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Sample records for fine-scaled human genetic

  1. Fine-scaled human genetic structure revealed by SNP microarrays.

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure.

  2. Fine-scale genetic characterization of Plasmodium falciparum ...

    RESEARCH ARTICLE. Fine-scale genetic characterization of Plasmodium falciparum .... Materials and methods. The DNA ... the order and location of genes (as per the PlasmoDB data resources, available at ... There is currently an. Figure 5.

  3. Fine-Scale Genetic Structure in Finland

    Sini Kerminen

    2017-10-01

    Full Text Available Coupling dense genotype data with new computational methods offers unprecedented opportunities for individual-level ancestry estimation once geographically precisely defined reference data sets become available. We study such a reference data set for Finland containing 2376 such individuals from the FINRISK Study survey of 1997 both of whose parents were born close to each other. This sampling strategy focuses on the population structure present in Finland before the 1950s. By using the recent haplotype-based methods ChromoPainter (CP and FineSTRUCTURE (FS we reveal a highly geographically clustered genetic structure in Finland and report its connections to the settlement history as well as to the current dialectal regions of the Finnish language. The main genetic division within Finland shows striking concordance with the 1323 borderline of the treaty of Nöteborg. In general, we detect genetic substructure throughout the country, which reflects stronger regional genetic differences in Finland compared to, for example, the UK, which in a similar analysis was dominated by a single unstructured population. We expect that similar population genetic reference data sets will become available for many more populations in the near future with important applications, for example, in forensic genetics and in genetic association studies. With this in mind, we report those extensions of the CP + FS approach that we found most useful in our analyses of the Finnish data.

  4. Fine-scale population genetic structure of the Bengal tiger (Panthera tigris tigris) in a human-dominated western Terai Arc Landscape, India.

    Singh, Sujeet Kumar; Aspi, Jouni; Kvist, Laura; Sharma, Reeta; Pandey, Puneet; Mishra, Sudhanshu; Singh, Randeep; Agrawal, Manoj; Goyal, Surendra Prakash

    2017-01-01

    Despite massive global conservation strategies, tiger populations continued to decline until recently, mainly due to habitat loss, human-animal conflicts, and poaching. These factors are known to affect the genetic characteristics of tiger populations and decrease local effective population sizes. The Terai Arc Landscape (TAL) at the foothills of the Himalaya is one of the 42 source sites of tigers around the globe. Therefore, information on how landscape features and anthropogenic factors affect the fine-scale spatial genetic structure and variation of tigers in TAL is needed to develop proper management strategies for achieving long-term conservation goals. We document, for the first time, the genetic characteristics of this tiger population by genotyping 71 tiger samples using 13 microsatellite markers from the western region of TAL (WTAL) of 1800 km2. Specifically, we aimed to estimate the genetic variability, population structure, and gene flow. The microsatellite markers indicated that the levels of allelic diversity (MNA = 6.6) and genetic variation (Ho = 0.50, HE = 0.64) were slightly lower than those reported previously in other Bengal tiger populations. We observed moderate gene flow and significant genetic differentiation (FST= 0.060) and identified the presence of cryptic genetic structure using Bayesian and non-Bayesian approaches. There was low and significantly asymmetric migration between the two main subpopulations of the Rajaji Tiger Reserve and the Corbett Tiger Reserve in WTAL. Sibship relationships indicated that the functionality of the corridor between these subpopulations may be retained if the quality of the habitat does not deteriorate. However, we found that gene flow is not adequate in view of changing land use matrices. We discuss the need to maintain connectivity by implementing the measures that have been suggested previously to minimize the level of human disturbance, including relocation of villages and industries, prevention of

  5. Fine-scale population genetic structure of the Bengal tiger (Panthera tigris tigris in a human-dominated western Terai Arc Landscape, India.

    Sujeet Kumar Singh

    Full Text Available Despite massive global conservation strategies, tiger populations continued to decline until recently, mainly due to habitat loss, human-animal conflicts, and poaching. These factors are known to affect the genetic characteristics of tiger populations and decrease local effective population sizes. The Terai Arc Landscape (TAL at the foothills of the Himalaya is one of the 42 source sites of tigers around the globe. Therefore, information on how landscape features and anthropogenic factors affect the fine-scale spatial genetic structure and variation of tigers in TAL is needed to develop proper management strategies for achieving long-term conservation goals. We document, for the first time, the genetic characteristics of this tiger population by genotyping 71 tiger samples using 13 microsatellite markers from the western region of TAL (WTAL of 1800 km2. Specifically, we aimed to estimate the genetic variability, population structure, and gene flow. The microsatellite markers indicated that the levels of allelic diversity (MNA = 6.6 and genetic variation (Ho = 0.50, HE = 0.64 were slightly lower than those reported previously in other Bengal tiger populations. We observed moderate gene flow and significant genetic differentiation (FST= 0.060 and identified the presence of cryptic genetic structure using Bayesian and non-Bayesian approaches. There was low and significantly asymmetric migration between the two main subpopulations of the Rajaji Tiger Reserve and the Corbett Tiger Reserve in WTAL. Sibship relationships indicated that the functionality of the corridor between these subpopulations may be retained if the quality of the habitat does not deteriorate. However, we found that gene flow is not adequate in view of changing land use matrices. We discuss the need to maintain connectivity by implementing the measures that have been suggested previously to minimize the level of human disturbance, including relocation of villages and industries

  6. Cultural transmission of tool use combined with habitat specializations leads to fine-scale genetic structure in bottlenose dolphins

    Kopps, Anna M.; Ackermann, Corinne Y.; Sherwin, William B.; Allen, Simon J.; Bejder, Lars; Kruetzen, Michael

    2014-01-01

    Socially learned behaviours leading to genetic population structure have rarely been described outside humans. Here, we provide evidence of fine-scale genetic structure that has probably arisen based on socially transmitted behaviours in bottlenose dolphins (Tursiops sp.) in western Shark Bay,

  7. Lack of sex-biased dispersal promotes fine-scale genetic structure in alpine ungulates

    Gretchen H. Roffler; Sandra L. Talbot; Gordon Luikart; George K. Sage; Kristy L. Pilgrim; Layne G. Adams; Michael K. Schwartz

    2014-01-01

    Identifying patterns of fine-scale genetic structure in natural populations can advance understanding of critical ecological processes such as dispersal and gene flow across heterogeneous landscapes. Alpine ungulates generally exhibit high levels of genetic structure due to female philopatry and patchy configuration of mountain habitats. We assessed the spatial scale...

  8. Clonal growth and fine-scale genetic structure in tanoak (Notholithocarpus densiflorus: Fagaceae)

    Richard S. Dodd; Wasima Mayer; Alejandro Nettel; Zara Afzal-Rafii

    2013-01-01

    The combination of sprouting and reproduction by seed can have important consequences on fine-scale spatial distribution of genetic structure (SGS). SGS is an important consideration for species’ restoration because it determines the minimum distance among seed trees to maximize genetic diversity while not prejudicing locally adapted genotypes. Local environmental...

  9. Clonal diversity and fine-scale genetic structure in a high andean treeline population

    Peng, Y.; Macek, P.; Macková, Jana; Romoleroux, K.; Hensen, I.

    2015-01-01

    Roč. 47, č. 1 (2015), s. 59-65 ISSN 0006-3606 Grant - others:GA AV ČR(CZ) IAA601110702; GA MŠk(CZ) LM2010009 Program:IA Institutional support: RVO:60077344 Keywords : AFLP * clonal diversity * clonal propagation * fine-scale genetic structure * Polylepis reticulata * treeline Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.944, year: 2015

  10. Genetic and evolutionary correlates of fine-scale recombination rate variation in Drosophila persimilis.

    Stevison, Laurie S; Noor, Mohamed A F

    2010-12-01

    Recombination is fundamental to meiosis in many species and generates variation on which natural selection can act, yet fine-scale linkage maps are cumbersome to construct. We generated a fine-scale map of recombination rates across two major chromosomes in Drosophila persimilis using 181 SNP markers spanning two of five major chromosome arms. Using this map, we report significant fine-scale heterogeneity of local recombination rates. However, we also observed "recombinational neighborhoods," where adjacent intervals had similar recombination rates after excluding regions near the centromere and telomere. We further found significant positive associations of fine-scale recombination rate with repetitive element abundance and a 13-bp sequence motif known to associate with human recombination rates. We noted strong crossover interference extending 5-7 Mb from the initial crossover event. Further, we observed that fine-scale recombination rates in D. persimilis are strongly correlated with those obtained from a comparable study of its sister species, D. pseudoobscura. We documented a significant relationship between recombination rates and intron nucleotide sequence diversity within species, but no relationship between recombination rate and intron divergence between species. These results are consistent with selection models (hitchhiking and background selection) rather than mutagenic recombination models for explaining the relationship of recombination with nucleotide diversity within species. Finally, we found significant correlations between recombination rate and GC content, supporting both GC-biased gene conversion (BGC) models and selection-driven codon bias models. Overall, this genome-enabled map of fine-scale recombination rates allowed us to confirm findings of broader-scale studies and identify multiple novel features that merit further investigation.

  11. Dispersal, mating events and fine-scale genetic structure in the lesser flat-headed bats.

    Panyu Hua

    Full Text Available Population genetic structure has important consequences in evolutionary processes and conservation genetics in animals. Fine-scale population genetic structure depends on the pattern of landscape, the permanent movement of individuals, and the dispersal of their genes during temporary mating events. The lesser flat-headed bat (Tylonycteris pachypus is a nonmigratory Asian bat species that roosts in small groups within the internodes of bamboo stems and the habitats are fragmented. Our previous parentage analyses revealed considerable extra-group mating in this species. To assess the spatial limits and sex-biased nature of gene flow in the same population, we used 20 microsatellite loci and mtDNA sequencing of the ND2 gene to quantify genetic structure among 54 groups of adult flat-headed bats, at nine localities in South China. AMOVA and F(ST estimates revealed significant genetic differentiation among localities. Alternatively, the pairwise F(ST values among roosting groups appeared to be related to the incidence of associated extra-group breeding, suggesting the impact of mating events on fine-scale genetic structure. Global spatial autocorrelation analyses showed positive genetic correlation for up to 3 km, indicating the role of fragmented habitat and the specialized social organization as a barrier in the movement of individuals among bamboo forests. The male-biased dispersal pattern resulted in weaker spatial genetic structure between localities among males than among females, and fine-scale analyses supported that relatedness levels within internodes were higher among females than among males. Finally, only females were more related to their same sex roost mates than to individuals from neighbouring roosts, suggestive of natal philopatry in females.

  12. Dispersal, mating events and fine-scale genetic structure in the lesser flat-headed bats.

    Hua, Panyu; Zhang, Libiao; Guo, Tingting; Flanders, Jon; Zhang, Shuyi

    2013-01-01

    Population genetic structure has important consequences in evolutionary processes and conservation genetics in animals. Fine-scale population genetic structure depends on the pattern of landscape, the permanent movement of individuals, and the dispersal of their genes during temporary mating events. The lesser flat-headed bat (Tylonycteris pachypus) is a nonmigratory Asian bat species that roosts in small groups within the internodes of bamboo stems and the habitats are fragmented. Our previous parentage analyses revealed considerable extra-group mating in this species. To assess the spatial limits and sex-biased nature of gene flow in the same population, we used 20 microsatellite loci and mtDNA sequencing of the ND2 gene to quantify genetic structure among 54 groups of adult flat-headed bats, at nine localities in South China. AMOVA and F(ST) estimates revealed significant genetic differentiation among localities. Alternatively, the pairwise F(ST) values among roosting groups appeared to be related to the incidence of associated extra-group breeding, suggesting the impact of mating events on fine-scale genetic structure. Global spatial autocorrelation analyses showed positive genetic correlation for up to 3 km, indicating the role of fragmented habitat and the specialized social organization as a barrier in the movement of individuals among bamboo forests. The male-biased dispersal pattern resulted in weaker spatial genetic structure between localities among males than among females, and fine-scale analyses supported that relatedness levels within internodes were higher among females than among males. Finally, only females were more related to their same sex roost mates than to individuals from neighbouring roosts, suggestive of natal philopatry in females.

  13. Outlier SNP markers reveal fine-scale genetic structuring across European hake populations (Merluccius merluccius)

    Milano, I.; Babbucci, M.; Cariani, A.

    2014-01-01

    fishery. Analysis of 850 individuals from 19 locations across the entire distribution range showed evidence for several outlier loci, with significantly higher resolving power. While 299 putatively neutral SNPs confirmed the genetic break between basins (FCT = 0.016) and weak differentiation within basins...... even when neutral markers provide genetic homogeneity across populations. Here, 381 SNPs located in transcribed regions were used to assess largeand fine-scale population structure in the European hake (Merluccius merluccius), a widely distributed demersal species of high priority for the European...

  14. Fine-Scale Human Population Structure in Southern Africa Reflects Ecogeographic Boundaries.

    Uren, Caitlin; Kim, Minju; Martin, Alicia R; Bobo, Dean; Gignoux, Christopher R; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G; Henn, Brenna M

    2016-09-01

    Recent genetic studies have established that the KhoeSan populations of southern Africa are distinct from all other African populations and have remained largely isolated during human prehistory until ∼2000 years ago. Dozens of different KhoeSan groups exist, belonging to three different language families, but very little is known about their population history. We examine new genome-wide polymorphism data and whole mitochondrial genomes for >100 South Africans from the ≠Khomani San and Nama populations of the Northern Cape, analyzed in conjunction with 19 additional southern African populations. Our analyses reveal fine-scale population structure in and around the Kalahari Desert. Surprisingly, this structure does not always correspond to linguistic or subsistence categories as previously suggested, but rather reflects the role of geographic barriers and the ecology of the greater Kalahari Basin. Regardless of subsistence strategy, the indigenous Khoe-speaking Nama pastoralists and the N|u-speaking ≠Khomani (formerly hunter-gatherers) share ancestry with other Khoe-speaking forager populations that form a rim around the Kalahari Desert. We reconstruct earlier migration patterns and estimate that the southern Kalahari populations were among the last to experience gene flow from Bantu speakers, ∼14 generations ago. We conclude that local adoption of pastoralism, at least by the Nama, appears to have been primarily a cultural process with limited genetic impact from eastern Africa. Copyright © 2016 by the Genetics Society of America.

  15. Reduced fine-scale spatial genetic structure in grazed populations of Dianthus carthusianorum.

    Rico, Y; Wagner, H H

    2016-11-01

    Strong spatial genetic structure in plant populations can increase homozygosity, reducing genetic diversity and adaptive potential. The strength of spatial genetic structure largely depends on rates of seed dispersal and pollen flow. Seeds without dispersal adaptations are likely to be dispersed over short distances within the vicinity of the mother plant, resulting in spatial clustering of related genotypes (fine-scale spatial genetic structure, hereafter spatial genetic structure (SGS)). However, primary seed dispersal by zoochory can promote effective dispersal, increasing the mixing of seeds and influencing SGS within plant populations. In this study, we investigated the effects of seed dispersal by rotational sheep grazing on the strength of SGS and genetic diversity using 11 nuclear microsatellites for 49 populations of the calcareous grassland forb Dianthus carthusianorum. Populations connected by rotational sheep grazing showed significantly weaker SGS and higher genetic diversity than populations in ungrazed grasslands. Independent of grazing treatment, small populations showed significantly stronger SGS and lower genetic diversity than larger populations, likely due to genetic drift. A lack of significant differences in the strength of SGS and genetic diversity between populations that were recently colonized and pre-existing populations suggested that populations colonized after the reintroduction of rotational sheep grazing were likely founded by colonists from diverse source populations. We conclude that dispersal by rotational sheep grazing has the potential to considerably reduce SGS within D. carthusianorum populations. Our study highlights the effectiveness of landscape management by rotational sheep grazing to importantly reduce genetic structure at local scales within restored plant populations.

  16. Lack of sex-biased dispersal promotes fine-scale genetic structure in alpine ungulates

    Roffler, Gretchen H.; Talbot, Sandra L.; Luikart, Gordon; Sage, George K.; Pilgrim, Kristy L.; Adams, Layne G.; Schwartz, Michael K.

    2014-01-01

    Identifying patterns of fine-scale genetic structure in natural populations can advance understanding of critical ecological processes such as dispersal and gene flow across heterogeneous landscapes. Alpine ungulates generally exhibit high levels of genetic structure due to female philopatry and patchy configuration of mountain habitats. We assessed the spatial scale of genetic structure and the amount of gene flow in 301 Dall’s sheep (Ovis dalli dalli) at the landscape level using 15 nuclear microsatellites and 473 base pairs of the mitochondrial (mtDNA) control region. Dall’s sheep exhibited significant genetic structure within contiguous mountain ranges, but mtDNA structure occurred at a broader geographic scale than nuclear DNA within the study area, and mtDNA structure for other North American mountain sheep populations. No evidence of male-mediated gene flow or greater philopatry of females was observed; there was little difference between markers with different modes of inheritance (pairwise nuclear DNA F ST = 0.004–0.325; mtDNA F ST = 0.009–0.544), and males were no more likely than females to be recent immigrants. Historical patterns based on mtDNA indicate separate northern and southern lineages and a pattern of expansion following regional glacial retreat. Boundaries of genetic clusters aligned geographically with prominent mountain ranges, icefields, and major river valleys based on Bayesian and hierarchical modeling of microsatellite and mtDNA data. Our results suggest that fine-scale genetic structure in Dall’s sheep is influenced by limited dispersal, and structure may be weaker in populations occurring near ancestral levels of density and distribution in continuous habitats compared to other alpine ungulates that have experienced declines and marked habitat fragmentation.

  17. Breed locally, disperse globally: Fine-scale genetic structure despite landscape-scale panmixia in a fire-specialist

    Jennifer C. Pierson; Fred W. Allendorf; Pierre Drapeau; Michael K. Schwartz

    2013-01-01

    An exciting advance in the understanding of metapopulation dynamics has been the investigation of how populations respond to ephemeral patches that go 'extinct' during the lifetime of an individual. Previous research has shown that this scenario leads to genetic homogenization across large spatial scales. However, little is known about fine-scale genetic...

  18. Applications of random forest feature selection for fine-scale genetic population assignment.

    Sylvester, Emma V A; Bentzen, Paul; Bradbury, Ian R; Clément, Marie; Pearce, Jon; Horne, John; Beiko, Robert G

    2018-02-01

    Genetic population assignment used to inform wildlife management and conservation efforts requires panels of highly informative genetic markers and sensitive assignment tests. We explored the utility of machine-learning algorithms (random forest, regularized random forest and guided regularized random forest) compared with F ST ranking for selection of single nucleotide polymorphisms (SNP) for fine-scale population assignment. We applied these methods to an unpublished SNP data set for Atlantic salmon ( Salmo salar ) and a published SNP data set for Alaskan Chinook salmon ( Oncorhynchus tshawytscha ). In each species, we identified the minimum panel size required to obtain a self-assignment accuracy of at least 90% using each method to create panels of 50-700 markers Panels of SNPs identified using random forest-based methods performed up to 7.8 and 11.2 percentage points better than F ST -selected panels of similar size for the Atlantic salmon and Chinook salmon data, respectively. Self-assignment accuracy ≥90% was obtained with panels of 670 and 384 SNPs for each data set, respectively, a level of accuracy never reached for these species using F ST -selected panels. Our results demonstrate a role for machine-learning approaches in marker selection across large genomic data sets to improve assignment for management and conservation of exploited populations.

  19. The impact of mating systems and dispersal on fine-scale genetic structure at maternally, paternally and biparentally inherited markers.

    Shaw, Robyn E; Banks, Sam C; Peakall, Rod

    2018-01-01

    For decades, studies have focused on how dispersal and mating systems influence genetic structure across populations or social groups. However, we still lack a thorough understanding of how these processes and their interaction shape spatial genetic patterns over a finer scale (tens-hundreds of metres). Using uniparentally inherited markers may help answer these questions, yet their potential has not been fully explored. Here, we use individual-level simulations to investigate the effects of dispersal and mating system on fine-scale genetic structure at autosomal, mitochondrial and Y chromosome markers. Using genetic spatial autocorrelation analysis, we found that dispersal was the major driver of fine-scale genetic structure across maternally, paternally and biparentally inherited markers. However, when dispersal was restricted (mean distance = 100 m), variation in mating behaviour created strong differences in the comparative level of structure detected at maternally and paternally inherited markers. Promiscuity reduced spatial genetic structure at Y chromosome loci (relative to monogamy), whereas structure increased under polygyny. In contrast, mitochondrial and autosomal markers were robust to differences in the specific mating system, although genetic structure increased across all markers when reproductive success was skewed towards fewer individuals. Comparing males and females at Y chromosome vs. mitochondrial markers, respectively, revealed that some mating systems can generate similar patterns to those expected under sex-biased dispersal. This demonstrates the need for caution when inferring ecological and behavioural processes from genetic results. Comparing patterns between the sexes, across a range of marker types, may help us tease apart the processes shaping fine-scale genetic structure. © 2017 John Wiley & Sons Ltd.

  20. Fine-scale spatial genetic structure in predominantly selfing plants with limited seed dispersal: A rule or exception?

    Sergei Volis

    2016-04-01

    Full Text Available Gene flow at a fine scale is still poorly understood despite its recognized importance for plant population demographic and genetic processes. We tested the hypothesis that intensity of gene flow will be lower and strength of spatial genetic structure (SGS will be higher in more peripheral populations because of lower population density. The study was performed on the predominantly selfing Avena sterilis and included: (1 direct measurement of dispersal in a controlled environment; and (2 analyses of SGS in three natural populations, sampled in linear transects at fixed increasing inter-plant distances. We found that in A. sterilis major seed dispersal is by gravity in close (less than 2 m vicinity of the mother plant, with a minor additional effect of wind. Analysis of SGS with six nuclear SSRs revealed a significant autocorrelation for the distance class of 1 m only in the most peripheral desert population, while in the two core populations with Mediterranean conditions, no genetic structure was found. Our results support the hypothesis that intensity of SGS increases from the species core to periphery as a result of decreased within-population gene flow related to low plant density. Our findings also show that predominant self-pollination and highly localized seed dispersal lead to SGS at a very fine scale, but only if plant density is not too high.

  1. Fine-scale population structure and riverscape genetics of brook trout (Salvelinus fontinalis) distributed continuously along headwater channel networks

    Kanno, Yoichiro; Vokoun, Jason C.; Letcher, Benjamin H.

    2011-01-01

    Linear and heterogeneous habitat makes headwater stream networks an ideal ecosystem in which to test the influence of environmental factors on spatial genetic patterns of obligatory aquatic species. We investigated fine-scale population structure and influence of stream habitat on individual-level genetic differentiation in brook trout (Salvelinus fontinalis) by genotyping eight microsatellite loci in 740 individuals in two headwater channel networks (7.7 and 4.4 km) in Connecticut, USA. A weak but statistically significant isolation-by-distance pattern was common in both sites. In the field, many tagged individuals were recaptured in the same 50-m reaches within a single field season (summer to fall). One study site was characterized with a hierarchical population structure, where seasonal barriers (natural falls of 1.5–2.5 m in height during summer base-flow condition) greatly reduced gene flow and perceptible spatial patterns emerged because of the presence of tributaries, each with a group of genetically distinguishable individuals. Genetic differentiation increased when pairs of individuals were separated by high stream gradient (steep channel slope) or warm stream temperature in this site, although the evidence of their influence was equivocal. In a second site, evidence for genetic clusters was weak at best, but genetic differentiation between individuals was positively correlated with number of tributary confluences. We concluded that the population-level movement of brook trout was limited in the study headwater stream networks, resulting in the fine-scale population structure (genetic clusters and clines) even at distances of a few kilometres, and gene flow was mitigated by ‘riverscape’ variables, particularly by physical barriers, waterway distance (i.e. isolation-by-distance) and the presence of tributaries.

  2. Fine-scale genetic structure and cryptic associations reveal evidence of kin-based sociality in the African forest elephant.

    Stephanie G Schuttler

    Full Text Available Spatial patterns of relatedness within animal populations are important in the evolution of mating and social systems, and have the potential to reveal information on species that are difficult to observe in the wild. This study examines the fine-scale genetic structure and connectivity of groups within African forest elephants, Loxodonta cyclotis, which are often difficult to observe due to forest habitat. We tested the hypothesis that genetic similarity will decline with increasing geographic distance, as we expect kin to be in closer proximity, using spatial autocorrelation analyses and Tau K(r tests. Associations between individuals were investigated through a non-invasive genetic capture-recapture approach using network models, and were predicted to be more extensive than the small groups found in observational studies, similar to fission-fusion sociality found in African savanna (Loxodonta africana and Asian (Elephas maximus species. Dung samples were collected in Lopé National Park, Gabon in 2008 and 2010 and genotyped at 10 microsatellite loci, genetically sexed, and sequenced at the mitochondrial DNA control region. We conducted analyses on samples collected at three different temporal scales: a day, within six-day sampling sessions, and within each year. Spatial autocorrelation and Tau K(r tests revealed genetic structure, but results were weak and inconsistent between sampling sessions. Positive spatial autocorrelation was found in distance classes of 0-5 km, and was strongest for the single day session. Despite weak genetic structure, individuals within groups were significantly more related to each other than to individuals between groups. Social networks revealed some components to have large, extensive groups of up to 22 individuals, and most groups were composed of individuals of the same matriline. Although fine-scale population genetic structure was weak, forest elephants are typically found in groups consisting of kin and

  3. Fine-scale genetic structure and cryptic associations reveal evidence of kin-based sociality in the African forest elephant.

    Schuttler, Stephanie G; Philbrick, Jessica A; Jeffery, Kathryn J; Eggert, Lori S

    2014-01-01

    Spatial patterns of relatedness within animal populations are important in the evolution of mating and social systems, and have the potential to reveal information on species that are difficult to observe in the wild. This study examines the fine-scale genetic structure and connectivity of groups within African forest elephants, Loxodonta cyclotis, which are often difficult to observe due to forest habitat. We tested the hypothesis that genetic similarity will decline with increasing geographic distance, as we expect kin to be in closer proximity, using spatial autocorrelation analyses and Tau K(r) tests. Associations between individuals were investigated through a non-invasive genetic capture-recapture approach using network models, and were predicted to be more extensive than the small groups found in observational studies, similar to fission-fusion sociality found in African savanna (Loxodonta africana) and Asian (Elephas maximus) species. Dung samples were collected in Lopé National Park, Gabon in 2008 and 2010 and genotyped at 10 microsatellite loci, genetically sexed, and sequenced at the mitochondrial DNA control region. We conducted analyses on samples collected at three different temporal scales: a day, within six-day sampling sessions, and within each year. Spatial autocorrelation and Tau K(r) tests revealed genetic structure, but results were weak and inconsistent between sampling sessions. Positive spatial autocorrelation was found in distance classes of 0-5 km, and was strongest for the single day session. Despite weak genetic structure, individuals within groups were significantly more related to each other than to individuals between groups. Social networks revealed some components to have large, extensive groups of up to 22 individuals, and most groups were composed of individuals of the same matriline. Although fine-scale population genetic structure was weak, forest elephants are typically found in groups consisting of kin and based on matrilines

  4. Landscape-Level and Fine-Scale Genetic Structure of the Neo tropical Tree Protium spruceanum (Burseraceae)

    Vieira, F.D.A.; Fajardo, C.G.; De Souza, A.M.; Dulciniea De Carvalho, D.

    2010-01-01

    Knowledge of genetic structure at different scales and correlation with the current landscape is fundamental for evaluating the importance of evolutionary processes and identifying conservation units. Here, we used allozyme loci to examine the spatial genetic structure (SGS) of 230 individuals of Protium spruceanum, a native canopy-emergent in five fragments of Brazilian Atlantic forest (1 to 11.8 ha), and four ecological corridors (460 to 1000 m length). Wright's FST statistic and Mantel tests revealed little evidence of significant genetic structure at the landscape-scale (FST=0.027; rM=-0.051, P=.539). At fine-scale SGS, low levels of relatedness within fragments and corridors (Sp=0.008, P>.05) were observed. Differences in the levels and distribution of the SGS at both spatial scales are discussed in relation to biological and conservation strategies of corridors and forest fragments.

  5. Landscape genetic analyses reveal fine-scale effects of forest fragmentation in an insular tropical bird.

    Khimoun, Aurélie; Peterman, William; Eraud, Cyril; Faivre, Bruno; Navarro, Nicolas; Garnier, Stéphane

    2017-10-01

    Within the framework of landscape genetics, resistance surface modelling is particularly relevant to explicitly test competing hypotheses about landscape effects on gene flow. To investigate how fragmentation of tropical forest affects population connectivity in a forest specialist bird species, we optimized resistance surfaces without a priori specification, using least-cost (LCP) or resistance (IBR) distances. We implemented a two-step procedure in order (i) to objectively define the landscape thematic resolution (level of detail in classification scheme to describe landscape variables) and spatial extent (area within the landscape boundaries) and then (ii) to test the relative role of several landscape features (elevation, roads, land cover) in genetic differentiation in the Plumbeous Warbler (Setophaga plumbea). We detected a small-scale reduction of gene flow mainly driven by land cover, with a negative impact of the nonforest matrix on landscape functional connectivity. However, matrix components did not equally constrain gene flow, as their conductivity increased with increasing structural similarity with forest habitat: urban areas and meadows had the highest resistance values whereas agricultural areas had intermediate resistance values. Our results revealed a higher performance of IBR compared to LCP in explaining gene flow, reflecting suboptimal movements across this human-modified landscape, challenging the common use of LCP to design habitat corridors and advocating for a broader use of circuit theory modelling. Finally, our results emphasize the need for an objective definition of landscape scales (landscape extent and thematic resolution) and highlight potential pitfalls associated with parameterization of resistance surfaces. © 2017 John Wiley & Sons Ltd.

  6. Fine-scale variation and genetic determinants of alternative splicing across individuals.

    Jasmin Coulombe-Huntington

    2009-12-01

    Full Text Available Recently, thanks to the increasing throughput of new technologies, we have begun to explore the full extent of alternative pre-mRNA splicing (AS in the human transcriptome. This is unveiling a vast layer of complexity in isoform-level expression differences between individuals. We used previously published splicing sensitive microarray data from lymphoblastoid cell lines to conduct an in-depth analysis on splicing efficiency of known and predicted exons. By combining publicly available AS annotation with a novel algorithm designed to search for AS, we show that many real AS events can be detected within the usually unexploited, speculative majority of the array and at significance levels much below standard multiple-testing thresholds, demonstrating that the extent of cis-regulated differential splicing between individuals is potentially far greater than previously reported. Specifically, many genes show subtle but significant genetically controlled differences in splice-site usage. PCR validation shows that 42 out of 58 (72% candidate gene regions undergo detectable AS, amounting to the largest scale validation of isoform eQTLs to date. Targeted sequencing revealed a likely causative SNP in most validated cases. In all 17 incidences where a SNP affected a splice-site region, in silico splice-site strength modeling correctly predicted the direction of the micro-array and PCR results. In 13 other cases, we identified likely causative SNPs disrupting predicted splicing enhancers. Using Fst and REHH analysis, we uncovered significant evidence that 2 putative causative SNPs have undergone recent positive selection. We verified the effect of five SNPs using in vivo minigene assays. This study shows that splicing differences between individuals, including quantitative differences in isoform ratios, are frequent in human populations and that causative SNPs can be identified using in silico predictions. Several cases affected disease-relevant genes and

  7. Fine-scale genetic structure of natural Tuber aestivum sites in southern Germany

    Molinier, V.; Murat, C.; Baltensweiler, A.; Büntgen, Ulf; Martin, F.; Meier, B.; Moser, B.; Sproll, L.; Stobbe, U.; Tegel, W.; Egli, S.; Peter, M.

    2016-01-01

    Roč. 26, č. 8 (2016), s. 895-907 ISSN 0940-6360 Institutional support: RVO:67179843 Keywords : mating-type distribution * vegetative incompatibility * ectomycorrhizal communities * truffle cultivation * population-genetics * genus tuber * Burgundy truffle * Mating-type genes * Population genetics * Propagation strategy * SSR markers Subject RIV: EH - Ecology, Behaviour Impact factor: 3.047, year: 2016

  8. Local topography shapes fine-scale spatial genetic structure in the Arkansas Valley evening primrose, Oenothera harringtonii (Onagraceae).

    Rhodes, Matthew K; Fant, Jeremie B; Skogen, Krissa A

    2014-01-01

    Identifying factors that shape the spatial distribution of genetic variation is crucial to understanding many population- and landscape-level processes. In this study, we explore fine-scale spatial genetic structure in Oenothera harringtonii (Onagraceae), an insect-pollinated, gravity-dispersed herb endemic to the grasslands of south-central and southeastern Colorado, USA. We genotyped 315 individuals with 11 microsatellite markers and utilized a combination of spatial autocorrelation analyses and landscape genetic models to relate life history traits and landscape features to dispersal processes. Spatial genetic structure was consistent with theoretical expectations of isolation by distance, but this pattern was weak (Sp = 0.00374). Anisotropic analyses indicated that spatial genetic structure was markedly directional, in this case consistent with increased dispersal along prominent slopes. Landscape genetic models subsequently confirmed that spatial genetic variation was significantly influenced by local topographic heterogeneity, specifically that geographic distance, elevation and aspect were important predictors of spatial genetic structure. Among these variables, geographic distance was ~68% more important than elevation in describing spatial genetic variation, and elevation was ~42% more important than aspect after removing the effect of geographic distance. From these results, we infer a mechanism of hydrochorous seed dispersal along major drainages aided by seasonal monsoon rains. Our findings suggest that landscape features may shape microevolutionary processes at much finer spatial scales than typically considered, and stress the importance of considering how particular dispersal vectors are influenced by their environmental context. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Fine-scale population genetic structure of arctic foxes (Vulpes lagopus) in the High Arctic.

    Lai, Sandra; Quiles, Adrien; Lambourdière, Josie; Berteaux, Dominique; Lalis, Aude

    2017-12-01

    The arctic fox (Vulpes lagopus) is a circumpolar species inhabiting all accessible Arctic tundra habitats. The species forms a panmictic population over areas connected by sea ice, but recently, kin clustering and population differentiation were detected even in regions where sea ice was present. The purpose of this study was to examine the genetic structure of a population in the High Arctic using a robust panel of highly polymorphic microsatellites. We analyzed the genotypes of 210 individuals from Bylot Island, Nunavut, Canada, using 15 microsatellite loci. No pattern of isolation-by-distance was detected, but a spatial principal component analysis (sPCA) revealed the presence of genetic subdivisions. Overall, the sPCA revealed two spatially distinct genetic clusters corresponding to the northern and southern parts of the study area, plus another subdivision within each of these two clusters. The north-south genetic differentiation partly matched the distribution of a snow goose colony, which could reflect a preference for settling into familiar ecological environments. Secondary clusters may result from higher-order social structures (neighbourhoods) that use landscape features to delimit their borders. The cryptic genetic subdivisions found in our population may highlight ecological processes deserving further investigations in arctic foxes at larger, regional spatial scales.

  10. Pollen-mediated gene flow and fine-scale spatial genetic structure in Olea europaea subsp. europaea var. sylvestris.

    Beghè, D; Piotti, A; Satovic, Z; de la Rosa, R; Belaj, A

    2017-03-01

    Wild olive ( Olea europaea subsp. europaea var. sylvestris ) is important from an economic and ecological point of view. The effects of anthropogenic activities may lead to the genetic erosion of its genetic patrimony, which has high value for breeding programmes. In particular, the consequences of the introgression from cultivated stands are strongly dependent on the extent of gene flow and therefore this work aims at quantitatively describing contemporary gene flow patterns in wild olive natural populations. The studied wild population is located in an undisturbed forest, in southern Spain, considered one of the few extant hotspots of true oleaster diversity. A total of 225 potential father trees and seeds issued from five mother trees were genotyped by eight microsatellite markers. Levels of contemporary pollen flow, in terms of both pollen immigration rates and within-population dynamics, were measured through paternity analyses. Moreover, the extent of fine-scale spatial genetic structure (SGS) was studied to assess the relative importance of seed and pollen dispersal in shaping the spatial distribution of genetic variation. The results showed that the population under study is characterized by a high genetic diversity, a relatively high pollen immigration rate (0·57), an average within-population pollen dispersal of about 107 m and weak but significant SGS up to 40 m. The population is a mosaic of several intermingled genetic clusters that is likely to be generated by spatially restricted seed dispersal. Moreover, wild oleasters were found to be self-incompatible and preferential mating between some genotypes was revealed. Knowledge of the within-population genetic structure and gene flow dynamics will lead to identifying possible strategies aimed at limiting the effect of anthropogenic activities and improving breeding programmes for the conservation of olive tree forest genetic resources. © The Author 2016. Published by Oxford University Press on behalf

  11. High genetic diversity and fine-scale spatial structure in the marine flagellate Oxyrrhis marina (Dinophyceae uncovered by microsatellite loci.

    Chris D Lowe

    2010-12-01

    Full Text Available Free-living marine protists are often assumed to be broadly distributed and genetically homogeneous on large spatial scales. However, an increasing application of highly polymorphic genetic markers (e.g., microsatellites has provided evidence for high genetic diversity and population structuring on small spatial scales in many free-living protists. Here we characterise a panel of new microsatellite markers for the common marine flagellate Oxyrrhis marina. Nine microsatellite loci were used to assess genotypic diversity at two spatial scales by genotyping 200 isolates of O. marina from 6 broad geographic regions around Great Britain and Ireland; in one region, a single 2 km shore line was sampled intensively to assess fine-scale genetic diversity. Microsatellite loci resolved between 1-6 and 7-23 distinct alleles per region in the least and most variable loci respectively, with corresponding variation in expected heterozygosities (H(e of 0.00-0.30 and 0.81-0.93. Across the dataset, genotypic diversity was high with 183 genotypes detected from 200 isolates. Bayesian analysis of population structure supported two model populations. One population was distributed across all sampled regions; the other was confined to the intensively sampled shore, and thus two distinct populations co-occurred at this site. Whilst model-based analysis inferred a single UK-wide population, pairwise regional F(ST values indicated weak to moderate population sub-division (0.01-0.12, but no clear correlation between spatial and genetic distance was evident. Data presented in this study highlight extensive genetic diversity for O. marina; however, it remains a substantial challenge to uncover the mechanisms that drive genetic diversity in free-living microorganisms.

  12. Fine-scale genetic structure and social organization in female white-tailed deer.

    Comer, Christopher E.; Kilgo, John C.; D' Angelo, Gino J.; Glenn, Travis C.; Miller, Karl V.

    2005-07-01

    Abstract: Social behavior of white-tailed deer (Odocoileus virginianus) can have important management implications. The formation of matrilineal social groups among female deer has been documented and management strategies have been proposed based on this well-developed social structure. Using radiocollared (n = 17) and hunter or vehicle-killed (n = 21) does, we examined spatial and genetic structure in white-tailed deer on a 7,000-ha portion of the Savannah River Site in the upper Coastal Plain of South Carolina, USA. We used 14 microsatellite DNA loci to calculate pairwise relatedness among individual deer and to assign doe pairs to putative relationship categories. Linear distance and genetic relatedness were weakly correlated (r = –0.08, P = 0.058). Relationship categories differed in mean spatial distance, but only 60% of first-degree-related doe pairs (full sibling or mother–offspring pairs) and 38% of second-degree-related doe pairs (half sibling, grandmother–granddaughter pairs) were members of the same social group based on spatial association. Heavy hunting pressure in this population has created a young age structure among does, where the average age is <2.5 years, and <4% of does are >4.5 years old. This—combined with potentially elevated dispersal among young does—could limit the formation of persistent, cohesive social groups. Our results question the universal applicability of recently proposed models of spatial and genetic structuring in white-tailed deer, particularly in areas with differing harvest histories.

  13. Fine-scale genetic analysis of species-specific female preference in Drosophila simulans.

    Laturney, M; Moehring, A J

    2012-09-01

    Behavioural differences are thought to be the first components to contribute to species isolation, yet the precise genetic basis of behavioural isolation remains poorly understood. Here, we used a combination of behaviour assays and genetic mapping to provide the first refined map locating candidate genes for interspecific female preference isolating Drosophila simulans from D. melanogaster. First, we tested whether two genes identified as affecting D. melanogaster female intraspecific mate choice also affect interspecific mate choice; neither of these genes was found to contribute to species-specific female preference. Next, we used deficiency mapping to locate genes on the right arm of the third chromosome for species-specific female preference and identified five small significant regions that contain candidate genes contributing to behavioural isolation. All five regions were located in areas that would have low interspecific recombination, which mirrors the results of other behavioural isolation studies that used quantitative trait locus (QTL) mapping, but without the potential concern of bias towards regions of low recombination that QTL mapping may have. As this model system may be refined to the individual gene level using the same methodology, this initial map we provide may potentially serve as a ready template for the identification and characterization of the first behavioural isolation genes. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  14. Fine scale population genetic structure and within tree distribution of mating types of Venturia effusa, cause of pecan scab in the USA

    Scab (caused by Venturia effusa) is the major disease of pecan in the southeastern USA. There is no information available on the fine scale population genetic diversity. Four cv. Wichita trees (populations) were sampled hierarchically. Within each tree canopy, 4 approximately evenly spaced terminals...

  15. Higher fine-scale genetic structure in peripheral than in core populations of a long-lived and mixed-mating conifer - eastern white cedar (Thuja occidentalis L.)

    2012-01-01

    Background Fine-scale or spatial genetic structure (SGS) is one of the key genetic characteristics of plant populations. Several evolutionary and ecological processes and population characteristics influence the level of SGS within plant populations. Higher fine-scale genetic structure may be expected in peripheral than core populations of long-lived forest trees, owing to the differences in the magnitude of operating evolutionary and ecological forces such as gene flow, genetic drift, effective population size and founder effects. We addressed this question using eastern white cedar (Thuja occidentalis) as a model species for declining to endangered long-lived tree species with mixed-mating system. Results We determined the SGS in two core and two peripheral populations of eastern white cedar from its Maritime Canadian eastern range using six nuclear microsatellite DNA markers. Significant SGS ranging from 15 m to 75 m distance classes was observed in the four studied populations. An analysis of combined four populations revealed significant positive SGS up to the 45 m distance class. The mean positive significant SGS observed in the peripheral populations was up to six times (up to 90 m) of that observed in the core populations (15 m). Spatial autocorrelation coefficients and correlograms of single and sub-sets of populations were statistically significant. The extent of within-population SGS was significantly negatively correlated with all genetic diversity parameters. Significant heterogeneity of within-population SGS was observed for 0-15 m and 61-90 m between core and peripheral populations. Average Sp, and gene flow distances were higher in peripheral (Sp = 0.023, σg = 135 m) than in core (Sp = 0.014, σg = 109 m) populations. However, the mean neighborhood size was higher in the core (Nb = 82) than in the peripheral (Nb = 48) populations. Conclusion Eastern white cedar populations have significant fine-scale genetic structure at short distances. Peripheral

  16. Higher fine-scale genetic structure in peripheral than in core populations of a long-lived and mixed-mating conifer - eastern white cedar (Thuja occidentalis L.

    Pandey Madhav

    2012-04-01

    Full Text Available Abstract Background Fine-scale or spatial genetic structure (SGS is one of the key genetic characteristics of plant populations. Several evolutionary and ecological processes and population characteristics influence the level of SGS within plant populations. Higher fine-scale genetic structure may be expected in peripheral than core populations of long-lived forest trees, owing to the differences in the magnitude of operating evolutionary and ecological forces such as gene flow, genetic drift, effective population size and founder effects. We addressed this question using eastern white cedar (Thuja occidentalis as a model species for declining to endangered long-lived tree species with mixed-mating system. Results We determined the SGS in two core and two peripheral populations of eastern white cedar from its Maritime Canadian eastern range using six nuclear microsatellite DNA markers. Significant SGS ranging from 15 m to 75 m distance classes was observed in the four studied populations. An analysis of combined four populations revealed significant positive SGS up to the 45 m distance class. The mean positive significant SGS observed in the peripheral populations was up to six times (up to 90 m of that observed in the core populations (15 m. Spatial autocorrelation coefficients and correlograms of single and sub-sets of populations were statistically significant. The extent of within-population SGS was significantly negatively correlated with all genetic diversity parameters. Significant heterogeneity of within-population SGS was observed for 0-15 m and 61-90 m between core and peripheral populations. Average Sp, and gene flow distances were higher in peripheral (Sp = 0.023, σg = 135 m than in core (Sp = 0.014, σg = 109 m populations. However, the mean neighborhood size was higher in the core (Nb = 82 than in the peripheral (Nb = 48 populations. Conclusion Eastern white cedar populations have significant fine-scale genetic structure at short

  17. Fine-Scale Cartography of Human Impacts along French Mediterranean Coasts: A Relevant Map for the Management of Marine Ecosystems.

    Florian Holon

    Full Text Available Ecosystem services provided by oceans and seas support most human needs but are threatened by human activities. Despite existing maps illustrating human impacts on marine ecosystems, information remains either large-scale but rough and insufficient for stakeholders (1 km² grid, lack of data along the coast or fine-scale but fragmentary and heterogeneous in methodology. The objectives of this study are to map and quantify the main pressures exerted on near-coast marine ecosystems, at a large spatial scale though in fine and relevant resolution for managers (one pixel = 20 x 20 m. It focuses on the French Mediterranean coast (1,700 km of coastline including Corsica at a depth of 0 to 80 m. After completing and homogenizing data presently available under GIS on the bathymetry and anthropogenic pressures but also on the seabed nature and ecosystem vulnerability, we provide a fine modeling of the extent and impacts of 10 anthropogenic pressures on marine habitats. The considered pressures are man-made coastline, boat anchoring, aquaculture, urban effluents, industrial effluents, urbanization, agriculture, coastline erosion, coastal population and fishing. A 1:10 000 continuous habitat map is provided considering 11 habitat classes. The marine bottom is mostly covered by three habitats: infralittoral soft bottom, Posidonia oceanica meadows and circalittoral soft bottom. Around two thirds of the bottoms are found within medium and medium high cumulative impact categories. Seagrass meadows are the most impacted habitats. The most important pressures (in area and intensity are urbanization, coastal population, coastal erosion and man-made coastline. We also identified areas in need of a special management interest. This work should contribute to prioritize environmental needs, as well as enhance the development of indicators for the assessment of the ecological status of coastal systems. It could also help better apply and coordinate management measures

  18. Fine-Scale Cartography of Human Impacts along French Mediterranean Coasts: A Relevant Map for the Management of Marine Ecosystems.

    Holon, Florian; Mouquet, Nicolas; Boissery, Pierre; Bouchoucha, Marc; Delaruelle, Gwenaelle; Tribot, Anne-Sophie; Deter, Julie

    2015-01-01

    Ecosystem services provided by oceans and seas support most human needs but are threatened by human activities. Despite existing maps illustrating human impacts on marine ecosystems, information remains either large-scale but rough and insufficient for stakeholders (1 km² grid, lack of data along the coast) or fine-scale but fragmentary and heterogeneous in methodology. The objectives of this study are to map and quantify the main pressures exerted on near-coast marine ecosystems, at a large spatial scale though in fine and relevant resolution for managers (one pixel = 20 x 20 m). It focuses on the French Mediterranean coast (1,700 km of coastline including Corsica) at a depth of 0 to 80 m. After completing and homogenizing data presently available under GIS on the bathymetry and anthropogenic pressures but also on the seabed nature and ecosystem vulnerability, we provide a fine modeling of the extent and impacts of 10 anthropogenic pressures on marine habitats. The considered pressures are man-made coastline, boat anchoring, aquaculture, urban effluents, industrial effluents, urbanization, agriculture, coastline erosion, coastal population and fishing. A 1:10 000 continuous habitat map is provided considering 11 habitat classes. The marine bottom is mostly covered by three habitats: infralittoral soft bottom, Posidonia oceanica meadows and circalittoral soft bottom. Around two thirds of the bottoms are found within medium and medium high cumulative impact categories. Seagrass meadows are the most impacted habitats. The most important pressures (in area and intensity) are urbanization, coastal population, coastal erosion and man-made coastline. We also identified areas in need of a special management interest. This work should contribute to prioritize environmental needs, as well as enhance the development of indicators for the assessment of the ecological status of coastal systems. It could also help better apply and coordinate management measures at a relevant

  19. Human Social Behavior and Demography Drive Patterns of Fine-Scale Dengue Transmission in Endemic Areas of Colombia.

    Harish Padmanabha

    Full Text Available Dengue is known to transmit between humans and A. aegypti mosquitoes living in neighboring houses. Although transmission is thought to be highly heterogeneous in both space and time, little is known about the patterns and drivers of transmission in groups of houses in endemic settings. We carried out surveys of PCR positivity in children residing in 2-block patches of highly endemic cities of Colombia. We found high levels of heterogeneity in PCR positivity, varying from less than 30% in 8 of the 10 patches to 56 and 96%, with the latter patch containing 22 children simultaneously PCR positive (PCR22 for DEN2. We then used an agent-based model to assess the likely eco-epidemiological context of this observation. Our model, simulating daily dengue dynamics over a 20 year period in a single two block patch, suggests that the observed heterogeneity most likely derived from variation in the density of susceptible people. Two aspects of human adaptive behavior were critical to determining this density: external social relationships favoring viral introduction (by susceptible residents or infectious visitors and immigration of households from non-endemic areas. External social relationships generating frequent viral introduction constituted a particularly strong constraint on susceptible densities, thereby limiting the potential for explosive outbreaks and dampening the impact of heightened vectorial capacity. Dengue transmission can be highly explosive locally, even in neighborhoods with significant immunity in the human population. Variation among neighborhoods in the density of local social networks and rural-to-urban migration is likely to produce significant fine-scale heterogeneity in dengue dynamics, constraining or amplifying the impacts of changes in mosquito populations and cross immunity between serotypes.

  20. Exploiting fine-scale genetic and physiological variation of closely related microbes to reveal unknown enzyme functions.

    Badur, Ahmet H; Plutz, Matthew J; Yalamanchili, Geethika; Jagtap, Sujit Sadashiv; Schweder, Thomas; Unfried, Frank; Markert, Stephanie; Polz, Martin F; Hehemann, Jan-Hendrik; Rao, Christopher V

    2017-08-04

    Polysaccharide degradation by marine microbes represents one of the largest and most rapid heterotrophic transformations of organic matter in the environment. Microbes employ systems of complementary carbohydrate-specific enzymes to deconstruct algal or plant polysaccharides (glycans) into monosaccharides. Because of the high diversity of glycan substrates, the functions of these enzymes are often difficult to establish. One solution to this problem may lie within naturally occurring microdiversity; varying numbers of enzymes, due to gene loss, duplication, or transfer, among closely related environmental microbes create metabolic differences akin to those generated by knock-out strains engineered in the laboratory used to establish the functions of unknown genes. Inspired by this natural fine-scale microbial diversity, we show here that it can be used to develop hypotheses guiding biochemical experiments for establishing the role of these enzymes in nature. In this work, we investigated alginate degradation among closely related strains of the marine bacterium Vibrio splendidus One strain, V. splendidus 13B01, exhibited high extracellular alginate lyase activity compared with other V. splendidus strains. To identify the enzymes responsible for this high extracellular activity, we compared V. splendidus 13B01 with the previously characterized V. splendidus 12B01, which has low extracellular activity and lacks two alginate lyase genes present in V. splendidus 13B01. Using a combination of genomics, proteomics, biochemical, and functional screening, we identified a polysaccharide lyase family 7 enzyme that is unique to V. splendidus 13B01, secreted, and responsible for the rapid digestion of extracellular alginate. These results demonstrate the value of querying the enzymatic repertoires of closely related microbes to rapidly pinpoint key proteins with beneficial functions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Linking movement behavior and fine-scale genetic structure to model landscape connectivity for bobcats (Lynx rufus)

    Dawn M. Reding; Samuel A. Cushman; Todd E. Gosselink; William R. Clark

    2013-01-01

    Spatial heterogeneity can constrain the movement of individuals and consequently genes across a landscape, influencing demographic and genetic processes. In this study, we linked information on landscape composition, movement behavior, and genetic differentiation to gain a mechanistic understanding of how spatial heterogeneity may influence movement and gene flow of...

