphibian. Bufo exsul inhabits four springs in the Deep Springs Valley high desert basin and has never been observed more than several meters from any source of water. My results reveal limited gene flow and moderately high levels of population structure (F(ST) = 0.051-0.063) between all but the two closest springs. I found that the geographic distance across the arid scrub habitat between springs is significantly correlated with genetic structure when distance accounts for topography and barriers to dispersal. I also found very low effective population sizes (N(e) = 7-30) and substantial evidence for historical population bottlenecks in all four populations. Together, these results suggest that the desert landscape and B. exsul's high habitat specificity contribute significantly to population structure and demography in this species and emphasize the importance of considering behavioural and landscape data in conservation genetic studies of natural systems.

Phylogenetic and morphological investigation of the Mochlus afer-sundevallii species complex (Squamata: Scincidae) across the arid corridor of sub-Saharan Africa.

PubMed

Freitas, Elyse S; Bauer, Aaron M; Siler, Cameron D; Broadley, Donald G; Jackman, Todd R

2018-06-02

The aridification of Africa resulted in the fragmentation of forests and the expansion of an arid corridor stretching from the northeast to southwest portion of sub-Saharan Africa, but the role this corridor has had in species-level diversification of southern African vertebrates is poorly understood. The skink species Mochlus afer and M. sundevallii inhabit wide areas of the arid corridor and are therefore an ideal species pair for studying patterns of genetic and phenotypic diversity associated with this landscape. However, species boundaries between these taxa have been controversial. Using multi-locus molecular and morphological datasets, we investigate diversification patterns of the M. afer-sundevallii Species Complex across the arid corridor. Although analyses of genetic data reveals some genetic structure among geographic populations, results of phylogenetic and morphological analyses provide little support for two distinct evolutionary lineages, suggesting that populations previously referred to as M. afer and M. sundevallii represent a single species, Mochlus sundevallii. Genetic diversity is unequally distributed across the arid corridor, with observed patterns consistent with aridification-facilitated diversification southward across southern Africa. Additional geographic and population-level sampling is necessary before more conclusive inferences can be drawn about the role historical climate transitions have played in skink diversification patterns across southern Africa. Copyright © 2018 Elsevier Inc. All rights reserved.

A craniometric perspective on the transition to agriculture in Europe.

PubMed

Pinhasi, Ron; von Cramon-Taubadel, Noreen

2012-02-01

Debates surrounding the nature of the Neolithic demographic transition in Europe have historically centered on two opposing models: a "demic" diffusion model whereby incoming farmers from the Near East and Anatolia effectively replaced or completely assimilated indigenous Mesolithic foraging communities, and an "indigenist" model resting on the assumption that ideas relating to agriculture and animal domestication diffused from the Near East but with little or no gene flow. The extreme versions of these dichotomous models were heavily contested primarily on the basis of archeological and modern genetic data. However, in recent years a growing acceptance has arisen of the likelihood that both processes were ongoing throughout the Neolithic transition and that a more complex, regional approach is required to fully understand the change from a foraging to a primarily agricultural mode of subsistence in Europe. Craniometric data were particularly useful for testing these more complex scenarios, as they can reliably be employed as a proxy for the genetic relationships among Mesolithic and Neolithic populations. In contrast, modern genetic data assume that modern European populations accurately reflect the genetic structure of Europe at the time of the Neolithic transition, while ancient DNA data are still not geographically or temporally detailed enough to test continent-wide processes. Here, with particular emphasis on the role of craniometric analyses, we review the current state of knowledge regarding the cultural and biological nature of the Neolithic transition in Europe.

The Value of Extended Pedigrees for Next-Generation Analysis of Complex Disease in the Rhesus Macaque

PubMed Central

Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

2013-01-01

Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease. PMID:24174435

New insights from monogenic diabetes for “common” type 2 diabetes

PubMed Central

Tallapragada, Divya Sri Priyanka; Bhaskar, Seema; Chandak, Giriraj R.

