oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 50 )

2018 ( 319 )

2017 ( 291 )

2016 ( 456 )

Custom range...

Search Results: 1 - 10 of 298321 matches for " Clarke Angus J "
All listed articles are free for downloading (OA Articles)
Page 1 /298321
Display every page Item
Musings on genome medicine: the value of family history
Angus Clarke
Genome Medicine , 2009, DOI: 10.1186/gm75
Abstract: Family history information has been used for decades in the process of genetic risk assessment [1] and is used extensively to identify those at risk of inherited conditions and those at increased risk of common diseases, such as colorectal cancer, breast cancer and coronary artery disease [2]. Those at risk may then benefit from targeted genetic testing to distinguish between those who are actually at high risk of disease and those who are in fact not. Once genomic sequence information has become readily available, on patients and on healthy individuals, will this completely obviate the need for family history information, so that the taking of family histories becomes obsolete? In short, can everything important be written with just the four letters A, C, G and T?Undergraduate medical students are taught to take a family history for all their patients and this is also recommended in many clinical specialty training programs, including those for primary care practitioners. It not only helps to identify those at increased risk of an inherited disorder or of a single-gene (Mendelian) subset of a common disorder, but also provides useful social information about the patient and his or her family. Even if this family information were to add no further precision to estimates of disease risk, the clinician would still wish to continue collecting family histories for the additional insights they provide. One gathers not only the structure of the family and some knowledge of the diseases that have affected the various individuals but also a rich understanding of social context, occupation, family relationships (who talks to whom), and perhaps lifestyles and habits too. The process of collecting this information allows a relationship to develop between professional and patient, which is useful to the practitioner and valued by the patient [3]. Through this, one can often sense the real concerns of the patient or client: what do they fear? Do they feel destined to follow the
‘Sifting the significance from the data’ - the impact of high-throughput genomic technologies on human genetics and health care
Clarke Angus J,Cooper David N,Krawczak Michael,Tyler-Smith Chris
Human Genomics , 2012, DOI: 10.1186/1479-7364-6-11
Abstract: This report is of a round-table discussion held in Cardiff in September 2009 for Cesagen, a research centre within the Genomics Network of the UK’s Economic and Social Research Council. The meeting was arranged to explore ideas as to the likely future course of human genomics. The achievements of genomics research were reviewed, and the likely constraints on the pace of future progress were explored. New knowledge is transforming biology and our understanding of evolution and human disease. The difficulties we face now concern the interpretation rather than the generation of new sequence data. Our understanding of gene-environment interaction is held back by our current primitive tools for measuring environmental factors, and in addition, there may be fundamental constraints on what can be known about these complex interactions.
'Genomic counseling'? Genetic counseling in the genomic era
Angus Clarke, Katie Thirlaway
Genome Medicine , 2011, DOI: 10.1186/gm221
Abstract: For now, no reputable professional - genetic counselor or other clinician - is using SNP array results in relation to complex diseases as the basis of health care interventions or to support recommendations about lifestyle: the validity of such interpretations is insufficiently robust and there has been no demonstration of clinical utility [4,5]. However, once genome sequencing is widely available and readily affordable, many of the obstacles to the demonstration of validity will (eventually) disappear, although it will take time for the clinical research community to develop confidence in the interpretation of the accumulating data. At that point, whenever that comes to pass, will genetic counselors embrace the genomics of complex disease as well as the genetics of Mendelian disease?Our answer is a Yes and a No and a Maybe.The principal clinical application of genome sequencing has so far been the recognition of 'new' Mendelian loci responsible either for previously unrecognized disorders or for additional loci contributing to known clinical entities. As the cost of genome sequencing approaches the cost of mutation searching in multiple loci associated with a disease presentation, such as hypertrophic cardiomyopathy or retinitis pigmentosa, genome sequencing will be performed because it will be a cheaper means to resolve the locus heterogeneity or to distinguish the unusual Mendelian forms of a common disease from the much more frequent sporadic cases. The clinical application will be driven by a Mendelian logic: even conservative and cautious genetic counselors will use such information gratefully as it will allow them to give useful answers to their patients and their patients' relatives more frequently and more rapidly.There will, however, be a less clearly useful - and less welcome - spate of information to flow from the genome sequencers. Alongside the information that is actively sought and desired because it is of practical relevance, there will be informati