  2. Development of a multiplex PCR assay for fine-scale population genetic analysis of the Komodo monitor Varanus komodoensis based on 18 polymorphic microsatellite loci.

    Ciofi, Claudio; Tzika, Athanasia C; Natali, Chiara; Watts, Phillip C; Sulandari, Sri; Zein, Moch S A; Milinkovitch, Michel C

    2011-05-01

    Multiplex PCR assays for the coamplification of microsatellite loci allow rapid and cost-effective genetic analyses and the production of efficient screening protocols for international breeding programs. We constructed a partial genomic library enriched for di-nucleotide repeats and characterized 14 new microsatellite loci for the Komodo monitor (or Komodo dragon, Varanus komodoensis). Using these novel microsatellites and four previously described loci, we developed multiplex PCR assays that may be loaded on a genetic analyser in three separate panels. We tested the novel set of microsatellites for polymorphism using 69 individuals from three island populations and evaluated the resolving power of the entire panel of 18 loci by conducting (i) a preliminary assignment test to determine population(s) of origin and (ii) a parentage analysis for 43 captive Komodo monitors. This panel of polymorphic loci proved useful for both purposes and thus can be exploited for fine-scale population genetic analyses and as part of international captive breeding programs directed at maintaining genetically viable ex situ populations and reintroductions. © 2011 Blackwell Publishing Ltd.

  3. Fine-scale population genetic structure and short-range sex-biased dispersal in a solitary carnivore, Lutra lutra

    Quaglietta, L.; Fonseca, V. C.; Hájková, Petra; Mira, A.; Boitani, L.

    2013-01-01

    Roč. 94, č. 3 (2013), s. 561-571 ISSN 0022-2372 Institutional support: RVO:68081766 Keywords : conservation genetics * dispersal distances * Eurasian otter * isolation by distance * radiotracking * restricted gene flow * spatial relatedness structure * spatiotemporal scale Subject RIV: EG - Zoology Impact factor: 2.225, year: 2013

  4. Fine-scale analysis of genetic structure in the brooding coral Seriatopora hystrix from the Red Sea

    Maier, E.; Tollrian, R.; Nürnberger, B.

    2009-09-01

    The dispersal of gametes and larvae plays a key role in the population dynamics of sessile marine invertebrates. Species with internal fertilisation are often associated with very localised larval dispersal, which may cause small-scale patterns of neutral genetic variation. This study on the brooding coral Seriatopora hystrix from the Red Sea focused on the smallest possible scale: Two S. hystrix stands (~100 colonies each) near Dahab were completely sampled, mapped and analysed at five microsatellite markers. The sexual mode of reproduction, the likely occurrence of selfing and the level of immigration were in agreement with previous studies on this species. Contrary to previous findings, both stands were in Hardy-Weinberg proportions. Also, no evidence for spatially restricted larval dispersal within the sampled areas was found. Differences between this and previous studies on S. hystrix could reflect variation in life history or varying environmental conditions, which opens intriguing questions for future research.

  5. Pinpointing cryptic borders: Fine-scale phylogeography and genetic landscape analysis of the Hormogaster elisae complex (Oligochaeta, Hormogastridae).

    Marchán, Daniel F; Fernández, Rosa; de Sosa, Irene; Díaz Cosín, Darío J; Novo, Marta

    2017-07-01

    Spatial and temporal aspects of the evolution of cryptic species complexes have received less attention than species delimitation within them. The phylogeography of the cryptic complex Hormogaster elisae (Oligochaeta, Hormogastridae) lacks knowledge on several aspects, including the small-scale distribution of its lineages or the palaeogeographic context of their diversification. To shed light on these topics, a dense specimen collection was performed in the center of the Iberian Peninsula - resulting in 28 new H. elisae collecting points, some of them as close as 760m from each other- for a higher resolution of the distribution of the cryptic lineages and the relationships between the populations. Seven molecular regions were amplified: mitochondrial subunit 1 of cytochrome c oxidase (COI), 16S rRNA and tRNA Leu, Ala, and Ser (16S t-RNAs), one nuclear ribosomal gene (a fragment of 28S rRNA) and one nuclear protein-encoding gene (histone H3) in order to infer their phylogenetic relationships. Different representation methods of the pairwise divergence in the cytochrome oxidase I sequence (heatmap and genetic landscape graphs) were used to visualize the genetic structure of H. elisae. A nested approach sensu Mairal et al. (2015) (connecting the evolutionary rates of two datasets of different taxonomic coverage) was used to obtain one approximation to a time-calibrated phylogenetic tree based on external Clitellata fossils and a wide molecular dataset. Our results indicate that limited active dispersal ability and ecological or biotic barriers could explain the isolation of the different cryptic lineages, which never co-occur. Rare events of long distance dispersal through hydrochory appear as one of the possible causes of range expansion. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Higher fine-scale genetic structure in peripheral than in core populations of a long-lived and mixed-mating conifer--eastern white cedar (Thuja occidentalis L.).

    Pandey, Madhav; Rajora, Om P

    2012-04-05

    Fine-scale or spatial genetic structure (SGS) is one of the key genetic characteristics of plant populations. Several evolutionary and ecological processes and population characteristics influence the level of SGS within plant populations. Higher fine-scale genetic structure may be expected in peripheral than core populations of long-lived forest trees, owing to the differences in the magnitude of operating evolutionary and ecological forces such as gene flow, genetic drift, effective population size and founder effects. We addressed this question using eastern white cedar (Thuja occidentalis) as a model species for declining to endangered long-lived tree species with mixed-mating system. We determined the SGS in two core and two peripheral populations of eastern white cedar from its Maritime Canadian eastern range using six nuclear microsatellite DNA markers. Significant SGS ranging from 15 m to 75 m distance classes was observed in the four studied populations. An analysis of combined four populations revealed significant positive SGS up to the 45 m distance class. The mean positive significant SGS observed in the peripheral populations was up to six times (up to 90 m) of that observed in the core populations (15 m). Spatial autocorrelation coefficients and correlograms of single and sub-sets of populations were statistically significant. The extent of within-population SGS was significantly negatively correlated with all genetic diversity parameters. Significant heterogeneity of within-population SGS was observed for 0-15 m and 61-90 m between core and peripheral populations. Average Sp, and gene flow distances were higher in peripheral (Sp = 0.023, σg = 135 m) than in core (Sp = 0.014, σg = 109 m) populations. However, the mean neighborhood size was higher in the core (Nb = 82) than in the peripheral (Nb = 48) populations. Eastern white cedar populations have significant fine-scale genetic structure at short distances. Peripheral populations have several

  7. Genome-Wide Fine-Scale Recombination Rate Variation in Drosophila melanogaster

    Song, Yun S.

    2012-01-01

    Estimating fine-scale recombination maps of Drosophila from population genomic data is a challenging problem, in particular because of the high background recombination rate. In this paper, a new computational method is developed to address this challenge. Through an extensive simulation study, it is demonstrated that the method allows more accurate inference, and exhibits greater robustness to the effects of natural selection and noise, compared to a well-used previous method developed for studying fine-scale recombination rate variation in the human genome. As an application, a genome-wide analysis of genetic variation data is performed for two Drosophila melanogaster populations, one from North America (Raleigh, USA) and the other from Africa (Gikongoro, Rwanda). It is shown that fine-scale recombination rate variation is widespread throughout the D. melanogaster genome, across all chromosomes and in both populations. At the fine-scale, a conservative, systematic search for evidence of recombination hotspots suggests the existence of a handful of putative hotspots each with at least a tenfold increase in intensity over the background rate. A wavelet analysis is carried out to compare the estimated recombination maps in the two populations and to quantify the extent to which recombination rates are conserved. In general, similarity is observed at very broad scales, but substantial differences are seen at fine scales. The average recombination rate of the X chromosome appears to be higher than that of the autosomes in both populations, and this pattern is much more pronounced in the African population than the North American population. The correlation between various genomic features—including recombination rates, diversity, divergence, GC content, gene content, and sequence quality—is examined using the wavelet analysis, and it is shown that the most notable difference between D. melanogaster and humans is in the correlation between recombination and

  8. Relationships between population density, fine-scale genetic structure, mating system and pollen dispersal in a timber tree from African rainforests.

    Duminil, J; Daïnou, K; Kaviriri, D K; Gillet, P; Loo, J; Doucet, J-L; Hardy, O J

    2016-03-01

    Owing to the reduction of population density and/or the environmental changes it induces, selective logging could affect the demography, reproductive biology and evolutionary potential of forest trees. This is particularly relevant in tropical forests where natural population densities can be low and isolated trees may be subject to outcross pollen limitation and/or produce low-quality selfed seeds that exhibit inbreeding depression. Comparing reproductive biology processes and genetic diversity of populations at different densities can provide indirect evidence of the potential impacts of logging. Here, we analysed patterns of genetic diversity, mating system and gene flow in three Central African populations of the self-compatible legume timber species Erythrophleum suaveolens with contrasting densities (0.11, 0.68 and 1.72 adults per ha). The comparison of inbreeding levels among cohorts suggests that selfing is detrimental as inbred individuals are eliminated between seedling and adult stages. Levels of genetic diversity, selfing rates (∼16%) and patterns of spatial genetic structure (Sp ∼0.006) were similar in all three populations. However, the extent of gene dispersal differed markedly among populations: the average distance of pollen dispersal increased with decreasing density (from 200 m in the high-density population to 1000 m in the low-density one). Overall, our results suggest that the reproductive biology and genetic diversity of the species are not affected by current logging practices. However, further investigations need to be conducted in low-density populations to evaluate (1) whether pollen limitation may reduce seed production and (2) the regeneration potential of the species.

  9. Relationships between population density, fine-scale genetic structure, mating system and pollen dispersal in a timber tree from African rainforests

    Duminil, J; Daïnou, K; Kaviriri, D K; Gillet, P; Loo, J; Doucet, J-L; Hardy, O J

    2016-01-01

    Owing to the reduction of population density and/or the environmental changes it induces, selective logging could affect the demography, reproductive biology and evolutionary potential of forest trees. This is particularly relevant in tropical forests where natural population densities can be low and isolated trees may be subject to outcross pollen limitation and/or produce low-quality selfed seeds that exhibit inbreeding depression. Comparing reproductive biology processes and genetic diversity of populations at different densities can provide indirect evidence of the potential impacts of logging. Here, we analysed patterns of genetic diversity, mating system and gene flow in three Central African populations of the self-compatible legume timber species Erythrophleum suaveolens with contrasting densities (0.11, 0.68 and 1.72 adults per ha). The comparison of inbreeding levels among cohorts suggests that selfing is detrimental as inbred individuals are eliminated between seedling and adult stages. Levels of genetic diversity, selfing rates (∼16%) and patterns of spatial genetic structure (Sp ∼0.006) were similar in all three populations. However, the extent of gene dispersal differed markedly among populations: the average distance of pollen dispersal increased with decreasing density (from 200 m in the high-density population to 1000 m in the low-density one). Overall, our results suggest that the reproductive biology and genetic diversity of the species are not affected by current logging practices. However, further investigations need to be conducted in low-density populations to evaluate (1) whether pollen limitation may reduce seed production and (2) the regeneration potential of the species. PMID:26696137

  10. Fine-scale estimation of carbon monoxide and fine particulate matter concentrations in proximity to a road intersection by using wavelet neural network with genetic algorithm

    Wang, Zhanyong; Lu, Feng; He, Hong-di; Lu, Qing-Chang; Wang, Dongsheng; Peng, Zhong-Ren

    2015-03-01

    At road intersections, vehicles frequently stop with idling engines during the red-light period and speed up rapidly in the green-light period, which generates higher velocity fluctuation and thus higher emission rates. Additionally, the frequent changes of wind direction further add the highly variable dispersion of pollutants at the street scale. It is, therefore, very difficult to estimate the distribution of pollutant concentrations using conventional deterministic causal models. For this reason, a hybrid model combining wavelet neural network and genetic algorithm (GA-WNN) is proposed for predicting 5-min series of carbon monoxide (CO) and fine particulate matter (PM2.5) concentrations in proximity to an intersection. The proposed model is examined based on the measured data under two situations. As the measured pollutant concentrations are found to be dependent on the distance to the intersection, the model is evaluated in three locations respectively, i.e. 110 m, 330 m and 500 m. Due to the different variation of pollutant concentrations on varied time, the model is also evaluated in peak and off-peak traffic time periods separately. Additionally, the proposed model, together with the back-propagation neural network (BPNN), is examined with the measured data in these situations. The proposed model is found to perform better in predictability and precision for both CO and PM2.5 than BPNN does, implying that the hybrid model can be an effective tool to improve the accuracy of estimating pollutants' distribution pattern at intersections. The outputs of these findings demonstrate the potential of the proposed model to be applicable to forecast the distribution pattern of air pollution in real-time in proximity to road intersection.

  11. Fine-scale genetic mapping of a hybrid sterility factor between Drosophila simulans and D. mauritiana: the varied and elusive functions of "speciation genes"

    Lemos Bernardo

    2010-12-01

    Full Text Available Abstract Background Hybrid male sterility (HMS is a usual outcome of hybridization between closely related animal species. It arises because interactions between alleles that are functional within one species may be disrupted in hybrids. The identification of genes leading to hybrid sterility is of great interest for understanding the evolutionary process of speciation. In the current work we used marked P-element insertions as dominant markers to efficiently locate one genetic factor causing a severe reduction in fertility in hybrid males of Drosophila simulans and D. mauritiana. Results Our mapping effort identified a region of 9 kb on chromosome 3, containing three complete and one partial coding sequences. Within this region, two annotated genes are suggested as candidates for the HMS factor, based on the comparative molecular characterization and public-source information. Gene Taf1 is partially contained in the region, but yet shows high polymorphism with four fixed non-synonymous substitutions between the two species. Its molecular functions involve sequence-specific DNA binding and transcription factor activity. Gene agt is a small, intronless gene, whose molecular function is annotated as methylated-DNA-protein-cysteine S-methyltransferase activity. High polymorphism and one fixed non-synonymous substitution suggest this is a fast evolving gene. The gene trees of both genes perfectly separate D. simulans and D. mauritiana into monophyletic groups. Analysis of gene expression using microarray revealed trends that were similar to those previously found in comparisons between whole-genome hybrids and parental species. Conclusions The identification following confirmation of the HMS candidate gene will add another case study leading to understanding the evolutionary process of hybrid incompatibility.

  12. Fine-scale genetic mapping of a hybrid sterility factor between Drosophila simulans and D. mauritiana: the varied and elusive functions of "speciation genes".

    Araripe, Luciana O; Montenegro, Horácio; Lemos, Bernardo; Hartl, Daniel L

    2010-12-14

    Hybrid male sterility (HMS) is a usual outcome of hybridization between closely related animal species. It arises because interactions between alleles that are functional within one species may be disrupted in hybrids. The identification of genes leading to hybrid sterility is of great interest for understanding the evolutionary process of speciation. In the current work we used marked P-element insertions as dominant markers to efficiently locate one genetic factor causing a severe reduction in fertility in hybrid males of Drosophila simulans and D. mauritiana. Our mapping effort identified a region of 9 kb on chromosome 3, containing three complete and one partial coding sequences. Within this region, two annotated genes are suggested as candidates for the HMS factor, based on the comparative molecular characterization and public-source information. Gene Taf1 is partially contained in the region, but yet shows high polymorphism with four fixed non-synonymous substitutions between the two species. Its molecular functions involve sequence-specific DNA binding and transcription factor activity. Gene agt is a small, intronless gene, whose molecular function is annotated as methylated-DNA-protein-cysteine S-methyltransferase activity. High polymorphism and one fixed non-synonymous substitution suggest this is a fast evolving gene. The gene trees of both genes perfectly separate D. simulans and D. mauritiana into monophyletic groups. Analysis of gene expression using microarray revealed trends that were similar to those previously found in comparisons between whole-genome hybrids and parental species. The identification following confirmation of the HMS candidate gene will add another case study leading to understanding the evolutionary process of hybrid incompatibility.

  13. A genetic atlas of human admixture history

    Hellenthal, Garrett; Busby, George B.J.; Band, Gavin; Wilson, James F.; Capelli, Cristian

    2014-01-01

    Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations. PMID:24531965

  14. A genetic atlas of human admixture history.

    Hellenthal, Garrett; Busby, George B J; Band, Gavin; Wilson, James F; Capelli, Cristian; Falush, Daniel; Myers, Simon

    2014-02-14

    Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed by using genetic data alone and encompassing over 100 events occurring over the past 4000 years. We identified events whose dates and participants suggest they describe genetic impacts of the Mongol empire, Arab slave trade, Bantu expansion, first millennium CE migrations in Eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations.

  15. Evaluating human genetic diversity

    This book assesses the scientific value and merit of research on human genetic differences--including a collection of DNA samples that represents the whole of human genetic diversity--and the ethical...

  16. Fine-Scale Evaluation of Giant Panda Habitats and Countermeasures against the Future Impacts of Climate Change and Human Disturbance (2015–2050: A Case Study in Ya’an, China

    Jing Zhen

    2018-04-01

    Full Text Available The accelerating impact of climate change on giant panda (Ailuropoda melanoleuca habitats have become an international research topic. Recently, many studies have also focused on medium-sized mountain ranges or entire giant panda habitats to predict how habitats will change as the climate warms, but few say in detail what to do or where to focus efforts. To fill this gap, this paper presents a new method to take comprehensive, fine-scale evaluations incorporating climate change, human disturbance, and current conservation networks and translate them into practical countermeasures in order to help decision-makers set priority regions for conservation. This study looked at the core area of the Sichuan Giant Panda Sanctuaries United Nations Educational, Scientific and Cultural Organisation (UNESCO World Natural Heritage site, namely Ya’an Prefecture, as a case study. The research employs the Maximum Entropy (MaxEnt modeling algorithm to analyze how climate change will affect the habitats by 2050 under two scenarios: only considering the influence of climate change, and thinking about the coupled influence of climate change and human disturbance together. The results showed the following: (1 only considering climate change, the overall habitat that can be used by giant pandas in this region will increase, which differs from most of the previous results showing a decrease; (2 the new suitable habitat will shift westward, northward and eastward in this region; (3 conversely, the suitable habitat will be significantly reduced (about 58.56% and fragmentized when taking into account human disturbance factors; (4 at present, the three small nature reserves are far from each other and cannot cover the present habitat well nor protect the potentially suitable habitats. Based on the comprehensive analysis of habitat shifts and our two field investigations, we suggest two regions that can be expanded into the conservation network to contain more potentially

  17. Sexual recombination in Colletotrichum lindemuthianum occurs on a fine scale.

    Souza, E A; Camargo, O A; Pinto, J M A

    2010-09-08

    Glomerella cingulata f. sp phaseoli is the sexual phase of the fungus Colletotrichum lindemuthianum, the causal agent of common bean anthracnose. This fungus is of great concern, because it causes large economic losses in common bean crops. RAPD markers of five populations of G. cingulata f. sp phaseoli from two Brazilian states were analyzed to determine if this population possesses the sexual reproductive potential to generate the genetic variation that is observed in this phytopathogen. We identified 128 polymorphic bands, amplified by 28 random primers. The estimates of genetic similarity in this analysis ranged from 0.43 to 1.00, and the dendrogram generated from analysis of all genotypes displayed five principal groups, coinciding with the five populations. Genetic differentiation was observed between the populations (GST=0.6455); 69% of the overall observed genetic variation was between individual populations and 31% of the variance was within the sub-populations. We identified significant levels of linkage disequilibrium in all populations. However, the values of the disequilibrium ranged from low to moderate, indicating that this pathogen maintains a genetic structure consistent with sexual reproduction. The mean contribution of sexual reproduction was determined by comparison of the amplitudes of genetic similarity of isolates from sexual and asexual phases. These results support the hypothesis that recombination plays an important role in determining the amplitude of variability in this pathogen population and that this determination occurs on a fine scale.

  18. Fine-scale population structure and the era of next-generation sequencing.

    Henn, Brenna M; Gravel, Simon; Moreno-Estrada, Andres; Acevedo-Acevedo, Suehelay; Bustamante, Carlos D

    2010-10-15

    Fine-scale population structure characterizes most continents and is especially pronounced in non-cosmopolitan populations. Roughly half of the world's population remains non-cosmopolitan and even populations within cities often assort along ethnic and linguistic categories. Barriers to random mating can be ecologically extreme, such as the Sahara Desert, or cultural, such as the Indian caste system. In either case, subpopulations accumulate genetic differences if the barrier is maintained over multiple generations. Genome-wide polymorphism data, initially with only a few hundred autosomal microsatellites, have clearly established differences in allele frequency not only among continental regions, but also within continents and within countries. We review recent evidence from the analysis of genome-wide polymorphism data for genetic boundaries delineating human population structure and the main demographic and genomic processes shaping variation, and discuss the implications of population structure for the distribution and discovery of disease-causing genetic variants, in the light of the imminent availability of sequencing data for a multitude of diverse human genomes.

  19. Evaluating human genetic diversity

    ... into human evolution and origins and serving as a springboard for important medical research. It also addresses issues of confidentiality and individual privacy for participants in genetic diversity research studies.

  20. Genetics of human hydrocephalus

    Williams, Michael A.; Rigamonti, Daniele

    2006-01-01

    Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human

  1. Fine-scale genetic characterization of Plasmodium falciparum

    We have initiated such a study and presented herewith the results from the in silico understanding of a seventh chromosomal region of the malarial parasite Plasmodium falciparum encompassing the antigenic var genes (coding pfemp1) and the drug-resistant gene pfcrt located at a specified region of the chromosome 7.

  2. Advances in human genetics

    Harris, H.; Hirschhorn, K. (eds.)

    1993-01-01

    This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.

  3. Predictive Modelling to Identify Near-Shore, Fine-Scale Seabird Distributions during the Breeding Season.

    Warwick-Evans, Victoria C; Atkinson, Philip W; Robinson, Leonie A; Green, Jonathan A

    2016-01-01

    During the breeding season seabirds are constrained to coastal areas and are restricted in their movements, spending much of their time in near-shore waters either loafing or foraging. However, in using these areas they may be threatened by anthropogenic activities such as fishing, watersports and coastal developments including marine renewable energy installations. Although many studies describe large scale interactions between seabirds and the environment, the drivers behind near-shore, fine-scale distributions are not well understood. For example, Alderney is an important breeding ground for many species of seabird and has a diversity of human uses of the marine environment, thus providing an ideal location to investigate the near-shore fine-scale interactions between seabirds and the environment. We used vantage point observations of seabird distribution, collected during the 2013 breeding season in order to identify and quantify some of the environmental variables affecting the near-shore, fine-scale distribution of seabirds in Alderney's coastal waters. We validate the models with observation data collected in 2014 and show that water depth, distance to the intertidal zone, and distance to the nearest seabird nest are key predictors in the distribution of Alderney's seabirds. AUC values for each species suggest that these models perform well, although the model for shags performed better than those for auks and gulls. While further unexplained underlying localised variation in the environmental conditions will undoubtedly effect the fine-scale distribution of seabirds in near-shore waters we demonstrate the potential of this approach in marine planning and decision making.

  4. Predictive Modelling to Identify Near-Shore, Fine-Scale Seabird Distributions during the Breeding Season.

    Victoria C Warwick-Evans

    Full Text Available During the breeding season seabirds are constrained to coastal areas and are restricted in their movements, spending much of their time in near-shore waters either loafing or foraging. However, in using these areas they may be threatened by anthropogenic activities such as fishing, watersports and coastal developments including marine renewable energy installations. Although many studies describe large scale interactions between seabirds and the environment, the drivers behind near-shore, fine-scale distributions are not well understood. For example, Alderney is an important breeding ground for many species of seabird and has a diversity of human uses of the marine environment, thus providing an ideal location to investigate the near-shore fine-scale interactions between seabirds and the environment. We used vantage point observations of seabird distribution, collected during the 2013 breeding season in order to identify and quantify some of the environmental variables affecting the near-shore, fine-scale distribution of seabirds in Alderney's coastal waters. We validate the models with observation data collected in 2014 and show that water depth, distance to the intertidal zone, and distance to the nearest seabird nest are key predictors in the distribution of Alderney's seabirds. AUC values for each species suggest that these models perform well, although the model for shags performed better than those for auks and gulls. While further unexplained underlying localised variation in the environmental conditions will undoubtedly effect the fine-scale distribution of seabirds in near-shore waters we demonstrate the potential of this approach in marine planning and decision making.

  5. Protocols in human molecular genetics

    Mathew, Christopher G

    1991-01-01

    ... sequences has led to the development of DNA fingerprinting. The application of these techniques to the study of the human genome has culminated in major advances such as the cloning of the cystic fibrosis gene, the construction of genetic linkage maps of each human chromosome, the mapping of many genes responsible for human inherited disorders, genet...

  6. The influence of recombination on human genetic diversity.

    Chris C A Spencer

    2006-09-01

    Full Text Available In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution.

  7. A quantitative analysis of fine scale distribution of intertidal meiofauna in response to food resources

    Ansari, Z.A.; Gauns, M.

    Fine scale vertical and spatial distribution of meiofauna in relation to food abundance was studied in the intertidal sediment at Dias Beach. The major abiotic factors showed significant changes and progressive fine scale decrease in vertical...

  8. Basic Genetics: A Human Approach.

    Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.

    This document (which has the form of a magazine) provides a variety of articles, stories, editorials, letters, interviews, and other types of magazine features (such as book reviews) which focus on human genetics. In addition to providing information about the principles of genetics, nearly all of the sections in the "magazine" address moral,…

  9. Parallel integer sorting with medium and fine-scale parallelism

    Dagum, Leonardo

    1993-01-01

    Two new parallel integer sorting algorithms, queue-sort and barrel-sort, are presented and analyzed in detail. These algorithms do not have optimal parallel complexity, yet they show very good performance in practice. Queue-sort designed for fine-scale parallel architectures which allow the queueing of multiple messages to the same destination. Barrel-sort is designed for medium-scale parallel architectures with a high message passing overhead. The performance results from the implementation of queue-sort on a Connection Machine CM-2 and barrel-sort on a 128 processor iPSC/860 are given. The two implementations are found to be comparable in performance but not as good as a fully vectorized bucket sort on the Cray YMP.

  10. Electromagnetic characterization of fine-scale particulate composite materials

    Talbot, P.; Konn, A.M.; Brosseau, C.

    2002-01-01

    We report the results of the composition and frequency-dependent complex permittivity and permeability of ZnO and γ-Fe 2 O 3 composites prepared by powder pressing. The electromagnetic properties of these materials exhibit a strong dependence on the powder size of the starting materials. In the microwave frequency range, the permittivity and permeability show nonlinear variations with volume fraction of Fe 2 O 3 . As the particle size decreases from a few micrometers to a few tens of nanometers, the data indicate that local mesostructural factors such as shape anisotropy, porosity and possible effect of the binder are likely to be intertwined in the understanding of electromagnetic properties of fine-scale particulate composite materials

  11. Human genetics and sleep behavior.

    Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

    2017-06-01

    Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Determination of the piezoelectric properties of fine scale PZT fibres

    Nelson, L.J.; Bowen, C.R. [Bath Univ. (United Kingdom). Dept. of Engineering and Applied Science

    2002-07-01

    Finite element (FE) modelling is used to determine the effect of fibre volume fraction, aspect ratio and polymer matrix stiffness on the d{sub 33} coefficients of 1-3 connectivity piezoelectric fibre composites. The aim is to use these observations as a means of determining the d{sub 33} of fine scale lead zirconate titanate (PZT) fibres. Results from a 1-D analytical model fit well with FE predictions for low aspect ratios. Two commercially available PZT-5A fibres, produced via the viscous suspension spinning process (VSSP) and an extrusion process, were fabricated into 1-3 composites with varying fibre volume fractions. The composite d{sub 33} measurements are compared to the model predictions and used to determine the d{sub 33} coefficients of the fibers. The d{sub 33} of the VSSP fibres and extruded fibres is measured as 365 pCN{sup -1} and 235 pCN{sup -1} respectively using this method. The large difference in the piezoelectric coefficients is possibly linked to the grain size and porosity, which is examined using scanning electron microscopy. (orig.)

  13. Variation in human recombination rates and its genetic determinants.

    Adi Fledel-Alon

    Full Text Available Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution.Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation.These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes.

  14. Nest suitability, fine-scale population structure and male-mediated dispersal of a solitary ground nesting bee in an urban landscape.

    López-Uribe, Margarita M; Morreale, Stephen J; Santiago, Christine K; Danforth, Bryan N

    2015-01-01

    Bees are the primary pollinators of flowering plants in almost all ecosystems. Worldwide declines in bee populations have raised awareness about the importance of their ecological role in maintaining ecosystem functioning. The naturally strong philopatric behavior that some bee species show can be detrimental to population viability through increased probability of inbreeding. Furthermore, bee populations found in human-altered landscapes, such as urban areas, can experience lower levels of gene flow and effective population sizes, increasing potential for inbreeding depression in wild bee populations. In this study, we investigated the fine-scale population structure of the solitary bee Colletes inaequalis in an urbanized landscape. First, we developed a predictive spatial model to detect suitable nesting habitat for this ground nesting bee and to inform our field search for nests. We genotyped 18 microsatellites in 548 female individuals collected from nest aggregations throughout the study area. Genetic relatedness estimates revealed that genetic similarity among individuals was slightly greater within nest aggregations than among randomly chosen individuals. However, genetic structure among nest aggregations was low (Nei's GST = 0.011). Reconstruction of parental genotypes revealed greater genetic relatedness among females than among males within nest aggregations, suggesting male-mediated dispersal as a potentially important mechanism of population connectivity and inbreeding avoidance. Size of nesting patch was positively correlated with effective population size, but not with other estimators of genetic diversity. We detected a positive trend between geographic distance and genetic differentiation between nest aggregations. Our landscape genetic models suggest that increased urbanization is likely associated with higher levels of inbreeding. Overall, these findings emphasize the importance of density and distribution of suitable nesting patches for enhancing

  15. Nest suitability, fine-scale population structure and male-mediated dispersal of a solitary ground nesting bee in an urban landscape.

    Margarita M López-Uribe

    Full Text Available Bees are the primary pollinators of flowering plants in almost all ecosystems. Worldwide declines in bee populations have raised awareness about the importance of their ecological role in maintaining ecosystem functioning. The naturally strong philopatric behavior that some bee species show can be detrimental to population viability through increased probability of inbreeding. Furthermore, bee populations found in human-altered landscapes, such as urban areas, can experience lower levels of gene flow and effective population sizes, increasing potential for inbreeding depression in wild bee populations. In this study, we investigated the fine-scale population structure of the solitary bee Colletes inaequalis in an urbanized landscape. First, we developed a predictive spatial model to detect suitable nesting habitat for this ground nesting bee and to inform our field search for nests. We genotyped 18 microsatellites in 548 female individuals collected from nest aggregations throughout the study area. Genetic relatedness estimates revealed that genetic similarity among individuals was slightly greater within nest aggregations than among randomly chosen individuals. However, genetic structure among nest aggregations was low (Nei's GST = 0.011. Reconstruction of parental genotypes revealed greater genetic relatedness among females than among males within nest aggregations, suggesting male-mediated dispersal as a potentially important mechanism of population connectivity and inbreeding avoidance. Size of nesting patch was positively correlated with effective population size, but not with other estimators of genetic diversity. We detected a positive trend between geographic distance and genetic differentiation between nest aggregations. Our landscape genetic models suggest that increased urbanization is likely associated with higher levels of inbreeding. Overall, these findings emphasize the importance of density and distribution of suitable nesting

  16. Image-Based Fine-Scale Infrastructure Monitoring

    Detchev, Ivan Denislavov

    Monitoring the physical health of civil infrastructure systems is an important task that must be performed frequently in order to ensure their serviceability and sustainability. Additionally, laboratory experiments where individual system components are tested on the fine-scale level provide essential information during the structural design process. This type of inspection, i.e., measurements of deflections and/or cracks, has traditionally been performed with instrumentation that requires access to, or contact with, the structural element being tested; performs deformation measurements in only one dimension or direction; and/or provides no permanent visual record. To avoid the downsides of such instrumentation, this dissertation proposes a remote sensing approach based on a photogrammetric system capable of three-dimensional reconstruction. The proposed system is low-cost, consists of off-the-shelf components, and is capable of reconstructing objects or surfaces with homogeneous texture. The scientific contributions of this research work address the drawbacks in currently existing literature. Methods for in-situ multi-camera system calibration and system stability analysis are proposed in addition to methods for deflection/displacement monitoring, and crack detection and characterization in three dimensions. The mathematical model for the system calibration is based on a single or multiple reference camera(s) and built-in relative orientation constraints where the interior orientation and the mounting parameters for all cameras are explicitly estimated. The methods for system stability analysis can be used to comprehensively check for the cumulative impact of any changes in the system parameters. They also provide a quantitative measure of this impact on the reconstruction process in terms of image space units. Deflection/displacement monitoring of dynamic surfaces in three dimensions is achieved with the system by performing an innovative sinusoidal fitting

  17. Archives: Egyptian Journal of Medical Human Genetics

    Items 1 - 34 of 34 ... Archives: Egyptian Journal of Medical Human Genetics. Journal Home > Archives: Egyptian Journal of Medical Human Genetics. Log in or Register to get access to full text downloads.

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

    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 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.

  19. A genome-wide, fine-scale map of natural pigmentation variation in Drosophila melanogaster.

    Héloïse Bastide

    2013-06-01

    Full Text Available Various approaches can be applied to uncover the genetic basis of natural phenotypic variation, each with their specific strengths and limitations. Here, we use a replicated genome-wide association approach (Pool-GWAS to fine-scale map genomic regions contributing to natural variation in female abdominal pigmentation in Drosophila melanogaster, a trait that is highly variable in natural populations and highly heritable in the laboratory. We examined abdominal pigmentation phenotypes in approximately 8000 female European D. melanogaster, isolating 1000 individuals with extreme phenotypes. We then used whole-genome Illumina sequencing to identify single nucleotide polymorphisms (SNPs segregating in our sample, and tested these for associations with pigmentation by contrasting allele frequencies between replicate pools of light and dark individuals. We identify two small regions near the pigmentation genes tan and bric-à-brac 1, both corresponding to known cis-regulatory regions, which contain SNPs showing significant associations with pigmentation variation. While the Pool-GWAS approach suffers some limitations, its cost advantage facilitates replication and it can be applied to any non-model system with an available reference genome.

  20. A genome-wide, fine-scale map of natural pigmentation variation in Drosophila melanogaster.

    Bastide, Héloïse; Betancourt, Andrea; Nolte, Viola; Tobler, Raymond; Stöbe, Petra; Futschik, Andreas; Schlötterer, Christian

    2013-06-01

    Various approaches can be applied to uncover the genetic basis of natural phenotypic variation, each with their specific strengths and limitations. Here, we use a replicated genome-wide association approach (Pool-GWAS) to fine-scale map genomic regions contributing to natural variation in female abdominal pigmentation in Drosophila melanogaster, a trait that is highly variable in natural populations and highly heritable in the laboratory. We examined abdominal pigmentation phenotypes in approximately 8000 female European D. melanogaster, isolating 1000 individuals with extreme phenotypes. We then used whole-genome Illumina sequencing to identify single nucleotide polymorphisms (SNPs) segregating in our sample, and tested these for associations with pigmentation by contrasting allele frequencies between replicate pools of light and dark individuals. We identify two small regions near the pigmentation genes tan and bric-à-brac 1, both corresponding to known cis-regulatory regions, which contain SNPs showing significant associations with pigmentation variation. While the Pool-GWAS approach suffers some limitations, its cost advantage facilitates replication and it can be applied to any non-model system with an available reference genome.

  1. [Quality assurance in human genetic testing].

    Stuhrmann-Spangenberg, Manfred

    2015-02-01

    Advances in technical developments of genetic diagnostics for more than 50 years, as well as the fact that human genetic testing is usually performed only once in a lifetime, with additional impact for blood relatives, are determining the extraordinary importance of quality assurance in human genetic testing. Abidance of laws, directives, and guidelines plays a major role. This article aims to present the major laws, directives, and guidelines with respect to quality assurance of human genetic testing, paying careful attention to internal and external quality assurance. The information on quality assurance of human genetic testing was obtained through a web-based search of the web pages that are referred to in this article. Further information was retrieved from publications in the German Society of Human Genetics and through a PubMed-search using term quality + assurance + genetic + diagnostics. The most important laws, directives, and guidelines for quality assurance of human genetic testing are the gene diagnostics law (GenDG), the directive of the Federal Medical Council for quality control of clinical laboratory analysis (RiliBÄK), and the S2K guideline for human genetic diagnostics and counselling. In addition, voluntary accreditation under DIN EN ISO 15189:2013 offers a most recommended contribution towards quality assurance of human genetic testing. Legal restraints on quality assurance of human genetic testing as mentioned in § 5 GenDG are fulfilled once RiliBÄK requirements are followed.

  2. Genetics of Human and Canine Dilated Cardiomyopathy

    Siobhan Simpson

    2015-01-01

    Full Text Available Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

  3. Genetics of Human and Canine Dilated Cardiomyopathy.

    Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F N; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

  4. Personalized medicine and human genetic diversity.

    Lu, Yi-Fan; Goldstein, David B; Angrist, Misha; Cavalleri, Gianpiero

    2014-07-24

    Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Fine-scale topography in sensory systems: insights from Drosophila and vertebrates.

    Kaneko, Takuya; Ye, Bing

    2015-09-01

    To encode the positions of sensory stimuli, sensory circuits form topographic maps in the central nervous system through specific point-to-point connections between pre- and postsynaptic neurons. In vertebrate visual systems, the establishment of topographic maps involves the formation of a coarse topography followed by that of fine-scale topography that distinguishes the axon terminals of neighboring neurons. It is known that intrinsic differences in the form of broad gradients of guidance molecules instruct coarse topography while neuronal activity is required for fine-scale topography. On the other hand, studies in the Drosophila visual system have shown that intrinsic differences in cell adhesion among the axon terminals of neighboring neurons instruct the fine-scale topography. Recent studies on activity-dependent topography in the Drosophila somatosensory system have revealed a role of neuronal activity in creating molecular differences among sensory neurons for establishing fine-scale topography, implicating a conserved principle. Here we review the findings in both Drosophila and vertebrates and propose an integrated model for fine-scale topography.

  6. The utility of satellite observations for constraining fine-scale and transient methane sources

    Turner, A. J.; Jacob, D.; Benmergui, J. S.; Brandman, J.; White, L.; Randles, C. A.

    2017-12-01

    Resolving differences between top-down and bottom-up emissions of methane from the oil and gas industry is difficult due, in part, to their fine-scale and often transient nature. There is considerable interest in using atmospheric observations to detect these sources. Satellite-based instruments are an attractive tool for this purpose and, more generally, for quantifying methane emissions on fine scales. A number of instruments are planned for launch in the coming years from both low earth and geostationary orbit, but the extent to which they can provide fine-scale information on sources has yet to be explored. Here we present an observation system simulation experiment (OSSE) exploring the tradeoffs between pixel resolution, measurement frequency, and instrument precision on the fine-scale information content of a space-borne instrument measuring methane. We use the WRF-STILT Lagrangian transport model to generate more than 200,000 column footprints at 1.3×1.3 km2 spatial resolution and hourly temporal resolution over the Barnett Shale in Texas. We sub-sample these footprints to match the observing characteristics of the planned TROPOMI and GeoCARB instruments as well as different hypothetical observing configurations. The information content of the various observing systems is evaluated using the Fisher information matrix and its singular values. We draw conclusions on the capabilities of the planned satellite instruments and how these capabilities could be improved for fine-scale source detection.

  7. Spatial Downscaling of TRMM Precipitation Using Geostatistics and Fine Scale Environmental Variables

    No-Wook Park

    2013-01-01

    Full Text Available A geostatistical downscaling scheme is presented and can generate fine scale precipitation information from coarse scale Tropical Rainfall Measuring Mission (TRMM data by incorporating auxiliary fine scale environmental variables. Within the geostatistical framework, the TRMM precipitation data are first decomposed into trend and residual components. Quantitative relationships between coarse scale TRMM data and environmental variables are then estimated via regression analysis and used to derive trend components at a fine scale. Next, the residual components, which are the differences between the trend components and the original TRMM data, are then downscaled at a target fine scale via area-to-point kriging. The trend and residual components are finally added to generate fine scale precipitation estimates. Stochastic simulation is also applied to the residual components in order to generate multiple alternative realizations and to compute uncertainty measures. From an experiment using a digital elevation model (DEM and normalized difference vegetation index (NDVI, the geostatistical downscaling scheme generated the downscaling results that reflected detailed characteristics with better predictive performance, when compared with downscaling without the environmental variables. Multiple realizations and uncertainty measures from simulation also provided useful information for interpretations and further environmental modeling.

  8. Fishermen Follow Fine-Scale Physical Ocean Features for Finance

    James R. Watson

    2018-02-01

    Full Text Available The seascapes on which many millions of people make their living and secure food have complex and dynamic spatial features—the figurative hills and valleys—that influence where and how people work at sea. Here, we quantify the physical mosaic of the surface ocean by identifying Lagrangian Coherent Structures for a whole seascape—the U.S. California Current Large Marine Ecosystem—and assess their impact on the spatial distribution of fishing. We observe that there is a mixed response: some fisheries track these physical features, and others avoid them. These spatial behaviors map to economic impacts, in particular we find that tuna fishermen can expect to make three times more revenue per trip if fishing occurs on strong Lagrangian Coherent Structures. However, we find no relationship for salmon and pink shrimp fishing trips. These results highlight a connection between the biophysical state of the oceans, the spatial patterns of human activity, and ultimately the economic welfare of coastal communities.

  9. Fine-scale flight strategies of gulls in urban airflows indicate risk and reward in city living.

    Shepard, Emily L C; Williamson, Cara; Windsor, Shane P

    2016-09-26

    Birds modulate their flight paths in relation to regional and global airflows in order to reduce their travel costs. Birds should also respond to fine-scale airflows, although the incidence and value of this remains largely unknown. We resolved the three-dimensional trajectories of gulls flying along a built-up coastline, and used computational fluid dynamic models to examine how gulls reacted to airflows around buildings. Birds systematically altered their flight trajectories with wind conditions to exploit updraughts over features as small as a row of low-rise buildings. This provides the first evidence that human activities can change patterns of space-use in flying birds by altering the profitability of the airscape. At finer scales still, gulls varied their position to select a narrow range of updraught values, rather than exploiting the strongest updraughts available, and their precise positions were consistent with a strategy to increase their velocity control in gusty conditions. Ultimately, strategies such as these could help unmanned aerial vehicles negotiate complex airflows. Overall, airflows around fine-scale features have profound implications for flight control and energy use, and consideration of this could lead to a paradigm-shift in the way ecologists view the urban environment.This article is part of the themed issue 'Moving in a moving medium: new perspectives on flight'. © 2016 The Author(s).

  10. Phylogeography of var gene repertoires reveals fine-scale geospatial clustering of Plasmodium falciparum populations in a highly endemic area.

    Tessema, Sofonias K; Monk, Stephanie L; Schultz, Mark B; Tavul, Livingstone; Reeder, John C; Siba, Peter M; Mueller, Ivo; Barry, Alyssa E

    2015-01-01

    Plasmodium falciparum malaria is a major global health problem that is being targeted for progressive elimination. Knowledge of local disease transmission patterns in endemic countries is critical to these elimination efforts. To investigate fine-scale patterns of malaria transmission, we have compared repertoires of rapidly evolving var genes in a highly endemic area. A total of 3680 high-quality DBLα-sequences were obtained from 68 P. falciparum isolates from ten villages spread over two distinct catchment areas on the north coast of Papua New Guinea (PNG). Modelling of the extent of var gene diversity in the two parasite populations predicts more than twice as many var gene alleles circulating within each catchment (Mugil = 906; Wosera = 1094) than previously recognized in PNG (Amele = 369). In addition, there were limited levels of var gene sharing between populations, consistent with local parasite population structure. Phylogeographic analyses demonstrate that while neutrally evolving microsatellite markers identified population structure only at the catchment level, var gene repertoires reveal further fine-scale geospatial clustering of parasite isolates. The clustering of parasite isolates by village in Mugil, but not in Wosera was consistent with the physical and cultural isolation of the human populations in the two catchments. The study highlights the microheterogeneity of P. falciparum transmission in highly endemic areas and demonstrates the potential of var genes as markers of local patterns of parasite population structure. © 2014 John Wiley & Sons Ltd.

  11. Fine-Scale Population Estimation by 3D Reconstruction of Urban Residential Buildings

    Wang, Shixin; Tian, Ye; Zhou, Yi; Liu, Wenliang; Lin, Chenxi

    2016-01-01

    Fine-scale population estimation is essential in emergency response and epidemiological applications as well as urban planning and management. However, representing populations in heterogeneous urban regions with a finer resolution is a challenge. This study aims to obtain fine-scale population distribution based on 3D reconstruction of urban residential buildings with morphological operations using optical high-resolution (HR) images from the Chinese No. 3 Resources Satellite (ZY-3). Specifically, the research area was first divided into three categories when dasymetric mapping was taken into consideration. The results demonstrate that the morphological building index (MBI) yielded better results than built-up presence index (PanTex) in building detection, and the morphological shadow index (MSI) outperformed color invariant indices (CIIT) in shadow extraction and height retrieval. Building extraction and height retrieval were then combined to reconstruct 3D models and to estimate population. Final results show that this approach is effective in fine-scale population estimation, with a mean relative error of 16.46% and an overall Relative Total Absolute Error (RATE) of 0.158. This study gives significant insights into fine-scale population estimation in complicated urban landscapes, when detailed 3D information of buildings is unavailable. PMID:27775670

  12. Fine-Scale Population Estimation by 3D Reconstruction of Urban Residential Buildings

    Shixin Wang

    2016-10-01

    Full Text Available Fine-scale population estimation is essential in emergency response and epidemiological applications as well as urban planning and management. However, representing populations in heterogeneous urban regions with a finer resolution is a challenge. This study aims to obtain fine-scale population distribution based on 3D reconstruction of urban residential buildings with morphological operations using optical high-resolution (HR images from the Chinese No. 3 Resources Satellite (ZY-3. Specifically, the research area was first divided into three categories when dasymetric mapping was taken into consideration. The results demonstrate that the morphological building index (MBI yielded better results than built-up presence index (PanTex in building detection, and the morphological shadow index (MSI outperformed color invariant indices (CIIT in shadow extraction and height retrieval. Building extraction and height retrieval were then combined to reconstruct 3D models and to estimate population. Final results show that this approach is effective in fine-scale population estimation, with a mean relative error of 16.46% and an overall Relative Total Absolute Error (RATE of 0.158. This study gives significant insights into fine-scale population estimation in complicated urban landscapes, when detailed 3D information of buildings is unavailable.

  13. Measuring Fine-Scale White-Tailed Deer Movements and Environmental Influences Using GPS Collars

    Webb, S.L.; Strickland, B.K.; Demarais, S.; Webb, S.L.; Gee, K.L.; DeYoung, R.W.

    2010-01-01

    Few studies have documented fine-scale movements of ungulate species, including white-tailed deer (Odocoileus virginianus), despite the advent of global positioning system (GPS) technology incorporated into tracking devices. We collected fine-scale temporal location estimates (i.e., 15 min/relocation attempt) from 17 female and 15 male white-tailed deer over 7 years and 3 seasons in Oklahoma, USA. Our objectives were to document fine-scale movements of females and males and determine effects of reproductive phase, moon phase, and short-term weather patterns on movements. Female and male movements were primarily crepuscular. Male total daily movements were 20% greater during rut (7,363? 364) than postrut (6,156 m±260). Female daily movements were greatest during post parturition (3,357 91), followed by parturition (2,902 m±107), and pre parturition (2,682 m±121). We found moon phase had no effect on daily, nocturnal, and diurnal deer movements and fine-scale temporal weather conditions had an inconsistent influence on deer movement patterns within season. Our data suggest that hourly and daily variation in weather events have minimal impact on movements of white-tailed deer in southern latitudes. Instead, routine crepuscular movements, presumed to maximize thermoregulation and minimize predation risk, appear to be the most important factors influencing movements.

  14. Measuring Fine-Scale White-Tailed Deer Movements and Environmental Influences Using GPS Collars

    Stephen L. Webb

    2010-01-01

    Full Text Available Few studies have documented fine-scale movements of ungulate species, including white-tailed deer (Odocoileus virginianus, despite the advent of global positioning system (GPS technology incorporated into tracking devices. We collected fine-scale temporal location estimates (i.e., 15 min/relocation attempt from 17 female and 15 male white-tailed deer over 7 years and 3 seasons in Oklahoma, USA. Our objectives were to document fine-scale movements of females and males and determine effects of reproductive phase, moon phase, and short-term weather patterns on movements. Female and male movements were primarily crepuscular. Male total daily movements were 20% greater during rut (7,363m±364 than postrut (6,156m±260. Female daily movements were greatest during postparturition (3,357m±91, followed by parturition (2,902m±107, and preparturition (2,682m±121. We found moon phase had no effect on daily, nocturnal, and diurnal deer movements and fine-scale temporal weather conditions had an inconsistent influence on deer movement patterns within season. Our data suggest that hourly and daily variation in weather events have minimal impact on movements of white-tailed deer in southern latitudes. Instead, routine crepuscular movements, presumed to maximize thermoregulation and minimize predation risk, appear to be the most important factors influencing movements.

  15. GeneRecon—A coalescent based tool for fine-scale association mapping

    Mailund, Thomas; Schierup, Mikkel Heide; Pedersen, Christian Nørgaard Storm

    2006-01-01

    GeneRecon is a tool for fine-scale association mapping using a coalescence model. GeneRecon takes as input case-control data from phased or unphased SNP and micro-satellite genotypes. The posterior distribution of disease locus position is obtained by Metropolis Hastings sampling in the state space...

  16. 75 FR 60407 - Gulf of the Farallones National Marine Sanctuary Permit Application Project Titled: Fine Scale...

    2010-09-30

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Gulf of the Farallones National Marine Sanctuary Permit Application Project Titled: Fine Scale, Long-Term Tracking of Adult White Sharks AGENCY: Office of National Marine Sanctuaries (ONMS), National Ocean Service (NOS), National...

  17. Coherent fine scale eddies in turbulence transition of spatially-developing mixing layer

    Wang, Y.; Tanahashi, M.; Miyauchi, T.