2015-01-01

Boundaries between monogenic and complex genetic diseases are becoming increasingly blurred, as a result of better understanding of phenotypes and their genetic determinants. This had a large impact on the way complex disease genetics is now being investigated. Starting with conventional approaches like familial linkage, positional cloning and candidate genes strategies, the scope of complex disease genetics has grown exponentially with scientific and technological advances in recent times. Despite identification of multiple loci harboring common and rare variants associated with complex diseases, interpreting and evaluating their functional role has proven to be difficult. Information from monogenic diseases, especially related to the intermediate traits associated with complex diseases comes handy. The significant overlap between traits and phenotypes of monogenic diseases with related complex diseases provides a platform to understand the disease biology better. In this review, we would discuss about one such complex disease, type 2 diabetes, which shares marked similarity of intermediate traits with different forms of monogenic diabetes. PMID:26300908

Directional selection can drive the evolution of modularity in complex traits

PubMed Central

Melo, Diogo; Marroig, Gabriel

2015-01-01

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection. PMID:25548154

Directional selection can drive the evolution of modularity in complex traits.

PubMed

Melo, Diogo; Marroig, Gabriel

2015-01-13

Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.

Headwater Capture Evidenced by Paleo-Rivers Reconstruction and Population Genetic Structure of the Armored Catfish (Pareiorhaphis garbei) in the Serra do Mar Mountains of Southeastern Brazil

PubMed Central

Lima, Sergio M. Q.; Berbel-Filho, Waldir M.; Araújo, Thais F. P.; Lazzarotto, Henrique; Tatarenkov, Andrey; Avise, John C.

2017-01-01

Paleo-drainage connections and headwater stream-captures are two main historical processes shaping the distribution of strictly freshwater fishes. Recently, bathymetric-based methods of paleo-drainage reconstruction have opened new possibilities to investigate how these processes have shaped the genetic structure of freshwater organisms. In this context, the present study used paleo-drainage reconstructions and single-locus cluster delimitation analyses to examine genetic structure on the whole distribution of Pareiorhaphis garbei, a ‘near threatened’ armored catfish from the Fluminense freshwater ecoregion in Southeastern Brazil. Sequences of two mitochondrial genes (cytochrome b and cytochrome c oxidase subunit 1) were obtained from five sampling sites in four coastal drainages: Macaé (KAE), São João (SJO), Guapi-Macacu [sub-basins Guapiaçu (GAC) and Guapimirim (GMI)], and Santo Aleixo (SAL). Pronounced genetic structure was found, involving 10 haplotypes for cytB and 6 for coi, with no haplotypes shared between localities. Coalescent-based delineation methods as well as distance-based methods revealed genetic clusters corresponding to each sample site. Paleo-drainage reconstructions showed two putative paleo-rivers: an eastern one connecting KAE and SJO; and a western one merging in the Guanabara Bay (GAC, GMI, and SAL). A disagreement was uncovered between the inferred past riverine connections and current population genetic structure. Although KAE and SJO belong to the same paleo-river, the latter is more closely related to specimens from the Guanabara paleo-river. This discordance between paleo-drainage connections and phylogenetic structure may indicate an ancient stream-capture event in headwaters of this region. Furthermore, all analyses showed high divergence between KAE and the other lineages, suggesting at least one cryptic species in the latter, and that the nominal species should be restricted to the Macaé river basin, its type locality. In this drainage, impacts such as the invasive species and habitat loss can be especially threatening for such species with a narrow range. Our results also suggest that freshwater fishes from headwaters in the Serra do Mar mountains might have different biogeographical patterns than those from the lowlands, indicating a complex and dynamic climatic and geomorphological history. PMID:29259623

Headwater Capture Evidenced by Paleo-Rivers Reconstruction and Population Genetic Structure of the Armored Catfish (Pareiorhaphis garbei) in the Serra do Mar Mountains of Southeastern Brazil.