A Nonsense Mutation in the IKBKG Gene in Mares with Incontinentia Pigmenti
Rachel E. Towers, Leonardo Murgiano, David S. Millar, Elise Glen, Ana Topf, Vidhya Jagannathan, Cord Dr?gemüller, Judith A. Goodship, Angus J. Clarke, Tosso Leeb
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081625
Abstract: Ectodermal dysplasias (EDs) are a large and heterogeneous group of hereditary disorders characterized by abnormalities in structures of ectodermal origin. Incontinentia pigmenti (IP) is an ED characterized by skin lesions evolving over time, as well as dental, nail, and ocular abnormalities. Due to X-linked dominant inheritance IP symptoms can only be seen in female individuals while affected males die during development in utero. We observed a family of horses, in which several mares developed signs of a skin disorder reminiscent of human IP. Cutaneous manifestations in affected horses included the development of pruritic, exudative lesions soon after birth. These developed into wart-like lesions and areas of alopecia with occasional wooly hair re-growth. Affected horses also had streaks of darker and lighter coat coloration from birth. The observation that only females were affected together with a high number of spontaneous abortions suggested an X-linked dominant mechanism of transmission. Using next generation sequencing we sequenced the whole genome of one affected mare. We analyzed the sequence data for non-synonymous variants in candidate genes and found a heterozygous nonsense variant in the X-chromosomal IKBKG gene (c.184C>T; p.Arg62*). Mutations in IKBKG were previously reported to cause IP in humans and the homologous p.Arg62* variant has already been observed in a human IP patient. The comparative data thus strongly suggest that this is also the causative variant for the observed IP in horses. To our knowledge this is the first large animal model for IP.
Speciation and Gene Flow between Snails of Opposite Chirality
Angus Davison,Satoshi Chiba,Nicholas H. Barton,Bryan Clarke
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0030282
Abstract: Left-right asymmetry in snails is intriguing because individuals of opposite chirality are either unable to mate or can only mate with difficulty, so could be reproductively isolated from each other. We have therefore investigated chiral evolution in the Japanese land snail genus Euhadra to understand whether changes in chirality have promoted speciation. In particular, we aimed to understand the effect of the maternal inheritance of chirality on reproductive isolation and gene flow. We found that the mitochondrial DNA phylogeny of Euhadra is consistent with a single, relatively ancient evolution of sinistral species and suggests either recent “single-gene speciation” or gene flow between chiral morphs that are unable to mate. To clarify the conditions under which new chiral morphs might evolve and whether single-gene speciation can occur, we developed a mathematical model that is relevant to any maternal-effect gene. The model shows that reproductive character displacement can promote the evolution of new chiral morphs, tending to counteract the positive frequency-dependent selection that would otherwise drive the more common chiral morph to fixation. This therefore suggests a general mechanism as to how chiral variation arises in snails. In populations that contain both chiral morphs, two different situations are then possible. In the first, gene flow is substantial between morphs even without interchiral mating, because of the maternal inheritance of chirality. In the second, reproductive isolation is possible but unstable, and will also lead to gene flow if intrachiral matings occasionally produce offspring with the opposite chirality. Together, the results imply that speciation by chiral reversal is only meaningful in the context of a complex biogeographical process, and so must usually involve other factors. In order to understand the roles of reproductive character displacement and gene flow in the chiral evolution of Euhadra, it will be necessary to investigate populations in which both chiral morphs coexist.
Speciation and gene flow between snails of opposite chirality.