    2007-01-01

    To investigate the relationship between characteristics of the coherent fine scale eddy and a laminar-turbulent transition, a direct numerical simulation (DNS) of a spatially-developing turbulent mixing layer with Re ω,0 = 700 was conducted. On the onset of the transition, strong coherent fine scale eddies appears in the mixing layer. The most expected value of maximum azimuthal velocity of the eddy is 2.0 times Kolmogorov velocity (u k ), and decreases to 1.2u k , which is an asymptotic value in the fully-developed state, through the transition. The energy dissipation rate around the eddy is twice as high compared with that in the fully-developed state. However, the most expected diameter and eigenvalues ratio of strain rate acting on the coherent fine scale eddy are maintained to be 8 times Kolmogorov length (η) and α:β:γ = -5:1:4 in the transition process. In addition to Kelvin-Helmholtz rollers, rib structures do not disappear in the transition process and are composed of lots of coherent fine scale eddies in the fully-developed state instead of a single eddy observed in early stage of the transition or in laminar flow

  18. Fine scale heterogeneity in the Earth's upper mantle - observation and interpretation

    Thybo, Hans

    2014-01-01

    can be correlated to main plate tectonic features, such as oceanic spreading centres, continental rift zones and subducting slabs. Much seismological mantle research is now concentrated on imaging fine scale heterogeneity, which may be detected and imaged with high-resolution seismic data with dense...

  19. Spatial variability of night temperatures at a fine scale over the Stellenbosch wine district, South Africa

    Valérie Bonnardot

    2012-03-01

    Significance and impact of the study: In the context of climate change, it is crucial to improve knowledge of current climatic conditions at fine scale during periods of grapevine growth and berry ripening in order to have a baseline from which to work when discussing and considering future local adaptations to accommodate to a warmer environnement.

  20. Fine-scale spatial distribution of plants and resources on a sandy soil in the Sahel

    Rietkerk, M.G.; Ouedraogo, T.; Kumar, L.; Sanou, S.; Langevelde, F. van; Kiema, A.; Koppel, J. van de; Andel, J. van; Hearne, J.; Skidmore, A.K.; Ridder, N. de; Stroosnijder, L.; Prins, H.H.T.

    2002-01-01

    We studied fine-scale spatial plant distribution in relation to the spatial distribution of erodible soil particles, organic matter, nutrients and soil water on a sandy to sandy loam soil in the Sahel. We hypothesized that the distribution of annual plants would be highly spatially autocorrelated

  1. GeneRecon Users' Manual — A coalescent based tool for fine-scale association mapping

    Mailund, T

    2006-01-01

    GeneRecon is a software package for linkage disequilibrium mapping using coalescent theory. It is based on Bayesian Markov-chain Monte Carlo (MCMC) method for fine-scale linkage-disequilibrium gene mapping using high-density marker maps. GeneRecon explicitly models the genealogy of a sample of th...

  2. Comparing three spaceborne optical sensors via fine scale pixel-based urban land cover classification products

    Breytenbach, Andre

    2013-08-01

    Full Text Available Accessibility to higher resolution earth observation satellites suggests an improvement in the potential for fine scale image classification. In this comparative study, imagery from three optical satellites (WorldView-2, Pléiades and RapidEye) were...

  3. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus

    Meyer, Kerstin B; O'Reilly, Martin; Michailidou, Kyriaki

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of...

  4. Genetics of Human and Canine Dilated Cardiomyopathy

    Siobhan Simpson; Jennifer Edwards; Thomas F. N. Ferguson-Mignan; Malcolm Cobb; Nigel P. Mongan; Catrin S. Rutland

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In th...

  5. Human genetics of diabetic vascular complications

    Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play ...

  6. Animal models for human genetic diseases

    Sharif Sons

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

  7. 130 FEMINISM AND HUMAN GENETIC ENGINEERING: A ...

    Ike Odimegwu

    genetic engineering to reconstruct the life of the human person. Negatively .... height, beauty or intelligence. Apart from ... cloning and stem-cell researches, artificial insemination. ..... form of manufacturing children involving their quality control.

  8. Human genetic factors in tuberculosis: an update.

    van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

    2017-09-01

    Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

  9. Behavior genetic modeling of human fertility

    Rodgers, J L; Kohler, H P; Kyvik, K O

    2001-01-01

    Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (First......Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males....... A bivariate analysis indicated significant shared genetic variance between NumCh and FirstTry....

  10. Property and Human Genetic Information

    Nielsen, Morten Ebbe Juul; Kongsholm, Nana Cecilie Halmsted; Schovsbo, Jens Hemmingsen

    2018-01-01

    Do donors (of samples from which genetic information is derived) have some sort of pre-legal (moral) or legal property right tothat information? In this paper, we address this question from both a moral philosophical and a legal point of view. We argue thatphilosophical theories about property do...

  11. Microsatellite variation suggests a recent fine-scale population structure of Drosophila sechellia, a species endemic of the Seychelles archipelago.

    Legrand, Delphine; Vautrin, Dominique; Lachaise, Daniel; Cariou, Marie-Louise

    2011-07-01

    Drosophila sechellia is closely related to the cosmopolitan and widespread model species, D. simulans. This species, endemic to the Seychelles archipelago, is specialized on the fruits of Morinda citrifolia, and harbours the lowest overall genetic diversity compared to other species of Drosophila. This low diversity is associated with a small population size. In addition, no obvious population structure has been evidenced so far across islands of the Seychelles archipelago. Here, a microsatellite panel of 17 loci in ten populations from nine islands of the Seychelles was used to assess the effect of the D. sechellia's fragmented distribution on the fine-scale population genetic structure, the migration pattern, as well as on the demography of the species. Contrary to previous results, also based on microsatellites, no evidence for population contraction in D. sechellia was found. The results confirm previous studies based on gene sequence polymorphism that showed a long-term stable population size for this species. Interestingly, a pattern of Isolation By Distance which had not been described yet in D. sechellia was found, with evidence of first-generation migrants between some neighbouring islands. Bayesian structuring algorithm results were consistent with a split of D. sechellia into two main groups of populations: Silhouette/Mahé versus all the other islands. Thus, microsatellites suggest that variability in D. sechellia is most likely explained by local genetic exchanges between neighbouring islands that have recently resulted in slight differentiation of the two largest island populations from all the others.

  12. An overview of human genetic privacy.

    Shi, Xinghua; Wu, Xintao

    2017-01-01

    The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. © 2016 New York Academy of Sciences.

  13. An overview of human genetic privacy

    Shi, Xinghua; Wu, Xintao

    2016-01-01

    The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. PMID:27626905

  14. Data, data everywhere: detecting spatial patterns in fine-scale ecological information collected across a continent

    Kevin M. Potter; Frank H. Koch; Christopher M. Oswalt; Basil V. Iannone

    2016-01-01

    Context Fine-scale ecological data collected across broad regions are becoming increasingly available. Appropriate geographic analyses of these data can help identify locations of ecological concern. Objectives We present one such approach, spatial association of scalable hexagons (SASH), whichidentifies locations where ecological phenomena occur at greater...

  15. FINE-SCALE STRUCTURES OF FLUX ROPES TRACKED BY ERUPTING MATERIAL

    Li Ting; Zhang Jun, E-mail: liting@nao.cas.cn, E-mail: zjun@nao.cas.cn [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

    2013-06-20

    We present Solar Dynamics Observatory observations of two flux ropes tracked out by material from a surge and a failed filament eruption on 2012 July 29 and August 4, respectively. For the first event, the interaction between the erupting surge and a loop-shaped filament in the east seems to 'peel off' the filament and add bright mass into the flux rope body. The second event is associated with a C-class flare that occurs several minutes before the filament activation. The two flux ropes are, respectively, composed of 85 {+-} 12 and 102 {+-} 15 fine-scale structures, with an average width of about 1.''6. Our observations show that two extreme ends of the flux rope are rooted in opposite polarity fields and each end is composed of multiple footpoints (FPs) of fine-scale structures. The FPs of the fine-scale structures are located at network magnetic fields, with magnetic fluxes from 5.6 Multiplication-Sign 10{sup 18} Mx to 8.6 Multiplication-Sign 10{sup 19} Mx. Moreover, almost half of the FPs show converging motion of smaller magnetic structures over 10 hr before the appearance of the flux rope. By calculating the magnetic fields of the FPs, we deduce that the two flux ropes occupy at least 4.3 Multiplication-Sign 10{sup 20} Mx and 7.6 Multiplication-Sign 10{sup 20} Mx magnetic fluxes, respectively.

  16. Property and Human Genetic Information

    Nielsen, Morten Ebbe Juul; Kongsholm, Nana Cecilie Halmsted; Schovsbo, Jens Hemmingsen

    2018-01-01

    Do donors (of samples from which genetic information is derived) have some sort of pre-legal (moral) or legal property right to that information? In this paper, we address this question from both a moral philosophical and a legal point of view. We argue that philosophical theories about property do...... innovation in society. A balancing of interest must take place and we have to make sure that patent protection serves general societal interests and not just those of special interest groups be that inventors or donors....

  17. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

    Zeng, Chenjie; Guo, Xingyi; Long, Jirong; Kuchenbaecker, Karoline B.; Droit, Arnaud; Michailidou, Kyriaki; Ghoussaini, Maya; Kar, Siddhartha; Freeman, Adam; Hopper, John L.; Milne, Roger L.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Agata, Simona

    2016-01-01

    Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast C...

  18. Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.

    Hoh, Boon-Peng; Deng, Lian; Julia-Ashazila, Mat Jusoh; Zuraihan, Zakaria; Nur-Hasnah, Ma'amor; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Endom, Ismail; Zilfalil, Bin Alwi; Khalid, Yusoff; Xu, Shuhua

    2015-07-22

    Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

  19. Fine-scale genetic structure and social organization in female white-tailed deer

    Christopher E. Comer; John C. Kilgo; Gino J. D' Angelo; Travis C. Glenn; Karl V. Miller

    2005-01-01

    Social behavior of white-tailed deer (Odocoileus virginianus) can have important management implications. The formation of matrilineal social groups among female deer has been documented and management strategies have been proposed based on this well-developed social structure. Using radiocollared (n = 17) and hunter or vehicle-killed (n = 21) does, we examined spatial...

  20. Environmental and genetic interactions in human cancer

    Paterson, M.C.

    Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)

  1. An overview of human genetic privacy

    Shi, Xinghua; Wu, Xintao

    2016-01-01

    The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that nee...

  2. Human genetics: international projects and personalized medicine.

    Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina

    2016-03-01

    In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015.

  3. Assessment of fine-scale resource selection and spatially explicit habitat suitability modelling for a re-introduced tiger (Panthera tigris population in central India

    Mriganka Shekhar Sarkar

    2017-11-01

    Full Text Available Background Large carnivores influence ecosystem functions at various scales. Thus, their local extinction is not only a species-specific conservation concern, but also reflects on the overall habitat quality and ecosystem value. Species-habitat relationships at fine scale reflect the individuals’ ability to procure resources and negotiate intraspecific competition. Such fine scale habitat choices are more pronounced in large carnivores such as tiger (Panthera tigris, which exhibits competitive exclusion in habitat and mate selection strategies. Although landscape level policies and conservation strategies are increasingly promoted for tiger conservation, specific management interventions require knowledge of the habitat correlates at fine scale. Methods We studied nine radio-collared individuals of a successfully reintroduced tiger population in Panna Tiger Reserve, central India, focussing on the species-habitat relationship at fine scales. With 16 eco-geographical variables, we performed Manly’s selection ratio and K-select analyses to define population-level and individual-level variation in resource selection, respectively. We analysed the data obtained during the exploratory period of six tigers and during the settled period of eight tigers separately, and compared the consequent results. We further used the settled period characteristics to model and map habitat suitability based on the Mahalanobis D2 method and the Boyce index. Results There was a clear difference in habitat selection by tigers between the exploratory and the settled period. During the exploratory period, tigers selected dense canopy and bamboo forests, but also spent time near villages and relocated village sites. However, settled tigers predominantly selected bamboo forests in complex terrain, riverine forests and teak-mixed forest, and totally avoided human settlements and agriculture areas. There were individual variations in habitat selection between exploratory

  4. Assessment of fine-scale resource selection and spatially explicit habitat suitability modelling for a re-introduced tiger (Panthera tigris) population in central India.

    Sarkar, Mriganka Shekhar; Krishnamurthy, Ramesh; Johnson, Jeyaraj A; Sen, Subharanjan; Saha, Goutam Kumar

    2017-01-01

    Large carnivores influence ecosystem functions at various scales. Thus, their local extinction is not only a species-specific conservation concern, but also reflects on the overall habitat quality and ecosystem value. Species-habitat relationships at fine scale reflect the individuals' ability to procure resources and negotiate intraspecific competition. Such fine scale habitat choices are more pronounced in large carnivores such as tiger ( Panthera tigris ), which exhibits competitive exclusion in habitat and mate selection strategies. Although landscape level policies and conservation strategies are increasingly promoted for tiger conservation, specific management interventions require knowledge of the habitat correlates at fine scale. We studied nine radio-collared individuals of a successfully reintroduced tiger population in Panna Tiger Reserve, central India, focussing on the species-habitat relationship at fine scales. With 16 eco-geographical variables, we performed Manly's selection ratio and K-select analyses to define population-level and individual-level variation in resource selection, respectively. We analysed the data obtained during the exploratory period of six tigers and during the settled period of eight tigers separately, and compared the consequent results. We further used the settled period characteristics to model and map habitat suitability based on the Mahalanobis D 2 method and the Boyce index. There was a clear difference in habitat selection by tigers between the exploratory and the settled period. During the exploratory period, tigers selected dense canopy and bamboo forests, but also spent time near villages and relocated village sites. However, settled tigers predominantly selected bamboo forests in complex terrain, riverine forests and teak-mixed forest, and totally avoided human settlements and agriculture areas. There were individual variations in habitat selection between exploratory and settled periods. Based on threshold limits

  5. The genetic component of human longevity

    Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

    2018-01-01

    In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic ...

  6. A global reference for human genetic variation

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David

    2015-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals ...

  7. Antigenic and genetic variability of human metapneumoviruses

    S. Herfst (Sander); L. Sprong; P.A. Cane; E. Forleo-Neto; A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); R.L. de Swart (Rik); B.G. van den Hoogen (Bernadette)

    2004-01-01

    textabstractHuman metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For

  8. Modelling Soil-Landscapes in Coastal California Hills Using Fine Scale Terrestrial Lidar

    Prentice, S.; Bookhagen, B.; Kyriakidis, P. C.; Chadwick, O.

    2013-12-01

    Digital elevation models (DEMs) are the dominant input to spatially explicit digital soil mapping (DSM) efforts due to their increasing availability and the tight coupling between topography and soil variability. Accurate characterization of this coupling is dependent on DEM spatial resolution and soil sampling density, both of which may limit analyses. For example, DEM resolution may be too coarse to accurately reflect scale-dependent soil properties yet downscaling introduces artifactual uncertainty unrelated to deterministic or stochastic soil processes. We tackle these limitations through a DSM effort that couples moderately high density soil sampling with a very fine scale terrestrial lidar dataset (20 cm) implemented in a semiarid rolling hillslope domain where terrain variables change rapidly but smoothly over short distances. Our guiding hypothesis is that in this diffusion-dominated landscape, soil thickness is readily predicted by continuous terrain attributes coupled with catenary hillslope segmentation. We choose soil thickness as our keystone dependent variable for its geomorphic and hydrologic significance, and its tendency to be a primary input to synthetic ecosystem models. In defining catenary hillslope position we adapt a logical rule-set approach that parses common terrain derivatives of curvature and specific catchment area into discrete landform elements (LE). Variograms and curvature-area plots are used to distill domain-scale terrain thresholds from short range order noise characteristic of very fine-scale spatial data. The revealed spatial thresholds are used to condition LE rule-set inputs, rendering a catenary LE map that leverages the robustness of fine-scale terrain data to create a generalized interpretation of soil geomorphic domains. Preliminary regressions show that continuous terrain variables alone (curvature, specific catchment area) only partially explain soil thickness, and only in a subset of soils. For example, at spatial

  9. Development of a remote sensing network for time-sensitive detection of fine scale damage to transportation infrastructure : [final report].

    2015-09-23

    This research project aimed to develop a remote sensing system capable of rapidly identifying fine-scale damage to critical transportation infrastructure following hazard events. Such a system must be pre-planned for rapid deployment, automate proces...

  10. Assessment of plant species diversity based on hyperspectral indices at a fine scale.

    Peng, Yu; Fan, Min; Song, Jingyi; Cui, Tiantian; Li, Rui

    2018-03-19

    Fast and nondestructive approaches of measuring plant species diversity have been a subject of excessive scientific curiosity and disquiet to environmentalists and field ecologists worldwide. In this study, we measured the hyperspectral reflectances and plant species diversity indices at a fine scale (0.8 meter) in central Hunshandak Sandland of Inner Mongolia, China. The first-order derivative value (FD) at each waveband and 37 hyperspectral indices were used to assess plant species diversity. Results demonstrated that the stepwise linear regression of FD can accurately estimate the Simpson (R 2  = 0.83), Pielou (R 2  = 0.87) and Shannon-Wiener index (R 2  = 0.88). Stepwise linear regression of FD (R 2  = 0.81, R 2  = 0.82) and spectral vegetation indices (R 2  = 0.51, R 2  = 0.58) significantly predicted the Margalef and Gleason index. It was proposed that the Simpson, Pielou and Shannon-Wiener indices, which are widely used as plant species diversity indicators, can be precisely estimated through hyperspectral indices at a fine scale. This research promotes the development of methods for assessment of plant diversity using hyperspectral data.

  11. Fine scale distribution constrains cadmium accumulation rates in two geographical groups of Franciscana dolphin from Argentina

    Polizzi, P.S.; Chiodi Boudet, L.N.; Romero, M.B.; Denuncio, P.E.; Rodríguez, D.H.

    2013-01-01

    Highlights: • Fine scale distribution of two Argentine stocks constrains the Cd accumulation rates. • Cadmium levels and accumulation patterns were different between geographic groups. • Marine diet has a major influence than the impact degree of origin environment. • Engraulis anchoita is the main Cd vector species in Argentine shelf for Franciscana. • Information is valuable for the conservation of Franciscana, a vulnerable species. -- Abstract: Franciscana dolphin is an endemic cetacean in the southwestern Atlantic Ocean and is classified as Vulnerable A3d by the International Union for Conservation of Nature. Cadmium accumulation was assessed in two geographic groups from Argentina; one inhabits the La Plata River estuary, a high anthropogenic impacted environment, and the other is distributed in marine coastal, with negligible pollution. Despite the environment, marine dolphins showed an increase of renal Cd concentrations since trophic independence; while in estuarine dolphins was from 6 years. This is associated with dietary Argentine anchovy which was absent in the diet of estuarine dolphins, being a trophic vector of cadmium in shelf waters of Argentina. Cluster analysis also showed high levels of cd in association with the presence of anchovy in the stomach. The difference in the fine scale distribution of species influences dietary exposure to Cd and, along with other data, indicates two stocks in Argentina

  12. Networks Depicting the Fine-Scale Co-Occurrences of Fungi in Soil Horizons.

    Toju, Hirokazu; Kishida, Osamu; Katayama, Noboru; Takagi, Kentaro

    2016-01-01

    Fungi in soil play pivotal roles in nutrient cycling, pest controls, and plant community succession in terrestrial ecosystems. Despite the ecosystem functions provided by soil fungi, our knowledge of the assembly processes of belowground fungi has been limited. In particular, we still have limited knowledge of how diverse functional groups of fungi interact with each other in facilitative and competitive ways in soil. Based on the high-throughput sequencing data of fungi in a cool-temperate forest in northern Japan, we analyzed how taxonomically and functionally diverse fungi showed correlated fine-scale distributions in soil. By uncovering pairs of fungi that frequently co-occurred in the same soil samples, networks depicting fine-scale co-occurrences of fungi were inferred at the O (organic matter) and A (surface soil) horizons. The results then led to the working hypothesis that mycorrhizal, endophytic, saprotrophic, and pathogenic fungi could form compartmentalized (modular) networks of facilitative, antagonistic, and/or competitive interactions in belowground ecosystems. Overall, this study provides a research basis for further understanding how interspecific interactions, along with sharing of niches among fungi, drive the dynamics of poorly explored biospheres in soil.

  13. Fine-Scale Spatial Heterogeneity in the Distribution of Waterborne Protozoa in a Drinking Water Reservoir.

    Burnet, Jean-Baptiste; Ogorzaly, Leslie; Penny, Christian; Cauchie, Henry-Michel

    2015-09-23

    The occurrence of faecal pathogens in drinking water resources constitutes a threat to the supply of safe drinking water, even in industrialized nations. To efficiently assess and monitor the risk posed by these pathogens, sampling deserves careful design, based on preliminary knowledge on their distribution dynamics in water. For the protozoan pathogens Cryptosporidium and Giardia, only little is known about their spatial distribution within drinking water supplies, especially at fine scale. Two-dimensional distribution maps were generated by sampling cross-sections at meter resolution in two different zones of a drinking water reservoir. Samples were analysed for protozoan pathogens as well as for E. coli, turbidity and physico-chemical parameters. Parasites displayed heterogeneous distribution patterns, as reflected by significant (oo)cyst density gradients along reservoir depth. Spatial correlations between parasites and E. coli were observed near the reservoir inlet but were absent in the downstream lacustrine zone. Measurements of surface and subsurface flow velocities suggest a role of local hydrodynamics on these spatial patterns. This fine-scale spatial study emphasizes the importance of sampling design (site, depth and position on the reservoir) for the acquisition of representative parasite data and for optimization of microbial risk assessment and monitoring. Such spatial information should prove useful to the modelling of pathogen transport dynamics in drinking water supplies.

  14. Human Genetics of Diabetic Retinopathy: Current Perspectives

    Daniel P. K. Ng

    2010-01-01

    Full Text Available Diabetic retinopathy (DR is a most severe microvascular complication which, if left unchecked, can be sight-threatening. With the global prevalence of diabetes being relentlessly projected to rise to 438 million subjects by 2030, DR will undoubtedly pose a major public health concern. Efforts to unravel the human genetics of DR have been undertaken using the candidate gene and linkage approaches, while GWAS efforts are still lacking. Aside from evidence for a few genes including aldose reductase and vascular endothelial growth factor, the genetics of DR remain poorly elucidated. Nevertheless, the promise of impactful scientific discoveries may be realized if concerted and collaborative efforts are mounted to identify the genes for DR. Harnessing new genetic technologies and resources such as the upcoming 1000 Genomes Project will help advance this field of research, and potentially lead to a rich harvest of insights into the biological mechanisms underlying this debilitating complication.

  15. Human Genetic Engineering: A Survey of Student Value Stances

    Wilson, Sara McCormack; And Others

    1975-01-01

    Assesses the values of high school and college students relative to human genetic engineering and recommends that biology educators explore instructional strategies merging human genetic information with value clarification techniques. (LS)

  16. Human genetics in troubled times and places.

    Harper, Peter S

    2018-01-01

    The development of human genetics world-wide during the twentieth century, especially across Europe, has occurred against a background of repeated catastrophes, including two world wars and the ideological problems and repression posed by Nazism and Communism. The published scientific literature gives few hints of these problems and there is a danger that they will be forgotten. The First World War was largely indiscriminate in its carnage, but World War 2 and the preceding years of fascism were associated with widespread migration, especially of Jewish workers expelled from Germany, and of their children, a number of whom would become major contributors to the post-war generation of human and medical geneticists in Britain and America. In Germany itself, eminent geneticists were also involved in the abuses carried out in the name of 'eugenics' and 'race biology'. However, geneticists in America, Britain and the rest of Europe were largely responsible for the ideological foundations of these abuses. In the Soviet Union, geneticists and genetics itself became the object of persecution from the 1930s till as late as the mid 1960s, with an almost complete destruction of the field during this time; this extended also to Eastern Europe and China as part of the influence of Russian communism. Most recently, at the end of the twentieth century, China saw a renewal of government sponsored eugenics programmes, now mostly discarded. During the post-world war 2 decades, human genetics research benefited greatly from recognition of the genetic dangers posed by exposure to radiation, following the atomic bomb explosions in Japan, atmospheric testing and successive accidental nuclear disasters in Russia. Documenting and remembering these traumatic events, now largely forgotten among younger workers, is essential if we are to fully understand the history of human genetics and avoid the repetition of similar disasters in the future. The power of modern human genetic and genomic

  17. The genetic component of human longevity

    Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

    2018-01-01

    In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic...... pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin-like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1......, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP-SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes...

  18. Human genetics in troubled times and places

    Harper, Peter S.

    2017-01-01

    The development of human genetics world-wide during the twentieth century, especially across Europe, has occurred against a background of repeated catastrophes, including two world wars and the ideological problems and repression posed by Nazism and Communism. The published scientific literature gives few hints of these problems and there is a danger that they will be forgotten. The First World War was largely indiscriminate in its carnage, but World War 2 and the preceding years of fascism w...

  19. Research for genetic instability of human genome

    Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M. (National Inst. of Radiological Sciences, Chiba (Japan)); Murata, M.

    1992-01-01

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author).

  20. Research for genetic instability of human genome

    Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M.; Murata, M.

    1992-01-01

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author)

  1. Genome-wide survey of single-nucleotide polymorphisms reveals fine-scale population structure and signs of selection in the threatened Caribbean elkhorn coral, Acropora palmata

    Meghann K. Devlin-Durante

    2017-11-01

    Full Text Available The advent of next-generation sequencing tools has made it possible to conduct fine-scale surveys of population differentiation and genome-wide scans for signatures of selection in non-model organisms. Such surveys are of particular importance in sharply declining coral species, since knowledge of population boundaries and signs of local adaptation can inform restoration and conservation efforts. Here, we use genome-wide surveys of single-nucleotide polymorphisms in the threatened Caribbean elkhorn coral, Acropora palmata, to reveal fine-scale population structure and infer the major barrier to gene flow that separates the eastern and western Caribbean populations between the Bahamas and Puerto Rico. The exact location of this break had been subject to discussion because two previous studies based on microsatellite data had come to differing conclusions. We investigate this contradiction by analyzing an extended set of 11 microsatellite markers including the five previously employed and discovered that one of the original microsatellite loci is apparently under selection. Exclusion of this locus reconciles the results from the SNP and the microsatellite datasets. Scans for outlier loci in the SNP data detected 13 candidate loci under positive selection, however there was no correlation between available environmental parameters and genetic distance. Together, these results suggest that reef restoration efforts should use local sources and utilize existing functional variation among geographic regions in ex situ crossing experiments to improve stress resistance of this species.

  2. Genome-wide survey of single-nucleotide polymorphisms reveals fine-scale population structure and signs of selection in the threatened Caribbean elkhorn coral, Acropora palmata.

    Devlin-Durante, Meghann K; Baums, Iliana B

    2017-01-01

    The advent of next-generation sequencing tools has made it possible to conduct fine-scale surveys of population differentiation and genome-wide scans for signatures of selection in non-model organisms. Such surveys are of particular importance in sharply declining coral species, since knowledge of population boundaries and signs of local adaptation can inform restoration and conservation efforts. Here, we use genome-wide surveys of single-nucleotide polymorphisms in the threatened Caribbean elkhorn coral, Acropora palmata , to reveal fine-scale population structure and infer the major barrier to gene flow that separates the eastern and western Caribbean populations between the Bahamas and Puerto Rico. The exact location of this break had been subject to discussion because two previous studies based on microsatellite data had come to differing conclusions. We investigate this contradiction by analyzing an extended set of 11 microsatellite markers including the five previously employed and discovered that one of the original microsatellite loci is apparently under selection. Exclusion of this locus reconciles the results from the SNP and the microsatellite datasets. Scans for outlier loci in the SNP data detected 13 candidate loci under positive selection, however there was no correlation between available environmental parameters and genetic distance. Together, these results suggest that reef restoration efforts should use local sources and utilize existing functional variation among geographic regions in ex situ crossing experiments to improve stress resistance of this species.

  3. Does genetic diversity predict health in humans?

    Hanne C Lie

    2009-07-01

    Full Text Available Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC, has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d(2 at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d(2 at nonMHC loci and at one MHC locus, linked to HLA-DRB1, reported fewer symptoms over a four-month period than individuals with lower d(2. In contrast, there were no associations between MHC or nonMHC heterozygosity and health. NonMHC-d(2 has previously been found to predict male preferences for female faces. Thus, the current findings suggest that nonMHC diversity may play a role in both natural and sexual selection acting on human populations.

  4. Genetic & epigenetic approach to human obesity

    K Rajender Rao

    2014-01-01

    Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  5. Fine-scale features on bioreplicated decoys of the emerald ash borer provide necessary visual verisimilitude

    Domingue, Michael J.; Pulsifer, Drew P.; Narkhede, Mahesh S.; Engel, Leland G.; Martín-Palma, Raúl J.; Kumar, Jayant; Baker, Thomas C.; Lakhtakia, Akhlesh

    2014-03-01

    The emerald ash borer (EAB), Agrilus planipennis, is an invasive tree-killing pest in North America. Like other buprestid beetles, it has an iridescent coloring, produced by a periodically layered cuticle whose reflectance peaks at 540 nm wavelength. The males perform a visually mediated ritualistic mating flight directly onto females poised on sunlit leaves. We attempted to evoke this behavior using artificial visual decoys of three types. To fabricate decoys of the first type, a polymer sheet coated with a Bragg-stack reflector was loosely stamped by a bioreplicating die. For decoys of the second type, a polymer sheet coated with a Bragg-stack reflector was heavily stamped by the same die and then painted green. Every decoy of these two types had an underlying black absorber layer. Decoys of the third type were produced by a rapid prototyping machine and painted green. Fine-scale features were absent on the third type. Experiments were performed in an American ash forest infested with EAB, and a European oak forest home to a similar pest, the two-spotted oak borer (TSOB), Agrilus biguttatus. When pinned to leaves, dead EAB females, dead TSOB females, and bioreplicated decoys of both types often evoked the complete ritualized flight behavior. Males also initiated approaches to the rapidly prototyped decoy, but would divert elsewhere without making contact. The attraction of the bioreplicated decoys was also demonstrated by providing a high dc voltage across the decoys that stunned and killed approaching beetles. Thus, true bioreplication with fine-scale features is necessary to fully evoke ritualized visual responses in insects, and provides an opportunity for developing insecttrapping technologies.

  6. Fine-scale variability of isopycnal salinity in the California Current System

    Itoh, Sachihiko; Rudnick, Daniel L.

    2017-09-01

    This paper examines the fine-scale structure and seasonal fluctuations of the isopycnal salinity of the California Current System from 2007 to 2013 using temperature and salinity profiles obtained from a series of underwater glider surveys. The seasonal mean distributions of the spectral power of the isopycnal salinity gradient averaged over submesoscale (12-30 km) and mesoscale (30-60 km) ranges along three survey lines off Monterey Bay, Point Conception, and Dana Point were obtained from 298 transects. The mesoscale and submesoscale variance increased as coastal upwelling caused the isopycnal salinity gradient to steepen. Areas of elevated variance were clearly observed around the salinity front during the summer then spread offshore through the fall and winter. The high fine-scale variances were observed typically above 25.8 kg m-3 and decreased with depth to a minimum at around 26.3 kg m-3. The mean spectral slope of the isopycnal salinity gradient with respect to wavenumber was 0.19 ± 0.27 over the horizontal scale of 12-60 km, and 31%-35% of the spectra had significantly positive slopes. In contrast, the spectral slope over 12-30 km was mostly flat, with mean values of -0.025 ± 0.32. An increase in submesoscale variability accompanying the steepening of the spectral slope was often observed in inshore areas; e.g., off Monterey Bay in winter, where a sharp front developed between the California Current and the California Under Current, and the lower layers of the Southern California Bight, where vigorous interaction between a synoptic current and bottom topography is to be expected.

  7. Human genetic issues from scientific and Islamic perspectives | Alwi ...

    This paper aims at revealing the Human Genome Project (HGP) and human genetic issues arising from science and Islamic perspectives such as Darwin's evolutionary theory, human cloning and eugenics. Finally, issues arising from the applications of human genetic technology need to be addressed to the best possible ...

  8. Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

    Rabino, Isaac

    2003-01-01

    Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)

  9. Human-modified landscapes: patterns of fine-scale woody vegetation structure in communal savannah rangelands

    Fisher, T

    2011-11-01

    Full Text Available structure in five communal rangelands around 12 settlements in Bushbuckridge, a municipality in the Kruger to Canyons Biosphere Reserve (South Africa). The importance of underlying abiotic factors was evaluated by measuring size class distributions across...

  10. Genetics of human sensitivity to ultraviolet radiation

    Cleaver, James E.

    1994-07-01

    the major human health effects of solar and artificial UV light occur from the UVB and UVC wavelength ranges and involve a variety of short-term and long-term deleterious changes to the skin and eyes. the more important initial damage to cellular macromolecules involves dimerization of adjacent pyrimidines in DNA to produce cyclobutane pyrimidine dimes, (6-4) pyrimidine- pyrimidone, and (6-4) dewar photoproducts. these photoproducts can be repaired by a genetically regulated enzyme system (nucleotide excision repair) which removes oligonucleotides 29-30 nucleotides long that contain the photoproducts, and synthesizes replacement patches. At least a dozen gene products are involved in the process of recognizing photoproducts in DNA, altering local DNA helicity and cleaving the polynucleotide chain at defined positions either side of a photoproduct. Hereditary mutations in many of these genes are recognized in the human genetic disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Several of the gene products have other functions involving the regulation of gene transcription which accounts for the complex clinical presentation of repair deficient diseases that involve sensitivity of the skin and eyes to UV light, increased solar carcinogenesis (in XP), demyelination, and ganglial calcification (in CS), hair abnormalities (in TTD), and developmental and neurological abnormalities

  11. Fine-scale maps of recombination rates and hotspots in the mouse genome.

    Brunschwig, Hadassa; Levi, Liat; Ben-David, Eyal; Williams, Robert W; Yakir, Benjamin; Shifman, Sagiv

    2012-07-01

    Recombination events are not uniformly distributed and often cluster in narrow regions known as recombination hotspots. Several studies using different approaches have dramatically advanced our understanding of recombination hotspot regulation. Population genetic data have been used to map and quantify hotspots in the human genome. Genetic variation in recombination rates and hotspots usage have been explored in human pedigrees, mouse intercrosses, and by sperm typing. These studies pointed to the central role of the PRDM9 gene in hotspot modulation. In this study, we used single nucleotide polymorphisms (SNPs) from whole-genome resequencing and genotyping studies of mouse inbred strains to estimate recombination rates across the mouse genome and identified 47,068 historical hotspots--an average of over 2477 per chromosome. We show by simulation that inbred mouse strains can be used to identify positions of historical hotspots. Recombination hotspots were found to be enriched for the predicted binding sequences for different alleles of the PRDM9 protein. Recombination rates were on average lower near transcription start sites (TSS). Comparing the inferred historical recombination hotspots with the recent genome-wide mapping of double-strand breaks (DSBs) in mouse sperm revealed a significant overlap, especially toward the telomeres. Our results suggest that inbred strains can be used to characterize and study the dynamics of historical recombination hotspots. They also strengthen previous findings on mouse recombination hotspots, and specifically the impact of sequence variants in Prdm9.

  12. Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population

    McInnes, L. Alison; Service, Susan K.; Reus, Victor I.; Barnes, Glenn; Charlat, Olga; Jawahar, Satya; Lewitzky, Steve; Yang, Qing; Duong, Quyen; Spesny, Mitzi; Araya, Carmen; Araya, Xinia; Gallegos, Alvaro; Meza, Luis; Molina, Julio; Ramirez, Rolando; Mendez, Roxana; Silva, Sandra; Fournier, Eduardo; Batki, Steven L.; Mathews, Carol A.; Neylan, Thomas; Glatt, Charles E.; Escamilla, Michael A.; Luo, David; Gajiwala, Paresh; Song, Terry; Crook, Stephen; Nguyen, Jasmine B.; Roche, Erin; Meyer, Joanne M.; Leon, Pedro; Sandkuijl, Lodewijk A.; Freimer, Nelson B.; Chen, Hong

    2001-01-01

    We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders. PMID:11572994

  13. Genetic loading on human loving styles.

    Emanuele, Enzo; Brondino, Natascia; Pesenti, Sara; Re, Simona; Geroldi, Diego

    2007-12-01

    It has been hypothesized that cerebral neurotransmitters such as dopamine and serotonin could play a role in human romantic bonding. However, no data on the genetic basis of human romantic love are currently available. To address this issue, we looked for associations between markers in neurotransmitter genes (the serotonin transporter gene, 5-HTT; the serotonin receptor 2A, 5HT2A; the dopamine D2 receptor gene, DRD2; and the dopamine D4 receptor gene, DRD4) and the six styles of love as conceptualized by Lee (Eros, Ludus, Storge, Pragma, Mania and Agape). A total of 350 healthy young adults (165 males and 185 females, mean age: 24.1+/-3.9 years, range 18-32 years) filled the 24-item Love Attitudes Scale (LAS) and were genotyped for the following six polymorphic markers: the serotonin transporter-linked polymorphic region (5-HTTLPR), the 5HT2A T102C and C516T polymorphisms, the DRD2 TaqI A and TaqI B variants, and the DRD4 exon 3 VNTR polymorphism. Statistical analysis revealed a significant association between the DRD2 TaqI A genotypes and "Eros" (a loving style characterized by a tendency to develop intense emotional experiences based on the physical attraction to the partner), as well as between the C516T 5HT2A polymorphism and "Mania" (a possessive and dependent romantic attachment, characterized by self-defeating emotions). These associations were present in both sexes and remained significant even after adjustment for potential confounders. Our data provide the first evidence of a possible genetic loading on human loving styles.

  14. Fine-scale patterns of population stratification confound rare variant association tests.

    Timothy D O'Connor

    Full Text Available Advances in next-generation sequencing technology have enabled systematic exploration of the contribution of rare variation to Mendelian and complex diseases. Although it is well known that population stratification can generate spurious associations with common alleles, its impact on rare variant association methods remains poorly understood. Here, we performed exhaustive coalescent simulations with demographic parameters calibrated from exome sequence data to evaluate the performance of nine rare variant association methods in the presence of fine-scale population structure. We find that all methods have an inflated spurious association rate for parameter values that are consistent with levels of differentiation typical of European populations. For example, at a nominal significance level of 5%, some test statistics have a spurious association rate as high as 40%. Finally, we empirically assess the impact of population stratification in a large data set of 4,298 European American exomes. Our results have important implications for the design, analysis, and interpretation of rare variant genome-wide association studies.

  15. Simulating Fine-Scale Marine Pollution Plumes for Autonomous Robotic Environmental Monitoring

    Muhammad Fahad

    2018-05-01

    Full Text Available Marine plumes exhibit characteristics such as intermittency, sinuous structure, shape and flow field coherency, and a time varying concentration profile. Due to the lack of experimental quantification of these characteristics for marine plumes, existing work often assumes marine plumes exhibit behavior similar to aerial plumes and are commonly modeled by filament based Lagrangian models. Our previous field experiments with Rhodamine dye plumes at Makai Research Pier at Oahu, Hawaii revealed that marine plumes show similar characteristics to aerial plumes qualitatively, but quantitatively they are disparate. Based on the field data collected, this paper presents a calibrated Eulerian plume model that exhibits the qualitative and quantitative characteristics exhibited by experimentally generated marine plumes. We propose a modified model with an intermittent source, and implement it in a Robot Operating System (ROS based simulator. Concentration time series of stationary sampling points and dynamic sampling points across cross-sections and plume fronts are collected and analyzed for statistical parameters of the simulated plume. These parameters are then compared with statistical parameters from experimentally generated plumes. The comparison validates that the simulated plumes exhibit fine-scale qualitative and quantitative characteristics similar to experimental plumes. The ROS plume simulator facilitates future evaluations of environmental monitoring strategies by marine robots, and is made available for community use.

  16. Fine scale microstructure in cast and aged duplex stainless steels investigated by small angle neutron scattering

    Epperson, J.E.; Lin, J.S.; Spooner, S.

    1986-02-01

    Small angle neutron scattering (SANS) allows clustering phenomena to be studied in systems for which the constituent atoms do not differ greatly in atomic number. This investigation used SANS to characterize the fine scale microstructure in two cast and aged duplex stainless steels; aging times extended up to eight years. The steels differed in ferrite content by about a factor of two. The scattering at lowest q was dominated by magnetic scattering effects associated with the ferrite phase. In the range 0.025 less than or equal to q less than or equal to 0.2A -1 , additional scattering due to a precipitating phase rich in Ni and Si was observed. This scattering was rather intense and revealed a volume fraction of precipitate, in the ferrite, estimated to be 12 to 18% after long time aging. After about 70,000 hours at 400 0 C, there were about 10 18 precipitate particles per cm 3 some 50A in mean diameter, and they were distributed in a nonrandom manner, i.e., spatially, short-range-ordered. This investigation suggests that after aging some 70,000 hours at 400 0 C, the precipitate in the ferrite phase is undergoing Ostwald ripening. The present data are insufficient to indicate at what time this ripening process began

  17. Mapping to Support Fine Scale Epidemiological Cholera Investigations: A Case Study of Spatial Video in Haiti

    Andrew Curtis

    2016-02-01

    Full Text Available The cartographic challenge in many developing world environments suffering a high disease burden is a lack of granular environmental covariates suitable for modeling disease outcomes. As a result, epidemiological questions, such as how disease diffuses at intra urban scales are extremely difficult to answer. This paper presents a novel geospatial methodology, spatial video, which can be used to collect and map environmental covariates, while also supporting field epidemiology. An example of epidemic cholera in a coastal town of Haiti is used to illustrate the potential of this new method. Water risks from a 2012 spatial video collection are used to guide a 2014 survey, which concurrently included the collection of water samples, two of which resulted in positive lab results “of interest” (bacteriophage specific for clinical cholera strains to the current cholera situation. By overlaying sample sites on 2012 water risk maps, a further fifteen proposed water sample locations are suggested. These resulted in a third spatial video survey and an additional “of interest” positive water sample. A potential spatial connection between the “of interest” water samples is suggested. The paper concludes with how spatial video can be an integral part of future fine-scale epidemiological investigations for different pathogens.

  18. Coarse- and fine-scale patterns of distribution and habitat selection places an Amazonian floodplain curassow in double jeopardy

    Gabriel A. Leite

    2018-05-01

    Full Text Available Patterns of habitat selection are influenced by local productivity, resource availability, and predation risk. Species have taken millions of years to hone the macro- and micro-habitats they occupy, but these may now overlap with contemporary human threats within natural species ranges. Wattled Curassow (Crax globulosa, an endemic galliform species of the western Amazon, is threatened by both hunting and habitat loss, and is restricted to white-water floodplain forests of major Amazonian rivers. In this study conducted along the Juruá River, Amazonas, Brazil, we quantified the ranging ecology and fine-scale patterns of habitat selection of the species. We estimated the home range size of C. globulosa using conventional VHF telemetry. To estimate patterns of habitat selection, we used geo-locations of day ranges to examine the extent and intensity of use across the floodplain, which were then compared to a high-resolution flood map of the study area. We captured two females and one male, which we monitored for 13 months between September 2014 and September 2015. Average home range size was 283 ha, based on the 95% aLoCoH estimator. Wattled Curassows selected areas of prolonged flood pulses (six to eight months/year and had a consistent tendency to be near open water, usually in close proximity to river banks and lakes, especially during the dry season. Amazonian floodplains are densely settled, and the small portions of floodplain habitat used by Wattled Curassows are both the most accessible to hunters and most vulnerable to deforestation. As a result, the geographic and ecological distribution of Wattled Curassows places them at much higher extinction risk at multiple spatial scales, highlighting the need to consider habitat preferences within their conservation strategy.

  19. Introducing close-range photogrammetry for characterizing forest understory plant diversity and surface fuel structure at fine scales

    Benjamin C. Bright; E. Louise Loudermilk; Scott M. Pokswinski; Andrew T. Hudak; Joseph J. O' Brien

    2016-01-01

    Methods characterizing fine-scale fuels and plant diversity can advance understanding of plant-fire interactions across scales and help in efforts to monitor important ecosystems such as longleaf pine (Pinus palustris Mill.) forests of the southeastern United States. Here, we evaluate the utility of close-range photogrammetry for measuring fuels and plant...

  20. Race, genetics, and human reproductive strategies.

    Rushton, J P

    1996-02-01

    The international literature on racial differences is reviewed, novel data are reported, and a distinct pattern is found. People of east Asian ancestry and people of African ancestry average at opposite ends of a continuum, with people of European ancestry averaging intermediately, albeit with much variability within each major race. The racial matrix emerges from measures taken of reproductive behavior, sex hormones, twinning rate, speed of physical maturation, personality, family stability, brain size, intelligence, law abidingness, and social organization. An evolutionary theory of human reproduction is proposed, familiar to biologists as the r-K scale of reproductive strategies. At one end of this scale are r-strategies, which emphasize high reproductive rates; at the other end are K-strategies, which emphasize high levels of parental investment. This scale is generally used to compare the life histories of widely disparate species, but here it is used to describe the immensely smaller variations among human races. It is hypothesized that, again on average, Mongoloid people are more K-selected than Caucasoids, who are more K-selected than Negroids. The r-K scale of reproductive strategies is also mapped on to human evolution. Genetic distances indicate that Africans emerged from the ancestral hominid line about 200,000 years ago, with an African/non-African split about 110,000 years ago, and a Caucasoid/Mongoloid split about 41,000 years ago. Such an ordering fits with and explains how and why the variables cluster.

  1. Analogs of human genetic skin disease in domesticated animals

    Justin Finch, MD

    2017-09-01

    The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.

  2. Ultra-Fine Scale Spatially-Integrated Mapping of Habitat and Occupancy Using Structure-From-Motion.

    Philip McDowall

    Full Text Available Organisms respond to and often simultaneously modify their environment. While these interactions are apparent at the landscape extent, the driving mechanisms often occur at very fine spatial scales. Structure-from-Motion (SfM, a computer vision technique, allows the simultaneous mapping of organisms and fine scale habitat, and will greatly improve our understanding of habitat suitability, ecophysiology, and the bi-directional relationship between geomorphology and habitat use. SfM can be used to create high-resolution (centimeter-scale three-dimensional (3D habitat models at low cost. These models can capture the abiotic conditions formed by terrain and simultaneously record the position of individual organisms within that terrain. While coloniality is common in seabird species, we have a poor understanding of the extent to which dense breeding aggregations are driven by fine-scale active aggregation or limited suitable habitat. We demonstrate the use of SfM for fine-scale habitat suitability by reconstructing the locations of nests in a gentoo penguin colony and fitting models that explicitly account for conspecific attraction. The resulting digital elevation models (DEMs are used as covariates in an inhomogeneous hybrid point process model. We find that gentoo penguin nest site selection is a function of the topography of the landscape, but that nests are far more aggregated than would be expected based on terrain alone, suggesting a strong role of behavioral aggregation in driving coloniality in this species. This integrated mapping of organisms and fine scale habitat will greatly improve our understanding of fine-scale habitat suitability, ecophysiology, and the complex bi-directional relationship between geomorphology and habitat use.

  3. Genetically modified plants and human health.

    Key, Suzie; Ma, Julian K-C; Drake, Pascal Mw

    2008-06-01

    Genetically modified (or GM) plants have attracted a large amount of media attention in recent years and continue to do so. Despite this, the general public remains largely unaware of what a GM plant actually is or what advantages and disadvantages the technology has to offer, particularly with regard to the range of applications for which they can be used. From the first generation of GM crops, two main areas of concern have emerged, namely risk to the environment and risk to human health. As GM plants are gradually being introduced into the European Union there is likely to be increasing public concern regarding potential health issues. Although it is now commonplace for the press to adopt 'health campaigns', the information they publish is often unreliable and unrepresentative of the available scientific evidence. We consider it important that the medical profession should be aware of the state of the art, and, as they are often the first port of call for a concerned patient, be in a position to provide an informed opinion. This review will examine how GM plants may impact on human health both directly - through applications targeted at nutrition and enhancement of recombinant medicine production - but also indirectly, through potential effects on the environment. Finally, it will examine the most important opposition currently facing the worldwide adoption of this technology: public opinion.

  4. Fine Scale ANUClimate Data for Ecosystem Modeling and Assessment of Plant Functional Types

    Hutchinson, M. F.; Kesteven, J. L.; Xu, T.; Evans, B. J.; Togashi, H. F.; Stein, J. L.

    2015-12-01

    High resolution spatially extended values of climate variables play a central role in the assessment of climate and projected future climate in ecosystem modeling. The ground based meteorological network remains a key resource for deriving these spatially extended climate variables. We report on the production, and applications, of new anomaly based fine scale spatial interpolations of key climate variables at daily and monthly time scale, across the Australian continent. The methods incorporate several innovations that have significantly improved spatial predictive accuracy, as well as providing a platform for the incorporation of additional remotely sensed data. The interpolated climate data are supporting many continent-wide ecosystem modeling applications and are playing a key role in testing optimality hypotheses associated with plant functional types (PFTs). The accuracy, and robustness to data error, of anomaly-based interpolation has been enhanced by incorporating physical process aspects of the different climate variables and employing robust statistical methods implemented in the ANUSPLIN package. New regression procedures have also been developed to estimate "background" monthly climate normals from all stations with minimal records to substantially increase the density of supporting spatial networks. Monthly mean temperature interpolation has been enhanced by incorporating process based coastal effects that have reduced predictive error by around 10%. Overall errors in interpolated monthly temperature fields are around 25% less than errors reported by an earlier study. For monthly and daily precipitation, a new anomaly structure has been devised to take account of the skewness in precipitation data and the large proportion of zero values that present significant challenges to standard interpolation methods. The many applications include continent-wide Gross Primary Production modeling and assessing constraints on light and water use efficiency derived

  5. Regulation of the demographic structure in isomorphic biphasic life cycles at the spatial fine scale.

    Vasco Manuel Nobre de Carvalho da Silva Vieira

    Full Text Available Isomorphic biphasic algal life cycles often occur in the environment at ploidy abundance ratios (Haploid:Diploid different from 1. Its spatial variability occurs within populations related to intertidal height and hydrodynamic stress, possibly reflecting the niche partitioning driven by their diverging adaptation to the environment argued necessary for their prevalence (evolutionary stability. Demographic models based in matrix algebra were developed to investigate which vital rates may efficiently generate an H:D variability at a fine spatial resolution. It was also taken into account time variation and type of life strategy. Ploidy dissimilarities in fecundity rates set an H:D spatial structure miss-fitting the ploidy fitness ratio. The same happened with ploidy dissimilarities in ramet growth whenever reproductive output dominated the population demography. Only through ploidy dissimilarities in looping rates (stasis, breakage and clonal growth did the life cycle respond to a spatially heterogeneous environment efficiently creating a niche partition. Marginal locations were more sensitive than central locations. Related results have been obtained experimentally and numerically for widely different life cycles from the plant and animal kingdoms. Spore dispersal smoothed the effects of ploidy dissimilarities in fertility and enhanced the effects of ploidy dissimilarities looping rates. Ploidy dissimilarities in spore dispersal could also create the necessary niche partition, both over the space and time dimensions, even in spatial homogeneous environments and without the need for conditional differentiation of the ramets. Fine scale spatial variability may be the key for the prevalence of isomorphic biphasic life cycles, which has been neglected so far.

  6. Alpine Ecohydrology Across Scales: Propagating Fine-scale Heterogeneity to the Catchment and Beyond

    Mastrotheodoros, T.; Pappas, C.; Molnar, P.; Burlando, P.; Hadjidoukas, P.; Fatichi, S.