PubMed

Lima, Sergio M Q; Berbel-Filho, Waldir M; Araújo, Thais F P; Lazzarotto, Henrique; Tatarenkov, Andrey; Avise, John C

2017-01-01

Paleo-drainage connections and headwater stream-captures are two main historical processes shaping the distribution of strictly freshwater fishes. Recently, bathymetric-based methods of paleo-drainage reconstruction have opened new possibilities to investigate how these processes have shaped the genetic structure of freshwater organisms. In this context, the present study used paleo-drainage reconstructions and single-locus cluster delimitation analyses to examine genetic structure on the whole distribution of Pareiorhaphis garbei , a 'near threatened' armored catfish from the Fluminense freshwater ecoregion in Southeastern Brazil. Sequences of two mitochondrial genes (cytochrome b and cytochrome c oxidase subunit 1) were obtained from five sampling sites in four coastal drainages: Macaé (KAE), São João (SJO), Guapi-Macacu [sub-basins Guapiaçu (GAC) and Guapimirim (GMI)], and Santo Aleixo (SAL). Pronounced genetic structure was found, involving 10 haplotypes for cytB and 6 for coi , with no haplotypes shared between localities. Coalescent-based delineation methods as well as distance-based methods revealed genetic clusters corresponding to each sample site. Paleo-drainage reconstructions showed two putative paleo-rivers: an eastern one connecting KAE and SJO; and a western one merging in the Guanabara Bay (GAC, GMI, and SAL). A disagreement was uncovered between the inferred past riverine connections and current population genetic structure. Although KAE and SJO belong to the same paleo-river, the latter is more closely related to specimens from the Guanabara paleo-river. This discordance between paleo-drainage connections and phylogenetic structure may indicate an ancient stream-capture event in headwaters of this region. Furthermore, all analyses showed high divergence between KAE and the other lineages, suggesting at least one cryptic species in the latter, and that the nominal species should be restricted to the Macaé river basin, its type locality. In this drainage, impacts such as the invasive species and habitat loss can be especially threatening for such species with a narrow range. Our results also suggest that freshwater fishes from headwaters in the Serra do Mar mountains might have different biogeographical patterns than those from the lowlands, indicating a complex and dynamic climatic and geomorphological history.

The impact of CRISPR repeat sequence on structures of a Cas6 protein-RNA complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ruiying; Zheng, Han; Preamplume, Gan

The repeat-associated mysterious proteins (RAMPs) comprise the most abundant family of proteins involved in prokaryotic immunity against invading genetic elements conferred by the clustered regularly interspaced short palindromic repeat (CRISPR) system. Cas6 is one of the first characterized RAMP proteins and is a key enzyme required for CRISPR RNA maturation. Despite a strong structural homology with other RAMP proteins that bind hairpin RNA, Cas6 distinctly recognizes single-stranded RNA. Previous structural and biochemical studies show that Cas6 captures the 5' end while cleaving the 3' end of the CRISPR RNA. Here, we describe three structures and complementary biochemical analysis of amore » noncatalytic Cas6 homolog from Pyrococcus horikoshii bound to CRISPR repeat RNA of different sequences. Our study confirms the specificity of the Cas6 protein for single-stranded RNA and further reveals the importance of the bases at Positions 5-7 in Cas6-RNA interactions. Substitutions of these bases result in structural changes in the protein-RNA complex including its oligomerization state.« less

Screening protein – Single stranded RNA complexes by NMR spectroscopy for structure determination☆

PubMed Central

Foot, Jaelle N.; Feracci, Mikael; Dominguez, Cyril

2014-01-01

In the past few years, RNA molecules have been revealed to be at the center of numerous biological processes. Long considered as passive molecules transferring genetic information from DNA to proteins, it is now well established that RNA molecules play important regulatory roles. Associated with that, the number of identified RNA binding proteins (RBPs) has increased considerably and mutations in RNA molecules or RBP have been shown to cause various diseases, such as cancers. It is therefore crucial to understand at the molecular level how these proteins specifically recognise their RNA targets in order to design new generation drug therapies targeting protein–RNA complexes. Nuclear magnetic resonance (NMR) is a particularly well-suited technique to study such protein–RNA complexes at the atomic level and can provide valuable information for new drug discovery programs. In this article, we describe the NMR strategy that we and other laboratories use for screening optimal conditions necessary for structural studies of protein-single stranded RNA complexes, using two proteins, Sam68 and T-STAR, as examples. PMID:24096002

Solution structure of the core SMN–Gemin2 complex

PubMed Central

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.

2012-01-01

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. PMID:22607171

Crystal structure, biochemical and genetic characterization of yeast and E. cuniculi TAF(II)5 N-terminal domain: implications for TFIID assembly.