Davison Angus,Chiba Satoshi,Barton Nicholas H,Clarke Bryan
PLOS Biology , 2005,
Abstract: Left-right asymmetry in snails is intriguing because individuals of opposite chirality are either unable to mate or can only mate with difficulty, so could be reproductively isolated from each other. We have therefore investigated chiral evolution in the Japanese land snail genus Euhadra to understand whether changes in chirality have promoted speciation. In particular, we aimed to understand the effect of the maternal inheritance of chirality on reproductive isolation and gene flow. We found that the mitochondrial DNA phylogeny of Euhadra is consistent with a single, relatively ancient evolution of sinistral species and suggests either recent "single-gene speciation" or gene flow between chiral morphs that are unable to mate. To clarify the conditions under which new chiral morphs might evolve and whether single-gene speciation can occur, we developed a mathematical model that is relevant to any maternal-effect gene. The model shows that reproductive character displacement can promote the evolution of new chiral morphs, tending to counteract the positive frequency-dependent selection that would otherwise drive the more common chiral morph to fixation. This therefore suggests a general mechanism as to how chiral variation arises in snails. In populations that contain both chiral morphs, two different situations are then possible. In the first, gene flow is substantial between morphs even without interchiral mating, because of the maternal inheritance of chirality. In the second, reproductive isolation is possible but unstable, and will also lead to gene flow if intrachiral matings occasionally produce offspring with the opposite chirality. Together, the results imply that speciation by chiral reversal is only meaningful in the context of a complex biogeographical process, and so must usually involve other factors. In order to understand the roles of reproductive character displacement and gene flow in the chiral evolution of Euhadra, it will be necessary to investigate populations in which both chiral morphs coexist.
Speciation and Gene Flow between Snails of Opposite Chirality
Angus Davison ,Satoshi Chiba,Nicholas H Barton,Bryan Clarke
PLOS Biology , 2005, DOI: 10.1371/journal.pbio.0030282
Abstract: Left-right asymmetry in snails is intriguing because individuals of opposite chirality are either unable to mate or can only mate with difficulty, so could be reproductively isolated from each other. We have therefore investigated chiral evolution in the Japanese land snail genus Euhadra to understand whether changes in chirality have promoted speciation. In particular, we aimed to understand the effect of the maternal inheritance of chirality on reproductive isolation and gene flow. We found that the mitochondrial DNA phylogeny of Euhadra is consistent with a single, relatively ancient evolution of sinistral species and suggests either recent “single-gene speciation” or gene flow between chiral morphs that are unable to mate. To clarify the conditions under which new chiral morphs might evolve and whether single-gene speciation can occur, we developed a mathematical model that is relevant to any maternal-effect gene. The model shows that reproductive character displacement can promote the evolution of new chiral morphs, tending to counteract the positive frequency-dependent selection that would otherwise drive the more common chiral morph to fixation. This therefore suggests a general mechanism as to how chiral variation arises in snails. In populations that contain both chiral morphs, two different situations are then possible. In the first, gene flow is substantial between morphs even without interchiral mating, because of the maternal inheritance of chirality. In the second, reproductive isolation is possible but unstable, and will also lead to gene flow if intrachiral matings occasionally produce offspring with the opposite chirality. Together, the results imply that speciation by chiral reversal is only meaningful in the context of a complex biogeographical process, and so must usually involve other factors. In order to understand the roles of reproductive character displacement and gene flow in the chiral evolution of Euhadra, it will be necessary to investigate populations in which both chiral morphs coexist.