    2017-12-01

    In mountainous ecosystems, complex topography and landscape heterogeneity govern ecohydrological states and fluxes. Here, we investigate topographic controls on water, energy and carbon fluxes across different climatic regimes and vegetation types representative of the European Alps. We use an ecohydrological model to perform fine-scale numerical experiments on a synthetic domain that comprises a symmetric mountain with eight catchments draining along the cardinal and intercardinal directions. Distributed meteorological model input variables are generated using observations from Switzerland. The model computes the incoming solar radiation based on the local topography. We implement a multivariate statistical framework to disentangle the impact of landscape heterogeneity (i.e., elevation, aspect, flow contributing area, vegetation type) on the simulated water, carbon, and energy dynamics. This allows us to identify the sensitivities of several ecohydrological variables (including leaf area index, evapotranspiration, snow-cover and net primary productivity) to topographic and meteorological inputs at different spatial and temporal scales. We also use an alpine catchment as a real case study to investigate how the natural variability of soil and land cover affects the idealized relationships that arise from the synthetic domain. In accordance with previous studies, our analysis shows a complex pattern of vegetation response to radiation. We find also different patterns of ecosystem sensitivity to topography-driven heterogeneity depending on the hydrological regime (i.e., wet vs. dry conditions). Our results suggest that topography-driven variability in ecohydrological variables (e.g. transpiration) at the fine spatial scale can exceed 50%, but it is substantially reduced ( 5%) when integrated at the catchment scale.

  7. Quantitative rainfall metrics for comparing volumetric rainfall retrievals to fine scale models

    Collis, Scott; Tao, Wei-Kuo; Giangrande, Scott; Fridlind, Ann; Theisen, Adam; Jensen, Michael

    2013-04-01

    Precipitation processes play a significant role in the energy balance of convective systems for example, through latent heating and evaporative cooling. Heavy precipitation "cores" can also be a proxy for vigorous convection and vertical motions. However, comparisons between rainfall rate retrievals from volumetric remote sensors with forecast rain fields from high-resolution numerical weather prediction simulations are complicated by differences in the location and timing of storm morphological features. This presentation will outline a series of metrics for diagnosing the spatial variability and statistical properties of precipitation maps produced both from models and retrievals. We include existing metrics such as Contoured by Frequency Altitude Diagrams (Yuter and Houze 1995) and Statistical Coverage Products (May and Lane 2009) and propose new metrics based on morphology, cell and feature based statistics. Work presented focuses on observations from the ARM Southern Great Plains radar network consisting of three agile X-Band radar systems with a very dense coverage pattern and a C Band system providing site wide coverage. By combining multiple sensors resolutions of 250m2 can be achieved, allowing improved characterization of fine-scale features. Analyses compare data collected during the Midlattitude Continental Convective Clouds Experiment (MC3E) with simulations of observed systems using the NASA Unified Weather Research and Forecasting model. May, P. T., and T. P. Lane, 2009: A method for using weather radar data to test cloud resolving models. Meteorological Applications, 16, 425-425, doi:10.1002/met.150, 10.1002/met.150. Yuter, S. E., and R. A. Houze, 1995: Three-Dimensional Kinematic and Microphysical Evolution of Florida Cumulonimbus. Part II: Frequency Distributions of Vertical Velocity, Reflectivity, and Differential Reflectivity. Mon. Wea. Rev., 123, 1941-1963, doi:10.1175/1520-0493(1995)1232.0.CO;2.

  8. Fine-scale movement decisions of tropical forest birds in a fragmented landscape.

    Gillies, Cameron S; Beyer, Hawthorne L; St Clair, Colleen Cassady

    2011-04-01

    The persistence of forest-dependent species in fragmented landscapes is fundamentally linked to the movement of individuals among subpopulations. The paths taken by dispersing individuals can be considered a series of steps built from individual route choices. Despite the importance of these fine-scale movement decisions, it has proved difficult to collect such data that reveal how forest birds move in novel landscapes. We collected unprecedented route information about the movement of translocated forest birds from two species in the highly fragmented tropical dry forest of Costa Rica. In this pasture-dominated landscape, forest remains in patches or riparian corridors, with lesser amounts of living fencerows and individual trees or "stepping stones." We used step selection functions to quantify how route choice was influenced by these habitat elements. We found that the amount of risk these birds were willing to take by crossing open habitat was context dependent. The forest-specialist Barred Antshrike (Thamnophilus doliatus) exhibited stronger selection for forested routes when moving in novel landscapes distant from its territory relative to locations closer to its territory. It also selected forested routes when its step originated in forest habitat. It preferred steps ending in stepping stones when the available routes had little forest cover, but avoided them when routes had greater forest cover. The forest-generalist Rufous-naped Wren (Campylorhynchus rufinucha) preferred steps that contained more pasture, but only when starting from non-forest habitats. Our results showed that forested corridors (i.e., riparian corridors) best facilitated the movement of a sensitive forest specialist through this fragmented landscape. They also suggested that stepping stones can be important in highly fragmented forests with little remaining forest cover. We expect that naturally dispersing birds and species with greater forest dependence would exhibit even stronger

  9. Using Moss to Detect Fine-Scaled Deposition of Heavy Metals in Urban Environments

    Jovan, S.; Donovan, G.; Demetrios, G.; Monleon, V. J.; Amacher, M. C.

    2017-12-01

    Mosses are commonly used as bio-indicators of heavy metal deposition to forests. Their application in urban airsheds is relatively rare. Our objective was to develop fine-scaled, city-wide maps for heavy metals in Portland, Oregon, to identify pollution "hotspots" and serve as a screening tool for more effective placement of air quality monitoring instruments. In 2013 we measured twenty-two elements in epiphytic moss sampled on a 1km x1km sampling grid (n = 346). We detected large hotspots of cadmium and arsenic in two neighborhoods associated with stained glass manufacturers. Air instruments deployed by local regulators measured cadmium concentrations 49 times and arsenic levels 155 times the state health benchmarks. Moss maps also detected a large nickel hotspot in a neighborhood near a forge where air instruments later measured concentrations 4 times the health benchmark. In response, the facilities implemented new pollution controls, air quality improved in all three affected neighborhoods, revision of regulations for stained glass furnace emissions are underway, and Oregon's governor launched an initiative to develop health-based (vs technology-based) regulations for air toxics in the state. The moss maps also indicated a couple dozen smaller hotspots of heavy metals, including lead, chromium, and cobalt, in Portland neighborhoods. Ongoing follow-up work includes: 1) use of moss sampling by local regulators to investigate source and extent of the smaller hotspots, 2) use of lead isotopes to determine origins of higher lead levels observed in moss collected from the inner city, and 3) co-location of air instruments and moss sampling to determine accuracy, timeframe represented, and seasonality of heavy metals in moss.

  10. Whole-genome patterns of linkage disequilibrium across flycatcher populations clarify the causes and consequences of fine-scale recombination rate variation in birds.

    Kawakami, Takeshi; Mugal, Carina F; Suh, Alexander; Nater, Alexander; Burri, Reto; Smeds, Linnéa; Ellegren, Hans

    2017-08-01

    Recombination rate is heterogeneous across the genome of various species and so are genetic diversity and differentiation as a consequence of linked selection. However, we still lack a clear picture of the underlying mechanisms for regulating recombination. Here we estimated fine-scale population recombination rate based on the patterns of linkage disequilibrium across the genomes of multiple populations of two closely related flycatcher species (Ficedula albicollis and F. hypoleuca). This revealed an overall conservation of the recombination landscape between these species at the scale of 200 kb, but we also identified differences in the local rate of recombination despite their recent divergence (recombination rate in a lineage-specific manner, indicating differences in the extent of linked selection between species. We detected 400-3,085 recombination hotspots per population. Location of hotspots was conserved between species, but the intensity of hotspot activity varied between species. Recombination hotspots were primarily associated with CpG islands (CGIs), regardless of whether CGIs were at promoter regions or away from genes. Recombination hotspots were also associated with specific transposable elements (TEs), but this association appears indirect due to shared preferences of the transposition machinery and the recombination machinery for accessible open chromatin regions. Our results suggest that CGIs are a major determinant of the localization of recombination hotspots, and we propose that both the distribution of TEs and fine-scale variation in recombination rate may be associated with the evolution of the epigenetic landscape. © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  11. Human population genetics and “ancestrality” business

    André Langaney

    2009-01-01

    Following the foundation of theoretical population genetics by Wright, Fischer, Haldane and Malécot, in the first half of the 20th century, applied human population genetics developed with great success with the improvement and accumulation of new technologies to measure genetic polymorphism, first through protein polymorphisms since the 1960’s, then through DNA typing and sequencing since the 1980’s. The field of population genetics and biological anthropology was developed by a handful of d...

  12. An existential analysis of genetic engineering and human rights ...

    Genetic engineering for purposes of human enhancement poses risks that justify regulation. However, this paper argues philosophically that it is inappropriate to use human rights treaties to prohibit germ-line genetic engineering whether therapeutic or for purposes of enhancement. When also looked at existentially, the ...

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

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

  14. Using fine-scale fuel measurements to assess wildland fuels, potential fire behavior and hazard mitigation treatments in the southeastern USA

    Roger D. Ottmar; John I. Blake; William T. Crolly

    2012-01-01

    The inherent spatial and temporal heterogeneity of fuel beds in forests of the southeastern United States may require fine scale fuel measurements for providing reliable fire hazard and fuel treatment effectiveness estimates. In a series of five papers, an intensive, fine scale fuel inventory from the Savanna River Site in the southeastern United States is used for...

  15. Genetic differences between avian and human isolates of Candida dubliniensis.

    McManus, Brenda A

    2009-09-01

    When Candida dubliniensis isolates obtained from seabird excrement and from humans in Ireland were compared by using multilocus sequence typing, 13 of 14 avian isolates were genetically distinct from human isolates. The remaining avian isolate was indistinguishable from a human isolate, suggesting that transmission may occur between humans and birds.

  16. Fine-scale crustal structure of the Azores Islands from teleseismic receiver functions

    Spieker, K.; Rondenay, S.; Ramalho, R. S.; Thomas, C.; Helffrich, G. R.

    2016-12-01

    The Azores plateau is located near the Mid-Atlantic Ridge (MAR) and consists of nine islands, most of which lie east of the MAR. Various methods including seismic reflection, gravity, and passive seismic imaging have been used to investigate the crustal thickness beneath the islands. They have yielded thickness estimates that range between roughly 10 km and 30 km, but until now models of the fine-scale crustal structure have been lacking. A comparison of the crustal structure beneath the islands that lie west and east of the MAR might give further constraints on the evolution of the islands. For example, geochemical studies carried out across the region predict the existence of volcanic interfaces that should be detected seismically within the shallow crust of some of the islands. In this study, we use data from ten seismic stations located on the Azores Islands to investigate the crustal structure with teleseismic P-wave receiver functions. We query our resulting receiver functions for signals associated with the volcanic edifice, the crust-mantle boundary, and potential underplated layers beneath the various islands. The islands west of the MAR have a crustal structure comprising two discontinuities - an upper one at 1-2 km depth marking the base of the volcanic edifice, and a lower one at 10 km depth that we interpret as crust-mantle boundary. The islands east of the MAR can be subdivided into two groups. The central islands that are closer to the MAR exhibit a crustal structure similar to that of the western islands, with a volcanic edifice reaching a depth of 2 km and an average crust-mantle boundary at around 12 km depth. The easternmost islands, located on the oldest lithosphere, exhibit a more complex crustal structure with evidence for a mid-crustal interface and an underplated layer, yielding an effective crust-mantle boundary at >15 km depth. The difference in structure between proximal and distal islands might be related to the age of the plate at the

  17. Fine-scale differences in diel activity among nocturnal freshwater planarias (Platyhelminthes: Tricladida

    Cicolani Bruno

    2011-04-01

    , consistent with their photonegative characteristics. The fine-scale differences in diel behavior among these three triclad species may not be sufficient to allow coexistence in the wild, with the nonnative D. tigrina eventually displacing D. polychroa and P. tenuis in many European waters. The link between planarian diel rhythms and ecological characteristics are worth of further, detailed investigation.

  18. Fine-scale structure of the mid-mantle characterised by global stacks of PP precursors

    Bentham, H. L. M.; Rost, S.; Thorne, M. S.

    2017-08-01

    Subduction zones are likely a major source of compositional heterogeneities in the mantle, which may preserve a record of the subduction history and mantle convection processes. The fine-scale structure associated with mantle heterogeneities can be studied using the scattered seismic wavefield that arrives as coda to or as energy preceding many body wave arrivals. In this study we analyse precursors to PP by creating stacks recorded at globally distributed stations. We create stacks aligned on the PP arrival in 5° distance bins (with range 70-120°) from 600 earthquakes recorded at 193 stations stacking a total of 7320 seismic records. As the energy trailing the direct P arrival, the P coda, interferes with the PP precursors, we suppress the P coda by subtracting a best fitting exponential curve to this energy. The resultant stacks show that PP precursors related to scattering from heterogeneities in the mantle are present for all distances. Lateral variations are explored by producing two regional stacks across the Atlantic and Pacific hemispheres, but we find only negligible differences in the precursory signature between these two regions. The similarity of these two regions suggests that well mixed subducted material can survive at upper and mid-mantle depth. To describe the scattered wavefield in the mantle, we compare the global stacks to synthetic seismograms generated using a Monte Carlo phonon scattering technique. We propose a best-fitting layered heterogeneity model, BRT2017, characterised by a three layer mantle with a background heterogeneity strength (ɛ = 0.8%) and a depth-interval of increased heterogeneity strength (ɛ = 1%) between 1000 km and 1800 km. The scalelength of heterogeneity is found to be 8 km throughout the mantle. Since mantle heterogeneity of 8 km scale may be linked to subducted oceanic crust, the detection of increased heterogeneity at mid-mantle depths could be associated with stalled slabs due to increases in viscosity

  19. Inferences of Recent and Ancient Human Population History Using Genetic and Non-Genetic Data

    Kitchen, Andrew

    2008-01-01

    I have adopted complementary approaches to inferring human demographic history utilizing human and non-human genetic data as well as cultural data. These complementary approaches form an interdisciplinary perspective that allows one to make inferences of human history at varying timescales, from the events that occurred tens of thousands of years…

  20. Seeking perfection: a Kantian look at human genetic engineering.

    Gunderson, Martin

    2007-01-01

    It is tempting to argue that Kantian moral philosophy justifies prohibiting both human germ-line genetic engineering and non-therapeutic genetic engineering because they fail to respect human dignity. There are, however, good reasons for resisting this temptation. In fact, Kant's moral philosophy provides reasons that support genetic engineering-even germ-line and non-therapeutic. This is true of Kant's imperfect duties to seek one's own perfection and the happiness of others. It is also true of the categorical imperative. Kant's moral philosophy does, however, provide limits to justifiable genetic engineering.

  1. Genetic contributions to human brain morphology and intelligence

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...

  2. Egyptian Journal of Medical Human Genetics

    ... and genetic counseling as well as advances in prevention and treatment of genetic disorders. ... Clinical application of genomics and next generation sequencing ... vectors and SIN channels further relieves the limitations of gene therapy ... 3 gene in Malaysian subjects with neovascular age-related macular degeneration ...

  3. Host genetic variation impacts microbiome composition across human body sites.

    Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

    2015-09-15

    The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

  4. Demonstrating the Uneven Importance of Fine-Scale Forest Structure on Snow Distributions using High Resolution Modeling

    Broxton, P. D.; Harpold, A. A.; van Leeuwen, W.; Biederman, J. A.

    2016-12-01

    Quantifying the amount of snow in forested mountainous environments, as well as how it may change due to warming and forest disturbance, is critical given its importance for water supply and ecosystem health. Forest canopies affect snow accumulation and ablation in ways that are difficult to observe and model. Furthermore, fine-scale forest structure can accentuate or diminish the effects of forest-snow interactions. Despite decades of research demonstrating the importance of fine-scale forest structure (e.g. canopy edges and gaps) on snow, we still lack a comprehensive understanding of where and when forest structure has the largest impact on snowpack mass and energy budgets. Here, we use a hyper-resolution (1 meter spatial resolution) mass and energy balance snow model called the Snow Physics and Laser Mapping (SnowPALM) model along with LIDAR-derived forest structure to determine where spatial variability of fine-scale forest structure has the largest influence on large scale mass and energy budgets. SnowPALM was set up and calibrated at sites representing diverse climates in New Mexico, Arizona, and California. Then, we compared simulations at different model resolutions (i.e. 1, 10, and 100 m) to elucidate the effects of including versus not including information about fine scale canopy structure. These experiments were repeated for different prescribed topographies (i.e. flat, 30% slope north, and south-facing) at each site. Higher resolution simulations had more snow at lower canopy cover, with the opposite being true at high canopy cover. Furthermore, there is considerable scatter, indicating that different canopy arrangements can lead to different amounts of snow, even when the overall canopy coverage is the same. This modeling is contributing to the development of a high resolution machine learning algorithm called the Snow Water Artificial Network (SWANN) model to generate predictions of snow distributions over much larger domains, which has implications

  5. Fetal magnetic resonance imaging and human genetics

    Hengstschlaeger, Markus

    2006-01-01

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data

  6. Fetal magnetic resonance imaging and human genetics

    Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at

    2006-02-15

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.

  7. Insights into the genetic foundations of human communication.

    Graham, Sarah A; Deriziotis, Pelagia; Fisher, Simon E

    2015-03-01

    The human capacity to acquire sophisticated language is unmatched in the animal kingdom. Despite the discontinuity in communicative abilities between humans and other primates, language is built on ancient genetic foundations, which are being illuminated by comparative genomics. The genetic architecture of the language faculty is also being uncovered by research into neurodevelopmental disorders that disrupt the normally effortless process of language acquisition. In this article, we discuss the strategies that researchers are using to reveal genetic factors contributing to communicative abilities, and review progress in identifying the relevant genes and genetic variants. The first gene directly implicated in a speech and language disorder was FOXP2. Using this gene as a case study, we illustrate how evidence from genetics, molecular cell biology, animal models and human neuroimaging has converged to build a picture of the role of FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge the gaps between genes, brains and behavior.

  8. Genetic testing and its implications: human genetics researchers grapple with ethical issues.

    Rabino, Isaac

    2003-01-01

    To better understand ethical issues involved in the field of human genetics and promote debate within the scientific community, the author surveyed scientists who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. This study contributes systematic data on attitudes of scientific experts. The survey finds respondents are highly supportive of voluntary testing and the right to know one's genetic heritage. The majority consider in utero testing and consequent pregnancy termination acceptable for cases involving likelihood of serious disease but disapprove for genetic reasons they consider arbitrary, leaving a gray area of distinguishing between treatment of disorders and enhancement still to be resolved. While safeguarding patient confidentiality versus protecting at-risk third parties (kin, reproductive partners) presents a dilemma, preserving privacy from misuse by institutional third parties (employers, insurers) garners strong consensus for legislation against discrimination. Finally, a call is made for greater genetic literacy.

  9. Human Genetics. Informational and Educational Materials, Vol. I, No. 1.

    National Clearinghouse for Human Genetic Diseases (DHEW/PHS), Rockville, MD.

    This catalogue, prepared by the National Clearinghouse for Human Genetic Diseases, provides educational and informational materials on the latest advances in testing, diagnosing, counseling, and treating individuals with a concern for genetic diseases. The materials include books, brochures, pamphlets, journal articles, audio cassettes,…

  10. Human genetics in Johannesburg, South Africa: Past, present and ...

    Genetic screening was then initiated for the Jewish community because of their high carrier rate for Tay-Sachs disease. Educational courses in human genetics were offered at Wits Medical School, and medical as well as other health professionals began to be trained. Research, supported by national and international ...

  11. Darkness in El Dorado: human genetics on trial

    Unknown

    Human Genetics Research Division, University of Southampton, Southampton SO16 6YD, UK. A recent ..... advice' he acknowledges in his book (p. xviii), leading to revision .... Venezuelan government, held his team back from giving medical ...

  12. Genetic and environmental factors in experimental and human cancer

    Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.

    1980-01-01

    Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.

  13. Fine-Scale Bacterial Beta Diversity within a Complex Ecosystem (Zodletone Spring, OK, USA): The Role of the Rare Biosphere

    Youssef, Noha H.; Couger, M. B.; Elshahed, Mostafa S.

    2010-01-01

    Background The adaptation of pyrosequencing technologies for use in culture-independent diversity surveys allowed for deeper sampling of ecosystems of interest. One extremely well suited area of interest for pyrosequencing-based diversity surveys that has received surprisingly little attention so far, is examining fine scale (e.g. micrometer to millimeter) beta diversity in complex microbial ecosystems. Methodology/Principal Findings We examined the patterns of fine scale Beta diversity in four adjacent sediment samples (1mm apart) from the source of an anaerobic sulfide and sulfur rich spring (Zodletone spring) in southwestern Oklahoma, USA. Using pyrosequencing, a total of 292,130 16S rRNA gene sequences were obtained. The beta diversity patterns within the four datasets were examined using various qualitative and quantitative similarity indices. Low levels of Beta diversity (high similarity indices) were observed between the four samples at the phylum-level. However, at a putative species (OTU0.03) level, higher levels of beta diversity (lower similarity indices) were observed. Further examination of beta diversity patterns within dominant and rare members of the community indicated that at the putative species level, beta diversity is much higher within rare members of the community. Finally, sub-classification of rare members of Zodletone spring community based on patterns of novelty and uniqueness, and further examination of fine scale beta diversity of each of these subgroups indicated that members of the community that are unique, but non novel showed the highest beta diversity within these subgroups of the rare biosphere. Conclusions/Significance The results demonstrate the occurrence of high inter-sample diversity within seemingly identical samples from a complex habitat. We reason that such unexpected diversity should be taken into consideration when exploring gamma diversity of various ecosystems, as well as planning for sequencing-intensive metagenomic

  14. New Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) Scheme for Fine-Scale Monitoring and Microevolution-Related Study of Ralstonia pseudosolanacearum Phylotype I Populations

    Guinard, Jérémy; Latreille, Anne; Guérin, Fabien; Poussier, Stéphane

    2016-01-01

    ABSTRACT Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) is considered one of the most harmful plant diseases in the world. Special attention should be paid to R. pseudosolanacearum phylotype I due to its large host range, its worldwide distribution, and its high evolutionary potential. So far, the molecular epidemiology and population genetics of this bacterium are poorly understood. Until now, the genetic structure of the RSSC has been analyzed on the worldwide and regional scales. Emerging questions regarding evolutionary forces in RSSC adaptation to hosts now require genetic markers that are able to monitor RSSC field populations. In this study, we aimed to evaluate the multilocus variable-number tandem-repeat analysis (MLVA) approach for its ability to discriminate genetically close phylotype I strains and for population genetics studies. We developed a new MLVA scheme (MLVA-7) allowing us to genotype 580 R. pseudosolanacearum phylotype I strains extracted from susceptible and resistant hosts and from different habitats (stem, soil, and rhizosphere). Based on specificity, polymorphism, and the amplification success rate, we selected seven fast-evolving variable-number tandem-repeat (VNTR) markers. The newly developed MLVA-7 scheme showed higher discriminatory power than the previously published MLVA-13 scheme when applied to collections sampled from the same location on different dates and to collections from different locations on very small scales. Our study provides a valuable tool for fine-scale monitoring and microevolution-related study of R. pseudosolanacearum phylotype I populations. IMPORTANCE Understanding the evolutionary dynamics of adaptation of plant pathogens to new hosts or ecological niches has become a key point for the development of innovative disease management strategies, including durable resistance. Whereas the molecular mechanisms underlying virulence or pathogenicity changes have been studied thoroughly, the

  15. Genetic Expeditions with Haploid Human Cells

    Jae, L.T.

    2015-01-01

    Random mutagenesis followed by phenotypic selection (forward genetics) is among the most powerful tools to elucidate the molecular basis of intricate biological processes and has been used in a suite of model organisms throughout the last century. However, its application to cultured mammalian cells

  16. Genetic effects on gene expression across human tissues

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

    2017-01-01

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

  17. Fine scale mapping of genomic introgressions within the Drosophila yakuba clade.

    Turissini, David A; Matute, Daniel R

    2017-09-01

    The process of speciation involves populations diverging over time until they are genetically and reproductively isolated. Hybridization between nascent species was long thought to directly oppose speciation. However, the amount of interspecific genetic exchange (introgression) mediated by hybridization remains largely unknown, although recent progress in genome sequencing has made measuring introgression more tractable. A natural place to look for individuals with admixed ancestry (indicative of introgression) is in regions where species co-occur. In west Africa, D. santomea and D. yakuba hybridize on the island of São Tomé, while D. yakuba and D. teissieri hybridize on the nearby island of Bioko. In this report, we quantify the genomic extent of introgression between the three species of the Drosophila yakuba clade (D. yakuba, D. santomea), D. teissieri). We sequenced the genomes of 86 individuals from all three species. We also developed and applied a new statistical framework, using a hidden Markov approach, to identify introgression. We found that introgression has occurred between both species pairs but most introgressed segments are small (on the order of a few kilobases). After ruling out the retention of ancestral polymorphism as an explanation for these similar regions, we find that the sizes of introgressed haplotypes indicate that genetic exchange is not recent (>1,000 generations ago). We additionally show that in both cases, introgression was rarer on X chromosomes than on autosomes which is consistent with sex chromosomes playing a large role in reproductive isolation. Even though the two species pairs have stable contemporary hybrid zones, providing the opportunity for ongoing gene flow, our results indicate that genetic exchange between these species is currently rare.

  18. Human genome and genetic sequencing research and informed consent

    Iwakawa, Mayumi

    2003-01-01

    On March 29, 2001, the Ethical Guidelines for Human Genome and Genetic Sequencing Research were established. They have intended to serve as ethical guidelines for all human genome and genetic sequencing research practice, for the purpose of upholding respect for human dignity and rights and enforcing use of proper methods in the pursuit of human genome and genetic sequencing research, with the understanding and cooperation of the public. The RadGenomics Project has prepared a research protocol and informed consent document that follow these ethical guidelines. We have endeavored to protect the privacy of individual information, and have established a procedure for examination of research practices by an ethics committee. Here we report our procedure in order to offer this concept to the patients. (authors)

  19. Incorporating fine-scale drought information into an eastern US wildfire hazard model

    Matthew P. Peters; Louis R. Iverson

    2017-01-01

    Wildfires in the eastern United States are generally caused by humans in locations where human development and natural vegetation intermingle, e.g. the wildland–urban interface (WUI). Knowing where wildfire hazards are elevated across the forested landscape may help land managers and property owners plan or allocate resources for potential wildfire threats. In an...

  20. Fine-scale ecological and economic assessment of climate change on olive in the Mediterranean Basin reveals winners and losers.

    Ponti, Luigi; Gutierrez, Andrew Paul; Ruti, Paolo Michele; Dell'Aquila, Alessandro

    2014-04-15

    The Mediterranean Basin is a climate and biodiversity hot spot, and climate change threatens agro-ecosystems such as olive, an ancient drought-tolerant crop of considerable ecological and socioeconomic importance. Climate change will impact the interactions of olive and the obligate olive fruit fly (Bactrocera oleae), and alter the economics of olive culture across the Basin. We estimate the effects of climate change on the dynamics and interaction of olive and the fly using physiologically based demographic models in a geographic information system context as driven by daily climate change scenario weather. A regional climate model that includes fine-scale representation of the effects of topography and the influence of the Mediterranean Sea on regional climate was used to scale the global climate data. The system model for olive/olive fly was used as the production function in our economic analysis, replacing the commonly used production-damage control function. Climate warming will affect olive yield and fly infestation levels across the Basin, resulting in economic winners and losers at the local and regional scales. At the local scale, profitability of small olive farms in many marginal areas of Europe and elsewhere in the Basin will decrease, leading to increased abandonment. These marginal farms are critical to conserving soil, maintaining biodiversity, and reducing fire risk in these areas. Our fine-scale bioeconomic approach provides a realistic prototype for assessing climate change impacts in other Mediterranean agro-ecosystems facing extant and new invasive pests.

  1. Landscape management of fire and grazing regimes alters the fine-scale habitat utilisation by feral cats.

    McGregor, Hugh W; Legge, Sarah; Jones, Menna E; Johnson, Christopher N

    2014-01-01

    Intensification of fires and grazing by large herbivores has caused population declines in small vertebrates in many ecosystems worldwide. Impacts are rarely direct, and usually appear driven via indirect pathways, such as changes to predator-prey dynamics. Fire events and grazing may improve habitat and/or hunting success for the predators of small mammals, however, such impacts have not been documented. To test for such an interaction, we investigated fine-scale habitat selection by feral cats in relation to fire, grazing and small-mammal abundance. Our study was conducted in north-western Australia, where small mammal populations are sensitive to changes in fire and grazing management. We deployed GPS collars on 32 cats in landscapes with contrasting fire and grazing treatments. Fine-scale habitat selection was determined using discrete choice modelling of cat movements. We found that cats selected areas with open grass cover, including heavily-grazed areas. They strongly selected for areas recently burnt by intense fires, but only in habitats that typically support high abundance of small mammals. Intense fires and grazing by introduced herbivores created conditions that are favoured by cats, probably because their hunting success is improved. This mechanism could explain why, in northern Australia, impacts of feral cats on small mammals might have increased. Our results suggest the impact of feral cats could be reduced in most ecosystems by maximising grass cover, minimising the incidence of intense fires, and reducing grazing by large herbivores.

  2. Landscape management of fire and grazing regimes alters the fine-scale habitat utilisation by feral cats.

    Hugh W McGregor

    Full Text Available Intensification of fires and grazing by large herbivores has caused population declines in small vertebrates in many ecosystems worldwide. Impacts are rarely direct, and usually appear driven via indirect pathways, such as changes to predator-prey dynamics. Fire events and grazing may improve habitat and/or hunting success for the predators of small mammals, however, such impacts have not been documented. To test for such an interaction, we investigated fine-scale habitat selection by feral cats in relation to fire, grazing and small-mammal abundance. Our study was conducted in north-western Australia, where small mammal populations are sensitive to changes in fire and grazing management. We deployed GPS collars on 32 cats in landscapes with contrasting fire and grazing treatments. Fine-scale habitat selection was determined using discrete choice modelling of cat movements. We found that cats selected areas with open grass cover, including heavily-grazed areas. They strongly selected for areas recently burnt by intense fires, but only in habitats that typically support high abundance of small mammals. Intense fires and grazing by introduced herbivores created conditions that are favoured by cats, probably because their hunting success is improved. This mechanism could explain why, in northern Australia, impacts of feral cats on small mammals might have increased. Our results suggest the impact of feral cats could be reduced in most ecosystems by maximising grass cover, minimising the incidence of intense fires, and reducing grazing by large herbivores.

  3. Tracking fine-scale seasonal evolution of surface water extent in Central Alaska and the Canadian Shield

    Cooley, S. W.; Smith, L. C.; Pitcher, L. H.; Pavelsky, T.; Topp, S.

    2017-12-01

    Quantifying spatial and temporal variability in surface water storage at high latitudes is critical for assessing environmental sensitivity to climate change. Traditionally the tradeoff between high spatial and high temporal resolution space-borne optical imagery has limited the ability to track fine-scale changes in surface water extent. However, the recent launch of hundreds of earth-imaging CubeSats by commercial satellite companies such as Planet opens up new possibilities for monitoring surface water from space. In this study we present a comparison of seasonal evolution of surface water extent in two study areas with differing geologic, hydrologic and permafrost regimes, namely, the Yukon Flats in Central Alaska and the Canadian Shield north of Yellowknife, N.W.T. Using near-daily 3m Planet CubeSat imagery, we track individual lake surface area from break-up to freeze-up during summer 2017 and quantify the spatial and temporal variability in inundation extent. We validate our water delineation method and inundation extent time series using WorldView imagery, coincident in situ lake shoreline mapping and pressure transducer data for 19 lakes in the Northwest Territories and Alaska collected during the NASA Arctic Boreal Vulnerability Experiment (ABoVE) 2017 field campaign. The results of this analysis demonstrate the value of CubeSat imagery for dynamic surface water research particularly at high latitudes and illuminate fine-scale drivers of cold regions surface water extent.

  4. The influence of fine-scale habitat features on regional variation in population performance of alpine White-tailed Ptarmigan

    Fedy, B.; Martin, K.

    2011-01-01

    It is often assumed (explicitly or implicitly) that animals select habitat features to maximize fitness. However, there is often a mismatch between preferred habitats and indices of individual and population measures of performance. We examined the influence of fine-scale habitat selection on the overall population performance of the White-tailed Ptarmigan (Lagopus leucura), an alpine specialist, in two subdivided populations whose habitat patches are configured differently. The central region of Vancouver Island, Canada, has more continuous and larger habitat patches than the southern region. In 2003 and 2004, using paired logistic regression between used (n = 176) and available (n = 324) sites, we identified food availability, distance to standing water, and predator cover as preferred habitat components . We then quantified variation in population performance in the two regions in terms of sex ratio, age structure (n = 182 adults and yearlings), and reproductive success (n = 98 females) on the basis of 8 years of data (1995-1999, 2002-2004). Region strongly influenced females' breeding success, which, unsuccessful hens included, was consistently higher in the central region (n = 77 females) of the island than in the south (n = 21 females, P = 0.01). The central region also had a much higher proportion of successful hens (87%) than did the south (55%, P < 0.001). In light of our findings, we suggest that population performance is influenced by a combination of fine-scale habitat features and coarse-scale habitat configuration. ?? The Cooper Ornithological Society 2011.

  5. Human genetics of infectious diseases: a unified theory

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

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

  6. Human genetics of diabetic vascular complications

    Abstract. Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the ..... cohort with nominal significance, and a recent meta-analysis ..... Whereas it is generally thought that lysine acetylation is.

  7. Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

    Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E

    1998-01-01

    The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

  8. Primer on molecular genetics. DOE Human Genome Program

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  9. DNA fingerprinting and new tools for fine-scale discrimination of Arabidopsis thaliana accessions.

    Simon, Matthieu; Simon, Adeline; Martins, Fréderic; Botran, Lucy; Tisné, Sébastien; Granier, Fabienne; Loudet, Olivier; Camilleri, Christine

    2012-03-01

    One of the main strengths of Arabidopsis thaliana as a model species is the impressive number of public resources available to the scientific community. Exploring species genetic diversity--and therefore adaptation--relies on collections of individuals from natural populations taken from diverse environments. Nevertheless, due to a few mislabeling events or genotype mixtures, some variants available in stock centers have been misidentified, causing inconsistencies and limiting the potential of genetic analyses. To improve the identification of natural accessions, we genotyped 1311 seed stocks from our Versailles Arabidopsis Stock Center and from other collections to determine their molecular profiles at 341 single nucleotide polymorphism markers. These profiles were used to compare genotypes at both the intra- and inter-accession levels. We confirmed previously described inconsistencies and revealed new ones, and suggest likely identities for accessions whose lineage had been lost. We also developed two new tools: a minimal fingerprint computation to quickly verify the identity of an accession, and an optimized marker set to assist in the identification of unknown or mixed accessions. These tools are available on a dedicated web interface called ANATool (https://www.versailles.inra.fr/ijpb/crb/anatool) that provides a simple and efficient means to verify or determine the identity of A. thaliana accessions in any laboratory, without the need for any specific or expensive technology. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  10. Inauguration of the cameroonian society of human genetics.

    Wonkam, Ambroise; Kenfack, Marcel Azabji; Bigoga, Jude; Nkegoum, Blaise; Muna, Wali

    2009-10-20

    The conjunction of "hard genetics" research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009) was an excellent opportunity to get together in synergy the entire Cameroonian "DNA/RNA scientists" . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health". The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year's conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993). The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe). Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the "brain drain" to "brain circulation" that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was the creation of the National Human

  11. Urban landscape genomics identifies fine-scale gene flow patterns in an avian invasive.

    Low, G W; Chattopadhyay, B; Garg, K M; Irestedt, M; Ericson, Pgp; Yap, G; Tang, Q; Wu, S; Rheindt, F E

    2018-01-01

    Invasive species exert a serious impact on native fauna and flora and have been the target of many eradication and management efforts worldwide. However, a lack of data on population structure and history, exacerbated by the recency of many species introductions, limits the efficiency with which such species can be kept at bay. In this study we generated a novel genome of high assembly quality and genotyped 4735 genome-wide single nucleotide polymorphic (SNP) markers from 78 individuals of an invasive population of the Javan Myna Acridotheres javanicus across the island of Singapore. We inferred limited population subdivision at a micro-geographic level, a genetic patch size (~13-14 km) indicative of a pronounced dispersal ability, and barely an increase in effective population size since introduction despite an increase of four to five orders of magnitude in actual population size, suggesting that low population-genetic diversity following a bottleneck has not impeded establishment success. Landscape genomic analyses identified urban features, such as low-rise neighborhoods, that constitute pronounced barriers to gene flow. Based on our data, we consider an approach targeting the complete eradication of Javan Mynas across Singapore to be unfeasible. Instead, a mixed approach of localized mitigation measures taking into account urban geographic features and planning policy may be the most promising avenue to reducing the adverse impacts of this urban pest. Our study demonstrates how genomic methods can directly inform the management and control of invasive species, even in geographically limited datasets with high gene flow rates.

  12. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Abram, Nicola K; MacMillan, Douglas C; Xofis, Panteleimon; Ancrenaz, Marc; Tzanopoulos, Joseph; Ong, Robert; Goossens, Benoit; Koh, Lian Pin; Del Valle, Christian; Peter, Lucy; Morel, Alexandra C; Lackman, Isabelle; Chung, Robin; Kler, Harjinder; Ambu, Laurentius; Baya, William; Knight, Andrew T

    2016-01-01

    Reducing Emissions from Deforestation and forest Degradation (REDD+) aims to avoid forest conversion to alternative land-uses through financial incentives. Oil-palm has high opportunity costs, which according to current literature questions the financial competitiveness of REDD+ in tropical lowlands. To understand this more, we undertook regional fine-scale and coarse-scale analyses (through carbon mapping and economic modelling) to assess the financial viability of REDD+ in safeguarding unprotected forest (30,173 ha) in the Lower Kinabatangan floodplain in Malaysian Borneo. Results estimate 4.7 million metric tons of carbon (MgC) in unprotected forest, with 64% allocated for oil-palm cultivations. Through fine-scale mapping and carbon accounting, we demonstrated that REDD+ can outcompete oil-palm in regions with low suitability, with low carbon prices and low carbon stock. In areas with medium oil-palm suitability, REDD+ could outcompete oil palm in areas with: very high carbon and lower carbon price; medium carbon price and average carbon stock; or, low carbon stock and high carbon price. Areas with high oil palm suitability, REDD+ could only outcompete with higher carbon price and higher carbon stock. In the coarse-scale model, oil-palm outcompeted REDD+ in all cases. For the fine-scale models at the landscape level, low carbon offset prices (US $3 MgCO2e) would enable REDD+ to outcompete oil-palm in 55% of the unprotected forests requiring US $27 million to secure these areas for 25 years. Higher carbon offset price (US $30 MgCO2e) would increase the competitiveness of REDD+ within the landscape but would still only capture between 69%-74% of the unprotected forest, requiring US $380-416 million in carbon financing. REDD+ has been identified as a strategy to mitigate climate change by many countries (including Malaysia). Although REDD+ in certain scenarios cannot outcompete oil palm, this research contributes to the global REDD+ debate by: highlighting REDD

  13. Fine-scale hydrodynamics influence the spatio-temporal distribution of harbour porpoises at a coastal hotspot

    Jones, A. R.; Hosegood, P.; Wynn, R. B.; De Boer, M. N.; Butler-Cowdry, S.; Embling, C. B.

    2014-11-01

    The coastal Runnelstone Reef, off southwest Cornwall (UK), is characterised by complex topography and strong tidal flows and is a known high-density site for harbour porpoise (Phocoena phocoena); a European protected species. Using a multidisciplinary dataset including: porpoise sightings from a multi-year land-based survey, Acoustic Doppler Current Profiling (ADCP), vertical profiling of water properties and high-resolution bathymetry; we investigate how interactions between tidal flow and topography drive the fine-scale porpoise spatio-temporal distribution at the site. Porpoise sightings were distributed non-uniformly within the survey area with highest sighting density recorded in areas with steep slopes and moderate depths. Greater numbers of sightings were recorded during strong westward (ebbing) tidal flows compared to strong eastward (flooding) flows and slack water periods. ADCP and Conductivity Temperature Depth (CTD) data identified fine-scale hydrodynamic features, associated with cross-reef tidal flows in the sections of the survey area with the highest recorded densities of porpoises. We observed layered, vertically sheared flows that were susceptible to the generation of turbulence by shear instability. Additionally, the intense, oscillatory near surface currents led to hydraulically controlled flow that transitioned from subcritical to supercritical conditions; indicating that highly turbulent and energetic hydraulic jumps were generated along the eastern and western slopes of the reef. The depression and release of isopycnals in the lee of the reef during cross-reef flows revealed that the flow released lee waves during upslope currents at specific phases of the tidal cycle when the highest sighting rates were recorded. The results of this unique, fine-scale field study provide new insights into specific hydrodynamic features, produced through tidal forcing, that may be important for creating predictable foraging opportunities for porpoises at a

  14. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Nicola K Abram

    Full Text Available Reducing Emissions from Deforestation and forest Degradation (REDD+ aims to avoid forest conversion to alternative land-uses through financial incentives. Oil-palm has high opportunity costs, which according to current literature questions the financial competitiveness of REDD+ in tropical lowlands. To understand this more, we undertook regional fine-scale and coarse-scale analyses (through carbon mapping and economic modelling to assess the financial viability of REDD+ in safeguarding unprotected forest (30,173 ha in the Lower Kinabatangan floodplain in Malaysian Borneo. Results estimate 4.7 million metric tons of carbon (MgC in unprotected forest, with 64% allocated for oil-palm cultivations. Through fine-scale mapping and carbon accounting, we demonstrated that REDD+ can outcompete oil-palm in regions with low suitability, with low carbon prices and low carbon stock. In areas with medium oil-palm suitability, REDD+ could outcompete oil palm in areas with: very high carbon and lower carbon price; medium carbon price and average carbon stock; or, low carbon stock and high carbon price. Areas with high oil palm suitability, REDD+ could only outcompete with higher carbon price and higher carbon stock. In the coarse-scale model, oil-palm outcompeted REDD+ in all cases. For the fine-scale models at the landscape level, low carbon offset prices (US $3 MgCO2e would enable REDD+ to outcompete oil-palm in 55% of the unprotected forests requiring US $27 million to secure these areas for 25 years. Higher carbon offset price (US $30 MgCO2e would increase the competitiveness of REDD+ within the landscape but would still only capture between 69%-74% of the unprotected forest, requiring US $380-416 million in carbon financing. REDD+ has been identified as a strategy to mitigate climate change by many countries (including Malaysia. Although REDD+ in certain scenarios cannot outcompete oil palm, this research contributes to the global REDD+ debate by

  15. Human fertility, molecular genetics, and natural selection in modern societies.

    Felix C Tropf

    Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  16. Inauguration of the Cameroonian Society of Human Genetics

    Jude Bigoga

    2009-10-01

    Full Text Available The conjunction of “hard genetics” research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009 was an excellent opportunity to get together in synergy the entire Cameroonian “DNA/RNA scientists” . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health”. The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year’s conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993. The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe. Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the “brain drain” to “brain circulation” that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was

  17. Genetic variation in an individual human exome.

    Pauline C Ng

    2008-08-01

    Full Text Available There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's 'exome,' which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the approximately 12,500 variants that affect the protein coding portion of an individual's genome. We identified approximately 10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs in this individual, of which approximately 15-20% are rare in the human population. We predict approximately 1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the approximately 700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of approximately 12,500 nonsilent coding variants by approximately 8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation.

  18. Different differences: The use of ‘genetic ancestry’ versus race in biomedical human genetic research

    Fujimura, Joan H.; Rajagopalan, Ramya

    2011-01-01

    This article presents findings from our ethnographic research on biomedical scientists’ studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetics analysis. Their method allows them to operationalize their concept of ‘genetic ancestry’ without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software’s algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease. We introduce the concept of ‘genome geography’, to analyze how some researchers studying human genetic variation ‘locate’ stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Neverthless, we also highlight the slipperiness of genome geography and the

  19. Assessment of genetic risk for human exposure to radiation

    Sevcenko, V.A.; Rubanovic, A.V.

    2002-01-01

    Full text: The methodology of assessing the genetic risk of radiation exposure is based on the concept of 'hitting the target' in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the U N Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolation, integral and palpitation criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Based on the reports of UNSCEAR for the period from 1958 to 2001 the paper presents a retrospective analysis of the use of direct methods and the doubling dose method for quantitative determination of the genetic risk of human exposure expressed as different hereditary diseases. As early as 1962 UNSCEAR estimated the doubling dose (a dose causing as many mutations as those occurring spontaneously during one generation) at 1 Gy for cases of exposure to ionizing radiations with low LET at a low dose rate and this value was confirmed in the next UNSCEAR reports up to now. For cases of acute irradiation the doubling dose was estimated at 0,3-0,4 Gy for the period under review. The paper considers the evolution of the concepts of human natural hereditary variability which is a basis for assessing the risk of exposure by the doubling dose method. The level of human natural genetic variability per 1 000 000 newborns is estimated at 738 000 hereditary diseases including mendelian, chromosomal and multifactorial ones. The greatest difficulties in assessing the doubling dose value were found to occur in the case of multifactorial diseases the pheno typical expression of which depends on mutational events in polygenic systems and on numerous environmental factors. The introduction in calculations of the potential recoverability correction factor (RPCF) made it possible to assess the genetic risk taking into account this class of

  20. Fine-scale patterns of vegetation assembly in the monitoring of changes in coastal sand-dune landscapes

    J. Honrado

    2010-02-01

    Full Text Available Understanding dune ecosystem responses to multi-scale environmental changes can provide the framework for reliable forecasts and cost-efficient protocols for detecting shifts in prevailing coastal dynamics. Based on the hypothesis that stress and disturbance interact as primary community controls in coastal dunes, we studied the fine-scale floristic assembly of foredune vegetation, in its relation to topography, along regional and local environmental gradients in the 200 km long coastline of northern Portugal, encompassing a major biogeographic transition in western Europe. Thirty topographic profiles perpendicular to the shoreline were recorded at ten sites along the regional climate gradient, and vegetation was sampled by recording the frequency of plant species along those profiles. Quantitative topographic attributes of vegetated dune profiles (e.g. length or height exhibited wide variations relatable to differences in prevailing coastal dynamics. Metrics of taxonomic diversity (e.g. total species richness and its additive beta component and of the functional composition of vegetation were highly correlated to attributes of dune topography. Under transgressive dynamics, vegetation profiles have fewer species, increased dominance, lower turnover rates, and lower total vegetation cover. These changes may drive a decrease in structural and functional diversity, with important consequences for resistance, resilience and other ecosystem properties. Moreover, differences in both vegetation assembly (in meta-stable dunes and response to increased disturbance (in eroding dunes between distinct biogeographic contexts highlight a possible decline in facilitation efficiency under extreme physical stress (i.e. under Mediterranean climate and support the significance of functional approaches in the study of local ecosystem responses to disturbance along regional gradients. Our results strongly suggest that assessing fine-scale community assembly can

  1. Seasonal variation in coastal marine habitat use by the European shag: Insights from fine scale habitat selection modeling and diet

    Michelot, Candice; Pinaud, David; Fortin, Matthieu; Maes, Philippe; Callard, Benjamin; Leicher, Marine; Barbraud, Christophe

    2017-07-01

    Studies of habitat selection by higher trophic level species are necessary for using top predator species as indicators of ecosystem functioning. However, contrary to terrestrial ecosystems, few habitat selection studies have been conducted at a fine scale for coastal marine top predator species, and fewer have coupled diet data with habitat selection modeling to highlight a link between prey selection and habitat use. The aim of this study was to characterize spatially and oceanographically, at a fine scale, the habitats used by the European Shag Phalacrocorax aristotelis in the Special Protection Area (SPA) of Houat-Hœdic in the Mor Braz Bay during its foraging activity. Habitat selection models were built using in situ observation data of foraging shags (transect sampling) and spatially explicit environmental data to characterize marine benthic habitats. Observations were first adjusted for detectability biases and shag abundance was subsequently spatialized. The influence of habitat variables on shag abundance was tested using Generalized Linear Models (GLMs). Diet data were finally confronted to habitat selection models. Results showed that European shags breeding in the Mor Braz Bay changed foraging habitats according to the season and to the different environmental and energetic constraints. The proportion of the main preys also varied seasonally. Rocky and coarse sand habitats were clearly preferred compared to fine or muddy sand habitats. Shags appeared to be more selective in their foraging habitats during the breeding period and the rearing of chicks, using essentially rocky areas close to the colony and consuming preferentially fish from the Labridae family and three other fish families in lower proportions. During the post-breeding period shags used a broader range of habitats and mainly consumed Gadidae. Thus, European shags seem to adjust their feeding strategy to minimize energetic costs, to avoid intra-specific competition and to maximize access

  2. Fine-scale mapping of vector habitats using very high resolution satellite imagery: a liver fluke case-study.

    De Roeck, Els; Van Coillie, Frieke; De Wulf, Robert; Soenen, Karen; Charlier, Johannes; Vercruysse, Jozef; Hantson, Wouter; Ducheyne, Els; Hendrickx, Guy

    2014-12-01

    The visualization of vector occurrence in space and time is an important aspect of studying vector-borne diseases. Detailed maps of possible vector habitats provide valuable information for the prediction of infection risk zones but are currently lacking for most parts of the world. Nonetheless, monitoring vector habitats from the finest scales up to farm level is of key importance to refine currently existing broad-scale infection risk models. Using Fasciola hepatica, a parasite liver fluke, as a case in point, this study illustrates the potential of very high resolution (VHR) optical satellite imagery to efficiently and semi-automatically detect detailed vector habitats. A WorldView2 satellite image capable of transmitted by freshwater snails. The vector thrives in small water bodies (SWBs), such as ponds, ditches and other humid areas consisting of open water, aquatic vegetation and/or inundated grass. These water bodies can be as small as a few m2 and are most often not present on existing land cover maps because of their small size. We present a classification procedure based on object-based image analysis (OBIA) that proved valuable to detect SWBs at a fine scale in an operational and semi-automated way. The classification results were compared to field and other reference data such as existing broad-scale maps and expert knowledge. Overall, the SWB detection accuracy reached up to 87%. The resulting fine-scale SWB map can be used as input for spatial distribution modelling of the liver fluke snail vector to enable development of improved infection risk mapping and management advice adapted to specific, local farm situations.

  3. The mobile genetic element Alu in the human genome

    Novick, G.E. [Florida International Univ., Miami, FL (United States); Batzer, M.A.; Deininger, P.L. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

    1996-01-01

    Genetic material has been traditionally envisioned as relatively static with the exception of occasional, often deleterious mutations. The sequence DNA-to-RNA-to-protein represented for many years the central dogma relating gene structure and function. Recently, the field of molecular genetics has provided revolutionary information on the dynamic role of repetitive elements in the function of the genetic material and the evolution of humans and other organisms. Alu sequences represent the largest family of short interspersed repetitive elements (SINEs) in humans, being present in an excess of 500,000 copies per haploid genome. Alu elements, as well as the other repetitive elements, were once considered to be useless. Today, the biology of Alu transposable elements is being widely examined in order to determine the molecular basis of a growing number of identified diseases and to provide new directions in genome mapping and biomedical research. 66 refs., 5 figs.

  4. Mapping genetic influences on the corticospinal motor system in humans

    Cheeran, B J; Ritter, C; Rothwell, J C

    2009-01-01

    of the contribution of single nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the corticospinal motor system is essential to the acquisition of fine manual motor skills which require a finely tuned coordination of activity in distal forelimb muscles. Here we review recent brain mapping......It is becoming increasingly clear that genetic variations account for a certain amount of variance in the acquisition and maintenance of different skills. Until now, several levels of genetic influences were examined, ranging from global heritability estimates down to the analysis...... studies that have begun to explore the influence of functional genetic variation as well as mutations on function and structure of the human corticospinal motor system, and also the clinical implications of these studies. Transcranial magnetic stimulation of the primary motor hand area revealed...