PubMed

Romier, Christophe; James, Nicole; Birck, Catherine; Cavarelli, Jean; Vivarès, Christian; Collart, Martine A; Moras, Dino

2007-05-18

General transcription factor TFIID plays an essential role in transcription initiation by RNA polymerase II at numerous promoters. However, understanding of the assembly and a full structural characterization of this large 15 subunit complex is lacking. TFIID subunit TAF(II)5 has been shown to be present twice in this complex and to be critical for the function and assembly of TFIID. Especially, the TAF(II)5 N-terminal domain is required for its incorporation within TFIID and immuno-labelling experiments carried out by electron microscopy at low resolution have suggested that this domain might homodimerize, possibly explaining the three-lobed architecture of TFIID. However, the resolution at which the electron microscopy (EM) analyses were conducted is not sufficient to determine whether homodimerization occurs or whether a more intricate assembly implying other subunits is required. Here we report the X-ray structures of the fully evolutionary conserved C-terminal sub-domain of the TAF(II)5 N terminus, from yeast and the mammalian parasite Encephalitozoon cuniculi. This sub-domain displays a novel fold with specific surfaces having conserved physico-chemical properties that can form protein-protein interactions. Although a crystallographic dimer implying one of these surfaces is present in one of the crystal forms, several biochemical analyses show that this sub-domain is monomeric in solution, even at various salt conditions and in presence of different divalent cations. Consequently, the N-terminal sub-domain of the TAF(II)5 N terminus, which is homologous to a dimerization motif but has not been fully conserved during evolution, was studied by analytical ultracentrifugation and yeast genetics. Our results show that this sub-domain dimerizes at very high concentration but is neither required for yeast viability, nor for incorporation of two TAF(II)5 molecules within TFIID and for the assembly of this complex. Altogether, although our results do not argue in favour of a homodimerization of the TAF(II)5 N-terminal domain, our structural analyses suggest a role for this domain in assembly of TFIID and its related complexes SAGA, STAGA, TFTC and PCAF.

Fine-scale spatial genetic dynamics over the life cycle of the tropical tree Prunus africana.

PubMed

Berens, D G; Braun, C; González-Martínez, S C; Griebeler, E M; Nathan, R; Böhning-Gaese, K

2014-11-01

Studying fine-scale spatial genetic patterns across life stages is a powerful approach to identify ecological processes acting within tree populations. We investigated spatial genetic dynamics across five life stages in the insect-pollinated and vertebrate-dispersed tropical tree Prunus africana in Kakamega Forest, Kenya. Using six highly polymorphic microsatellite loci, we assessed genetic diversity and spatial genetic structure (SGS) from seed rain and seedlings, and different sapling stages to adult trees. We found significant SGS in all stages, potentially caused by limited seed dispersal and high recruitment rates in areas with high light availability. SGS decreased from seed and early seedling stages to older juvenile stages. Interestingly, SGS was stronger in adults than in late juveniles. The initial decrease in SGS was probably driven by both random and non-random thinning of offspring clusters during recruitment. Intergenerational variation in SGS could have been driven by variation in gene flow processes, overlapping generations in the adult stage or local selection. Our study shows that complex sequential processes during recruitment contribute to SGS of tree populations.

Early developmental gene enhancers affect subcortical volumes in the adult human brain.

PubMed

Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

2016-05-01

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Novel Concordance Between Geographic, Environmental, and Genetic Structure in the Ecological Generalist Prickly Sculpin (Cottus asper) in California.