Social Capital as Dehumanizing Terminology  [PDF]
Robert J. Taormina, Angus C. H. Kuok, Wei Wei
Advances in Applied Sociology (AASoci) , 2012, DOI: 10.4236/aasoci.2012.22019
Abstract: This paper argues that the term “social capital” is an inappropriate terminology that is unsuited for theory or scientific empirical research. The arguments challenge the metaphor and definition by revealing the phrase to be dehumanizing, oxymoronic, anachronistic, and demeaning, which makes it incorrect, and even immoral, for proper use. It is also argued that the term is 1984-ish vis-à-vis Doublethink and Newspeak. It is recommended that the metaphors for “social capital” and its related term, “human capital,” should be dropped from use. It is further recommended, for the purpose of increased clarity for theory building and for empirical research, and to avoid using dehumanizing terminology, that it is more appropriate to retain the term “social networking” as the general name for the process; such that, when attempting to measure related social networking concepts, researchers should specify operationally defined variable names that are more suited to proper scientific measurement of the research domains. For example, if “friends” are studied as helpers in a social network, that term may be used as a variable name, but under no circumstances should one’s friends, or other people, be referred to or regarded as “capital.”
Exploring Trends in Microcrack Properties of Sedimentary Rocks: An Audit of Dry and Water Saturated Sandstone Core Velocity–Stress Measurements  [PDF]
Doug A. Angus, Quentin J. Fisher, James P. Verdon
International Journal of Geosciences (IJG) , 2012, DOI: 10.4236/ijg.2012.324083
Abstract: Stress dependent rock physics models are being used more routinely to link mechanical deformation and stress perturbations to changes in seismic velocities and seismic anisotropy. In this paper, we invert for the effective non-linear microstructural parameters of 69 dry and saturated sandstone core samples. We evaluate the results in terms of the model input parameters of two non-linear rock physics models: A discrete and an analytic microstructural stress-dependent formulation. The results for the analytic model suggest that the global trend of the initial crack density is lower and initial aspect ratio is larger for the saturated samples compared to the corresponding dry samples. The initial aspect ratios for both the dry and saturated samples are tightly clustered between 0.0002 and 0.001, whereas the initial crack densities show more scatter. The results for the discrete model show higher crack densities for the saturated samples when compared to the corresponding dry samples. With increasing confining stress the crack densities decreases to almost identical values for both the dry and saturated samples. A key result of this paper is that there appears to be a stress dependence of the compliance ratio BN/BT within many of the samples, possibly related to changing microcrack geometry with increasing confining stress. Furthermore, although the compliance ratio BN/BT for dry samples shows a diffuse distribution between 0.4 and 2.0, for saturated samples the distribution is very tightly clustered around 0.5. As confining stresses increase the compliance ratio distributions for the dry and saturated samples become more diffuse but still noticeably different. This result is significant because it reaffirms previous observations that the compliance ratio can be used as an indicator of fluid content within cracks and fractures. From a practical perspective, an overarching purpose of this paper is to investigate the range of input parameters of the microstructural models under both dry and saturated conditions to improve prediction of stress dependent seismic velocity and anisotropy observed in time-lapse seismic data due to hydro-mechanical effects related to fluid production and injection.
Irish Cepaea nemoralis Land Snails Have a Cryptic Franco-Iberian Origin That Is Most Easily Explained by the Movements of Mesolithic Humans
Adele J. Grindon, Angus Davison
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065792
Abstract: The origins of flora and fauna that are only found in Ireland and Iberia, but which are absent from intervening countries, is one of the enduring questions of biogeography. As Southern French, Iberian and Irish populations of the land snail Cepaea nemoralis sometimes have a similar shell character, we used mitochondrial phylogenies to begin to understand if there is a shared “Lusitanian” history. Although much of Europe contains snails with A and D lineages, by far the majority of Irish individuals have a lineage, C, that in mainland Europe was only found in a restricted region of the Eastern Pyrenees. A past extinction of lineage C in the rest of Europe cannot be ruled out, but as there is a more than 8000 year continuous record of Cepaea fossils in Ireland, the species has long been a food source in the Pyrenees, and the Garonne river that flanks the Pyrenees is an ancient human route to the Atlantic, then we suggest that the unusual distribution of the C lineage is most easily explained by the movements of Mesolithic humans. If other Irish species have a similarly cryptic Lusitanian element, then this raises the possibility of a more widespread and significant pattern.
Page 1 /298321
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.