  5. Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.

    Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J

    2016-04-01

    Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. Copyright © 2016. Published by Elsevier Ltd.

  6. Articulated Human Motion Tracking Using Sequential Immune Genetic Algorithm

    Yi Li

    2013-01-01

    Full Text Available We formulate human motion tracking as a high-dimensional constrained optimization problem. A novel generative method is proposed for human motion tracking in the framework of evolutionary computation. The main contribution is that we introduce immune genetic algorithm (IGA for pose optimization in latent space of human motion. Firstly, we perform human motion analysis in the learnt latent space of human motion. As the latent space is low dimensional and contents the prior knowledge of human motion, it makes pose analysis more efficient and accurate. Then, in the search strategy, we apply IGA for pose optimization. Compared with genetic algorithm and other evolutionary methods, its main advantage is the ability to use the prior knowledge of human motion. We design an IGA-based method to estimate human pose from static images for initialization of motion tracking. And we propose a sequential IGA (S-IGA algorithm for motion tracking by incorporating the temporal continuity information into the traditional IGA. Experimental results on different videos of different motion types show that our IGA-based pose estimation method can be used for initialization of motion tracking. The S-IGA-based motion tracking method can achieve accurate and stable tracking of 3D human motion.

  7. Study of human genetic diversity : inferences on population origin and history

    Haber, Marc, 1980-

    2013-01-01

    Patterns of human genetic diversity suggest that all modern humans originated from a small population in Africa that expanded rapidly 50,000 years ago to occupy the whole world. While moving into new environments, genetic drift and natural selection affected populations differently, creating genetic structure. By understanding the genetic structure of human populations, we can reconstruct human history and understand the genetic basis of diseases. The work presented here contributes to the on...

  8. Improved genetic manipulation of human embryonic stem cells.

    Braam, S.R.; Denning, C.; van den Brink, S.; Kats, P.; Hochstenbach, R.; Passier, R.; Mummery, C.L.

    2008-01-01

    Low efficiency of transfection limits the ability to genetically manipulate human embryonic stem cells (hESCs), and differences in cell derivation and culture methods require optimization of transfection protocols. We transiently transferred multiple independent hESC lines with different growth

  9. Inauguration of the Cameroonian Society of Human Genetics ...

    CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health”. The AfSHG and CSHG invited leading African and international scientists in ...

  10. Somatic retrotransposition alters the genetic landscape of the human brain

    Baillie, J.K.; Barnett, M.W.; Upton, K.R.; Gerhardt, D.J.; Richmond, T.A.; De Sapio, F.; Brennan, P.; Rizzu, P.; Smith, S.; Fell, M.; Talbot, R.T.; Gustincich, S.; Freeman, T.C.; Mattick, J.S.; Hume, D.A.; Heutink, P.; Carninci, P.; Jeddeloh, J.A.; Faulkner, G.J.

    2011-01-01

    Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes1. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and

  11. Public Attitudes toward Human Genetic Manipulation: A Revitalization of Eugenics?

    Veglia, Geremia; And Others

    The purpose of this investigation was to measure the attitudes of college students across the United States concerning the possible use of genetic manipulation, especially in terms of enhancing human physical and intellectual characteristics. The instrument used was divided into three general areas of inquiry: the first, designed to measure the…

  12. Common genetic variants influence human subcortical brain structures

    Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias-Vasquez, A.; Desrivières, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Biks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.K.; Cuellar-Partida, G.; den Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santiañez, R.; Rose, E.J.; Salami, A.; Sämann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J.; van Eijk, K.R.; Walters, R.K.; Westlye, L.T.; Welan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.H.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.G.A.M.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.M.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.A.M.; Reese McKay, D.; Needham, M.; Nugent, A.C.; Pütz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; van der Marel, S.S.L.; van Hulzen, K.J.E.; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; de Zubicaray, G.I.; Dillman, A.; Duggirala, R.; Dyer, T.D.; Erk, S.; Fedko, I.O.; Ferrucci, L.; Foroud, T.M.; Fox, P.T.; Fukunaga, M.; Gibbs, J.R.; Göring, H.H.H.; Green, R.C.; Guelfi, S.; Hansell, N.K.; Hartman, C.A.; Hegenscheid, K.; Heinz, A.; Hernandez, D.G.; Heslenfeld, D.J.; Hoekstra, P.J.; Holsboer, F.; Homuth, G.; Hottenga, J.J.; Ikeda, M.; Jack, C.R., Jr.; Jenkinson, M.; Johnson, R.; Kanai, R.; Keil, M.; Kent, J.W. Jr.; Kochunov, P.; Kwok, J.B.; Lawrie, S.M.; Liu, X.; Longo, D.L.; McMahon, K.L.; Meisenzahl, E.; Melle, I.; Mohnke, S.; Montgomery, G.W.; Mostert, J.C.; Mühleisen, T.W.; Nalls, M.A.; Nichols, T.E.; Nilsson, L.G.; Nöthen, M.M.; Ohi, K.; Olvera, R.L.; Perez-Iglesias, R.; Pike, G.B.; Potkin, S.G.; Reinvang, I.; Reppermund, S.; Rietschel, M.; Romanczuk-Seiferth, N.; Rosen, G.D.; Rujescu, D.; Schnell, K.; Schofield, P.R.; Smith, C.; Steen, V.M.; Sussmann, J.E.; Thalamuthu, A.; Toga, A.W.; Traynor, B.J.; Troncoso, J.; Turner, J.A.; Valdés Hernández, M.C.; van t Ent, D.; van der Brug, M.; van der Wee, N.J.A.; van Tol, M.J.; Veltman, D.J.; Wassink, T.H.; Westmann, E.; Zielke, R.H.; Zonderman, A.B.; Ashbrook, D.G.; Hager, R.; Lu, L.; McMahon, F.J.; Morris, D.W.; Williams, R.W.; Brunner, H.G.; Buckner, R.L.; Buitelaar, J.K.; Cahn, W.; Calhoun, V.D.; Cavalleri, G.L.; Crespo-Facorro, B.; Dale, A.M.; Davies, G.E.; Delanty, N.; Depondt, C.; Djurovic, S.; Drevets, W.C.; Espeseth, T.; Gollub, R.L.; Ho, B.C.; Hoffmann, W.; Hosten, N.; Kahn, R.S.; Le Hellard, S.; Meyer-Lindenberg, A.; Müller-Myhsok, B.; Nauck, M.; Nyberg, L.; Pandolfo, M.; Penninx, B.W.J.H.; Roffman, J.L.; Sisodiya, SM; Smoller, J.W.; van Bokhoven, H.; van Haren, N.E.M.; Völzke, H.; Walter, H.; Weiner, M.W.; Wen, W.; White, T.; Agartz, I.; Andreassen, O.A.; Blangero, J.; Boomsma, D.I.; Brouwer, R.M.; Cannon, D.M.; Cookson, M.R.; de Geus, E.J.C.; Deary, I.J.; Donohoe, G.; Fernandez, G.; Fisher, S.E.; Francks, C.; Glahn, D.C.; Grabe, H.J.; Gruber, O.; Hardy, J.; Hashimoto, R.; Hulshoff Pol, H.E.; Jönsson, E.G.; Kloszewska, I.; Lovestone, S.; Mattay, V.S.; Mecocci, P.; McDonald, C.; McIntosh, A.M.; Ophoff, R.A.; Paus, T.; Pausova, Z.; Ryten, M.; Sachdev, P.S.; Saykin, A.J.; Simmons, A.; Singleton, A.; Soininen, H.; Wardlaw, J.M.; Weale, M.E.; Weinberger, D.R.; Adams, H.H.H.; Launer, L.J.; Seiler, S.; Schmidt, R.; Chauhan, G.; Satizabal, C.L.; Becker, J.T.; Yanek, L.; van der Lee, S.J.; Ebling, M.; Fischl, B.; Longstreth, Jr. W.T.; Greve, D.; Schmidt, H.; Nyquist, P.; Vinke, L.N.; van Duijn, C.M.; Xue, L.; Mazoyer, B.; Bis, J.C.; Gudnason, V.; Seshadri, S.; Arfan Ikram, M.; Martin, N.G.; Wright, M.J.; Schumann, G.; Franke, B.; Thompson, P.M.; Medland, S.E.

    2015-01-01

    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

  13. Common genetic variants influence human subcortical brain structures

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

    2015-01-01

    textabstractThe 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

  14. Common genetic variants influence human subcortical brain structures

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, 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.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, 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.; Puetz, 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; Goering, 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.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, 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.; Valdes Hernandez, 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; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-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.; Voelzke, 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; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, 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 influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To

  15. Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...

    The presence of human immunodeficiency virus (HIV) type-1 diversity has an impact on vaccine efficacy and drug resistance. It is important to know the circulating genetic variants and associated drug-resistance mutations in the context of scale up of antiretroviral therapy (ART) in Nigeria. The objective of this study was to ...

  16. Human life: genetic or social construction?

    Yudin, Boris

    2005-01-01

    I am going to discuss some present-day tendencies in the development of the very old debate on nature vs nurture. There is a widespread position describing the history of this debate as a pendulum-like process. Some three decades ago there was a time of overwhelming prevalence of the position stressing social factors in determining human character and behavior; now the pendulum has come to the opposite side and those who stress the role of biology, of genes are in favor. Yet in my view rather acute opposition of both positions still exists. Its existence depends not so much on new scientific discoveries as on some social and cultural factors which are more conservative than the development of science. More than that, we can even talk about competition of these two positions.

  17. MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

    Santa-Rita Pedro

    2005-06-01

    Full Text Available Abstract Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143 of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a breeds tend to display haplotypes belonging to different haplogroups; (b haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the

  18. Fine-scale variation in meiotic recombination in Mimulus inferred from population shotgun sequencing

    Hellsten, Uffe [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Wright, Kevin M. [Harvard Univ., Cambridge, MA (United States); Jenkins, Jerry [USDOE Joint Genome Inst., Walnut Creek, CA (United States); HudsonAlpha Inst. of Biotechnology, Huntsville, AL (United States); Shu, Shengqiang [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Yuan, Yao-Wu [Univ. of Connecticut, Storrs, CT (United States); Wessler, Susan R. [Univ. of California, Riverside, CA (United States); Schmutz, Jeremy [USDOE Joint Genome Inst., Walnut Creek, CA (United States); HudsonAlpha Inst. of Biotechnology, Huntsville, AL (United States); Willis, John H. [Duke Univ., Durham, NC (United States); Rokhsar, Daniel S. [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Univ. of California, Berkeley, CA (United States)

    2013-11-13

    Meiotic recombination rates can vary widely across genomes, with hotspots of intense activity interspersed among cold regions. In yeast, hotspots tend to occur in promoter regions of genes, whereas in humans and mice hotspots are largely defined by binding sites of the PRDM9 protein. To investigate the detailed recombination pattern in a flowering plant we use shotgun resequencing of a wild population of the monkeyflower Mimulus guttatus to precisely locate over 400,000 boundaries of historic crossovers or gene conversion tracts. Their distribution defines some 13,000 hotspots of varying strengths, interspersed with cold regions of undetectably low recombination. Average recombination rates peak near starts of genes and fall off sharply, exhibiting polarity. Within genes, recombination tracts are more likely to terminate in exons than in introns. The general pattern is similar to that observed in yeast, as well as in PRDM9-knockout mice, suggesting that recombination initiation described here in Mimulus may reflect ancient and conserved eukaryotic mechanisms

  19. The comparative radiation genetics of humans and mice

    Neel, J.V.

    1990-01-01

    The attempt by geneticists to predict the genetic consequences for humans of exposure to ionizing radiation has arguably been one of the most serious social responsibilities they have faced in the past half century. Important for its own sake, this issue also serves as a prototype for the effort to evaluate the ultimate genetic impact on ourselves of other human perturbations of the environment in which our species functions. Recently the authors have been developing the thesis that according to the results of studies on the children of survivors of the atomic bombings, humans may not be as sensitive to the genetic effects of radiation as has been projected by various committees on the basis of data from the most commonly employed paradigm, the laboratory mouse. In this paper, the authors attempt as detailed a comparison as space permits of the findings on humans and mice, presenting the data in a fashion that will enable those who at certain critical points in the argument wish to make other assumptions, to do so. The authors argue that a reconsideration that includes all the data now available on mice brings the estimate of the doubling dose for mice into satisfactory agreement with the higher estimate based on humans

  20. Resources for human genetics on the World Wide Web.

    Osborne, L R; Lee, J R; Scherer, S W

    1997-09-01

    A little over a century ago, the HMS Beagle sailed the Pacific Ocean bringing Charles Darwin to the perfect environment in which to piece together his observations forming the theory of evolution. Now, geneticists and laypeople alike surf the equally formidable waters of the internet in search of enlightenment. Here, we attempt to help you navigate towards resources for human genetics by providing maps to three destinations: The Human Genome Project (Box 1), education (Box 2), and human genetic diseases (Box 3). For each, we highlight a few sites that we consider are the most informative and original. A more extensive list containing other useful sites has been compiled and posted on a 'jump site' at: http:/(/)www.cgdn.generes.ca/.

  1. Fishing for space: fine-scale multi-sector maritime activities influence fisher location choice.

    Alex N Tidd

    Full Text Available The European Union and other states are moving towards Ecosystem Based Fisheries Management to balance food production and security with wider ecosystem concerns. Fishing is only one of several sectors operating within the ocean environment, competing for renewable and non-renewable resources that overlap in a limited space. Other sectors include marine mining, energy generation, recreation, transport and conservation. Trade-offs of these competing sectors are already part of the process but attempts to detail how the seas are being utilised have been primarily based on compilations of data on human activity at large spatial scales. Advances including satellite and shipping automatic tracking enable investigation of factors influencing fishers' choice of fishing grounds at spatial scales relevant to decision-making, including the presence or avoidance of activities by other sectors. We analyse the determinants of English and Welsh scallop-dredging fleet behaviour, including competing sectors, operating in the eastern English Channel. Results indicate aggregate mining activity, maritime traffic, increased fishing costs, and the English inshore 6 and French 12 nautical mile limits negatively impact fishers' likelihood of fishing in otherwise suitable areas. Past success, net-benefits and fishing within the 12 NM predispose fishers to use areas. Systematic conservation planning has yet to be widely applied in marine systems, and the dynamics of spatial overlap of fishing with other activities have not been studied at scales relevant to fisher decision-making. This study demonstrates fisher decision-making is indeed affected by the real-time presence of other sectors in an area, and therefore trade-offs which need to be accounted for in marine planning. As marine resource extraction demands intensify, governments will need to take a more proactive approach to resolving these trade-offs, and studies such as this will be required as the evidential

  2. Fishing for space: fine-scale multi-sector maritime activities influence fisher location choice.

    Tidd, Alex N; Vermard, Youen; Marchal, Paul; Pinnegar, John; Blanchard, Julia L; Milner-Gulland, E J

    2015-01-01

    The European Union and other states are moving towards Ecosystem Based Fisheries Management to balance food production and security with wider ecosystem concerns. Fishing is only one of several sectors operating within the ocean environment, competing for renewable and non-renewable resources that overlap in a limited space. Other sectors include marine mining, energy generation, recreation, transport and conservation. Trade-offs of these competing sectors are already part of the process but attempts to detail how the seas are being utilised have been primarily based on compilations of data on human activity at large spatial scales. Advances including satellite and shipping automatic tracking enable investigation of factors influencing fishers' choice of fishing grounds at spatial scales relevant to decision-making, including the presence or avoidance of activities by other sectors. We analyse the determinants of English and Welsh scallop-dredging fleet behaviour, including competing sectors, operating in the eastern English Channel. Results indicate aggregate mining activity, maritime traffic, increased fishing costs, and the English inshore 6 and French 12 nautical mile limits negatively impact fishers' likelihood of fishing in otherwise suitable areas. Past success, net-benefits and fishing within the 12 NM predispose fishers to use areas. Systematic conservation planning has yet to be widely applied in marine systems, and the dynamics of spatial overlap of fishing with other activities have not been studied at scales relevant to fisher decision-making. This study demonstrates fisher decision-making is indeed affected by the real-time presence of other sectors in an area, and therefore trade-offs which need to be accounted for in marine planning. As marine resource extraction demands intensify, governments will need to take a more proactive approach to resolving these trade-offs, and studies such as this will be required as the evidential foundation for future

  3. Genetical genomic determinants of alcohol consumption in rats and humans

    Mangion Jonathan

    2009-10-01

    Full Text Available Abstract Background We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs. Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results In the HXB/BXH recombinant inbred (RI rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume

  4. Swiss Federal Law on the Genetic Testing of Humans

    森, 芳周

    2009-01-01

    To add an article against the misuse of a reproductive technology and a genetic engineering, theSwiss Federal Constitution was revised in 1992 through an initiative in 1987. On the basis of thisarticle of the constitution, the Reproductive Medicine Act and the Stem Cell Research Act wereenacted in turns; then, the Federal Law on the Genetic Testing of Humans was enacted in October2004. This paper treats a process of the revision of the constitution in 1992 and the enactment of thelaw in 2004....

  5. Recent Demographic History and Present Fine-Scale Structure in the Northwest Atlantic Leatherback (Dermochelys coriacea) Turtle Population

    Molfetti, Érica; Torres Vilaça, Sibelle; Georges, Jean-Yves; Plot, Virginie; Delcroix, Eric; Le Scao, Rozen; Lavergne, Anne; Barrioz, Sébastien; dos Santos, Fabrício Rodrigues; de Thoisy, Benoît

    2013-01-01

    The leatherback turtle Dermochelys coriacea is the most widely distributed sea turtle species in the world. It exhibits complex life traits: female homing and migration, migrations of juveniles and males that remain poorly known, and a strong climatic influence on resources, breeding success and sex-ratio. It is consequently challenging to understand population dynamics. Leatherbacks are critically endangered, yet the group from the Northwest Atlantic is currently considered to be under lower risk than other populations while hosting some of the largest rookeries. Here, we investigated the genetic diversity and the demographic history of contrasted rookeries from this group, namely two large nesting populations in French Guiana, and a smaller one in the French West Indies. We used 10 microsatellite loci, of which four are newly isolated, and mitochondrial DNA sequences of the control region and cytochrome b. Both mitochondrial and nuclear markers revealed that the Northwest Atlantic stock of leatherbacks derives from a single ancestral origin, but show current genetic structuration at the scale of nesting sites, with the maintenance of migrants amongst rookeries. Low nuclear genetic diversities are related to founder effects that followed consequent bottlenecks during the late Pleistocene/Holocene. Most probably in response to climatic oscillations, with a possible influence of early human hunting, female effective population sizes collapsed from 2 million to 200. Evidence of founder effects and high numbers of migrants make it possible to reconsider the population dynamics of the species, formerly considered as a metapopulation model: we propose a more relaxed island model, which we expect to be a key element in the currently observed recovering of populations. Although these Northwest Atlantic rookeries should be considered as a single evolutionary unit, we stress that local conservation efforts remain necessary since each nesting site hosts part of the genetic

  6. Genetic evidence for a Paleolithic human population expansion in Africa

    Reich, David E.; Goldstein, David B.

    1998-01-01

    Human populations have undergone dramatic expansions in size, but other than the growth associated with agriculture, the dates and magnitudes of those expansions have never been resolved. Here, we introduce two new statistical tests for population expansion, which use variation at a number of unlinked genetic markers to study the demographic histories of natural populations. By analyzing genetic variation in various aboriginal populations from throughout the world, we show highly significant evidence for a major human population expansion in Africa, but no evidence of expansion outside of Africa. The inferred African expansion is estimated to have occurred between 49,000 and 640,000 years ago, certainly before the Neolithic expansions, and probably before the splitting of African and non-African populations. In showing a significant difference between African and non-African populations, our analysis supports the unique role of Africa in human evolutionary history, as has been suggested by most other genetic work. In addition, the missing signal in non-African populations may be the result of a population bottleneck associated with the emergence of these populations from Africa, as postulated in the “Out of Africa” model of modern human origins. PMID:9653150

  7. The human pain genetics database: an interview with Luda Diatchenko.

    Diatchenko, Luda

    2018-06-05

    Luda Diatchenko, MD, PhD is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia and Faculty of Dentistry at McGill University, Alan Edwards Centre for Research on Pain. She earned her MD and PhD in the field of molecular biology from the Russian State Medical University. She started her career in industry, she was a Leader of the RNA Expression Group at Clontech, Inc., and subsequently, Director of Gene Discovery at Attagene, Inc. During this time, she was actively involved in the development of several widely used and widely cited molecular tools for the analysis of gene expression and regulation. Her academic career started at 2000 in the Center for Neurosensory Disorders at University of North Carolina. Her research since then is focused on determining the cellular and molecular biological mechanisms by which functional genetic variations impact human pain perception and risk of development of chronic pain conditions, enabling new approaches to identify new drug targets, treatment responses to analgesics and diagnostic. Multiple collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms to animal models and ultimately to human clinical trials. In total, she has authored or co-authored over 120 peer-reviewed research papers in journals, ten book chapters and edited a book in human pain genetics. She is a member and an active officer of several national and international scientific societies, including the International Association for the Study of Pain and the American Pain Society.

  8. Identification of fine scale and landscape scale drivers of urban aboveground carbon stocks using high-resolution modeling and mapping.

    Mitchell, Matthew G E; Johansen, Kasper; Maron, Martine; McAlpine, Clive A; Wu, Dan; Rhodes, Jonathan R

    2018-05-01

    Urban areas are sources of land use change and CO 2 emissions that contribute to global climate change. Despite this, assessments of urban vegetation carbon stocks often fail to identify important landscape-scale drivers of variation in urban carbon, especially the potential effects of landscape structure variables at different spatial scales. We combined field measurements with Light Detection And Ranging (LiDAR) data to build high-resolution models of woody plant aboveground carbon across the urban portion of Brisbane, Australia, and then identified landscape scale drivers of these carbon stocks. First, we used LiDAR data to quantify the extent and vertical structure of vegetation across the city at high resolution (5×5m). Next, we paired this data with aboveground carbon measurements at 219 sites to create boosted regression tree models and map aboveground carbon across the city. We then used these maps to determine how spatial variation in land cover/land use and landscape structure affects these carbon stocks. Foliage densities above 5m height, tree canopy height, and the presence of ground openings had the strongest relationships with aboveground carbon. Using these fine-scale relationships, we estimate that 2.2±0.4 TgC are stored aboveground in the urban portion of Brisbane, with mean densities of 32.6±5.8MgCha -1 calculated across the entire urban land area, and 110.9±19.7MgCha -1 calculated within treed areas. Predicted carbon densities within treed areas showed strong positive relationships with the proportion of surrounding tree cover and how clumped that tree cover was at both 1km 2 and 1ha resolutions. Our models predict that even dense urban areas with low tree cover can have high carbon densities at fine scales. We conclude that actions and policies aimed at increasing urban carbon should focus on those areas where urban tree cover is most fragmented. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Effects of land use and fine-scale environmental heterogeneity on net ecosystem production over a temperate coniferous forest landscape

    Turner, David P.; Guzy, Michael; Lefsky, Michael A.; Tuyl, Steve van; Sun, Osbert; Law, Beverly E. [Oregon State Univ. Corvallis, OR (United States). Dept. of Forest Science; Daly, Chris [Oregon State Univ., Corvallis, OR (United States). Dept. of Geosciences

    2003-04-01

    In temperate coniferous forests, spatial variation in net ecosystem production (NEP) is often associated with variation in stand age and heterogeneity in environmental factors such as soil depth. However, coarse spatial resolution analyses used to evaluate the terrestrial contribution to global NEP do not generally incorporate these effects. In this study, a fine-scale (25 m grid) analysis of NEP over a 164-km{sup 2} area of productive coniferous forests in the Pacific Northwest region of the United States was made to evaluate the effects of including fine scale information in landscape-scale NEP assessments. The Enhanced Thematic Mapper (ETM+) sensor resolved five cover classes in the study area and further differentiated between young, mature and old-growth conifer stands. ETM+ was also used to map current leaf area index (LAI) based on an empirical relationship of observed LAI to spectral vegetation indices. A daily time step climatology, based on 18 years of meteorological observations, was distributed (1 km resolution) over the mountainous terrain of the study area using the DAYMET model. Estimates of carbon pools and flux associated with soil, litter, coarse woody debris and live trees were then generated by running a carbon cycle model (Biome-BGC) to a state that reflected the current successional status and LAI of each grid cell, as indicated by the remote sensing observations. Estimated annual NEP for 1997 over the complete study area averaged 230 g C m{sup 2}, with most of the area acting as a carbon sink. The area-wide NEP is strongly positive because of reduced harvesting in the last decade and the recovery of areas harvested between 1940 and 1990. The average value was greater than would be indicated if the entire area was assumed to be a mature conifer stand, as in a coarse-scale analysis. The mean NEP varied interannually by over a factor of two. This variation was 38% less than the interannual variation for a single point. The integration of process

  10. Effects of land use and fine-scale environmental heterogeneity on net ecosystem production over a temperate coniferous forest landscape

    Turner, David P.; Guzy, Michael; Lefsky, Michael A.; Tuyl, Steve van; Sun, Osbert; Law, Beverly E.; Daly, Chris

    2003-01-01

    In temperate coniferous forests, spatial variation in net ecosystem production (NEP) is often associated with variation in stand age and heterogeneity in environmental factors such as soil depth. However, coarse spatial resolution analyses used to evaluate the terrestrial contribution to global NEP do not generally incorporate these effects. In this study, a fine-scale (25 m grid) analysis of NEP over a 164-km 2 area of productive coniferous forests in the Pacific Northwest region of the United States was made to evaluate the effects of including fine scale information in landscape-scale NEP assessments. The Enhanced Thematic Mapper (ETM+) sensor resolved five cover classes in the study area and further differentiated between young, mature and old-growth conifer stands. ETM+ was also used to map current leaf area index (LAI) based on an empirical relationship of observed LAI to spectral vegetation indices. A daily time step climatology, based on 18 years of meteorological observations, was distributed (1 km resolution) over the mountainous terrain of the study area using the DAYMET model. Estimates of carbon pools and flux associated with soil, litter, coarse woody debris and live trees were then generated by running a carbon cycle model (Biome-BGC) to a state that reflected the current successional status and LAI of each grid cell, as indicated by the remote sensing observations. Estimated annual NEP for 1997 over the complete study area averaged 230 g C m 2 , with most of the area acting as a carbon sink. The area-wide NEP is strongly positive because of reduced harvesting in the last decade and the recovery of areas harvested between 1940 and 1990. The average value was greater than would be indicated if the entire area was assumed to be a mature conifer stand, as in a coarse-scale analysis. The mean NEP varied interannually by over a factor of two. This variation was 38% less than the interannual variation for a single point. The integration of process models

  11. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

    Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

    2014-04-08

    Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

  12. Common genetic variants influence human subcortical brain structures.

    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.

  13. The ethics of human genetic intervention: a postmodern perspective.

    Dyer, A R

    1997-03-01

    Gene therapy for a particular disease like Parkinson's involves ethical principles worked out for other diseases. The major ethical issues for gene therapy (and the corresponding ethical principles) are safety (nonmalfeasance), efficacy (beneficence), informed consent (autonomy), and allocation of resources (justice). Yet genetic engineering (germ-line interventions or interventions to enhance human potentialities) raises emotions and fears that might cause resistance to gene therapies. Looking at these technologies in a postmodern perspective helps one to appreciate the issues at stake in social and cultural change with a new technology such as gene therapy. While "modern" technology and ethics have focused on the autonomy of the individual, we are beginning to see a lessening of such emphasis on individualism and autonomy and more emphasis on the health of the population. Such a social change could cause technologies about which society may currently be cautious (such as human genetic interventions) to become more acceptable or even expected.

  14. Genetic engineering in nonhuman primates for human disease modeling.

    Sato, Kenya; Sasaki, Erika

    2018-02-01

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

  15. Genetic recombination between human and animal parasites creates novel strains of human pathogen.

    Wendy Gibson

    2015-03-01

    Full Text Available Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr responsible for sleeping sickness (Human African Trypanosomiasis, HAT in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.

  16. Genetic recombination between human and animal parasites creates novel strains of human pathogen.

    Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

    2015-03-01

    Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.

  17. Human genetics of infectious diseases: a unified theory

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

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

  18. Fine-scale habitat preference of green sturgeon (Acipenser medirostris) within three spawning locations in the Sacramento River, California

    Wyman, Megan T.; Thomas, Michael J.; McDonald, Richard R.; Hearn, Alexander R.; Battleson, Ryan D.; Chapman, Eric D.; Kinzel, Paul J.; Minear, J. Tobey; Mora, Ethan A.; Nelson, Jonathan M.; Pagel, Matthew D.; Klimley, A. Peter

    2018-01-01

    Vast sections of the Sacramento River have been listed as critical habitat by the National Marine Fisheries Service for green sturgeon spawning (Acipenser medirostris), yet spawning is known to occur at only a few specific locations. This study reveals the range of physical habitat variables selected by adult green sturgeon during their spawning period. We integrated fine-scale fish positions, physical habitat characteristics, discharge, bathymetry, and simulated velocity and depth using a 2-dimensional hydraulic model (FaSTMECH). The objective was to create habitat suitability curves for depth, velocity, and substrate type within three known spawning locations over two years. An overall cumulative habitat suitability score was calculated that averaged the depth, velocity, and substrate scores over all fish, sites, and years. A weighted usable area (WUA) index was calculated throughout the sampling periods for each of the three sites. Cumulative results indicate that the microhabitat characteristics most preferred by green sturgeon in these three spawning locations were velocities between 1.0-1.1 m/s, depths of 8-9 m, and gravel and sand substrate. This study provides guidance for those who may in the future want to increase spawning habitat for green sturgeon within the Sacramento River.

  19. Intraspecific differences in lipid content of calanoid copepods across fine-scale depth ranges within the photic layer.

    Margarita Zarubin

    Full Text Available Copepods are among the most abundant and diverse groups of mesozooplankton in the world's oceans. Each species has a certain depth range within which different individuals (of the same life stage and sex are found. Lipids are accumulated in many calanoid copepods for energy storage and reproduction. Lipid content in some species increases with depth, however studies so far focused mostly on temperate and high-latitude seasonal vertically migrating copepods and compared lipid contents among individuals either from coarse layers or between diapausing, deep-dwelling copepods and individuals found in the photic, near-surface layer. Here we examined whether lipid contents of individual calanoid copepods of the same species, life stage/sex differ between finer depth layers within the upper water column of subtropical and Arctic seas. A total of 6 calanoid species were collected from samples taken at precise depths within the photic layer in both cold eutrophic and warm oligotrophic environments using SCUBA diving, MOCNESS and Multinet. Measurements of lipid content were obtained from digitized photographs of the collected individuals. The results revealed significant differences in lipid content across depth differences as small as 12-15 meters for Mecynocera clausi C5 and Ctenocalanus vanus C5 (Red Sea, Clausocalanus furcatus males and two clausocalanid C5s (Mediterranean Sea, and Calanus glacialis C5 (Arctic. We suggest two possible explanations for the differences in lipid content with depth on such a fine scale: predator avoidance and buoyancy.

  20. Aviation Model: A Fine-Scale Numerical Weather Prediction System for Aviation Applications at the Hong Kong International Airport

    Wai-Kin Wong

    2013-01-01

    Full Text Available The Hong Kong Observatory (HKO is planning to implement a fine-resolution Numerical Weather Prediction (NWP model for supporting the aviation weather applications at the Hong Kong International Airport (HKIA. This new NWP model system, called Aviation Model (AVM, is configured at a horizontal grid spacing of 600 m and 200 m. It is based on the WRF-ARW (Advance Research WRF model that can have sufficient computation efficiency in order to produce hourly updated forecasts up to 9 hours ahead on a future high performance computer system with theoretical peak performance of around 10 TFLOPS. AVM will be nested inside the operational mesoscale NWP model of HKO with horizontal resolution of 2 km. In this paper, initial numerical experiment results in forecast of windshear events due to seabreeze and terrain effect are discussed. The simulation of sea-breeze-related windshear is quite successful, and the headwind change observed from flight data could be reproduced in the model forecast. Some impacts of physical processes on generating the fine-scale wind circulation and development of significant convection are illustrated. The paper also discusses the limitations in the current model setup and proposes methods for the future development of AVM.

  1. Fine-scale spatial distribution of orchid mycorrhizal fungi in the soil of host-rich grasslands.

    Voyron, Samuele; Ercole, Enrico; Ghignone, Stefano; Perotto, Silvia; Girlanda, Mariangela

    2017-02-01

    Mycorrhizal fungi are essential for the survival of orchid seedlings under natural conditions. The distribution of these fungi in soil can constrain the establishment and resulting spatial arrangement of orchids at the local scale, but the actual extent of occurrence and spatial patterns of orchid mycorrhizal (OrM) fungi in soil remain largely unknown. We addressed the fine-scale spatial distribution of OrM fungi in two orchid-rich Mediterranean grasslands by means of high-throughput sequencing of fungal ITS2 amplicons, obtained from soil samples collected either directly beneath or at a distance from adult Anacamptis morio and Ophrys sphegodes plants. Like ectomycorrhizal and arbuscular mycobionts, OrM fungi (tulasnelloid, ceratobasidioid, sebacinoid and pezizoid fungi) exhibited significant horizontal spatial autocorrelation in soil. However, OrM fungal read numbers did not correlate with distance from adult orchid plants, and several of these fungi were extremely sporadic or undetected even in the soil samples containing the orchid roots. Orchid mycorrhizal 'rhizoctonias' are commonly regarded as unspecialized saprotrophs. The sporadic occurrence of mycobionts of grassland orchids in host-rich stands questions the view of these mycorrhizal fungi as capable of sustained growth in soil. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  2. Resource selection models are useful in predicting fine-scale distributions of black-footed ferrets in prairie dog colonies

    Eads, David A.; Jachowski, David S.; Biggins, Dean E.; Livieri, Travis M.; Matchett, Marc R.; Millspaugh, Joshua J.

    2012-01-01

    Wildlife-habitat relationships are often conceptualized as resource selection functions (RSFs)—models increasingly used to estimate species distributions and prioritize habitat conservation. We evaluated the predictive capabilities of 2 black-footed ferret (Mustela nigripes) RSFs developed on a 452-ha colony of black-tailed prairie dogs (Cynomys ludovicianus) in the Conata Basin, South Dakota. We used the RSFs to project the relative probability of occurrence of ferrets throughout an adjacent 227-ha colony. We evaluated performance of the RSFs using ferret space use data collected via postbreeding spotlight surveys June–October 2005–2006. In home ranges and core areas, ferrets selected the predicted "very high" and "high" occurrence categories of both RSFs. Count metrics also suggested selection of these categories; for each model in each year, approximately 81% of ferret locations occurred in areas of very high or high predicted occurrence. These results suggest usefulness of the RSFs in estimating the distribution of ferrets throughout a black-tailed prairie dog colony. The RSFs provide a fine-scale habitat assessment for ferrets that can be used to prioritize releases of ferrets and habitat restoration for prairie dogs and ferrets. A method to quickly inventory the distribution of prairie dog burrow openings would greatly facilitate application of the RSFs.

  3. Fine-scale habitat use of reintroduced black-footed ferrets on prairie dog colonies in New Mexico

    Chipault, Jennifer G.; Biggins, Dean E.; Detling, James K.; Long, Dustin H.; Reich, Robin M.

    2012-01-01

    Black-footed ferrets (Mustela nigripes) are among the most endangered animals in North America. Reintroductions of captive-born ferrets onto prairie dog (Cynomys spp.) colonies are crucial to the conservation of the species. In September 2007, captive-born ferrets were released on a black-tailed prairie dog (Cynomys ludovicianus) colony at the Vermejo Park Ranch, New Mexico. Ferret kits experimentally released in areas of comparatively low and high prairie dog burrow densities were located via spotlight surveys. Some maturing ferret kits were subsequently translocated to areas of low and high burrow densities on nearby prairie dog colonies. For 2 months, fine-scale habitat use was quantified by mapping all burrow openings within a 30-m radius of each ferret location. Spatial statistics accounted for autocorrelation in the burrow densities in areas used by ferrets. It was hypothesized that ferrets would select areas of high burrow densities within colonies; however, burrow densities in areas used by ferrets were generally similar to the available burrow densities. Because ferrets used areas with burrow densities similar to densities available at the colony level and because of the potential energetic benefits for ferrets using areas with high burrow densities, releasing ferrets on colonies with high burrow densities might increase reintroduction success.

  4. Fine-scale acoustic telemetry reveals unexpected lake trout, Salvelinus namaycush, spawning habitats in northern Lake Huron, North America

    Binder, Thomas; Farha, Steve A.; Thompson, Henry T.; Holbrook, Christopher; Bergstedt, Roger A.; Riley, Stephen; Bronte, Charles R.; He, Ji; Krueger, Charles C.

    2018-01-01

    Previous studies of lake trout, Salvelinus namaycush, spawning habitat in the Laurentian Great Lakes have used time- and labour-intensive survey methods and have focused on areas with historic observations of spawning aggregations and on habitats prejudged by researchers to be suitable for spawning. As an alternative, we used fine-scale acoustic telemetry to locate, describe and compare lake trout spawning habitats. Adult lake trout were implanted with acoustic transmitters and tracked during five consecutive spawning seasons in a 19–27 km2 region of the Drummond Island Refuge, Lake Huron, using the VEMCO Positioning System. Acoustic telemetry revealed discrete areas of aggregation on at least five reefs in the study area, subsequently confirmed by divers to contain deposited eggs. Notably, several identified spawning sites would likely not have been discovered using traditional methods because either they were too small and obscure to stand out on a bathymetric map or because they did not conform to the conceptual model of spawning habitat held by many biologists. Our most unique observation was egg deposition in gravel and rubble substrates located at the base of and beneath overhanging edges of large boulders. Spawning sites typically comprised <10% of the reef area and were used consistently over the 5-year study. Evaluation of habitat selection from the perspective of fish behaviour through use of acoustic transmitters offers potential to expand current conceptual models of critical spawning habitat.

  5. Activity patterns and fine-scale resource partitioning in the gregarious Kihansi spray toad Nectophrynoides asperginis in captivity.

    Rija, Alfan A; Goboro, Ezekiel M; Mwamende, Kuruthumu A; Said, Abubakari; Kohi, Edward M; Hassan, Shombe N

    2014-01-01

    Understanding the behavior of species threatened with extinction is important for conservation planning and for solving problems facing species in captivity and the wild. We examined diurnal activity budgets and habitat use of the extinct in the wild Kihansi spray toad to provide insights into ongoing conservation initiatives for this species. Observations on eight target behaviors were made each morning and evening for 14 days, in two subpopulations at Kihansi and University of Dar es Salaam captive breeding centers. There were significantly more bouts of resting than calling, amplexing, hunting, walking, climbing, or feeding. There was no difference in mean time spent in each activity between the two subpopulations. The use of habitat was variable between age classes, subpopulations and sampling time. Young toads spent significantly more time resting at the top of vegetation and on walls while adults rested more on logs. Further, adults foraged more on the walls and vegetation in the morning and on the ground in the evening. Contrastingly, young toads foraged more on the ground in the morning and switched to elevated patches during evening. The similarity of the toads' behavior suggests that important biological traits are still maintained in captivity and retained across toad generations. Furthermore, temporal and spatial variations in the use of habitat structures between age groups suggest fine-scale resource partitioning to reduce competition in this gregarious species. These results highlight the importance of maintaining diverse habitat structures in captivity and are useful for planning species reintroduction and future restocking programs. © 2014 Wiley Periodicals, Inc.

  6. Fine-scale distribution of zooplankton is linked to phytoplankton species composition and abundance in a North Norwegian fjord system

    Norrbin, F.; Priou, P. D.; Varela, A. P.

    2016-02-01

    We studied the influence of dense layers of phytoplankton and aggregates on shaping the vertical distribution of zooplankton in a North Norwegian fjord using a Video Plankton Recorder (VPR). This instrument provided fine-scale vertical distribution (cm-m scale) of planktonic organisms as well as aggregates of marine snow in relation to environmental conditions. At the height - later stage of the spring phytoplankton bloom in May, the outer part of the fjord was dominated by Phaeocystis pouchetii, while diatoms (Chaetoceros spp.) were dominating in the innermost basin. Small copepods species like Pseudocalanus spp., Microsetella norvegica, and Oithona spp. prevailed over larger copepod species in the inner part of the fjord whereas the outer part was dominated by large copepods like Calanus finmarchicus. While the zooplankton where spread out over the water column during the early stage of the bloom, in May they were linked to the phytoplankton vertical distribution and in the winter situation they were found in deeper waters. Herbivorous zooplankton species were affected by phytoplankton species composition; C. finmarchicus and Pseudocalanus spp. avoided the dense layer of P. pouchetii while herbivorous zooplankton matched the distribution of the diatom-dominated bloom. Small, omnivorous copepod species like Microsetella sp., Oithona sp. and Pseudocalanus sp. were often associated with dense layers of snow aggregates. This distribution may provide a shelter from predators as well as a food source. Natural or anthropogenic-induced changes in phytoplankton composition and aggregate distribution may thus influence food-web interactions.

  7. Improving low-relief coastal LiDAR DEMs with hydro-conditioning of fine-scale and artificial drainages

    Thomas Richard Allen

    2015-11-01

    Full Text Available Improvements in Light Detection and Ranging (LiDAR technology and spatial analysis of high-resolution digital elevation models (DEMs have advanced the accuracy and diversity of applications for coastal hazards and natural resources management. This article presents a concise synthesis of LiDAR analysis for coastal flooding and management applications in low-relief coastal plains and a case study demonstration of a new, efficient drainage mapping algorithm. The impetus for these LiDAR applications follows historic flooding from Hurricane Floyd in 1999, after which the State of North Carolina and the Federal Emergency Management Agency undertook extensive LiDAR data acquisition and technological developments for high-resolution floodplain mapping. An efficient algorithm is outlined for hydro-conditioning bare earth LiDAR DEMs using available US Geological Survey National Hydrography Dataset canal and ditch vectors. The methodology is illustrated in Moyock, North Carolina, for refinement of hydro-conditioning by combines pre-existing bare earth DEMs with spatial analysis of LiDAR point clouds in segmented and buffered ditch and canal networks. The methodology produces improved maps of fine-scale drainage, reduced omission of areal flood inundation, and subwatershed delineations that typify heavily ditched and canalled drainage areas. These preliminary results illustrate the capability of the technique to improve the representation of ditches in DEMs as well as subsequent flow and inundation modeling that could spur further research on low-relief coastal LiDAR applications.

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

    Gaschignard, J; Scurr, E; Alcaïs, A

    2013-06-01

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

  9. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

    C. Zeng (Chenjie); Guo, X. (Xingyi); J. Long (Jirong); K.B. Kuchenbaecker (Karoline); A. Droit (Arnaud); K. Michailidou (Kyriaki); M. Ghoussaini (Maya); S. Kar (Siddhartha); Freeman, A. (Adam); J.L. Hopper (John); R.L. Milne (Roger); M.K. Bolla (Manjeet K.); Wang, Q. (Qin); J. Dennis (Joe); S. Agata (Simona); S. Ahmed (Shahana); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Antonenkova, N.N. (Natalia N.); A. Arason (Adalgeir); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); F. Bacot (Francois); D. Barrowdale (Daniel); Baynes, C. (Caroline); A. Beeghly-Fadiel (Alicia); J. Benítez (Javier); M. Bermisheva (Marina); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); J.S. Brand (Judith S.); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); A. Broeks (Annegien); T. Brüning (Thomas); B. Burwinkel (Barbara); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); T.A. Carpenter (Adrian); J. Chang-Claude (Jenny); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); C. Clarke (Christine); A. Cox (Angela); S.S. Cross (Simon); K. Czene (Kamila); M.B. Daly (Mary B.); M. de La Hoya (Miguel); K. De Leeneer (Kim); P. Devilee (Peter); O. Díez (Orland); S.M. Domchek (Susan); M. Doody (Michele); C.M. Dorfling (Cecilia); T. Dörk (Thilo); I. dos Santos Silva (Isabel); M. Dumont (Martine); M. Dwek (Miriam); Dworniczak, B. (Bernd); K.M. Egan (Kathleen); U. Eilber (Ursula); Z. Einbeigi (Zakaria); B. Ejlertsen (Bent); S.D. Ellis (Steve); D. Frost (Debra); F. Lalloo (Fiona); P.A. Fasching (Peter); J.D. Figueroa (Jonine); H. Flyger (Henrik); M. Friedlander (Michael); E. Friedman (Eitan); Gambino, G. (Gaetana); Gao, Y.-T. (Yu-Tang); J. Garber (Judy); M. García-Closas (Montserrat); P.A. Gehrig (Paola A.); F. Damiola (Francesca); F. Lesueur (Fabienne); S. Mazoyer (Sylvie); D. Stoppa-Lyonnet (Dominique); Giles, G.G. (Graham G.); A.K. Godwin (Andrew K.); D. Goldgar (David); A. González-Neira (Anna); M.H. Greene (Mark H.); P. Guénel (Pascal); L. Haeberle (Lothar); C.A. Haiman (Christopher A.); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); S. Hart (Stewart); J.M. Hartikainen (J.); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); F.B.L. Hogervorst (Frans); S. Verhoef; Hendricks, C.B. (Carolyn B.); P. Hillemanns (Peter); A. Hollestelle (Antoinette); P.J. Hulick (Peter); D. Hunter (David); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); Jaworska-Bieniek, K. (Katarzyna); U.B. Jensen; E.M. John (Esther); Joly Beauparlant, C. (Charles); M. Jones (Michael); M. Kabisch (Maria); D. Kang (Daehee); Karlan, B.Y. (Beth Y.); S. Kauppila (Saila); M. Kerin (Michael); S. Khan (Sofia); E.K. Khusnutdinova (Elza); J.A. Knight (Julia); I. Konstantopoulou (I.); P. Kraft (Peter); A. Kwong (Ava); Y. Laitman (Yael); Lambrechts, D. (Diether); C. Lazaro (Conxi); L. Le Marchand (Loic); C.N. Lee (Chuen); M.H. Lee (Min Hyuk); K.J. Lester (Kathryn); J. Li (Jingmei); A. Liljegren (Annelie); A. Lindblom (Annika); A. Lophatananon (Artitaya); J. Lubinski (Jan); P.L. Mai (Phuong); A. Mannermaa (Arto); S. Manoukian (Siranoush); S. Margolin (Sara); Marme, F. (Frederik); K. Matsuo (Keitaro); L. McGuffog (Lesley); A. Meindl (Alfons); F. Menegaux (Florence); M. Montagna (Marco); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); P. Newcomb (Polly); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); C. Olswold (Curtis); A. Osorio (Ana); L. Papi (Laura); T.-W. Park-Simon; Paulsson-Karlsson, Y. (Ylva); S.T.H. Peeters (Stephanie); B. Peissel (Bernard); P. Peterlongo (Paolo); J. Peto (Julian); G. Pfeiler (Georg); C. Phelan (Catherine); Presneau, N. (Nadege); P. Radice (Paolo); N. Rahman (Nazneen); S.J. Ramus (Susan); M.U. Rashid (Muhammad); G. Rennert (Gad); K. Rhiem (Kerstin); Rudolph, A. (Anja); R. Salani (Ritu); Sangrajrang, S. (Suleeporn); E.J. Sawyer (Elinor); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); M. Schoemaker (Minouk); P. Schürmann (Peter); C.M. Seynaeve (Caroline); C.-Y. Shen (Chen-Yang); M. Shrubsole (Martha); X.-O. Shu (Xiao-Ou); A.J. Sigurdson (Alice); C.F. Singer (Christian); S. Slager (Susan); Soucy, P. (Penny); M.C. Southey (Melissa); D. Steinemann (Doris); A.J. Swerdlow (Anthony ); C. Szabo (Csilla); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo (Soo-Hwang); M.B. Terry (Mary Beth); D.C. Tessier (Daniel C.); A. Teulé (A.); M. Thomassen (Mads); L. Tihomirova (Laima); M. Tischkowitz (Marc); A.E. Toland (Amanda); N. Tung (Nadine); C. Turnbull (Clare); A.M.W. van den Ouweland (Ans); E.J. van Rensburg (Elizabeth); ven den Berg, D. (David); J. Vijai (Joseph); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); A.S. Whittemore (Alice); R. Winqvist (Robert); Wong, T.Y. (Tien Y.); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); J-C. Yu (Jyh-Cherng); P.D.P. Pharoah (Paul); P. Hall (Per); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); J. Simard (Jacques); F.J. Couch (Fergus); A.C. Antoniou (Antonis C.); D.F. Easton (Douglas F.); W. Zheng (Wei)

    2016-01-01

    textabstractBackground: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more

  10. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    Vigorito, E.; Kuchenbaecker, K.B.; Beesley, J.; Adlard, J.; Agnarsson, B.A.; Andrulis, I.L.; Arun, B.K.; Barjhoux, L.; Belotti, M.; Benitez, J.; Berger, A.; Bojesen, A.; Bonanni, B.; Brewer, C.; Caldes, T.; Caligo, M.A.; Campbell, I.; Chan, S.B.; Claes, K.B.; Cohn, D.E.; Cook, J.; Daly, M.B.; Damiola, F.; Davidson, R.; Pauw, A. de; Delnatte, C.; Diez, O.; Domchek, S.M.; Dumont, M.; Durda, K.; Dworniczak, B.; Easton, D.F.; Eccles, D.; Edwinsdotter Ardnor, C.; Eeles, R.; Ejlertsen, B.; Ellis, S.; Evans, D.G.; Feliubadalo, L.; Fostira, F.; Foulkes, W.D.; Friedman, E.; Frost, D.; Gaddam, P.; Ganz, P.A.; Garber, J.; Garcia-Barberan, V.; Gauthier-Villars, M.; Gehrig, A.; Gerdes, A.M.; Giraud, S.; Godwin, A.K.; Goldgar, D.E.; Hake, C.R.; Hansen, T.V.; Healey, S.; Hodgson, S.; Hogervorst, F.B.; Houdayer, C.; Hulick, P.J.; Imyanitov, E.N.; Isaacs, C.; Izatt, L.; Izquierdo, A.; Jacobs, L; Jakubowska, A.; Janavicius, R.; Jaworska-Bieniek, K.; Jensen, U.B.; John, E.M.; Vijai, J.; Karlan, B.Y.; Kast, K.; Khan, S.; Kwong, A.; Laitman, Y.; Lester, J.; Lesueur, F.; Liljegren, A.; Lubinski, J.; Mai, P.L.; Manoukian, S.; Mazoyer, S.; Meindl, A.; Mensenkamp, A.R.; Montagna, M.; Nathanson, K.L.; Neuhausen, S.L.; Nevanlinna, H.; Niederacher, D.; Olah, E.; Olopade, O.I.; Ong, K.R.; Osorio, A.; Park, S.K.; Paulsson-Karlsson, Y.; Pedersen, I.S.; Peissel, B.; Peterlongo, P.; et al.,

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2

  11. Using fine-scale fuel measurements to assess wildland fuels, potential fire behavior and hazard mitigation treatments in the southeastern USA

    Ottmar, Roger D.; Blake, John I.; Crolly, William T.

    2012-01-01

    The inherent spatial and temporal heterogeneity of fuelbeds in forests of the southeastern United States may require fine scale fuel measurements for providing reliable fire hazard and fuel treatment effectiveness estimates. In a series of five papers, an intensive, fine scale fuel inventory from the Savanna River Site in the southeastern United States is used for building fuelbeds and mapping fire behavior potential, evaluating fuel treatment options for effectiveness, and providing a comparative analysis of landscape modeled fire behavior using three different data sources including the Fuel Characteristic Classification System, LANDFIRE, and the Southern Wildfire Risk Assessment. The research demonstrates that fine scale fuel measurements associated with fuel inventories repeated over time can be used to assess broad scale wildland fire potential and hazard mitigation treatment effectiveness in the southeastern USA and similar fire prone regions. Additional investigations will be needed to modify and improve these processes and capture the true potential of these fine scale data sets for fire and fuel management planning.