PubMed

Baumsteiger, Jason; Kinziger, Andrew P; Aguilar, Andres

2016-11-01

Ecological generalists may contain a wealth of information concerning diversity, ecology, and geographic connectivity throughout their range. We explored these ideas in prickly sculpin (Cottus asper), a small generalist freshwater fish species where coastal forms have potentially undergone radiations into inland lacustrine and riverine environments. Using a 962bp cytochrome b mtDNA marker and 11 microsatellites, we estimated diversity, divergence times, gene flow, and structure among populations at 43 locations throughout California. We then incorporated genetic and GIS data into ecological niche models to assess ecological conditions within identified groups. Though not reciprocally monophyletic, unique mtDNA haplotypes, microsatellite clustering, and measures of isolation by distance (Coastal: r = 0.960, P < 0.001; Inland: r = 0.277, P = 0.148) suggest 2 novel taxonomic groups, Coastal and Inland (constrained to Great Central Valley). Divergence estimates of 41-191 kya combined with the regional biogeographic history suggest geographic barriers are absent between groups since divergence, but ecological niche modeling revealed significant environmental differences (t = 10.84, P < 0.001). Introgressed individuals were also discovered between groups in an ecologically and geographically intermediate region. Population structure was limited, predominately found in tributaries of the San Joaquin basin in the Inland group. Overall, C. asper exhibited substantial genetic diversity, despite its ecological generality, reflecting California's historically unique and complex hydrology. More broadly, this study illustrates variable environments within the range of a generalist species may mask genetic divergences and should not be overlooked in biodiversity assessments. © The American Genetic Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Crosses prior to parthenogenesis explain the current genetic diversity of tropical plant-parasitic Meloidogyne species (Nematoda: Tylenchida).

PubMed

Fargette, Mireille; Berthier, Karine; Richaud, Myriam; Lollier, Virginie; Franck, Pierre; Hernandez, Adan; Frutos, Roger

2010-08-01

The tropical and subtropical parthenogenetic plant-parasitic nematodes Meloidogyne are polyphagous major agricultural pests. Implementing proper pest management approaches requires a good understanding of mechanisms, population structure, evolutionary patterns and species identification. A comparative analysis of the mitochondrial vs nuclear diversity was conducted on a selected set of Meloidogyne lines from various geographic origins. Mitochondrial co2-16S sequences and AFLP markers of total DNA were applied because of their ability to evidence discrete genetic variation between closely related isolates. Several distinct maternal lineages were present, now associated with different genetic backgrounds. Relative discordances were found when comparing mitochondrial and nuclear diversity patterns. These patterns are most likely related to crosses within one ancestral genetic pool, followed by the establishment of parthenogenesis. In this case, they mirror the genetic backgrounds of the original individuals. Another aspect could be that species emergence was recent or on process from this original genetic pool and that the relatively short time elapsed since then and before parthenogenesis settlement did not allow for lineage sorting. This could also be compatible with the hypothesis of hybrids between closely related species. This genetic pool would correspond to a species as defined by the species interbreeding concept, but also including the grey area of species boundaries. This complex process has implications on the way genotypic and phenotypic diversity should be addressed. The phenotype of parthenogenetic lines is at least for part determined by the ancestral amphimictic genetic background. A direct consequence is, therefore, in terms of risk management, the limited confidence one can have on the direct association of an agronomic threat to a simple typing or species delineation. Risk management strategies and tools must thus consider this complexity when designing quarantine implementation, resistance breeding programmes or molecular diagnostic. Copyright 2009 Elsevier B.V. All rights reserved.

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

Multiple origins of elytral reticulation modifications in the west palearctic Agabus bipustulatus complex (coleoptera, dytiscidae).

PubMed

Drotz, Marcus K; Brodin, Tomas; Nilsson, Anders N

2010-02-03

The Agabus bipustulatus complex includes one of Europe's most widely distributed and common diving beetles. This complex, which is known for its large morphological variation, has a complex demographic and altitudinal variation in elytral reticulation. The various depth of the reticulation imprint, both in smaller and larger meshes, results in both mat and shiny individuals, as well as intermediate forms. The West Palearctic lowland is inhabited by a sexually dimorphic form, with shiny males and mat females. In mountain regions, shiny individuals of both sexes are found intermixed with mat individuals or in pure populations in central and southern areas, whereas pure populations of mat individuals are exclusively found in the northern region at high altitude. Sexual selection is proposed as a driving force in shaping this variation. However, the occurrence of different types of reticulation in both sexes and disjunct geographical distribution patterns suggest an additional function of the reticulation. Here we investigate the phylogeographical history, genetic structure and reticulation variation of several named forms within the Agabus bipustulatus complex including A. nevadensis. The molecular analyses recognised several well-supported clades within the complex. Several of the named forms had two or more independent origins. Few south European populations were uniform in reticulation patterns, and the males were found to display large variation. Reticulation diversity and population genetic variability were clearly correlated to altitude, but no genetic differences were detected among populations with mixed or homogenous forms. Observed reduction in secondary reticulation in female and increased variance in male at high altitude in South Europe may be explained by the occurrence of an additional selective force, beside sexual selection. The combined effect of these selective processes is here demonstrated in an extreme case to generate isolation barriers between populations at high altitudes. Here we discuss this selective force in relation to thermal selection.