  12. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 ...

  13. Genetic alterations affecting cholesterol metabolism and human fertility.

    DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

    2014-11-01

    Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

  14. Scaling up: human genetics as a Cold War network.

    Lindee, Susan

    2014-09-01

    In this commentary I explore how the papers here illuminate the processes of collection that have been so central to the history of human genetics since 1945. The development of human population genetics in the Cold War period produced databases and biobanks that have endured into the present, and that continue to be used and debated. In the decades after the bomb, scientists collected and transferred human biological materials and information from populations of interest, and as they moved these biological resources or biosocial resources acquired new meanings and uses. The papers here collate these practices and map their desires and ironies. They explore how a large international network of geneticists, biological anthropologists, virologists and other physicians and scientists interacted with local informants, research subjects and public officials. They also track the networks and standards that mobilized the transfer of information, genealogies, tissue and blood samples. As Joanna Radin suggests here, the massive collections of human biological materials and data were often understood to be resources for an "as-yet-unknown" future. The stories told here contain elements of surveillance, extraction, salvage and eschatology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Common genetic variants influence human subcortical brain structures

    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

  16. Human impacts on genetic diversity in forest ecosystems

    Ledig, F T [Inst. of Forest Genetics, Southwest Forest and Range Experiment Station, USDA Forest Service, Berkeley (US)

    1992-01-01

    Humans have converted forest to agricultural and urban uses, exploited species, fragmented wildlands, changed the demographic structure of forests, altered habitat, degraded the environment with atmospheric and soil pollutants, introduced exotic pests and competitors, and domesticated favored species. None of these activities is new; perhaps with the exception of atmospheric pollution, they date back to prehistory. All have impacted genetic diversity by their influence on the evolutionary processes of extinction, selection, drift, gene flow, and mutation, sometimes increasing diversity, as int he case of domestication, but often reducing it. Even in the absence of changes in diversity, mating systems were altered, changing the genetic structure of populations. Demographic changes influenced selection by increasing the incidence of disease. Introduction of exotic diseases, insects, mammalian herbivores, and competing vegetation has had the best-documented effects on genetic diversity, reducing both species diversity and intraspecific diversity. Deforestation has operated on a vast scale to reduce diversity by direct elimination of locally-adapted populations. Atmospheric pollution and global warming will be a major threat in the near future, particularly because forests are fragmented and migration is impeded. Past impacts can be estimated with reference to expert knowledge, but hard data are often laching. Baselines are needed to quantify future impacts and provide an early warning of problems. Genetic inventories of indicator species can provide the baselines against which to measure changes in diversity. (author) (44 refs.).

  17. African Americans' opinions about human-genetics research.

    Achter, Paul; Parrott, Roxanne; Silk, Kami

    2004-03-01

    Research on attitudes toward genetics and medicine registers skepticism among minority communities, but the reasons for this skepticism are not well known. In the past, studies linked mistrust of the medical system to historical ethics violations involving minority groups and to suspicions about ideological premise and political intent. To assess public knowledge, attitudes, and behavior regarding human-genetics research, we surveyed 858 Americans onsite in four community settings or online in a geographically nonspecific manner. Compared to participants as a whole, African Americans were significantly more likely to believe that clinical trials might be dangerous and that the federal government knowingly conducted unethical research, including studies in which risky vaccines were administered to prison populations. However, African Americans were also significantly more likely to believe that the federal government worked to prevent environmental exposure to toxicants harmful to people with genetic vulnerabilities. Our data suggest that most Americans trust government to act ethically in sponsoring and conducting research, including genetics research, but that African Americans are particularly likely to see government as powerfully protective in some settings yet selectively disingenuous in others.

  18. Functional characterization of genetic enzyme variations in human lipoxygenases

    Thomas Horn

    2013-01-01

    Full Text Available Mammalian lipoxygenases play a role in normal cell development and differentiation but they have also been implicated in the pathogenesis of cardiovascular, hyperproliferative and neurodegenerative diseases. As lipid peroxidizing enzymes they are involved in the regulation of cellular redox homeostasis since they produce lipid hydroperoxides, which serve as an efficient source for free radicals. There are various epidemiological correlation studies relating naturally occurring variations in the six human lipoxygenase genes (SNPs or rare mutations to the frequency for various diseases in these individuals, but for most of the described variations no functional data are available. Employing a combined bioinformatical and enzymological strategy, which included structural modeling and experimental site-directed mutagenesis, we systematically explored the structural and functional consequences of non-synonymous genetic variations in four different human lipoxygenase genes (ALOX5, ALOX12, ALOX15, and ALOX15B that have been identified in the human 1000 genome project. Due to a lack of a functional expression system we resigned to analyze the functionality of genetic variations in the hALOX12B and hALOXE3 gene. We found that most of the frequent non-synonymous coding SNPs are located at the enzyme surface and hardly alter the enzyme functionality. In contrast, genetic variations which affect functional important amino acid residues or lead to truncated enzyme variations (nonsense mutations are usually rare with a global allele frequency<0.1%. This data suggest that there appears to be an evolutionary pressure on the coding regions of the lipoxygenase genes preventing the accumulation of loss-of-function variations in the human population.

  19. Genetic Markers of Human Evolution Are Enriched in Schizophrenia

    Srinivasan, Saurabh; Bettella, Francesco; Mattingsdal, Morten

    2016-01-01

    BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking...... and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score. RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone...... phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development. CONCLUSIONS: Our results suggest that there is a polygenic overlap...

  20. Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

    Shuji Mizumoto

    2014-01-01

    Full Text Available Glycosaminoglycans (GAGs are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs.

  1. Fine-scale community structure analysis of ANME in Nyegga sediments with high and low methane flux

    Irene eRoalkvam

    2012-06-01

    Full Text Available To obtain knowledge on how regional variations in methane seepage rates influence the stratification, abundance and diversity of anaerobic methanotrophs (ANME we analyzed the vertical microbial stratification in a gravity core from a methane micro-seeping area at Nyegga by using 454-pyrosequencing of 16S rRNA gene tagged amplicons and quantitative PCR. The results were compared with previously obtained data from the more active G11 pockmark, characterized by higher methane flux. A downcore stratification and high relative abundance of ANME was observed in both cores, with transition from an ANME-2a/b dominated community in low-sulfide and low-methane horizons to ANME-1 dominance in horizons near the sulfate methane transition zone (SMTZ. The stratification was over a wider spatial region and at greater depth in the core with lower methane flux, and the total 16S rRNA copy numbers were two orders of magnitude lower than in the sediments at G11 pockmark. A fine-scale view into the ANME communities at each location was achieved through OTU clustering of ANME-affiliated sequences. The majority of ANME-1 sequences from both sampling sites clustered within one OTU, while ANME-2a/b sequences were represented in unique OTUs. We suggest that free living ANME-1 is the most abundant taxon in Nyegga cold seeps, and also the main consumer of methane. The specific ANME-2a/b ecotypes could reflect adaptations to the geochemical composition at each location, with different affinities to methane. Given that the ANME-2a/b population could be sustained in less active seepage areas, this subgroup could be potential seed populations in newly developed methane-enriched environments.

  2. Fine-scale tracking and diet information of a marine predator reveals the origin and contrasting spatial distribution of prey

    Alonso, Hany; Granadeiro, José P.; Dias, Maria P.; Catry, Teresa; Catry, Paulo

    2018-03-01

    The distribution of many marine organisms is still poorly understood, particularly in oceanic regions. Seabirds, as aerial predators which cover extensive areas across the oceans, can potentially be used to enhance our knowledge on the distribution and abundance of their prey. In this study, we combined tracking data and dietary data from individual Cory's shearwaters Calonectris borealis (n = 68) breeding in Selvagens archipelago, Madeira, Portugal, during the chick-rearing periods of 2011 and 2016, in order to infer prey origin within shearwaters' main foraging areas. The digestion state of each prey item in the diet was assessed and classified; and compared to digestion states from known prey items fed to captive birds. In a novel approach, we combined tracking data with information on the prey digestion duration and data on the transit times from foraging grounds to the colony to estimate the location of prey capture. We found a consistent heterogeneity in prey distribution across four different marine domains: Selvagens, deep-sea, seamounts, and continental shelf. In oceanic areas, the chub mackerel Scomber colias, the main prey of Cory's shearwaters, was strongly associated with seamounts and insular shelves, whereas oceanic species like pilot-fish, flying-squid, flying-fish were clearly associated with deep-sea waters. Sardines Sardina pilchardus, anchovies Engraulis encrasicolus and other coastal species were associated with the African shelf. Prey origin assignment was robust across three different sets of assumptions, and was also supported by information on the digestion state of prey collected over a large independent sampling period (671 samples, collected in 2008-2010). The integration of fine-scale dietary and foraging trip data from marine predators provides a new framework to gain insights into the distribution and abundance of prey species in poorly known oceanic areas.

  3. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

    Zeng, Chenjie; Guo, Xingyi; Long, Jirong; Kuchenbaecker, Karoline B; Droit, Arnaud; Michailidou, Kyriaki; Ghoussaini, Maya; Kar, Siddhartha; Freeman, Adam; Hopper, John L; Milne, Roger L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Agata, Simona; Ahmed, Shahana; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Arason, Adalgeir; Arndt, Volker; Arun, Banu K; Arver, Brita; Bacot, Francois; Barrowdale, Daniel; Baynes, Caroline; Beeghly-Fadiel, Alicia; Benitez, Javier; Bermisheva, Marina; Blomqvist, Carl; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Carpenter, Jane; Chang-Claude, Jenny; Choi, Ji-Yeob; Claes, Kathleen B M; Clarke, Christine; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; de la Hoya, Miguel; De Leeneer, Kim; Devilee, Peter; Diez, Orland; Domchek, Susan M; Doody, Michele; Dorfling, Cecilia M; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Dwek, Miriam; Dworniczak, Bernd; Egan, Kathleen; Eilber, Ursula; Einbeigi, Zakaria; Ejlertsen, Bent; Ellis, Steve; Frost, Debra; Lalloo, Fiona; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Friedlander, Michael; Friedman, Eitan; Gambino, Gaetana; Gao, Yu-Tang; Garber, Judy; García-Closas, Montserrat; Gehrig, Andrea; Damiola, Francesca; Lesueur, Fabienne; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Giles, Graham G; Godwin, Andrew K; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hartikainen, Jaana M; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Hogervorst, Frans B L; Verhoef, Senno; Hendricks, Carolyn B; Hillemanns, Peter; Hollestelle, Antoinette; Hulick, Peter J; Hunter, David J; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Joly Beauparlant, Charles; Jones, Michael; Kabisch, Maria; Kang, Daehee; Karlan, Beth Y; Kauppila, Saila; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Knight, Julia A; Konstantopoulou, Irene; Kraft, Peter; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Le Marchand, Loic; Lee, Chuen Neng; Lee, Min Hyuk; Lester, Jenny; Li, Jingmei; Liljegren, Annelie; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mai, Phuong L; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McGuffog, Lesley; Meindl, Alfons; Menegaux, Florence; Montagna, Marco; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Newcomb, Polly A; Nord, Silje; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olswold, Curtis; Osorio, Ana; Papi, Laura; Park-Simon, Tjoung-Won; Paulsson-Karlsson, Ylva; Peeters, Stephanie; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Pfeiler, Georg; Phelan, Catherine M; Presneau, Nadege; Radice, Paolo; Rahman, Nazneen; Ramus, Susan J; Rashid, Muhammad Usman; Rennert, Gad; Rhiem, Kerstin; Rudolph, Anja; Salani, Ritu; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Schoemaker, Minouk J; Schürmann, Peter; Seynaeve, Caroline; Shen, Chen-Yang; Shrubsole, Martha J; Shu, Xiao-Ou; Sigurdson, Alice; Singer, Christian F; Slager, Susan; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Swerdlow, Anthony; Szabo, Csilla I; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Mary Beth; Tessier, Daniel C; Teulé, Alex; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda E; Tung, Nadine; Turnbull, Clare; van den Ouweland, Ans M W; van Rensburg, Elizabeth J; Ven den Berg, David; Vijai, Joseph; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Whittemore, Alice S; Winqvist, Robert; Wong, Tien Y; Wu, Anna H; Yannoukakos, Drakoulis; Yu, Jyh-Cherng; Pharoah, Paul D P; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison M; Simard, Jacques; Couch, Fergus J; Antoniou, Antonis C; Easton, Douglas F; Zheng, Wei

    2016-06-21

    Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P association signals at

  4. Genetic regulation of pituitary gland development in human and mouse.

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

    2009-12-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

  5. Integrating common and rare genetic variation in diverse human populations.

    Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

    2010-09-02

    Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

  6. A genetic basis for mechanosensory traits in humans.

    Henning Frenzel

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

  7. Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

    Varki, Ajit

    2004-06-01

    At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

  8. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  9. Liberal or Conservative? Genetic Rhetoric, Disability, and Human Species Modification

    Christopher F. Goodey

    2016-11-01

    Full Text Available A certain political rhetoric is implicit and sometimes explicit in the advocacy of human genetic modification (indicating here both the enhancement and the prevention of disability. The main claim is that it belongs to a liberal tradition. From a perspective supplied by the history and philosophy of science rather than by ethics, the content of that claim is examined to see if such a self-description is justified. The techniques are analyzed by which apparently liberal arguments get to be presented as “reasonable” in a juridical sense that draws on theories of law and rhetoric.

  10. The impact of preimplantation genetic diagnosis on human embryos

    García-Ferreyra J.

    2016-12-01

    Full Text Available Chromosome abnormalities are extremely common in human oocytes and embryos and are associated with a variety of negative outcomes for both natural cycles and those using assisted reproduction techniques. Aneuploidies embryos may fail to implant in the uterus, miscarry, or lead to children with serious medical problems (e.g., Down syndrome. Preimplantation genetic diagnosis (PGD is a technique that allows the detection of aneuploidy in embryos and seeks to improve the clinical outcomes od assisted reproduction treatments, by ensuring that the embryos chosen for the transfer are chromosomally normal.

  11. Genetics and Human Agency: Comment on Dar-Nimrod and Heine (2011)

    Turkheimer, Eric

    2011-01-01

    Dar-Nimrod and Heine (2011) decried genetic essentialism without denying the importance of genetics in the genesis of human behavior, and although I agree on both counts, a deeper issue remains unaddressed: how should we adjust our cognitions about our own behavior in light of genetic influence, or is it perhaps not necessary to take genetics into…

  12. Alu repeats as markers for human population genetics

    Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Bazan, H. [Louisiana State Univ., New Orleans, LA (United States). Medical Center] [and others

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  13. Comparative genetics: synergizing human and NOD mouse studies for identifying genetic causation of type 1 diabetes.

    Driver, John P; Chen, Yi-Guang; Mathews, Clayton E

    2012-01-01

    Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

  14. Genetic contributions to human brain morphology and intelligence

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.......79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0......Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...

  15. HSP90 Shapes the Consequences of Human Genetic Variation.

    Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

    2017-02-23

    HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Psychological aspects of human cloning and genetic manipulation: the identity and uniqueness of human beings.

    Morales, N M

    2009-01-01

    Human cloning has become one of the most controversial debates about reproduction in Western civilization. Human cloning represents asexual reproduction, but the critics of human cloning argue that the result of cloning is not a new individual who is genetically unique. There is also awareness in the scientific community, including the medical community, that human cloning and the creation of clones are inevitable. Psychology and other social sciences, together with the natural sciences, will need to find ways to help the healthcare system, to be prepared to face the new challenges introduced by the techniques of human cloning. One of those challenges is to help the healthcare system to find specific standards of behaviour that could be used to help potential parents to interact properly with cloned babies or children created through genetic manipulation. In this paper, the concepts of personality, identity and uniqueness are discussed in relationship to the contribution of twin studies in these areas. The author argues that an individual created by human cloning techniques or any other type of genetic manipulation will not show the donor's characteristics to the extent of compromising uniqueness. Therefore, claims to such an effect are needlessly alarmist.

  17. Understanding human genetic variation in the era of high-throughput sequencing

    Knight, Julian C.

    2010-01-01

    The EMBO/EMBL symposium ‘Human Variation: Cause and Consequence' highlighted advances in understanding the molecular basis of human genetic variation and its myriad implications for biology, human origins and disease.

  18. G protein-coupled receptor mutations and human genetic disease.

    Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

    2014-01-01

    Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

  19. Genetic Variants Contribute to Gene Expression Variability in Humans

    Hulse, Amanda M.; Cai, James J.

    2013-01-01

    Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

  20. Estimating mobility using sparse data: Application to human genetic variation.

    Loog, Liisa; Mirazón Lahr, Marta; Kovacevic, Mirna; Manica, Andrea; Eriksson, Anders; Thomas, Mark G

    2017-11-14

    Mobility is one of the most important processes shaping spatiotemporal patterns of variation in genetic, morphological, and cultural traits. However, current approaches for inferring past migration episodes in the fields of archaeology and population genetics lack either temporal resolution or formal quantification of the underlying mobility, are poorly suited to spatially and temporally sparsely sampled data, and permit only limited systematic comparison between different time periods or geographic regions. Here we present an estimator of past mobility that addresses these issues by explicitly linking trait differentiation in space and time. We demonstrate the efficacy of this estimator using spatiotemporally explicit simulations and apply it to a large set of ancient genomic data from Western Eurasia. We identify a sequence of changes in human mobility from the Late Pleistocene to the Iron Age. We find that mobility among European Holocene farmers was significantly higher than among European hunter-gatherers both pre- and postdating the Last Glacial Maximum. We also infer that this Holocene rise in mobility occurred in at least three distinct stages: the first centering on the well-known population expansion at the beginning of the Neolithic, and the second and third centering on the beginning of the Bronze Age and the late Iron Age, respectively. These findings suggest a strong link between technological change and human mobility in Holocene Western Eurasia and demonstrate the utility of this framework for exploring changes in mobility through space and time. Copyright © 2017 the Author(s). Published by PNAS.

  1. Human lipodystrophies: genetic and acquired diseases of adipose tissue

    Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

    2010-01-01

    Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

  2. Biomarkers of genetic damage in human populations exposed to pesticides

    Aiassa, Delia; Manas, Fernando; Bosch, Beatriz; Gentile, Natalia; Bernardi, Natali; Gorla, Nora

    2012-01-01

    The effect of pesticides on human, animal and environmental health has been cause of concern in the scientific community for a long time. Numerous studies have reported that pesticides are not harmless and that their use can lead to harmful biological effects in the medium and long term, in exposed human and animals, and their offspring. The importance of early detection of genetic damage is that it allows us to take the necessary measures to reduce or eliminate the exposure to the deleterious agent when damage is still reversible, and thus to prevent and to diminish the risk of developing tumors or other alterations. In this paper we reviewed the main concepts in the field, the usefulness of genotoxicity studies and we compiled studies performed during the last twenty years on genetic monitoring of people occupationally exposed to pesticides. we think that genotoxicity tests, including that include chromosomal aberrations, micronucleus, sister chromatid exchanges and comet assays, should be considered as essential tools in the implementation of complete medical supervision for people exposed to potential environmental pollutants, particularly for those living in the same place as others who were others have already developed some type of malignancy. This action is particularly important at early stages to prevent the occurrence of tumors, especially from environmental origins.

  3. Spatially explicit multi-threat assessment of food tree species in Burkina Faso: A fine-scale approach.

    Hannes Gaisberger

    Full Text Available Over the last decades agroforestry parklands in Burkina Faso have come under increasing demographic as well as climatic pressures, which are threatening indigenous tree species that contribute substantially to income generation and nutrition in rural households. Analyzing the threats as well as the species vulnerability to them is fundamental for priority setting in conservation planning. Guided by literature and local experts we selected 16 important food tree species (Acacia macrostachya, Acacia senegal, Adansonia digitata, Annona senegalensis, Balanites aegyptiaca, Bombax costatum, Boscia senegalensis, Detarium microcarpum, Lannea microcarpa, Parkia biglobosa, Sclerocarya birrea, Strychnos spinosa, Tamarindus indica, Vitellaria paradoxa, Ximenia americana, Ziziphus mauritiana and six key threats to them (overexploitation, overgrazing, fire, cotton production, mining and climate change. We developed a species-specific and spatially explicit approach combining freely accessible datasets, species distribution models (SDMs, climate models and expert survey results to predict, at fine scale, where these threats are likely to have the greatest impact. We find that all species face serious threats throughout much of their distribution in Burkina Faso and that climate change is predicted to be the most prevalent threat in the long term, whereas overexploitation and cotton production are the most important short-term threats. Tree populations growing in areas designated as 'highly threatened' due to climate change should be used as seed sources for ex situ conservation and planting in areas where future climate is predicting suitable habitats. Assisted regeneration is suggested for populations in areas where suitable habitat under future climate conditions coincides with high threat levels due to short-term threats. In the case of Vitellaria paradoxa, we suggest collecting seed along the northern margins of its distribution and considering assisted

  4. Egyptian Journal of Medical Human Genetics - Vol 14, No 3 (2013)

    Egyptian Journal of Medical Human Genetics - Vol 14, No 3 (2013) ... Comparative study: Parameters of gait in Down syndrome versus matched obese and ... episodes in a Japanese child: Clinical, radiological and molecular genetic analysis ...

  5. Computational Integration of Human Genetic Data to Evaluate AOP-Specific Susceptibility

    There is a need for approaches to efficiently evaluate human genetic variability and susceptibility related to environmental chemical exposure. Direct estimation of the genetic contribution to variability in susceptibility to environmental chemicals is only possible in special ca...

  6. Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels

    Emdin, Connor A.; Khera, Amit V.; Natarajan, Pradeep; Klarin, Derek; Won, Hong-Hee; Peloso, Gina M.; Stitziel, Nathan O.; Nomura, Akihiro; Zekavat, Seyedeh M.; Bick, Alexander G.; Gupta, Namrata; Asselta, Rosanna; Duga, Stefano; Merlini, Piera Angelica; Correa, Adolfo; Kessler, Thorsten; Wilson, James G.; Bown, Matthew J.; Hall, Alistair S.; Braund, Peter S.; Samani, Nilesh J.; Schunkert, Heribert; Marrugat, Jaume; Elosua, Roberto; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Willer, Cristen; Abecasis, Gonçalo R.; Felix, Janine F.; Vasan, Ramachandran S.; Lander, Eric; Rader, Daniel J.; Danesh, John; Ardissino, Diego; Gabriel, Stacey; Saleheen, Danish; Kathiresan, Sekar

    2017-01-01

    BACKGROUND Genomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose-response curve of target perturbation. OBJECTIVES We attempted to establish the full phenotypic impact of LPA gene variation and to estimate a dose-response curve between genetically altered plasma Lp(a) and risk for CHD. METHODS We leveraged genetic variants at the LPA gene from 3 data sources: individual-level data from 112,338 participants in the UK Biobank; summary association results from large-scale genome-wide association studies; and LPA gene sequencing results from cases with and controls free of CHD. RESULTS One standard deviation genetically lowered Lp(a) level was associated with 29% lower risk of CHD (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.69 to 0.73), 31% lower risk of peripheral vascular disease (OR: 0.69; 95% CI: 0.59 to 0.80), 13% lower risk of stroke (OR: 0.87; 95% CI: 0.79 to 0.96), 17% lower risk of heart failure (OR: 0.83; 95% CI: 0.73 to 0.94), and 37% lower risk of aortic stenosis (OR: 0.63; 95% CI: 0.47 to 0.83). We observed no association with 31 other disorders including type 2 diabetes and cancer. Variants that led to gain of LPA gene function increased risk for CHD whereas those that led to loss of gene function reduced CHD risk. CONCLUSIONS Beyond CHD, genetically lowered Lp(a) is associated with a lower risk of peripheral vascular disease, stroke, heart failure, and aortic stenosis. As such, pharmacological lowering of plasma Lp(a) may impact a range of atherosclerosis-related diseases. PMID:28007139

  7. Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts.

    Gagnon, Kenneth B; Delpire, Eric

    2013-04-15

    Among the over 300 members of the solute carrier (SLC) group of integral plasma membrane transport proteins are the nine electroneutral cation-chloride cotransporters belonging to the SLC12 gene family. Seven of these transporters have been functionally described as coupling the electrically silent movement of chloride with sodium and/or potassium. Although in silico analysis has identified two additional SLC12 family members, no physiological role has been ascribed to the proteins encoded by either the SLC12A8 or the SLC12A9 genes. Evolutionary conservation of this gene family from protists to humans confirms their importance. A wealth of physiological, immunohistochemical, and biochemical studies have revealed a great deal of information regarding the importance of this gene family to human health and disease. The sequencing of the human genome has provided investigators with the capability to link several human diseases with mutations in the genes encoding these plasma membrane proteins. The availability of bacterial artificial chromosomes, recombination engineering techniques, and the mouse genome sequence has simplified the creation of targeting constructs to manipulate the expression/function of these cation-chloride cotransporters in the mouse in an attempt to recapitulate some of these human pathologies. This review will summarize the three human disorders that have been linked to the mutation/dysfunction of the Na-Cl, Na-K-2Cl, and K-Cl cotransporters (i.e., Bartter's, Gitleman's, and Andermann's syndromes), examine some additional pathologies arising from genetically modified mouse models of these cotransporters including deafness, blood pressure, hyperexcitability, and epithelial transport deficit phenotypes.

  8. Genetic Characterization and Classification of Human and Animal Sapoviruses.

    Tomoichiro Oka

    Full Text Available Sapoviruses (SaVs are enteric caliciviruses that have been detected in multiple mammalian species, including humans, pigs, mink, dogs, sea lions, chimpanzees, and rats. They show a high level of diversity. A SaV genome commonly encodes seven nonstructural proteins (NSs, including the RNA polymerase protein NS7, and two structural proteins (VP1 and VP2. We classified human and animal SaVs into 15 genogroups (G based on available VP1 sequences, including three newly characterized genomes from this study. We sequenced the full length genomes of one new genogroup V (GV, one GVII and one GVIII porcine SaV using long range RT-PCR including newly designed forward primers located in the conserved motifs of the putative NS3, and also 5' RACE methods. We also determined the 5'- and 3'-ends of sea lion GV SaV and canine GXIII SaV. Although the complete genomic sequences of GIX-GXII, and GXV SaVs are unavailable, common features of SaV genomes include: 1 "GTG" at the 5'-end of the genome, and a short (9~14 nt 5'-untranslated region; and 2 the first five amino acids (M [A/V] S [K/R] P of the putative NS1 and the five amino acids (FEMEG surrounding the putative cleavage site between NS7 and VP1 were conserved among the chimpanzee, two of five genogroups of pig (GV and GVIII, sea lion, canine, and human SaVs. In contrast, these two amino acid motifs were clearly different in three genogroups of porcine (GIII, GVI and GVII, and bat SaVs. Our results suggest that several animal SaVs have genetic similarities to human SaVs. However, the ability of SaVs to be transmitted between humans and animals is uncertain.

  9. Derivation of novel genetically diverse human embryonic stem cell lines.

    Stefanova, Valentina T; Grifo, James A; Hansis, Christoph

    2012-06-10

    Human embryonic stem cells (hESCs) have the potential to revolutionize many biomedical fields ranging from basic research to disease modeling, regenerative medicine, drug discovery, and toxicity testing. A multitude of hESC lines have been derived worldwide since the first 5 lines by Thomson et al. 13 years ago, but many of these are poorly characterized, unavailable, or do not represent desired traits, thus making them unsuitable for application purposes. In order to provide the scientific community with better options, we have derived 12 new hESC lines at New York University from discarded genetically normal and abnormal embryos using the latest techniques. We examined the genetic status of the NYUES lines in detail as well as their molecular and cellular features and DNA fingerprinting profile. Furthermore, we differentiated our hESCs into the tissues most affected by a specific condition or into clinically desired cell types. To our knowledge, a number of characteristics of our hESCs have not been previously reported, for example, mutation for alpha thalassemia X-linked mental retardation syndrome, linkage to conditions with a genetic component such as asthma or poor sperm morphology, and novel combinations of ethnic backgrounds. Importantly, all of our undifferentiated euploid female lines tested to date did not show X chromosome inactivation, believed to result in superior potency. We continue to derive new hESC lines and add them to the NIH registry and other registries. This should facilitate the use of our hESCs and lead to advancements for patient-benefitting applications.

  10. The human noncoding genome defined by genetic diversity.

    di Iulio, Julia; Bartha, Istvan; Wong, Emily H M; Yu, Hung-Chun; Lavrenko, Victor; Yang, Dongchan; Jung, Inkyung; Hicks, Michael A; Shah, Naisha; Kirkness, Ewen F; Fabani, Martin M; Biggs, William H; Ren, Bing; Venter, J Craig; Telenti, Amalio

    2018-03-01

    Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome. Using new Hi-C experimental data, we describe a strong pattern of coordination over 2 Mb where the most constrained regulatory elements associate with the most essential genes. Constrained regions of the noncoding genome are up to 52-fold enriched for known pathogenic variants as compared to unconstrained regions (21-fold when compared to the genome average). This map of sequence constraint across thousands of individuals is an asset to help interpret noncoding elements in the human genome, prioritize variants and reconsider gene units at a larger scale.

  11. Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

    Hilda Montero

    2012-01-01

    Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.

  12. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    Swati Chaturvedi

    2016-01-01

    Full Text Available One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches.

  13. Human genetics of infectious diseases: Unique insights into immunological redundancy.

    Casanova, Jean-Laurent; Abel, Laurent

    2018-04-01

    For almost any given human-tropic virus, bacterium, fungus, or parasite, the clinical outcome of primary infection is enormously variable, ranging from asymptomatic to lethal infection. This variability has long been thought to be largely determined by the germline genetics of the human host, and this is increasingly being demonstrated to be the case. The number and diversity of known inborn errors of immunity is continually increasing, and we focus here on autosomal and X-linked recessive traits underlying complete deficiencies of the encoded protein. Schematically, four types of infectious phenotype have been observed in individuals with such deficiencies, each providing information about the redundancy of the corresponding human gene, in terms of host defense in natural conditions. The lack of a protein can confer vulnerability to a broad range of microbes in most, if not all patients, through the disruption of a key immunological component. In such cases, the gene concerned is of low redundancy. However, the lack of a protein may also confer vulnerability to a narrow range of microbes, sometimes a single pathogen, and not necessarily in all patients. In such cases, the gene concerned is highly redundant. Conversely, the deficiency may be apparently neutral, conferring no detectable predisposition to infection in any individual. In such cases, the gene concerned is completely redundant. Finally, the lack of a protein may, paradoxically, be advantageous to the host, conferring resistance to one or more infections. In such cases, the gene is considered to display beneficial redundancy. These findings reflect the current state of evolution of humans and microbes, and should not be considered predictive of redundancy, or of a lack of redundancy, in the distant future. Nevertheless, these observations are of potential interest to present-day biologists testing immunological hypotheses experimentally and physicians managing patients with immunological or infectious

  14. Long term human impacts on genetic structure of Italian walnut inferred by SSR markers

    Paola Pollegioni; Keith Woeste; Irene Olimpieri; Danilo Marandola; Francesco Cannata; Maria E Malvolti

    2011-01-01

    Life history traits, historic factors, and human activities can all shape the genetic diversity of a species. In Italy, walnut (Juglans regia L.) has a long history of cultivation both for wood and edible nuts. To better understand the genetic variability of current Italian walnut resources, we analyzed the relationships among the genetic structure...

  15. Functional modules, mutational load and human genetic disease.

    Zaghloul, Norann A; Katsanis, Nicholas

    2010-04-01

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

  16. [Constant or break? On the relations between human genetics and eugenics in the Twentieth Century].

    Germann, Pascal

    2015-07-01

    The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations.

  17. Analysis of the genetic basis of disease in the context of worldwide human relationships and migration.

    Erik Corona

    2013-05-01

    Full Text Available Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.

  18. An atlas of genetic correlations across human diseases and traits

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are t...

  19. The need for interaction between assisted reproduction technology and genetics: recommendations of the European Societies of Human Genetics and Human Reproduction and Embryology.

    2006-08-01

    Infertility and reproductive genetic risk are both increasing in our societies because of lifestyle changes and possibly environmental factors. Owing to the magnitude of the problem, they have implications not only at the individual and family levels but also at the community level. This leads to an increasing demand for access to assisted reproduction technology (ART) and genetic services, especially when the cause of infertility may be genetic in origin. The increasing application of genetics in reproductive medicine and vice versa requires closer collaboration between the two disciplines. ART and genetics are rapidly evolving fields where new technologies are currently introduced without sufficient knowledge of their potential long-term effects. As for any medical procedures, there are possible unexpected effects which need to be envisaged to make sure that the balance between benefits and risks is clearly on the benefit side. The development of ART and genetics as scientific activities is creating an opportunity to understand the early stages of human development, which is leading to new and challenging findings/knowledge. However, there are opinions against investigating the early stages of development in humans who deserve respect and attention. For all these reasons, these two societies, European Society of Human Genetics (ESHG) and European Society of Human Reproduction and Embryology (ESHRE), have joined efforts to explore the issues at stake and to set up recommendations to maximize the benefit for the couples in need and for the community.

  20. Fine-scale heat flow, shallow heat sources, and decoupled circulation systems at two sea-floor hydrothermal sites, Middle Valley, northern Juan de Fuca Ridge

    Stein, J. S.; Fisher, A. T.; Langseth, M.; Jin, W.; Iturrino, G.; Davis, E.

    1998-12-01

    Fine-scale heat-flow patterns at two areas of active venting in Middle Valley, a sedimented rift on the northern Juan de Fuca Ridge, provide thermal evidence of shallow hydrothermal reservoirs beneath the vent fields. The extreme variability of heat flow is explained by conductive heating immediately adjacent to vents and shallow circulation within sediments above the reservoir. This secondary circulation is hydrologically separated from the deeper system feeding the vents by a shallow conductive lid within the sediments. A similar separation of shallow and deep circulation may also occur at sediment-free ridge-crest hydrothermal environments.

  1. Temporal changes in vegetation of a virgin beech woodland remnant: stand-scale stability with intensive fine-scale dynamics governed by stand dynamic events

    Tibor Standovár

    2017-03-01

    Full Text Available The aim of this resurvey study is to check if herbaceous vegetation on the forest floor exhibits overall stability at the stand-scale in spite of intensive dynamics at the scale of individual plots and stand dynamic events (driven by natural fine scale canopy gap dynamics. In 1996, we sampled a 1.5 ha patch using 0.25 m² plots placed along a 5 m × 5 m grid in the best remnant of central European montane beech woods in Hungary. All species in the herbaceous layer and their cover estimates were recorded. Five patches representing different stand developmental situations (SDS were selected for resurvey. In 2013, 306 plots were resurveyed by using blocks of four 0.25 m² plots to test the effects of imperfect relocation. We found very intensive fine-scale dynamics in the herbaceous layer with high species turnover and sharp changes in ground layer cover at the local-scale (< 1 m2. A decrease in species richness and herbaceous layer cover, as well as high species turnover, characterized the closing gaps. Colonization events and increasing species richness and herbaceous layer cover prevailed in the two newly created gaps. A pronounced decrease in the total cover, but low species turnover and survival of the majority of the closed forest specialists was detected by the resurvey at the stand-scale. The test aiming at assessing the effect of relocation showed a higher time effect than the effect of imprecise relocation. The very intensive fine-scale dynamics of the studied beech forest are profoundly determined by natural stand dynamics. Extinction and colonisation episodes even out at the stand-scale, implying an overall compositional stability of the herbaceous vegetation at the given spatial and temporal scale. We argue that fine-scale gap dynamics, driven by natural processes or applied as a management method, can warrant the survival of many closed forest specialist species in the long-run. Nomenclature: Flora Europaea (Tutin et al. 2010 for

  2. Elements of the geological structure of the Western Siberian platform determined from a review of fine-scale satellite photographs in oil and gas prospecting research

    Borovskii, V V; Klopov, A L; Peskovskii, I D; Podsosova, L L

    1980-01-01

    Dislocations with breaks in continuity and annular objects are identified on fine-scale satellite photographs within the region of the Western Siberian platform. Based on an integrated interpretation of the geological and geophysical data, it is predicted that there exists a relation between the annular objects and the geological structure of deep portions of the earth's crust, the pre-Jurassic basement, and certain levels of the platform mantle. Procedural techniques for the use of magnetic and gravitional data for the purpose of obtaining information about the geological nature of the identified objects are considered.

  3. Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations

    Affifi, Ramsey

    2017-01-01

    This paper describes some likely semiotic consequences of genetic engineering on what Gregory Bateson has called ?the mental ecology? (1979) of future humans, consequences that are less often raised in discussions surrounding the safety of GMOs (genetically modified organisms). The effects are as follows: an increased 1) habituation to the presence of GMOs in the environment, 2) normalization of empirically false assumptions grounding genetic reductionism, 3) acceptance that humans are capabl...

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

    Amr T. M. Saeb

    2016-01-01

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

  5. Assessment of genetic risk for human exposure to radiation. State of the art

    Shevchenko, V.A.

    2000-01-01

    Historical aspects of the conception of genetic risk of human irradiation for recent 40 years. Methodology of assessing the genetic risk of radiation exposure is based on the concept of hitting the target. To predict genetic risk of irradiation, the direct and indirect methods of assessment, extrapolation, integral and populational criteria of risk analysis is widely used. Combination of these methods permits to calculate the risk from human exposure on the basis of data obtained for mice. Method of doubling dose based on determination of the dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. Till 1972 the main model for assessing the genetic risk was the human/mouse model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period from 1972 till 1994 the mouse/mouse model was intensively elaborated in many laboratories. This model was also used in this period to analyse the genetic risk of human irradiation. Recent achievements associated with the study of molecular nature of many hereditary human diseases as well as the criticism of a fundamental principles of the mouse/mouse model for estimating the genetic risk on a new basis. Estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method [ru

  6. Human diseases with genetically altered DNA repair processes

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  7. Human diseases with genetically altered DNA repair processes

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  8. Genetic association between human chitinases and lung function in COPD.

    Aminuddin, F; Akhabir, L; Stefanowicz, D; Paré, P D; Connett, J E; Anthonisen, N R; Fahy, J V; Seibold, M A; Burchard, E G; Eng, C; Gulsvik, A; Bakke, P; Cho, M H; Litonjua, A; Lomas, D A; Anderson, W H; Beaty, T H; Crapo, J D; Silverman, E K; Sandford, A J

    2012-07-01

    Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

  9. Morphological and Genetic Diversity of Trichuris spp. recovered from Humans and Pigs

    Nissen, Sofie; Nejsum, Peter; Christensen, Henrik

    2009-01-01

    The nematodes, Trichuris suis and Trichuris trichiura are believed to be two separate but closely related species. The aim of our study was to examine the morphological and genetic diversity of Trichuris spp. recovered from pigs and humans. Sympatric worm material isolated from 10 humans and 5 pigs...... found in pig-derived worms (31% of the human-derived worms, consensus sequence 531 nucleotides long). The results indicated that the nematodes found in pigs belong to a genetically distinct species (T. suis) whereas the nematodes in humans showed considerable genetic variability either related...... to ancestral polymorphism or more recent cross-breeding between T. trichiura and T. suis....

  10. Measuring the genetic influence on human life span: gene-environment interaction and sex-specific genetic effects

    Tan, Qihua; De Benedictis, G; Yashin, Annatoli

    2001-01-01

    New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographicinf......New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic...

  11. Multiple SNP markers reveal fine-scale population and deep phylogeographic structure in European anchovy (Engraulis encrasicolus L.).

    Zarraonaindia, Iratxe

    2012-07-30

    Geographic surveys of allozymes, microsatellites, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have detected several genetic subdivisions among European anchovy populations. However, these studies have been limited in their power to detect some aspects of population structure by the use of a single or a few molecular markers, or by limited geographic sampling. We use a multi-marker approach, 47 nDNA and 15 mtDNA single nucleotide polymorphisms (SNPs), to analyze 626 European anchovies from the whole range of the species to resolve shallow and deep levels of population structure. Nuclear SNPs define 10 genetic entities within two larger genetically distinctive groups associated with oceanic variables and different life-history traits. MtDNA SNPs define two deep phylogroups that reflect ancient dispersals and colonizations. These markers define two ecological groups. One major group of Iberian-Atlantic populations is associated with upwelling areas on narrow continental shelves and includes populations spawning and overwintering in coastal areas. A second major group includes northern populations in the North East (NE) Atlantic (including the Bay of Biscay) and the Mediterranean and is associated with wide continental shelves with local larval retention currents. This group tends to spawn and overwinter in oceanic areas. These two groups encompass ten populations that differ from previously defined management stocks in the Alboran Sea, Iberian-Atlantic and Bay of Biscay regions. In addition, a new North Sea-English Channel stock is defined. SNPs indicate that some populations in the Bay of Biscay are genetically closer to North Western (NW) Mediterranean populations than to other populations in the NE Atlantic, likely due to colonizations of the Bay of Biscay and NW Mediterranean by migrants from a common ancestral population. Northern NE Atlantic populations were subsequently established by migrants from the Bay of Biscay. Populations along the Iberian

  12. Fine Scale Spatiotemporal Clustering of Dengue Virus Transmission in Children and Aedes aegypti in Rural Thai Villages

    Yoon, I.K.; Getis, A.; Aldstadt, J.; Rothman, A.L.; Tannitisupawong, D.; Koenraadt, C.J.M.; Fansiri, T.; Jones, J.W.; Morrison, A.C.; Jarman, R.G.; Nisalak, A.; Mammen Jr., M.P.; Thammapalo, S.; Srikiatkhachorn, A.; Green, S.; Libraty, D.H.; Gibbons, R.V.; Endy, T.; Pimgate, C.; Scott, T.W.

    2012-01-01

    Background Based on spatiotemporal clustering of human dengue virus (DENV) infections, transmission is thought to occur at fine spatiotemporal scales by horizontal transfer of virus between humans and mosquito vectors. To define the dimensions of local transmission and quantify the factors that

  13. Internal variability of fine-scale components of meteorological fields in extended-range limited-area model simulations with atmospheric and surface nudging

    Separovic, Leo; Husain, Syed Zahid; Yu, Wei

    2015-09-01

    Internal variability (IV) in dynamical downscaling with limited-area models (LAMs) represents a source of error inherent to the downscaled fields, which originates from the sensitive dependence of the models to arbitrarily small modifications. If IV is large it may impose the need for probabilistic verification of the downscaled information. Atmospheric spectral nudging (ASN) can reduce IV in LAMs as it constrains the large-scale components of LAM fields in the interior of the computational domain and thus prevents any considerable penetration of sensitively dependent deviations into the range of large scales. Using initial condition ensembles, the present study quantifies the impact of ASN on IV in LAM simulations in the range of fine scales that are not controlled by spectral nudging. Four simulation configurations that all include strong ASN but differ in the nudging settings are considered. In the fifth configuration, grid nudging of land surface variables toward high-resolution surface analyses is applied. The results show that the IV at scales larger than 300 km can be suppressed by selecting an appropriate ASN setup. At scales between 300 and 30 km, however, in all configurations, the hourly near-surface temperature, humidity, and winds are only partly reproducible. Nudging the land surface variables is found to have the potential to significantly reduce IV, particularly for fine-scale temperature and humidity. On the other hand, hourly precipitation accumulations at these scales are generally irreproducible in all configurations, and probabilistic approach to downscaling is therefore recommended.

  14. A face in the crowd: a non-invasive and cost effective photo-identification methodology to understand the fine scale movement of eastern water dragons.

    Riana Zanarivero Gardiner

    Full Text Available Ectothermic vertebrates face many challenges of thermoregulation. Many species rely on behavioral thermoregulation and move within their landscape to maintain homeostasis. Understanding the fine-scale nature of this regulation through tracking techniques can provide a better understanding of the relationships between such species and their dynamic environments. The use of animal tracking and telemetry technology has allowed the extensive collection of such data which has enabled us to better understand the ways animals move within their landscape. However, such technologies do not come without certain costs: they are generally invasive, relatively expensive, can be too heavy for small sized animals and unreliable in certain habitats. This study provides a cost-effective and non-invasive method through photo-identification, to determine fine scale movements of individuals. With our methodology, we have been able to find that male eastern water dragons (Intellagama leuseurii have home ranges one and a half times larger than those of females. Furthermore, we found intraspecific differences in the size of home ranges depending on the time of the day. Lastly, we found that location mostly influenced females' home ranges, but not males and discuss why this may be so. Overall, we provide valuable information regarding the ecology of the eastern water dragon, but most importantly demonstrate that non-invasive photo-identification can be successfully applied to the study of reptiles.

  15. A face in the crowd: a non-invasive and cost effective photo-identification methodology to understand the fine scale movement of eastern water dragons.

    Gardiner, Riana Zanarivero; Doran, Erik; Strickland, Kasha; Carpenter-Bundhoo, Luke; Frère, Celine

    2014-01-01

    Ectothermic vertebrates face many challenges of thermoregulation. Many species rely on behavioral thermoregulation and move within their landscape to maintain homeostasis. Understanding the fine-scale nature of this regulation through tracking techniques can provide a better understanding of the relationships between such species and their dynamic environments. The use of animal tracking and telemetry technology has allowed the extensive collection of such data which has enabled us to better understand the ways animals move within their landscape. However, such technologies do not come without certain costs: they are generally invasive, relatively expensive, can be too heavy for small sized animals and unreliable in certain habitats. This study provides a cost-effective and non-invasive method through photo-identification, to determine fine scale movements of individuals. With our methodology, we have been able to find that male eastern water dragons (Intellagama leuseurii) have home ranges one and a half times larger than those of females. Furthermore, we found intraspecific differences in the size of home ranges depending on the time of the day. Lastly, we found that location mostly influenced females' home ranges, but not males and discuss why this may be so. Overall, we provide valuable information regarding the ecology of the eastern water dragon, but most importantly demonstrate that non-invasive photo-identification can be successfully applied to the study of reptiles.

  16. Multiscale modeling and nested simulations of three-dimensional ionospheric plasmas: Rayleigh–Taylor turbulence and nonequilibrium layer dynamics at fine scales

    Mahalov, Alex

    2014-01-01

    Multiscale modeling and high resolution three-dimensional simulations of nonequilibrium ionospheric dynamics are major frontiers in the field of space sciences. The latest developments in fast computational algorithms and novel numerical methods have advanced reliable forecasting of ionospheric environments at fine scales. These new capabilities include improved physics-based predictive modeling, nesting and implicit relaxation techniques that are designed to integrate models of disparate scales. A range of scales, from mesoscale to ionospheric microscale, are included in a 3D modeling framework. Analyses and simulations of primary and secondary Rayleigh–Taylor instabilities in the equatorial spread F (ESF), the response of the plasma density to the neutral turbulent dynamics, and wave breaking in the lower region of the ionosphere and nonequilibrium layer dynamics at fine scales are presented for coupled systems (ions, electrons and neutral winds), thus enabling studies of mesoscale/microscale dynamics for a range of altitudes that encompass the ionospheric E and F layers. We examine the organizing mixing patterns for plasma flows, which occur due to polarized gravity wave excitations in the neutral field, using Lagrangian coherent structures (LCS). LCS objectively depict the flow topology and the extracted scintillation-producing irregularities that indicate a generation of ionospheric density gradients, due to the accumulation of plasma. The scintillation effects in propagation, through strongly inhomogeneous ionospheric media, are induced by trapping electromagnetic (EM) waves in parabolic cavities, which are created by the refractive index gradients along the propagation paths. (paper)

  17. Investigating the Relationships between Canopy Characteristics and Snow Depth Distribution at Fine Scales: Preliminary Results from the SnowEX TLS Campaign

    Glenn, N. F.; Uhlmann, Z.; Spaete, L.; Tennant, C.; Hiemstra, C. A.; McNamara, J.

    2017-12-01

    Predicting changes in forested seasonal snowpacks under altered climate scenarios is one of the most pressing hydrologic challenges facing today's society. Airborne- and satellite-based remote sensing methods hold the potential to transform measurements of terrestrial water stores in snowpack, improve process representations of snowpack accumulation and ablation, and to generate high quality predictions that inform potential strategies to better manage water resources. While the effects of forest on snowpack are well documented, many of the fine-scale processes influenced by the forest-canopy are not directly accounted for because most snow models don't explicitly represent canopy structure and canopy heterogeneity. This study investigates the influence of forest canopy on snowpack distribution at fine scales and quantifies the influence of canopy heterogeneity on snowpack accumulation and ablation processes. We use terrestrial laser scanning (TLS) data collected during the SnowEX campaign to discover how the relationships between canopy and snow distributions change across scales. Our sample scales range from individual trees to patches of trees across the Grand Mesa, CO, SnowEx site.

  18. Farms, pastures and woodlands: the fine-scale distribution of Palearctic Culicoides spp. biting midges along an agro-ecological gradient.

    Rigot, T; Drubbel, M Vercauteren; Delécolle, J-C; Gilbert, M

    2013-03-01

    The spatial epidemiology of Bluetongue virus (BTV) at the landscape level relates to the fine-scale distribution and dispersal capacities of its vectors, midges belonging to the genus Culicoides Latreille (Diptera: Ceratopogonidae). Although many previous researches have carried out Culicoides sampling on farms, little is known of the fine-scale distribution of Culicoides in the landscape immediately surrounding farms. The aim of this study was to gain a better understanding of Culicoides populations at increasing distances from typical dairy farms in north-west Europe, through the use of eight Onderstepoort-type black-light traps positioned along linear transects departing from farms, going through pastures and entering woodlands. A total of 16 902 Culicoides were collected in autumn 2008 and spring 2009. The majority were females, of which more than 97% were recognized as potential vectors. In pastures, we found decreasing numbers of female Culicoides as a function of the distance to the farm. This pattern was modelled by leptokurtic models, with parameters depending on season and species. By contrast, the low number of male Culicoides caught were homogeneously distributed along the transects. When transects entered woodlands, we found a higher abundance of Culicoides than expected considering the distance of the sampling sites to the farm, although this varied according to species. © 2012 The Authors. Medical and Veterinary Entomology © 2012 The Royal Entomological Society.

  19. Accelerating epistasis analysis in human genetics with consumer graphics hardware

    Cancare Fabio

    2009-07-01

    Full Text Available Abstract Background Human geneticists are now capable of measuring more than one million DNA sequence variations from across the human genome. The new challenge is to develop computationally feasible methods capable of analyzing these data for associations with common human disease, particularly in the context of epistasis. Epistasis describes the situation where multiple genes interact in a complex non-linear manner to determine an individual's disease risk and is thought to be ubiquitous for common diseases. Multifactor Dimensionality Reduction (MDR is an algorithm capable of detecting epistasis. An exhaustive analysis with MDR is often computationally expensive, particularly for high order interactions. This challenge has previously been met with parallel computation and expensive hardware. The option we examine here exploits commodity hardware designed for computer graphics. In modern computers Graphics Processing Units (GPUs have more memory bandwidth and computational capability than Central Processing Units (CPUs and are well suited to this problem. Advances in the video game industry have led to an economy of scale creating a situation where these powerful components are readily available at very low cost. Here we implement and evaluate the performance of the MDR algorithm on GPUs. Of primary interest are the time required for an epistasis analysis and the price to performance ratio of available solutions. Findings We found that using MDR on GPUs consistently increased performance per machine over both a feature rich Java software package and a C++ cluster implementation. The performance of a GPU workstation running a GPU implementation reduces computation time by a factor of 160 compared to an 8-core workstation running the Java implementation on CPUs. This GPU workstation performs similarly to 150 cores running an optimized C++ implementation on a Beowulf cluster. Furthermore this GPU system provides extremely cost effective

  20. Accelerating epistasis analysis in human genetics with consumer graphics hardware.

    Sinnott-Armstrong, Nicholas A; Greene, Casey S; Cancare, Fabio; Moore, Jason H

    2009-07-24

    Human geneticists are now capable of measuring more than one million DNA sequence variations from across the human genome. The new challenge is to develop computationally feasible methods capable of analyzing these data for associations with common human disease, particularly in the context of epistasis. Epistasis describes the situation where multiple genes interact in a complex non-linear manner to determine an individual's disease risk and is thought to be ubiquitous for common diseases. Multifactor Dimensionality Reduction (MDR) is an algorithm capable of detecting epistasis. An exhaustive analysis with MDR is often computationally expensive, particularly for high order interactions. This challenge has previously been met with parallel computation and expensive hardware. The option we examine here exploits commodity hardware designed for computer graphics. In modern computers Graphics Processing Units (GPUs) have more memory bandwidth and computational capability than Central Processing Units (CPUs) and are well suited to this problem. Advances in the video game industry have led to an economy of scale creating a situation where these powerful components are readily available at very low cost. Here we implement and evaluate the performance of the MDR algorithm on GPUs. Of primary interest are the time required for an epistasis analysis and the price to performance ratio of available solutions. We found that using MDR on GPUs consistently increased performance per machine over both a feature rich Java software package and a C++ cluster implementation. The performance of a GPU workstation running a GPU implementation reduces computation time by a factor of 160 compared to an 8-core workstation running the Java implementation on CPUs. This GPU workstation performs similarly to 150 cores running an optimized C++ implementation on a Beowulf cluster. Furthermore this GPU system provides extremely cost effective performance while leaving the CPU available for other

  1. The history and development of the Human Genetics Society of Australasia.

    Sutherland, Grant R

    2008-08-01

    The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.

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

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

    2014-01-01

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

  3. Fine-scale population structure of two anemones (Stichodactyla gigantea and Heteractis magnifica) in Kimbe Bay, Papua New Guinea

    Gatins, Remy

    2014-12-01

    Anemonefish are one of the main groups that have been used over the last decade to empirically measure larval dispersal and connectivity in coral reef populations. A few species of anemones are integral to the life history of these fish, as well as other obligate symbionts, yet the biology and population structure of these anemones remains poorly understood. The aim of this study was to measure the genetic structure of these anemones within and between two reefs in order to assess their reproductive mode and dispersal potential. To do this, we sampled almost exhaustively two anemones species (Stichodactyla gigantea and Heteractis magnifica) at two small islands in Kimbe Bay (Papua New Guinea) separated by approximately 25 km. Both the host anemones and the anemonefish are heavily targeted for the aquarium trade, in addition to the populations being affected by bleaching pressures (Hill and Scott 2012; Hobbs et al. 2013; Saenz- Agudelo et al. 2011; Thomas et al. 2014), therefore understanding their biology is crucial for better management strategies. Panels of microsatellite markers were developed for each species using next generation sequencing tools. Clonality analyses confirm six pairs of identical genotypes for S. gigantea (n=350) and zero for H. magnifica (n=128), indicating presence/absence of asexual reproduction in this region. S. gigantea showed low structure between islands (FST= 0.003, p-value= 0.000), however, even if the majority of the individuals were unrelated (r~0), 81 families that shared 50% of their genetic material formed from two to four members were found. Out of these families, 45% were found with individuals only within Tuare Island, 11% only in Kimbe Island, and 44% were sharing individuals among islands. In comparison, H. magnifica showed no structure (FST= 0.002, p-value= 0.278), mean relatedness indicated the majority of individuals were unrelated, and 31 families were identified. Families again consisted from two to four members and

  4. The concept of human dignity in the ethics of genetic research.

    Chan, David K

    2015-05-01

    Despite criticism that dignity is a vague and slippery concept, a number of international guidelines on bioethics have cautioned against research that is contrary to human dignity, with reference specifically to genetic technology. What is the connection between genetic research and human dignity? In this article, I investigate the concept of human dignity in its various historical forms, and examine its status as a moral concept. Unlike Kant's ideal concept of human dignity, the empirical or relational concept takes human dignity as something that is affected by one's circumstances and what others do. I argue that the dignity objection to some forms of genetic research rests on a view of human nature that gives humans a special status in nature - one that is threatened by the potential of genetic research to reduce individuals to their genetic endowment. I distinguish two main philosophical accounts of human nature. One of these, the Aristotelian view, is compatible with the use of genetic technology to help humans realize their inherent potential to a fuller extent. © 2014 John Wiley & Sons Ltd.

  5. human genetic engineering and social justice in south africa

    resources, are also acutely visible in the health-care sector. Genetic ... engineering (GE)2 from a South African perspective might not, initially, seem like an obvious ... prevalence of so-called genetic tourism, where couples from developed countries travel to countries in the developing world to undergo in vitro fertilisation ...

  6. Genetic polymorphisms and lipid response to dietary changes in humans

    Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Ramos-Galluzzi, J.; Katan, M.B.

    2001-01-01

    Previous studies on the effects of genetic polymorphisms on the serum cholesterol response to dietary treatments were often inconsistent and frequently involved small numbers of subjects. We studied the effect of 10 genetic polymorphisms on the responses of serum cholesterol to saturated and trans

  7. Genetic variation and effects on human eating behavior

    de Krom, Mariken; Bauer, Florianne; Collier, David; Adan, R. A. H.; la Fleur, Susanne E.

    2009-01-01

    Feeding is a physiological process, influenced by genetic factors and the environment. In recent years, many studies have been performed to unravel the involvement of genetics in both eating behavior and its pathological forms: eating disorders and obesity. In this review, we provide a condensed

  8. Formal genetic maps | Salem | Egyptian Journal of Medical Human ...

    Formal genetic maps are databases, represented as text or graphic figures, that can be collected/organized/formulated and constructed for nearly any, and every, structural or functional region of the genetic material. Though these maps are basically descriptive, their analysis can provide relevant crucial data that can be ...

  9. Fine-scale mapping of natural variation in fly fecundity identifies neuronal domain of expression and function of an aquaporin.

    Alan O Bergland

    Full Text Available To gain insight into the molecular genetic basis of standing variation in fitness related traits, we identify a novel factor that regulates the molecular and physiological basis of natural variation in female Drosophila melanogaster fecundity. Genetic variation in female fecundity in flies derived from a wild orchard population is heritable and largely independent of other measured life history traits. We map a portion of this variation to a single QTL and then use deficiency mapping to further refine this QTL to 5 candidate genes. Ubiquitous expression of RNAi against only one of these genes, an aquaporin encoded by Drip, reduces fecundity. Within our mapping population Drip mRNA level in the head, but not other tissues, is positively correlated with fecundity. We localize Drip expression to a small population of corazonin producing neurons located in the dorsolateral posterior compartments of the protocerebrum. Expression of Drip-RNAi using both the pan-neuronal ELAV-Gal4 and the Crz-Gal4 drivers reduces fecundity. Low-fecundity RILs have decreased Crz expression and increased expression of pale, the enzyme encoding the rate-limiting step in the production of dopamine, a modulator of insect life histories. Taken together these data suggest that natural variation in Drip expression in the corazonin producing neurons contributes to standing variation in fitness by altering the concentration of two neurohormones.

  10. Genetic regulation of immunoglobulin E level in different pathological states: integration of mouse and human genetics

    Gusareva, Elena; Kurey, Irina; Grekov, Igor; Lipoldová, Marie

    2014-01-01

    Roč. 89, č. 2 (2014), s. 375-405 ISSN 1464-7931 R&D Projects: GA ČR GA310/08/1697; GA MŠk LH12049 Institutional support: RVO:68378050 Keywords : Genetic control of complex diseases * Immunoglobulin E * Epistasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.670, year: 2014

  11. A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca, Pumas (Puma concolor, and Ocelots (Leopardus pardalis in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone.

    Claudia Wultsch

    Full Text Available With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca, pumas (Puma concolor, and ocelots (Leopardus pardalis. We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09, followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16, and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08. We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes.

  12. The impact of advances in human molecular biology on radiation genetic risk estimation in man

    Sankaranarayanan, K.

    1996-01-01

    This paper provides an overview of the conceptual framework, the data base, methods and assumptions used thus far to assess the genetic risks of exposure of human populations to ionising radiation. These are then re-examined in the contemporary context of the rapidly expanding knowledge of the molecular biology of human mendelian diseases. This re-examination reveals that (i) many of the assumptions used thus far in radiation genetic risk estimation may not be fully valid and (ii) the current genetic risk estimates are probably conservative, but provide an adequate margin of safety for radiological protection. The view is expressed that further advances in the field of genetic risk estimation will be largely driven by advances in the molecular biology of human genetic diseases. (author). 37 refs., 5 tabs

  13. Insights from human genetic studies of lung and organ fibrosis.

    Garcia, Christine Kim

    2018-01-02

    Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. This Review focuses on pathways underlying lung fibrosis that are generalizable to other organs. Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. Genetic studies provide a window into the downstream cascade of maladaptive responses and pathways that lead to tissue fibrosis. In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. The discovery of forces counterbalancing inherited risk alleles identifies potential therapeutic targets, thus providing hope for future prevention or reversal of fibrosis.

  14. Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...

    PROGMANAGER

    2013-04-24

    Apr 24, 2013 ... objective of this study was to determine the genetic diversity of HIV-1 and the prevalence of antiretroviral (ARV) ... individuals in resource limited settings. Key words: ... management of HIV infection even as antiretroviral (ARV).

  15. Evaluation of the role of genetic factors in human radioresistance

    Telnov, Vitaliy I.; Sotnik, Natalie V.

    2002-01-01

    This study was focused on evaluation of the role of genetic factors in development of chronic radiation sickness (CRS) due to occupational exposure to external γ -rays. This study was based on results of molecular-genetic studies for 985 nuclear workers of the Mayak Production Association. CRS occurrence was related to the genetic haptoglobin (Hp) system among a number of studied genetic markers. Excess risk of CRS was revealed at similar exposure doses for individuals-carriers of Hp 2-2 (1.96) versus lower risks for carriers of Hp 1-1 and 2-1 (0.64). The contribution of genetic factors to CRS development was implemented in a rather narrow dose range, i.e. it was of a relative nature. A scheme of the relationship of affecting factor and differences in genetic radioresistance was presented in terms of deterministic effects. The obtained data did not confirm the idea that A-bomb survivors were more radioresistant, thus being not representative for radiation risk estimation

  16. Regulating human genetic research in Latin America: a race to the top or a race together?

    Rosario Isasi

    2016-05-01

    Full Text Available Balancing the therapeutic potential of genetic science with the adoption of policies that reflect social values has proven to be a formidable task for Latin American countries. This essay presents some reflections on human genetics research policy in Latin America and explores a path forward for policy development.

  17. Using human genetics to predict the effects and side-effects of drugs

    Stender, Stefan; Tybjærg-Hansen, Anne

    2016-01-01

    PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG-Coenzyme A re...

  18. An integrated map of genetic variation from 1.092 human genomes

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination ...

  19. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo

    2016-01-01

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic...

  20. Precision Medicine and Advancing Genetic Technologies—Disability and Human Rights Perspectives

    Aisling de Paor

    2016-08-01

    Full Text Available Scientific and technological developments are propelling genetics and genetic technologies into the public sphere. Scientific and technological innovation is becoming more refined, resulting in an increase in the availability and use of genetic testing, and other cutting edge genetic technologies, including gene editing. These genetic advances not only signal a growing trend towards precision medicine, but also provoke consideration of the protection of genetic information as an emerging human rights concern. Particular ethical and legal issues arise from a disability perspective, including the potential for discrimination and privacy violations. In consideration of the intersection of genetics and disability, this article highlights the significant concerns raised as genetic science and technology advances, and the consequences for disability rights, particularly the core concepts of non-discrimination, and respect for diversity and difference. On examining international human rights perspectives, it looks particularly at the UN Convention on the Rights of Persons with Disabilities and how it may be used to guide best practice in this area. With an acknowledgement of historical abuses of genetic science, this article highlights the need to maintain caution as to the potential consequences of advancing genetic technologies on persons with disabilities and indeed on society as a whole.

  1. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

    Zeng, Chenjie; Guo, Xingyi; Long, Jirong

    2016-01-01

    BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300...... Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants...... with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P 

  2. Fine-scale environmental effects on Cape hake survey catch rates in the Northern Benguela, using data from a trawl-mounted instrument package

    Kainge, Paulus Inekela; Wieland, Kai

    2017-01-01

    We investigated fine-scale effects of environmental variables associated with habitat distribution for 4 size groups of Cape hakes, Merluccius capensis and M. paradoxus, using generalized additive models (GAMs) with a negative binominal error distribution. This study took place during the Namibian...... hake trawl survey of 2016, and was made possible for the first time in Namibia by collecting oceanographic information with a trawl-mounted instrument package concurrently with the catch data. Depth, geographical position, bottom oxygen and bottom temperature had the most pronounced effect on the catch...... rates of both hake species, whereas solar zenith angle representing diel effects and surface layer chlorophyll appeared to be less important. The explained deviance for the best models ranged from 71.4% for M. capensis to 92.7% for M. paradoxus between 43 and 57 cm in length. Differences in catch rates...

  3. Egyptian Journal of Medical Human Genetics - Vol 11, No 1 (2010)

    Egyptian Journal of Medical Human Genetics - Vol 11, No 1 (2010) ... Gene polymorphisms of TNF-α and IL-10 related to rheumatic heart disease · EMAIL ... with familial Mediterranean fever · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  4. Egyptian Journal of Medical Human Genetics - Vol 13, No 2 (2012)

    Egyptian Journal of Medical Human Genetics - Vol 13, No 2 (2012) ... as independent indicators for B-CLL: Correlation to response to treatment and disease ... Profile of disorders of sexual differentiation in the Northeast region of Cairo, Egypt ...

  5. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans

    Verloop, H.; Dekkers, O.M.; Peeters, R.P.; Schoones, J.W.; Smit, J.W.

    2014-01-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple

  6. Fine-scale assessment of home ranges and activity patterns for resident black vultures (Coragyps atratus and turkey vultures (Cathartes aura.

    Amanda E Holland

    Full Text Available Knowledge of black vulture (Coragyps atratus and turkey vulture (Cathartes aura spatial ecology is surprisingly limited despite their vital ecological roles. Fine-scale assessments of space use patterns and resource selection are particularly lacking, although development of tracking technologies has allowed data collection at finer temporal and spatial resolution. Objectives of this study were to conduct the first assessment of monthly home range and core area sizes of resident black and turkey vultures with consideration to sex, as well as elucidate differences in monthly, seasonal, and annual activity patterns based on fine-scale movement data analyses. We collected 2.8-million locations for 9 black and 9 turkey vultures from June 2013 -August 2015 using solar-powered GSM/GPS transmitters. We quantified home ranges and core areas using the dynamic Brownian bridge movement model and evaluated differences as a function of species, sex, and month. Mean monthly home ranges for turkey vultures were ~50% larger than those of black vultures, although mean core area sizes did not differ between species. Turkey vulture home ranges varied little across months, with exception to a notable reduction in space-use in May, which corresponds with timing of chick-rearing activities. Black vulture home ranges and core areas as well as turkey vulture core areas were larger in breeding season months (January-April. Comparison of space use between male and female vultures was only possible for black vultures, and space use was only slightly larger for females during breeding months (February-May. Analysis of activity patterns revealed turkey vultures spend more time in flight and switch motion states (between flight and stationary more frequently than black vultures across temporal scales. This study reveals substantive variability in space use and activity rates between sympatric black and turkey vultures, providing insights into potential behavioral mechanisms

  7. Modelling Deep Water Habitats to Develop a Spatially Explicit, Fine Scale Understanding of the Distribution of the Western Rock Lobster, Panulirus cygnus

    Hovey, Renae K.; Van Niel, Kimberly P.; Bellchambers, Lynda M.; Pember, Matthew B.

    2012-01-01

    Background The western rock lobster, Panulirus cygnus, is endemic to Western Australia and supports substantial commercial and recreational fisheries. Due to and its wide distribution and the commercial and recreational importance of the species a key component of managing western rock lobster is understanding the ecological processes and interactions that may influence lobster abundance and distribution. Using terrain analyses and distribution models of substrate and benthic biota, we assess the physical drivers that influence the distribution of lobsters at a key fishery site. Methods and Findings Using data collected from hydroacoustic and towed video surveys, 20 variables (including geophysical, substrate and biota variables) were developed to predict the distributions of substrate type (three classes of reef, rhodoliths and sand) and dominant biota (kelp, sessile invertebrates and macroalgae) within a 40 km2 area about 30 km off the west Australian coast. Lobster presence/absence data were collected within this area using georeferenced pots. These datasets were used to develop a classification tree model for predicting the distribution of the western rock lobster. Interestingly, kelp and reef were not selected as predictors. Instead, the model selected geophysical and geomorphic scalar variables, which emphasise a mix of terrain within limited distances. The model of lobster presence had an adjusted D2 of 64 and an 80% correct classification. Conclusions Species distribution models indicate that juxtaposition in fine scale terrain is most important to the western rock lobster. While key features like kelp and reef may be important to lobster distribution at a broad scale, it is the fine scale features in terrain that are likely to define its ecological niche. Determining the most appropriate landscape configuration and scale will be essential to refining niche habitats and will aid in selecting appropriate sites for protecting critical lobster habitats. PMID

  8. Understory Plant Community Composition Is Associated with Fine-Scale Above- and Below-Ground Resource Heterogeneity in Mature Lodgepole Pine (Pinus contorta Forests.

    Anne C S McIntosh

    Full Text Available Understory plant communities play critical ecological roles in forest ecosystems. Both above- and below-ground ecosystem properties and processes influence these communities but relatively little is known about such effects at fine (i.e., one to several meters within-stand scales, particularly for forests in which the canopy is dominated by a single species. An improved understanding of these effects is critical for understanding how understory biodiversity is regulated in such forests and for anticipating impacts of changing disturbance regimes. Our primary objective was to examine the patterns of fine-scale variation in understory plant communities and their relationships to above- and below-ground resource and environmental heterogeneity within mature lodgepole pine forests. We assessed composition and diversity of understory vegetation in relation to heterogeneity of both the above-ground (canopy tree density, canopy and tall shrub basal area and cover, downed wood biomass, litter cover and below-ground (soil nutrient availability, decomposition, forest floor thickness, pH, and phospholipid fatty acids (PLFAs and multiple carbon-source substrate-induced respiration (MSIR of the forest floor microbial community environment. There was notable variation in fine-scale plant community composition; cluster and indicator species analyses of the 24 most commonly occurring understory species distinguished four assemblages, one for which a pioneer forb species had the highest cover levels, and three others that were characterized by different bryophyte species having the highest cover. Constrained ordination (distance-based redundancy analysis showed that two above-ground (mean tree diameter, litter cover and eight below-ground (forest floor pH, plant available boron, microbial community composition and function as indicated by MSIR and PLFAs properties were associated with variation in understory plant community composition. These results provide

  9. Understory Plant Community Composition Is Associated with Fine-Scale Above- and Below-Ground Resource Heterogeneity in Mature Lodgepole Pine (Pinus contorta) Forests.

    McIntosh, Anne C S; Macdonald, S Ellen; Quideau, Sylvie A

    2016-01-01

    Understory plant communities play critical ecological roles in forest ecosystems. Both above- and below-ground ecosystem properties and processes influence these communities but relatively little is known about such effects at fine (i.e., one to several meters within-stand) scales, particularly for forests in which the canopy is dominated by a single species. An improved understanding of these effects is critical for understanding how understory biodiversity is regulated in such forests and for anticipating impacts of changing disturbance regimes. Our primary objective was to examine the patterns of fine-scale variation in understory plant communities and their relationships to above- and below-ground resource and environmental heterogeneity within mature lodgepole pine forests. We assessed composition and diversity of understory vegetation in relation to heterogeneity of both the above-ground (canopy tree density, canopy and tall shrub basal area and cover, downed wood biomass, litter cover) and below-ground (soil nutrient availability, decomposition, forest floor thickness, pH, and phospholipid fatty acids (PLFAs) and multiple carbon-source substrate-induced respiration (MSIR) of the forest floor microbial community) environment. There was notable variation in fine-scale plant community composition; cluster and indicator species analyses of the 24 most commonly occurring understory species distinguished four assemblages, one for which a pioneer forb species had the highest cover levels, and three others that were characterized by different bryophyte species having the highest cover. Constrained ordination (distance-based redundancy analysis) showed that two above-ground (mean tree diameter, litter cover) and eight below-ground (forest floor pH, plant available boron, microbial community composition and function as indicated by MSIR and PLFAs) properties were associated with variation in understory plant community composition. These results provide novel insights

  10. Modelling deep water habitats to develop a spatially explicit, fine scale understanding of the distribution of the western rock lobster, Panulirus cygnus.

    Renae K Hovey

    Full Text Available BACKGROUND: The western rock lobster, Panulirus cygnus, is endemic to Western Australia and supports substantial commercial and recreational fisheries. Due to and its wide distribution and the commercial and recreational importance of the species a key component of managing western rock lobster is understanding the ecological processes and interactions that may influence lobster abundance and distribution. Using terrain analyses and distribution models of substrate and benthic biota, we assess the physical drivers that influence the distribution of lobsters at a key fishery site. METHODS AND FINDINGS: Using data collected from hydroacoustic and towed video surveys, 20 variables (including geophysical, substrate and biota variables were developed to predict the distributions of substrate type (three classes of reef, rhodoliths and sand and dominant biota (kelp, sessile invertebrates and macroalgae within a 40 km(2 area about 30 km off the west Australian coast. Lobster presence/absence data were collected within this area using georeferenced pots. These datasets were used to develop a classification tree model for predicting the distribution of the western rock lobster. Interestingly, kelp and reef were not selected as predictors. Instead, the model selected geophysical and geomorphic scalar variables, which emphasise a mix of terrain within limited distances. The model of lobster presence had an adjusted D(2 of 64 and an 80% correct classification. CONCLUSIONS: Species distribution models indicate that juxtaposition in fine scale terrain is most important to the western rock lobster. While key features like kelp and reef may be important to lobster distribution at a broad scale, it is the fine scale features in terrain that are likely to define its ecological niche. Determining the most appropriate landscape configuration and scale will be essential to refining niche habitats and will aid in selecting appropriate sites for protecting critical

  11. Natural selection drives the fine-scale divergence of a coevolutionary arms race involving a long-mouthed weevil and its obligate host plant

    Toju Hirokazu

    2009-01-01

    Full Text Available Abstract Background One of the major recent advances in evolutionary biology is the recognition that evolutionary interactions between species are substantially differentiated among geographic populations. To date, several authors have revealed natural selection pressures mediating the geographically-divergent processes of coevolution. How local, then, is the geographic structuring of natural selection in coevolutionary systems? Results I examined the spatial scale of a "geographic selection mosaic," focusing on a system involving a seed-predatory insect, the camellia weevil (Curculio camelliae, and its host plant, the Japanese camellia (Camellia japonica. In this system, female weevils excavate camellia fruits with their extremely-long mouthparts to lay eggs into seeds, while camellia seeds are protected by thick pericarps. Quantitative evaluation of natural selection demonstrated that thicker camellia pericarps are significantly favored in some, but not all, populations within a small island (Yakushima Island, Japan; diameter ca. 30 km. At the extreme, camellia populations separated by only several kilometers were subject to different selection pressures. Interestingly, in a population with the thickest pericarps, camellia individuals with intermediate pericarp thickness had relatively high fitness when the potential costs of producing thick pericarps were considered. Also importantly, some parameters of the weevil - camellia interaction such as the severity of seed infestation showed clines along temperature, suggesting the effects of climate on the fine-scale geographic differentiation of the coevolutionary processes. Conclusion These results show that natural selection can drive the geographic differentiation of interspecific interactions at surprisingly small spatial scales. Future studies should reveal the evolutionary/ecological outcomes of the "fine scale geographic mosaics" in biological communities.

  12. Understory Plant Community Composition Is Associated with Fine-Scale Above- and Below-Ground Resource Heterogeneity in Mature Lodgepole Pine (Pinus contorta) Forests

    McIntosh, Anne C. S.; Macdonald, S. Ellen; Quideau, Sylvie A.

    2016-01-01

    Understory plant communities play critical ecological roles in forest ecosystems. Both above- and below-ground ecosystem properties and processes influence these communities but relatively little is known about such effects at fine (i.e., one to several meters within-stand) scales, particularly for forests in which the canopy is dominated by a single species. An improved understanding of these effects is critical for understanding how understory biodiversity is regulated in such forests and for anticipating impacts of changing disturbance regimes. Our primary objective was to examine the patterns of fine-scale variation in understory plant communities and their relationships to above- and below-ground resource and environmental heterogeneity within mature lodgepole pine forests. We assessed composition and diversity of understory vegetation in relation to heterogeneity of both the above-ground (canopy tree density, canopy and tall shrub basal area and cover, downed wood biomass, litter cover) and below-ground (soil nutrient availability, decomposition, forest floor thickness, pH, and phospholipid fatty acids (PLFAs) and multiple carbon-source substrate-induced respiration (MSIR) of the forest floor microbial community) environment. There was notable variation in fine-scale plant community composition; cluster and indicator species analyses of the 24 most commonly occurring understory species distinguished four assemblages, one for which a pioneer forb species had the highest cover levels, and three others that were characterized by different bryophyte species having the highest cover. Constrained ordination (distance-based redundancy analysis) showed that two above-ground (mean tree diameter, litter cover) and eight below-ground (forest floor pH, plant available boron, microbial community composition and function as indicated by MSIR and PLFAs) properties were associated with variation in understory plant community composition. These results provide novel insights

  13. Modelling deep water habitats to develop a spatially explicit, fine scale understanding of the distribution of the western rock lobster, Panulirus cygnus.

    Hovey, Renae K; Van Niel, Kimberly P; Bellchambers, Lynda M; Pember, Matthew B

    2012-01-01

    The western rock lobster, Panulirus cygnus, is endemic to Western Australia and supports substantial commercial and recreational fisheries. Due to and its wide distribution and the commercial and recreational importance of the species a key component of managing western rock lobster is understanding the ecological processes and interactions that may influence lobster abundance and distribution. Using terrain analyses and distribution models of substrate and benthic biota, we assess the physical drivers that influence the distribution of lobsters at a key fishery site. Using data collected from hydroacoustic and towed video surveys, 20 variables (including geophysical, substrate and biota variables) were developed to predict the distributions of substrate type (three classes of reef, rhodoliths and sand) and dominant biota (kelp, sessile invertebrates and macroalgae) within a 40 km(2) area about 30 km off the west Australian coast. Lobster presence/absence data were collected within this area using georeferenced pots. These datasets were used to develop a classification tree model for predicting the distribution of the western rock lobster. Interestingly, kelp and reef were not selected as predictors. Instead, the model selected geophysical and geomorphic scalar variables, which emphasise a mix of terrain within limited distances. The model of lobster presence had an adjusted D(2) of 64 and an 80% correct classification. Species distribution models indicate that juxtaposition in fine scale terrain is most important to the western rock lobster. While key features like kelp and reef may be important to lobster distribution at a broad scale, it is the fine scale features in terrain that are likely to define its ecological niche. Determining the most appropriate landscape configuration and scale will be essential to refining niche habitats and will aid in selecting appropriate sites for protecting critical lobster habitats.

  14. The ecological imperative and its application to ethical issues in human genetic technology

    W. Malcolm Byrnes

    2003-01-01

    As a species, we are on the cusp of being able to alter that which makes us uniquely human, our genome. Two new genetic technologies, embryo selection and germline engineering, are either in use today or may be developed in the future. Embryo selection acts to alter the human gene pool, reducing genetic diversity, while germline engineering will have the ability to alter directly the genomes of engineered individuals. Our genome has come to be what it is through an evolutionary process extend...

  15. The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

    Pinborg, Lars H; Arfan, Haroon; Haugbol, Steven

    2007-01-01

    With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human...... brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between...

  16. Lineage range estimation method reveals fine-scale endemism linked to Pleistocene stability in Australian rainforest herpetofauna.

    Rosauer, Dan F; Catullo, Renee A; VanDerWal, Jeremy; Moussalli, Adnan; Moritz, Craig

    2015-01-01

    Areas of suitable habitat for species and communities have arisen, shifted, and disappeared with Pleistocene climate cycles, and through this shifting landscape, current biodiversity has found paths to the present. Evolutionary refugia, areas of relative habitat stability in this shifting landscape, support persistence of lineages through time, and are thus crucial to the accumulation and maintenance of biodiversity. Areas of endemism are indicative of refugial areas where diversity has persisted, and endemism of intraspecific lineages in particular is strongly associated with late-Pleistocene habitat stability. However, it remains a challenge to consistently estimate the geographic ranges of intraspecific lineages and thus infer phylogeographic endemism, because spatial sampling for genetic analyses is typically sparse relative to species records. We present a novel technique to model the geographic distribution of intraspecific lineages, which is informed by the ecological niche of a species and known locations of its constituent lineages. Our approach allows for the effects of isolation by unsuitable habitat, and captures uncertainty in the extent of lineage ranges. Applying this method to the arc of rainforest areas spanning 3500 km in eastern Australia, we estimated lineage endemism for 53 species of rainforest dependent herpetofauna with available phylogeographic data. We related endemism to the stability of rainforest habitat over the past 120,000 years and identified distinct concentrations of lineage endemism that can be considered putative refugia. These areas of lineage endemism are strongly related to historical stability of rainforest habitat, after controlling for the effects of current environment. In fact, a dynamic stability model that allows movement to track suitable habitat over time was the most important factor in explaining current patterns of endemism. The techniques presented here provide an objective, practical method for estimating

  17. Human genetics as a tool to identify progranulin regulators.

    Nicholson, Alexandra M; Finch, NiCole A; Rademakers, Rosa

    2011-11-01

    Frontotemporal lobar degeneration (FTLD) is a common neurodegenerative disorder that predominantly affects individuals under the age of 65. It is known that the most common pathological subtype is FTLD with TAR DNA-binding protein 43 inclusions (FTLD-TDP). FTLD has a strong genetic component with about 50% of cases having a positive family history. Mutations identified in the progranulin gene (GRN) have been shown to cause FTLD-TDP as a result of progranulin haploinsufficiency. These findings suggest a progranulin-dependent mechanism in this pathological FTLD subtype. Thus, identifying regulators of progranulin levels is essential for new therapies and treatments for FTLD and related disorders. In this review, we discuss the role of genetic studies in identifying progranulin regulators, beginning with the discovery of pathogenic GRN mutations and additional GRN risk variants. We also cover more recent genetic advances, including the detection of variants in the transmembrane protein 106 B gene that increase FTLD-TDP risk presumably by modulating progranulin levels and the identification of a potential progranulin receptor, sortilin. This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases.

  18. Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.

    Gu, Yulong; Warren, James Roy; Day, Karen Jean

    2011-01-01

    This study aimed to characterize the challenges in using genetic information in health care and to identify opportunities for improvement. Taking a grounded theory approach, semistructured interviews were conducted with 48 participants to collect multiple stakeholder perspectives on genetic services in New Zealand. Three themes emerged from the data: (1) four service delivery models were identified in operation, including both those expected models involving genetic counselors and variations that do not route through the formal genetic service program; (2) multiple barriers to sharing and using genetic information were perceived, including technological, organizational, institutional, legal, ethical, and social issues; and (3) impediments to wider use of genetic testing technology, including variable understanding of genetic test utilities among clinicians and the limited capacity of clinical genetic services. Targeting these problems, information technologies and knowledge management tools have the potential to support key tasks in genetic services delivery, improve knowledge processes, and enhance knowledge networks. Because of the effect of issues in genetic information and knowledge management, the potential of human genetic variation knowledge to enhance health care delivery has been put on a "leash."

  19. Human Genome Epidemiology : A scientific foundation for using genetic information to improve health and prevent disease

    Stefania Boccia

    2005-03-01

    Full Text Available

    Human health is determined by the interplay of genetic factors and the environment. In this context the recent advances in human genomics are expected to play a central role in medicine and public health by providing genetic information for disease prediction and prevention.

    After the completion of the human genome sequencing, a fundamental step will be represented by the translation of these discoveries into meaningful actions to improve health and prevent diseases, and the field of epidemiology plays a central role in this effort. These are some of the issues addressed by Human Genome Epidemiology –A scientific foundation for using genetic information to improve health and prevent disease, a volume edited by Prof. M. Khoury, Prof. J. Little, Prof.W. Burke and published by Oxford university Press 2004.

    This book describes the important role that epidemiological methods play in the continuum from gene discovery to the development and application of genetic tests. The Authors calls this continuum human genome epidemiology (HuGE to denote an evolving field of inquiry that uses systematic applications of epidemiological methods to assess the impact of human genetic variation on health and disease.

    The book is divided into four sections and it is structured to allow readers to proceed systematically from the fundamentals of genome technology and discovery, to the epidemiological approaches, to gene characterisation, to the evaluation of genetic tests and their use in health services and public health.

  20. Human Genetic Variation and Parkinson’s Disease

    Sun Ju Chung

    2010-05-01

    Full Text Available Parkinson’s disease (PD is a chronic neurodegenerative disorder with multifactorial etiology. In the past decade, the genetic causes of monogenic forms of familial PD have been defined. However, the etiology and pathogenesis of the majority of sporadic PD cases that occur in outbred populations have yet to be clarified. The recent development of resources such as the International HapMap Project and technological advances in high-throughput genotyping have provided new basis for genetic association studies of common complex diseases, including PD. A new generation of genome-wide association studies will soon offer a potentially powerful approach for mapping causal genes and will likely change treatment and alter our perception of the genetic determinants of PD. However, the execution and analysis of such studies will require great care.

  1. Fine-scale genetic analysis of Daphnia host populations infected by two virulent parasites - strong fluctuations in clonal structure at small temporal and spatial scales

    Yin, M.; Petrusek, A.; Seďa, Jaromír; Wolinska, J.

    2012-01-01

    Roč. 42, č. 1 (2012), s. 115-121 ISSN 0020-7519 R&D Projects: GA AV ČR(CZ) IAA600960901 Institutional support: RVO:60077344 Keywords : Caullerya mesnili * clonal composition * hybridization * Metschnikowia * microsatellite * taxon composition Subject RIV: EG - Zoology Impact factor: 3.637, year: 2012

  2. Genetics of Human Sexual Behavior: Where We Are, Where We Are Going.

    Jannini, Emmanuele A; Burri, Andrea; Jern, Patrick; Novelli, Giuseppe

    2015-04-01

    One of the never-ending debates in the developing field of sexual medicine is the extent to which genetics and experiences (i.e., "nature and nurture") contribute to sexuality. The debate continues despite the fact that these two sides have different abilities to create a scientific environment to support their cause. Contemporary genetics has produced plenty of recent evidence, however, not always confirmed or sufficiently robust. On the other hand, the more traditional social theorists, frequently without direct evidence confirming their positions, criticize, sometimes with good arguments, the methods and results of the other side. The aim of this article is to critically evaluate existent evidence that used genetic approaches to understand human sexuality. An expert in sexual medicine (E.A.J.), an expert in medical genetics (G.N.), and two experts in genetic epidemiology and quantitative genetics, with particular scientific experience in female sexual dysfunction (A.B.) and in premature ejaculation (P.J.), contributed to this review. Expert opinion supported by critical review of the currently available literature. The existing literature on human sexuality provides evidence that many sexuality-related behaviors previously considered to be the result of cultural influences (such as mating strategies, attractiveness and sex appeal, propensity to fidelity or infidelity, and sexual orientation) or dysfunctions (such as premature ejaculation or female sexual dysfunction) seem to have a genetic component. Current evidence from genetic epidemiologic studies underlines the existence of biological and congenital factors regulating male and female sexuality. However, these relatively recent findings ask for replication in methodologically more elaborated studies. Clearly, increased research efforts are needed to further improve understanding the genetics of human sexuality. Jannini EA, Burri A, Jern P, and Novelli G. Genetics of human sexual behavior: Where we are, where

  3. Triplet repeat DNA structures and human genetic disease

    Laboratory of DNA Structure and Mutagenesis, Center for Genome Research, Institute of Biosciences and Technology, Texas A&M University System Health Sciences Center, 2121 West Holcombe Blvd., Houston, TX 77030-3303, USA; Hospital for Sick Children, Department of Genetics, 555 University Avenue, Elm Wing, ...

  4. Inauguration of the Cameroonian Society of Human Genetics ...

    The conjunction of “hard genetics” research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual ... The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an ...

  5. Genetical genomic determinants of alcohol consumption in rats and humans

    Tabakoff, B.; Saba, L.; Printz, M.; Flodman, P.; Hodgkinson, C.; Goldman, D.; Koob, G.; Richardson, H.N.; Kechris, K.; Bell, R.L.; Hübner, N.; Heinig, M.; Pravenec, Michal; Mangion, J.; Legault, L.; Dongier, M.; Conigrave, K.M.; Whitfield, J.B.; Saunders, J.; Grant, B.; Hoffman, P.L.

    2009-01-01

    Roč. 7, - (2009), s. 70-70 ISSN 1741-7007 R&D Projects: GA MŠk(CZ) 1M0520 Grant - others:Howard Hughes Medical Institute(US) 55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : alcohol consumption * rat * gene expression profiles Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.636, year: 2009

  6. Fine-Scale Movements and Behaviors of Whale Sharks, Rhincodon typus, in a Seasonal Aggregation near Al Lith, Saudi Arabia

    Sun, Lu

    2016-12-01

    Movement and behavior studies are traditional yet effective ways to understand the biology and ecology of a species. For an endangered species like the whale shark (Rhincodon typus), a comprehensive knowledge of its movement and behavior is particularly critical for successful management and conservation. For this dissertation, acoustic telemetry and biologging tagging studies were carried out at a seasonal whale shark aggregation site near Al Lith in the Saudi Arabian Red Sea. Acoustic telemetry data revealed consistent path usage in a narrow longshore area with patterns in seasonality and diel horizontal movements within a smaller scale. Some individuals specifically concentrated on this path and made non-stop back and forth movements along it. In another dimension, depth use of whale sharks derived from biologgers showed distinct diel patterns. The sharks heavily utilized shallow waters with mixed depth usage consisting of surface swimming and varied types of dives, which explained the data of previous visual surveys. Vertical velocities indicated potential energy expenditure strategies that were further investigated based on acceleration data. Energy expenditure data suggested strategies that fine-tuned foraging efforts to optimize the balance between feeding and foraging. However, while these strategies fit well in the natural habitat, local human impacts could be of great disturbance if not well managed.

  7. The genetics of human longevity: an intricacy of genes, environment, culture and microbiome.

    Dato, Serena; Rose, Giuseppina; Crocco, Paolina; Monti, Daniela; Garagnani, Paolo; Franceschi, Claudio; Passarino, Giuseppe

    2017-07-01

    Approximately one-quarter of the variation in lifespan in developed countries can be attributed to genetic factors. However, even large population based studies investigating genetic influence on human lifespan have been disappointing, identifying only a few genes accounting for genetic susceptibility to longevity. Some environmental and lifestyle determinants associated with longevity have been identified, which interplay with genetic factors in an intricate way. The study of gene-environment and gene-gene interactions can significantly improve our chance to disentangle this complex scenario. In this review, we first describe the most recent approaches for genetic studies of longevity, from those enriched with health parameters and frailty measures to pathway-based and SNP-SNP interaction analyses. Then, we go deeper into the concept of "environmental influences" in human aging and longevity, focusing on the contribution of life style changes, social and cultural influences, as important determinants of survival differences among individuals in a population. Finally, we discuss the contribution of the microbiome in human longevity, as an example of complex interaction between organism and environment. In conclusion, evidences collected from the latest studies on human longevity provide a support for the collection of life-long genetic and environmental/lifestyle variables with beneficial or detrimental effects on health, to improve our understanding of the determinants of human lifespan. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Human genetic studies in areas of high natural radiation VI. Genetical load and ethnic group

    Freire-Maia, A [Faculdade de Ciencias Medicas e Biologicas de Botucatu (Brazil). Departamento de Genetica

    1974-01-01

    The load of mutations disclosed by inbreeding, according to the ethnic group of the parents, has been analyzed in our data. Besides the total of the population, a sample with no alien ancestrals has also been analyzed. Genetic load has been studied for absortions, still births, pos-natal mortality, total mortality, anomalies, total mortality + anomalies, and abnormalities in general.

  9. Human genetic studies in areas of high natural radiation VI. Genetical load and ethnic group

    Freire-Maia, A.

    1974-01-01

    The load of mutations disclosed by inbreeding, according to the ethnic group of the parents, has been analyzed in our data. Besides the total of the population, a sample with no alien ancestrals has also been analyzed. Genetic load has been studied for absortions, still births, pos-natal mortality, total mortality, anomalies, total mortality + anomalies, and abnormalities in general [pt

  10. Comparison of French and Estonian Students' Conceptions in Genetic Determinism of Human Behaviours

    Castera, Jeremy; Sarapuu, Tago; Clement, Pierre

    2013-01-01

    Innatism is the belief that most of the human personality can be determined by genes. This ideology is dangerous, especially when it claims to be scientific. The present study investigates conceptions of 1060 students from Estonia and France related to genetic determinism of some human behaviours. Factors taken into account included students'…

  11. Human genetics studies in areas of high natural radiation, 7

    Freire-Maia, A.

    1975-01-01

    Two methods to estimate the inbreeding load, employed in our analysis, are reviewed. Besides the total population, a sample constituted of individuals with no alien ancestral is also analysed. The measurements by genetic load models show any clear effect of natural radioactivity (especially for abortions, pre-natal mortality, anomalies, and abnormalities in general). The results on stillbirths and post-natal and total mortalities are discussed and it is concluded that uncontrolled concomitant variables (if not chance alone) cause the differences [pt

  12. Genetic Regulation of Pituitary Gland Development in Human and Mouse

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

    2009-01-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndr...

  13. Population genetic analysis of Enterocytozoon bieneusi in humans.

    Li, Wei; Cama, Vitaliano; Feng, Yaoyu; Gilman, Robert H; Bern, Caryn; Zhang, Xichen; Xiao, Lihua

    2012-01-01

    Genotyping based on sequence analysis of the ribosomal internal transcribed spacer has revealed significant genetic diversity in Enterocytozoonbieneusi. Thus far, the population genetics of E. bieneusi and its significance in the epidemiology of microsporidiosis have not been examined. In this study, a multilocus sequence typing of E. bieneusi in AIDS patients in Lima, Peru was conducted, using 72 specimens previously genotyped as A, D, IV, EbpC, WL11, Peru7, Peru8, Peru10 and Peru11 at the internal transcribed spacer locus. Altogether, 39 multilocus genotypes were identified among the 72 specimens. The observation of strong intragenic linkage disequilibria and limited genetic recombination among markers were indicative of an overall clonal population structure of E. bieneusi. Measures of pair-wise intergenic linkage disequilibria and a standardised index of association (IAS) based on allelic profile data further supported this conclusion. Both sequence-based and allelic profile-based phylogenetic analyses showed the presence of two genetically isolated groups in the study population, one (group 1) containing isolates of the anthroponotic internal transcribed spacer genotype A, and the other (group 2) containing isolates of multiple internal transcribed spacer genotypes (mainly genotypes D and IV) with zoonotic potential. The measurement of linkage disequilibria and recombination indicated group 2 had a clonal population structure, whereas group 1 had an epidemic population structure. The formation of the two sub-populations was confirmed by STRUCTURE and Wright's fixation index (FST) analyses. The data highlight the power of MLST in understanding the epidemiology of E. bieneusi. Published by Elsevier Ltd.

  14. Genetic analysis of variation in human meiotic recombination.

    Reshmi Chowdhury

    2009-09-01

    Full Text Available The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize recombination landscape and to map the genetic variants that contribute to variation in recombination phenotypes. We found six genetic loci that are associated with recombination phenotypes. Two of these (RNF212 and an inversion on chromosome 17q21.31 were previously reported in the Icelandic population, and this is the first replication in any other population. Of the four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1, results from expression studies provide support for their roles in meiosis. Each of the variants that we identified explains only a small fraction of the individual variation in recombination. Notably, we found different sequence variants associated with female and male recombination phenotypes, suggesting that they are regulated by different genes. Characterization of genetic variants that influence natural variation in meiotic recombination will lead to a better understanding of normal meiotic events as well as of non-disjunction, the primary cause of pregnancy loss.

  15. Genetic recombination as a major cause of mutagenesis in the human globin gene clusters.

    Borg, Joseph; Georgitsi, Marianthi; Aleporou-Marinou, Vassiliki; Kollia, Panagoula; Patrinos, George P

    2009-12-01

    Homologous recombination is a frequent phenomenon in multigene families and as such it occurs several times in both the alpha- and beta-like globin gene families. In numerous occasions, genetic recombination has been previously implicated as a major mechanism that drives mutagenesis in the human globin gene clusters, either in the form of unequal crossover or gene conversion. Unequal crossover results in the increase or decrease of the human globin gene copies, accompanied in the majority of cases with minor phenotypic consequences, while gene conversion contributes either to maintaining sequence homogeneity or generating sequence diversity. The role of genetic recombination, particularly gene conversion in the evolution of the human globin gene families has been discussed elsewhere. Here, we summarize our current knowledge and review existing experimental evidence outlining the role of genetic recombination in the mutagenic process in the human globin gene families.

  16. Genetic consequences of the influence of ionizing radiation on humans

    Mosse, I.B.

    2011-01-01

    There is no direct evidence that exposure of parents to ionizing radiation leads to excess heritable disease in offspring. What is the difference between human and other species in which radiation induced mutations are easily registered? During evolution germ cell selection ex vivo has been changed to a selection in vivo and we cannot observe such selection of radiation damaged cells in human.

  17. Human genetics studies in areas of high natural radiation. VII. Genetic load

    Freire-Maia, A [Faculdade de Ciencias Medicas e Biologicas de Botucatu (Brazil). Departamento de Genetica

    1975-01-01

    Two methods to estimate the inbreeding load, employed in our analysis, are reviewed. Besides the total population, a sample constituted of individuals with no alien ancesters is also analyzed. The measurements by genetic load models show a clear effect of natural radioactivity (especially for abortions, pre-natal mortality, anomalies, and abnormalities in general). The results on stillbirths and post-natal and total mortalities are discussed and it is concluded that uncontrolled concomitant variables (if not chance alone) cause the differences.

  18. Genetic Evidence of Human Adaptation to a Cooked Diet.

    Carmody, Rachel N; Dannemann, Michael; Briggs, Adrian W; Nickel, Birgit; Groopman, Emily E; Wrangham, Richard W; Kelso, Janet

    2016-04-13

    Humans have been argued to be biologically adapted to a cooked diet, but this hypothesis has not been tested at the molecular level. Here, we combine controlled feeding experiments in mice with comparative primate genomics to show that consumption of a cooked diet influences gene expression and that affected genes bear signals of positive selection in the human lineage. Liver gene expression profiles in mice fed standardized diets of meat or tuber were affected by food type and cooking, but not by caloric intake or consumer energy balance. Genes affected by cooking were highly correlated with genes known to be differentially expressed in liver between humans and other primates, and more genes in this overlap set show signals of positive selection in humans than would be expected by chance. Sequence changes in the genes under selection appear before the split between modern humans and two archaic human groups, Neandertals and Denisovans, supporting the idea that human adaptation to a cooked diet had begun by at least 275,000 years ago. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Evolutionary anthropology and genes: investigating the genetics of human evolution from excavated skeletal remains.

    Anastasiou, Evilena; Mitchell, Piers D

    2013-10-01

    The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis.

    Li, Jingting; Sen, George L

    2015-12-14

    Organotypic cultures allow the reconstitution of a 3D environment critical for cell-cell contact and cell-matrix interactions which mimics the function and physiology of their in vivo tissue counterparts. This is exemplified by organotypic skin cultures which faithfully recapitulates the epidermal differentiation and stratification program. Primary human epidermal keratinocytes are genetically manipulable through retroviruses where genes can be easily overexpressed or knocked down. These genetically modified keratinocytes can then be used to regenerate human epidermis in organotypic skin cultures providing a powerful model to study genetic pathways impacting epidermal growth, differentiation, and disease progression. The protocols presented here describe methods to prepare devitalized human dermis as well as to genetically manipulate primary human keratinocytes in order to generate organotypic skin cultures. Regenerated human skin can be used in downstream applications such as gene expression profiling, immunostaining, and chromatin immunoprecipitations followed by high throughput sequencing. Thus, generation of these genetically modified organotypic skin cultures will allow the determination of genes that are critical for maintaining skin homeostasis.

  1. Progress report on research on human genetics in Iceland

    None

    1980-10-31

    Records of the Icelandic population are being used to investigate the possible inheritance of disabilities and diseases as well as other characteristics and the effect of environment on man. The progress report of research covers the period from 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  2. Research on human genetics in Iceland. Progress report

    None

    1980-10-31

    Records of the Icelandic Population are being used to investigate the possible inheritance of disabilities and diseases as well as other characters and the effect of environment on man. The progress report of research covers the period 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  3. Human genetics: measuring the raw material of evolution.

    Armour, John A L

    2009-09-15

    By direct sequencing of two Y chromosomes inherited from the same paternal ancestor, a landmark study has derived a good direct estimate for the rate of base substitution mutations on the human Y chromosome.

  4. Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

    Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

    2017-09-12

    Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

  5. Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy

    Douglas, Darlene S.; Popko, Brian

    2009-01-01

    Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175

  6. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

    Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

    2015-04-09

    Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The New World of Human Genetics: A dialogue between Practitioners & the General Public on Ethical, Legal & Social Implications of the Human Genome Project

    Schofield, Amy

    2014-12-08

    The history and reasons for launching the Human Genome project and the current uses of genetic human material; Identifying and discussing the major issues stemming directly from genetic research and therapy-including genetic discrimination, medical/ person privacy, allocation of government resources and individual finances, and the effect on the way in which we perceive the value of human life; Discussing the sometimes hidden ethical, social and legislative implications of genetic research and therapy such as informed consent, screening and preservation of genetic materials, efficacy of medical procedures, the role of the government, and equal access to medical coverage.

  8. Genetics and human rights: Two histories: restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil

    Penchaszadeh, Victor B.; Schuler-Faccini, Lavinia

    2014-01-01

    Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to i...

  9. The commercialization of human genetic information and related circumstances within Turkish law.

    Memiş, Tekin

    2011-01-01

    Today, human genetic information is used for commercial purposes as well. This means, based on the case, the direct or indirect commercialization of genetic information. In this study, this specific issue is analyzed in light of the new legal regulations as to the subject in the Turkish Law. Specifically, this study focuses on the issue of whether the commercialization of genetic information is allowed under the Turkish Law. This study also attempts to clarify the issue of whether there is any limitations for the commercialization of genetic information in the Turkish Law provided that the commercialization of genetic information is permitted. Prior to this legal analysis, the problems of the legal ownership for genetic information and of whether genetic information should be considered as an organ of human body is discussed. Accordingly, relevant Turkish laws and regulations are individually analyzed within this context. In the mean time legal regulations of some countries in this respect are taken into account with a comparative approach. In the end a general evaluation and suggestions are provided to the reader.

  10. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    Lemaire, D.; Barbosa, T.; Rihet, P.