Genetic identification and molecular modeling characterization reveal a novel PROM1 mutation in Stargardt4-like macular dystrophy

PubMed Central

Imani, Saber; Cheng, Jingliang; Shasaltaneh, Marzieh Dehghan; Wei, Chunli; Yang, Lisha; Fu, Shangyi; Zou, Hui; Khan, Md. Asaduzzaman; Zhang, Xianqin; Chen, Hanchun; Zhang, Dianzheng; Duan, Chengxia; Lv, Hongbin; Li, Yumei; Chen, Rui; Fu, Junjiang

2018-01-01

Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder. In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD. We found a novel heterozygous missense mutation, c.734T>C (p.L245P) in the PROM1 gene. Structurally, this mutation most likely impairs PROM1 protein stability, flexibility, and amino acid interaction network after changing the amino acid residue Leucine into Proline in the basic helix-loop-helix leucine zipper domain. Molecular dynamic simulation and principal component analysis provide compelling evidence that this PROM1 mutation contributes to disease causativeness or susceptibility variants in patients with STGD4-like MD. Thus, this finding defines new approaches in genetic characterization, accurate diagnosis, and prevention of STGD4-like MD. PMID:29416601

Plant defense phenotypes determine the consequences of volatile emission for individuals and neighbors

PubMed Central

Schuman, Meredith C; Allmann, Silke; Baldwin, Ian T

2015-01-01

Plants are at the trophic base of terrestrial ecosystems, and the diversity of plant species in an ecosystem is a principle determinant of community structure. This may arise from diverse functional traits among species. In fact, genetic diversity within species can have similarly large effects. However, studies of intraspecific genetic diversity have used genotypes varying in several complex traits, obscuring the specific phenotypic variation responsible for community-level effects. Using lines of the wild tobacco Nicotiana attenuata genetically altered in specific well-characterized defense traits and planted into experimental populations in their native habitat, we investigated community-level effects of trait diversity in populations of otherwise isogenic plants. We conclude that the frequency of defense traits in a population can determine the outcomes of these traits for individuals. Furthermore, our results suggest that some ecosystem-level services afforded by genetically diverse plant populations could be recaptured in intensive monocultures engineered to be functionally diverse. DOI: http://dx.doi.org/10.7554/eLife.04490.001 PMID:25873033

Writing DNA with GenoCAD.

PubMed

Czar, Michael J; Cai, Yizhi; Peccoud, Jean

2009-07-01

Chemical synthesis of custom DNA made to order calls for software streamlining the design of synthetic DNA sequences. GenoCAD (www.genocad.org) is a free web-based application to design protein expression vectors, artificial gene networks and other genetic constructs composed of multiple functional blocks called genetic parts. By capturing design strategies in grammatical models of DNA sequences, GenoCAD guides the user through the design process. By successively clicking on icons representing structural features or actual genetic parts, complex constructs composed of dozens of functional blocks can be designed in a matter of minutes. GenoCAD automatically derives the construct sequence from its comprehensive libraries of genetic parts. Upon completion of the design process, users can download the sequence for synthesis or further analysis. Users who elect to create a personal account on the system can customize their workspace by creating their own parts libraries, adding new parts to the libraries, or reusing designs to quickly generate sets of related constructs.

High-Throughput Phenotyping and QTL Mapping Reveals the Genetic Architecture of Maize Plant Growth.

PubMed

Zhang, Xuehai; Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Xiong, Lizhong; Yang, Wanneng; Yan, Jianbing

2017-03-01

With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize ( Zea mays ) recombinant inbred line population ( n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. © 2017 American Society of Plant Biologists. All Rights Reserved.

High-Throughput Phenotyping and QTL Mapping Reveals the Genetic Architecture of Maize Plant Growth1[OPEN

PubMed Central

Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Yang, Wanneng

2017-01-01

With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize (Zea mays) recombinant inbred line population (n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. PMID:28153923

The impact of shrimp farming effluent on bacterial communities in mangrove waters, Ceará, Brazil.

PubMed

Sousa, O V; Macrae, A; Menezes, F G R; Gomes, N C M; Vieira, R H S F; Mendonça-Hagler, L C S

2006-12-01

The effects of shrimp farm effluents on bacterial communities in mangroves have been infrequently reported. Classic and molecular biology methods were used to survey bacterial communities from four mangroves systems. Water temperature, salinity, pH, total heterotrophic bacteria and maximum probable numbers of Vibrio spp. were investigated. Genetic profiles of bacterial communities were also characterized by polymerase chain reaction (PCR) amplification of eubacterial and Vibrio 16S rDNA using denaturing gradient gel electrophoresis (DGGE). Highest heterotrophic counts were registered in the mangrove not directly polluted by shrimp farming. The Enterobacteriaceae and Chryseomonas luteola dominated the heterotrophic isolates. Vibrio spp. pathogenic to humans and shrimps were identified. Eubacterial genetic profiles suggest a shared community structure independent of mangrove system. Vibrio genetic profiles were mangrove specific. Neither microbial counts nor genetic profiling revealed a significant decrease in species richness associated with shrimp farm effluent. The complex nature of mangrove ecosystems and their microbial communities is discussed.

Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair

PubMed Central

Yang, Hui; Zhang, Tianlong; Tao, Ye; Wang, Fang; Tong, Liang; Ding, Jianping

2013-01-01

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair. PMID:24003026

Evolutionary diversification of protein–protein interactions by interface add-ons

PubMed Central

Plach, Maximilian G.; Semmelmann, Florian; Busch, Florian; Busch, Markus; Heizinger, Leonhard; Wysocki, Vicki H.; Sterner, Reinhard

2017-01-01

Cells contain a multitude of protein complexes whose subunits interact with high specificity. However, the number of different protein folds and interface geometries found in nature is limited. This raises the question of how protein–protein interaction specificity is achieved on the structural level and how the formation of nonphysiological complexes is avoided. Here, we describe structural elements called interface add-ons that fulfill this function and elucidate their role for the diversification of protein–protein interactions during evolution. We identified interface add-ons in 10% of a representative set of bacterial, heteromeric protein complexes. The importance of interface add-ons for protein–protein interaction specificity is demonstrated by an exemplary experimental characterization of over 30 cognate and hybrid glutamine amidotransferase complexes in combination with comprehensive genetic profiling and protein design. Moreover, growth experiments showed that the lack of interface add-ons can lead to physiologically harmful cross-talk between essential biosynthetic pathways. In sum, our complementary in silico, in vitro, and in vivo analysis argues that interface add-ons are a practical and widespread evolutionary strategy to prevent the formation of nonphysiological complexes by specializing protein–protein interactions. PMID:28923934

Strong genetic structure corresponds to small-scale geographic breaks in the Australian alpine grasshopper Kosciuscola tristis.

PubMed

Slatyer, Rachel A; Nash, Michael A; Miller, Adam D; Endo, Yoshinori; Umbers, Kate D L; Hoffmann, Ary A

2014-10-02

Mountain landscapes are topographically complex, creating discontinuous 'islands' of alpine and sub-alpine habitat with a dynamic history. Changing climatic conditions drive their expansion and contraction, leaving signatures on the genetic structure of their flora and fauna. Australia's high country covers a small, highly fragmented area. Although the area is thought to have experienced periods of relative continuity during Pleistocene glacial periods, small-scale studies suggest deep lineage divergence across low-elevation gaps. Using both DNA sequence data and microsatellite markers, we tested the hypothesis that genetic partitioning reflects observable geographic structuring across Australia's mainland high country, in the widespread alpine grasshopper Kosciuscola tristis (Sjösted). We found broadly congruent patterns of regional structure between the DNA sequence and microsatellite datasets, corresponding to strong divergence among isolated mountain regions. Small and isolated mountains in the south of the range were particularly distinct, with well-supported divergence corresponding to climate cycles during the late Pliocene and Pleistocene. We found mixed support, however, for divergence among other mountain regions. Interestingly, within areas of largely contiguous alpine and sub-alpine habitat around Mt Kosciuszko, microsatellite data suggested significant population structure, accompanied by a strong signature of isolation-by-distance. Consistent patterns of strong lineage divergence among different molecular datasets indicate genetic breaks between populations inhabiting geographically distinct mountain regions. Three primary phylogeographic groups were evident in the highly fragmented Victorian high country, while within-region structure detected with microsatellites may reflect more recent population isolation. Despite the small area of Australia's alpine and sub-alpine habitats, their low topographic relief and lack of extensive glaciation, divergence among populations was on the same scale as that detected in much more extensive Northern hemisphere mountain systems. The processes driving divergence in the Australian mountains might therefore differ from their Northern hemisphere counterparts.

Ecogeographic Genetic Epidemiology

PubMed Central

Sloan, Chantel D.; Duell, Eric J.; Shi, Xun; Irwin, Rebecca; Andrew, Angeline S.; Williams, Scott M.; Moore, Jason H.

2009-01-01

Complex diseases such as cancer and heart disease result from interactions between an individual's genetics and environment, i.e. their human ecology. Rates of complex diseases have consistently demonstrated geographic patterns of incidence, or spatial “clusters” of increased incidence relative to the general population. Likewise, genetic subpopulations and environmental influences are not evenly distributed across space. Merging appropriate methods from genetic epidemiology, ecology and geography will provide a more complete understanding of the spatial interactions between genetics and environment that result in spatial patterning of disease rates. Geographic Information Systems (GIS), which are tools designed specifically for dealing with geographic data and performing spatial analyses to determine their relationship, are key to this kind of data integration. Here the authors introduce a new interdisciplinary paradigm, ecogeographic genetic epidemiology, which uses GIS and spatial statistical analyses to layer genetic subpopulation and environmental data with disease rates and thereby discern the complex gene-environment interactions which result in spatial patterns of incidence. PMID:19025788

Genetic Interactions Between the Meiosis-Specific Cohesin Components, STAG3, REC8, and RAD21L.

PubMed

Ward, Ayobami; Hopkins, Jessica; Mckay, Matthew; Murray, Steve; Jordan, Philip W

2016-06-01

Cohesin is an essential structural component of chromosomes that ensures accurate chromosome segregation during mitosis and meiosis. Previous studies have shown that there are cohesin complexes specific to meiosis, required to mediate homologous chromosome pairing, synapsis, recombination, and segregation. Meiosis-specific cohesin complexes consist of two structural maintenance of chromosomes proteins (SMC1α/SMC1β and SMC3), an α-kleisin protein (RAD21, RAD21L, or REC8), and a stromal antigen protein (STAG1, 2, or 3). STAG3 is exclusively expressed during meiosis, and is the predominant STAG protein component of cohesin complexes in primary spermatocytes from mouse, interacting directly with each α-kleisin subunit. REC8 and RAD21L are also meiosis-specific cohesin components. Stag3 mutant spermatocytes arrest in early prophase ("zygotene-like" stage), displaying failed homolog synapsis and persistent DNA damage, as a result of unstable loading of cohesin onto the chromosome axes. Interestingly, Rec8, Rad21L double mutants resulted in an earlier "leptotene-like" arrest, accompanied by complete absence of STAG3 loading. To assess genetic interactions between STAG3 and α-kleisin subunits RAD21L and REC8, our lab generated Stag3, Rad21L, and Stag3, Rec8 double knockout mice, and compared them to the Rec8, Rad21L double mutant. These double mutants are phenotypically distinct from one another, and more severe than each single knockout mutant with regards to chromosome axis formation, cohesin loading, and sister chromatid cohesion. The Stag3, Rad21L, and Stag3, Rec8 double mutants both progress further into prophase I than the Rec8, Rad21L double mutant. Our genetic analysis demonstrates that cohesins containing STAG3 and REC8 are the main complex required for centromeric cohesion, and RAD21L cohesins are required for normal clustering of pericentromeric heterochromatin. Furthermore, the STAG3/REC8 and STAG3/RAD21L cohesins are the primary cohesins required for axis formation. Copyright © 2016 Ward et al.