    2011-01-01

    Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data

  11. Human genetics for non-scientists: Practical workshops for policy makers and opinion leaders

    NONE

    1995-12-31

    These workshops form part of a series of workshops that the Banbury and the DNA Learning Centers of Cold Spring Harbor Laboratory have held for a number of years, introducing genetics, and the ways in which scientific research is done, to non-scientists. The purpose of the workshops as stated in the grant application was: {open_quotes}Our objective is to foster a better understanding of the societal impact of human genome research by providing basic information on genetics to non-scientists whose professions or special interests interface with genetic technology.... Participants will be chosen for their interest in human genetics and for their roles as opinion leaders in their own communities. Primary care physicians are of particular interest to us for this series of workshops.{close_quotes} Two workshops were held under this grant. The first was held in 21-24 April, 1994 and attended by 20 participants, and the second was held 16-19 November, 1995, and attended by 16 participants. In each case, there was a combination of concept lectures on the foundations of human molecular genetics; lectures by invited specialists; and laboratory experiments to introduce non-scientists to the techniques used in molecular genetics.

  12. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

    2005-01-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  13. Systematic documentation and analysis of human genetic variation using the microattribution approach

    Giardine, Belinda; Borg, Joseph; Higgs, Douglas R.; Peterson, Kenneth R.; Maglott, Donna; Basak, A. Nazli; Clark, Barnaby; Faustino, Paula; Felice, Alex E.; Francina, Alain; Gallivan, Monica V. E.; Georgitsi, Marianthi; Gibbons, Richard J.; Giordano, Piero C.; Harteveld, Cornelis L.; Joly, Philippe; Kanavakis, Emmanuel; Kollia, Panagoula; Menzel, Stephan; Miller, Webb; Moradkhani, Kamran; Old, John; Papachatzopoulou, Adamantia; Papadakis, Manoussos N.; Papadopoulos, Petros; Pavlovic, Sonja; Philipsen, Sjaak; Radmilovic, Milena; Riemer, Cathy; Schrijver, Iris; Stojiljkovic, Maja; Thein, Swee Lay; Traeger-Synodinos, Jan; Tully, Ray; Wada, Takahito; Waye, John; Wiemann, Claudia; Zukic, Branka; Chui, David H. K.; Wajcman, Henri; Hardison, Ross C.; Patrinos, George P.

    2013-01-01

    We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to these disorders, and then implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories 1. A total of 1,941 unique genetic variants in 37 genes, encoding globins (HBA2, HBA1, HBG2, HBG1, HBD, HBB) and other erythroid proteins (ALOX5AP, AQP9, ARG2, ASS1, ATRX, BCL11A, CNTNAP2, CSNK2A1, EPAS1, ERCC2, FLT1, GATA1, GPM6B, HAO2, HBS1L, KDR, KL, KLF1, MAP2K1, MAP3K5, MAP3K7, MYB, NOS1, NOS2, NOS3, NOX3, NUP133, PDE7B, SMAD3, SMAD6, and TOX) are currently documented in these databases with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants and now provides a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The large repository of previously reported data, together with more recent data, acquired by microattribution, demonstrates how the comprehensive documentation of human variation will provide key insights into normal biological processes and how these are perturbed in human genetic disease. Using the microattribution process set out here, datasets which took decades to accumulate for the globin genes could be assembled rapidly for other genes and disease systems. The principles established here for the globin gene system will serve as a model for other systems and the analysis of other common and/or complex human genetic diseases. PMID:21423179

  14. Modulation of habitat-based conservation plans by fishery opportunity costs: a New Caledonia case study using fine-scale catch data.

    Marilyn Deas

    Full Text Available Numerous threats impact coral reefs and conservation actions are urgently needed. Fast production of marine habitat maps promotes the use of habitat-only conservation plans, where a given percentage of the area of each habitat is set as conservation objectives. However, marine reserves can impact access to fishing grounds and generate opportunity costs for fishers that need to be minimized. In New Caledonia (Southwest Pacific, we used fine-scale fishery catch maps to define nineteen opportunity costs layers (expressed as biomass catch loss considering i total catches, ii target fish families, iii local marine tenure, and iv gear type. The expected lower impacts on fishery catch when using the different cost constraints were ranked according to effectiveness in decreasing the costs generated by the habitat-only scenarios. The exercise was done for two habitat maps with different thematic richness. In most cases, habitat conservation objectives remained achievable, but effectiveness varied widely between scenarios and between habitat maps. The results provide practical guidelines for coral reef conservation and management. Habitat-only scenarios can be used to initiate conservation projects with stakeholders but the costs induced by such scenarios can be lowered by up to 50-60% when detailed exhaustive fishery data are used. When using partial data, the gain would be only in the 15-25% range. The best compromises are achieved when using local data.

  15. Fine-scale spatio-temporal variation in tiger Panthera tigris diet: Effect of study duration and extent on estimates of tiger diet in Chitwan National Park, Nepal

    Kapfer, Paul M.; Streby, Henry M.; Gurung, B.; Simcharoen, A.; McDougal, C.C.; Smith, J.L.D.

    2011-01-01

    Attempts to conserve declining tiger Panthera tigris populations and distributions have experienced limited success. The poaching of tiger prey is a key threat to tiger persistence; a clear understanding of tiger diet is a prerequisite to conserve dwindling populations. We used unpublished data on tiger diet in combination with two previously published studies to examine fine-scale spatio-temporal changes in tiger diet relative to prey abundance in Chitwan National Park, Nepal, and aggregated data from the three studies to examine the effect that study duration and the size of the study area have on estimates of tiger diet. Our results correspond with those of previous studies: in all three studies, tiger diet was dominated by members of Cervidae; small to medium-sized prey was important in one study. Tiger diet was unrelated to prey abundance, and the aggregation of studies indicates that increasing study duration and study area size both result in increased dietary diversity in terms of prey categories consumed, and increasing study duration changed which prey species contributed most to tiger diet. Based on our results, we suggest that managers focus their efforts on minimizing the poaching of all tiger prey, and that future studies of tiger diet be of long duration and large spatial extent to improve our understanding of spatio-temporal variation in estimates of tiger diet. ?? 2011 Wildlife Biology, NKV.

  16. Fine-scale movements of rural free-ranging dogs in conservation areas in the temperate rainforest of the coastal range of southern Chile

    Sepulveda, Maximiliano; Pelican, Katherine; Cross, Paul C.; Eguren, Antonieta; Singer, Randall S.

    2015-01-01

    Domestic dogs can play a variety of important roles for farmers. However, when in proximity to conservation areas, the presence of rural free-ranging dogs can be problematic due to the potential for predation of, competition with, or transmission of infectious disease to local threatened fauna. We used a frequent location radio tracking technology to study rural free-ranging dog movements and habitat use into sensitive conservation habitats. To achieve a better understanding of foray behaviors in dogs we monitored dogs (n = 14) in rural households located in an isolated area between the Valdivian Coastal Reserve and the Alerce Costero National Park in southern Chile. Dogs were mostly located near households (habitat compared to forest habitat including protected lands. Foraying dogs rarely used forest habitat and, when entered, trails and/or roads were selected for movement. Our study provides important information about how dogs interact in a fine-scale with wildlife habitat, and, in particular, protected lands, providing insight into how dog behavior might drive wildlife interactions, and, in turn, how an understanding of dog behavior can be used to manage these interactions.

  17. Toward an operational framework for fine-scale urban land-cover mapping in Wallonia using submeter remote sensing and ancillary vector data

    Beaumont, Benjamin; Grippa, Tais; Lennert, Moritz; Vanhuysse, Sabine; Stephenne, Nathalie; Wolff, Eléonore

    2017-07-01

    Encouraged by the EU INSPIRE directive requirements and recommendations, the Walloon authorities, similar to other EU regional or national authorities, want to develop operational land-cover (LC) and land-use (LU) mapping methods using existing geodata. Urban planners and environmental monitoring stakeholders of Wallonia have to rely on outdated, mixed, and incomplete LC and LU information. The current reference map is 10-years old. The two object-based classification methods, i.e., a rule- and a classifier-based method, for detailed regional urban LC mapping are compared. The added value of using the different existing geospatial datasets in the process is assessed. This includes the comparison between satellite and aerial optical data in terms of mapping accuracies, visual quality of the map, costs, processing, data availability, and property rights. The combination of spectral, tridimensional, and vector data provides accuracy values close to 0.90 for mapping the LC into nine categories with a minimum mapping unit of 15 m2. Such a detailed LC map offers opportunities for fine-scale environmental and spatial planning activities. Still, the regional application poses challenges regarding automation, big data handling, and processing time, which are discussed.

  18. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2...... mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively...... of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest...

  19. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

    Ruth Hershberg

    2008-12-01

    Full Text Available Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC. However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

  20. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  1. Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics.

    Simpson, Siobhan; Dunning, Mark David; de Brot, Simone; Grau-Roma, Llorenç; Mongan, Nigel Patrick; Rutland, Catrin Sian

    2017-10-24

    Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.

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

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

    2009-09-01

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

  3. [The development of molecular human genetics and its significance for perspectives of modern medicine].

    Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

    1989-01-01

    The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

  4. Genetic and Epigenetic Regulation of Human Cardiac Reprogramming and Differentiation in Regenerative Medicine.

    Burridge, Paul W; Sharma, Arun; Wu, Joseph C

    2015-01-01

    Regeneration or replacement of lost cardiomyocytes within the heart has the potential to revolutionize cardiovascular medicine. Numerous methodologies have been used to achieve this aim, including the engraftment of bone marrow- and heart-derived cells as well as the identification of modulators of adult cardiomyocyte proliferation. Recently, the conversion of human somatic cells into induced pluripotent stem cells and induced cardiomyocyte-like cells has transformed potential approaches toward this goal, and the engraftment of cardiac progenitors derived from human embryonic stem cells into patients is now feasible. Here we review recent advances in our understanding of the genetic and epigenetic control of human cardiogenesis, cardiac differentiation, and the induced reprogramming of somatic cells to cardiomyocytes. We also cover genetic programs for inducing the proliferation of endogenous cardiomyocytes and discuss the genetic state of cells used in cardiac regenerative medicine.

  5. Human Genetic Marker for Resistance to Radiation and Chemicals

    Lieberman, Howard B.

    2001-01-01

    TO characterize the human HRDAD9 gene and evaluate its potential as a biomarker to predict susceptibility to the deleterious health effects potentially caused by exposure to radiations or chemicals present at DOE hazardous waste cleanup sites. HRAD9 is a human gene that is highly conserved throughout evolution. Related genes have been isolated from yeasts and mice, underscoring its biological significance. Most of our previous work involved characterization of the yeast gene cognate, wherein it was determined that the corresponding protein plays a significant role in promoting resistance of cells to radiations and chemicals, and in particular, controlling cell growth in response to DNA damage

  6. Global Distribution of Human-Associated Fecal Genetic Markers in Reference Samples from Six Continents.

    Mayer, René E; Reischer, Georg H; Ixenmaier, Simone K; Derx, Julia; Blaschke, Alfred Paul; Ebdon, James E; Linke, Rita; Egle, Lukas; Ahmed, Warish; Blanch, Anicet R; Byamukama, Denis; Savill, Marion; Mushi, Douglas; Cristóbal, Héctor A; Edge, Thomas A; Schade, Margit A; Aslan, Asli; Brooks, Yolanda M; Sommer, Regina; Masago, Yoshifumi; Sato, Maria I; Taylor, Huw D; Rose, Joan B; Wuertz, Stefan; Shanks, Orin C; Piringer, Harald; Mach, Robert L; Savio, Domenico; Zessner, Matthias; Farnleitner, Andreas H

    2018-05-01

    Numerous bacterial genetic markers are available for the molecular detection of human sources of fecal pollution in environmental waters. However, widespread application is hindered by a lack of knowledge regarding geographical stability, limiting implementation to a small number of well-characterized regions. This study investigates the geographic distribution of five human-associated genetic markers (HF183/BFDrev, HF183/BacR287, BacHum-UCD, BacH, and Lachno2) in municipal wastewaters (raw and treated) from 29 urban and rural wastewater treatment plants (750-4 400 000 population equivalents) from 13 countries spanning six continents. In addition, genetic markers were tested against 280 human and nonhuman fecal samples from domesticated, agricultural and wild animal sources. Findings revealed that all genetic markers are present in consistently high concentrations in raw (median log 10 7.2-8.0 marker equivalents (ME) 100 mL -1 ) and biologically treated wastewater samples (median log 10 4.6-6.0 ME 100 mL -1 ) regardless of location and population. The false positive rates of the various markers in nonhuman fecal samples ranged from 5% to 47%. Results suggest that several genetic markers have considerable potential for measuring human-associated contamination in polluted environmental waters. This will be helpful in water quality monitoring, pollution modeling and health risk assessment (as demonstrated by QMRAcatch) to guide target-oriented water safety management across the globe.

  7. Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.

    Lindee, Susan

    2016-02-01

    In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Ethical Concerns About Human Genetic Enhancement in the Malay Science Fiction Novels.

    Isa, Noor Munirah; Hj Safian Shuri, Muhammad Fakhruddin

    2018-02-01

    Advancements in science and technology have not only brought hope to humankind to produce disease-free offspring, but also offer possibilities to genetically enhance the next generation's traits and capacities. Human genetic enhancement, however, raises complex ethical questions, such as to what extent should it be allowed? It has been a great challenge for humankind to develop robust ethical guidelines for human genetic enhancement that address both public concerns and needs. We believe that research about public concerns is necessary prior to developing such guidelines, yet the issues have not been thoroughly investigated in many countries, including Malaysia. Since the novel often functions as a medium for the public to express their concerns, this paper explores ethical concerns about human genetic enhancement expressed in four Malay science fiction novels namely Klon, Leksikon Ledang, Transgenesis Bisikan Rimba and Transgenik Sifar. Religion has a strong influence on the worldview of the Malays therefore some concerns such as playing God are obviously religious. Association of the negative image of scientists as well as the private research companies with the research on human genetic enhancement reflects the authors' concerns about the main motivations for conducting such research and the extent to which such research will benefit society.

  9. Characterization of Large Structural Genetic Mosaicism in Human Autosomes

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

    2015-01-01

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

  10. A Trio of Human Molecular Genetics PCR Assays

    Reinking, Jeffrey L.; Waldo, Jennifer T.; Dinsmore, Jannett

    2013-01-01

    This laboratory exercise demonstrates three different analytical forms of the polymerase chain reaction (PCR) that allow students to genotype themselves at four different loci. Here, we present protocols to allow students to a) genotype a non-coding polymorphic Variable Number of Tandem Repeat (VNTR) locus on human chromosome 5 using conventional…

  11. Human impacts on genetic diversity in forest ecosystems

    F. Thomas Ledig

    1992-01-01

    Humans have converted forest to agricultural and urban uses, exploited species, fragmented wildlands. changed the demographic structure of forests, altered habitat, degraded the environment with atmospheric and soil pollutants, introduced exotic pests and competitors, and domesticated favored species. None of they activities is new; perhaps with the exception of...

  12. Mapping genetic variants for cranial vault shape in humans

    Roosenboom, Jasmien; Lee, Myoung Keun; Hecht, Jacqueline T

    2018-01-01

    The shape of the cranial vault, a region comprising interlocking flat bones surrounding the cerebral cortex, varies considerably in humans. Strongly influenced by brain size and shape, cranial vault morphology has both clinical and evolutionary relevance. However, little is known about the geneti...

  13. MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome.

    Wang, Julia; Al-Ouran, Rami; Hu, Yanhui; Kim, Seon-Young; Wan, Ying-Wooi; Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan; Comjean, Aram; Mohr, Stephanie E; Perrimon, Norbert; Liu, Zhandong; Bellen, Hugo J

    2017-06-01

    One major challenge encountered with interpreting human genetic variants is the limited understanding of the functional impact of genetic alterations on biological processes. Furthermore, there remains an unmet demand for an efficient survey of the wealth of information on human homologs in model organisms across numerous databases. To efficiently assess the large volume of publically available information, it is important to provide a concise summary of the most relevant information in a rapid user-friendly format. To this end, we created MARRVEL (model organism aggregated resources for rare variant exploration). MARRVEL is a publicly available website that integrates information from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. Importantly, it curates model organism-specific databases to concurrently display a concise summary regarding the human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage. Experiment-based information on tissue expression, protein subcellular localization, biological process, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Hence, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information by searching once through MARRVEL. Altogether, MARRVEL dramatically improves efficiency and accessibility to data collection and facilitates analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  14. Evolving hard problems: Generating human genetics datasets with a complex etiology

    Himmelstein Daniel S

    2011-07-01

    Full Text Available Abstract Background A goal of human genetics is to discover genetic factors that influence individuals' susceptibility to common diseases. Most common diseases are thought to result from the joint failure of two or more interacting components instead of single component failures. This greatly complicates both the task of selecting informative genetic variants and the task of modeling interactions between them. We and others have previously developed algorithms to detect and model the relationships between these genetic factors and disease. Previously these methods have been evaluated with datasets simulated according to pre-defined genetic models. Results Here we develop and evaluate a model free evolution strategy to generate datasets which display a complex relationship between individual genotype and disease susceptibility. We show that this model free approach is capable of generating a diverse array of datasets with distinct gene-disease relationships for an arbitrary interaction order and sample size. We specifically generate eight-hundred Pareto fronts; one for each independent run of our algorithm. In each run the predictiveness of single genetic variation and pairs of genetic variants have been minimized, while the predictiveness of third, fourth, or fifth-order combinations is maximized. Two hundred runs of the algorithm are further dedicated to creating datasets with predictive four or five order interactions and minimized lower-level effects. Conclusions This method and the resulting datasets will allow the capabilities of novel methods to be tested without pre-specified genetic models. This allows researchers to evaluate which methods will succeed on human genetics problems where the model is not known in advance. We further make freely available to the community the entire Pareto-optimal front of datasets from each run so that novel methods may be rigorously evaluated. These 76,600 datasets are available from http://discovery.dartmouth.edu/model_free_data/.

  15. Human genetics and genomics a decade after the release of the draft sequence of the human genome

    2011-01-01

    Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

  16. Genetics of the pig tapeworm in madagascar reveal a history of human dispersal and colonization.

    Yanagida, Tetsuya; Carod, Jean-François; Sako, Yasuhito; Nakao, Minoru; Hoberg, Eric P; Ito, Akira

    2014-01-01

    An intricate history of human dispersal and geographic colonization has strongly affected the distribution of human pathogens. The pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serious neglected tropical diseases. Discrete genetic lineages of T. solium in Asia and Africa/Latin America are geographically disjunct; only in Madagascar are they sympatric. Linguistic, archaeological and genetic evidence has indicated that the people in Madagascar have mixed ancestry from Island Southeast Asia and East Africa. Hence, anthropogenic introduction of the tapeworm from Southeast Asia and Africa had been postulated. This study shows that the major mitochondrial haplotype of T. solium in Madagascar is closely related to those from the Indian Subcontinent. Parasitological evidence presented here, and human genetics previously reported, support the hypothesis of an Indian influence on Malagasy culture coinciding with periods of early human migration onto the island. We also found evidence of nuclear-mitochondrial discordance in single tapeworms, indicating unexpected cross-fertilization between the two lineages of T. solium. Analyses of genetic and geographic populations of T. solium in Madagascar will shed light on apparently rapid evolution of this organism driven by recent (<2,000 yr) human migrations, following tens of thousands of years of geographic isolation.

  17. Proliferation of Genetically Modified Human Cells on Electrospun Nanofiber Scaffolds

    Mandula Borjigin

    2012-01-01

    Full Text Available Gene editing is a process by which single base mutations can be corrected, in the context of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs. The survival and proliferation of the corrected cells bearing modified genes, however, are impeded by a phenomenon known as reduced proliferation phenotype (RPP; this is a barrier to practical implementation. To overcome the RPP problem, we utilized nanofiber scaffolds as templates on which modified cells were allowed to recover, grow, and expand after gene editing. Here, we present evidence that some HCT116-19, bearing an integrated, mutated enhanced green fluorescent protein (eGFP gene and corrected by gene editing, proliferate on polylysine or fibronectin-coated polycaprolactone (PCL nanofiber scaffolds. In contrast, no cells from the same reaction protocol plated on both regular dish surfaces and polylysine (or fibronectin-coated dish surfaces proliferate. Therefore, growing genetically modified (edited cells on electrospun nanofiber scaffolds promotes the reversal of the RPP and increases the potential of gene editing as an ex vivo gene therapy application.

  18. Human genetic studies in areas of high natural radiation

    Freire-Maia, A.; Krieger, H.

    1978-01-01

    Data have been obtained by a genetic-epidemiological survey of a population living in the State of Espirito Santo (Brazil), and subjected to mean levels of natural radiation, per locality, ranging from 7 to 133 μrad/hr. Multiple regression models have been applied to the data, and the results showed no detectable effect of natural radiation on the sex ratio at birth, on the occurrence of congenital anomalies, and on the numbers of pregnancy terminations, stillbirths, livebirths, and post-infant mortality in the children, as well as fecundity and fertility of the couples (these observations contradict some data from the literature, based on official records and without analyses of the concomitant effects of other variables). However, nonsignificant results cannot be considered as disproving harmful effects of natural radiation on mortality and morbidity. These results may simply mean that other causes of mortality and morbidity are so important, under the conditions of the study, that the contribution of low-level, chronic natural radiation is made negligible. (author)

  19. Molecular genetics of human primary microcephaly: an overview

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  20. A CRISPR New World: Attitudes in the Public toward Innovations in Human Genetic Modification.

    Weisberg, Steven M; Badgio, Daniel; Chatterjee, Anjan

    2017-01-01

    The potential to genetically modify human germlines has reached a critical tipping point with recent applications of CRISPR-Cas9. Even as researchers, clinicians, and ethicists weigh the scientific and ethical repercussions of these advances, we know virtually nothing about public attitudes on the topic. Understanding such attitudes will be critical to determining the degree of broad support there might be for any public policy or regulation developed for genetic modification research. To fill this gap, we gave an online survey to a large (2,493 subjects) and diverse sample of Americans. Respondents supported genetic modification research, although demographic variables influenced these attitudes-conservatives, women, African-Americans, and older respondents, while supportive, were more cautious than liberals, men, other ethnicities, and younger respondents. Support was also was slightly muted when the risks (unanticipated mutations and possibility of eugenics) were made explicit. The information about genetic modification was also presented as contrasting vignettes, using one of five frames: genetic editing, engineering, hacking, modification, or surgery. Despite the fact that the media and academic use of frames describing the technology varies, these frames did not influence people's attitudes. These data contribute a current snapshot of public attitudes to inform policy with regard to human genetic modification.

  1. A CRISPR New World: Attitudes in the Public toward Innovations in Human Genetic Modification

    Steven M. Weisberg

    2017-05-01

    Full Text Available The potential to genetically modify human germlines has reached a critical tipping point with recent applications of CRISPR-Cas9. Even as researchers, clinicians, and ethicists weigh the scientific and ethical repercussions of these advances, we know virtually nothing about public attitudes on the topic. Understanding such attitudes will be critical to determining the degree of broad support there might be for any public policy or regulation developed for genetic modification research. To fill this gap, we gave an online survey to a large (2,493 subjects and diverse sample of Americans. Respondents supported genetic modification research, although demographic variables influenced these attitudes—conservatives, women, African-Americans, and older respondents, while supportive, were more cautious than liberals, men, other ethnicities, and younger respondents. Support was also was slightly muted when the risks (unanticipated mutations and possibility of eugenics were made explicit. The information about genetic modification was also presented as contrasting vignettes, using one of five frames: genetic editing, engineering, hacking, modification, or surgery. Despite the fact that the media and academic use of frames describing the technology varies, these frames did not influence people’s attitudes. These data contribute a current snapshot of public attitudes to inform policy with regard to human genetic modification.

  2. Genetic population structure accounts for contemporary ecogeographic patterns in tropic and subtropic-dwelling humans.

    Hruschka, Daniel J; Hadley, Craig; Brewis, Alexandra A; Stojanowski, Christopher M

    2015-01-01

    Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R2 = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R2 = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

  3. Genetic population structure accounts for contemporary ecogeographic patterns in tropic and subtropic-dwelling humans.

    Daniel J Hruschka

    Full Text Available Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R2 = 0.14-0.28. However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R2 = 0.50-0.74. Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

  4. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene.

    Cai, Pei-qiang; Tang, Xun; Lin, Yue-qiu; Martin, Oudega; Sun, Guang-yun; Xu, Lin; Yang, Yun-kang; Zhou, Tian-hua

    2006-02-01

    To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  5. Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.

    Scott G Kitchen

    Full Text Available There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR. Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

  6. Genetic adaptation of the antibacterial human innate immunity network

    Lazarus Ross

    2011-07-01

    Full Text Available Abstract Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  7. Genetic adaptation of the antibacterial human innate immunity network.

    Casals, Ferran; Sikora, Martin; Laayouni, Hafid; Montanucci, Ludovica; Muntasell, Aura; Lazarus, Ross; Calafell, Francesc; Awadalla, Philip; Netea, Mihai G; Bertranpetit, Jaume

    2011-07-11

    Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

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

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

    2009-01-01

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

  9. Comparing ESC and iPSC?Based Models for Human Genetic Disorders

    Halevy, Tomer; Urbach, Achia

    2014-01-01

    Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients’ somatic cells, and the ne...

  10. Fine-scale variation in microclimate across an urban landscape shapes variation in mosquito population dynamics and the potential of Aedes albopictus to transmit arboviral disease.

    Murdock, Courtney C; Evans, Michelle V; McClanahan, Taylor D; Miazgowicz, Kerri L; Tesla, Blanka

    2017-05-01

    Most statistical and mechanistic models used to predict mosquito-borne disease transmission incorporate climate drivers of disease transmission by utilizing environmental data collected at geographic scales that are potentially coarser than what mosquito populations may actually experience. Temperature and relative humidity can vary greatly between indoor and outdoor environments, and can be influenced strongly by variation in landscape features. In the Aedes albopictus system, we conducted a proof-of-concept study in the vicinity of the University of Georgia to explore the effects of fine-scale microclimate variation on mosquito life history and vectorial capacity (VC). We placed Ae. albopictus larvae in artificial pots distributed across three replicate sites within three different land uses-urban, suburban, and rural, which were characterized by high, intermediate, and low proportions of impervious surfaces. Data loggers were placed into each larval environment and in nearby vegetation to record daily variation in water and ambient temperature and relative humidity. The number of adults emerging from each pot and their body size and sex were recorded daily. We found mosquito microclimate to significantly vary across the season as well as with land use. Urban sites were in general warmer and less humid than suburban and rural sites, translating into decreased larval survival, smaller body sizes, and lower per capita growth rates of mosquitoes on urban sites. Dengue transmission potential was predicted to be higher in the summer than the fall. Additionally, the effects of land use on dengue transmission potential varied by season. Warm summers resulted in a higher predicted VC on the cooler, rural sites, while warmer, urban sites had a higher predicted VC during the cooler fall season.

  11. Fine-scale variation in microclimate across an urban landscape shapes variation in mosquito population dynamics and the potential of Aedes albopictus to transmit arboviral disease.

    Courtney C Murdock

    2017-05-01

    Full Text Available Most statistical and mechanistic models used to predict mosquito-borne disease transmission incorporate climate drivers of disease transmission by utilizing environmental data collected at geographic scales that are potentially coarser than what mosquito populations may actually experience. Temperature and relative humidity can vary greatly between indoor and outdoor environments, and can be influenced strongly by variation in landscape features. In the Aedes albopictus system, we conducted a proof-of-concept study in the vicinity of the University of Georgia to explore the effects of fine-scale microclimate variation on mosquito life history and vectorial capacity (VC. We placed Ae. albopictus larvae in artificial pots distributed across three replicate sites within three different land uses-urban, suburban, and rural, which were characterized by high, intermediate, and low proportions of impervious surfaces. Data loggers were placed into each larval environment and in nearby vegetation to record daily variation in water and ambient temperature and relative humidity. The number of adults emerging from each pot and their body size and sex were recorded daily. We found mosquito microclimate to significantly vary across the season as well as with land use. Urban sites were in general warmer and less humid than suburban and rural sites, translating into decreased larval survival, smaller body sizes, and lower per capita growth rates of mosquitoes on urban sites. Dengue transmission potential was predicted to be higher in the summer than the fall. Additionally, the effects of land use on dengue transmission potential varied by season. Warm summers resulted in a higher predicted VC on the cooler, rural sites, while warmer, urban sites had a higher predicted VC during the cooler fall season.

  12. Imaging the Fine-Scale Structure of the San Andreas Fault in the Northern Gabilan Range with Explosion and Earthquake Sources

    Xin, H.; Thurber, C. H.; Zhang, H.; Wang, F.

    2014-12-01

    A number of geophysical studies have been carried out along the San Andreas Fault (SAF) in the Northern Gabilan Range (NGR) with the purpose of characterizing in detail the fault zone structure. Previous seismic research has revealed the complex structure of the crustal volume in the NGR region in two-dimensions (Thurber et al., 1996, 1997), and there has been some work on the three-dimensional (3D) structure at a coarser scale (Lin and Roecker, 1997). In our study we use earthquake body-wave arrival times and differential times (P and S) and explosion arrival times (only P) to image the 3D P- and S-wave velocity structure of the upper crust along the SAF in the NGR using double-difference (DD) tomography. The earthquake and explosion data types have complementary strengths - the earthquake data have good resolution at depth and resolve both Vp and Vs structure, although only where there are sufficient seismic rays between hypocenter and stations, whereas the explosions contribute very good near-surface resolution but for P waves only. The original dataset analyzed by Thurber et al. (1996, 1997) included data from 77 local earthquakes and 8 explosions. We enlarge the dataset with 114 more earthquakes that occurred in the study area, obtain improved S-wave picks using an automated picker, and include absolute and cross-correlation differential times. The inversion code we use is the algorithm tomoDD (Zhang and Thurber, 2003). We assess how the P and S velocity models and earthquake locations vary as we alter the inversion parameters and the inversion grid. The new inversion results show clearly the fine-scale structure of the SAF at depth in 3D, sharpening the image of the velocity contrast from the southwest side to the northeast side.

  13. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    Elena Vigorito

    Full Text Available Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases BRCA1 and 8,211 (631 ovarian cancer cases BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16. These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6. The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

  14. Disappearing Arctic tundra ponds: Fine-scale analysis of surface hydrology in drained thaw lake basins over a 65 year period (1948-2013)

    Andresen, Christian G.; Lougheed, Vanessa L.

    2015-03-01

    Long-term fine-scale dynamics of surface hydrology in Arctic tundra ponds (less than 1 ha) are largely unknown; however, these small water bodies may contribute substantially to carbon fluxes, energy balance, and biodiversity in the Arctic system. Change in pond area and abundance across the upper Barrow Peninsula, Alaska, was assessed by comparing historic aerial imagery (1948) and modern submeter resolution satellite imagery (2002, 2008, and 2010). This was complemented by photogrammetric analysis of low-altitude kite-borne imagery in combination with field observations (2010-2013) of pond water and thaw depth transects in seven ponds of the International Biological Program historic research site. Over 2800 ponds in 22 drained thaw lake basins (DTLB) with different geological ages were analyzed. We observed a net decrease of 30.3% in area and 17.1% in number of ponds over the 62 year period. The inclusion of field observations of pond areas in 1972 from a historic research site confirms the linear downward trend in area. Pond area and number were dependent on the age of DTLB; however, changes through time were independent of DTLB age, with potential long-term implications for the hypothesized geomorphologic landscape succession of the thaw lake cycle. These losses were coincident with increases in air temperature, active layer, and density and cover of aquatic emergent plants in ponds. Increased evaporation due to warmer and longer summers, permafrost degradation, and transpiration from encroaching aquatic emergent macrophytes are likely the factors contributing to the decline in surface area and number of ponds.

  15. Fine-scale spatial variability of heat-related mortality in Philadelphia County, USA, from 1983-2008: a case-series analysis

    Hondula David M

    2012-03-01

    Full Text Available Abstract Background High temperature and humidity conditions are associated with short-term elevations in the mortality rate in many United States cities. Previous research has quantified this relationship in an aggregate manner over large metropolitan areas, but within these areas the response may differ based on local-scale variability in climate, population characteristics, and socio-economic factors. Methods We compared the mortality response for 48 Zip Code Tabulation Areas (ZCTAs comprising Philadelphia County, PA to determine if certain areas are associated with elevated risk during high heat stress conditions. A randomization test was used to identify mortality exceedances for various apparent temperature thresholds at both the city and local scale. We then sought to identify the environmental, demographic, and social factors associated with high-risk areas via principal components regression. Results Citywide mortality increases by 9.3% on days following those with apparent temperatures over 34°C observed at 7:00 p.m. local time. During these conditions, elevated mortality rates were found for 10 of the 48 ZCTAs concentrated in the west-central portion of the County. Factors related to high heat mortality risk included proximity to locally high surface temperatures, low socioeconomic status, high density residential zoning, and age. Conclusions Within the larger Philadelphia metropolitan area, there exists statistically significant fine-scale spatial variability in the mortality response to high apparent temperatures. Future heat warning systems and mitigation and intervention measures could target these high risk areas to reduce the burden of extreme weather on summertime morbidity and mortality.

  16. An Efficient Upscaling Process Based on a Unified Fine-scale Multi-Physics Model for Flow Simulation in Naturally Fracture Carbonate Karst Reservoirs

    Bi, Linfeng

    2009-01-01

    The main challenges in modeling fluid flow through naturally-fractured carbonate karst reservoirs are how to address various flow physics in complex geological architectures due to the presence of vugs and caves which are connected via fracture networks at multiple scales. In this paper, we present a unified multi-physics model that adapts to the complex flow regime through naturally-fractured carbonate karst reservoirs. This approach generalizes Stokes-Brinkman model (Popov et al. 2007). The fracture networks provide the essential connection between the caves in carbonate karst reservoirs. It is thus very important to resolve the flow in fracture network and the interaction between fractures and caves to better understand the complex flow behavior. The idea is to use Stokes-Brinkman model to represent flow through rock matrix, void caves as well as intermediate flows in very high permeability regions and to use an idea similar to discrete fracture network model to represent flow in fracture network. Consequently, various numerical solution strategies can be efficiently applied to greatly improve the computational efficiency in flow simulations. We have applied this unified multi-physics model as a fine-scale flow solver in scale-up computations. Both local and global scale-up are considered. It is found that global scale-up has much more accurate than local scale-up. Global scale-up requires the solution of global flow problems on fine grid, which generally is computationally expensive. The proposed model has the ability to deal with large number of fractures and caves, which facilitate the application of Stokes-Brinkman model in global scale-up computation. The proposed model flexibly adapts to the different flow physics in naturally-fractured carbonate karst reservoirs in a simple and effective way. It certainly extends modeling and predicting capability in efficient development of this important type of reservoir.

  17. Egyptian Journal of Medical Human Genetics - Vol 12, No 2 (2011)

    Egyptian Journal of Medical Human Genetics - Vol 12, No 2 (2011) ... Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers · EMAIL FREE FULL TEXT EMAIL FREE FULL ... LB Salah, CB Salem, F B'Chir, K Bouraoui, F Broly, S Saguem, 183-186.

  18. Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    Castéra, Jérémy; Clément, Pierre

    2014-02-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. genetic determinism to justify intellectual likeness between individuals such as twins) or in relation to groups of humans (e.g. genetic determinism to justify gender differences or the superiority of some human ethnic groups). A between-factor analysis discriminates between countries, showing very significant differences. There is more innatism among teachers' conceptions in African countries and Lebanon than in European countries, Brazil and Australia. Among the other controlled parameters, only two are significantly independent of the country: the level of training and the level of knowledge of biology. A co-inertia analysis shows a strong correlation between non-citizen attitudes towards and innatist conceptions of genetic determinism regarding human groups. We discuss these findings and their implications for education.

  19. Teachers' Conceptions about the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    Castéra, Jérémy; Clément, Pierre

    2014-01-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed…

  20. The genetic influences on oxycodone response characteristics in human experimental pain

    Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia M

    2015-01-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic respon......; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone....

  1. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

    2012-01-01

    Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified ...

  2. Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission.

    Shuzhen Sim

    Full Text Available Dengue virus (DENV infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly characterized. To track changes in viral intra-host genetic diversity during horizontal transmission, we infected Aedes aegypti mosquitoes by allowing them to feed on DENV2-infected patients. We then performed whole-genome deep-sequencing of human- and matched mosquito-derived DENV samples on the Illumina platform and used a sensitive variant-caller to detect single nucleotide variants (SNVs within each sample. >90% of SNVs were lost upon transition from human to mosquito, as well as from mosquito abdomen to salivary glands. Levels of viral diversity were maintained, however, by the regeneration of new SNVs at each stage of transmission. We further show that SNVs maintained across transmission stages were transmitted as a unit of two at maximum, suggesting the presence of numerous variant genomes carrying only one or two SNVs each. We also present evidence for differences in selection pressures between human and mosquito hosts, particularly on the structural and NS1 genes. This analysis provides insights into how population drops during transmission shape RNA virus genetic diversity, has direct implications for virus evolution, and illustrates the value of high-coverage, whole-genome next-generation sequencing for understanding viral intra-host genetic diversity.

  3. PGG.Population: a database for understanding the genomic diversity and genetic ancestry of human populations.

    Zhang, Chao; Gao, Yang; Liu, Jiaojiao; Xue, Zhe; Lu, Yan; Deng, Lian; Tian, Lei; Feng, Qidi; Xu, Shuhua

    2018-01-04

    There are a growing number of studies focusing on delineating genetic variations that are associated with complex human traits and diseases due to recent advances in next-generation sequencing technologies. However, identifying and prioritizing disease-associated causal variants relies on understanding the distribution of genetic variations within and among populations. The PGG.Population database documents 7122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry. These data and information can facilitate the design of research studies and the interpretation of results of both evolutionary and medical studies involving human populations. The database is carefully maintained and constantly updated when new data are available. We included miscellaneous functions and a user-friendly graphical interface for visualization of genomic diversity, population relationships (genetic affinity), ancestral makeup, footprints of natural selection, and population history etc. Moreover, PGG.Population provides a useful feature for users to analyze data and visualize results in a dynamic style via online illustration. The long-term ambition of the PGG.Population, together with the joint efforts from other researchers who contribute their data to our database, is to create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators. PGG.Population is available at https://www.pggpopulation.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Recombination in the human Pseudoautosomal region PAR1.

    Anjali G Hinch

    2014-07-01

    Full Text Available The pseudoautosomal region (PAR is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

  5. Genetics and human rights. Two histories: Restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil.

    Penchaszadeh, Victor B; Schuler-Faccini, Lavinia

    2014-03-01

    Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.

  6. Genetics and human rights. Two histories: Restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil

    Penchaszadeh, Victor B.; Schuler-Faccini, Lavinia

    2014-01-01

    Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976–1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program “Reencontro”, which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind. PMID:24764764

  7. Genetics and human rights: Two histories: restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil

    Victor B. Penchaszadeh

    2014-01-01

    Full Text Available Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.

  8. The ecological imperative and its application to ethical issues in human genetic technology

    W. Malcolm Byrnes

    2003-08-01

    Full Text Available As a species, we are on the cusp of being able to alter that which makes us uniquely human, our genome. Two new genetic technologies, embryo selection and germline engineering, are either in use today or may be developed in the future. Embryo selection acts to alter the human gene pool, reducing genetic diversity, while germline engineering will have the ability to alter directly the genomes of engineered individuals. Our genome has come to be what it is through an evolutionary process extending over millions of years, a process that has involved exceedingly complex and unpredictable interactions between ourselves or our ancestors and myriad other life forms within Earth's biosphere. In this paper, the ecological imperativ e, which states that we must not alter the human genome or the collective human genetic inheritance, will be introduced. It will be argued based on ecological principles that embryo selection and germline engineering are unethical and unwise because they will diminish our survivability as a species, will disrupt our relationship with the natural world, and will destroy the very basis of that which makes us human.

  9. Monkey-based research on human disease: the implications of genetic differences.

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.

  10. Insects feeding on cadavers as an alternative source of human genetic material

    Rafał Skowronek

    2015-03-01

    Full Text Available In some criminal cases, the use of classical sources of human genetic material is difficult or even impossible. One solution may be the use of insects, especially blowfly larvae which feed on corpses. A recent review of case reports and experimental studies available in biomedical databases has shown that insects can be a valuable source of human mitochondrial and genomic deoxyribonucleic acid (DNA, allowing for an effective analysis of hypervariable region (HVR sequences and short tandem repeat (STR profiles, respectively. The optimal source of human DNA is the crop (a part of the gut of active third-instar blowfly larvae. Pupae and insect faeces can be also used in forensic genetic practice instead of the contents of the alimentary tract.

  11. Use of Traditional and Genetically Modified Probiotics in Human Health: What Does the Future Hold?

    Bermúdez-Humarán, Luis G; Langella, Philippe

    2017-09-01

    Probiotics are live, nonpathogenic microorganisms that confer benefits to human health when administered in adequate amounts. Among the frequent proposed health benefits attributed to probiotics, their ability to interact with the host immune system is now well demonstrated. Although history has revealed that probiotics were part of fermented foods in the past, clinicians have started to use them therapeutically in regular diets. Moreover, the use of genetically modified probiotics to deliver molecules of therapeutic interest is gaining importance as an extension of the probiotic concept. This chapter summarizes some of the recent findings and perspectives on the use of both traditional and genetically modified probiotics to treat human diseases as well as what the future may hold concerning the use of these probiotics in humans.

  12. Genetics

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  13. Blood groups and human groups: collecting and calibrating genetic data after World War Two.

    Bangham, Jenny

    2014-09-01

    Arthur Mourant's The Distribution of the Human Blood Groups (1954) was an "indispensable" reference book on the "anthropology of blood groups" containing a vast collection of human genetic data. It was based on the results of blood-grouping tests carried out on half-a-million people and drew together studies on diverse populations around the world: from rural communities, to religious exiles, to volunteer transfusion donors. This paper pieces together sequential stages in the production of a small fraction of the blood-group data in Mourant's book, to examine how he and his colleagues made genetic data from people. Using sources from several collecting projects, I follow how blood was encountered, how it was inscribed, and how it was turned into a laboratory resource. I trace Mourant's analytical and representational strategies to make blood groups both credibly 'genetic' and understood as relevant to human ancestry, race and history. In this story, 'populations' were not simply given, but were produced through public health, colonial and post-colonial institutions, and by the labour and expertise of subjects, assistants and mediators. Genetic data were not self-evidently 'biological', but were shaped by existing historical and geographical identities, by political relationships, and by notions of kinship and belonging. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  14. Genetic variation in lipid desaturases and its impact on the development of human disease.

    Merino, Diana M; Ma, David W L; Mutch, David M

    2010-06-18

    Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

  15. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

    Ivana Antonucci

    2016-04-01

    Full Text Available In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

  16. The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia.

    Deng, Lian; Hoh, Boon Peng; Lu, Dongsheng; Fu, Ruiqing; Phipps, Maude E; Li, Shilin; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Ismail, Endom; Mokhtar, Siti Shuhada; Jin, Li; Zilfalil, Bin Alwi; Marshall, Christian R; Scherer, Stephen W; Al-Mulla, Fahd; Xu, Shuhua

    2014-09-01

    Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration

  17. Scale-dependent effects of a heterogeneous landscape on genetic differentiation in the Central American squirrel monkey (Saimiri oerstedii.

    Mary E Blair

    Full Text Available Landscape genetic studies offer a fine-scale understanding of how habitat heterogeneity influences population genetic structure. We examined population genetic structure and conducted a landscape genetic analysis for the endangered Central American Squirrel Monkey (Saimiri oerstedii that lives in the fragmented, human-modified habitats of the Central Pacific region of Costa Rica. We analyzed non-invasively collected fecal samples from 244 individuals from 14 groups for 16 microsatellite markers. We found two geographically separate genetic clusters in the Central Pacific region with evidence of recent gene flow among them. We also found significant differentiation among groups of S. o. citrinellus using pairwise F(ST comparisons. These groups are in fragments of secondary forest separated by unsuitable "matrix" habitats such as cattle pasture, commercial African oil palm plantations, and human residential areas. We used an individual-based landscape genetic approach to measure spatial patterns of genetic variance while taking into account landscape heterogeneity. We found that large, commercial oil palm plantations represent moderate barriers to gene flow between populations, but cattle pastures, rivers, and residential areas do not. However, the influence of oil palm plantations on genetic variance was diminished when we restricted analyses to within population pairs, suggesting that their effect is scale-dependent and manifests during longer dispersal events among populations. We show that when landscape genetic methods are applied rigorously and at the right scale, they are sensitive enough to track population processes even in species with long, overlapping generations such as primates. Thus landscape genetic approaches are extremely valuable for the conservation management of a diverse array of endangered species in heterogeneous, human-modified habitats. Our results also stress the importance of explicitly considering the heterogeneity of

  18. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

    2000-01-01

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  19. Fine-scale linkage mapping reveals a small set of candidate genes influencing honey bee grooming behavior in response to Varroa mites.

    Miguel E Arechavaleta-Velasco

    Full Text Available Populations of honey bees in North America have been experiencing high annual colony mortality for 15-20 years. Many apicultural researchers believe that introduced parasites called Varroa mites (V. destructor are the most important factor in colony deaths. One important resistance mechanism that limits mite population growth in colonies is the ability of some lines of honey bees to groom mites from their bodies. To search for genes influencing this trait, we used an Illumina Bead Station genotyping array to determine the genotypes of several hundred worker bees at over a thousand single-nucleotide polymorphisms in a family that was apparently segregating for alleles influencing this behavior. Linkage analyses provided a genetic map with 1,313 markers anchored to genome sequence. Genotypes were analyzed for association with grooming behavior, measured as the time that individual bees took to initiate grooming after mites were placed on their thoraces. Quantitative-trait-locus interval mapping identified a single chromosomal region that was significant at the chromosome-wide level (p<0.05 on chromosome 5 with a LOD score of 2.72. The 95% confidence interval for quantitative trait locus location contained only 27 genes (honey bee official gene annotation set 2 including Atlastin, Ataxin and Neurexin-1 (AmNrx1, which have potential neurodevelopmental and behavioral effects. Atlastin and Ataxin homologs are associated with neurological diseases in humans. AmNrx1 codes for a presynaptic protein with many alternatively spliced isoforms. Neurexin-1 influences the growth, maintenance and maturation of synapses in the brain, as well as the type of receptors most prominent within synapses. Neurexin-1 has also been associated with autism spectrum disorder and schizophrenia in humans, and self-grooming behavior in mice.

  20. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  1. Building capacity for human genetics and genomics research in Trinidad and Tobago

    Allana Roach

    Full Text Available Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well-known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations that is informed by public health needs and contextual realities of the nation.

  2. A population genetic interpretation of GWAS findings for human quantitative traits

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

    2018-01-01

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

  3. Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.

    Marchi, Nina; Hegay, Tatyana; Mennecier, Philippe; Georges, Myriam; Laurent, Romain; Whitten, Mark; Endicott, Philipp; Aldashev, Almaz; Dorzhu, Choduraa; Nasyrova, Firuza; Chichlo, Boris; Ségurel, Laure; Heyer, Evelyne

    2017-04-01

    Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure. © 2017 Wiley Periodicals, Inc.

  4. Genetics

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  5. Evaluation of seabed mapping methods for fine-scale classification of extremely shallow benthic habitats - Application to the Venice Lagoon, Italy

    Montereale Gavazzi, G.; Madricardo, F.; Janowski, L.; Kruss, A.; Blondel, P.; Sigovini, M.; Foglini, F.

    2016-03-01

    Recent technological developments of multibeam echosounder systems (MBES) allow mapping of benthic habitats with unprecedented detail. MBES can now be employed in extremely shallow waters, challenging data acquisition (as these instruments were often designed for deeper waters) and data interpretation (honed on datasets with resolution sometimes orders of magnitude lower). With extremely high-resolution bathymetry and co-located backscatter data, it is now possible to map the spatial distribution of fine scale benthic habitats, even identifying the acoustic signatures of single sponges. In this context, it is necessary to understand which of the commonly used segmentation methods is best suited to account for such level of detail. At the same time, new sampling protocols for precisely geo-referenced ground truth data need to be developed to validate the benthic environmental classification. This study focuses on a dataset collected in a shallow (2-10 m deep) tidal channel of the Lagoon of Venice, Italy. Using 0.05-m and 0.2-m raster grids, we compared a range of classifications, both pixel-based and object-based approaches, including manual, Maximum Likelihood Classifier, Jenks Optimization clustering, textural analysis and Object Based Image Analysis. Through a comprehensive and accurately geo-referenced ground truth dataset, we were able to identify five different classes of the substrate composition, including sponges, mixed submerged aquatic vegetation, mixed detritic bottom (fine and coarse) and unconsolidated bare sediment. We computed estimates of accuracy (namely Overall, User, Producer Accuracies and the Kappa statistic) by cross tabulating predicted and reference instances. Overall, pixel based segmentations produced the highest accuracies and the accuracy assessment is strongly dependent on the number of classes chosen for the thematic output. Tidal channels in the Venice Lagoon are extremely important in terms of habitats and sediment distribution

  6. Screening Out Controversy: Human Genetics, Emerging Techniques of Diagnosis, and the Origins of the Social Issues Committee of the American Society of Human Genetics, 1964-1973.

    Mitchell, M X

    2017-05-01

    In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945-1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance.

  7. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  8. Anthropogenics: human influence on global and genetic homogenization of parasite populations.

    Zarlenga, Dante S; Hoberg, Eric; Rosenthal, Benjamin; Mattiucci, Simonetta; Nascetti, Giuseppe

    2014-12-01

    The distribution, abundance, and diversity of life on Earth have been greatly shaped by human activities. This includes the geographic expansion of parasites; however, measuring the extent to which humans have influenced the dissemination and population structure of parasites has been challenging. In-depth comparisons among parasite populations extending to landscape-level processes affecting disease emergence have remained elusive. New research methods have enhanced our capacity to discern human impact, where the tools of population genetics and molecular epidemiology have begun to shed light on our historical and ongoing influence. Only since the 1990s have parasitologists coupled morphological diagnosis, long considered the basis of surveillance and biodiversity studies, with state-of-the-art tools enabling variation to be examined among, and within, parasite populations. Prior to this time, populations were characterized only by phenotypic attributes such as virulence, infectivity, host range, and geographical location. The advent of genetic/molecular methodologies (multilocus allozyme electrophoresis, polymerase chain reaction-DNA [PCR-DNA] fragments analysis, DNA sequencing, DNA microsatellites, single nucleotide polymorphisms, etc.) have transformed our abilities to reveal variation among, and within, populations at local, regional, landscape, and global scales, and thereby enhanced our understanding of the biosphere. Numerous factors can affect population structure among parasites, e.g., evolutionary and ecological history, mode of reproduction and transmission, host dispersal, and life-cycle complexity. Although such influences can vary considerably among parasite taxa, anthropogenic factors are demonstrably perturbing parasite fauna. Minimal genetic structure among many geographically distinct (isolated) populations is a hallmark of human activity, hastened by geographic introductions, environmental perturbation, and global warming. Accelerating

  9. Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin.

    He, Bin Z; Ludwig, Michael Z; Dickerson, Desiree A; Barse, Levi; Arun, Bharath; Vilhjálmsson, Bjarni J; Jiang, Pengyao; Park, Soo-Young; Tamarina, Natalia A; Selleck, Scott B; Wittkopp, Patricia J; Bell, Graeme I; Kreitman, Martin

    2014-02-01

    The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS(C96Y)) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINS(C96Y) background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS(C96Y)-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanis