Evidence for social learning in wild lemurs (Lemur catta).

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Kendal, Rachel L; Custance, Deborah M; Kendal, Jeremy R; Vale, Gillian; Stoinski, Tara S; Rakotomalala, Nirina Lalaina; Rasamimanana, Hantanirina

2010-08-01

Interest in social learning has been fueled by claims of culture in wild animals. These remain controversial because alternative explanations to social learning, such as asocial learning or ecological differences, remain difficult to refute. Compared with laboratory-based research, the study of social learning in natural contexts is in its infancy. Here, for the first time, we apply two new statistical methods, option-bias analysis and network-based diffusion analysis, to data from the wild, complemented by standard inferential statistics. Contrary to common thought regarding the cognitive abilities of prosimian primates, our evidence is consistent with social learning within subgroups in the ring-tailed lemur (Lemur catta), supporting the theory of directed social learning (Coussi-Korbel & Fragaszy, 1995). We also caution that, as the toolbox for capturing social learning in natural contexts grows, care is required in ensuring that the methods employed are appropriate-in particular, regarding social dynamics among study subjects. Supplemental materials for this article may be downloaded from http://lb.psychonomic-journals.org/content/supplemental.

Interspecific semantic alarm call recognition in the solitary Sahamalaza sportive lemur, Lepilemur sahamalazensis.

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Melanie Seiler

Full Text Available As alarm calls indicate the presence of predators, the correct interpretation of alarm calls, including those of other species, is essential for predator avoidance. Conversely, communication calls of other species might indicate the perceived absence of a predator and hence allow a reduction in vigilance. This "eavesdropping" was demonstrated in birds and mammals, including lemur species. Interspecific communication between taxonomic groups has so far been reported in some reptiles and mammals, including three primate species. So far, neither semantic nor interspecific communication has been tested in a solitary and nocturnal lemur species. The aim of this study was to investigate if the nocturnal and solitary Sahamalaza sportive lemur, Lepilemur sahamalazensis, is able to access semantic information of sympatric species. During the day, this species faces the risk of falling prey to aerial and terrestrial predators and therefore shows high levels of vigilance. We presented alarm calls of the crested coua, the Madagascar magpie-robin and aerial, terrestrial and agitation alarm calls of the blue-eyed black lemur to 19 individual Sahamalaza sportive lemurs resting in tree holes. Songs of both bird species' and contact calls of the blue-eyed black lemur were used as a control. After alarm calls of crested coua, Madagascar magpie-robin and aerial alarm of the blue-eyed black lemur, the lemurs scanned up and their vigilance increased significantly. After presentation of terrestrial alarm and agitation calls of the blue-eyed black lemur, the animals did not show significant changes in scanning direction or in the duration of vigilance. Sportive lemur vigilance decreased after playbacks of songs of the bird species and contact calls of blue-eyed black lemurs. Our results indicate that the Sahamalaza sportive lemur is capable of using information on predator presence as well as predator type of different sympatric species, using their referential

Signals of recent spatial expansions in the grey mouse lemur (Microcebus murinus

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Chikhi Lounès

2010-04-01

Full Text Available Abstract Background Pleistocene events have shaped the phylogeography of many taxa worldwide. Their genetic signatures in tropical species have been much less explored than in those living in temperate regions. We analysed the genetic structure of a Malagasy primate species, a mouse lemur with a wide distribution (M. murinus, in order to investigate such phylogeographic processes on a large tropical island. We also evaluated the effects of anthropogenic pressures (fragmentation/deforestation and natural features (geographic distance, rivers on genetic structure in order to complement our understanding of past and present processes of genetic differentiation. Results The analysis of the mitochondrial D-loop sequences of 195 samples from 15 study sites (10 from a continuous forest and five from isolated forest fragments from two adjacent Inter-River-Systems (IRSs revealed that forest fragmentation and the river restrict gene flow, thereby leading to an increased genetic differentiation between populations beyond the effect of isolation-by-distance. Demographic simulations detected signals of two successive spatial expansions that could be preliminarily dated to the late Pleistocene and early Holocene. The haplotype network revealed geographic structure and showed deep molecular divergences within and between the IRSs that would be congruent with a two-step colonization scenario. Conclusions This study supports the hypothesis of a relatively recent spatial expansion of the grey mouse lemur in northwestern Madagascar, which may also explain why this taxon, in contrast to its congeners, has not yet undergone allopatric speciation in the studied area and possibly across its presently wide range.

Systemic effects of Leucaena leucocephala ingestion on ringtailed lemurs (Lemur catta) at Berenty Reserve, Madagascar.

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Crawford, Graham; Puschner, Birgit; Affolter, Verena; Stalis, Ilse; Davidson, Autumn; Baker, Tomas; Tahara, John; Jolly, Alison; Ostapak, Susan

2015-06-01

Leucaena (Leucaena leucocephala) is a leguminous tree that is nutritious forage for domestic livestock when ingested in limited amounts. Unfortunately, leucaena contains mimosine, a plant amino acid, that can be toxic when ingested at higher concentrations. Reported toxic effects include alopecia (fur loss), poor body condition, infertility, low birth weight, thyroid gland dysfunction, and organ toxicity. Originally native to Mexico and Central America, leucaena has been introduced throughout the tropics, including Berenty Reserve, Madagascar where it was planted as supplemental browse for livestock. In Berenty, a seasonal syndrome of alopecia in ringtailed lemurs (Lemur catta) is associated with eating leucaena. Although much is known about the toxic effects of leucaena and mimosine on domestic animals and humans, the systemic effects on wildlife had not been studied. In a comparison of lemurs that include leucaena in their diet and those that do not, we found that animals that ingest leucaena absorb mimosine but that ingestion does not affect body condition, cause kidney or liver toxicity, or affect the intestinal tract. Alopecia is due to mimosine's interference of the hair follicle cycle. Leucaena ingestion is associated with higher serum albumin, α-tocopherol, and thyroxine concentrations, suggesting that leucaena may provide some nutritional benefit and that lemurs can detoxify and convert mimosine to a thyroid stimulating metabolite. The primary conservation consequence of leucaena ingestion at Berenty may be increased infant mortality due to the infants' inability cling to their alopecic mothers. The widespread introduction of leucaena throughout the tropics and its rapid spread in secondary forest conditions mean that many other leaf-eating mammals may be including this tree in their diet. Thus, exposure to leucaena should be considered when wildlife health is being evaluated, and the potential effects on wildlife health should be considered when

Seroprevalence of Toxoplasma gondii, Sarcocystis neurona, and Encephalitozoon cuniculi in three species of lemurs from St. Catherines Island, GA, USA.

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Yabsley, Michael J; Jordan, Carly N; Mitchell, Sheila M; Norton, Terry M; Lindsay, David S

2007-03-15

In the current study, we determined the seroprevalence of Toxoplasma gondii, Sarcocystis neurona, and Encephalitozoon cuniculi in three species of lemurs from St. Catherines Island, Georgia. Serum samples were tested from 52 ring-tailed lemurs (Lemur catta), six blue-eyed black lemurs (Eulemur macaco flavifrons), and four black and white ruffed lemurs (Varecia variegata variegata) using an agglutination assay. Three ring-tailed lemurs (5.8%) were positive for T. gondii (titer of 1:50); one ring-tailed lemur (1.9%) and one black and white ruffed lemur (25%) were positive for S. neurona (titers of 1:1000); and one ring-tailed lemur (1.9%) was positive for E. cuniculi (titer of 1:400). All blue-eyed black lemurs were negative for antibodies to T. gondii, S. neurona, and E. cuniculi. This is the first detection of antibodies to T. gondii in ring-tailed lemurs and antibodies to S. neurona and E. cuniculi in any species of prosimian.

Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

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Jean-Luc Picq

Full Text Available The mouse lemur (Microcebus murinus is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12 and aged (n = 8 adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.

Modeling the origins of mammalian sociality: moderate evidence for matrilineal signatures in mouse lemur vocalizations.

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Kessler, Sharon E; Radespiel, Ute; Hasiniaina, Alida I F; Leliveld, Lisette M C; Nash, Leanne T; Zimmermann, Elke

2014-02-20

moderately distinctive by matriline. Because sleeping groups consisted of close maternal kin, both genetics and social learning may have generated these acoustic signatures. As mouse lemurs are models for solitary foragers, we recommend further studies testing whether the lemurs use these calls to recognize kin. This would enable further modeling of how kin recognition in ancestral species could have shaped the evolution of complex sociality.

Does habitat disturbance affect stress, body condition and parasitism in two sympatric lemurs?

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Rakotoniaina, Josué H; Kappeler, Peter M; Ravoniarimbinina, Pascaline; Pechouskova, Eva; Hämäläinen, Anni M; Grass, Juliane; Kirschbaum, Clemens; Kraus, Cornelia

2016-01-01

Understanding how animals react to human-induced changes in their environment is a key question in conservation biology. Owing to their potential correlation with fitness, several physiological parameters are commonly used to assess the effect of habitat disturbance on animals' general health status. Here, we studied how two lemur species, the fat-tailed dwarf lemur (Cheirogaleus medius) and the grey mouse lemur (Microcebus murinus), respond to changing environmental conditions by comparing their stress levels (measured as hair cortisol concentration), parasitism and general body condition across four habitats ordered along a gradient of human disturbance at Kirindy Forest, Western Madagascar. These two species previously revealed contrasting responses to human disturbance; whereas M. murinus is known as a resilient species, C. medius is rarely encountered in highly disturbed habitats. However, neither hair cortisol concentrations nor parasitism patterns (prevalence, parasite species richness and rate of multiple infections) and body condition varied across the gradient of anthropogenic disturbance. Our results indicate that the effect of anthropogenic activities at Kirindy Forest is not reflected in the general health status of both species, which may have developed a range of behavioural adaptations to deal with suboptimal conditions. Nonetheless, a difference in relative density among sites suggests that the carrying capacity of disturbed habitat is lower, and both species respond differently to environmental changes, with C. medius being more negatively affected. Thus, even for behaviourally flexible species, extended habitat deterioration could hamper long-term viability of populations.

Coat condition of ringtailed lemurs, Lemur catta at Berenty Reserve, Madagascar: I. Differences by age, sex, density and tourism, 1996-2006.

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Jolly, Alison

2009-03-01

An index of coat condition can be a non-invasive tool for tracking health and stress at population level. Coat condition in ringtailed lemurs, Lemur catta, was recorded during September-November birth seasons of 1996, 1997, 1999, and 2001-2006 at Berenty Reserve, Madagascar. Condition was scored on a scale from 0: full, fluffy coat with guard hairs present, to 5: half or more of body hairless. Adult males did not differ overall from adult females. Coats were worse in adults than in 2-year-old subadults; 1-year-old juveniles were intermediate. Mothers and adult males lost coat condition as the season progressed: non-mother females maintained condition. Years 1999-2002 scored better coats than either 1996-1997 or 2003-2006. Lemurs in high population density areas had worse coats than in natural forest, but tourist presence had less effect than density. Monitoring coat condition in an apparently healthy population reveals differences between population segments, and in a forest fragment with limited immigration or emigration it can track progressive changes, correcting impressions of progressive improvement or degradation over time. Above all it gives a baseline for response to climate changes or eventual pathology. (c) 2008 Wiley-Liss, Inc.

Better Few than Hungry: Flexible Feeding Ecology of Collared Lemurs Eulemur collaris in Littoral Forest Fragments

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Donati, Giuseppe; Kesch, Kristina; Ndremifidy, Kelard; Schmidt, Stacey L.; Ramanamanjato, Jean-Baptiste; Borgognini-Tarli, Silvana M.; Ganzhorn, Joerg U.

2011-01-01

Background Frugivorous primates are known to encounter many problems to cope with habitat degradation, due to the fluctuating spatial and temporal distribution of their food resources. Since lemur communities evolved strategies to deal with periods of food scarcity, these primates are expected to be naturally adapted to fluctuating ecological conditions and to tolerate a certain degree of habitat changes. However, behavioral and ecological strategies adopted by frugivorous lemurs to survive in secondary habitats have been little investigated. Here, we compared the behavioral ecology of collared lemurs (Eulemur collaris) in a degraded fragment of littoral forest of south-east Madagascar, Mandena, with that of their conspecifics in a more intact habitat, Sainte Luce. Methodology/Principal Findings Lemur groups in Mandena and in Sainte Luce were censused in 2004/2007 and in 2000, respectively. Data were collected via instantaneous sampling on five lemur groups totaling 1,698 observation hours. The Shannon index was used to determine dietary diversity and nutritional analyses were conducted to assess food quality. All feeding trees were identified and measured, and ranging areas determined via the minimum convex polygon. In the degraded area lemurs were able to modify several aspects of their feeding strategies by decreasing group size and by increasing feeding time, ranging areas, and number of feeding trees. The above strategies were apparently able to counteract a clear reduction in both food quality and size of feeding trees. Conclusions/Significance Our findings indicate that collared lemurs in littoral forest fragments modified their behavior to cope with the pressures of fluctuating resource availability. The observed flexibility is likely to be an adaptation to Malagasy rainforests, which are known to undergo periods of fruit scarcity and low productivity. These results should be carefully considered when relocating lemurs or when selecting suitable areas for

Anatomy, histology, and ultrasonography of the normal adrenal gland in brown lemur: Eulemur fulvus.

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Raharison, Fidiniaina; Bourges Abella, Nathalie; Sautet, Jean; Deviers, Alexandra; Mogicato, Giovanni

2017-04-01

The medical care currently to brown lemurs (Eulemur fulvus) is limited by a lack of knowledge of their anatomy. The aim of this study was to describe the anatomy and histology and obtain ultrasonographic measurements of normal adrenal glands in these animals. The adrenal glands of four lemurs cadavers were used for the anatomical and histological studies, and those of 15 anesthetized lemurs were examined by ultrasonography. Anatomically, the adrenal glands of brown lemurs are comparable to those of other species. The histological findings showed that the cortex is organized into three distinct layers, whereas most domestic mammals have an additional zone. The surface area of the adrenal glands increased with body weight, and the area of the right adrenal was slightly larger than the left. We suggest using ultrasonography to aid the etiological diagnosis of behavioral abnormalities that might be due to dysfunctions of the adrenal gland. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mutual tolerance or reproductive competition? Patterns of reproductive skew among male redfronted lemurs (Eulemur fulvus rufus)

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Kappeler, Peter M.; Port, Markus

2008-01-01

The social organization of gregarious lemurs significantly deviates from predictions of the socioecological model, as they form small groups in which the number of males approximately equals the number of females. This study uses models of reproductive skew theory as a new approach to explain this unusual group composition, in particular the high number of males, in a representative of these lemurs, the redfronted lemur (Eulemur fulvus rufus). We tested two central predictions of “concession”...

Synthetic smooth muscle in the outer blood plexus of the rhinarium skin of Lemur catta L.

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Elofsson, Rolf; Kröger, Ronald H H

2017-01-01

The skin of the lemur nose tip (rhinarium) has arterioles in the outer vascular plexus that are endowed with an unusual coat of smooth muscle cells. Comparison with the arterioles of the same area in a number of unrelated mammalians shows that the lemur pattern is unique. The vascular smooth muscle cells belong to the synthetic type. The function of synthetic smooth muscles around the terminal vessels in the lemur rhinarium is unclear but may have additional functions beyond regulation of vessel diameter.

Hybridization of mouse lemurs: different patterns under different ecological conditions

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Rosenkranz David

2011-10-01

Full Text Available Abstract Background Several mechanistic models aim to explain the diversification of the multitude of endemic species on Madagascar. The island's biogeographic history probably offered numerous opportunities for secondary contact and subsequent hybridization. Existing diversification models do not consider a possible role of these processes. One key question for a better understanding of their potential importance is how they are influenced by different environmental settings. Here, we characterized a contact zone between two species of mouse lemurs, Microcebus griseorufus and M. murinus, in dry spiny bush and mesic gallery forest that border each other sharply without intermediate habitats between them. We performed population genetic analyses based on mtDNA sequences and nine nuclear microsatellites and compared the results to a known hybrid zone of the same species in a nearby wide gradient from dry spiny bush over transitional forest to humid littoral forest. Results In the spiny-gallery system, Microcebus griseorufus is restricted to the spiny bush; Microcebus murinus occurs in gallery forest and locally invades the dryer habitat of its congener. We found evidence for bidirectional introgressive hybridization, which is closely linked to increased spatial overlap within the spiny bush. Within 159 individuals, we observed 18 hybrids with mitochondrial haplotypes of both species. Analyses of simulated microsatellite data indicate that we identified hybrids with great accuracy and that we probably underestimated their true number. We discuss short-term climatic fluctuations as potential trigger for the dynamic of invasion and subsequent hybridization. In the gradient hybrid zone in turn, long-term aridification could have favored unidirectional nuclear introgression from Microcebus griseorufus into M. murinus in transitional forest. Conclusions Madagascar's southeastern transitional zone harbors two very different hybrid zones of mouse lemurs

Lemurs - Ambassadors for Madagascar | Thalmann | Madagascar ...

African Journals Online (AJOL)

In this short article on lemurs I give a concise introduction for non-specialists to these conspicuous and unique animals on the island of Madagascar. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/mcd.v1i1.44043 · AJOL African ...

Illegal captive lemurs in Madagascar: Comparing the use of online and in-person data collection methods.

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Reuter, Kim E; Schaefer, Melissa S

2017-11-01

Although it is illegal to capture, sell, and trade lemurs, the live capture of lemurs in Madagascar is ongoing and may have impacted over 28,000 lemurs between 2010 and 2013. Only one study has examined this trade and did so using in-person interviews in northern Madagascar. The current study sought to expand this existing dataset and examine the comparability of online surveys to more traditional on-location data collection methods. In this study, we collected data through a web-based survey resulting in 302 sightings of 685 captive lemurs. We also collected data from 171 hotel and 43 restaurant websites and social media profiles. Survey submissions included sightings of 30 species from 10 genera, nearly twice as many species as identified via the in-person interviews. Lemur catta, Varecia variegata, and Eulemur fulvus were the most common species sighted in captivity. Captive lemurs were reported in 19 of Madagascar's 22 administrative regions and most were seen in urban areas near their habitat ranges. This represents a wider geographic distribution of captive lemurs than previously found through in-person interviews. The online survey results were broadly similar to those of the in-person surveys though greater in species and geographic diversity demonstrating advantages to the use of online surveys. The online research methods were low in cost (USD $100) compared to on-location data collection (USD $12,000). Identified disadvantages included sample bias; most of the respondents to the online survey were researchers and many captive sightings were near study sites. The results illustrate the benefits of incorporating a social science approach using online surveys as a complement to traditional fieldwork. Am. J. Primatol. 79:e22541, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The microbiome of Haemaphysalis lemuris (Acari: Ixodidae), a possible vector of pathogens of endangered lemur species in Madagascar.

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Lado, Paula; Qurollo, Barbara; Williams, Cathy; Junge, Randall; Klompen, Hans

2018-05-02

Lemurs are primate species that are endemic to Madagascar. At present, about 90% of lemur species are endangered, and 5 species are among the 25 most endangered primates worldwide. Health status is a major factor impacting the viability of wild populations of many endangered species including lemurs. Given this context, we analyzed the microbiome of 24 specimens of Haemaphysalis lemuris, the most common tick parasitizing lemurs in their native habitats. Ticks were collected from 6 lemur species and microbiomes analyzed using next-generation sequencing. Our results show that the H. lemuris microbiome is highly diverse, including over 500 taxa, 267 of which were identified to genus level. Analysis of the microbiome also shows that there is a distinct "host" (lemur species) component when explaining the differences among and between microbial communities of H. lemuris. This "host" component seems to overwhelm any "locality" (geographic origin of the sample) component. In addition to the microbiome data, targeted PCR was used to test for the presence of three pathogens recently detected in the blood of wild lemurs: Borrelia sp., Candidatus Neoehrlichia sp., and Babesia sp. Overall, the presence of DNA of Rickettsia spp., Bartonella spp., Francisella spp., and a Babesia sp., in H. lemuris, is consistent with the hypothesis that these ectoparasites may act as vector for these pathogens. Further studies assessing vector competence are needed to confirm this hypothesis. Copyright © 2018 Elsevier GmbH. All rights reserved.

"Life history space": a multivariate analysis of life history variation in extant and extinct Malagasy lemurs.

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Catlett, Kierstin K; Schwartz, Gary T; Godfrey, Laurie R; Jungers, William L

2010-07-01

Studies of primate life history variation are constrained by the fact that all large-bodied extant primates are haplorhines. However, large-bodied strepsirrhines recently existed. If we can extract life history information from their skeletons, these species can contribute to our understanding of primate life history variation. This is particularly important in light of new critiques of the classic "fast-slow continuum" as a descriptor of variation in life history profiles across mammals in general. We use established dental histological methods to estimate gestation length and age at weaning for five extinct lemur species. On the basis of these estimates, we reconstruct minimum interbirth intervals and maximum reproductive rates. We utilize principal components analysis to create a multivariate "life history space" that captures the relationships among reproductive parameters and brain and body size in extinct and extant lemurs. Our data show that, whereas large-bodied extinct lemurs can be described as "slow" in some fashion, they also varied greatly in their life history profiles. Those with relatively large brains also weaned their offspring late and had long interbirth intervals. These were not the largest of extinct lemurs. Thus, we distinguish size-related life history variation from variation that linked more strongly to ecological factors. Because all lemur species larger than 10 kg, regardless of life history profile, succumbed to extinction after humans arrived in Madagascar, we argue that large body size increased the probability of extinction independently of reproductive rate. We also provide some evidence that, among lemurs, brain size predicts reproductive rate better than body size. (c) 2010 Wiley-Liss, Inc.

Fatal infection with Taenia martis metacestodes in a ring-tailed lemur (Lemur catta) living in an Italian zoological garden.

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De Liberato, Claudio; Berrilli, Federica; Meoli, Roberta; Friedrich, Klaus G; Di Cerbo, Pilar; Cocumelli, Cristiano; Eleni, Claudia

2014-10-01

A case of fatal infection caused by larval forms of Taenia martis in a ring-tailed lemur (Lemur catta) living in the Rome zoological garden is described. The animal, living in a semi-natural pen with other 15 conspecific individuals and being fed with fresh fruit and vegetables, yoghurt and eggs, was transported to the Istituto Zooprofilattico of Rome for post-mortem examination. The anamnesis included, ten days before the death, apathy, lack of appetite, abdominal distension and diarrhoea. A severe exudative fibrinous-purulent peritonitis with numerous adhesions between the abdominal wall and the bowel loops was detected. After intestine removal, two free and viable, 4 cm long, whitish, leaf-like parasitic forms were pinpointed. Macroscopic examination of the two parasites allowed their identification as larval stages of cestodes, identified via molecular analysis as T. martis metacestodes. This report represents the first record of T. martis infection in the host species and in a zoological garden and for the pathological relevance of the infection. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Anatomy and ultrasonography of the normal kidney in brown lemurs: Eulemur fulvus.

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Raharison, Fidiniaina; Mogicato, Giovanni; Sautet, Jean

2009-08-01

The purpose of this study is to describe the anatomy and obtain echographic measurements of normal kidneys in brown lemurs (Eulemur fulvus). The anatomical findings show that brown lemur kidneys are comparable to those of rats except for an elongated papilla. The kidneys of 16 (7 females and 9 males) lemurs were examined with two-dimensional and power Doppler ultrasonography under general anesthesia. Morphometrically, the left and right kidney surface areas are comparable (3.29 and 3.51 cm(2)). Kidney area has a significant linear correlation with body weight. Echo-Doppler findings show that the mean renal arterial blood flow speeds for the left and right kidneys are comparable (0.70 and 0.73 m/s). However, flow speed is higher in the male (0.79 m/s) than in the female (0.60 m/s). The renal arterial diameters are between 1.0 and 1.8 mm. The fact that anesthesia can have hemodynamic effects on renal vasculature should be taken into consideration when assessing these echographic results.

Sight or scent: lemur sensory reliance in detecting food quality varies with feeding ecology.

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Julie Rushmore

Full Text Available Visual and olfactory cues provide important information to foragers, yet we know little about species differences in sensory reliance during food selection. In a series of experimental foraging studies, we examined the relative reliance on vision versus olfaction in three diurnal, primate species with diverse feeding ecologies, including folivorous Coquerel's sifakas (Propithecus coquereli, frugivorous ruffed lemurs (Varecia variegata spp, and generalist ring-tailed lemurs (Lemur catta. We used animals with known color-vision status and foods for which different maturation stages (and hence quality produce distinct visual and olfactory cues (the latter determined chemically. We first showed that lemurs preferentially selected high-quality foods over low-quality foods when visual and olfactory cues were simultaneously available for both food types. Next, using a novel apparatus in a series of discrimination trials, we either manipulated food quality (while holding sensory cues constant or manipulated sensory cues (while holding food quality constant. Among our study subjects that showed relatively strong preferences for high-quality foods, folivores required both sensory cues combined to reliably identify their preferred foods, whereas generalists could identify their preferred foods using either cue alone, and frugivores could identify their preferred foods using olfactory, but not visual, cues alone. Moreover, when only high-quality foods were available, folivores and generalists used visual rather than olfactory cues to select food, whereas frugivores used both cue types equally. Lastly, individuals in all three of the study species predominantly relied on sight when choosing between low-quality foods, but species differed in the strength of their sensory biases. Our results generally emphasize visual over olfactory reliance in foraging lemurs, but we suggest that the relative sensory reliance of animals may vary with their feeding ecology.

Gender markedly modulates behavioral thermoregulation in a non-human primate species, the mouse lemur (Microcebus murinus).

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Terrien, J; Perret, M; Aujard, F

2010-11-02

Age and gender are known to significantly modulate thermoregulatory capacities in mammals, suggesting strong impacts on behavioral adjustments, which are used to minimize the energy costs of thermoregulation. We tested the effects of sex and age on spontaneous choice of ambient temperature (Ta) in a non-human primate species, the mouse lemur (Microcebus murinus). The animals acclimated to both winter and summer photoperiods, two seasons significantly modifying thermoregulation function, were experimented in a thermal gradient device. During winter, adult males did not show preference for warm Tas whereas old males did. In contrast, female mouse lemurs of both age categories exhibited great preferences for warm Tas. Acclimation to summer revealed that males selected colder Ta for the day than during the night. Such behavior did not exist in females. Old females explored and selected warmer nests than adult ones. This study raised novel issues on the effect of gender on thermoregulatory capacities in the mouse lemur. Females probably use behavioral adjustments to limit energy expenditure and might prefer to preserve energy for maternal investment by anticipation of and during the breeding season. Further experiments focusing on female thermoregulatory capacities are needed to better understand the energy challenge that may occur during winter and summer in female mouse lemurs, and whether this trade-off changes during aging. Copyright © 2010 Elsevier Inc. All rights reserved.

Biomedical evaluation of free-ranging red ruffed lemurs (Varecia rubra) within the Masoala National Park, Madagascar.

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Dutton, Christopher J; Junge, Randall E; Louis, Edward E

2008-03-01

Complete health assessments were performed on 22 adult red ruffed lemurs (Varecia rubra), comprising nine males and 13 females, found within the Masoala National Park in northeast Madagascar. Each animal was anesthetized using tiletamine and zolazepam and underwent a thorough physical examination, including measurement of its weight and vital signs; blood collection for hematology, plasma total protein concentration, serum chemistries, fat-soluble vitamins, trace minerals, assessment of iron metabolism, toxoplasmosis serology, viral serologies, and examination for hemoparasites; fecal collection for bacterial culture and parasite examination; and collection of a representative number of any ectoparasites. Comparison of blood values with those of captive lemurs demonstrated a number of significant differences thought to be associated with physiologic state (e.g., reproductive stage and stress), hydration, and diet. There was no evidence of serious infectious diseases, and hemoparasites were not detected. The enteric flora appeared unremarkable; however, results may have been skewed toward more cold-tolerant bacteria. The fecal parasite burden was low. Lemurostrongylus spp. was identified in two of the lemurs, and there were moderate numbers of Laelapidae mites present on approximately one third of the lemurs. This study demonstrated the substantial amount of data that can be collected from free-ranging populations, considered invaluable in the management of captive populations, in reducing the incidence of captivity-related diseases, and in the risk assessment associated with reintroduction programs.

High frequency/ultrasonic communication in a critically endangered nocturnal primate, Claire's mouse lemur (Microcebus mamiratra).

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Hasiniaina, Alida F; Scheumann, Marina; Rina Evasoa, Mamy; Braud, Diane; Rasoloharijaona, Solofonirina; Randrianambinina, Blanchard; Zimmermann, Elke

2018-05-02

The critically endangered Claire's mouse lemur, only found in the evergreen rain forest of the National Park Lokobe (LNP) and a few lowland evergreen rain forest fragments of northern Madagascar, was described recently. The present study provides the first quantified information on vocal acoustics of calls, sound associated behavioral context, acoustic niche, and vocal activity of this species. We recorded vocal and social behavior of six male-female and six male-male dyads in a standardized social-encounter paradigm in June and July 2016 at the LNP, Nosy Bé island. Over six successive nights per dyad, we audio recorded and observed behaviors for 3 hr at the beginning of the activity period. Based on the visual inspection of spectrograms and standardized multiparametric sound analysis, we identified seven different call types. Call types can be discriminated based on a combination of harmonicity, fundamental frequency variation, call duration, and degree of tonality. Acoustic features of tonal call types showed that for communication, mouse lemurs use the cryptic, high frequency/ultrasonic frequency niche. Two call types, the Tsak and the Grunt call, were emitted most frequently. Significant differences in vocal activity of the Tsak call were found between male-female and male-male dyads, linked primarily to agonistic conflicts. Dominant mouse lemurs vocalized more than subdominant ones, suggesting that signaling may present an honest indicator of fitness. A comparison of our findings of the Claire's mouse lemur with published findings of five bioacoustically studied mouse lemur species points to the notion that a complex interplay between ecology, predation pressure, and phylogenetic relatedness may shape the evolution of acoustic divergence between species in this smallest-bodied primate radiation. Thus, comparative bioacoustic studies, using standardized procedures, are promising to unravel the role of vocalization for primate species diversity and evolution

Phylogeny and Divergence Times of Lemurs Inferred with Recent and Ancient Fossils in the Tree.

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Herrera, James P; Dávalos, Liliana M

2016-09-01

Paleontological and neontological systematics seek to answer evolutionary questions with different data sets. Phylogenies inferred for combined extant and extinct taxa provide novel insights into the evolutionary history of life. Primates have an extensive, diverse fossil record and molecular data for living and extinct taxa are rapidly becoming available. We used two models to infer the phylogeny and divergence times for living and fossil primates, the tip-dating (TD) and fossilized birth-death process (FBD). We collected new morphological data, especially on the living and extinct endemic lemurs of Madagascar. We combined the morphological data with published DNA sequences to infer near-complete (88% of lemurs) time-calibrated phylogenies. The results suggest that primates originated around the Cretaceous-Tertiary boundary, slightly earlier than indicated by the fossil record and later than previously inferred from molecular data alone. We infer novel relationships among extinct lemurs, and strong support for relationships that were previously unresolved. Dates inferred with TD were significantly older than those inferred with FBD, most likely related to an assumption of a uniform branching process in the TD compared with a birth-death process assumed in the FBD. This is the first study to combine morphological and DNA sequence data from extinct and extant primates to infer evolutionary relationships and divergence times, and our results shed new light on the tempo of lemur evolution and the efficacy of combined phylogenetic analyses. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evolution of facial color pattern complexity in lemurs

OpenAIRE

Rakotonirina, Hanitriniaina; Kappeler, Peter M.; Fichtel, Claudia

2017-01-01

Interspecific variation in facial color patterns across New and Old World primates has been linked to species recognition and group size. Because group size has opposite effects on interspecific variation in facial color patterns in these two radiations, a study of the third large primate radiation may shed light on convergences and divergences in this context. We therefore compiled published social and ecological data and analyzed facial photographs of 65 lemur species to categorize variatio...

The influence of visitor interaction on the behavior of captive crowned lemurs (Eulemur coronatus) and implications for welfare.

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Jones, H; McGregor, P K; Farmer, H L A; Baker, K R

2016-05-01

Research suggests that zoo visitors can have positive, negative, and neutral impacts on captive primate welfare; however, research investigating the implications of visitor-animal feeding experiences is extremely limited. In the UK, a large proportion of BIAZA zoos that house lemur species offer visitor interaction experiences (16 out of 33). This study investigated the impact on the behavior of a family group of crowned lemurs (Eulemur coronatus) housed at Newquay Zoo, UK of visitors, accompanied by a keeper, entering the enclosure to feed the lemurs. Behavior was observed under four conditions: (i) during visitor feed; (ii) 30 min post-visitor feed; (iii) during a keeper feed; and (iv) 30 min post-keeper feed. Keeper feeds were conducted by keepers only, on the day after visitor feeds. The lemur group spent significantly less time performing aggressive behavior and was also significantly more interactive with keepers during visitor feeds compared with keeper-only feeds. There was no significant difference in behaviors performed immediately after interacting with visitors. Over the study period, there was a tendency for interactions with visitors to increase, and for interactions with keepers during visitor feeds to decrease. After a 28-day interval without visitor interaction, the lemurs' interaction with visitors had returned to the level recorded at the start of the study. In conclusion, visitor interaction did not compromise the welfare of the study subjects in either the short- or long-term, while an increase in visitor interactions over time has interesting implications for the enrichment properties of, or habituation to, unfamiliar humans. Zoo Biol. 35:222-227, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Voxel-based morphometry analyses of in-vivo MRI in the aging mouse lemur primate

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Stephen John Sawiak

2014-05-01

Full Text Available Cerebral atrophy is one of the most widely brain alterations associated to aging. A clear relationship has been established between age-associated cognitive impairments and cerebral atrophy. The mouse lemur (Microcebus murinus is a small primate used as a model of age-related neurodegenerative processes. It is the first nonhuman primate in which cerebral atrophy has been correlated with cognitive deficits. Previous studies of cerebral atrophy in this model were based on time consuming manual delineation or measurement of selected brain regions from magnetic resonance images (MRI. These measures could not be used to analyse regions that cannot be easily outlined such as the nucleus basalis of Meynert or the subiculum. In humans, morphometric assessment of structural changes with age is generally performed with automated procedures such as voxel-based morphometry (VBM. The objective of our work was to perform user-independent assessment of age-related morphological changes in the whole brain of large mouse lemur populations thanks to VBM. The study was based on the SPMMouse toolbox of SPM 8 and involved thirty mouse lemurs aged from 1.9 to 11.3 years. The automatic method revealed for the first time atrophy in regions where manual delineation is prohibitive (nucleus basalis of Meynert, subiculum, prepiriform cortex, Brodmann areas 13-16, hypothalamus, putamen, thalamus, corpus callosum. Some of these regions are described as particularly sensitive to age-associated alterations in humans. The method revealed also age-associated atrophy in cortical regions (cingulate, occipital, parietal, nucleus septalis, and the caudate. Manual measures performed in some of these regions were in good agreement with results from automatic measures. The templates generated in this study as well as the toolbox for SPM8 can be downloaded. These tools will be valuable for future evaluation of various treatments that are tested to modulate cerebral aging in lemurs.

Genetic variants and multiple myeloma risk

DEFF Research Database (Denmark)

Martino, Alessandro; Campa, Daniele; Jurczyszyn, Artur

2014-01-01

BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies. METHODS...... with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women. CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors. IMPACT: Independent validation studies are crucial to identify true genetic risk...

Genetic variations in multiple myeloma I

DEFF Research Database (Denmark)

Vangsted, A.; Klausen, T.W.; Vogel, Ulla Birgitte

2012-01-01

Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variab......Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis...

Hybridization between mouse lemurs in an ecological transition zone in southern Madagascar.

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Gligor, M; Ganzhorn, J U; Rakotondravony, D; Ramilijaona, O R; Razafimahatratra, E; Zischler, H; Hapke, A

2009-02-01

Hybrid zones in ecotones can be useful model systems for the study of evolutionary processes that shape the distribution and discreteness of species. Such studies could be important for an improved understanding of the complex biogeography of Madagascar, which is renowned for its outstanding degree of small-scale endemism. Certain forest remnants in central Madagascar indicate that transitional corridors across the island could have connected microendemics in different forest types in the past. Evolutionary processes in such corridors are difficult to study because most of these corridors have disappeared due to deforestation in central Madagascar. We studied a hybrid zone in one of the few remaining ecotonal corridors between dry and humid forests in Madagascar, which connects two species of mouse lemurs, Microcebus griseorufus in dry spiny forest and Microcebus murinus in humid littoral forest. We sampled 162 mouse lemurs at nine sites across this boundary. Morphometric analyses revealed intermediate morphotypes of many individuals in transitional habitat. Bayesian clustering of microsatellite genotypes and assignment tests yielded evidence for a mixed ancestry of mouse lemurs in the ecotone, where we also observed significant linkage disequilibria and heterozygote deficiency. In contrast to these observations, mitochondrial haplotypes displayed a sharply delimited boundary at the eastern edge of spiny forest, which was noncoincident with the signals from microsatellite data. Among several alternative scenarios, we propose asymmetric nuclear introgression due to male-biased dispersal, divergent environmental selection, and an expansion of dry spiny forest in the course of aridification as a probable explanation of our observations.

Multiple ectoparasites infest Microcebus griseorufus at Beza ...

African Journals Online (AJOL)

Multiple ectoparasites infest Microcebus griseorufus at Beza Mahafaly Special Reserve, Madagascar. IA Rodriguez, E Rasoazanabary, LR Godfrey. Abstract. The mouse lemur Microcebus griseorufus at the Beza Mahafaly Special Reserve and general vicinity in southwestern Madagascar were surveyed for ectoparasites as ...

The socio-matrix reloaded: from hierarchy to dominance profile in wild lemurs.

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Norscia, Ivan; Palagi, Elisabetta

2015-01-01

Dominance hierarchy influences the life quality of social animals, and its definition should in principle be based on the outcome of agonistic interactions. However, defining and comparing the dominance profile of social groups is difficult due to the different dominance measures used and because no one measure explains it all. We applied different analytical methods to winner-loser sociomatrices to determine the dominance profile of five groups of wild lemurs (species: Lemur catta, Propithecus verreauxi, and Eulemur rufus x collaris) from the Berenty forest (Madagascar). They are an excellent study model because they share the same habitat and an apparently similar dominance profile: linear hierarchy and female dominance. Data were collected over more than 1200 h of observation. Our approach included four steps: (1) by applying the binary dyadic dominance relationship method (I&SI) on either aggressions or supplant sociomatrices we verified whether hierarchy was aggression or submission based; (2) by calculating normalized David's scores and measuring steepness from aggression sociomatrices we evaluated whether hierarchy was shallow or steep; (3) by comparing the ranking orders obtained with methods 1 and 2 we assessed whether hierarchy was consistent or not; and (4) by assessing triangle transitivity and comparing it with the linearity index and the level of group cohesion we determined if hierarchy was more or less cohesive. Our results show that L. catta groups have got a steep, consistent, highly transitive and cohesive hierarchy. P. verreauxi groups are characterized by a moderately steep and consistent hierarchy, with variable levels of triangle transitivity and cohesion. E. rufus x collaris group possesses a shallow and inconsistent hierarchy, with lower (but not lowest) levels of transitivity and cohesion. A multiple analytical approach on winner-loser sociomatrices other than leading to an in-depth description of the dominance profile, allows intergroup

The socio-matrix reloaded: from hierarchy to dominance profile in wild lemurs

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Ivan Norscia

2015-01-01

Full Text Available Dominance hierarchy influences the life quality of social animals, and its definition should in principle be based on the outcome of agonistic interactions. However, defining and comparing the dominance profile of social groups is difficult due to the different dominance measures used and because no one measure explains it all. We applied different analytical methods to winner-loser sociomatrices to determine the dominance profile of five groups of wild lemurs (species: Lemur catta, Propithecus verreauxi, and Eulemur rufus x collaris from the Berenty forest (Madagascar. They are an excellent study model because they share the same habitat and an apparently similar dominance profile: linear hierarchy and female dominance. Data were collected over more than 1200 h of observation. Our approach included four steps: (1 by applying the binary dyadic dominance relationship method (I&SI on either aggressions or supplant sociomatrices we verified whether hierarchy was aggression or submission based; (2 by calculating normalized David’s scores and measuring steepness from aggression sociomatrices we evaluated whether hierarchy was shallow or steep; (3 by comparing the ranking orders obtained with methods 1 and 2 we assessed whether hierarchy was consistent or not; and (4 by assessing triangle transitivity and comparing it with the linearity index and the level of group cohesion we determined if hierarchy was more or less cohesive. Our results show that L. catta groups have got a steep, consistent, highly transitive and cohesive hierarchy. P. verreauxi groups are characterized by a moderately steep and consistent hierarchy, with variable levels of triangle transitivity and cohesion. E. rufus x collaris group possesses a shallow and inconsistent hierarchy, with lower (but not lowest levels of transitivity and cohesion. A multiple analytical approach on winner-loser sociomatrices other than leading to an in-depth description of the dominance profile

Micro-MRI study of cerebral aging: ex vivo detection of hippocampal sub-field reorganization, micro-hemorrhages and amyloid plaques in mouse lemur primates

International Nuclear Information System (INIS)

Bertrand, Anne; Petiet, Alexandra; Dhenain, Marc; Pasquier, Adrien; Kraska, Audrey; Joseph-Mathurin, Nelly; Wiggins, Christopher; Aujard, Fabienne; Mestre-Frances, Nadine

2013-01-01

Mouse lemurs are non-human primate models of cerebral aging and neuro-degeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 μm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral micro-hemorrhages. (authors)

Can black-and-white ruffed lemurs (Varecia variegata) solve object permanence tasks?

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Mallavarapu, Suma; Perdue, Bonnie M; Stoinski, Tara S; Maple, Terry L

2013-04-01

We examined object permanence in black-and-white-ruffed lemurs (Varecia variegata) at Zoo Atlanta. A series of visible and invisible displacement tasks with suitable controls were presented to five adult subjects. Subjects performed significantly above chance on all regular tasks, except for the double invisible displacements. Subjects failed visible and invisible controls. Failure on the control trials did not appear to be because subjects used the "last box touched" strategy (subjects did not choose the last box touched significantly more than expected by chance). However, a substantial percentage of choices was made to the last box touched by the experimenter. There was no significant difference between this percentage, and the percentage of choices made to the baited box (on both visible and invisible controls), which indicates that subjects were drawn to both boxes which the experimenter visited/touched, and thus failed the controls. Based on the results from the present study, we believe that there is no evidence that black-and-white ruffed lemurs understand visible and invisible tasks in the traditional object permanence battery. © 2013 Wiley Periodicals, Inc.

A genome sequence resource for the aye-aye (Daubentonia madagascariensis), a nocturnal lemur from Madagascar.

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Perry, George H; Reeves, Darryl; Melsted, Páll; Ratan, Aakrosh; Miller, Webb; Michelini, Katelyn; Louis, Edward E; Pritchard, Jonathan K; Mason, Christopher E; Gilad, Yoav

2012-01-01

We present a high-coverage draft genome assembly of the aye-aye (Daubentonia madagascariensis), a highly unusual nocturnal primate from Madagascar. Our assembly totals ~3.0 billion bp (3.0 Gb), roughly the size of the human genome, comprised of ~2.6 million scaffolds (N50 scaffold size = 13,597 bp) based on short paired-end sequencing reads. We compared the aye-aye genome sequence data with four other published primate genomes (human, chimpanzee, orangutan, and rhesus macaque) as well as with the mouse and dog genomes as nonprimate outgroups. Unexpectedly, we observed strong evidence for a relatively slow substitution rate in the aye-aye lineage compared with these and other primates. In fact, the aye-aye branch length is estimated to be ~10% shorter than that of the human lineage, which is known for its low substitution rate. This finding may be explained, in part, by the protracted aye-aye life-history pattern, including late weaning and age of first reproduction relative to other lemurs. Additionally, the availability of this draft lemur genome sequence allowed us to polarize nucleotide and protein sequence changes to the ancestral primate lineage-a critical period in primate evolution, for which the relevant fossil record is sparse. Finally, we identified 293,800 high-confidence single nucleotide polymorphisms in the donor individual for our aye-aye genome sequence, a captive-born individual from two wild-born parents. The resulting heterozygosity estimate of 0.051% is the lowest of any primate studied to date, which is understandable considering the aye-aye's extensive home-range size and relatively low population densities. Yet this level of genetic diversity also suggests that conservation efforts benefiting this unusual species should be prioritized, especially in the face of the accelerating degradation and fragmentation of Madagascar's forests.

Characterization of blood biochemical markers during aging in the Grey Mouse Lemur (Microcebus murinus: impact of gender and season

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Marchal Julia

2012-11-01

Full Text Available Abstract Background Hematologic and biochemical data are needed to characterize the health status of animal populations over time to determine the habitat quality and captivity conditions. Blood components and the chemical entities that they transport change predominantly with sex and age. The aim of this study was to utilize blood chemistry monitoring to establish the reference levels in a small prosimian primate, the Grey Mouse Lemur (Microcebus murinus. Method In the captive colony, mouse lemurs may live 10–12 years, and three age groups for both males and females were studied: young (1–3 years, middle-aged (4–5 years and old (6–10 years. Blood biochemical markers were measured using the VetScan Comprehensive Diagnostic Profile. Because many life history traits of this primate are highly dependent on the photoperiod (body mass and reproduction, the effect of season was also assessed. Results The main effect of age was observed in blood markers of renal functions such as creatinine, which was higher among females. Additionally, blood urea nitrogen significantly increased with age and is potentially linked to chronic renal insufficiency, which has been described in captive mouse lemurs. The results demonstrated significant effects related to season, especially in blood protein levels and glucose rates; these effects were observed regardless of gender or age and were likely due to seasonal variations in food intake, which is very marked in this species. Conclusion These results were highly similar with those obtained in other primate species and can serve as references for future research of the Grey Mouse Lemur.

Phylogeographic analysis of the true lemurs (genus Eulemur) underlines the role of river catchments for the evolution of micro-endemism in Madagascar.

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Markolf, Matthias; Kappeler, Peter M

2013-11-14

Due to its remarkable species diversity and micro-endemism, Madagascar has recently been suggested to serve as a biogeographic model region. However, hypothesis-based tests of various diversification mechanisms that have been proposed for the evolution of the island's micro-endemic lineages are still limited. Here, we test the fit of several diversification hypotheses with new data on the broadly distributed genus Eulemur using coalescent-based phylogeographic analyses. Time-calibrated species tree analyses and population genetic clustering resolved the previously polytomic species relationships among eulemurs. The most recent common ancestor of eulemurs was estimated to have lived about 4.45 million years ago (mya). Divergence date estimates furthermore suggested a very recent diversification among the members of the "brown lemur complex", i.e. former subspecies of E. fulvus, during the Pleistocene (0.33-1.43 mya). Phylogeographic model comparisons of past migration rates showed significant levels of gene flow between lineages of neighboring river catchments as well as between eastern and western populations of the redfronted lemur (E. rufifrons). Together, our results are concordant with the centers of endemism hypothesis (Wilmé et al. 2006, Science 312:1063-1065), highlight the importance of river catchments for the evolution of Madagascar's micro-endemic biota, and they underline the usefulness of testing diversification mechanisms using coalescent-based phylogeographic methods.

Cytokine and Antioxidant Regulation in the Intestine of the Gray Mouse Lemur (Microcebus murinus During Torpor

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Shannon N. Tessier

2015-04-01

Full Text Available During food shortages, the gray mouse lemur (Microcebus murinus of Madagascar experiences daily torpor thereby reducing energy expenditures. The present study aimed to understand the impacts of torpor on the immune system and antioxidant response in the gut of these animals. This interaction may be of critical importance given the trade-off between the energetically costly immune response and the need to defend against pathogen entry during hypometabolism. The protein levels of cytokines and antioxidants were measured in the small intestine (duodenum, jejunum, and ileum and large intestine of aroused and torpid lemurs. While there was a significant decrease of some pro-inflammatory cytokines (IL-6 and TNF-α in the duodenum and jejunum during torpor as compared to aroused animals, there was no change in anti-inflammatory cytokines. We observed decreased levels of cytokines (IL-12p70 and M-CSF, and several chemokines (MCP-1 and MIP-2 but an increase in MIP-1α in the jejunum of the torpid animals. In addition, we evaluated antioxidant response by examining the protein levels of antioxidant enzymes and total antioxidant capacity provided by metabolites such as glutathione (and others. Our results indicated that levels of antioxidant enzymes did not change between torpor and aroused states, although antioxidant capacity was significantly higher in the ileum during torpor. These data suggest a suppression of the immune response, likely as an energy conservation measure, and a limited role of antioxidant defenses in supporting torpor in lemur intestine.

Innovation and behavioral flexibility in wild redfronted lemurs (Eulemur rufifrons).

Science.gov (United States)

Huebner, Franziska; Fichtel, Claudia

2015-05-01

Innovations and problem-solving abilities can provide animals with important ecological advantages as they allow individuals to deal with novel social and ecological challenges. Innovation is a solution to a novel problem or a novel solution to an old problem, with the latter being especially difficult. Finding a new solution to an old problem requires individuals to inhibit previously applied solutions to invent new strategies and to behave flexibly. We examined the role of experience on cognitive flexibility to innovate and to find new problem-solving solutions with an artificial feeding task in wild redfronted lemurs (Eulemur rufifrons). Four groups of lemurs were tested with feeding boxes, each offering three different techniques to extract food, with only one technique being available at a time. After the subjects learned a technique, this solution was no longer successful and subjects had to invent a new technique. For the first transition between task 1 and 2, subjects had to rely on their experience of the previous technique to solve task 2. For the second transition, subjects had to inhibit the previously learned technique to learn the new task 3. Tasks 1 and 2 were solved by most subjects, whereas task 3 was solved by only a few subjects. In this task, besides behavioral flexibility, especially persistence, i.e., constant trying, was important for individual success during innovation. Thus, wild strepsirrhine primates are able to innovate flexibly, suggesting a general ecological relevance of behavioral flexibility and persistence during innovation and problem solving across all primates.

Comparison of biomedical evaluation for white-fronted brown lemurs (Eulemur fulvus albifrons) from four sites in Madagascar.

Science.gov (United States)

Junge, Randall E; Dutton, Christopher J; Knightly, Felicia; Williams, Cathy V; Rasambainarivo, Fidisoa T; Louis, Edward E

2008-12-01

Health and nutritional assessments of wildlife are important management tools and can provide a means to evaluate ecosystem health. Such examinations were performed on 37 white-fronted brown lemurs (Eulemur fulvus albifrons) from four sites in Madagascar. Comparison of health parameters between sites revealed statistically significant differences in body weight, body temperature, respiratory rate, hematology parameters (white cell count, hematocrit, segmented neutrophil count, and lymphocyte count), serum chemistry parameters (aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, total protein, albumin, phosphorus, calcium, sodium, chloride, and creatinine phosphokinase), and nutrition parameters (copper, zinc, ferritin, retinol, tocopherol, and 25-hydroxycholecalciferol). Two of 10 lemurs tested were positive for toxoplasmosis; none of 10 were positive for Cryptosporidium or Giardia. Enteric bacteria and endo- and ectoparasites were typical. Statistically different values in hematology and chemistry values probably do not reflect clinically significant differences, whereas nutrition parameter differences are likely related to season, soil, and forage availability.

Resveratrol Metabolism in a Non-Human Primate, the Grey Mouse Lemur (Microcebus murinus), Using Ultra-High-Performance Liquid Chromatography–Quadrupole Time of Flight

Science.gov (United States)

Menet, Marie-Claude; Marchal, Julia; Dal-Pan, Alexandre; Taghi, Méryam; Nivet-Antoine, Valérie; Dargère, Delphine; Laprévote, Olivier; Beaudeux, Jean-Louis; Aujard, Fabienne; Epelbaum, Jacques; Cottart, Charles-Henry

2014-01-01

The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg−1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism. PMID:24663435

Sleep deprivation impairs spatial retrieval but not spatial learning in the non-human primate grey mouse lemur.

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Anisur Rahman

Full Text Available A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus, which is an interesting model of aging and Alzheimer's disease (AD. Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.

Omega-3 PUFA supplementation differentially affects behavior and cognition in the young and aged non-human primate Grey mouse lemur (Microcebus murinus

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Pifferi Fabien

2014-01-01

Full Text Available Data are divergent about the ability of dietary ω3 fatty acids to prevent age-associated cognitive decline. Most of the clinical trials failed to demonstrate a protective effect of ω3 fatty acids against cognitive decline and methodological issues are still under debate. Conversely to human studies, experiments performed in adult rodents clearly indicate that long chain ω3 fatty acids play a beneficial role in behavioral and cognitive functions. Inconsistent observations between human and rodent studies highlight the importance of the use of non-human primate models. We recently started a series of experiments on Grey mouse lemurs, an emerging non-human primate model of aging in order to assess the impact of ω3 fatty acids dietary supplementation on several brain functions. These experiments started with the determination of the fatty acids composition of target organs (brain, adipose tissue, liver, plasma of animals fed under control diet. We then explored the impact of ω3 polyunsaturated fatty acids (PUFA supplementation on cognition and behavior in young and aged grey mouse lemurs. The aim of the present review is to compare the observations made in young and aged grey mouse lemurs and to explore the possibilities of new experiments in order to bridge the gap between rodents and Humans.

Tsidy, Repahaka sy Fotsife: 15 years research on nocturnal lemurs in the Ankarafantsika National Park, Madagascar Tsidy, Repahaka sy Fotsife :15 ans de recherche sur les lémuriens nocturnes dans le Parc National d´Ankarafantsika, Madagascar

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Marine Joly

2011-10-01

Full Text Available Tsidy, Repahaka sy Fotsife from the Malagasy: Mouse lemur, sportive lemur and woolly lemur. "The Ankarafantsika Lemur Project", is based at the field station of Ampijoroa in the National Park of Ankarafantsika in the North-West of Madagascar and is conducted by the Institute of Zoology from the University of Veterinary Medicine Hanover (Germany in close collaboration with the local universities of Antananarivo, of Mahajanga and Madagascar National Parks (authorities for the management of protected areas in Madagascar. The project started in 1996. The goal is to enhance our knowledge on the adaptation and evolution of a previously neglected group of primates, the nocturnal lemurs, and to contribute to their conservation. Thus, researchers study the diversity, ecology, communication and socio-biology of the nocturnal lemurs. They discovered one new mouse lemur species (Microcebus ravelobensis in this area. They characterised aspects of the morphometry, genetics, communication, ecology, social traits and recently, cognitive abilities of sympatrically living mouse-sized (Microcebus murinus and M. ravelobensis and cat-sized lemur species (Lepilemur edwardsi and Avahi occidentalis. Some major results are presented in this article showing the importance of exchanging experience, educating Malagasy students and field guides and joint work with Malagasy partners in order to deepen our knowledge on the biology of endemic species. This knowledge is crucial to establish efficient management plans and thus contribute to the conservation of threatened species.Tsidy, Repahaka sy Fotsife en langue Malgache : Microcèbe, Lépilémur et Avahi. Le projet de recherche sur les lémuriens nocturnes d´Ankarafantsika est basé à la station d´Ampijoroa dans le Parc National d´Ankarafantsika dans le nord-ouest de Madagascar. Il est mené par l´Institut de Zoologie de l´Ecole Vétérinaire de Hanovre (Allemagne en collaboration étroite avec les universit

Genetic Algorithms for Multiple-Choice Problems

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Aickelin, Uwe

2010-04-01

This thesis investigates the use of problem-specific knowledge to enhance a genetic algorithm approach to multiple-choice optimisation problems.It shows that such information can significantly enhance performance, but that the choice of information and the way it is included are important factors for success.Two multiple-choice problems are considered.The first is constructing a feasible nurse roster that considers as many requests as possible.In the second problem, shops are allocated to locations in a mall subject to constraints and maximising the overall income.Genetic algorithms are chosen for their well-known robustness and ability to solve large and complex discrete optimisation problems.However, a survey of the literature reveals room for further research into generic ways to include constraints into a genetic algorithm framework.Hence, the main theme of this work is to balance feasibility and cost of solutions.In particular, co-operative co-evolution with hierarchical sub-populations, problem structure exploiting repair schemes and indirect genetic algorithms with self-adjusting decoder functions are identified as promising approaches.The research starts by applying standard genetic algorithms to the problems and explaining the failure of such approaches due to epistasis.To overcome this, problem-specific information is added in a variety of ways, some of which are designed to increase the number of feasible solutions found whilst others are intended to improve the quality of such solutions.As well as a theoretical discussion as to the underlying reasons for using each operator,extensive computational experiments are carried out on a variety of data.These show that the indirect approach relies less on problem structure and hence is easier to implement and superior in solution quality.

Parallel germline infiltration of a lentivirus in two Malagasy lemurs.

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Clément Gilbert

2009-03-01

Full Text Available Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera -- Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host-virus interactions.

First insights into the social organisation of Goodman's mouse lemur (Microcebus lehilahytsara)--testing predictions from socio-ecological hypotheses in the Masoala hall of Zurich Zoo.

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Jürges, Vivian; Kitzler, Johanne; Zingg, Robert; Radespiel, Ute

2013-01-01

Following current socio-ecological hypotheses, the social organisation of a species is mainly determined by resource quality and distribution. In the case of Microcebus spp., a taxon-specific socio-ecological model was formulated earlier to explain their variable social organisation. The aim of this study was to test predictions from this model in Goodman's mouse lemur based on a data set from animals living in the semi-free colony of Zurich Zoo. During a 2-month study, we observed 5 females and 5 males using radiotelemetry. We collected data on space use and social behaviour, on sleeping sites and on sleeping group composition. Predictions were only partly confirmed. As expected, Goodman's mouse lemurs were solitary foragers with an increased level of sociality due to crowding effects at the feeding stations. In contrast to the prediction, females and males formed unisexual sleeping groups, which were stable in females and of a fission-fusion type in males. Whereas the formation of sleeping groups by both sexes may be triggered by thermoregulatory benefits, the formation of unisexual sleeping groups may result from divergent interests of the sexes. We conclude that the existing model for the evolution of mouse lemur social organisation needs to be refined. Copyright © 2013 S. Karger AG, Basel.

Lemur tyrosine kinase-2 signalling regulates kinesin-1 light chain-2 phosphorylation and binding of Smad2 cargo.

LENUS (Irish Health Repository)

Manser, C

2012-05-31

A recent genome-wide association study identified the gene encoding lemur tyrosine kinase-2 (LMTK2) as a susceptibility gene for prostate cancer. The identified genetic alteration is within intron 9, but the mechanisms by which LMTK2 may impact upon prostate cancer are not clear because the functions of LMTK2 are poorly understood. Here, we show that LMTK2 regulates a known pathway that controls phosphorylation of kinesin-1 light chain-2 (KLC2) by glycogen synthase kinase-3β (GSK3β). KLC2 phosphorylation by GSK3β induces the release of cargo from KLC2. LMTK2 signals via protein phosphatase-1C (PP1C) to increase inhibitory phosphorylation of GSK3β on serine-9 that reduces KLC2 phosphorylation and promotes binding of the known KLC2 cargo Smad2. Smad2 signals to the nucleus in response to transforming growth factor-β (TGFβ) receptor stimulation and transport of Smad2 by kinesin-1 is required for this signalling. We show that small interfering RNA loss of LMTK2 not only reduces binding of Smad2 to KLC2, but also inhibits TGFβ-induced Smad2 signalling. Thus, LMTK2 may regulate the activity of kinesin-1 motor function and Smad2 signalling.

Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

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Philipp eHohenbrink

2014-09-01

Full Text Available The vomeronasal organ (VNO is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR genes comprise two families of chemosensory genes (V1R and V2R that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the grey mouse lemur (Microcebus murinus, the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83% – 97% of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29% to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.

Novel applications of multitask learning and multiple output regression to multiple genetic trait prediction.

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He, Dan; Kuhn, David; Parida, Laxmi

2016-06-15

Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait prediction is usually represented as linear regression models. In many cases, for the same set of samples and markers, multiple traits are observed. Some of these traits might be correlated with each other. Therefore, modeling all the multiple traits together may improve the prediction accuracy. In this work, we view the multitrait prediction problem from a machine learning angle: as either a multitask learning problem or a multiple output regression problem, depending on whether different traits share the same genotype matrix or not. We then adapted multitask learning algorithms and multiple output regression algorithms to solve the multitrait prediction problem. We proposed a few strategies to improve the least square error of the prediction from these algorithms. Our experiments show that modeling multiple traits together could improve the prediction accuracy for correlated traits. The programs we used are either public or directly from the referred authors, such as MALSAR (http://www.public.asu.edu/~jye02/Software/MALSAR/) package. The Avocado data set has not been published yet and is available upon request. dhe@us.ibm.com. © The Author 2016. Published by Oxford University Press.

The lemur revolution starts now: the genomic coming of age for a non-model organism.

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Yoder, Anne D

2013-02-01

Morris Goodman was a revolutionary. Together with a mere handful of like-minded scientists, Morris established himself as a leader in the molecular phylogenetic revolution of the 1960s. The effects of this revolution are most evident in this journal, which he founded in 1992. Happily for lemur biologists, one of Morris Goodman's primary interests was in reconstructing the phylogeny of the primates, including the tooth-combed Lorisifomes of Africa and Asia, and the Lemuriformes of Madagascar (collectively referred to as the suborder Strepsirrhini). This paper traces the development of molecular phylogenetic and evolutionary genetic trends and methods over the 50-year expanse of Morris Goodman's career, particularly as they apply to our understanding of lemuriform phylogeny, biogeography, and biology. Notably, this perspective reveals that the lemuriform genome is sufficiently rich in phylogenetic signal such that the very earliest molecular phylogenetic studies - many of which were conducted by Goodman himself - have been validated by contemporary studies that have exploited advanced computational methods applied to phylogenomic scale data; studies that were beyond imagining in the earliest days of phylogeny reconstruction. Nonetheless, the frontier still beckons. New technologies for gathering and analyzing genomic data will allow investigators to build upon what can now be considered a nearly-known phylogeny of the Lemuriformes in order to ask innovative questions about the evolutionary mechanisms that generate and maintain the extraordinary breadth and depth of biological diversity within this remarkable clade of primates. Copyright © 2012 Elsevier Inc. All rights reserved.

Genetic regulation of parasite infection: empirical evidence of the functional significance of an IL4 gene SNP on nematode infections in wild primates

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Kappeler Peter M

2011-04-01

Full Text Available Abstract Background Susceptibility to parasite infection affects fitness-related processes, such as mate choice and survival, yet its genetic regulation remains poorly understood. Interleukin-4 (IL4 plays a central role in the humoral immune defence against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The evolutionary and functional significance of single nucleotide polymorphisms (SNPs in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking. Using samples from a population of wild red-fronted lemurs (Eulemur fulvus rufus, Primates: Lemuridae, from western Madagascar, we explored the association of IL4-gene promoter polymorphisms with nematode infections and investigated a possible functional role of the IL4 polymorphism on male reproductive success. Results Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area. Carriers of the genotype T/T showed higher nematode infection intensities than individuals of genotypes C/T and C/C. Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected. Conclusions Our results suggest a regulatory effect of an IL4 gene promoter polymorphism on the intensity of parasite infections in a natural population of red-fronted lemurs, with a seemingly disadvantageous genotype represented in low frequencies. Long-term population analyses, however, point in the direction of a negative frequency-dependent association, giving a fitness advantage to the rare genotype. Due to low frequencies of the genotype in question conclusive evidence of a functional role of IL4 polymorphism cannot be drawn here; still, we suggest the use of IL4 polymorphism as a new molecular tool for quick assessment of individual genetic constitution with regard to nematode infection intensities, contributing to a better

Genetic variation and selection of MHC class I loci differ in two congeneric frogs.

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Kiemnec-Tyburczy, Karen M; Tracy, Karen E; Lips, Karen R; Zamudio, Kelly R

2018-04-01

Major histocompatibility complex (MHC) genes encode proteins in the acquired immune response pathway that often show distinctive selection-driven patterns in wild vertebrate populations. We examined genetic variation and signatures of selection in the MHC class I alpha 1 (A1)- and alpha 2 (A2)-domain encoding exons of two frog congeners [Agalychnis callidryas (n = 20) and A. lemur (n = 20)] from a single locality in Panama. We also investigated how historical demographic processes may have impacted MHC genetic diversity by analyzing a neutral mitochondrial marker. We found that both MHC domains were highly variable in both species, with both species likely expressing three loci. Our analyses revealed different signatures of selection between the two species, most notably that the A. callidryas A2 domain had experienced positive selection while the A2 domain of A. lemur had not. Diversifying selection acted on the same number of A1 and A2 allelic lineages, but on a higher percentage of A1 sites compared to A2 sites. Neutrality tests of mitochondrial haplotypes predominately indicated that the two species were at genetic equilibrium when the samples were collected. In addition, two historical tests of demography indicated both species have had relatively stable population sizes over the past 100,000 years; thus large population size changes are unlikely to have greatly influenced MHC diversity in either species during this time period. In conclusion, our results suggest that the impact of selection on MHC diversity varied between these two closely related species, likely due to a combination of distinct ecological conditions and past pathogenic pressures.

[Application of Multiple Genetic Markers in a Case of Determination of Half Sibling].

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Yang, Xue; Shi, Mei-sen; Yuan, Li; Lu, Di

2016-02-01

A case of half sibling was determined with multiple genetic markers, which could be potentially applied for determination of half sibling relationship from same father. Half sibling relationship was detected by 39 autosomal STR genetic markers, 23 Y-chromosomal STR genetic markers and 12 X -chromosomal STR genetic markers among ZHAO -1, ZHAO -2, ZHAO -3, ZHAO -4, and ZHAO-5. According to autosomal STR, Y-STR and X-STR genotyping results, it was determined that ZHAO-4 (alleged half sibling) was unrelated with ZHAO-1 and ZHAO-2; however, ZHAO-3 (alleged half sibling), ZHAO-5 (alleged half sibling) shared same genetic profile with ZHAO-1, and ZHAO-2 from same father. It is reliable to use multiple genetic markers and family gene reconstruction to determine half sibling relationship from same father, but it is difficult to determination by calculating half sibling index with ITO and discriminant functions.

Multiple-Trait Genomic Selection Methods Increase Genetic Value Prediction Accuracy

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Jia, Yi; Jannink, Jean-Luc

2012-01-01

Genetic correlations between quantitative traits measured in many breeding programs are pervasive. These correlations indicate that measurements of one trait carry information on other traits. Current single-trait (univariate) genomic selection does not take advantage of this information. Multivariate genomic selection on multiple traits could accomplish this but has been little explored and tested in practical breeding programs. In this study, three multivariate linear models (i.e., GBLUP, BayesA, and BayesCπ) were presented and compared to univariate models using simulated and real quantitative traits controlled by different genetic architectures. We also extended BayesA with fixed hyperparameters to a full hierarchical model that estimated hyperparameters and BayesCπ to impute missing phenotypes. We found that optimal marker-effect variance priors depended on the genetic architecture of the trait so that estimating them was beneficial. We showed that the prediction accuracy for a low-heritability trait could be significantly increased by multivariate genomic selection when a correlated high-heritability trait was available. Further, multiple-trait genomic selection had higher prediction accuracy than single-trait genomic selection when phenotypes are not available on all individuals and traits. Additional factors affecting the performance of multiple-trait genomic selection were explored. PMID:23086217

Structural characterization of neutral and acidic oligosaccharides in the milks of strepsirrhine primates: greater galago, aye-aye, Coquerel's sifaka and mongoose lemur.

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Taufik, Epi; Fukuda, Kenji; Senda, Akitsugu; Saito, Tadao; Williams, Cathy; Tilden, Chris; Eisert, Regina; Oftedal, Olav; Urashima, Tadasu

2012-04-01

The structures of milk oligosaccharides were characterized for four strepsirrhine primates to examine the extent to which they resemble milk oligosaccharides in other primates. Neutral and acidic oligosaccharides were isolated from milk of the greater galago (Galagidae: Otolemur crassicaudatus), aye-aye (Daubentoniidae: Daubentonia madagascariensis), Coquerel's sifaka (Indriidae: Propithecus coquereli) and mongoose lemur (Lemuridae: Eulemur mongoz), and their chemical structures were characterized by (1)H-NMR spectroscopy. The oligosaccharide patterns observed among strepsirrhines did not appear to correlate to phylogeny, sociality or pattern of infant care. Both type I and type II neutral oligosaccharides were found in the milk of the aye-aye, but type II predominate over type I. Only type II oligosaccharides were identified in other strepsirrhine milks. α3'-GL (isoglobotriose, Gal(α1-3)Gal(β1-4)Glc) was found in the milks of Coquerel's sifaka and mongoose lemur, which is the first report of this oligosaccharide in the milk of any primate species. 2'-FL (Fuc(α1-2)Gal(β1-4)Glc) was found in the milk of an aye-aye with an ill infant. Oligosaccharides containing the Lewis x epitope were found in aye-aye and mongoose lemur milk. Among acidic oligosaccharides, 3'-N-acetylneuraminyllactose (3'-SL-NAc, Neu5Ac(α2-3)Gal(β1-4)Glc) was found in all studied species, whereas 6'-N-acetylneuraminyllactose (6'-SL-NAc, Neu5Ac(α2-6)Gal(β1-4)Glc) was found in all species except greater galago. Greater galago milk also contained 3'-N-glycolylneuraminyllactose (3'-SL-NGc, Neu5Gc(α2-3)Gal(β1-4)Glc). The finding of a variety of neutral and acidic oligosaccharides in the milks of strepsirrhines, as previously reported for haplorhines, suggests that such constituents are ancient rather than derived features, and are as characteristic of primate lactation is the classic disaccharide, lactose.

The genetics of multiple sclerosis: review of current and emerging candidates

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Muñoz-Culla M

2013-08-01

Full Text Available Maider Muñoz-Culla,1,2 Haritz Irizar,1,2 David Otaegui1,2 1Multiple Sclerosis Unit, Instituto Biodonostia, San Sebastián, Spain; 2Red Española de Esclerosis Múltiple (REEM, Barcelona, Spain Abstract: Multiple sclerosis (MS is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. Keywords: multiple sclerosis, genetics, gene expression, microRNA

Efficient multiple-trait association and estimation of genetic correlation using the matrix-variate linear mixed model.

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Furlotte, Nicholas A; Eskin, Eleazar

2015-05-01

Multiple-trait association mapping, in which multiple traits are used simultaneously in the identification of genetic variants affecting those traits, has recently attracted interest. One class of approaches for this problem builds on classical variance component methodology, utilizing a multitrait version of a linear mixed model. These approaches both increase power and provide insights into the genetic architecture of multiple traits. In particular, it is possible to estimate the genetic correlation, which is a measure of the portion of the total correlation between traits that is due to additive genetic effects. Unfortunately, the practical utility of these methods is limited since they are computationally intractable for large sample sizes. In this article, we introduce a reformulation of the multiple-trait association mapping approach by defining the matrix-variate linear mixed model. Our approach reduces the computational time necessary to perform maximum-likelihood inference in a multiple-trait model by utilizing a data transformation. By utilizing a well-studied human cohort, we show that our approach provides more than a 10-fold speedup, making multiple-trait association feasible in a large population cohort on the genome-wide scale. We take advantage of the efficiency of our approach to analyze gene expression data. By decomposing gene coexpression into a genetic and environmental component, we show that our method provides fundamental insights into the nature of coexpressed genes. An implementation of this method is available at http://genetics.cs.ucla.edu/mvLMM. Copyright © 2015 by the Genetics Society of America.

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.

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Simpson, Siobhan; Dunning, Mark D; Brownlie, Serena; Patel, Janika; Godden, Megan; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

2016-01-01

Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

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Siobhan Simpson

2016-01-01

Full Text Available Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM, yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

Flying lemurs – The 'flying tree shrews'? Molecular cytogenetic evidence for a Scandentia-Dermoptera sister clade

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Volobouev Vitaly

2008-05-01

Full Text Available Abstract Background Flying lemurs or Colugos (order Dermoptera represent an ancient mammalian lineage that contains only two extant species. Although molecular evidence strongly supports that the orders Dermoptera, Scandentia, Lagomorpha, Rodentia and Primates form a superordinal clade called Supraprimates (or Euarchontoglires, the phylogenetic placement of Dermoptera within Supraprimates remains ambiguous. Results To search for cytogenetic signatures that could help to clarify the evolutionary affinities within this superordinal group, we have established a genome-wide comparative map between human and the Malayan flying lemur (Galeopterus variegatus by reciprocal chromosome painting using both human and G. variegatus chromosome-specific probes. The 22 human autosomal paints and the X chromosome paint defined 44 homologous segments in the G. variegatus genome. A putative inversion on GVA 11 was revealed by the hybridization patterns of human chromosome probes 16 and 19. Fifteen associations of human chromosome segments (HSA were detected in the G. variegatus genome: HSA1/3, 1/10, 2/21, 3/21, 4/8, 4/18, 7/15, 7/16, 7/19, 10/16, 12/22 (twice, 14/15, 16/19 (twice. Reverse painting of G. variegatus chromosome-specific paints onto human chromosomes confirmed the above results, and defined the origin of the homologous human chromosomal segments in these associations. In total, G. variegatus paints revealed 49 homologous chromosomal segments in the HSA genome. Conclusion Comparative analysis of our map with published maps from representative species of other placental orders, including Scandentia, Primates, Lagomorpha and Rodentia, suggests a signature rearrangement (HSA2q/21 association that links Scandentia and Dermoptera to one sister clade. Our results thus provide new evidence for the hypothesis that Scandentia and Dermoptera have a closer phylogenetic relationship to each other than either of them has to Primates.

A yeast screening system for simultaneously monitoring multiple genetic endpoints

International Nuclear Information System (INIS)

Dixon, M.L.; Mortimer, R.K.

1986-01-01

Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)

On coding genotypes for genetic markers with multiple alleles in genetic association study of quantitative traits

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Wang Tao

2011-09-01

Full Text Available Abstract Background In genetic association study of quantitative traits using F∞ models, how to code the marker genotypes and interpret the model parameters appropriately is important for constructing hypothesis tests and making statistical inferences. Currently, the coding of marker genotypes in building F∞ models has mainly focused on the biallelic case. A thorough work on the coding of marker genotypes and interpretation of model parameters for F∞ models is needed especially for genetic markers with multiple alleles. Results In this study, we will formulate F∞ genetic models under various regression model frameworks and introduce three genotype coding schemes for genetic markers with multiple alleles. Starting from an allele-based modeling strategy, we first describe a regression framework to model the expected genotypic values at given markers. Then, as extension from the biallelic case, we introduce three coding schemes for constructing fully parameterized one-locus F∞ models and discuss the relationships between the model parameters and the expected genotypic values. Next, under a simplified modeling framework for the expected genotypic values, we consider several reduced one-locus F∞ models from the three coding schemes on the estimability and interpretation of their model parameters. Finally, we explore some extensions of the one-locus F∞ models to two loci. Several fully parameterized as well as reduced two-locus F∞ models are addressed. Conclusions The genotype coding schemes provide different ways to construct F∞ models for association testing of multi-allele genetic markers with quantitative traits. Which coding scheme should be applied depends on how convenient it can provide the statistical inferences on the parameters of our research interests. Based on these F∞ models, the standard regression model fitting tools can be used to estimate and test for various genetic effects through statistical contrasts with the

Multiple depots vehicle routing based on the ant colony with the genetic algorithm

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ChunYing Liu

2013-09-01

Full Text Available Purpose: the distribution routing plans of multi-depots vehicle scheduling problem will increase exponentially along with the adding of customers. So, it becomes an important studying trend to solve the vehicle scheduling problem with heuristic algorithm. On the basis of building the model of multi-depots vehicle scheduling problem, in order to improve the efficiency of the multiple depots vehicle routing, the paper puts forward a fusion algorithm on multiple depots vehicle routing based on the ant colony algorithm with genetic algorithm. Design/methodology/approach: to achieve this objective, the genetic algorithm optimizes the parameters of the ant colony algorithm. The fusion algorithm on multiple depots vehicle based on the ant colony algorithm with genetic algorithm is proposed. Findings: simulation experiment indicates that the result of the fusion algorithm is more excellent than the other algorithm, and the improved algorithm has better convergence effective and global ability. Research limitations/implications: in this research, there are some assumption that might affect the accuracy of the model such as the pheromone volatile factor, heuristic factor in each period, and the selected multiple depots. These assumptions can be relaxed in future work. Originality/value: In this research, a new method for the multiple depots vehicle routing is proposed. The fusion algorithm eliminate the influence of the selected parameter by optimizing the heuristic factor, evaporation factor, initial pheromone distribute, and have the strong global searching ability. The Ant Colony algorithm imports cross operator and mutation operator for operating the first best solution and the second best solution in every iteration, and reserves the best solution. The cross and mutation operator extend the solution space and improve the convergence effective and the global ability. This research shows that considering both the ant colony and genetic algorithm

Social behaviour and gut microbiota in red-bellied lemurs (Eulemur rubriventer): In search of the role of immunity in the evolution of sociality.

Science.gov (United States)

Raulo, Aura; Ruokolainen, Lasse; Lane, Avery; Amato, Katherine; Knight, Rob; Leigh, Steven; Stumpf, Rebecca; White, Bryan; Nelson, Karen E; Baden, Andrea L; Tecot, Stacey R

2018-03-01

Vertebrate gut microbiota form a key component of immunity and a dynamic link between an individual and the ecosystem. Microbiota might play a role in social systems as well, because microbes are transmitted during social contact and can affect host behaviour. Combining methods from behavioural and molecular research, we describe the relationship between social dynamics and gut microbiota of a group-living cooperative species of primate, the red-bellied lemur (Eulemur rubriventer). Specifically, we ask whether patterns of social contact (group membership, group size, position in social network, individual sociality) are associated with patterns of gut microbial composition (diversity and similarity) between individuals and across time. Red-bellied lemurs were found to have gut microbiota with slight temporal fluctuations and strong social group-specific composition. Contrary to expectations, individual sociality was negatively associated with gut microbial diversity. However, position within the social network predicted gut microbial composition. These results emphasize the role of the social environment in determining the microbiota of adult animals. Since social transmission of gut microbiota has the potential to enhance immunity, microbiota might have played an escalating role in the evolution of sociality. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Effects of acute administration of donepezil or memantine on sleep-deprivation-induced spatial memory deficit in young and aged non-human primate grey mouse lemurs (Microcebus murinus.

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Anisur Rahman

Full Text Available The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON and the N-methyl-D-aspartate antagonist memantine (MEM provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation. The non-human primate grey mouse lemur (Microcebus murinus is increasingly used in aging research, but there is no published results related to the impact of known pharmacological treatments on age-related cognitive impairment observed in this primate. In the present study we investigated the effects of DON and MEM on sleep-deprivation (SD-induced memory impairment in young and aged male mouse lemurs. In particular, spatial memory impairment was evaluated using a circular platform task after 8 h of total SD. Acute single doses of DON or MEM (0.1 and 1mg/kg or vehicle were administered intraperitoneally 3 h before the cognitive task during the SD procedure. Results indicated that both doses of DON were able to prevent the SD-induced deficits in retrieval of spatial memory as compared to vehicle-treated animals, both in young and aged animals Likewise, MEM show a similar profile at 1 mg/kg but not at 0.1mg/kg. Taken together, these results indicate that two widely used drugs for mitigating cognitive deficits in AD were partially effective in sleep deprived mouse lemurs, which further support the translational potential of this animal model. Our findings demonstrate the utility of this primate model for further testing cognitive enhancing drugs in development for AD or other neuropsychiatric conditions.

Genomic multiple sequence alignments: refinement using a genetic algorithm

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Lefkowitz Elliot J

2005-08-01

Full Text Available Abstract Background Genomic sequence data cannot be fully appreciated in isolation. Comparative genomics – the practice of comparing genomic sequences from different species – plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program. Results We tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned regions of the orthopoxvirus alignment. Overall sequence identity increased only

Uncovering the genetic landscape for multiple sleep-wake traits.

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Christopher J Winrow

Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

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Iksoo Huh

Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

Le mythe du microcèbe primitif The myth of the primitive mouse lemur

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Fabien Génin

2011-10-01

Full Text Available Les microcèbes (genre Microcebus, famille Cheirogaleidés sont de très petits lémuriens nocturnes endémiques de Madagascar, souvent vus comme les plus archaïques de tous les primates. Dans cette contribution, nous critiquons cette vue, véritable mythe des origines, qui n’est supportée ni par le registre fossile ni par les phylogénies les plus récentes. Nous proposons l’alternative d’une réduction de taille corporelle ou nanisme, un phénomène particulièrement fréquent sur les îles et dans les régions géographiquement isolées et soumises à des sécheresses imprévisibles provoquées par le phénomène El Niño. Nous confirmons le modèle de progénèse de Gould, qui explique le nanisme par des conditions hypervariables entrainant une accélération de l’histoire de vie. Les Cheirogaleidés apparaissent comme des nains paedomorphes comparés à leur groupe frère les Lépilémuridés (Lepilemur. Ils ont probablement subi au moins 3 évènements indépendants de nanisme, qui ont conduit à des changements parallèles des proportions de la tête et des membres (allométrie. Le premier (nanisme a conduit à une diminution de la taille du corps et des membres, sans changement significatif de la forme du crâne (à l’exception des dents chez les plus grandes formes de Cheirogaleidés (Phaner, Mirza, et les grandes formes du genre Cheirogaleus. Le second (hyper-nanisme a conduit à des changements parallèles de la forme du crâne chez les plus petites formes (Allocebus, Microcebus et les petites formes du genre Cheirogaleus, associés à des traits paedomorphiques typiques (grands yeux et petit museau pointu. Cette nouvelle hypothèse explique de nombreuses caractéristiques uniques de ce groupe de lémuriens, en particulier leurs histoires de vie rapides.Mouse lemurs (genus Microcebus, family Cheirogaleidae are small, nocturnal lemurs endemic to Madagascar, often viewed as the most archaic primates. In this contribution, we

The effect of multiple paternity on genetic diversity of small populations during and after colonisation.

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Marina Rafajlović

Full Text Available Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping-stone fashion. Under these circumstances the level of multiple paternity is critical since multiply mated females bring more genetic variation into founder groups than single mated females. One such example is the marine snail Littorina saxatilis that during postglacial times has invaded mainland refuge areas and thereafter small islands emerging due to isostatic uplift by occasional rafting of multiply mated females. We modelled effects of varying degrees of multiple paternity on the genetic variation of island populations colonised by the founders spreading from the mainland, by quantifying the population heterozygosity during both the transient colonisation process, and after a steady state (with migration has been reached. During colonisation, multiple mating by [Formula: see text] males increased the heterozygosity by [Formula: see text] in comparison with single paternity, while in the steady state the increase was [Formula: see text] compared with single paternity. In the steady state the increase of heterozygosity due to multiple paternity is determined by a corresponding increase in effective population size. During colonisation, by contrast, the increase in heterozygosity is larger and it cannot be explained in terms of the effective population size alone. During the steady-state phase bursts of high genetic variation spread through the system, and far from the mainland this led to short periods of high diversity separated by long periods of low diversity. The size of these fluctuations was boosted by multiple paternity. We conclude that following glacial periods of extirpation, recolonization of isolated habitats by this species has been supported by its high level of multiple paternity.

The Effect of Multiple Paternity on Genetic Diversity of Small Populations during and after Colonisation

KAUST Repository

Rafajlović, Marina

2013-10-28

Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping-stone fashion. Under these circumstances the level of multiple paternity is critical since multiply mated females bring more genetic variation into founder groups than single mated females. One such example is the marine snail Littorina saxatilis that during postglacial times has invaded mainland refuge areas and thereafter small islands emerging due to isostatic uplift by occasional rafting of multiply mated females. We modelled effects of varying degrees of multiple paternity on the genetic variation of island populations colonised by the founders spreading from the mainland, by quantifying the population heterozygosity during both the transient colonisation process, and after a steady state (with migration) has been reached. During colonisation, multiple mating by 2-10 males increased the heterozygosity by 10-300% in comparison with single paternity, while in the steady state the increase was 10-50% compared with single paternity. In the steady state the increase of heterozygosity due to multiple paternity is determined by a corresponding increase in effective population size. During colonisation, by contrast, the increase in heterozygosity is larger and it cannot be explained in terms of the effective population size alone. During the steady-state phase bursts of high genetic variation spread through the system, and far from the mainland this led to short periods of high diversity separated by long periods of low diversity. The size of these fluctuations was boosted by multiple paternity. We conclude that following glacial periods of extirpation, recolonization of isolated habitats by this species has been supported by its high level of multiple paternity. 2013 Rafajlovi? et al.

Feature extraction from multiple data sources using genetic programming.

Energy Technology Data Exchange (ETDEWEB)

Szymanski, J. J. (John J.); Brumby, Steven P.; Pope, P. A. (Paul A.); Eads, D. R. (Damian R.); Galassi, M. C. (Mark C.); Harvey, N. R. (Neal R.); Perkins, S. J. (Simon J.); Porter, R. B. (Reid B.); Theiler, J. P. (James P.); Young, A. C. (Aaron Cody); Bloch, J. J. (Jeffrey J.); David, N. A. (Nancy A.); Esch-Mosher, D. M. (Diana M.)

2002-01-01

Feature extration from imagery is an important and long-standing problem in remote sensing. In this paper, we report on work using genetic programming to perform feature extraction simultaneously from multispectral and digital elevation model (DEM) data. The tool used is the GENetic Imagery Exploitation (GENIE) software, which produces image-processing software that inherently combines spatial and spectral processing. GENIE is particularly useful in exploratory studies of imagery, such as one often does in combining data from multiple sources. The user trains the software by painting the feature of interest with a simple graphical user interface. GENIE then uses genetic programming techniques to produce an image-processing pipeline. Here, we demonstrate evolution of image processing algorithms that extract a range of land-cover features including towns, grasslands, wild fire burn scars, and several types of forest. We use imagery from the DOE/NNSA Multispectral Thermal Imager (MTI) spacecraft, fused with USGS 1:24000 scale DEM data.

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

Science.gov (United States)

Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

2015-08-01

Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

KAUST Repository

James, Tojo; Lindé n, Magdalena; Morikawa, Hiromasa; Fernandes, Sunjay Jude; Ruhrmann, Sabrina; Huss, Mikael; Brandi, Maya; Piehl, Fredrik; Jagodic, Maja; Tegner, Jesper; Khademi, Mohsen; Olsson, Tomas; Gomez-Cabrero, David; Kockum, Ingrid

2018-01-01

Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS

Multiple genetic interaction experiments provide complementary information useful for gene function prediction.

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Magali Michaut

Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.

Effects of Resveratrol on Daily Rhythms of Locomotor Activity and Body Temperature in Young and Aged Grey Mouse Lemurs

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Fabien Pifferi

2013-01-01

Full Text Available In several species, resveratrol, a polyphenolic compound, activates sirtuin proteins implicated in the regulation of energy balance and biological clock processes. To demonstrate the effect of resveratrol on clock function in an aged primate, young and aged mouse lemurs (Microcebus murinus were studied over a 4-week dietary supplementation with resveratrol. Spontaneous locomotor activity and daily variations in body temperature were continuously recorded. Reduction in locomotor activity onset and changes in body temperature rhythm in resveratrol-supplemented aged animals suggest an improved synchronisation on the light-dark cycle. Resveratrol could be a good candidate to restore the circadian rhythms in the elderly.

Genetic diversity and population structure of Lantana camara in India indicates multiple introductions and gene flow.

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Ray, A; Quader, S

2014-05-01

Lantana camara is a highly invasive plant, which has spread over 60 countries and island groups of Asia, Africa and Australia. In India, it was introduced in the early nineteenth century, since when it has expanded and gradually established itself in almost every available ecosystem. We investigated the genetic diversity and population structure of this plant in India in order to understand its introduction, subsequent range expansion and gene flow. A total of 179 individuals were sequenced at three chloroplast loci and 218 individuals were genotyped for six nuclear microsatellites. Both chloroplasts (nine haplotypes) and microsatellites (83 alleles) showed high genetic diversity. Besides, each type of marker confirmed the presence of private polymorphism. We uncovered low to medium population structure in both markers, and found a faint signal of isolation by distance with microsatellites. Bayesian clustering analyses revealed multiple divergent genetic clusters. Taken together, these findings (i.e. high genetic diversity with private alleles and multiple genetic clusters) suggest that Lantana was introduced multiple times and gradually underwent spatial expansion with recurrent gene flow. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

What Is It Going to Be? Pattern and Potential Function of Natal Coat Change in Sexually Dichromatic Redfronted Lemurs (Eulemur fulvus rufus)

DEFF Research Database (Denmark)

Barthold, Julia A; Fichtel, Claudia; Kappeler, Peter M

2009-01-01

with adult male coloration and female infants subsequently undergo a change in coloration. Using digital pictures and behavioral data collected on eight mother-offspring dyads from birth until the end of the coloration change, we 1) described timing and pattern of pelage development in redfronted lemur...... infants and 2) examined behavioral developmental correlates of the coloration change. The color change took place between 7 and 17 weeks of age and coincided with advanced physical independence; a pattern also found in monochromatic primate species with natal coats. No behavioral differences between male...

Deficits of psychomotor and mnesic functions across aging in mouse lemur primates

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Solène eLanguille

2015-01-01

Full Text Available Owing to a similar cerebral neuro-anatomy, non-human primates are viewed as the most valid models for understanding cognitive deficits. This study evaluated psychomotor and mnesic functions of 41 young to old mouse lemurs (Microcebus murinus. Psychomotor capacities and anxiety-related behaviors decreased abruptly from middle to late adulthood. However, Mnesic functions were not affected in the same way with increasing age. While results of the spontaneous alternation task point to a progressive and widespread age-related decline of spatial working memory, both spatial reference and novel object recognition memory tasks did not reveal any tendency due to large inter-individual variability in the middle-aged and old animals. Indeed, some of the aged animals performed as well as younger ones, whereas some others had bad performances in the Barnes maze and in the object recognition test. Hierarchical cluster analysis revealed that declarative-like memory was strongly impaired only in 7 out of 25 middle-aged/old animals. These results suggest that this analysis allows to distinguish elder populations of good and bad performers in this non-human primate model and to closely compare this to human aging.

Anatomy is important, but need not be destiny: novel uses of the thumb in aye-ayes compared to other lemurs.

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Pellis, Sergio M; Pellis, Vivien C

2012-06-01

Aye-ayes (Daubentonia madagascerensis) have highly specialized hands with long digits, especially the thin middle one (D3), which is used for extracting food, such as beetle larvae, under bark. Due to the elongation of their fingers, including the thumb, it is presumed that aye-ayes have a rather limited capacity for delicate manipulation of objects. However, studies have reported independent movement of digits D3 and D4, and one report noted a seemingly independent thumb (D1) movement in holding food. Sixteen captive adult aye-ayes were videotaped feeding on a diverse range of foods so as to document how the thumb is used during food holding. To determine if the patterns observed were unique to aye-ayes, 24 individuals from 9 other species of lemurs were also videotaped. Two patterns of thumb use idiosyncratic to aye-ayes and one other lemur, the sifaka (Propithecus verreauxi), were identified: (1) when holding a food item in one hand, the thumb was used to secure the food, with the other digits playing a secondary role; (2) when holding a food item with both hands, the thumbs once again took a predominant role in securing the food. In the majority of these cases, whether held by one or two thumbs, the thumbs curled around the item, but some descriptive evidence is provided that suggests that aye-ayes exaggerate the role of the thumbs by shifting the hold to the outer edge. The novel uses of the thumbs in aye-ayes demonstrate that brain mechanisms can sometimes override the behavioral (or motor) limitations imposed by the morphology of the body. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimization of Multiple Traveling Salesman Problem Based on Simulated Annealing Genetic Algorithm

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Xu Mingji

2017-01-01

Full Text Available It is very effective to solve the multi variable optimization problem by using hierarchical genetic algorithm. This thesis analyzes both advantages and disadvantages of hierarchical genetic algorithm and puts forward an improved simulated annealing genetic algorithm. The new algorithm is applied to solve the multiple traveling salesman problem, which can improve the performance of the solution. First, it improves the design of chromosomes hierarchical structure in terms of redundant hierarchical algorithm, and it suggests a suffix design of chromosomes; Second, concerning to some premature problems of genetic algorithm, it proposes a self-identify crossover operator and mutation; Third, when it comes to the problem of weak ability of local search of genetic algorithm, it stretches the fitness by mixing genetic algorithm with simulated annealing algorithm. Forth, it emulates the problems of N traveling salesmen and M cities so as to verify its feasibility. The simulation and calculation shows that this improved algorithm can be quickly converged to a best global solution, which means the algorithm is encouraging in practical uses.

Genetic structuring of northern myotis (Myotis septentrionalis) at multiple spatial scales

Science.gov (United States)

Johnson, Joshua B.; Roberts, James H.; King, Timothy L.; Edwards, John W.; Ford, W. Mark; Ray, David A.

2014-01-01

Although groups of bats may be genetically distinguishable at large spatial scales, the effects of forest disturbances, particularly permanent land use conversions on fine-scale population structure and gene flow of summer aggregations of philopatric bat species are less clear. We genotyped and analyzed variation at 10 nuclear DNA microsatellite markers in 182 individuals of the forest-dwelling northern myotis (Myotis septentrionalis) at multiple spatial scales, from within first-order watersheds scaling up to larger regional areas in West Virginia and New York. Our results indicate that groups of northern myotis were genetically indistinguishable at any spatial scale we considered, and the collective population maintained high genetic diversity. It is likely that the ability to migrate, exploit small forest patches, and use networks of mating sites located throughout the Appalachian Mountains, Interior Highlands, and elsewhere in the hibernation range have allowed northern myotis to maintain high genetic diversity and gene flow regardless of forest disturbances at local and regional spatial scales. A consequence of maintaining high gene flow might be the potential to minimize genetic founder effects following population declines caused currently by the enzootic White-nose Syndrome.

Restless legs syndrome in Czech patients with multiple sclerosis: An epidemiological and genetic study

Czech Academy of Sciences Publication Activity Database

Vávrová, J.; Kemlink, D.; Šonka, K.; Havrdová, E.; Horáková, D.; Pardini, Barbara; Müller-Myhsok, B.; Winkelmann, J.

2012-01-01

Roč. 13, č. 7 (2012), s. 848-851 ISSN 1389-9457 R&D Projects: GA MZd NR8563 Grant - others:GA ČR(CZ) GD309/08/H079; GA MZd(CZ) NT12141 Institutional research plan: CEZ:AV0Z50390512 Keywords : Secondary restless legs syndrome * Multiple sclerosis * Genetic association study Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.487, year: 2012

Considering the Influence of Nonadaptive Evolution on Primate Color Vision.

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Rachel L Jacobs

Full Text Available Color vision in primates is variable across species, and it represents a rare trait in which the genetic mechanisms underlying phenotypic variation are fairly well-understood. Research on primate color vision has largely focused on adaptive explanations for observed variation, but it remains unclear why some species have trichromatic or polymorphic color vision while others are red-green color blind. Lemurs, in particular, are highly variable. While some species are polymorphic, many closely-related species are strictly dichromatic. We provide the first characterization of color vision in a wild population of red-bellied lemurs (Eulemur rubriventer, Ranomafana National Park, Madagascar with a sample size (87 individuals; NX chromosomes = 134 large enough to detect even rare variants (0.95 probability of detection at ≥ 3% frequency. By sequencing exon 5 of the X-linked opsin gene we identified opsin spectral sensitivity based on known diagnostic sites and found this population to be dichromatic and monomorphic for a long wavelength allele. Apparent fixation of this long allele is in contrast to previously published accounts of Eulemur species, which exhibit either polymorphic color vision or only the medium wavelength opsin. This unexpected result may represent loss of color vision variation, which could occur through selective processes and/or genetic drift (e.g., genetic bottleneck. To indirectly assess the latter scenario, we genotyped 55 adult red-bellied lemurs at seven variable microsatellite loci and used heterozygosity excess and M-ratio tests to assess if this population may have experienced a recent genetic bottleneck. Results of heterozygosity excess but not M-ratio tests suggest a bottleneck might have occurred in this red-bellied lemur population. Therefore, while selection may also play a role, the unique color vision observed in this population might have been influenced by a recent genetic bottleneck. These results emphasize the

Evidence for the possible occurrence of Grave's disease in a blue-eyed black lemur (Eulemur flavifrons).

Science.gov (United States)

Quintard, Benoît; Giorgiadis, Marine; Feirrera, Xavier; Lefaux, Brice; Schohn, Christophe; Lemberger, Karin

2018-03-01

The blue-eyed black lemur (Eulemur flavifrons) is classified by the International Union for Conservation of Nature (IUCN) as critically endangered. A 23-year-old male housed at Mulhouse Zoo presented with lethargy, polyphagia, alopecia, and chronic weight loss. Clinical examination suggested an endocrine pathology such as hyperthyroidism. Secondary examinations included cervical ultrasound, thyroid biopsy, and scintigraphy. The latter revealed elevated thyroid activity. Blood analysis was performed to measure the level of anti-receptor thyroid-stimulating hormone antibodies, which allowed us to test the autoimmune hypothesis. The high level of antibodies together with levels of thyroid-stimulating hormone and the scintigraphy images led to the diagnosis of Grave's disease. Carbimazole treatment followed by thyroidectomy resulted in a quick weight gain and general improvement in health status. The following breeding season, the treated individual sired an offspring. To the authors' knowledge, this is the first report of likely Grave's disease in a non-human primate.

Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.

Science.gov (United States)

Lima, Aline Dt; Alves, Vanessa R; Rocha, Andressa R; Martinhago, Ana C; Martinhago, Ciro; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Gebrim, Luiz H

2018-03-01

Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive βHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

DEFF Research Database (Denmark)

Goris, An; Pauwels, Ine; Gustavsen, Marte W

2015-01-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying...... differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed...... a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals...

A Hybrid Genetic Algorithm for the Multiple Crossdocks Problem

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Zhaowei Miao

2012-01-01

Full Text Available We study a multiple crossdocks problem with supplier and customer time windows, where any violation of time windows will incur a penalty cost and the flows through the crossdock are constrained by fixed transportation schedules and crossdock capacities. We prove this problem to be NP-hard in the strong sense and therefore focus on developing efficient heuristics. Based on the problem structure, we propose a hybrid genetic algorithm (HGA integrating greedy technique and variable neighborhood search method to solve the problem. Extensive experiments under different scenarios were conducted, and results show that HGA outperforms CPLEX solver, providing solutions in realistic timescales.

Low genetic diversity despite multiple introductions of the invasive plant species Impatiens glandulifera in Europe.

Science.gov (United States)

Hagenblad, Jenny; Hülskötter, Jennifer; Acharya, Kamal Prasad; Brunet, Jörg; Chabrerie, Olivier; Cousins, Sara A O; Dar, Pervaiz A; Diekmann, Martin; De Frenne, Pieter; Hermy, Martin; Jamoneau, Aurélien; Kolb, Annette; Lemke, Isgard; Plue, Jan; Reshi, Zafar A; Graae, Bente Jessen

2015-08-20

Invasive species can be a major threat to native biodiversity and the number of invasive plant species is increasing across the globe. Population genetic studies of invasive species can provide key insights into their invasion history and ensuing evolution, but also for their control. Here we genetically characterise populations of Impatiens glandulifera, an invasive plant in Europe that can have a major impact on native plant communities. We compared populations from the species' native range in Kashmir, India, to those in its invaded range, along a latitudinal gradient in Europe. For comparison, the results from 39 other studies of genetic diversity in invasive species were collated. Our results suggest that I. glandulifera was established in the wild in Europe at least twice, from an area outside of our Kashmir study area. Our results further revealed that the genetic diversity in invasive populations of I. glandulifera is unusually low compared to native populations, in particular when compared to other invasive species. Genetic drift rather than mutation seems to have played a role in differentiating populations in Europe. We find evidence of limitations to local gene flow after introduction to Europe, but somewhat less restrictions in the native range. I. glandulifera populations with significant inbreeding were only found in the species' native range and invasive species in general showed no increase in inbreeding upon leaving their native ranges. In Europe we detect cases of migration between distantly located populations. Human activities therefore seem to, at least partially, have facilitated not only introductions, but also further spread of I. glandulifera across Europe. Although multiple introductions will facilitate the retention of genetic diversity in invasive ranges, widespread invasive species can remain genetically relatively invariant also after multiple introductions. Phenotypic plasticity may therefore be an important component of the

Population genetics of the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis across multiple spatial scales.

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Shem D Unger

Full Text Available Conservation genetics is a powerful tool to assess the population structure of species and provides a framework for informing management of freshwater ecosystems. As lotic habitats become fragmented, the need to assess gene flow for species of conservation management becomes a priority. The eastern hellbender (Cryptobranchus alleganiensis alleganiensis is a large, fully aquatic paedamorphic salamander. Many populations are experiencing declines throughout their geographic range, yet the genetic ramifications of these declines are currently unknown. To this end, we examined levels of genetic variation and genetic structure at both range-wide and drainage (hierarchical scales. We collected 1,203 individuals from 77 rivers throughout nine states from June 2007 to August 2011. Levels of genetic diversity were relatively high among all sampling locations. We detected significant genetic structure across populations (Fst values ranged from 0.001 between rivers within a single watershed to 0.218 between states. We identified two genetically differentiated groups at the range-wide scale: 1 the Ohio River drainage and 2 the Tennessee River drainage. An analysis of molecular variance (AMOVA based on landscape-scale sampling of basins within the Tennessee River drainage revealed the majority of genetic variation (∼94-98% occurs within rivers. Eastern hellbenders show a strong pattern of isolation by stream distance (IBSD at the drainage level. Understanding levels of genetic variation and differentiation at multiple spatial and biological scales will enable natural resource managers to make more informed decisions and plan effective conservation strategies for cryptic, lotic species.

A general framework for the evaluation of genetic association studies using multiple marginal models

DEFF Research Database (Denmark)

Kitsche, Andreas; Ritz, Christian; Hothorn, Ludwig A.

2016-01-01

OBJECTIVE: In this study, we present a simultaneous inference procedure as a unified analysis framework for genetic association studies. METHODS: The method is based on the formulation of multiple marginal models that reflect different modes of inheritance. The basic advantage of this methodology...

Surgical and medical management for fractures of the second through fifth metacarpals in a red ruffed lemur (Varecia rubra).

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Cerveny, Shannon N S; Harper, Justin; Voges, Andra; Coke, Rob L

2013-03-01

A 21-yr-old female red ruffed lemur (Varecia rubra) was presented with swelling and disuse of the right manus. Severely displaced fractures of metacarpals II-V were diagnosed radiographically. The fractures were surgically stabilized with intramedullary Kirschner wires attached externally with an acrylic external fixator and a bone plate on the dorsal aspect of metacarpal III. The fractures of metacarpals II-V were predominantly healed on radiographs obtained 12 wk after surgery. However, diffuse disuse osteopenia and phalangeal contracture were present, with possible osteomyelitis. An exercise regimen of the affected hand was initiated due to the incomplete extension of the phalanges. After 4 wk of therapy, the extension of the phalanges had improved and the fractures appeared radiographically to be nearly completely healed. Although metacarpal fractures are common in nonhuman primates, they are reported infrequently in the literature.

76 FR 66954 - Endangered Species; Receipt of Applications for Permit

Science.gov (United States)

2011-10-28

...). black lemur (Eulemur macaco). brown lemur (Eulemur fulvus). black and white ruffed lemur (Varecia...). black and white ruffed lemur (Varecia variagata). red ruffed lemur (Varecia rubra). black lemur (Eulemur...

Estimation in a multiplicative mixed model involving a genetic relationship matrix

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Eccleston John A

2009-04-01

Full Text Available Abstract Genetic models partitioning additive and non-additive genetic effects for populations tested in replicated multi-environment trials (METs in a plant breeding program have recently been presented in the literature. For these data, the variance model involves the direct product of a large numerator relationship matrix A, and a complex structure for the genotype by environment interaction effects, generally of a factor analytic (FA form. With MET data, we expect a high correlation in genotype rankings between environments, leading to non-positive definite covariance matrices. Estimation methods for reduced rank models have been derived for the FA formulation with independent genotypes, and we employ these estimation methods for the more complex case involving the numerator relationship matrix. We examine the performance of differing genetic models for MET data with an embedded pedigree structure, and consider the magnitude of the non-additive variance. The capacity of existing software packages to fit these complex models is largely due to the use of the sparse matrix methodology and the average information algorithm. Here, we present an extension to the standard formulation necessary for estimation with a factor analytic structure across multiple environments.

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis.

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Goris, An; Pauwels, Ine; Gustavsen, Marte W; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D'Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G; Gourraud, Pierre-Antoine; Sawcer, Stephen J; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F

2015-03-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10(-16)). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10(-7)). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10(-37)). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10(-22)), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10(-6)). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such

Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

Science.gov (United States)

Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.

2015-01-01

Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such

Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

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Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

2016-09-01

Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of the genetic variation in Mycobacterium tuberculosis strains by multiple genome alignments

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Morales Juan

2008-11-01

Full Text Available Abstract Background The recent determination of the complete nucleotide sequence of several Mycobacterium tuberculosis (MTB genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C, along with the genomes of laboratory strains (H37Rv and H37Ra, provides new insights on the mechanisms of adaptation of this bacterium to the human host. Findings The genetic variation found in six M. tuberculosis strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software islandsanalyser, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms. Conclusion The comparison of multiple genomes demonstrates that the M. tuberculosis genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium.

Genetic susceptibility factors for multiple chemical sensitivity revisited

DEFF Research Database (Denmark)

Berg, Nikolaj Drimer; Rasmussen, Henrik Berg; Linneberg, Allan

2010-01-01

of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding......Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose...... significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when...

Genetic data suggest a natural prehuman origin of open habitats in northern Madagascar and question the deforestation narrative in this region.

Science.gov (United States)

Quéméré, Erwan; Amelot, Xavier; Pierson, Julie; Crouau-Roy, Brigitte; Chikhi, Lounès

2012-08-07

The impact of climate change and anthropogenic deforestation on biodiversity is of growing concern worldwide. Disentangling how past anthropogenic and natural factors contributed to current biome distribution is thus a crucial issue to understand their complex interactions on wider time scales and to improve predictions and conservation strategies. This is particularly important in biodiversity hotspots, such as Madagascar, dominated by large open habitats whose origins are increasingly debated. Although a dominant narrative argues that Madagascar was originally entirely covered by woodlands, which were destroyed by humans, a number of recent studies have suggested that past climatic fluctuations played a major role in shaping current biome distributions well before humans arrived. Here, we address the question of the origin of open habitats in the Daraina region in northern Madagascar, using a multiproxy approach combining population genetics modeling and remote-sensing analyses. We show that (i) contrary to most regions of Madagascar, the forest cover in Daraina remained remarkably stable over the past 60 y, and (ii) the golden-crowned sifaka (Propithecus tattersalli), a forest-dwelling lemur, underwent a strong population contraction before the arrival of the first humans, hence excluding an anthropogenic cause. Prehuman Holocene droughts may have led to a significant increase of grasslands and a reduction in the species' habitat. This contradicts the prevailing narrative that land cover changes are necessarily anthropogenic in Madagascar but does not preclude the later role played by humans in other regions in which recent lemur bottlenecks have been observed.

Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

Science.gov (United States)

Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

2012-07-01

Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

The genetics of multiple sclerosis: review of current and emerging candidates

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Muñoz-Culla, Maider; Irizar, Haritz; Otaegui, David

2013-01-01

Multiple sclerosis (MS) is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. PMID:24019748

Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

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Vercellino, Marco; Fenoglio, Chiara; Galimberti, Daniela; Mattioda, Alessandra; Chiavazza, Carlotta; Binello, Eleonora; Pinessi, Lorenzo; Giobbe, Dario; Scarpini, Elio; Cavalla, Paola

2016-07-01

Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia. In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery. We also evaluated serum progranulin levels in the different groups of GRN variants carriers. We found that incomplete recovery after a relapse is correlated with an increased frequency of the rs9897526 A allele (odds ratio (OR) 4.367, p = 0.005). A more severe disease course (Multiple Sclerosis Severity Score > 5) is correlated with an increased frequency of the rs9897526 A allele (OR 1.886, p = 0.002) and of the rs5848 T allele (OR 1.580, p = 0.019). Carriers of the variants associated with a more severe disease course (rs9897526 A, rs5848 T) have significantly lower levels of circulating progranulin (80.5 ± 9.1 ng/mL vs. 165.7 ng/mL, p = 0.01). GRN genetic polymorphisms likely influence disease course and relapse recovery in MS. © The Author(s), 2015.

Genetic classes and genetic categories : Protecting genetic groups through data protection law

NARCIS (Netherlands)

Hallinan, Dara; de Hert, Paul; Taylor, L.; Floridi, L.; van der Sloot, B.

2017-01-01

Each person shares genetic code with others. Thus, one individual’s genome can reveal information about other individuals. When multiple individuals share aspects of genetic architecture, they form a ‘genetic group’. From a social and legal perspective, two types of genetic group exist: Those which

Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles

DEFF Research Database (Denmark)

Mero, Inger-Lise; Gustavsen, Marte W; Sæther, Hanne S

2013-01-01

The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS). We applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating...

What Is It Going to Be? Pattern and Potential Function of Natal Coat Change in Sexually Dichromatic Redfronted Lemurs (Eulemur fulvus rufus)

DEFF Research Database (Denmark)

Barthold, Julia A; Fichtel, Claudia; Kappeler, Peter M

2009-01-01

In some primate species, pelage colorations at birth contrast with adult colorations. The intensity of natal coats and their phylogenetic distribution is highly variable within primates. Natal coat coloration seems to change to adult coloration in most species when infants become independent from...... their mothers, but an accepted functional explanation for natal coats is not available. Here we describe pelage coloration change in sexually dichromatic redfronted lemurs (Eulemur fulvus rufus) in Kirindy Forest, and propose a new functional hypothesis for this phenomenon. In this species, infants are born...... infants and 2) examined behavioral developmental correlates of the coloration change. The color change took place between 7 and 17 weeks of age and coincided with advanced physical independence; a pattern also found in monochromatic primate species with natal coats. No behavioral differences between male...

Genetic and infectious profiles of Japanese multiple sclerosis patients.

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Satoshi Yoshimura

Full Text Available BACKGROUND: Nationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed HLA-DRB1 and -DPB1 alleles, and IgG antibodies specific for Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus, and Epstein-Barr virus nuclear antigen (EBNA in 145 MS patients and 367 healthy controls (HCs. Frequencies of DRB1*0405 and DPB1*0301 were significantly higher, and DRB1*0901 and DPB1*0401 significantly lower, in MS patients as compared with HCs. MS patients with DRB1*0405 had a significantly earlier age of onset and lower Progression Index than patients without this allele. The proportion and absolute number of patients with DRB1*0405 successively increased with advancing year of birth. In MS patients without DRB1*0405, the frequency of the DRB1*1501 allele was significantly higher, while the DRB1*0901 allele was significantly lower, compared with HCs. Furthermore, DRB1*0405-negative MS patients were significantly more likely to be positive for EBNA antibodies compared with HCs. CONCLUSIONS: Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.

Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene

DEFF Research Database (Denmark)

Binzer, Stefanie; Stenager, Egon; Binzer, Michael

2016-01-01

BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted. OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants...... in the genetically homogenous population of the isolated Faroe Islands. METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK...... of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis....

Multiple genetic variants associated with primary biliary cirrhosis in a Han Chinese population.

Science.gov (United States)

Dong, Ming; Li, Jinxin; Tang, Ruqi; Zhu, Ping; Qiu, Fang; Wang, Chan; Qiu, Jie; Wang, Lan; Dai, Yaping; Xu, Ping; Gao, Yueqiu; Han, Chongxu; Wang, Yongzhong; Wu, Jian; Wu, Xudong; Zhang, Kui; Dai, Na; Sun, Weihao; Zhou, Jianpo; Hu, Zhigang; Liu, Lei; Jiang, Yuzhang; Nie, Jinshan; Zhao, Yi; Gong, Yuhua; Tian, Ye; Ji, Hualiang; Jiao, Zhijun; Jiang, Po; Shi, Xingjuan; Jawed, Rohil; Zhang, Yu; Huang, Qinghai; Li, Enling; Wei, Yiran; Xie, Wei; Zhao, Weifeng; Liu, Xiang; Zhu, Xiang; Qiu, Hong; He, Gengsheng; Chen, Weichang; Seldin, Michael F; Gershwin, M Eric; Liu, Xiangdong; Ma, Xiong

2015-06-01

Multiple genome-wide association studies of primary biliary cirrhosis (PBC) in both European and Japanese ancestries have shown significant associations of many genetic loci contributing to the susceptibility to PBC. Major differences in susceptibility loci between these two population groups were observed. In this study, we examined whether the most significant loci observed in either European and/or Japanese cohorts are associated with PBC in a Han Chinese population. In 1070 PBC patients and 1198 controls, we observed highly significant associations at CD80 (rs2293370, P = 2.67 × 10(-8)) and TNFSF15 (rs4979462, P = 3.86 × 10(-8)) and significant associations at 17q12-21 (rs9303277), PDGFB (rs715505), NF-κB1 (rs7665090), IL12RB2 (rs11209050), and STAT4 (rs7574865; all corrected P values rs7574865) was strongly associated after additional control samples were analyzed. Our study is the first large-scale genetic analysis in a Han Chinese PBC cohort. These results do not only reflect that Han Chinese PBC patients share common genetic susceptibility genes with both their Japanese and European counterparts but also suggest a distinctly different genetic susceptibility profile.

Development and amplification of multiple co-dominant genetic markers from single spores of arbuscular mycorrhizal fungi by nested multiplex PCR

DEFF Research Database (Denmark)

Holtgrewe-Stukenbrock, Eva; Rosendahl, Søren

2005-01-01

Multiple co-dominant genetic markers from single spores of the arbuscular mycorrhizal (AM) fungi Glomus mosseae, Glomus caledonium, and Glomus geosporum were amplified by nested multiplex PCR using a combination of primers for simultaneous amplification of five loci in one PCR. Subsequently, each...... marker was amplified separately in nested PCR using specific primers. Polymorphic loci within the three putative single copy genes GmFOX2, GmTOR2, and GmGIN1 were characterized by sequencing and single strand conformation polymorphisms (SSCP). Primers specific for the LSU rDNA D2 region were included...... are homokaryotic. All isolates of G. mosseae had unique genotypes. The amplification of multiple co-dominant genetic markers from single spores by the nested multiplex PCR approach provides an important tool for future studies of AM fungi population genetics and evolution....

Multiple exostotic hypochondroplasia: Syndrome of combined hypochondroplasia and multiple exostoses

International Nuclear Information System (INIS)

Dominguez, R.; Young, L.W.; Girdany, B.R.; Steele, M.W.

1984-01-01

This is a report of a family with major focus on the daughter who had short stature. The mother had hypochondroplasia and the father had multiple exostoses. The daughter's skeletal roentgenograms show features of both hypochondroplasia and multiple exostoses. The roentgenographic, clinical and genetic aspects of these skeletal dysplasias are reviewed and hypochrondroplasia is contrasted with achondroplasia. The genetic and counseling implications of the association of hypochondroplasia and multiple exostoses are discussed. (orig.)

Multiple exostotic hypochondroplasia: Syndrome of combined hypochondroplasia and multiple exostoses

Energy Technology Data Exchange (ETDEWEB)

Dominguez, R.; Young, L.W.; Girdany, B.R.; Steele, M.W.

1984-07-01

This is a report of a family with major focus on the daughter who had short stature. The mother had hypochondroplasia and the father had multiple exostoses. The daughter's skeletal roentgenograms show features of both hypochondroplasia and multiple exostoses. The roentgenographic, clinical and genetic aspects of these skeletal dysplasias are reviewed and hypochrondroplasia is contrasted with achondroplasia. The genetic and counseling implications of the association of hypochondroplasia and multiple exostoses are discussed.

Volatile terpenoids: multiple functions, biosynthesis, modulation and manipulation by genetic engineering.

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Abbas, Farhat; Ke, Yanguo; Yu, Rangcai; Yue, Yuechong; Amanullah, Sikandar; Jahangir, Muhammad Muzammil; Fan, Yanping

2017-11-01

Terpenoids play several physiological and ecological functions in plant life through direct and indirect plant defenses and also in human society because of their enormous applications in the pharmaceutical, food and cosmetics industries. Through the aid of genetic engineering its role can by magnified to broad spectrum by improving genetic ability of crop plants, enhancing the aroma quality of fruits and flowers and the production of pharmaceutical terpenoids contents in medicinal plants. Terpenoids are structurally diverse and the most abundant plant secondary metabolites, playing an important role in plant life through direct and indirect plant defenses, by attracting pollinators and through different interactions between the plants and their environment. Terpenoids are also significant because of their enormous applications in the pharmaceutical, food and cosmetics industries. Due to their broad distribution and functional versatility, efforts are being made to decode the biosynthetic pathways and comprehend the regulatory mechanisms of terpenoids. This review summarizes the recent advances in biosynthetic pathways, including the spatiotemporal, transcriptional and post-transcriptional regulatory mechanisms. Moreover, we discuss the multiple functions of the terpene synthase genes (TPS), their interaction with the surrounding environment and the use of genetic engineering for terpenoid production in model plants. Here, we also provide an overview of the significance of terpenoid metabolic engineering in crop protection, plant reproduction and plant metabolic engineering approaches for pharmaceutical terpenoids production and future scenarios in agriculture, which call for sustainable production platforms by improving different plant traits.

A major and stable QTL associated with seed weight in soybean across multiple environments and genetic backgrounds.

Science.gov (United States)

Kato, Shin; Sayama, Takashi; Fujii, Kenichiro; Yumoto, Setsuzo; Kono, Yuhi; Hwang, Tae-Young; Kikuchi, Akio; Takada, Yoshitake; Tanaka, Yu; Shiraiwa, Tatsuhiko; Ishimoto, Masao

2014-06-01

We detected a QTL for single seed weight in soybean that was stable across multiple environments and genetic backgrounds with the use of two recombinant inbred line populations. Single seed weight (SSW) in soybean is a key determinant of both seed yield and the quality of soy food products, and it exhibits wide variation. SSW is under genetic control, but the molecular mechanisms of such control remain unclear. We have now investigated quantitative trait loci (QTLs) for SSW in soybean and have identified such a QTL that is stable across multiple environments and genetic backgrounds. Two populations of 225 and 250 recombinant inbred lines were developed from crosses between Japanese and US cultivars of soybean that differ in SSW by a factor of ~2, and these populations were grown in at least three different environments. A whole-genome panel comprising 304 simple sequence repeat (SSR) loci was applied to mapping in each population. We identified 15 significant QTLs for SSW dispersed among 11 chromosomes in the two populations. One QTL located between Sat_284 and Sat_292 on chromosome 17 was detected (3.6 soybean.

Genetic evidence of multiple loci in dystocia - difficult labour

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Westgren Magnus

2010-06-01

Full Text Available Abstract Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT on chromosome 20 and oxytocin-receptor (OXTR on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15 on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts.

Genetic evidence of multiple loci in dystocia - difficult labour

Science.gov (United States)

2010-01-01

Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts. PMID:20587075

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

Science.gov (United States)

Petkau, T L; Hill, A; Leavitt, B R

2016-02-19

Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy.

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Ammar Al-Chalabi

Full Text Available BACKGROUND: Multiple system atrophy (MSA is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. Pathogenic mechanisms remain obscure but the neuropathological hallmark is the presence of alpha-synuclein-immunoreactive glial cytoplasmic inclusions. Genetic variants of the alpha-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson's disease has identified association of a SNP in SNCA with MSA. METHODOLOGY/FINDINGS: We evaluated 32 SNPs in the SNCA gene in a European population of 239 cases and 617 controls recruited as part of the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS study. We used 161 independently collected samples for replication. Two SNCA SNPs showed association with MSA: rs3822086 (P = 0.0044, and rs3775444 (P = 0.012, although only the first survived correction for multiple testing. In the MSA-C subgroup the association strengthened despite more than halving the number of cases: rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3-3.6; rs3775444 P = 0.0017, OR 4.386 (95% CI 1.6-11.7. A 7-SNP haplotype incorporating three SNPs either side of rs3822086 strengthened the association with MSA-C further (best haplotype, P = 8.7 x 10(-4. The association with rs3822086 was replicated in the independent samples (P = 0.035. CONCLUSIONS/SIGNIFICANCE: We report a genetic association between MSA and alpha-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00211224.

Directional genetic selection by pulp mill effluent on multiple natural populations of three-spined stickleback (Gasterosteus aculeatus).

Science.gov (United States)

Lind, Emma E; Grahn, Mats

2011-05-01

Contamination can cause a rapid environmental change which may require populations to respond with evolutionary changes. To evaluate the effects of pulp mill effluents on population genetics, we sampled three-spined sticklebacks (Gasterosteus aculeatus) near four pulp mills and four adjacent reference sites and analyzed Amplified Fragment Length Polymorphism (AFLP) to compare genetic variability. A fine scale genetic structure was detected and samples from polluted sites separated from reference sites in multidimensional scaling plots (Pselection. When removing 13 F(ST)-outlier loci, significant at the Pselective agent on natural populations of G. aculeatus, causing a convergence in genotype composition change at multiple sites in an open environment. © The Author(s) 2011. This article is published with open access at Springerlink.com

Population genetic diversity and fitness in multiple environments

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McGreevy Thomas J

2010-07-01

Full Text Available Abstract Background When a large number of alleles are lost from a population, increases in individual homozygosity may reduce individual fitness through inbreeding depression. Modest losses of allelic diversity may also negatively impact long-term population viability by reducing the capacity of populations to adapt to altered environments. However, it is not clear how much genetic diversity within populations may be lost before populations are put at significant risk. Development of tools to evaluate this relationship would be a valuable contribution to conservation biology. To address these issues, we have created an experimental system that uses laboratory populations of an estuarine crustacean, Americamysis bahia with experimentally manipulated levels of genetic diversity. We created replicate cultures with five distinct levels of genetic diversity and monitored them for 16 weeks in both permissive (ambient seawater and stressful conditions (diluted seawater. The relationship between molecular genetic diversity at presumptive neutral loci and population vulnerability was assessed by AFLP analysis. Results Populations with very low genetic diversity demonstrated reduced fitness relative to high diversity populations even under permissive conditions. Population performance decreased in the stressful environment for all levels of genetic diversity relative to performance in the permissive environment. Twenty percent of the lowest diversity populations went extinct before the end of the study in permissive conditions, whereas 73% of the low diversity lines went extinct in the stressful environment. All high genetic diversity populations persisted for the duration of the study, although population sizes and reproduction were reduced under stressful environmental conditions. Levels of fitness varied more among replicate low diversity populations than among replicate populations with high genetic diversity. There was a significant correlation

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Science.gov (United States)

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

2011-01-01

Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

The Season for Peace: Reconciliation in a Despotic Species (Lemur catta.

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Elisabetta Palagi

Full Text Available However despotic a social group may be, managing conflicts of interest is crucial to preserve group living benefits, mainly based on cooperation. In despotic groups, post-conflict management via reconciliation (the first post-conflict reunion between former opponents can occur, even if conciliatory rates are considerably different. Lemur catta is defined as a despotic species because groups are characterized by a strict linear hierarchy maintained by the adult females (the dominant sex mainly via aggression. Reconciliation was reported in one out of four captive groups of L. catta. Here we investigate which variables influence the occurrence of reconciliation in these despotic groups. We analyzed 2339 Post Conflict (PC-Matched Control (MC observation pairs, collected on eight groups (five in the Berenty forest, Madagascar; three hosted at the Pistoia Zoo, Italy. Since L. catta is characterized by steep female dominance but shows female-female coalitionary support, we expected to confirm the presence of reconciliation in the study species. Consistently, we found reconciliation in one captive group and two wild groups, thus providing the first evidence of the presence of this phenomenon in wild L. catta. Moreover, because this species is a seasonal breeder (with mating occurring once a year, we expected seasonal fluctuations in reconciliation levels. Via a GLMM analysis using data from all wild groups and on a captive group followed for more than one year, we found that season (but not rank; individuals' identity, sex, and age; or group identity significantly affected individual reconciliation rates, and such rates were lowest during the mating period. Thus, reconciliation can be present in groups in which dominants strongly influence and limit social relationships (steep dominance hierarchy except when the advantages of intra-group cooperation are overcome by competition, as occurs in seasonal breeders when reproduction is at stake. We conclude

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

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Hanysova Sandra

2017-08-01

Full Text Available Objective: The aim of our study was to determine the relation of particular genetic variants in selected genes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1; rs10735781 EVI5 to the risk of multiple sclerosis (MS development and find out the possible association with disease disability progression rate. Material and methods: Our study included 202 MS patients and 174 healthy control volunteers. MS patients were divided according to disability progression rate to three groups - slowly progressing, mid-rate progressing and rapidly progressing. All DNA samples were isolated from venous blood. Genotyping was performed by PCR-RFLP and multiplex PCR. Results: Our analysis showed that GSTT1 null genotype (OR 0.56; 95%CI 0.33 -0.95; p=0.04 and GSTM1, GSTT1 double null genotype (OR 0.32; 95%CI 0.14 - 0.74; p=0.006 are potentially protective in relation to MS. We observed similar result in GSTT1 null genotype in association with mid-rate progression (OR 0.48; 95%CI 0.24 - 0.97; p=0.05. Frequency of GSTM1 and GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (OR 0.22; 95%CI 0.05 - 0.98; p=0.05 and middle (OR 0.33; 95%CI 0.11 - 0.99; p=0.045. We did not show any significant association of genetic changes rs1695 in GSTP1 and rs10735781 in EVI5 with MS or rate of disease progression. Conclusions: Genetic basis of multiple sclerosis is still not fully elucidated. Further research may clarify our results and confirm the value of studied factors for clinical practice.

Genetic evaluation with major genes and polygenic inheritance when some animals are not genotyped using gene content multiple-trait BLUP.

Science.gov (United States)

Legarra, Andrés; Vitezica, Zulma G

2015-11-17

In pedigreed populations with a major gene segregating for a quantitative trait, it is not clear how to use pedigree, genotype and phenotype information when some individuals are not genotyped. We propose to consider gene content at the major gene as a second trait correlated to the quantitative trait, in a gene content multiple-trait best linear unbiased prediction (GCMTBLUP) method. The genetic covariance between the trait and gene content at the major gene is a function of the substitution effect of the gene. This genetic covariance can be written in a multiple-trait form that accommodates any pattern of missing values for either genotype or phenotype data. Effects of major gene alleles and the genetic covariance between genotype at the major gene and the phenotype can be estimated using standard EM-REML or Gibbs sampling. Prediction of breeding values with genotypes at the major gene can use multiple-trait BLUP software. Major genes with more than two alleles can be considered by including negative covariances between gene contents at each different allele. We simulated two scenarios: a selected and an unselected trait with heritabilities of 0.05 and 0.5, respectively. In both cases, the major gene explained half the genetic variation. Competing methods used imputed gene contents derived by the method of Gengler et al. or by iterative peeling. Imputed gene contents, in contrast to GCMTBLUP, do not consider information on the quantitative trait for genotype prediction. GCMTBLUP gave unbiased estimates of the gene effect, in contrast to the other methods, with less bias and better or equal accuracy of prediction. GCMTBLUP improved estimation of genotypes in non-genotyped individuals, in particular if these individuals had own phenotype records and the trait had a high heritability. Ignoring the major gene in genetic evaluation led to serious biases and decreased prediction accuracy. CGMTBLUP is the best linear predictor of additive genetic merit including

CRISPR/Cas9 : A molecular Swiss army knife for simultaneous introduction of multiple genetic modifications in Saccharomyces cerevisiae

NARCIS (Netherlands)

Mans, R.; Van Rossum, H.M.; Wijsman, M.; Backx, A.; Kuijpers, N.G.A.; van den Broek, M.; Daran-Lapujade, P.A.S.; Pronk, J.T.; Van Maris, A.J.A.; Daran, J.G.

2015-01-01

A variety of techniques for strain engineering in Saccharomyces cerevisiae have recently been developed. However, especially when multiple genetic manipulations are required, strain construction is still a time-consuming process. This study describes new CRISPR/Cas9-based approaches for easy, fast

A history of conservation politics in Madagascar

African Journals Online (AJOL)

1984-04-03

Apr 3, 1984 ... MADAGASCAR CONSERVATION & DEVELOPMENT ... across multiple geographic and institutional sites. .... lected cases, I provide only general organizational associations for ... began studying ring-tailed lemurs in 1962, followed by Robert ...... Coordination issues in policy implementation networks: an.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

DEFF Research Database (Denmark)

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

2011-01-01

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...... underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working...

A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

KAUST Repository

Alsharoa, Ahmad M.

2013-09-01

In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward (AF) protocol are optimally selected to maximize the sum rate of the secondary users without degrading the Quality of Service (QoS) of the primary users by respecting a tolerated interference threshold. A strong optimization tool based on genetic algorithm is employed to solve our formulated optimization problem where discrete relay power levels are considered. Our simulation results show that the practical heuristic approach achieves almost the same performance of the optimal multiple relay selection scheme either with discrete or continuous power distributions. Copyright © 2013 by the Institute of Electrical and Electronic Engineers, Inc.

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

KAUST Repository

Abkallo, Hussein M.

2016-10-01

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

A rapid and efficient protocol for in vitro multiplication of genetically uniform Stevia rebaudiana (Bertoni).

Science.gov (United States)

Khan, A; Jayanthi, M; Gantasala, Nagavara Prasad; Bhooshan, N; Rao, Uma

2016-07-01

Stevia rebaudiana (Bertoni), commonly called candy leaf or sweet leaf, endemic to South America, is an important medicinal plant. As a source of low calorie natural sweetener 'stevoside', it is used in obesity, diabetes, treatment of heartburn and tooth decay, and also serves as a food supplement. Large scale commercial propagation of S. rebaudiana demands a suitable protocol. Here, we propose an improved protocol for in vitro multiplication of S. rebaudiana from nodal explants. In this protocol, the effect of laboratory grade urea on multiple shoot induction from nodal explants was studied. The nodal explants were initially cultured on Murashige and Skoog (MS) basal media for 2 weeks which facilitated the axillary bud break. Further, culturing of these explants on MS medium fortified with 6 benzyl amninopurine (BAP) (2 mg/L) and Naphthalene acetic acid (NAA) (1 mg/L) with and .without urea (5 mg/L) for a period of 40 days revealed maximum shoot production of 44.56 from a single nodal explant in media supplemented with urea as compared to 22.44 without urea. The differences in the number of shoots produced were significant and these shoots readily rooted in MS media with NAA (4 mg/L). Primary and secondary hardening was successful in these plants. There were no visible morphological abnormalities observed in the micropropagated plantlets. Genetic analysis from random samples also revealed that these plants are genetically uniform. The advantage of the present protocol is that the complete process of multiple shoot induction, rooting and hardening could be completed within a period of 6 months as compared to the existing protocols.

Complete restoration of multiple dystrophin isoforms in genetically corrected Duchenne muscular dystrophy patient–derived cardiomyocytes

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Susi Zatti

2014-01-01

Full Text Available Duchenne muscular dystrophy (DMD–associated cardiac diseases are emerging as a major cause of morbidity and mortality in DMD patients, and many therapies for treatment of skeletal muscle failed to improve cardiac function. The reprogramming of patients' somatic cells into pluripotent stem cells, combined with technologies for correcting the genetic defect, possesses great potential for the development of new treatments for genetic diseases. In this study, we obtained human cardiomyocytes from DMD patient–derived, induced pluripotent stem cells genetically corrected with a human artificial chromosome carrying the whole dystrophin genomic sequence. Stimulation by cytokines was combined with cell culturing on hydrogel with physiological stiffness, allowing an adhesion-dependent maturation and a proper dystrophin expression. The obtained cardiomyocytes showed remarkable sarcomeric organization of cardiac troponin T and α-actinin, expressed cardiac-specific markers, and displayed electrically induced calcium transients lasting less than 1 second. We demonstrated that the human artificial chromosome carrying the whole dystrophin genomic sequence is stably maintained throughout the cardiac differentiation process and that multiple promoters of the dystrophin gene are properly activated, driving expression of different isoforms. These dystrophic cardiomyocytes can be a valuable source for in vitro modeling of DMD-associated cardiac disease. Furthermore, the derivation of genetically corrected, patient-specific cardiomyocytes represents a step toward the development of innovative cell and gene therapy approaches for DMD.

Lemur Tyrosine Kinase-3 Suppresses Growth of Prostate Cancer Via the AKT and MAPK Signaling Pathways

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Pengcheng Sun

2017-08-01

Full Text Available Background/Aims: Lemur tyrosine kinase (LMTK-3 is a member of the receptor tyrosine kinase (RTK family. Abnormal expression of LMTK-3 exists in various types of cancers, especially in endocrine-resistant breast cancers; however, the precise level of expression and the biological function in prostate cancer are poorly understood. Methods: In the present study, we determined the expression of LMTK-3 in prostate cancer using immunohistochemistry and Western blotting. We infected PC3 and LNCaP cells with lentivirus-LMTK-3 and observed the biologic characteristics of the PC3 and LNCaP cells in vitro with TUNEL, and migration and invasion assays, respectively. We also established a transplant tumor model of human prostate cancer with infected cells in 15 BALB/c-nu/nu nude mice. Results: LMTK-3 was expressed in prostate epithelial cells. There was a significant decline in the level of LMTK-3 expression in prostate cancers compared to normal tissues. LMTK-3 inhibited PC3 and LNCaP cell growth, migration, and invasion, and induced cell apoptosis in vitro. We also observed that LMTK-3 induced PC3 cell apoptosis in vivo. Further study showed that LMTK-3 inhibited phosphorylation of AKT and ERK, and promoted phosphorylation and activation of p38 kinase and Jun kinase (JNK. Conclusion: Recombinant lentivirus with enhanced expression of LMTK-3 inhibited prostate cancer cell growth and induced apoptosis in vitro and in vivo. AKT and MAPK signaling pathways may contribute to the process.

Genetic diversity and differentiation patterns in Micromeria from the Canary Islands are congruent with multiple colonization dynamics and the establishment of species syngameons.

Science.gov (United States)

Curto, M; Puppo, P; Kratschmer, S; Meimberg, H

2017-08-22

Especially on islands closer to the mainland, such as the Canary Islands, different lineages that originated by multiple colonization events could have merged by hybridization, which then could have promoted radiation events (Herben et al., J Ecol 93: 572-575, 2005; Saunders and Gibson, J Ecol 93: 649-652, 2005; Caujapé-Castells, Jesters, red queens, boomerangs and surfers: a molecular outlook on the diversity of the Canarian endemic flora, 2011). This is an alternative to the scenario where evolution is mostly driven by drift (Silvertown, J Ecol 92: 168-173, 2004; Silvertown et al., J Ecol 93: 653-657, 2005). In the former case hybridization should be reflected in the genetic structure and diversity patterns of island species. In the present work we investigate Micromeria from the Canary Islands by extensively studying their phylogeographic pattern based on 15 microsatellite loci and 945 samples. These results are interpreted according to the hypotheses outlined above. Genetic structure assessment allowed us to genetically differentiate most Micromeria species and supported their current classification. We found that populations on younger islands were significantly more genetically diverse and less differentiated than those on older islands. Moreover, we found that genetic distance on younger islands was in accordance with an isolation-by-distance pattern, while on the older islands this was not the case. We also found evidence of introgression among species and islands. These results are congruent with a scenario of multiple colonizations during the expansion onto new islands. Hybridization contributes to the grouping of multiple lineages into highly diverse populations. Thus, in our case, islands receive several colonization events from different sources, which are combined into sink populations. This mechanism is in accordance with the surfing syngameon hypothesis. Contrary to the surfing syngameon current form, our results may reflect a slightly different

Mapping the social network: tracking lice in a wild primate (Microcebus rufus population to infer social contacts and vector potential

Directory of Open Access Journals (Sweden)

Zohdy Sarah

2012-03-01

Full Text Available Abstract Background Studies of host-parasite interactions have the potential to provide insights into the ecology of both organisms involved. We monitored the movement of sucking lice (Lemurpediculus verruculosus, parasites that require direct host-host contact to be transferred, in their host population of wild mouse lemurs (Microcebus rufus. These lemurs live in the rainforests of Madagascar, are small (40 g, arboreal, nocturnal, solitary foraging primates for which data on population-wide interactions are difficult to obtain. We developed a simple, cost effective method exploiting the intimate relationship between louse and lemur, whereby individual lice were marked, without removal from their host, with an individualized code, and tracked throughout the lemur population. We then tested the hypotheses that 1 the frequency of louse transfers, and thus interactions, would decrease with increasing distance between paired individual lemurs; 2 due to host polygynandry, social interactions and hence louse transfers would increase during the onset of the breeding season; and 3 individual mouse lemurs would vary in their contributions to the spread of lice. Results We show that louse transfers involved 43.75% of the studied lemur population, exclusively males. Louse transfers peaked during the breeding season, perhaps due to increased social interactions between lemurs. Although trap-based individual lemur ranging patterns are restricted, louse transfer rate does not correlate with the distance between lemur trapping locales, indicating wider host ranging behavior and a greater risk of rapid population-wide pathogen transmission than predicted by standard trapping data alone. Furthermore, relatively few lemur individuals contributed disproportionately to the rapid spread of lice throughout the population. Conclusions Using a simple method, we were able to visualize exchanges of lice in a population of cryptic wild primates. This method not only

Genetic variations in multiple myeloma II

DEFF Research Database (Denmark)

Vangsted, A.; Klausen, T.W.; Vogel, U.

2012-01-01

Association studies on genetic variation to treatment effect may serve as a predictive marker for effect of treatment and can also uncover biological pathways behind drug effect. Single-nucleotide polymorphisms (SNPs) have been studied in relation to high-dose treatment (HDT), thalidomide- and bo...

GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

Directory of Open Access Journals (Sweden)

Wang Kai

2011-05-01

Full Text Available Abstract Background Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs have multiple cores, whereas Graphics Processing Units (GPUs also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Findings Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1 the interaction of SNPs within it in parallel, and 2 the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. Conclusions GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.

Genetic differentiation across multiple spatial scales of the Red Sea of the corals Stylophora pistillata and Pocillopora verrucosa

KAUST Repository

Monroe, Alison

2015-12-01

Observing populations at different spatial scales gives greater insight into the specific processes driving genetic differentiation and population structure. Here we determined population connectivity across multiple spatial scales in the Red Sea to determine the population structures of two reef building corals Stylophora pistillata and Pocillopora verrucosa. The Red sea is a 2,250 km long body of water with extremely variable latitudinal environmental gradients. Mitochondrial and microsatellite markers were used to determine distinct lineages and to look for genetic differentiation among sampling sites. No distinctive population structure across the latitudinal gradient was discovered within this study suggesting a phenotypic plasticity of both these species to various environments. Stylophora pistillata displayed a heterogeneous distribution of three distinct genetic populations on both a fine and large scale. Fst, Gst, and Dest were all significant (p-value<0.05) and showed moderate genetic differentiation between all sampling sites. However this seems to be byproduct of the heterogeneous distribution, as no distinct genetic population breaks were found. Stylophora pistillata showed greater population structure on a fine scale suggesting genetic selection based on fine scale environmental variations. However, further environmental and oceanographic data is needed to make more inferences on this structure at small spatial scales. This study highlights the deficits of knowledge of both the Red Sea and coral plasticity in regards to local environmental conditions.

Common genetic variants in the 9p21 region and their associations with multiple tumours.

Science.gov (United States)

Gu, F; Pfeiffer, R M; Bhattacharjee, S; Han, S S; Taylor, P R; Berndt, S; Yang, H; Sigurdson, A J; Toro, J; Mirabello, L; Greene, M H; Freedman, N D; Abnet, C C; Dawsey, S M; Hu, N; Qiao, Y-L; Ding, T; Brenner, A V; Garcia-Closas, M; Hayes, R; Brinton, L A; Lissowska, J; Wentzensen, N; Kratz, C; Moore, L E; Ziegler, R G; Chow, W-H; Savage, S A; Burdette, L; Yeager, M; Chanock, S J; Chatterjee, N; Tucker, M A; Goldstein, A M; Yang, X R

2013-04-02

The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (PASSET (P=0.007). Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia.

Science.gov (United States)

Tang, Jinsong; Fan, Yu; Li, Hong; Xiang, Qun; Zhang, Deng-Feng; Li, Zongchang; He, Ying; Liao, Yanhui; Wang, Ya; He, Fan; Zhang, Fengyu; Shugart, Yin Yao; Liu, Chunyu; Tang, Yanqing; Chan, Raymond C K; Wang, Chuan-Yue; Yao, Yong-Gang; Chen, Xiaogang

2017-06-20

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.

A new world monkey microsatellite (ap74) highly conserved in primates

International Nuclear Information System (INIS)

Oklander, Luciana Ines; Steinberg, Eliana Ruth; Dolores Mudry, Marta

2012-01-01

Given their great variability, microsatellites or STRS became the most commonly used genetic markers over the last 15 years. The analysis of these markers requires minimum quantities of DNA, allowing the use of noninvasive samples, such as feces or hair. We amplified the microsatellite ap74 in blood and hair samples in order to analyze the levels of genomic conservation among a wide range of primates including: lemur catta, alouatta caraya, ateles belzebuth, ateles chamek, pan troglodytes, papio sp., and Homo sapiens. in all cases we obtained amplification products that exhibited similar size both in monkeys and human (oscillating between 126 and 176 bp), except in the lemur where the detected fragment presented a size of approximately 1000 bp. the analysis of the nucleotide sequences permitted the evaluation of the molecular modifications experienced during the evolutionary process in primates.

Could age modify the effect of genetic variants in IL6 and TNF-α genes in multiple myeloma?

Science.gov (United States)

Martino, Alessandro; Buda, Gabriele; Maggini, Valentina; Lapi, Francesco; Lupia, Antonella; Di Bello, Domenica; Orciuolo, Enrico; Galimberti, Sara; Barale, Roberto; Petrini, Mario; Rossi, Anna Maria

2012-05-01

Cytokines play a central role in multiple myeloma (MM) pathogenesis thus genetic variations within cytokines coding genes could influence MM susceptibility and therapy outcome. We investigated the impact of 8 SNPs in these genes in 202 MM cases and 235 controls also evaluating their impact on therapy outcome in a subset of 91 patients. Despite the overall negative findings, we found a significant age-modified effect of IL6 and TNF-α SNPs, on MM risk and therapy outcome, respectively. Therefore, this observation suggests that genetic variation in inflammation-related genes could be an important mediator of the complex interplay between ageing and cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

77 FR 38652 - Endangered Species; Receipt of Applications for Permit

Science.gov (United States)

2012-06-28

.... Species: Ring-tailed lemur (Lemur catta) Black and white ruffed lemur (Varecia variegata) Cottontop tamarin (Saguinus oedipus) Snow leopard (Uncia uncia) Amur leopard (Panthera pardus orientalis) Siberian tiger (Panthera tigris altaica) Golden parakeet (Guarouba guarouba) Hooded crane (Grus monacha) Jackass...

Predictive value of testing for multiple genetic variants in multifactorial diseases: implications for the discourse on ethical, legal and social issues

Directory of Open Access Journals (Sweden)

A. Cecile J.W. Janssens

2006-12-01

Full Text Available Multifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. Unraveling the genetic origins of these diseases is expected to lead to individualized medicine, in which the prevention and treatment strategies are personalized on the basis of the results of predictive genetic tests. This great optimism is counterbalanced by concerns about the ethical, legal, and social implications of genomic medicine, such as the protection of privacy and autonomy, stigmatization, discrimination, and the psychological burden of genetic testing. These concerns are translated from genetic testing in monogenic disorders, but this translation may not be appropriate. Multiple genetic testing (genomic profiling has essential differences from genetic testing in monogenic disorders. The differences lie in the lower predictive value of the test results, the pleiotropic effects of susceptibility genes, and the low inheritance of genomic profiles. For these reasons, genomic profiling may be more similar to nongenetic tests than to predictive tests for monogenic diseases. Therefore, ethical, legal, and social issues that apply to predictive genetic testing for monogenic diseases may not be relevant for the prediction of multifactorial disorders in genomic medicine.

[Future challenges in multiple sclerosis].

Science.gov (United States)

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

Science.gov (United States)

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

2013-09-01

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

Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

Science.gov (United States)

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.

Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

Science.gov (United States)

Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

2016-03-01

Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

Multiple-trait genetic evaluation using genomic matrix

African Journals Online (AJOL)

Jane

2011-07-06

Jul 6, 2011 ... relationships was estimated through computer simulation and was compared with the accuracy of ... programs, detect animals with superior genetic and select ... genomic matrices in the mixed model equations of BLUP.

The effect of supplementation with vitamin A on serum and liver concentrations in Puerto Rican crested toads (Peltophryne lemur) and its lack of impact on brown skin disease.

Science.gov (United States)

Dutton, Christopher; Lentini, Andrew; Berkvens, Charlene; Crawshaw, Graham

2014-01-01

"Brown skin disease" (BSD) is a clinical syndrome of dysecdysis, chronic weight loss and death, previously reported in Puerto Rican crested toads (Peltophryne lemur). Although vitamin A deficiency has been suggested, its cause remains unknown and multiple treatments have failed to prevent or reverse the condition. This study compared the efficacy of vitamin A supplementation, administered in different forms and by different routes, in 48 captive born Puerto Rican crested toads fed from metamorphosis on gut-loaded, dusted, commercially raised crickets. Forty-five toads started to show clinical signs of BSD at 9 months of age; all toads were treated orally with an oil-based vitamin A formulation twice weekly for 2 months but continued to deteriorate. Two treatment groups were then compared: Animals in one group (n=19) received 2 IU injectable vitamin A (Aquasol-A) per gram bodyweight subcutaneously twice weekly for 3 months with no change in diet. Toads in the other group (n=22) received a single oral dose of vitamins A, D3 , and E, and were fed on earthworms and crickets gut-loaded with produce and a finely-ground alfalfa-based pellet, dusted with the same vitamin/mineral supplement. All affected animals developed severe BSD equally and died during, or were euthanized at the end of, the treatment regimen, with no clinical improvement. Animals supplemented with Aquasol-A had significantly higher liver vitamin A concentrations compared with the other treatment group, whereas serum retinol concentrations showed no significant difference. Vitamin A supplementation does not appear a successful treatment once BSD symptoms have developed. © 2014 Wiley Periodicals, Inc.

The multiple genetic causes of central hypothyroidism.

Science.gov (United States)

Persani, Luca; Bonomi, Marco

2017-03-01

An insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland represents the cause of Central Hypothyrodism (CeH). CeH is about 1000-folds rarer than Primary Hypothyroidism and often represents a real challenge for the clinicians, mainly because they cannot rely on adequately sensitive parameters for diagnosis or management, as it occurs with circulating TSH in PH. Therefore, CeH diagnosis can be frequently missed or delayed in patients with a previously unknown pituitary involvement. A series of genetic defects have been described to account for isolated CeH or combined pituitary hormone defects (CPHDs) with variable clinical characteristics and degrees of severity. The recently identified candidate gene IGSF1 appears frequently involved. This review provides an updated illustration of the different genetic defects accounting for CeH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of genetic algorithm - multiple linear regressions to predict the activity of RSK inhibitors

Directory of Open Access Journals (Sweden)

Avval Zhila Mohajeri

2015-01-01

Full Text Available This paper deals with developing a linear quantitative structure-activity relationship (QSAR model for predicting the RSK inhibition activity of some new compounds. A dataset consisting of 62 pyrazino [1,2-α] indole, diazepino [1,2-α] indole, and imidazole derivatives with known inhibitory activities was used. Multiple linear regressions (MLR technique combined with the stepwise (SW and the genetic algorithm (GA methods as variable selection tools was employed. For more checking stability, robustness and predictability of the proposed models, internal and external validation techniques were used. Comparison of the results obtained, indicate that the GA-MLR model is superior to the SW-MLR model and that it isapplicable for designing novel RSK inhibitors.

BPA genetic monitoring - BPA Genetic Monitoring Project

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Initiated in 1989, this study monitors genetic changes associated with hatchery propagation in multiple Snake River sub-basins for Chinook salmon and steelhead. We...

Molecular evolution of avian reovirus: evidence for genetic diversity and reassortment of the S-class genome segments and multiple cocirculating lineages

International Nuclear Information System (INIS)

Liu, Hung J.; Lee, Long H.; Hsu, Hsiao W.; Kuo, Liam C.; Liao, Ming H.

2003-01-01

Nucleotide sequences of the S-class genome segments of 17 field-isolates and vaccine strains of avian reovirus (ARV) isolated over a 23-year period from different hosts, pathotypes, and geographic locations were examined and analyzed to define phylogenetic profiles and evolutionary mechanism. The S1 genome segment showed noticeably higher divergence than the other S-class genes. The σC-encoding gene has evolved into six distinct lineages. In contrast, the other S-class genes showed less divergence than that of the σC-encoding gene and have evolved into two to three major distinct lineages, respectively. Comparative sequence analysis provided evidence indicating extensive sequence divergence between ARV and other orthoreoviruses. The evolutionary trees of each gene were distinct, suggesting that these genes evolve in an independent manner. Furthermore, variable topologies were the result of frequent genetic reassortment among multiple cocirculating lineages. Results showed genetic diversity correlated more closely with date of isolation and geographic sites than with host species and pathotypes. This is the first evidence demonstrating genetic variability among circulating ARVs through a combination of evolutionary mechanisms involving multiple cocirculating lineages and genetic reassortment. The evolutionary rates and patterns of base substitutions were examined. The evolutionary rate for the σC-encoding gene and σC protein was higher than for the other S-class genes and other family of viruses. With the exception of the σC-encoding gene, which nonsynonymous substitutions predominate over synonymous, the evolutionary process of the other S-class genes can be explained by the neutral theory of molecular evolution. Results revealed that synonymous substitutions predominate over nonsynonymous in the S-class genes, even though genetic diversity and substitution rates vary among the viruses

Characterization of recombination features and the genetic basis in multiple cattle breeds.

Science.gov (United States)

Shen, Botong; Jiang, Jicai; Seroussi, Eyal; Liu, George E; Ma, Li

2018-04-27

Crossover generated by meiotic recombination is a fundamental event that facilitates meiosis and sexual reproduction. Comparative studies have shown wide variation in recombination rate among species, but the characterization of recombination features between cattle breeds has not yet been performed. Cattle populations in North America count millions, and the dairy industry has genotyped millions of individuals with pedigree information that provide a unique opportunity to study breed-level variations in recombination. Based on large pedigrees of Jersey, Ayrshire and Brown Swiss cattle with genotype data, we identified over 3.4 million maternal and paternal crossover events from 161,309 three-generation families. We constructed six breed- and sex-specific genome-wide recombination maps using 58,982 autosomal SNPs for two sexes in the three dairy cattle breeds. A comparative analysis of the six recombination maps revealed similar global recombination patterns between cattle breeds but with significant differences between sexes. We confirmed that male recombination map is 10% longer than the female map in all three cattle breeds, consistent with previously reported results in Holstein cattle. When comparing recombination hotspot regions between cattle breeds, we found that 30% and 10% of the hotspots were shared between breeds in males and females, respectively, with each breed exhibiting some breed-specific hotspots. Finally, our multiple-breed GWAS found that SNPs in eight loci affected recombination rate and that the PRDM9 gene associated with hotspot usage in multiple cattle breeds, indicating a shared genetic basis for recombination across dairy cattle breeds. Collectively, our results generated breed- and sex-specific recombination maps for multiple cattle breeds, provided a comprehensive characterization and comparison of recombination patterns between breeds, and expanded our understanding of the breed-level variations in recombination features within an

Preimplantation genetic diagnosis for Duchenne muscular dystrophy by multiple displacement amplification.

Science.gov (United States)

Ren, Zi; Zeng, Hai-tao; Xu, Yan-wen; Zhuang, Guang-lun; Deng, Jie; Zhang, Cheng; Zhou, Can-quan

2009-02-01

To evaluate the use of multiple displacement amplification (MDA) in preimplantation genetic diagnosis (PGD) for female carriers with Duchenne muscular dystrophy (DMD). MDA was used to amplify a whole genome of single cells. Following the setup on single cells, the test was applied in two clinical cases of PGD. One mutant exon, six short tandem repeats (STR) markers within the dystrophin gene, and amelogenin were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products of single blastomeres. Center for reproductive medicine in First Affiliated Hospital, Sun Yat-sen University, China. Two female carriers with a duplication of exons 3-11 and a deletion of exons 47-50, respectively. The MDA of single cells and fluorescent PCR assays for PGD. The ability to analyze single blastomeres for DMD using MDA. The protocol setup previously allowed for the accurate diagnosis of each embryo. Two clinical cases resulted in a healthy girl, which was the first successful clinical application of MDA in PGD for DMD. We suggest that this protocol is reliable to increase the accuracy of the PGD for DMD.

[Genetics and epigenetics in autism].

Science.gov (United States)

Nakayama, Atsuo; Masaki, Shiego; Aoki, Eiko

2006-11-01

Autism is a behaviorally defined syndrome characterized by impaired social interaction and communication, and restricted, stereotyped interests and behaviors. Several lines of evidence support the contention that genetic factors are a large component to autism etiology. However, in spite of vigorous genetic studies, no single causative or susceptibility gene common in autism has been identified. Thus multiple susceptibility genes in interaction are considered to account for the disorder. Furthermore, environmental risk factors can accelerate the autism development of. Recent advances in understanding the epigenetic regulation may shed light on the interaction among multiple genetic factors and environmental factors.

Genetic educational needs and the role of genetics in primary care: a focus group study with multiple perspectives

Directory of Open Access Journals (Sweden)

van der Vleuten Cees

2011-02-01

Full Text Available Abstract Background Available evidence suggests that improvements in genetics education are needed to prepare primary care providers for the impact of ongoing rapid advances in genomics. Postgraduate (physician training and master (midwifery training programmes in primary care and public health are failing to meet these perceived educational needs. The aim of this study was to explore the role of genetics in primary care (i.e. family medicine and midwifery care and the need for education in this area as perceived by primary care providers, patient advocacy groups and clinical genetics professionals. Methods Forty-four participants took part in three types of focus groups: mono-disciplinary groups of general practitioners and midwives, respectively and multidisciplinary groups composed of a diverse set of experts. The focus group sessions were audio-taped, transcribed verbatim and analysed using content analysis. Recurrent themes were identified. Results Four themes emerged regarding the educational needs and the role of genetics in primary care: (1 genetics knowledge, (2 family history, (3 ethical dilemmas and psychosocial effects in relation to genetics and (4 insight into the organisation and role of clinical genetics services. These themes reflect a shift in the role of genetics in primary care with implications for education. Although all focus group participants acknowledged the importance of genetics education, general practitioners felt this need more urgently than midwives and more strongly emphasized their perceived knowledge deficiencies. Conclusion The responsibilities of primary care providers with regard to genetics require further study. The results of this study will help to develop effective genetics education strategies to improve primary care providers' competencies in this area. More research into the educational priorities in genetics is needed to design courses that are suitable for postgraduate and master programmes for

Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters

Science.gov (United States)

Knopik, Valerie S.; Marceau, Kristine; Palmer, Rohan H. C.; Smith, Taylor F.; Heath, Andrew C.

2016-01-01

Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the fetus. There is considerable debate about the best method of assessing SDP, including birth/medical records, timeline follow-back approaches, multiple reporters, and biological verification (e.g., cotinine). This is particularly salient for genetically-informed approaches where it is not always possible or practical to do a prospective study starting during the prenatal period when concurrent biological specimen samples can be collected with ease. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we: (1) compare rates of agreement across different types of report—maternal report of SDP, paternal report of maternal SDP, and SDP contained on birth records from the Department of Vital Statistics; (2) examine whether SDP is predictive of birth weight outcomes using our best SDP report as identified via step (1); and (3) use a sibling-comparison approach that controls for genetic and familial influences that siblings share in order to assess the effects of SDP on birth weight. Results show high agreement between reporters and support the utility of retrospective report of SDP. Further, we replicate a causal association between SDP and birth weight, wherein SDP results in reduced birth weight even when accounting for genetic and familial confounding factors via a sibling comparison approach. PMID:26494459

A multiobjective non-dominated sorting genetic algorithm (NSGA-II for the Multiple Traveling Salesman Problem

Directory of Open Access Journals (Sweden)

Rubén Iván Bolaños

2015-06-01

Full Text Available This paper considers a multi-objective version of the Multiple Traveling Salesman Problem (MOmTSP. In particular, two objectives are considered: the minimization of the total traveled distance and the balance of the working times of the traveling salesmen. The problem is formulated as an integer multi-objective optimization model. A non-dominated sorting genetic algorithm (NSGA-II is proposed to solve the MOmTSP. The solution scheme allows one to find a set of ordered solutions in Pareto fronts by considering the concept of dominance. Tests on real world instances and instances adapted from the literature show the effectiveness of the proposed algorithm.

Extinction and ecological retreat in a community of primates

Energy Technology Data Exchange (ETDEWEB)

Crowley, B. E.; Godfrey, L. R.; Guilderson, T. P.; Zermeno, P.; Koch, P. L.; Dominy, N. J.

2012-05-23

The lemurs of Madagascar represent a prodigious adaptive radiation. At least 17 species ranging from 11 to 160 kg have become extinct during the past 2000 years. The effect of this loss on contemporary lemurs is unknown. The concept of competitive release favours the expansion of living species into vacant niches. Alternatively, factors that triggered the extinction of some species could have also reduced community-wide niche breadth. Here, we use radiocarbon and stable isotope data to examine temporal shifts in the niches of extant lemur species following the extinction of eight large-bodied species. We focus on southwestern Madagascar and report profound isotopic shifts, both from the time when now-extinct lemurs abounded and from the time immediately following their decline to the present. Unexpectedly, the past environments exploited by lemurs were drier than the protected (albeit often degraded) riparian habitats assumed to be ideal for lemurs today. Neither competitive release nor niche contraction can explain these observed trends. We develop an alternative hypothesis: ecological retreat, which suggests that factors surrounding extinction may force surviving species into marginal or previously unfilled niches.

Human genetics of infectious diseases: a unified theory

Science.gov (United States)

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

The genetic legacy of multiple beaver reintroductions in Central Europe.

Science.gov (United States)

Frosch, Christiane; Kraus, Robert H S; Angst, Christof; Allgöwer, Rainer; Michaux, Johan; Teubner, Jana; Nowak, Carsten

2014-01-01

The comeback of the Eurasian beaver (Castor fiber) throughout western and central Europe is considered a major conservation success. Traditionally, several subspecies are recognised by morphology and mitochondrial haplotype, each linked to a relict population. During various reintroduction programs in the 20th century, beavers from multiple source localities were released and now form viable populations. These programs differed in their reintroduction strategies, i.e., using pure subspecies vs. mixed source populations. This inhomogeneity in management actions generated ongoing debates regarding the origin of present beaver populations and appropriate management plans for the future. By sequencing of the mitochondrial control region and microsatellite genotyping of 235 beaver individuals from five selected regions in Germany, Switzerland, Luxembourg, and Belgium we show that beavers from at least four source origins currently form admixed, genetically diverse populations that spread across the study region. While regional occurrences of invasive North American beavers (n = 20) were found, all but one C. fiber bore the mitochondrial haplotype of the autochthonous western Evolutionary Significant Unit (ESU). Considering this, as well as the viability of admixed populations and the fact that the fusion of different lineages is already progressing in all studied regions, we argue that admixture between different beaver source populations should be generally accepted.

Class II HLA interactions modulate genetic risk for multiple sclerosis

Science.gov (United States)

Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru

Science.gov (United States)

Akinyi, Sheila; Hayden, Tonya; Gamboa, Dionicia; Torres, Katherine; Bendezu, Jorge; Abdallah, Joseph F.; Griffing, Sean M.; Quezada, Wilmer Marquiño; Arrospide, Nancy; De Oliveira, Alexandre Macedo; Lucas, Carmen; Magill, Alan J.; Bacon, David J.; Barnwell, John W.; Udhayakumar, Venkatachalam

2013-01-01

The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. PMID:24077522

Predictive value of testing for multiple genetic variants in multifactorial

NARCIS (Netherlands)

A.C.J.W. Janssens (Cécile); M.J. Khoury (Muin Joseph)

2009-01-01

textabstractMultifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. Unraveling the genetic origins of these diseases is

Genetics Home Reference: multiple epiphyseal dysplasia

Science.gov (United States)

... Hamel BC, Spranger J, Zabel B, Cohn DH, Cole WG, Hecht JT, Superti-Furga A. Recessive multiple ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

Defining conservation units in a stocking-induced genetic melting pot: unraveling native and multiple exotic genetic imprints of recent and historical secondary contact in Adriatic grayling.

Science.gov (United States)

Meraner, Andreas; Cornetti, Luca; Gandolfi, Andrea

2014-04-01

The definition of conservation units is crucial for the sustainable management of endangered species, though particularly challenging when recent and past anthropogenic and natural gene flow might have played a role. The conservation of the European grayling, Thymallus thymallus, is particularly complex in its southern distribution area, where the Adriatic evolutionary lineage is endangered by a long history of anthropogenic disturbance, intensive stocking and potentially widespread genetic introgression. We provide mtDNA sequence and microsatellite data of 683 grayling from 30 sites of Adriatic as well as Danubian and Atlantic origin. We apply Bayesian clustering and Approximate Bayesian Computation (ABC) to detect microgeographic population structure and to infer the demographic history of the Adriatic populations, to define appropriate conservation units. Varying frequencies of indigenous genetic signatures of the Adriatic grayling were revealed, spanning from marginal genetic introgression to the collapse of native gene pools. Genetic introgression involved multiple exotic source populations of Danubian and Atlantic origin, thus evidencing the negative impact of few decades of stocking. Within the Adige River system, a contact zone of western Adriatic and eastern Danubian populations was detected, with ABC analyses suggesting a historical anthropogenic origin of eastern Adige populations, most likely founded by medieval translocations. Substantial river-specific population substructure within the Adriatic grayling Evolutionary Significant Unit points to the definition of different conservation units. We finally propose a catalog of management measures, including the legal prohibition of stocking exotic grayling and the use of molecular markers in supportive- and captive-breeding programs.

Achondroplasia and multiple-suture craniosynostosis.

Science.gov (United States)

Albino, Frank P; Wood, Benjamin C; Oluigbo, Chima O; Lee, Angela C; Oh, Albert K; Rogers, Gary F

2015-01-01

Genetic mutations in the fibroblast growth factor receptor 3 gene may lead to achondroplasia or syndromic forms of craniosynostosis. Despite sharing a common genetic basis, craniosynostosis has rarely been described in cases of confirmed achondroplasia. We report an infant with achondroplasia who developed progressive multiple-suture craniosynostosis to discuss the genetic link between these clinical entities and to describe the technical challenges associated with the operative management.

Comprehensive genetic assessment of the human embryo: can empiric application of microarray comparative genomic hybridization reduce multiple gestation rate by single fresh blastocyst transfer?

Science.gov (United States)

Sills, Eric Scott; Yang, Zhihong; Walsh, David J; Salem, Shala A

2012-09-01

The unacceptable multiple gestation rate currently associated with in vitro fertilization (IVF) would be substantially alleviated if the routine practice of transferring more than one embryo were reconsidered. While transferring a single embryo is an effective method to reduce the clinical problem of multiple gestation, rigid adherence to this approach has been criticized for negatively impacting clinical pregnancy success in IVF. In general, single embryo transfer is viewed cautiously by IVF patients although greater acceptance would result from a more effective embryo selection method. Selection of one embryo for fresh transfer on the basis of chromosomal normalcy should achieve the dual objective of maintaining satisfactory clinical pregnancy rates and minimizing the multiple gestation problem, because embryo aneuploidy is a major contributing factor in implantation failure and miscarriage in IVF. The initial techniques for preimplantation genetic screening unfortunately lacked sufficient sensitivity and did not yield the expected results in IVF. However, newer molecular genetic methods could be incorporated with standard IVF to bring the goal of single embryo transfer within reach. Aiming to make multiple embryo transfers obsolete and unnecessary, and recognizing that array comparative genomic hybridization (aCGH) will typically require an additional 12 h of laboratory time to complete, we propose adopting aCGH for mainstream use in clinical IVF practice. As aCGH technology continues to develop and becomes increasingly available at lower cost, it may soon be considered unusual for IVF laboratories to select a single embryo for fresh transfer without regard to its chromosomal competency. In this report, we provide a rationale supporting aCGH as the preferred methodology to provide a comprehensive genetic assessment of the single embryo before fresh transfer in IVF. The logistics and cost of integrating aCGH with IVF to enable fresh embryo transfer are also

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

Institute of Scientific and Technical Information of China (English)

Jinsong Tang; Fan He; Fengyu Zhang; Yin Yao Shugart; Chunyu Liu; Yanqing Tang; Raymond C.K.Chan; Chuan-Yue Wang; Yong-Gang Yao; Xiaogang Chen; Yu Fan; Hong Li; Qun Xiang; Deng-Feng Zhang; Zongchang Li; Ying He; Yanhui Liao; Ya Wang

2017-01-01

Schizophrenia is a common disorder with a high heritability,but its genetic architecture is still elusive.We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia.Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins,which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN,p.S2506T mutation in GCN1L1,IVS3+1G ＞ T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis.By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes,we were able to distill genetic alterations in several schizophrenia risk genes,including GAD1,PLXNA2,RELN and FEZ1.Four inherited copy number variations (CNVs;including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families,respectively.Most of families carried both missense DNMs and inherited risk variants,which might suggest that DNMs,inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility.Our results support that schizophrenia is caused by a combination of multiple genetic factors,with each DNM/variant showing a relatively small effect size.

Multispecies genetic objectives in spatial conservation planning.

Science.gov (United States)

Nielsen, Erica S; Beger, Maria; Henriques, Romina; Selkoe, Kimberly A; von der Heyden, Sophie

2017-08-01

Growing threats to biodiversity and global alteration of habitats and species distributions make it increasingly necessary to consider evolutionary patterns in conservation decision making. Yet, there is no clear-cut guidance on how genetic features can be incorporated into conservation-planning processes, despite multiple molecular markers and several genetic metrics for each marker type to choose from. Genetic patterns differ between species, but the potential tradeoffs among genetic objectives for multiple species in conservation planning are currently understudied. We compared spatial conservation prioritizations derived from 2 metrics of genetic diversity (nucleotide and haplotype diversity) and 2 metrics of genetic isolation (private haplotypes and local genetic differentiation) in mitochondrial DNA of 5 marine species. We compared outcomes of conservation plans based only on habitat representation with plans based on genetic data and habitat representation. Fewer priority areas were selected for conservation plans based solely on habitat representation than on plans that included habitat and genetic data. All 4 genetic metrics selected approximately similar conservation-priority areas, which is likely a result of prioritizing genetic patterns across a genetically diverse array of species. Largely, our results suggest that multispecies genetic conservation objectives are vital to creating protected-area networks that appropriately preserve community-level evolutionary patterns. © 2016 Society for Conservation Biology.

Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

African Journals Online (AJOL)

Solaf M. Elsayed

2016-10-25

Oct 25, 2016 ... a Genetics Unit, Children's Hospital, Ain Shams University, Egypt b Neurology Department ... Through the past 6 months, she started to develop short term memory loss with intact long term memory. There was no other motor ...

Programme Sahamalaza-Iles Radama de l’AEECL : étude et conservation des espèces menacées d’extinction de lémuriens dans le nord-ouest de Madagascar AEECL’s Sahamalaza-Iles Radama Program: study and conservation of threatened species of lemurs in north-west of Madagascar.

Directory of Open Access Journals (Sweden)

Alice Dumoulin

2011-10-01

Full Text Available L’AEECL, Association Européenne pour l’Etude et la Conservation des Lémuriens, est un consortium de parcs zoologiques et d’universités européennes mettant en commun leurs connaissances et leurs efforts en faveur de projets de recherche et de protection des lémuriens menacés d’extinction de Madagascar depuis plus de trente ans. Pour ce faire, l’AEECL mène ou finance des études afin d’améliorer les connaissances scientifiques concernant les lémuriens. Ces informations sont indispensables pour mettre en place les mesures concrètes adaptées pour protéger ces animaux. Ses travaux ont notamment aidé à la reconnaissance de la péninsule de Sahamalaza en tant que réserve de biosphère de l’UNESCO, en 2001 et à la création du parc national Sahamalaza-Iles Radama, en 2007, principal site de recherches menées par l’association. De plus l’AEECL met un point d’honneur à impliquer la population locale. Des associations communautaires locales ont été créées dans les villages de quatre communes. Elles ont le pouvoir de gérer les ressources naturelles de leur juridiction de façon durable.The European Association for the Study and Conservation of Lemurs (Association Européenne pour l’Etude et la Conservation des Lémuriens, AEECL is a consortium of European zoological gardens and universities who have joined forces to carry out conservation and research projects for Madagascar’s highly endangered lemurs since more than 30 years. AEECL implements or finances various different research projects to improve the scientific knowledge of lemurs. Information is essential to be able to develop comprehensive conservation and management plans to protect these animals. The work of AEECL has led to the implementation of a UNESCO Biosphere Reserve in Sahamalaza in 2001 and to the creation of the Sahamalaza-Iles Radama National Park in 2007. In addition to the research, AEECL is carrying out a community-based natural resource

Use of multiple-trait animal models for genetic evaluation of milk, fat and protein lactation yields of dairy cattle in Belgium

Directory of Open Access Journals (Sweden)

Pierre Coenraets

1997-01-01

Full Text Available Comparison of computation time between single-trait and multiple-trait evaluations showed that with the use of the canonicat transformation associated with multiple diagonalization of (covariance matrices, multiple-trait analysis for milk, fat and protein yields is not more expensive than three single-trait analyzes. Rank correlations between breeding values for 54,820 cows with records (for their 1,406 sires estimated with the single-trait and multiple-trait models were over .98 (.99 in fat yield and over .99 (.99 in milk and protein yields. The relative gain expressed as reduction in mean prediction error variance was 3% (1% in milk yield, 6% (3% in fat yield, and .4% (.2% in protein yield for cows (for sires. Relative genetic gains were 3% (1%, 6% (2% and .5% (.2% respectively in milk, fat and protein yields for cows (for sires. The use of multiple-trait models bas therefore the advantages of improved precision and reduced selection bics. Multiple-trait analysis could be extended for the analyzes of test-day records. Results show that this or similar multiple-trait animal model could be implemented immediately in Belgium at low computing cost, using the proposed algorithme and could be the first step to new, more advanced evaluation methods.

Genetic complexity and multiple infections with more Parvovirus species in naturally infected cats

Directory of Open Access Journals (Sweden)

Battilani Mara

2011-03-01

Full Text Available Abstract Parvoviruses of carnivores include three closely related autonomous parvoviruses: canine parvovirus (CPV, feline panleukopenia virus (FPV and mink enteritis virus (MEV. These viruses cause a variety of serious diseases, especially in young patients, since they have a remarkable predilection for replication in rapidly dividing cells. FPV is not the only parvovirus species which infects cats; in addition to MEV, the new variants of canine parvovirus, CPV-2a, 2b and 2c have also penetrated the feline host-range, and they are able to infect and replicate in cats, causing diseases indistinguishable from feline panleukopenia. Furthermore, as cats are susceptible to both CPV-2 and FPV viruses, superinfection and co-infection with multiple parvovirus strains may occur, potentially facilitating recombination and high genetic heterogeneity. In the light of the importance of cats as a potential source of genetic diversity for parvoviruses and, since feline panleukopenia virus has re-emerged as a major cause of mortality in felines, the present study has explored the molecular characteristics of parvovirus strains circulating in cat populations. The most significant findings reported in this study were (a the detection of mixed infection FPV/CPV with the presence of one parvovirus variant which is a true intermediate between FPV/CPV and (b the quasispecies cloud size of one CPV sample variant 2c. In conclusion, this study provides new important results about the evolutionary dynamics of CPV infections in cats, showing that CPV has presumably started a new process of readaptation in feline hosts.

The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks

Science.gov (United States)

2012-01-01

Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes is emerging from genome-wide association studies and work on genetically tractable model organisms. PMID:22348705

A Genetic Epidemiological Study of Behavioral Traits

NARCIS (Netherlands)

N. Amin (Najaf)

2011-01-01

textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to

Genetic counseling and testing for gynecological cancers ...

African Journals Online (AJOL)

undergraduates of universities in Ibadan to genetic counseling and testing (GCT) for ... questionnaire, information on their understanding of GCT, perception of implications, and ... by genetic counseling from suitably trained health-care providers and genetic testing of selected high-risk individuals ..... Multiple sexual partners.

Optimal planning approaches with multiple impulses for rendezvous based on hybrid genetic algorithm and control method

Directory of Open Access Journals (Sweden)

JingRui Zhang

2015-03-01

Full Text Available In this article, we focus on safe and effective completion of a rendezvous and docking task by looking at planning approaches and control with fuel-optimal rendezvous for a target spacecraft running on a near-circular reference orbit. A variety of existent practical path constraints are considered, including the constraints of field of view, impulses, and passive safety. A rendezvous approach is calculated by using a hybrid genetic algorithm with those constraints. Furthermore, a control method of trajectory tracking is adopted to overcome the external disturbances. Based on Clohessy–Wiltshire equations, we first construct the mathematical model of optimal planning approaches of multiple impulses with path constraints. Second, we introduce the principle of hybrid genetic algorithm with both stronger global searching ability and local searching ability. We additionally explain the application of this algorithm in the problem of trajectory planning. Then, we give three-impulse simulation examples to acquire an optimal rendezvous trajectory with the path constraints presented in this article. The effectiveness and applicability of the tracking control method are verified with the optimal trajectory above as control objective through the numerical simulation.

One Novel Multiple-Target Plasmid Reference Molecule Targeting Eight Genetically Modified Canola Events for Genetically Modified Canola Detection.

Science.gov (United States)

Li, Zhuqing; Li, Xiang; Wang, Canhua; Song, Guiwen; Pi, Liqun; Zheng, Lan; Zhang, Dabing; Yang, Litao

2017-09-27

Multiple-target plasmid DNA reference materials have been generated and utilized as good substitutes of matrix-based reference materials in the analysis of genetically modified organisms (GMOs). Herein, we report the construction of one multiple-target plasmid reference molecule, pCAN, which harbors eight GM canola event-specific sequences (RF1, RF2, MS1, MS8, Topas 19/2, Oxy235, RT73, and T45) and a partial sequence of the canola endogenous reference gene PEP. The applicability of this plasmid reference material in qualitative and quantitative PCR assays of the eight GM canola events was evaluated, including the analysis of specificity, limit of detection (LOD), limit of quantification (LOQ), and performance of pCAN in the analysis of various canola samples, etc. The LODs are 15 copies for RF2, MS1, and RT73 assays using pCAN as the calibrator and 10 genome copies for the other events. The LOQ in each event-specific real-time PCR assay is 20 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and PEP assays are between 91% and 97%, and the squared regression coefficients (R 2 ) are all higher than 0.99. The quantification bias values varied from 0.47% to 20.68% with relative standard deviation (RSD) from 1.06% to 24.61% in the quantification of simulated samples. Furthermore, 10 practical canola samples sampled from imported shipments in the port of Shanghai, China, were analyzed employing pCAN as the calibrator, and the results were comparable with those assays using commercial certified materials as the calibrator. Concluding from these results, we believe that this newly developed pCAN plasmid is one good candidate for being a plasmid DNA reference material in the detection and quantification of the eight GM canola events in routine analysis.

Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages.

Science.gov (United States)

Peterman, William; Brocato, Emily R; Semlitsch, Raymond D; Eggert, Lori S

2016-01-01

In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (F ST and D C ) and isolation-by-distance (IBD) among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using D C , the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis.

Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages

Directory of Open Access Journals (Sweden)

William Peterman

2016-03-01

Full Text Available In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (FST and DC and isolation-by-distance (IBD among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using DC, the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis.

Visual detection of multiple genetically modified organisms in a capillary array.

Science.gov (United States)

Shao, Ning; Chen, Jianwei; Hu, Jiaying; Li, Rong; Zhang, Dabing; Guo, Shujuan; Hui, Junhou; Liu, Peng; Yang, Litao; Tao, Sheng-Ce

2017-01-31

There is an urgent need for rapid, low-cost multiplex methodologies for the monitoring of genetically modified organisms (GMOs). Here, we report a C[combining low line]apillary A[combining low line]rray-based L[combining low line]oop-mediated isothermal amplification for M[combining low line]ultiplex visual detection of nucleic acids (CALM) platform for the simple and rapid monitoring of GMOs. In CALM, loop-mediated isothermal amplification (LAMP) primer sets are pre-fixed to the inner surface of capillaries. The surface of the capillary array is hydrophobic while the capillaries are hydrophilic, enabling the simultaneous loading and separation of the LAMP reaction mixtures into each capillary by capillary forces. LAMP reactions in the capillaries are then performed in parallel, and the results are visually detected by illumination with a hand-held UV device. Using CALM, we successfully detected seven frequently used transgenic genes/elements and five plant endogenous reference genes with high specificity and sensitivity. Moreover, we found that measurements of real-world blind samples by CALM are consistent with results obtained by independent real-time PCRs. Thus, with an ability to detect multiple nucleic acids in a single easy-to-operate test, we believe that CALM will become a widely applied technology in GMO monitoring.

Signal Timing Optimization for Corridors with Multiple Highway-Rail Grade Crossings Using Genetic Algorithm

Directory of Open Access Journals (Sweden)

Yifeng Chen

2018-01-01

Full Text Available Safety and efficiency are two critical issues at highway-rail grade crossings (HRGCs and their nearby intersections. Standard traffic signal optimization programs are not designed to work on roadway networks that contain multiple HRGCs, because their underlying assumption is that the roadway traffic is in a steady-state. During a train event, steady-state conditions do not occur. This is particularly true for corridors that experience high train traffic (e.g., over 2 trains per hour. In this situation, the non-steady-state conditions predominate. This paper develops a simulation-based methodology for optimizing traffic signal timing plan on corridors of this kind. The primary goal is to maximize safety, and the secondary goal is to minimize delay. A Genetic Algorithm (GA was used as the optimization approach in the proposed methodology. A new transition preemption strategy for dual tracks (TPS_DT and a train arrival prediction model were integrated in the proposed methodology. An urban road network with multiple HRGCs in Lincoln, NE, was used as the study network. The microsimulation model VISSIM was used for evaluation purposes and was calibrated to local traffic conditions. A sensitivity analysis with different train traffic scenarios was conducted. It was concluded that the methodology can significantly improve both the safety and efficiency of traffic corridors with HRGCs.

Predictability of Genetic Interactions from Functional Gene Modules

Directory of Open Access Journals (Sweden)

Jonathan H. Young

2017-02-01

Full Text Available Characterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets, yet experimentally determining whether genes interact is technically nontrivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.

Producing genetic knowledge and citizenship through the Internet: mothers, pediatric genetics, and cybermedicine.

Science.gov (United States)

Schaffer, Rebecca; Kuczynski, Kristine; Skinner, Debra

2008-01-01

This article analyses data from a longitudinal, ethnographic study conducted in the United States to examine how 100 mothers of children with genetic disorders used the Internet to interpret, produce, and circulate genetic knowledge pertaining to their child's condition. We describe how they came to value their own experiential knowledge, helped shift the boundaries of what counts as authoritative knowledge, and assumed the role of genetic citizen, fighting for specific rights while shouldering and contesting concomitant duties and obligations. This exploration of e-health use contributes to our understanding of the social practices and power relations that cut across online and off-line worlds to co-produce genetic knowledge and genetic citizenship in multiple contexts.

Sequential interactions of silver-silica nanocomposite (Ag-SiO2 NC) with cell wall, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple antibiotic-resistant bacterium

Digital Repository Service at National Institute of Oceanography (India)

Anas, A.; Jiya, J.; Rameez, M.J.; Anand, P.B.; Anantharaman, M.R.; Nair, S.

The study was carried out to understand the effect of silver–silica nanocomposite (Ag-SiO sub(2)NC) on the cell wall integrity, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple drug-resistant bacterium. Bacterial sensitivity...

Sequential interactions of silver-silica nanocomposite (Ag-SiO2NC) with cell wall, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple antibiotic-resistant bacterium

Digital Repository Service at National Institute of Oceanography (India)

Anas, A.; Jiya, J.; Rameez, M.J.; Anand, P.B.; Anantharaman, M.R.; Nair, S.

The study was carried out to understand the effect of silver-silica nanocomposite (Ag-SiO sub(2)NC) on the cell wall integrity, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple drug-resistant bacterium Bacterial sensitivity...

TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis

DEFF Research Database (Denmark)

Gregory, Adam P; Dendrou, Calliope A; Attfield, Kathrine E

2012-01-01

), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further...... make to disease risk has raised questions regarding their medical relevance. Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS...... substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases...

Beyond clinical utility: The multiple values of DTC genetics

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Mauro Turrini

2016-03-01

Full Text Available One point of consensus in the otherwise very controversial discussion about the benefits and dangers of DTC genetics in the health domain is the lack of substantial clinical utility. At the same time, both the empirical and conceptual literature indicate that health-related DTC tests can have value and utility outside of the clinic. We argue that a broader and multi-faceted conceptualization of utility and value would enrich the ethical and social discussion of DTC testing in several ways: First, looking at ways in which DTC testing can have personal and social value for users – in the form of entertainment, learning, or a way to relate to others – can help to explain why people still take DTC tests, and will, further down the line, foster a more nuanced understanding of secondary and tertiary uses of DTC test results (which could very well unearth new ethical and regulatory challenges. Second, considering the economic value and broader utility of DTC testing foregrounds wider social and political aspects than have been dominant in the ethical and regulatory debates surrounding DTC genetics so far. These wider political aspects include the profound power asymmetries that characterize the collection and use of personal genetic data in many contexts.

Convenience polyandry or convenience polygyny? Costly sex under female control in a promiscuous primate.

Science.gov (United States)

Huchard, Elise; Canale, Cindy I; Le Gros, Chloé; Perret, Martine; Henry, Pierre-Yves; Kappeler, Peter M

2012-04-07

Classic sex roles depict females as choosy, but polyandry is widespread. Empirical attempts to understand the evolution of polyandry have often focused on its adaptive value to females, whereas 'convenience polyandry' might simply decrease the costs of sexual harassment. We tested whether constraint-free female strategies favour promiscuity over mating selectivity through an original experimental design. We investigated variation in mating behaviour in response to a reversible alteration of sexual dimorphism in body mass in the grey mouse lemur, a small primate where female brief sexual receptivity allows quantifying polyandry. We manipulated body condition in captive females, predicting that convenience polyandry would increase when females are weaker than males, thus less likely to resist their solicitations. Our results rather support the alternative hypothesis of 'adaptive polyandry': females in better condition are more polyandrous. Furthermore, we reveal that multiple mating incurs significant energetic costs, which are strikingly symmetrical between the sexes. Our study shows that mouse lemur females exert tight control over mating and actively seek multiple mates. The benefits of remating are nevertheless not offset by its costs in low-condition females, suggesting that polyandry is a flexible strategy yielding moderate fitness benefits in this small mammal.

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

NARCIS (Netherlands)

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

Les activités de conservation des lémuriens par le Groupe d’Etude et de Recherche sur les Primates de Madagascar (GERP Conservation activities of lemurs by the Madagascar Primate Research Group (GERP- Groupe d’Etude et de Recherche sur les Primates de Madagascar

Directory of Open Access Journals (Sweden)

Rose Marie Randrianarison

2011-10-01

prosimian primates of Madagascar, the development of action plans for their conservation, the discovery of new species, the translocation of lemurs living in deforested or threatened habitats, the abundance estimates and the revision of area distributions and the publication of results research in national and international scientific journals. In fact, capacity building of local community associations and primary and higher education systems concerning lemur conservation linked to aiding the sustainable development of local communities, it seems necessary, so that the lemur conservation will be lasting.

Invasion genetics of a freshwater mussel (Dreissena rostriformis bugensis) in eastern Europe: high gene flow and multiple introductions.

Science.gov (United States)

Therriault, T W; Orlova, M I; Docker, M F; Macisaac, H J; Heath, D D

2005-07-01

In recent years, the quagga mussel, Dreissena rostriformis bugensis, native to the Dnieper and Bug Limans of the northern Black Sea, has been dispersed by human activities across the basin, throughout much of the Volga River system, and to the Laurentian Great Lakes. We used six published microsatellite markers to survey populations throughout its native and introduced range to identify relationships among potential source populations and introduced ones. Mussels from 12 sites in Eurasia, including the central Caspian Sea and one in North America (Lake Erie), were sampled. Field surveys in the Volga River basin suggested that the species first colonized the middle reach of the river near Kubyshev Reservoir, and thereafter spread both upstream and downstream. Evidence of considerable gene flow among populations was observed and genetic diversity was consistent with a larger, metapopulation that has not experienced bottlenecks or founder effects. We propose that high gene flow, possibly due to multiple invasions, has facilitated establishment of quagga mussel populations in the Volga River system. The Caspian Sea population (D. rostriformis rostriformis (=distincta)) was genetically more distinct than other populations, a finding that may be related to habitat differences. The geographical pattern of genetic divergence is not characteristic of isolation-by-distance but, rather, of long-distance dispersal, most likely mediated by commercial ships' ballast water transfer.

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics.

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Jill A Hollenbach

Full Text Available We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752 from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs, and the human leukocyte antigen (HLA genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents' information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

Science.gov (United States)

Hollenbach, Jill A.; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J.; Maiers, Martin

2015-01-01

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals. PMID:26287376

Multiple surveys employing a new sample-processing protocol reveal the genetic diversity of placozoans in Japan.

Science.gov (United States)

Miyazawa, Hideyuki; Nakano, Hiroaki

2018-03-01

Placozoans, flat free-living marine invertebrates, possess an extremely simple bauplan lacking neurons and muscle cells and represent one of the earliest-branching metazoan phyla. They are widely distributed from temperate to tropical oceans. Based on mitochondrial 16S rRNA sequences, 19 haplotypes forming seven distinct clades have been reported in placozoans to date. In Japan, placozoans have been found at nine locations, but 16S genotyping has been performed at only two of these locations. Here, we propose a new processing protocol, "ethanol-treated substrate sampling," for collecting placozoans from natural environments. We also report the collection of placozoans from three new locations, the islands of Shikine-jima, Chichi-jima, and Haha-jima, and we present the distribution of the 16S haplotypes of placozoans in Japan. Multiple surveys conducted at multiple locations yielded five haplotypes that were not reported previously, revealing high genetic diversity in Japan, especially at Shimoda and Shikine-jima Island. The observed geographic distribution patterns were different among haplotypes; some were widely distributed, while others were sampled only from a single location. However, samplings conducted on different dates at the same sites yielded different haplotypes, suggesting that placozoans of a given haplotype do not inhabit the same site constantly throughout the year. Continued sampling efforts conducted during all seasons at multiple locations worldwide and the development of molecular markers within the haplotypes are needed to reveal the geographic distribution pattern and dispersal history of placozoans in greater detail.

Precise localization of multiple epiphyseal dysplasia and pseudoachondroplasia mutations by genetic and physical mapping of chromosome 19

Energy Technology Data Exchange (ETDEWEB)

Knowlton, R.G.; Cekleniak, J.A. [Jefferson Medical College, Philadelphia, PA (United States); Cohn, D.H. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others

1994-09-01

Multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia resulting in peripheral joint deformities and premature osteoarthritis, and pseudoachondroplasia (PSACH), a more severe disorder associated with short-limbed dwarfism, have recently been mapped to the pericentromeric region of chromosome 19. Chondrocytes from some PSACH patients accumulate lamellar deposits in the endoplasmic reticulum that are immunologically cross-reactive with aggrecan. However, neither aggrecan nor any known candidate gene maps to the EDM1/PSACH region of chromosome 19. Genetic linkage mapping in two lage families had placed the disease locus between D19S215 (19p12) and D19S212 (19p13.1), an interval of about 3.5 Mb. With at least five potentially informative cross-overs within this interval, recombination mapping at greater resolution was undertaken. From cosmids assigned to the region by fluorescence in situ hybridization and contig assembly, dinucleotide repeat tracts were identified for use as polymorphic genetic markers. Linkage data from three new dinucleotide repeat markers from cosmids mapped between D19S212 and D19S215 limit the EDM1/PSACH locus to an interval spanning approximately 2 Mb.

Update on Sporadic Colorectal Cancer Genetics.

Science.gov (United States)

Hardiman, Karin M

2018-05-01

Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

Climate change and human colonization triggered habitat loss and fragmentation in Madagascar.

Science.gov (United States)

Salmona, Jordi; Heller, Rasmus; Quéméré, Erwan; Chikhi, Lounès

2017-10-01

The relative effect of past climate fluctuations and anthropogenic activities on current biome distribution is subject to increasing attention, notably in biodiversity hot spots. In Madagascar, where humans arrived in the last ~4 to 5,000 years, the exact causes of the demise of large vertebrates that cohabited with humans are yet unclear. The prevailing narrative holds that Madagascar was covered with forest before human arrival and that the expansion of grasslands was the result of human-driven deforestation. However, recent studies have shown that vegetation and fauna structure substantially fluctuated during the Holocene. Here, we study the Holocene history of habitat fragmentation in the north of Madagascar using a population genetics approach. To do so, we infer the demographic history of two northern Madagascar neighbouring, congeneric and critically endangered forest dwelling lemur species-Propithecus tattersalli and Propithecus perrieri-using population genetic analyses. Our results highlight the necessity to consider population structure and changes in connectivity in demographic history inferences. We show that both species underwent demographic fluctuations which most likely occurred after the mid-Holocene transition. While mid-Holocene climate change probably triggered major demographic changes in the two lemur species range and connectivity, human settlements that expanded over the last four millennia in northern Madagascar likely played a role in the loss and fragmentation of the forest cover. © 2017 John Wiley & Sons Ltd.

Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

Science.gov (United States)

Sadovnick, A. Dessa; Traboulsee, Anthony L.; Bernales, Cecily Q.; Ross, Jay P.; Forwell, Amanda L.; Yee, Irene M.; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A.; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T.; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K.; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M.; García-Martínez, Angel; Villar, Luisa M.; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C.; Zimprich, Alexander; Vilariño-Güell, Carles

2016-01-01

Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID:27194806

Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

Directory of Open Access Journals (Sweden)

A. Dessa Sadovnick

2016-07-01

Full Text Available Multiple sclerosis (MS is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D in plasminogen (PLG as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351 in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117, despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87. To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.

Genetics Home Reference: esophageal atresia/tracheoesophageal fistula

Science.gov (United States)

... are some genetic conditions more common in particular ethnic groups? Genetic Changes Isolated EA/TEF is considered to be a multifactorial condition, which means that multiple gene variations and environmental factors likely contribute to its occurrence. ...

Schedule Optimization of Imaging Missions for Multiple Satellites and Ground Stations Using Genetic Algorithm

Science.gov (United States)

Lee, Junghyun; Kim, Heewon; Chung, Hyun; Kim, Haedong; Choi, Sujin; Jung, Okchul; Chung, Daewon; Ko, Kwanghee

2018-04-01

In this paper, we propose a method that uses a genetic algorithm for the dynamic schedule optimization of imaging missions for multiple satellites and ground systems. In particular, the visibility conflicts of communication and mission operation using satellite resources (electric power and onboard memory) are integrated in sequence. Resource consumption and restoration are considered in the optimization process. Image acquisition is an essential part of satellite missions and is performed via a series of subtasks such as command uplink, image capturing, image storing, and image downlink. An objective function for optimization is designed to maximize the usability by considering the following components: user-assigned priority, resource consumption, and image-acquisition time. For the simulation, a series of hypothetical imaging missions are allocated to a multi-satellite control system comprising five satellites and three ground stations having S- and X-band antennas. To demonstrate the performance of the proposed method, simulations are performed via three operation modes: general, commercial, and tactical.

Multiple system atrophy: genetic risks and alpha-synuclein mutations [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Heather T Whittaker

2017-11-01

Full Text Available Multiple system atrophy (MSA is one of the few neurodegenerative disorders where we have a significant understanding of the clinical and pathological manifestations but where the aetiology remains almost completely unknown. Research to overcome this hurdle is gaining momentum through international research collaboration and a series of genetic and molecular discoveries in the last few years, which have advanced our knowledge of this rare synucleinopathy. In MSA, the discovery of α-synuclein pathology and glial cytoplasmic inclusions remain the most significant findings. Families with certain types of α-synuclein mutations develop diseases that mimic MSA, and the spectrum of clinical and pathological features in these families suggests a spectrum of severity, from late-onset Parkinson’s disease to MSA. Nonetheless, controversies persist, such as the role of common α-synuclein variants in MSA and whether this disorder shares a common mechanism of spreading pathology with other protein misfolding neurodegenerative diseases. Here, we review these issues, specifically focusing on α-synuclein mutations.

[Current description of multiple sclerosis].

Science.gov (United States)

Río, Jordi; Montalbán, Xavier

2014-12-01

Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Primate Torpor: Regulation of Stress-activated Protein Kinases During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus

Directory of Open Access Journals (Sweden)

Kyle K. Biggar

2015-04-01

Full Text Available Very few selected species of primates are known to be capable of entering torpor. This exciting discovery means that the ability to enter a natural state of dormancy is an ancestral trait among primates and, in phylogenetic terms, is very close to the human lineage. To explore the regulatory mechanisms that underlie primate torpor, we analyzed signal transduction cascades to discover those involved in coordinating tissue responses during torpor. The responses of mitogen-activated protein kinase (MAPK family members to primate torpor were compared in six organs of control (aroused versus torpid gray mouse lemurs, Microcebus murinus. The proteins examined include extracellular signal-regulated kinases (ERKs, c-jun NH2-terminal kinases (JNKs, MAPK kinase (MEK, and p38, in addition to stress-related proteins p53 and heat shock protein 27 (HSP27. The activation of specific MAPK signal transduction pathways may provide a mechanism to regulate the expression of torpor-responsive genes or the regulation of selected downstream cellular processes. In response to torpor, each MAPK subfamily responded differently during torpor and each showed organ-specific patterns of response. For example, skeletal muscle displayed elevated relative phosphorylation of ERK1/2 during torpor. Interestingly, adipose tissues showed the highest degree of MAPK activation. Brown adipose tissue displayed an activation of ERK1/2 and p38, whereas white adipose tissue showed activation of ERK1/2, p38, MEK, and JNK during torpor. Importantly, both adipose tissues possess specialized functions that are critical for torpor, with brown adipose required for non-shivering thermogenesis and white adipose utilized as the primary source of lipid fuel for torpor. Overall, these data indicate crucial roles of MAPKs in the regulation of primate organs during torpor.

Genetic variants influencing phenotypic variance heterogeneity.

Science.gov (United States)

Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

2018-03-01

Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

Genetic and demographic responses of mosquitofish (Gambusia holbrooki) populations exposed to mercury for multiple generations

Energy Technology Data Exchange (ETDEWEB)

Tatara, C.P.; Mulvey, M.; Newman, M.C.

1999-12-01

Genetic and demographic responses of mosquitofish were examined after multiple generations of exposure to mercury. Previous studies of acute lethal exposures of mosquitofish to either mercury or arsenic demonstrated a consistent correlation between time to death and genotype at the glucosephosphate isomerase-2 (Gpi-2) locus. A mesocosm study involving mosquitofish populations exposed to mercury for 111 d showed significant female sexual selection and fecundity selection at the Gpi-2 locus. Here the mesocosm study was extended to populations exposed to mercury for several (approx. four) generations. After 2 years, control and mercury-exposed populations met Hardy-Weinberg expectations and showed no evidence of genetic bottlenecks. The mean number of heterozygous loci did not differ significantly between the mercury-exposed and control populations. Significant differences in allele frequencies at the Gpi-2 locus were observed between the mercury-exposed and control populations. Relative to the initial and control allele frequencies, the GPI-2{sup 100} allele frequency was lower, the Gpi-2{sup 66} allele frequency increased, but the Gpi-2{sup 38} allele frequency did not change in mercury-exposed populations. No significant differences were found in standard length, weight, sex ratio, or age class ratio between the control and mercury-exposed populations. Allele frequency changes at the Gpi-2 locus suggest population-level response to chronic mercury exposure. Changes in allele frequency may be useful as indicators of population response to contaminants, provided that the population in question is well understood.

Moderate evidence for a Lombard effect in a phylogenetically basal primate

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Christian Schopf

2016-08-01

Full Text Available When exposed to enhanced background noise, humans avoid signal masking by increasing the amplitude of the voice, a phenomenon termed the Lombard effect. This auditory feedback-mediated voice control has also been found in monkeys, bats, cetaceans, fish and some frogs and birds. We studied the Lombard effect for the first time in a phylogenetically basal primate, the grey mouse lemur, Microcebus murinus. When background noise was increased, mouse lemurs were able to raise the amplitude of the voice, comparable to monkeys, but they did not show this effect consistently across context/individuals. The Lombard effect, even if representing a generic vocal communication system property of mammals, may thus be affected by more complex mechanisms. The present findings emphasize an effect of context, and individual, and the need for further standardized approaches to disentangle the multiple system properties of mammalian vocal communication, important for understanding the evolution of the unique human faculty of speech and language.

Genetic consequences of trumpeter swan (Cygnus buccinator) reintroductions

Science.gov (United States)

Ransler, F.A.; Quinn, T.W.; Oyler-McCance, S.J.

2011-01-01

Relocation programs are often initiated to restore threatened species to previously occupied portions of their range. A primary challenge of restoration efforts is to translocate individuals in a way that prevents loss of genetic diversity and decreases differentiation relative to source populations-a challenge that becomes increasingly difficult when remnant populations of the species are already genetically depauperate. Trumpeter swans were previously extirpated in the entire eastern half of their range. Physical translocations of birds over the last 70 years have restored the species to portions of its historical range. Despite the long history of management, there has been little monitoring of the genetic outcomes of these restoration attempts. We assessed the consequences of this reintroduction program by comparing patterns of genetic variation at 17 microsatellite loci across four restoration flocks (three wild-released, one captive) and their source populations. We found that a wild-released population established from a single source displayed a trend toward reduced genetic diversity relative to and significant genetic differentiation from its source population, though small founder population effects may also explain this pattern. Wild-released flocks restored from multiple populations maintained source levels of genetic variation and lacked significant differentiation from at least one of their sources. Further, the flock originating from a single source revealed significantly lower levels of genetic variation than those established from multiple sources. The distribution of genetic variation in the captive flock was similar to its source. While the case of trumpeter swans provides evidence that restorations from multiple versus single source populations may better preserve natural levels of genetic diversity, more studies are needed to understand the general applicability of this management strategy. ?? 2010 Springer Science+Business Media B.V. (outside

Implications of Heterogeneity in Multiple Myeloma

Directory of Open Access Journals (Sweden)

Sanjay de Mel

2014-01-01

Full Text Available Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated.

Genetics of osteoarthritis.

Science.gov (United States)

Rodriguez-Fontenla, Cristina; Gonzalez, Antonio

2015-01-01

Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have contributed to the discovery of genetic susceptibility factors in OA. The most relevant associations discovered until now are discussed in detail: GDF-5, 7q22 locus, MCF2L, DOT1L, NCOA3 and also some important findings from the arcOGEN study. Moreover, the different approaches that can be used to minimize the specific problems of the study of OA genetics are discussed. These include the study of microsatellites, phenotype standardization and other methods such as meta-analysis of GWAS and gene-based analysis. It is expected that these new approaches contribute to finding new susceptibility genetic factors for OA. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Evolution of resistance to a multiple-herbivore community: genetic correlations, diffuse coevolution, and constraints on the plant's response to selection.

Science.gov (United States)

Wise, Michael J; Rausher, Mark D

2013-06-01

Although plants are generally attacked by a community of several species of herbivores, relatively little is known about the strength of natural selection for resistance in multiple-herbivore communities-particularly how the strength of selection differs among herbivores that feed on different plant organs or how strongly genetic correlations in resistance affect the evolutionary responses of the plant. Here, we report on a field study measuring natural selection for resistance in a diverse community of herbivores of Solanum carolinense. Using linear phenotypic-selection analyses, we found that directional selection acted to increase resistance to seven species. Selection was strongest to increase resistance to fruit feeders, followed by flower feeders, then leaf feeders. Selection favored a decrease in resistance to a stem borer. Bootstrapping analyses showed that the plant population contained significant genetic variation for each of 14 measured resistance traits and significant covariances in one-third of the pairwise combinations of resistance traits. These genetic covariances reduced the plant's overall predicted evolutionary response for resistance against the herbivore community by about 60%. Diffuse (co)evolution was widespread in this community, and the diffuse interactions had an overwhelmingly constraining (rather than facilitative) effect on the plant's evolution of resistance. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

An association study of 13 SNPs from seven candidate genes with pediatric asthma and a preliminary study for genetic testing by multiple variants in Taiwanese population.

Science.gov (United States)

Wang, Jiu-Yao; Liou, Ya-Huei; Wu, Ying-Jye; Hsiao, Ya-Hsin; Wu, Lawrence Shih-Hsin

2009-03-01

Asthma is one of the most common chronic diseases in children. It is caused by complex interactions between various genetic factors and exposures to environmental allergens and irritants. Because of the heterogeneity of the disease and the genetic and cultural differences among different populations, a proper association study and genetic testing for asthma and susceptibility genes is difficult to perform. We assessed 13 single-nucleotide polymorphisms (SNPs) in seven well-known asthma susceptibility genes and looked for association with pediatric asthma using 449 asthmatic subjects and 512 non-asthma subjects in Taiwanese population. CD14-159 C/T and MS4A2 Glu237Gly were identified to have difference in genotype/allele frequencies between the control group and asthma patients. Moreover, the genotype synergistic analysis showed that the co-contribution of two functional SNPs was riskier or more protective from asthma attack. Our study provided a genotype synergistic method for studying gene-gene interaction on polymorphism basis and genetic testing using multiple polymorphisms.

Genetic parameters for litter size in Black Slavonian pigs

Energy Technology Data Exchange (ETDEWEB)

Skorput, D.; Gorjanc, G.; Dikic, M.; Lujovic, Z.

2014-06-01

The objective of this study was to estimate genetic parameters for litter size of Black Slavonian pigs using the repeatability, multiple trait, and random regression models, and to consider the possibility to increase litter size in Black Slavonian pigs by selection. A total of 4,733 litter records from the first to the sixth parity from sows that farrowed between January 1998 and December 2010 were included in the analysis. Individual record consisted of the following variables: breeding organisation (eight regions), parity (1-6), service boar, and farrowing season (monthyear interaction). Estimation of all the covariance components with three different models was based on the residual maximum likelihood method. Estimate of additive genetic variance and heritability for number of piglets born alive with repeatability model was 0.23 and 0.10, respectively. Estimates of additive genetic variance with multiple trait and random regression model were in a wider range from 0.05 to 0.65 across parities, and heritabilities were estimated in the range between 0.03 and 0.26. Estimates of phenotypic and additive genetic correlations were much smoother with random regression model in comparison with multiple trait model. Due to unexpected changes of variances along trajectory obtained with multiple trait and random regression model, the best option for genetic evaluation of litter size for now could be the use of repeatability model. With increasing number of data with proper data structure alternative modelling of litter size of Black Slavonian pig using multiple trait and random regression model could be taken into consideration. (Author)

Genetic parameters for litter size in Black Slavonian pigs

Directory of Open Access Journals (Sweden)

Dubravko Skorput

2014-02-01

Full Text Available The objective of this study was to estimate genetic parameters for litter size of Black Slavonian pigs using the repeatability, multiple trait, and random regression models, and to consider the possibility to increase litter size in Black Slavonian pigs by selection. A total of 4733 litter records from the first to the sixth parity from sows that farrowed between January 1998 and December 2010 were included in the analysis. Individual record consisted of the following variables: breeding organisation (eight regions, parity (1-6, service boar, and farrowing season (month-year interaction. Estimation of all the covariance components with three different models was based on the residual maximum likelihood method. Estimate of additive genetic variance and heritability for number of piglets born alive with repeatability model was 0.23 and 0.10, respectively. Estimates of additive genetic variance with multiple trait and random regression model were in a wider range from 0.05 to 0.65 across parities, and heritabilities were estimated in the range between 0.03 and 0.26. Estimates of phenotypic and additive genetic correlations were much smoother with random regression model in comparison with multiple trait model. Due to unexpected changes of variances along trajectory obtained with multiple trait and random regression model, the best option for genetic evaluation of litter size for now could be the use of repeatability model. With increasing number of data with proper data structure alternative modelling of litter size of Black Slavonian pig using multiple trait and random regression model could be taken into consideration.

(Strychnos madagascariensis) for conservation of L. ankaranensis)

African Journals Online (AJOL)

species such as sportive lemurs, one of the most species-rich groups of ... ventions to maintain or improve habitat quality for these lemurs. ..... 2008) and birds (as .... treatment of various skin disorders by a rural community in northern Ma-.

The grey mouse lemur uses season-dependent fat or protein sparing strategies to face chronic food restriction.

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Sylvain Giroud

2010-01-01

Full Text Available During moderate calorie restriction (CR the heterotherm Microcebus murinus is able to maintain a stable energy balance whatever the season, even if only wintering animals enter into torpor. To understand its energy saving strategies to respond to food shortages, we assessed protein and energy metabolisms associated with wintering torpor expression or summering torpor avoidance. We investigated body composition, whole body protein turnover, and daily energy expenditure (DEE, during a graded (40 and 80% 35-day CR in short-days (winter; SD40 and SD80, respectively and long-days (summer; LD40 and LD80, respectively acclimated animals. LD40 animals showed no change in fat mass (FM but a 12% fat free mass (FFM reduction. Protein balance being positive after CR, the FFM loss was early and rapid. The 25% DEE reduction, in LD40 group was mainly explained by FFM changes. LD80 animals showed a steady body mass loss and were excluded from the CR trial at day 22, reaching a survival-threatened body mass. No data were available for this group. SD40 animals significantly decreased their FM level by 21%, but maintained FFM. Protein sparing was achieved through a 35 and 39% decrease in protein synthesis and catabolism (protein turnover, respectively, overall maintaining nitrogen balance. The 21% reduction in energy requirement was explained by the 30% nitrogen flux drop but also by torpor as DEE FFM-adjusted remained 13% lower compared to ad-libitum. SD80 animals were unable to maintain energy and nitrogen balances, losing both FM and FFM. Thus summering mouse lemurs equilibrate energy balance by a rapid loss of active metabolic mass without using torpor, whereas wintering animals spare protein and energy through increased torpor expression. Both strategies have direct fitness implication: 1 to maintain activities at a lower body size during the mating season and 2 to preserve an optimal wintering muscle mass and function.

Hereditary multiple exostoses: from genetics to clinical syndrome and complications

Energy Technology Data Exchange (ETDEWEB)

Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

2001-12-01

Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses.

Hereditary multiple exostoses: from genetics to clinical syndrome and complications

International Nuclear Information System (INIS)

Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

2001-01-01

Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses

Genetic diagnosis of a Chinese multiple endocrine neoplasia type ...

Indian Academy of Sciences (India)

However, different families with MEN 2A due to the same RET mutation often have significant variability inthe clinical exhibition of disease and aggressiveness of the MTC, which implies additional genetic loci exsit beyondRET coding region. Whole genome sequencing (WGS) greatly expands the breadth of screening from ...

Melanoma genetics

DEFF Research Database (Denmark)

Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

2015-01-01

Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

Application of Multiple-Population Genetic Algorithm in Optimizing the Train-Set Circulation Plan Problem

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Yu Zhou

2017-01-01

Full Text Available The train-set circulation plan problem (TCPP belongs to the rolling stock scheduling (RSS problem and is similar to the aircraft routing problem (ARP in airline operations and the vehicle routing problem (VRP in the logistics field. However, TCPP involves additional complexity due to the maintenance constraint of train-sets: train-sets must conduct maintenance tasks after running for a certain time and distance. The TCPP is nondeterministic polynomial hard (NP-hard. There is no available algorithm that can obtain the optimal global solution, and many factors such as the utilization mode and the maintenance mode impact the solution of the TCPP. This paper proposes a train-set circulation optimization model to minimize the total connection time and maintenance costs and describes the design of an efficient multiple-population genetic algorithm (MPGA to solve this model. A realistic high-speed railway (HSR case is selected to verify our model and algorithm, and, then, a comparison of different algorithms is carried out. Furthermore, a new maintenance mode is proposed, and related implementation requirements are discussed.

Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

KAUST Repository

James, Tojo

2018-01-06

Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS). Since a large proportion of expression quantitative trait loci (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood mononuclear cells (PBMCs) from MS patients (n=145) to identify eQTLs in regions centered on 109 MS risk SNPs and seven associated HLA variants. We identified 77 statistically significant eQTL associations, including pseudogenes and non-coding RNAs. Thirty-eight out of 40 testable eQTL effects were colocalised with the disease association signal. Since many eQTLs are tissue specific, we aimed to detail their significance in different cell types. Approximately 70% of the eQTLs were replicated and characterized in at least one major PBMC derived cell type. Furthermore, 40% of eQTLs were found to be more pronounced in MS patients compared to noninflammatory neurological diseases patients. In addition, we found two SNPs to be significantly associated with the proportions of three different cell types. Mapping to enhancer histone marks and predicted transcription factor binding sites added additional functional evidence for eight eQTL regions. As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. This study provides many novel and validated targets for future functional characterization of MS and other diseases.

Magnetic resonance imaging in primates. The example of the mouse lemur (Microcebus murinus: From detection of pathological aging to therapeutic evaluations Imagerie par résonance magnétique chez les primates. L’exemple du microcèbe murin (Microcebus murinus : De la détection du vieillissement cérébral pathologique à l'évaluation thérapeutique

Directory of Open Access Journals (Sweden)

Nadine El Tannir El Tayara

2011-02-01

Full Text Available Cerebral aging is a major public health issue in our societies as the aged population increases dramatically. It leads in many cases to neurodegenerative diseases such as Alzheimer disease (AD. Rodents and particularly transgenic mice are widely used as models for research on physiopathology of cerebral aging, neurodegenerative diseases and for the evaluation of therapies. However these models do not mimic all the pathophysiological aspects of human diseases. Complementary models such as non-human primates are phylogenetically close to humans and thus more predictive of drug efficiency in humans. Mouse lemur (Microcebus murinus is a small primate (about 12cm, 100g described as a useful model of cerebral aging and as a potential model of AD. Indeed several animals develop age-associated cerebral alterations like amyloidosis and other cerebral changes. Non invasive medical imaging methods such as magnetic resonance imaging (MRI can be used to follow-up brain changes in these animals. In this review, we present how mouse lemurs can be followed-up by MRI and how MRI can be used during therapeutic evaluations and other applications in this model. MR images can be used to follow-up cerebral anatomy in mouse lemurs. It allows for the description of age-associated atrophic processes, age-associated iron accumulation, and vascular anatomy (thanks to MR angiography. Cerebral glucose uptake can be studied in mouse lemurs with other in vivo imaging modalities such as positron emission tomography (PET. In this case, MRI can be used as a support for quantification of radioligand uptake in specific structures. Ex vivo MR imaging is another MR protocol that can be used to describe cerebral aging in lemurs. It provides high resolution 3D histological brain images and allows for studying exquisite anatomical details or microhemorrhages. Finally, MRI can be used to practice cerebral surgery in lemurs and determine coordinates for stereotactic injections. It can

Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics.

Directory of Open Access Journals (Sweden)

Daniel D Buchanan

2010-07-01

Full Text Available Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC. Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps.We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37% individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02. For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004 after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes.A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

Genetics of ischaemic stroke in young adults

OpenAIRE

Terni, Eva; Giannini, Nicola; Brondi, Marco; Montano, Vincenzo; Bonuccelli, Ubaldo; Mancuso, Michelangelo

2015-01-01

Background: Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach. ...

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

Science.gov (United States)

García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

2017-12-01

Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Multiple organ histopathological changes in broiler chickens fed on genetically modified organism.

Science.gov (United States)

Cîrnatu, Daniela; Jompan, A; Sin, Anca Ileana; Zugravu, Cornelia Aurelia

2011-01-01

Diet can influence the structural characteristics of internal organs. An experiment involving 130 meat broilers was conducted during 42 days (life term for a meat broiler) to study the effect of feed with protein from genetically modified soy. The 1-day-old birds were randomly allocated to five study groups, fed with soy, sunflower, wheat, fish flour, PC starter. In the diet of each group, an amount of protein from soy was replaced with genetically modified soy (I - 0%, II - 25%, III - 50%, IV - 75%, V - 100% protein from genetically modified soy). The level of protein in soy, either modified, or non-modified, was the same. Organs and carcass weights were measured at about 42 days of age of the birds and histopathology exams were performed during May-June 2009. No statistically significant differences were observed in mortality, growth performance variables or carcass and organ yields between broilers consuming diets produced with genetically modified soybean fractions and those consuming diets produced with near-isoline control soybean fractions. Inflammatory and degenerative liver lesions, muscle hypertrophy, hemorrhagic necrosis of bursa, kidney focal tubular necrosis, necrosis and superficial ulceration of bowel and pancreatic dystrophies were found in tissues from broilers fed on protein from genetically modified soy. Different types of lesions found in our study might be due to other causes (parasites, viral) superimposed but their presence exclusively in groups fed with modified soy raises some serious questions about the consequences of use of this type of feed.

Structural model analysis of multiple quantitative traits.

Directory of Open Access Journals (Sweden)

Renhua Li

2006-07-01

Full Text Available We introduce a method for the analysis of multilocus, multitrait genetic data that provides an intuitive and precise characterization of genetic architecture. We show that it is possible to infer the magnitude and direction of causal relationships among multiple correlated phenotypes and illustrate the technique using body composition and bone density data from mouse intercross populations. Using these techniques we are able to distinguish genetic loci that affect adiposity from those that affect overall body size and thus reveal a shortcoming of standardized measures such as body mass index that are widely used in obesity research. The identification of causal networks sheds light on the nature of genetic heterogeneity and pleiotropy in complex genetic systems.

Aye-aye population genomic analyses highlight an important center of endemism in northern Madagascar.

Science.gov (United States)

Perry, George H; Louis, Edward E; Ratan, Aakrosh; Bedoya-Reina, Oscar C; Burhans, Richard C; Lei, Runhua; Johnson, Steig E; Schuster, Stephan C; Miller, Webb

2013-04-09

We performed a population genomics study of the aye-aye, a highly specialized nocturnal lemur from Madagascar. Aye-ayes have low population densities and extensive range requirements that could make this flagship species particularly susceptible to extinction. Therefore, knowledge of genetic diversity and differentiation among aye-aye populations is critical for conservation planning. Such information may also advance our general understanding of Malagasy biogeography, as aye-ayes have the largest species distribution of any lemur. We generated and analyzed whole-genome sequence data for 12 aye-ayes from three regions of Madagascar (North, West, and East). We found that the North population is genetically distinct, with strong differentiation from other aye-ayes over relatively short geographic distances. For comparison, the average FST value between the North and East aye-aye populations--separated by only 248 km--is over 2.1-times greater than that observed between human Africans and Europeans. This finding is consistent with prior watershed- and climate-based hypotheses of a center of endemism in northern Madagascar. Taken together, these results suggest a strong and long-term biogeographical barrier to gene flow. Thus, the specific attention that should be directed toward preserving large, contiguous aye-aye habitats in northern Madagascar may also benefit the conservation of other distinct taxonomic units. To help facilitate future ecological- and conservation-motivated population genomic analyses by noncomputational biologists, the analytical toolkit used in this study is available on the Galaxy Web site.

A simple method for combining genetic mapping data from multiple crosses and experimental designs.

Directory of Open Access Journals (Sweden)

Jeremy L Peirce

Full Text Available BACKGROUND: Over the past decade many linkage studies have defined chromosomal intervals containing polymorphisms that modulate a variety of traits. Many phenotypes are now associated with enough mapping data that meta-analysis could help refine locations of known QTLs and detect many novel QTLs. METHODOLOGY/PRINCIPAL FINDINGS: We describe a simple approach to combining QTL mapping results for multiple studies and demonstrate its utility using two hippocampus weight loci. Using data taken from two populations, a recombinant inbred strain set and an advanced intercross population we demonstrate considerable improvements in significance and resolution for both loci. 1-LOD support intervals were improved 51% for Hipp1a and 37% for Hipp9a. We first generate locus-wise permuted P-values for association with the phenotype from multiple maps, which can be done using a permutation method appropriate to each population. These results are then assigned to defined physical positions by interpolation between markers with known physical and genetic positions. We then use Fisher's combination test to combine position-by-position probabilities among experiments. Finally, we calculate genome-wide combined P-values by generating locus-specific P-values for each permuted map for each experiment. These permuted maps are then sampled with replacement and combined. The distribution of best locus-specific P-values for each combined map is the null distribution of genome-wide adjusted P-values. CONCLUSIONS/SIGNIFICANCE: Our approach is applicable to a wide variety of segregating and non-segregating mapping populations, facilitates rapid refinement of physical QTL position, is complementary to other QTL fine mapping methods, and provides an appropriate genome-wide criterion of significance for combined mapping results.

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

Science.gov (United States)

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

HYDRA: Revealing heterogeneity of imaging and genetic patterns through a multiple max-margin discriminative analysis framework.

Science.gov (United States)

Varol, Erdem; Sotiras, Aristeidis; Davatzikos, Christos

2017-01-15

Multivariate pattern analysis techniques have been increasingly used over the past decade to derive highly sensitive and specific biomarkers of diseases on an individual basis. The driving assumption behind the vast majority of the existing methodologies is that a single imaging pattern can distinguish between healthy and diseased populations, or between two subgroups of patients (e.g., progressors vs. non-progressors). This assumption effectively ignores the ample evidence for the heterogeneous nature of brain diseases. Neurodegenerative, neuropsychiatric and neurodevelopmental disorders are largely characterized by high clinical heterogeneity, which likely stems in part from underlying neuroanatomical heterogeneity of various pathologies. Detecting and characterizing heterogeneity may deepen our understanding of disease mechanisms and lead to patient-specific treatments. However, few approaches tackle disease subtype discovery in a principled machine learning framework. To address this challenge, we present a novel non-linear learning algorithm for simultaneous binary classification and subtype identification, termed HYDRA (Heterogeneity through Discriminative Analysis). Neuroanatomical subtypes are effectively captured by multiple linear hyperplanes, which form a convex polytope that separates two groups (e.g., healthy controls from pathologic samples); each face of this polytope effectively defines a disease subtype. We validated HYDRA on simulated and clinical data. In the latter case, we applied the proposed method independently to the imaging and genetic datasets of the Alzheimer's Disease Neuroimaging Initiative (ADNI 1) study. The imaging dataset consisted of T1-weighted volumetric magnetic resonance images of 123 AD patients and 177 controls. The genetic dataset consisted of single nucleotide polymorphism information of 103 AD patients and 139 controls. We identified 3 reproducible subtypes of atrophy in AD relative to controls: (1) diffuse and extensive

Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.

Science.gov (United States)

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."

Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

Science.gov (United States)

McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

2015-10-13

The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases

Genetics Home Reference: Noonan syndrome with multiple lentigines

Science.gov (United States)

... of Noonan syndrome with multiple lentigines include brown skin spots called lentigines that are similar to freckles, heart ... individuals may have thousands of small dark brown skin spots by the time they reach puberty. Unlike freckles, ...

Human genetics of infectious diseases: a unified theory

OpenAIRE

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...

National genetic improvement programmes in the United States beef ...

African Journals Online (AJOL)

cattle industry is accepting, in fact, demanding estimates of genetic values on yearling bulls. Single and multiple analy ... ordinary event occurred with the formation of the Beef ... assumed genetic trend was non-existent or relatively unimportant ...

Clinical and genetic spectrum of Birt–Hogg–Dubé syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature

Science.gov (United States)

Kunogi, Makiko; Kurihara, Masatoshi; Ikegami, Takako Shigihara; Kobayashi, Toshiyuki; Shindo, Noriko; Kumasaka, Toshio; Gunji, Yoko; Kikkawa, Mika; Iwakami, Shin-ichiro; Hino, Okio; Takahashi, Kazuhisa

2010-01-01

Background Birt–Hogg–Dubé syndrome (BHDS) is an inherited autosomal genodermatosis characterised by fibrofolliculomas of the skin, renal tumours and multiple lung cysts. Genetic studies have disclosed that the clinical picture as well as responsible germline FLCN mutations are diverse. Objectives BHDS may be caused by a germline deletion which cannot be detected by a conventional genetic approach. Real-time quantitative polymerase chain reaction (qPCR) may be able to identify such a mutation and thus provide us with a more accurate clinical picture of BHDS. Methods This study analysed 36 patients with multiple lung cysts of undetermined causes. Denaturing high performance liquid chromatography (DHPLC) was applied for mutation screening. If no abnormality was detected by DHPLC, the amount of each FLCN exon in genome was quantified by qPCR. Results An FLCN germline mutation was found in 23 (63.9%) of the 36 patients by DHPLC and direct sequencing (13 unique small nucleotide alterations which included 11 novel mutations). A large genomic deletion was identified in two of the remaining 13 patients by qPCR (one patient with exon 14 deletion and one patient with a deletion encompassing exons 9 to 14). Mutations including genomic deletions were most frequently identified in the 3′-end of the FLCN gene including exons 12 and 13 (13/25=52.0%). The BHDS patients whose multiple cysts prompted the diagnosis in this study showed a very low incidence of skin and renal involvement. Conclusions BHDS is due to large deletions as well as small nucleotide alterations. Racial differences may occur between Japanese and patients of European decent in terms of FLCN mutations and clinical manifestations. PMID:20413710

Shedding subspecies: The influence of genetics on reptile subspecies taxonomy.

Science.gov (United States)

Torstrom, Shannon M; Pangle, Kevin L; Swanson, Bradley J

2014-07-01

The subspecies concept influences multiple aspects of biology and management. The 'molecular revolution' altered traditional methods (morphological traits) of subspecies classification by applying genetic analyses resulting in alternative or contradictory classifications. We evaluated recent reptile literature for bias in the recommendations regarding subspecies status when genetic data were included. Reviewing characteristics of the study, genetic variables, genetic distance values and noting the species concepts, we found that subspecies were more likely elevated to species when using genetic analysis. However, there was no predictive relationship between variables used and taxonomic recommendation. There was a significant difference between the median genetic distance values when researchers elevated or collapsed a subspecies. Our review found nine different concepts of species used when recommending taxonomic change, and studies incorporating multiple species concepts were more likely to recommend a taxonomic change. Since using genetic techniques significantly alter reptile taxonomy there is a need to establish a standard method to determine the species-subspecies boundary in order to effectively use the subspecies classification for research and conservation purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

50 CFR 14.151 - Primary enclosures.

Science.gov (United States)

2010-10-01

... Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING... Wild Mammals and Birds to the United States Specifications for Sloths, Bats, and Flying Lemurs... located on the upper one-half of the primary enclosure. (b) No more than one sloth, bat, or flying lemur...

A Next-Generation Sequencing Strategy for Evaluating the Most Common Genetic Abnormalities in Multiple Myeloma.

Science.gov (United States)

Jiménez, Cristina; Jara-Acevedo, María; Corchete, Luis A; Castillo, David; Ordóñez, Gonzalo R; Sarasquete, María E; Puig, Noemí; Martínez-López, Joaquín; Prieto-Conde, María I; García-Álvarez, María; Chillón, María C; Balanzategui, Ana; Alcoceba, Miguel; Oriol, Albert; Rosiñol, Laura; Palomera, Luis; Teruel, Ana I; Lahuerta, Juan J; Bladé, Joan; Mateos, María V; Orfão, Alberto; San Miguel, Jesús F; González, Marcos; Gutiérrez, Norma C; García-Sanz, Ramón

2017-01-01

Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions. Forty-eight newly diagnosed myeloma patients were tested with the panel, which included IGH and six genes that are recurrently mutated in myeloma: NRAS, KRAS, HRAS, TP53, MYC, and BRAF. We identified 14 of 17 IGH translocations previously detected by FISH and three confirmed translocations not detected by FISH, with the additional advantage of breakpoint identification, which can be used as a target for evaluating minimal residual disease. IgH subclass and V(D)J rearrangements were identified in 77% and 65% of patients, respectively. Mutation analysis revealed the presence of missense protein-coding alterations in at least one of the evaluating genes in 16 of 48 patients (33%). This method may represent a time- and cost-effective diagnostic method for the molecular characterization of multiple myeloma. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Clustering and Genetic Algorithm Based Hybrid Flowshop Scheduling with Multiple Operations

Directory of Open Access Journals (Sweden)

Yingfeng Zhang

2014-01-01

Full Text Available This research is motivated by a flowshop scheduling problem of our collaborative manufacturing company for aeronautic products. The heat-treatment stage (HTS and precision forging stage (PFS of the case are selected as a two-stage hybrid flowshop system. In HTS, there are four parallel machines and each machine can process a batch of jobs simultaneously. In PFS, there are two machines. Each machine can install any module of the four modules for processing the workpeices with different sizes. The problem is characterized by many constraints, such as batching operation, blocking environment, and setup time and working time limitations of modules, and so forth. In order to deal with the above special characteristics, the clustering and genetic algorithm is used to calculate the good solution for the two-stage hybrid flowshop problem. The clustering is used to group the jobs according to the processing ranges of the different modules of PFS. The genetic algorithm is used to schedule the optimal sequence of the grouped jobs for the HTS and PFS. Finally, a case study is used to demonstrate the efficiency and effectiveness of the designed genetic algorithm.

A markerless protocol for genetic analysis of Aggregatibacter actinomycetemcomitans

Science.gov (United States)

Cheng, Ya-An; Jee, Jason; Hsu, Genie; Huang, Yanyan; Chen, Casey; Lin, Chun-Pin

2015-01-01

Background/Purpose The genomes of different Aggregatibacter actinomycetemcomitans strains contain many strain-specific genes and genomic islands (defined as DNA found in some but not all strains) of unknown functions. Genetic analysis for the functions of these islands will be constrained by the limited availability of genetic markers and vectors for A. actinomycetemcomitans. In this study we tested a novel genetic approach of gene deletion and restoration in a naturally competent A. actinomycetemcomitans strain D7S-1. Methods Specific genes’ deletion mutants and mutants restored with the deleted genes were constructed by a markerless loxP/Cre system. In mutants with sequential deletion of multiple genes loxP with different spacer regions were used to avoid unwanted recombinations between loxP sites. Results Eight single-gene deletion mutants, four multiple-gene deletion mutants, and two mutants with restored genes were constructed. No unintended non-specific deletion mutants were generated by this protocol. The protocol did not negatively affect the growth and biofilm formation of A. actinomycetemcomitans. Conclusion The protocol described in this study is efficient and specific for genetic manipulation of A. actinomycetemcomitans, and will be amenable for functional analysis of multiple genes in A. actinomycetemcomitans. PMID:24530245

régression linéaire multiple

African Journals Online (AJOL)

Mots clés: Alcools et phénols – Représentation numérique de la structure chimique – Facteur acentrique – Régression linéaire multiple – Modèle RSP hybride. English Title: Structure / acentric factor relationship of alcohols and phenols: genetic algorithm – multiple linear regression approach. English Abstract. The acentric ...

Patterns of genetic diversity of the cryptogenic red alga Polysiphonia morrowii (Ceramiales, Rhodophyta) suggest multiple origins of the Atlantic populations.

Science.gov (United States)

Geoffroy, Alexandre; Destombe, Christophe; Kim, Byeongseok; Mauger, Stéphane; Raffo, María Paula; Kim, Myung Sook; Le Gall, Line

2016-08-01

The red alga Polysiphonia morrowii, native to the North Pacific (Northeast Asia), has recently been reported worldwide. To determine the origin of the French and Argentine populations of this introduced species, we compared samples from these two areas with samples collected in Korea and at Hakodate, Japan, the type locality of the species. Combined analyses of chloroplastic (rbcL) and mitochondrial (cox1) DNA revealed that the French and Argentine populations are closely related and differ substantially from the Korean and Japanese populations. The genetic structure of P. morrowii populations from South Atlantic and North Atlantic, which showed high haplotype diversity compared with populations from the North Pacific, suggested the occurrence of multiple introduction events from areas outside of the so-called native regions. Although similar, the French and Argentine populations are not genetically identical. Thus, the genetic structure of these two introduced areas may have been modified by cryptic and recurrent introduction events directly from Asia or from other introduced areas that act as introduction relays. In addition, the large number of private cytoplasmic types identified in the two introduced regions strongly suggests that local populations of P. morrowii existed before the recent detection of these invasions. Our results suggest that the most likely scenario is that the source population(s) of the French and Argentine populations was not located only in the North Pacific and/or that P. morrowii is a cryptogenic species.

Unifying diseases from a genetic point of view: the example of the genetic theory of infectious diseases.

Science.gov (United States)

Darrason, Marie

2013-08-01

In the contemporary biomedical literature, every disease is considered genetic. This extension of the concept of genetic disease is usually interpreted either in a trivial or genocentrist sense, but it is never taken seriously as the expression of a genetic theory of disease. However, a group of French researchers defend the idea of a genetic theory of infectious diseases. By identifying four common genetic mechanisms (Mendelian predisposition to multiple infections, Mendelian predisposition to one infection, and major gene and polygenic predispositions), they attempt to unify infectious diseases from a genetic point of view. In this article, I analyze this explicit example of a genetic theory, which relies on mechanisms and is applied only to a specific category of diseases, what we call "a regional genetic theory." I have three aims: to prove that a genetic theory of disease can be devoid of genocentrism, to consider the possibility of a genetic theory applied to every disease, and to introduce two hypotheses about the form that such a genetic theory could take by distinguishing between a genetic theory of diseases and a genetic theory of Disease. Finally, I suggest that network medicine could be an interesting framework for a genetic theory of Disease.

New Genetic Insights and Therapy in Multiple Myeloma

NARCIS (Netherlands)

K.L. Wu

2007-01-01

textabstractIn the last decade, several significant advances in myeloma therapy have occurred with the pace of change accelerated with the introduction of new anti-myeloma agents. The approach to the treatment of multiple myeloma has become more complex with an array of therapeutic options,

Genetic and environmental interactions

International Nuclear Information System (INIS)

Strong, L.C.

1977-01-01

Cancer may result from a multistage process occurring over a long period of time. Presumably, initial and progressive stages of carcinogenesis may be modified by both genetic and environmental factors. Theoretically, genetic factors may alter susceptibility to the carcinogenic effects of an environmental agent at the initial exposure due to variation in metabolism of the carcinogen or variation in specific target cell response to the active carcinogen, or during the latent phase due to numerous factors that might increase the probability of tumor expression, including growth-promoting factors or immunodeficiency states. Observed genetic and environmental interactions in carcinogenesis include an association between genetically determined inducibility of aryl hydrocarbon hydroxylase and smoking-related cancers, familial susceptibility to certain environmental carcinogens, an association between hereditary disorders of mutagenesis and carcinogenesis, and enhancement of tissue-specific, dominantly inherited tumor predisposition by radiation. Multiple primary tumors occur frequently in genetically predisposed individuals. Specific markers for susceptibility must be sought in order that high-risk individuals be identified and appropriate measures taken for early cancer detection or prevention. Study of the nature of the genetically determined susceptibility and interactions with environmental agents may be revealing in the understanding of carcinogenesis in general

Genetic association of multiple sclerosis with the marker rs391745 near the endogenous retroviral locus HERV-Fc1: analysis of disease subtypes

DEFF Research Database (Denmark)

Hansen, Bettina; Oturai, Annette Bang; Harbo, Hanne F

2011-01-01

We have previously described the occurrence of multiple sclerosis (MS) to be associated with human endogenous retroviruses, specifically the X-linked viral locus HERV-Fc1. The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients......-Fc1 locus (p = 0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS....

Genetic architecture of carbon isotope composition and growth in Eucalyptus across multiple environments.

Science.gov (United States)

Bartholomé, Jérôme; Mabiala, André; Savelli, Bruno; Bert, Didier; Brendel, Oliver; Plomion, Christophe; Gion, Jean-Marc

2015-06-01

In the context of climate change, the water-use efficiency (WUE) of highly productive tree varieties, such as eucalypts, has become a major issue for breeding programmes. This study set out to dissect the genetic architecture of carbon isotope composition (δ(13) C), a proxy of WUE, across several environments. A family of Eucalyptus urophylla × E. grandis was planted in three trials and phenotyped for δ(13) C and growth traits. High-resolution genetic maps enabled us to target genomic regions underlying δ(13) C quantitative trait loci (QTLs) on the E. grandis genome. Of the 15 QTLs identified for δ(13) C, nine were stable across the environments and three displayed significant QTL-by-environment interaction, suggesting medium to high genetic determinism for this trait. Only one colocalization was found between growth and δ(13) C. Gene ontology (GO) term enrichment analysis suggested candidate genes related to foliar δ(13) C, including two involved in the regulation of stomatal movements. This study provides the first report of the genetic architecture of δ(13) C and its relation to growth in Eucalyptus. The low correlations found between the two traits at phenotypic and genetic levels suggest the possibility of improving the WUE of Eucalyptus varieties without having an impact on breeding for growth. © 2015 CIRAD. New Phytologist © 2015 New Phytologist Trust.

Use of multiple genetic markers in prediction of breeding values.

NARCIS (Netherlands)

Arendonk, van J.A.M.; Tier, B.; Kinghorn, B.P.

1994-01-01

Genotypes at a marker locus give information on transmission of genes from parents to offspring and that information can be used in predicting the individuals' additive genetic value at a linked quantitative trait locus (MQTL). In this paper a recursive method is presented to build the gametic

Genetic complexity underlying hybrid male sterility in Drosophila.

OpenAIRE

Sawamura, Kyoichi; Roote, John; Wu, Chung-I; Yamamoto, Masa-Toshi

2004-01-01

Recent genetic analyses of closely related species of Drosophila have indicated that hybrid male sterility is the consequence of highly complex synergistic effects among multiple genes, both conspecific and heterospecific. On the contrary, much evidence suggests the presence of major genes causing hybrid female sterility and inviability in the less-related species, D. melanogaster and D. simulans. Does this contrast reflect the genetic distance between species? Or, generally, is the genetic b...

The immunogenetics of multiple sclerosis

DEFF Research Database (Denmark)

Svejgaard, A.

2008-01-01

with complex genetic backgrounds. HLA controls immune response genes and HLA associations indicate the involvement of autoimmunity. Multiple sclerosis (MS) was one of the first conditions proven to be HLA associated involving primarily HLA class II factors. We review how HLA studies give fundamental...

Synthesizing genetic sequential logic circuit with clock pulse generator.

Science.gov (United States)

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

Multiple paternity in reptiles: patterns and processes.

Science.gov (United States)

Uller, Tobias; Olsson, Mats

2008-06-01

The evolution of female promiscuity poses an intriguing problem as benefits of mating with multiple males often have to arise via indirect, genetic, effects. Studies on birds have documented that multiple paternity is common in natural populations but strong evidence for selection via female benefits is lacking. In an attempt to evaluate the evidence more broadly, we review studies of multiple paternity in natural populations of all major groups of nonavian reptiles. Multiple paternity has been documented in all species investigated so far and commonly exists in over 50% of clutches, with particularly high levels in snakes and lizards. Marine turtles and lizards with prolonged pair-bonding have relatively low levels of multiple paternity but levels are nevertheless higher than in many vertebrates with parental care. There is no evidence that high levels of polyandry are driven by direct benefits to females and the evidence that multiple paternity arises from indirect genetic benefits is weak. Instead, we argue that the most parsimonious explanation for patterns of multiple paternity is that it represents the combined effect of mate-encounter frequency and conflict over mating rates between males and females driven by large male benefits and relatively small female costs, with only weak selection via indirect benefits. A crucial step for researchers is to move from correlative approaches to experimental tests of assumptions and predictions of theory under natural settings, using a combination of molecular techniques and behavioural observations.

Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

African Journals Online (AJOL)

Neurofibromatosis type I (NF1) is an autosomal dominant disorder with involvement of both the cutaneous and nervous systems. Patients are susceptible to neurological complication in the form of tumors of the brain and spinal cord. Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelinated axons ...

Genetic diversity in Trichomonas vaginalis.

Science.gov (United States)

Meade, John C; Carlton, Jane M

2013-09-01

Recent advances in genetic characterisation of Trichomonas vaginalis isolates show that the extensive clinical variability in trichomoniasis and its disease sequelae are matched by significant genetic diversity in the organism itself, suggesting a connection between the genetic identity of isolates and their clinical manifestations. Indeed, a high degree of genetic heterogeneity in T vaginalis isolates has been observed using multiple genotyping techniques. A unique two-type population structure that is both local and global in distribution has been identified, and there is evidence of recombination within each group, although sexual recombination between the groups appears to be constrained. There is conflicting evidence in these studies for correlations between T vaginalis genetic identity and clinical presentation, metronidazole susceptibility, and the presence of T vaginalis virus, underscoring the need for adoption of a common standard for genotyping the parasite. Moving forward, microsatellite genotyping and multilocus sequence typing are the most robust techniques for future investigations of T vaginalis genotype-phenotype associations.

Research on Innovating, Applying Multiple Paths Routing Technique Based on Fuzzy Logic and Genetic Algorithm for Routing Messages in Service - Oriented Routing

Directory of Open Access Journals (Sweden)

Nguyen Thanh Long

2015-02-01

Full Text Available MANET (short for Mobile Ad-Hoc Network consists of a set of mobile network nodes, network configuration changes very fast. In content based routing, data is transferred from source node to request nodes is not based on destination addresses. Therefore, it is very flexible and reliable, because source node does not need to know destination nodes. If We can find multiple paths that satisfies bandwidth requirement, split the original message into multiple smaller messages to transmit concurrently on these paths. On destination nodes, combine separated messages into the original message. Hence it can utilize better network resources, causes data transfer rate to be higher, load balancing, failover. Service Oriented Routing is inherited from the model of content based routing (CBR, combined with several advanced techniques such as Multicast, multiple path routing, Genetic algorithm to increase the data rate, and data encryption to ensure information security. Fuzzy logic is a logical field study evaluating the accuracy of the results based on the approximation of the components involved, make decisions based on many factors relative accuracy based on experimental or mathematical proof. This article presents some techniques to support multiple path routing from one network node to a set of nodes with guaranteed quality of service. By using these techniques can decrease the network load, congestion, use network resources efficiently.

Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

Science.gov (United States)

Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

2017-10-01

Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Parametric optimization of multiple quality characteristics in laser cutting of Inconel-718 by using hybrid approach of multiple regression analysis and genetic algorithm

Science.gov (United States)

Shrivastava, Prashant Kumar; Pandey, Arun Kumar

2018-06-01

Inconel-718 has found high demand in different industries due to their superior mechanical properties. The traditional cutting methods are facing difficulties for cutting these alloys due to their low thermal potential, lower elasticity and high chemical compatibility at inflated temperature. The challenges of machining and/or finishing of unusual shapes and/or sizes in these materials have also faced by traditional machining. Laser beam cutting may be applied for the miniaturization and ultra-precision cutting and/or finishing by appropriate control of different process parameter. This paper present multi-objective optimization the kerf deviation, kerf width and kerf taper in the laser cutting of Incone-718 sheet. The second order regression models have been developed for different quality characteristics by using the experimental data obtained through experimentation. The regression models have been used as objective function for multi-objective optimization based on the hybrid approach of multiple regression analysis and genetic algorithm. The comparison of optimization results to experimental results shows an improvement of 88%, 10.63% and 42.15% in kerf deviation, kerf width and kerf taper, respectively. Finally, the effects of different process parameters on quality characteristics have also been discussed.

Interacting effects of genetic variation for seed dormancy and flowering time on phenology, life history, and fitness of experimental Arabidopsis thaliana populations over multiple generations in the field.

Science.gov (United States)

Taylor, Mark A; Cooper, Martha D; Sellamuthu, Reena; Braun, Peter; Migneault, Andrew; Browning, Alyssa; Perry, Emily; Schmitt, Johanna

2017-10-01

Major alleles for seed dormancy and flowering time are well studied, and can interact to influence seasonal timing and fitness within generations. However, little is known about how this interaction controls phenology, life history, and population fitness across multiple generations in natural seasonal environments. To examine how seed dormancy and flowering time shape annual plant life cycles over multiple generations, we established naturally dispersing populations of recombinant inbred lines of Arabidopsis thaliana segregating early and late alleles for seed dormancy and flowering time in a field experiment. We recorded seasonal phenology and fitness of each genotype over 2 yr and several generations. Strong seed dormancy suppressed mid-summer germination in both early- and late-flowering genetic backgrounds. Strong dormancy and late-flowering genotypes were both necessary to confer a winter annual life history; other genotypes were rapid-cycling. Strong dormancy increased within-season fecundity in an early-flowering background, but decreased it in a late-flowering background. However, there were no detectable differences among genotypes in population growth rates. Seasonal phenology, life history, and cohort fitness over multiple generations depend strongly upon interacting genetic variation for dormancy and flowering. However, similar population growth rates across generations suggest that different life cycle genotypes can coexist in natural populations. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Molecular diagnosis of multiple endocrine neoplasia type 2A ...

African Journals Online (AJOL)

Molecular diagnosis of multiple endocrine neoplasia type 2A. RJ Pegoraro, DJ Hacking, RH Buck, L Rom, PA Lanning, GMB Berger. Abstract. Objective. To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. Subjects.

Using the Genetics Concept Assessment to document persistent conceptual difficulties in undergraduate genetics courses.

Science.gov (United States)

Smith, Michelle K; Knight, Jennifer K

2012-05-01

To help genetics instructors become aware of fundamental concepts that are persistently difficult for students, we have analyzed the evolution of student responses to multiple-choice questions from the Genetics Concept Assessment. In total, we examined pretest (before instruction) and posttest (after instruction) responses from 751 students enrolled in six genetics courses for either majors or nonmajors. Students improved on all 25 questions after instruction, but to varying degrees. Notably, there was a subgroup of nine questions for which a single incorrect answer, called the most common incorrect answer, was chosen by >20% of students on the posttest. To explore response patterns to these nine questions, we tracked individual student answers before and after instruction and found that particular conceptual difficulties about genetics are both more likely to persist and more likely to distract students than other incorrect ideas. Here we present an analysis of the evolution of these incorrect ideas to encourage instructor awareness of these genetics concepts and provide advice on how to address common conceptual difficulties in the classroom.

Acoustic divergence in the communication of cryptic species of nocturnal primates (Microcebus ssp.

Directory of Open Access Journals (Sweden)

Zimmermann Elke

2008-05-01

Full Text Available Abstract Background A central question in evolutionary biology is how cryptic species maintain species cohesiveness in an area of sympatry. The coexistence of sympatrically living cryptic species requires the evolution of species-specific signalling and recognition systems. In nocturnal, dispersed living species, specific vocalisations have been suggested to act as an ideal premating isolation mechanism. We studied the structure and perception of male advertisement calls of three nocturnal, dispersed living mouse lemur species, the grey mouse lemur (Microcebus murinus, the golden brown mouse lemur (M. ravelobensis and the Goodman's mouse lemur (M. lehilahytsara. The first two species occur sympatrically, the latter lives allopatrically to them. Results A multi-parameter sound analysis revealed prominent differences in the frequency contour and in the duration of advertisement calls. To test whether mouse lemurs respond specifically to calls of the different species, we conducted a playback experiment with M. murinus from the field using advertisement calls and alarm whistle calls of all three species. Individuals responded significantly stronger to conspecific than to heterospecific advertisement calls but there were no differences in response behaviour towards statistically similar whistle calls of the three species. Furthermore, sympatric calls evoked weaker interest than allopatric advertisement calls. Conclusion Our results provide the first evidence for a specific relevance of social calls for speciation in cryptic primates. They furthermore support that specific differences in signalling and recognition systems represent an efficient premating isolation mechanism contributing to species cohesiveness in sympatrically living species.

Coalgebraic structure of genetic inheritance.

Science.gov (United States)

Tian, Jianjun; Li, Bai-Lian

2004-09-01

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

Genetic Analysis of Multiple Endocrine Neoplasia Type 1 ( Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

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Dong Min Lee

2014-06-01

Full Text Available BackgroundMultiple endocrine neoplasia type 1 (MEN1 is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands. MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above.MethodsA 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1.ResultsGenomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion.ConclusionThere is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma

The genetic links between the big five personality traits and general interest domains.

Science.gov (United States)

Kandler, Christian; Bleidorn, Wiebke; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M

2011-12-01

This is the first genetically informative study in which multiple informants were used to quantify the genetic and environmental sources of individual differences in general interests as well as the phenotypic and genetic links between general interests and Big Five personality traits. Self-reports and two peer ratings from 844 individuals, including 225 monozygotic and 113 dizygotic complete twin pairs, were collected. Multiple-rater scores (composites) revealed that the averaged levels of genetic and environmental effects on seven broad interest domains were similar to those on personality traits. Multivariate analyses showed that about 35% of the genetic and 9% of the environmental variance in interests were explained by personality domains, in particular by Openness. The findings suggest that interests cannot easily be considered as a byproduct of the interactions between personality genotypes and the environmental influences but rather as an internal regulation of behavior with an own genetic basis.

Les lémuriens subfossiles dans le Nord-Ouest de Madagascar, du terrain à la diffusion des connaissances ou 15 ans de recherches franco-malgaches The subfossils lemurs from the North-West of Madagascar, from the fieldwork to the access of knowledge: 15 years of French-Malagasy research.

Directory of Open Access Journals (Sweden)

Beby Ramanivosoa

2011-10-01

a été mise en place.Madagascar is one of the most important hotspot of the world biodiversity. Among the numerous endemic animals living in the island, the lemurs are the more emblematic. Within the primate order, this group is one of the most diversified. If their origin is still not clear, numerous extinct subfossils species have been recorded for at least 26 000 years, the more recent ones being only a few hundred years old. The lemurs are mentioned in ancient texts or legends because of their size which made an impression on people. The causes of their extinction remain poorly known. Historically, the majority of the subfossil sites were known in two geographical areas: the South-West and the Center of Madagascar, which shared a few species. More recently, some subfossils have been discovered in the North of the island, but almost nothing was known in the North-West of Madagascar until 1997 when explorations were undertaken in the framework of a collaboration between malagasy and french researchers.Currently, 19 sites are known and many subfossils were discovered. A new species of extinct lemur was described, Palaeopropithecus kelyus. Numerous non-lemur taxa are recorded (micro-and macrofauna and contribute to understand the history of the past biodiversity and palaeoenvironments.This fair collaboration is also a human adventure. The different participants of the two countries take an equal part in the fieldwork, the studies, the technical and academic training of the students at the University of Mahajanga, and the popularization of the results. Through exhibitions the new Malagasy generations are sensitized to the preservation of their geological and natural heritage.

Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

Science.gov (United States)

Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

2011-01-01

Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

Generalizing genetical genomics: getting added value from environmental perturbation.

Science.gov (United States)

Li, Yang; Breitling, Rainer; Jansen, Ritsert C

2008-10-01

Genetical genomics is a useful approach for studying the effect of genetic perturbations on biological systems at the molecular level. However, molecular networks depend on the environmental conditions and, thus, a comprehensive understanding of biological systems requires studying them across multiple environments. We propose a generalization of genetical genomics, which combines genetic and sensibly chosen environmental perturbations, to study the plasticity of molecular networks. This strategy forms a crucial step toward understanding why individuals respond differently to drugs, toxins, pathogens, nutrients and other environmental influences. Here we outline a strategy for selecting and allocating individuals to particular treatments, and we discuss the promises and pitfalls of the generalized genetical genomics approach.

Targeted therapy of multiple myeloma.

Science.gov (United States)

Dolloff, Nathan G; Talamo, Giampaolo

2013-01-01

Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis.

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Polona Lavtar

Full Text Available Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized that this fact might be partially associated with the influence of latitude on circadian rhythm and consequently that genetic variability of key circadian rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian patients and 1024 healthy controls were compared for genetic signature at 8 SNPs, 4 for each of both genes. We found a statistically significant difference in genotype (ARNTL rs3789327, P = 7.5·10-5; CLOCK rs6811520 P = 0.02 distributions in patients and controls. The ARNTL rs3789327 CC genotype was associated with higher risk for multiple sclerosis at an OR of 1.67 (95% CI 1.35-2.07, P = 0.0001 and the CLOCK rs6811520 genotype CC at an OR of 1.40 (95% CI 1.13-1.73, P = 0.002. The results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis.

Heterogeneity in the multiple myeloma tumor clone

NARCIS (Netherlands)

Guikema, JEJ; Hovenga, S; Vellenga, E; Bos, NA

Multiple Myeloma ( MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome.

Genetic Analysis of Elevated Mastitis Risk Based on Mastitis Indicator Data

DEFF Research Database (Denmark)

Sørensen, Lars Peter; Løvendahl, Peter

Whole-genome sequences and multiple trait phenotypes from large numbers of individuals will soon be available. Well established statistical modeling approaches enable the genetic analyses of complex trait phenotypes while accounting for a variety of additive and non-additive genetic mechanisms....... These modeling approaches have proven to be highly useful to determine population genetic parameters as well as prediction of genetic risk or value. We present statistical modelling approaches that use prior biological information for evaluating the collective action of sets of genetic variants. We have applied...

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Research Article Volume 92 Issue 3 December 2013 pp 529-543 ... combining ability; NCII design; QTL analysis; digenic; multiple alleles. ... and Quantitative Genetics, College of Agricultural Science, Yangzhou University, 225009 Yangzhou, ...

Bayesian state space models for dynamic genetic network construction across multiple tissues.

Science.gov (United States)

Liang, Yulan; Kelemen, Arpad

2016-08-01

Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

CMCpy: Genetic Code-Message Coevolution Models in Python

Science.gov (United States)

Becich, Peter J.; Stark, Brian P.; Bhat, Harish S.; Ardell, David H.

2013-01-01

Code-message coevolution (CMC) models represent coevolution of a genetic code and a population of protein-coding genes (“messages”). Formally, CMC models are sets of quasispecies coupled together for fitness through a shared genetic code. Although CMC models display plausible explanations for the origin of multiple genetic code traits by natural selection, useful modern implementations of CMC models are not currently available. To meet this need we present CMCpy, an object-oriented Python API and command-line executable front-end that can reproduce all published results of CMC models. CMCpy implements multiple solvers for leading eigenpairs of quasispecies models. We also present novel analytical results that extend and generalize applications of perturbation theory to quasispecies models and pioneer the application of a homotopy method for quasispecies with non-unique maximally fit genotypes. Our results therefore facilitate the computational and analytical study of a variety of evolutionary systems. CMCpy is free open-source software available from http://pypi.python.org/pypi/CMCpy/. PMID:23532367

Heterogeneity in the multiple myeloma tumor clone

NARCIS (Netherlands)

Guikema, Jeroen E. J.; Hovenga, Sjoerd; Vellenga, Edo; Bos, Nicolaas A.

2004-01-01

Multiple Myeloma (MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome. Although

Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease

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Simone Cristina Pinto Matheus Fischer

2018-02-01

Full Text Available Abstract Background: Metabolic syndrome (MS is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS. Methods: Patients (n = 116, 68% males aged 56 (9 years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1, methylenotetrahydrofolate reductase (MTHFR, endothelial nitric oxide synthase (ENOS, angiotensin-converting enzyme (ACE, angiotensin II type 1 receptor (AT1R, apolipoprotein C3 (APOC3, lipoprotein lipase (LPL were analysed by polymerase chain reaction (PCR technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066, with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078. Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

Delay-independent stability of genetic regulatory networks.

Science.gov (United States)

Wu, Fang-Xiang

2011-11-01

Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

Advances in the genetically complex autoinflammatory diseases.

Science.gov (United States)

Ombrello, Michael J

2015-07-01

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

Pervasive sharing of genetic effects in autoimmune disease.

Directory of Open Access Journals (Sweden)

Chris Cotsapas

2011-08-01

Full Text Available Genome-wide association (GWA studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs and risk of common autoimmune and inflammatory (immune-mediated diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44% immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA<0.01. We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

Intelligence : shared genetic basis between Mendelian disorders and a polygenic trait

NARCIS (Netherlands)

Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

2015-01-01

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a

Multiple Epiphyseal Dysplasia: A Clinical and Molecular Genetic Study

NARCIS (Netherlands)

J.B.A. van Mourik (Jan)

1998-01-01

textabstractMultiple epiphyseal dysplasia (MED) is one of the most common osteochondrodysplasias [Wynne-Davies and Gormley 1985]. During childhood and adolescence it affects the epiphyses of the tubular bones, resulting in axial deformities and shorter limbs.·Later in life MED can lead to

The Effect of Multiple Paternity on Genetic Diversity of Small Populations during and after Colonisation

KAUST Repository

Rafajlović, Marina; Eriksson, Anders; Rimark, Anna; Hintz-Saltin, Sara; Charrier, Gré gory; Panova, Marina; André , Carl; Johannesson, Kerstin; Mehlig, Bernhard

2013-01-01

Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping

Multiple Paternity and Preliminary Population Genetics of Giant Pacific Octopuses, Enteroctopus dofleini, in Oregon, Washington and the Southeast Coast of Vancouver Island, BC

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Shawn Larson

2015-06-01

Full Text Available A total of 77 giant Pacific octopus, Enteroctopus dofleini, tissue samples were collected from the Oregon Coast (OR, Neah Bay Washington (NB, Puget Sound Washington (PS and the southeast coast of Vancouver Island, British Columbia, Canada (BC for genetic analyses. A suite of eight variable microsatellite markers developed from giant Pacific octopuses were amplified in these samples to determine population diversity, structure, relatedness and paternity. The majority of loci met Hardy-Weinberg equilibrium expectations within each population. We found moderate genetic diversity (average observed heterozygosity = 0.445, range = 0.307–0.515 and average expected heterozygosity = 0.567, range = 0.506–0.696 and moderate population structuring with distinct separation of groups (FST values ranged from 0.101 between BC and PS to 0.237 between BC and NB. Several egg strings from the BC population were collected from three female octopus dens for relatedness and paternity analyses. Results suggest strong support for multiple paternity within one egg clutch with progeny sired by between two to four males.

Evolution of Genetic Variance during Adaptive Radiation.

Science.gov (United States)

Walter, Greg M; Aguirre, J David; Blows, Mark W; Ortiz-Barrientos, Daniel

2018-04-01

Genetic correlations between traits can concentrate genetic variance into fewer phenotypic dimensions that can bias evolutionary trajectories along the axis of greatest genetic variance and away from optimal phenotypes, constraining the rate of evolution. If genetic correlations limit adaptation, rapid adaptive divergence between multiple contrasting environments may be difficult. However, if natural selection increases the frequency of rare alleles after colonization of new environments, an increase in genetic variance in the direction of selection can accelerate adaptive divergence. Here, we explored adaptive divergence of an Australian native wildflower by examining the alignment between divergence in phenotype mean and divergence in genetic variance among four contrasting ecotypes. We found divergence in mean multivariate phenotype along two major axes represented by different combinations of plant architecture and leaf traits. Ecotypes also showed divergence in the level of genetic variance in individual traits and the multivariate distribution of genetic variance among traits. Divergence in multivariate phenotypic mean aligned with divergence in genetic variance, with much of the divergence in phenotype among ecotypes associated with changes in trait combinations containing substantial levels of genetic variance. Overall, our results suggest that natural selection can alter the distribution of genetic variance underlying phenotypic traits, increasing the amount of genetic variance in the direction of natural selection and potentially facilitating rapid adaptive divergence during an adaptive radiation.

Young Adults' Belief in Genetic Determinism, and Knowledge and Attitudes towards Modern Genetics and Genomics: The PUGGS Questionnaire.

Science.gov (United States)

Carver, Rebecca Bruu; Castéra, Jérémy; Gericke, Niklas; Evangelista, Neima Alice Menezes; El-Hani, Charbel N

2017-01-01

In this paper we present the development and validation a comprehensive questionnaire to assess college students' knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies.

Young Adults’ Belief in Genetic Determinism, and Knowledge and Attitudes towards Modern Genetics and Genomics: The PUGGS Questionnaire

Science.gov (United States)

Carver, Rebecca Bruu; Castéra, Jérémy; Gericke, Niklas; Evangelista, Neima Alice Menezes

2017-01-01

In this paper we present the development and validation a comprehensive questionnaire to assess college students’ knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies. PMID:28114357

Plant regeneration and genetic transformation in Jatropha

KAUST Repository

Sujatha, M.; Nithianantham, S.; Reddy, Muppala P.

2012-01-01

Jatropha curcas, a non-edible oil bearing species with multiple uses, and considerable economic potential is emerging as a potential biofuel plant. The limited knowledge of this species, low and inconsistent yields, the narrow genetic variability

Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

Science.gov (United States)

Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

2015-01-01

Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

Genetic relationships between detailed reproductive traits and performance traits in Holstein-Friesian dairy cattle.

Science.gov (United States)

Carthy, T R; Ryan, D P; Fitzgerald, A M; Evans, R D; Berry, D P

2016-02-01

The objective of the study was to estimate the genetic relationships between detailed reproductive traits derived from ultrasound examination of the reproductive tract and a range of performance traits in Holstein-Friesian dairy cows. The performance traits investigated included calving performance, milk production, somatic cell score (i.e., logarithm transformation of somatic cell count), carcass traits, and body-related linear type traits. Detailed reproductive traits included (1) resumed cyclicity at the time of examination, (2) multiple ovulations, (3) early ovulation, (4) heat detection, (5) ovarian cystic structures, (6) embryo loss, and (7) uterine score, measured on a 1 (little or no fluid with normal tone) to 4 (large quantity of fluid with a flaccid tone) scale, based on the tone of the uterine wall and the quantity of fluid present in the uterus. (Co)variance components were estimated using a repeatability animal linear mixed model. Genetic merit for greater milk, fat, and protein yield was associated with a reduced ability to resume cyclicity postpartum (genetic correlations ranged from -0.25 to -0.15). Higher genetic merit for milk yield was also associated with a greater genetic susceptibility to multiple ovulations. Genetic predisposition to elevated somatic cell score was associated with a decreased likelihood of cyclicity postpartum (genetic correlation of -0.32) and a greater risk of both multiple ovulations (genetic correlation of 0.25) and embryo loss (genetic correlation of 0.32). Greater body condition score was genetically associated with an increased likelihood of resumption of cyclicity postpartum (genetic correlation of 0.52). Genetically heavier, fatter carcasses with better conformation were also associated with an increased likelihood of resumed cyclicity by the time of examination (genetic correlations ranged from 0.24 to 0.41). Genetically heavier carcasses were associated with an inferior uterine score as well as a greater

Evolutionary transition from single to multiple mating in fungus-growing ants

DEFF Research Database (Denmark)

Villesen, P.; Gertsch, Pia J.; Frydenberg, J.

1999-01-01

Queens of leafcutter ants exhibit the highest known levels of multiple mating (up to 10 mates per queen) among ants. Multiple mating may have been selected to increase genetic diversity among nestmate workers, which is hypothesized to be critical in social systems with large, long-lived colonies ...

Developmental cognitive genetics: How psychology can inform genetics and vice versa

Science.gov (United States)

Bishop, Dorothy V. M.

2006-01-01

Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination. PMID:16769616

Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors

Science.gov (United States)

Gianfrancesco, Milena A.; Acuna, Brigid; Shen, Ling; Briggs, Farren B.S.; Quach, Hong; Bellesis, Kalliope H.; Bernstein, Allan; Hedstrom, Anna K.; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F.

2014-01-01

Objective To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Methods Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1,235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. Results In analyses stratified by gender, being overweight at age 10 and 20 were associated with MS in females (prisk of MS for females with a BMI ≥ 30 kg/m2 was observed (OR = 2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20’s and MS in males were not observed. Multivariate modeling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. Interpretation Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20’s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. PMID:25263833

Genetic diversity and antimicrobial resistance of Escherichia coli from human and animal sources uncovers multiple resistances from human sources.

Directory of Open Access Journals (Sweden)

A Mark Ibekwe

Full Text Available Escherichia coli are widely used as indicators of fecal contamination, and in some cases to identify host sources of fecal contamination in surface water. Prevalence, genetic diversity and antimicrobial susceptibility were determined for 600 generic E. coli isolates obtained from surface water and sediment from creeks and channels along the middle Santa Ana River (MSAR watershed of southern California, USA, after a 12 month study. Evaluation of E. coli populations along the creeks and channels showed that E. coli were more prevalent in sediment compared to surface water. E. coli populations were not significantly different (P = 0.05 between urban runoff sources and agricultural sources, however, E. coli genotypes determined by pulsed-field gel electrophoresis (PFGE were less diverse in the agricultural sources than in urban runoff sources. PFGE also showed that E. coli populations in surface water were more diverse than in the sediment, suggesting isolates in sediment may be dominated by clonal populations.Twenty four percent (144 isolates of the 600 isolates exhibited resistance to more than one antimicrobial agent. Most multiple resistances were associated with inputs from urban runoff and involved the antimicrobials rifampicin, tetracycline, and erythromycin. The occurrence of a greater number of E. coli with multiple antibiotic resistances from urban runoff sources than agricultural sources in this watershed provides useful evidence in planning strategies for water quality management and public health protection.

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.

Science.gov (United States)

Thewissen, Kristof; Nuyts, Amber H; Deckx, Nathalie; Van Wijmeersch, Bart; Nagels, Guy; D'hooghe, Marie; Willekens, Barbara; Cras, Patrick; Eijnde, Bert O; Goossens, Herman; Van Tendeloo, Viggo F I; Stinissen, Piet; Berneman, Zwi N; Hellings, Niels; Cools, Nathalie

2014-04-01

The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

Non-linear nuclear engineering models as genetic programming application

International Nuclear Information System (INIS)

Domingos, Roberto P.; Schirru, Roberto; Martinez, Aquilino S.

1997-01-01

This work presents a Genetic Programming paradigm and a nuclear application. A field of Artificial Intelligence, based on the concepts of Species Evolution and Natural Selection, can be understood as a self-programming process where the computer is the main agent responsible for the discovery of a program able to solve a given problem. In the present case, the problem was to find a mathematical expression in symbolic form, able to express the existent relation between equivalent ratio of a fuel cell, the enrichment of fuel elements and the multiplication factor. Such expression would avoid repeatedly reactor physics codes execution for core optimization. The results were compared with those obtained by different techniques such as Neural Networks and Linear Multiple Regression. Genetic Programming has shown to present a performance as good as, and under some features superior to Neural Network and Linear Multiple Regression. (author). 10 refs., 8 figs., 1 tabs

Invasion success in Cogongrass (Imperata cylindrica): A population genetic approach exploring genetic diversity and historical introductions

Science.gov (United States)

Rima D. Lucardi; Lisa E. Wallace; Gary N. Ervin

2014-01-01

Propagule pressure significantly contributes to and limits the potential success of a biological invasion, especially during transport, introduction, and establishment. Events such as multiple introductions of foreign parent material and gene flow among them can increase genetic diversity in founding populations, often leading to greater invasion success. We applied...

[A case report of early-onset Alzheimer's disease with multiple psychotic symptoms, finally diagnosed as APPV717I mutation by genetic testing].

Science.gov (United States)

Ishimaru, Takashi; Ochi, Shinichiro; Matsumoto, Teruhisa; Yoshida, Taku; Abe, Masao; Toyota, Yasutaka; Fukuhara, Ryuji; Tanimukai, Satoshi; Ueno, Shu-ichi

2013-01-01

It is difficult to confirm a diagnosis of early-onset Alzheimer's disease (EOAD) because patients sometimes have non-specific cortical features, such as psychiatric symptoms, executive functional impairment, and pyramidal symptoms, along with typical symptoms, such as recent memory impairment and disorientation. We encountered a patient with multiple psychotic symptoms, finally diagnosed with EOAD on genetic testing. A right-handed sixty-year-old man, whose mother was suspected of having dementia, developed memory impairment at the age of fifty, disorientation at the age of fifty-six, and both visual hallucination and dressing apraxia at the age of fifty-nine. After admission to a psychiatric hospital for treatment, his symptoms disappeared with antipsychotic medication. However, his ADL were declining and so he was referred to our university hospital. He had frontal lobe symptoms, pyramidal signs, and extrapyramidal signs with severe dementia. Neuropsychological examinations were not possible because of sedation. On brain MRI, he showed diffuse atrophy of the cerebral cortex and hippocampus. HMPO-SPECT showed hypoperfusion of cerebral cortices diffusely. We decided to perform genetic testing because he had both family and alcohol abuse histories. He showed EOAD with V717I mutation of the amyloid precursor protein gene. After the discontinuation of antipsychotics, excessive sedation and extrapyramidal signs disappeared. A dose of 10 mg of donepezil was effective to improve motivation and activity, and his mini mental examination score was calculable after recovery. The case supports usefulness of applying genetic testing for Alzheimer's disease to patients with early onset dementia, even when they do not have a family history.

Nuclear reactors project optimization based on neural network and genetic algorithm

International Nuclear Information System (INIS)

Pereira, Claudio M.N.A.; Schirru, Roberto; Martinez, Aquilino S.

1997-01-01

This work presents a prototype of a system for nuclear reactor core design optimization based on genetic algorithms and artificial neural networks. A neural network is modeled and trained in order to predict the flux and the neutron multiplication factor values based in the enrichment, network pitch and cladding thickness, with average error less than 2%. The values predicted by the neural network are used by a genetic algorithm in this heuristic search, guided by an objective function that rewards the high flux values and penalizes multiplication factors far from the required value. Associating the quick prediction - that may substitute the reactor physics calculation code - with the global optimization capacity of the genetic algorithm, it was obtained a quick and effective system for nuclear reactor core design optimization. (author). 11 refs., 8 figs., 3 tabs

Polyglot programming in applications used for genetic data analysis.

Science.gov (United States)

Nowak, Robert M

2014-01-01

Applications used for the analysis of genetic data process large volumes of data with complex algorithms. High performance, flexibility, and a user interface with a web browser are required by these solutions, which can be achieved by using multiple programming languages. In this study, I developed a freely available framework for building software to analyze genetic data, which uses C++, Python, JavaScript, and several libraries. This system was used to build a number of genetic data processing applications and it reduced the time and costs of development.

Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings.

Science.gov (United States)

Segal, N L; Feng, R; McGuire, S A; Allison, D B; Miller, S

2009-01-01

Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race. Both non-additive genetic and common environmental contributions were significant in our model (P-valuesrole in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.

Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

Science.gov (United States)

Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

2012-01-01

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

Directory of Open Access Journals (Sweden)

Claire S Leblond

2012-02-01

Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls. We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4% patients and in 16 of 1,090 (1.5% controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70. In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013. Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Genetics of Gigantism and Acromegaly

Science.gov (United States)

Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A.

2016-01-01

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly. PMID:27657986

Genetics of gigantism and acromegaly.

Science.gov (United States)

Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly. Published by Elsevier Ltd.

MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival

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Pezzella Francesco

2011-05-01

Full Text Available Abstract Background MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0 of purified tumor (CD138+ cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS and 9 controls. Results Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129 were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40% suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59% of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14 and t(11;14 and del(13q. Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS in MM, ten of which were significant by univariate (logrank survival analysis. Conclusions In summary, this work has identified aberrantly expressed microRNAs associated with the

Genetically modified soybean plants and their ecosystem

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Milošević Mirjana B.

2004-01-01

Full Text Available Transgenic plants are developed by introgressing new genes using methods of molecular genetics and genetic engineering. The presence of these genes in plant genome is identified on the basis of specific oligonucleotides primers, and the use of PCR (Polymerase Chain Reaction and DNA fragments multiplication. Genetically modified plants such as soybean constitute a newly created bioenergetic potential whose gene expression can cause disturbance of the biological balance ecosystem, soil structure and soil microbiological activity. Genetically modified plants may acquire monogenic or polygenic traits causing genetic and physiological changes in these plants, which may elicit a certain reaction of the environment including changes of microbiological composition of soil rhizosphere. The aim of introgressing genes for certain traits into a cultivated plant is to enhance its yield and intensify food production. There are more and more genetically modified plant species such as soybean, corn, potato, rice and others and there is a pressure to use them as human food and animal feed. Genetically modified soybean plants with introgressed gene for resistance to total herbicides, such as Round-up, are more productive than non-modified herbicide-sensitive soybeans.

Stable coexistence of genetically divergent Atlantic cod ecotypes at multiple spatial scales

DEFF Research Database (Denmark)

Knutsen, Halvor; Jorde, Per Erik; Hutchings, Jeffrey A.

2018-01-01

Coexistence in the same habitat of closely related yet genetically different populations is a phenomenon that challenges our understanding of local population structure and adaptation. Identifying the underlying mechanisms for such coexistence can yield new insight into adaptive evolution...

Multiple paternity in the cultured yellow pond turtles (Mauremys mutica).

Science.gov (United States)

Zhang, Xin-Cheng; Zhao, Jian; Li, Wei; Wei, Cheng-Qing; Zhu, Xin-Ping

2017-08-01

As a result of hunting and habitat loss, wild populations of the yellow pond turtle, Mauremys mutica, are decreasing. The International Union for Conservation of Nature considers M. mutica to be an endangered species. All studied freshwater turtles have polyandrous mating with multiple paternity. To survey the mating strategies of M. mutica, 1year's genetic data of parents and all offspring in an artificially captive population were analyzed. Two groups of multiplex PCR containing 16 microsatellite loci were used to analyze the paternity of 302 hatchlings from 132 parents and from 159 clutches. The genetic data indicated that multiple paternity is rare in M. mutica, occurring in only seven of 138 clutches. Although the frequency of multiple paternity was only 5.07%, results of the present research indicate that M. mutica has a polyandrous mating system. In the breeding season, the successive clutches of 34 females each had the same paternity as the previous clutches. It was observed that four males (f85, f58, f87, and f76) had more than 20 offspring each, totaling 99 and representing 32.78% of all offspring. This finding implies that paternity is competitive in this artificially captive population and might bias the genetic diversity of the offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

Habitat fragmentation causes rapid genetic differentiation and ...

African Journals Online (AJOL)

... city buildings. These results were supported by multiple statistical analyses including Mantel's test, PCOORDA and AMOVA. Genetic enrichment and epigenetic variation studies can be included in habitat fragmentation analysis and its implications in inducing homogenization and susceptibility in natural plant populations.

The Danish Multiple Sclerosis Registry. History, data collection and validity

DEFF Research Database (Denmark)

Koch-Henriksen, N; Rasmussen, S; Stenager, E

2001-01-01

The Danish Multiple Sclerosis Registry was formally established in 1956 but started operating in 1949 with a nationwide prevalence survey. Since then, the Registry has continued collecting data on new and old cases of multiple sclerosis (MS) or suspected MS from multiple sources. The Registry...... instrument for monitoring incidence and prevalence, analysing survival, performing genetic analysis, providing unselected patient samples for clinical analyses, performing case-control studies and prospective studies and estimating the need for treatment and care....

Identification of evolutionary hotspots based on genetic data from multiple terrestrial and aquatic taxa and gap analysis of hotspots in protected lands encompassed by the South Atlantic Landscape Conservation Cooperative.

Science.gov (United States)

Robinson, J.; Snider, M.; Duke, J.; Moyer, G.R.

2014-01-01

 The southeastern United States is a recognized hotspot of biodiversity for a variety of aquatic taxa, including fish, amphibians, and mollusks. Unfortunately, the great diversity of the area is accompanied by a large proportion of species at risk of extinction . Gap analysis was employed to assess the representation of evolutionary hotspots in protected lands w h ere an evolutionary hotspot was defined as an area with high evolutionary potential and measured by atypical patterns of genetic divergence, genetic diversity, and to a lesser extent genetic similarity across multiple terrestrial or aquatic taxa. A survey of the primary literature produced 16 terrestrial and 14 aquatic genetic datasets for estimation of genetic divergence and diversity. Relative genetic diversity and divergence values for each terrestrial and aquatic dataset were used for interpolation of multispecies genetic surfaces and subsequent visualization using ArcGIS. The multispecies surfaces interpolated from relative divergences and diversity data identified numerous evolutionary hotspots for both terrestrial and aquatic taxa , many of which were afforded some current protection. For instance, 14% of the cells identified as hotspots of aquatic diversity were encompassed by currently protected areas. Additionally, 25% of the highest 1% of terrestrial diversity cells were afforded some level of protection. In contrast, areas of high and low divergence among species, and areas of high variance in diversity were poorly represented in the protected lands. Of particular interest were two areas that were consistently identified by several different measures as important from a conservation perspective. These included an area encompassing the panhandle of Florida and southern Georgia near the Apalachicola National Forest (displaying varying levels of genetic divergence and greater than average levels of genetic diversity) and a large portion of the coastal regions of North and South Carolina

Genetic parameters and genetic trends in the Chinese × European Tiameslan composite pig line. I. Genetic parameters

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Legault Christian

2000-01-01

Full Text Available Abstract Genetic parameters of body weight at 4 (W4 w, 8 (W8 w and 22 (W22 w weeks of age, days from 20 to 100 kg (DT, average backfat thickness at 100 kg (ABT, teat number (TEAT, number of good teats (GTEAT, total number of piglets born (TNB, born alive (NBA and weaned (NW per litter, and birth to weaning survival rate (SURV were estimated in the Chinese × European Tiameslan composite line using restricted maximum likelihood methodology applied to a multiple trait animal model. Performance data from a total of 4 881 males and 4 799 females from 1 341 litters were analysed. Different models were fitted to the data in order to estimate the importance of maternal effects on production traits, as well as genetic correlations between male and female performance. The results showed the existence of significant maternal effects on W4w, W8w and ABT and of variance heterogeneity between sexes for W22w, DT, ABT and GTEAT. Genetic correlations between sexes were 0.79, 0.71 and 0.82, respectively, for W22w, DT and ABT and above 0.90 for the other traits. Heritability estimates were larger than (ABT and TEAT or similar to (other traits average literature values. Some genetic antagonism was evidenced between production traits, particularly W4w, W8w and ABT, and reproductive traits.

Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk

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Carayol Jerome

2010-02-01

Full Text Available Abstract Background Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease. Method The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population. Results In both samples, odds ratios (ORs increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49. The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59. Conclusions These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk.

Genetic patterns across multiple introductions of the globally invasive crab genus Carcinus

Science.gov (United States)

The European green crab Carcinus maenas is one of the world's most successful aquatic invaders, having established populations on every continent with temperate shores. Here we describe patterns of genetic diversity across both the native and introduced ranges of C. maenas and it...

Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

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Satoshi Yoshimura

Full Text Available BACKGROUND: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF oligoclonal IgG bands (OBs and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. METHODOLOGY: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA, and varicella zoster virus (VZV in 94 patients with MS and 367 unrelated healthy controls (HCs. We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658. PRINCIPAL FINDINGS: CSF IgG abnormality was found in 59 of 94 (62.8% MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1 1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1 0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. CONCLUSIONS: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1 1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1 0405 and H. pylori infection are positively and negatively

Migraine genetics : from monogenic to complex forms

NARCIS (Netherlands)

Vanmolkot, Kaate Raymond Josepha

2008-01-01

Migraine has a strong genetic component, but the identification of these factors has proven difficult mainly because of the complex interaction of multiple loci and environmental factors. Unraveling its molecular basis and deciphering pathways leading to migraine attacks will help identifying novel

Behavior and diet of the Critically Endangered Eulemur cinereiceps in Manombo forest, southeast Madagascar

OpenAIRE

Nancy J. Stevens; Jonah H. Ratsimbazafy; Fidimalala B. Ralainasolo

2008-01-01

Manombo Special Reserve is a parcel of rainforest along the southeastern coast of Madagascar, containing eight lemur species, including the White-collared brown lemur (Eulemur cinereiceps [Eulemur albocollaris]). Following a drastic cyclone in the region in January of 1997, the population of E. cinereiceps at Manombo was reduced by half. Results indicate that individuals of this critically endangered species at Manombo consume a total of 54 plant species belonging to 24 families, with over tw...

Application of preimplantation genetic diagnosis in equine blastocysts

Directory of Open Access Journals (Sweden)

Grady ST

2016-08-01

Full Text Available Pre-implantation genetic diagnosis (PGD is a procedure used to screen in vitroproduced embryos or embryos recovered after uterine flush to determine genetic traits by DNA testing prior to transfer into the uterus. Biopsy methods to obtain a sample of cells for genetic analysis before implantation have been successful in small embryos (morulae and blastocysts 300 µm diameter. The successful biopsy of expanded equine blastocysts via micromanipulation, with subsequent normal pregnancy rates, was first reported in 2010. Direct PCR may be performed when evaluating only one gene, such as for embryo sexing, while whole genome amplification is effective for subsequent multiplex PCR of multiple genes.

Developing robotic behavior using a genetic programming model

International Nuclear Information System (INIS)

Pryor, R.J.

1998-01-01

This report describes the methodology for using a genetic programming model to develop tracking behaviors for autonomous, microscale robotic vehicles. The use of such vehicles for surveillance and detection operations has become increasingly important in defense and humanitarian applications. Through an evolutionary process similar to that found in nature, the genetic programming model generates a computer program that when downloaded onto a robotic vehicle's on-board computer will guide the robot to successfully accomplish its task. Simulations of multiple robots engaged in problem-solving tasks have demonstrated cooperative behaviors. This report also discusses the behavior model produced by genetic programming and presents some results achieved during the study

Statistical Methods for Studying Genetic Variation in Populations

Science.gov (United States)

2012-08-01

iteration will converge to a local optimum, similar to what happens in an EM algorithm. Empirically, a near global optimal can be obtained by multiple...and E Matthysen. Genetic variability and gene flow 131 in the globally , critically-endangered Taita thrush. Conservation Genetics, 1:45–55, 2000. 4.5.2...Libioulle, Edouard Louis, Sarah Hansoul, Cynthia Sandor, Frédéric Farnir, Denis Franchi - mont, Séverine Vermeire, Olivier Dewit, Martine de Vos, Anna

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

International Nuclear Information System (INIS)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

1988-01-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

Energy Technology Data Exchange (ETDEWEB)

Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

1988-04-01

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

Estimates of genetic parameters, genetic trends, and inbreeding in a crossbred dairy sheep research flock in the United States.

Science.gov (United States)

Murphy, T W; Berger, Y M; Holman, P W; Baldin, M; Burgett, R L; Thomas, D L

2017-10-01

For the past 2 decades, the Spooner Agriculture Research Station (ARS) of the University of Wisconsin-Madison operated the only dairy sheep research flock in North America. The objectives of the present study were to 1) obtain estimates of genetic parameters for lactation and reproductive traits in dairy ewes, 2) estimate the amount of genetic change in these traits over time, and 3) quantify the level of inbreeding in this flock over the last 20 yr. Multiple-trait repeatability models (MTRM) were used to analyze ewe traits through their first 6 parities. The first MTRM jointly analyzed milk (180-d-adjusted milk yield [180d MY]), fat (180-d-adjusted fat yield [180d FY]), and protein (180-d-adjusted protein yield [180d PY]) yields adjusted to 180 d of lactation; number of lambs born per ewe lambing (NLB); and lactation average test-day somatic cell score (LSCS). A second MTRM analyzed 180d MY, NLB, LSCS, and percentage milk fat (%F) and percentage milk protein (%P). The 3 yield traits were moderately heritable (0.26 to 0.32) and strongly genetically correlated (0.91 to 0.96). Percentage milk fat and %P were highly heritable (0.53 and 0.61, respectively) and moderately genetically correlated (0.61). Milk yield adjusted to 180 d was negatively genetically correlated with %F and %P (-0.31 and -0.34, respectively). Ewe prolificacy was not significantly ( > 0.67) genetically correlated with yield traits, %P, or LSCS but lowly negatively correlated with %F (-0.26). Lactation somatic cell score was unfavorably genetically correlated with yield traits (0.28 to 0.39) but not significantly ( > 0.09) correlated with %F, %P, and NLB. Within-trait multiple-trait models through the first 4 parities revealed that 180d MY, 180d FY, 180d PY, %F, and %P were strongly genetically correlated across parity (0.67 to 1.00). However, the genetic correlations across parity for NLB and LSCS were somewhat lower (0.51 to 0.96). Regressing predicted breeding values for 180d MY, without and with

Coronary artery disease-associated genetic variants and biomarkers of inflammation

DEFF Research Database (Denmark)

Christiansen, Morten Krogh; Larsen, Sanne Bøjet; Nyegaard, Mette

2017-01-01

score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. RESULTS:The minor allele (G) (CAD risk allele) of rs2075650......INTRODUCTION:Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD...

[Genetic factors in myocardial infarction].

Science.gov (United States)

Hara, Masahiko; Sakata, Yasuhiko; Sato, Hiroshi

2013-02-01

One of the main mechanisms of acute myocardial infarction (AMI) is plaque rupture or erosion followed by intraluminal thrombus formation and occlusion of the coronary arteries. Thus far, many underlying conditions or environmental factors, such as hypertension, diabetes, dyslipidemia, smoking or obesity, as well as a family history of coronary artery diseases have been identified as risks for the onset of AMI. These risks suggest that AMI occurs due to interactions between underlying conditions and multiple genetic susceptibilities. For this reason, many target gene-disease association studies have been performed with the recent introduction of genome-wide association studies (GWAS) that have further revealed new genetic susceptibilities for AMI. GWAS is a way to examine many common genetic variants in different individuals to see if any variant is associated with a trait in a case-control fashion, and typically focuses on associations between single-nucleotide polymorphisms (SNP) and traits. SNP on chromosome 9p21 is one of the robust susceptibility variants for AMI which has been identified by many GWAS. In this review, we overview the methodology of GWAS, introduce genetic variants identified by GWAS as those with susceptibility for AMI, and describe the foresight of using GWAS to investigate genetic susceptibility to AMI.

Radiation-sensitive genetically susceptible pediatric sub-populations

Energy Technology Data Exchange (ETDEWEB)

Kleinerman, Ruth A. [National Cancer Institute, NIH, DHHS, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rockville, MD (United States)

2009-02-15

Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation. (orig.)

Genetic Engineering Workshop Report, 2010

Energy Technology Data Exchange (ETDEWEB)

Allen, J; Slezak, T

2010-11-03

The Lawrence Livermore National Laboratory (LLNL) Bioinformatics group has recently taken on a role in DTRA's Transformation Medical Technologies (TMT) program. The high-level goal of TMT is to accelerate the development of broad-spectrum countermeasures. To achieve this goal, there is a need to assess the genetic engineering (GE) approaches, potential application as well as detection and mitigation strategies. LLNL was tasked to coordinate a workshop to determine the scope of investments that DTRA should make to stay current with the rapid advances in genetic engineering technologies, so that accidental or malicious uses of GE technologies could be adequately detected and characterized. Attachment A is an earlier report produced by LLNL for TMT that provides some relevant background on Genetic Engineering detection. A workshop was held on September 23-24, 2010 in Springfield, Virginia. It was attended by a total of 55 people (see Attachment B). Twenty four (44%) of the attendees were academic researchers involved in GE or bioinformatics technology, 6 (11%) were from DTRA or the TMT program management, 7 (13%) were current TMT performers (including Jonathan Allen and Tom Slezak of LLNL who hosted the workshop), 11 (20%) were from other Federal agencies, and 7 (13%) were from industries that are involved in genetic engineering. Several attendees could be placed in multiple categories. There were 26 attendees (47%) who were from out of the DC area and received travel assistance through Invitational Travel Orders (ITOs). We note that this workshop could not have been as successful without the ability to invite experts from outside of the Beltway region. This workshop was an unclassified discussion of the science behind current genetic engineering capabilities. US citizenship was not required for attendance. While this may have limited some discussions concerning risk, we felt that it was more important for this first workshop to focus on the scientific state of

Recognition of Epstein-Barr Virus in Multiple Sclerosis

NARCIS (Netherlands)

G.P. van Nierop (Gijs)

2018-01-01

textabstractMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Symptoms of MS include cognitive, motoric, sensory and visual impairment, pain and fatigue. The genetic background of the host and infection with the herpesvirus family member Epstein-Barr virus

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

Science.gov (United States)

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.

New developments in genetics of myositis.

Science.gov (United States)

Rothwell, Simon; Lamb, Janine A; Chinoy, Hector

2016-11-01

This article reviews the advances that have been made in our understanding of the genetics of the idiopathic inflammatory myopathies (IIM) in the past 2 years, with a particular focus on polymyositis, dermatomyositis and inclusion body myositis. Two large human leukocyte antigen (HLA) imputation studies have confirmed a strong association with the 8.1 ancestral haplotype in clinical subgroups of myositis and suggest multiple independent associations on this haplotype. Risk in these genes may be due to specific amino acid positions within the peptide-binding grooves of HLA molecules. A large genetic study in 2566 IIM patients revealed associations such as PTPN22, STAT4, UBE2L3 and BLK, which overlap with risk variants reported in other seropositive autoimmune diseases. There is also evidence of different genetic architectures in clinical subgroups of IIM. Candidate gene studies in the Japanese and Chinese populations have replicated previous IIM associations which suggest common aetiology between ethnicities. International collaborations have facilitated large genetic studies in IIM that have revealed much about the genetics of this rare complex disease both within the HLA region and genome-wide. Future approaches, such as sequencing and trans-ethnic meta-analyses, will advance our knowledge of IIM genetics.

Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors.

Science.gov (United States)

Gianfrancesco, Milena A; Acuna, Brigid; Shen, Ling; Briggs, Farren B S; Quach, Hong; Bellesis, Kalliope H; Bernstein, Allan; Hedstrom, Anna K; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F

2014-01-01

To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (pchildhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Genetics and presence of non-syndromic supernumerary teeth: A mystery case report and review of literature

Directory of Open Access Journals (Sweden)

Neha Khambete

2012-01-01

Full Text Available Presence of supernumerary teeth is well-recognized clinical phenomenon. However, it is uncommon to find multiple supernumeraries in individuals with no other associated disease or syndrome. Presence of multiple supernumerary teeth is thought to have genetic component. We report a rare case where multiple supernumerary teeth were seen without presence of any other syndrome in 3 generations; father, son, and two grandsons. We also present a review of similar cases published in literature till date. The role of genetics in development of supernumerary teeth is highlighted.

A global reference for human genetic variation

DEFF Research Database (Denmark)

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 ...

Plant regeneration and genetic transformation in Jatropha

KAUST Repository

Sujatha, M.

2012-07-01

Jatropha curcas, a non-edible oil bearing species with multiple uses, and considerable economic potential is emerging as a potential biofuel plant. The limited knowledge of this species, low and inconsistent yields, the narrow genetic variability, and vulnerability to insects and diseases are major constraints in successful cultivation of Jatropha as a biofuel crop. Hence, genetic improvement of Jatropha is essential by conventional and modern biotechnological tools to use as a viable alternative source of bio-diesel. Realising its potential as a bio-energy crop, in vitro regeneration methods have been established to meet the demand of large scale supply of superior clones, and also as a prelude for genetic improvement of the species through transgenic approaches. In this chapter, an overview of in vitro tissue culture and genetic transformation of Jatropha is discussed. © 2013 Springer Science+Business Media Dordrecht. All rights are reserved.

Enriching an intraspecific genetic map and identifying QTL for fiber quality and yield component traits across multiple environments in Upland cotton (Gossypium hirsutum L.).

Science.gov (United States)

Liu, Xueying; Teng, Zhonghua; Wang, Jinxia; Wu, Tiantian; Zhang, Zhiqin; Deng, Xianping; Fang, Xiaomei; Tan, Zhaoyun; Ali, Iftikhar; Liu, Dexin; Zhang, Jian; Liu, Dajun; Liu, Fang; Zhang, Zhengsheng

2017-12-01

Cotton is a significant commercial crop that plays an indispensable role in many domains. Constructing high-density genetic maps and identifying stable quantitative trait locus (QTL) controlling agronomic traits are necessary prerequisites for marker-assisted selection (MAS). A total of 14,899 SSR primer pairs designed from the genome sequence of G. raimondii were screened for polymorphic markers between mapping parents CCRI 35 and Yumian 1, and 712 SSR markers showing polymorphism were used to genotype 180 lines from a (CCRI 35 × Yumian 1) recombinant inbred line (RIL) population. Genetic linkage analysis was conducted on 726 loci obtained from the 712 polymorphic SSR markers, along with 1379 SSR loci obtained in our previous study, and a high-density genetic map with 2051 loci was constructed, which spanned 3508.29 cM with an average distance of 1.71 cM between adjacent markers. Marker orders on the linkage map are highly consistent with the corresponding physical orders on a G. hirsutum genome sequence. Based on fiber quality and yield component trait data collected from six environments, 113 QTLs were identified through two analytical methods. Among these 113 QTLs, 50 were considered stable (detected in multiple environments or for which phenotypic variance explained by additive effect was greater than environment effect), and 18 of these 50 were identified with stability by both methods. These 18 QTLs, including eleven for fiber quality and seven for yield component traits, could be priorities for MAS.

Genetics of Coronary Artery Disease

DEFF Research Database (Denmark)

McPherson, Ruth; Tybjærg-Hansen, Anne

2016-01-01

Genetic factors contribute importantly to the risk of coronary artery disease (CAD), and in the past decade, there has been major progress in this area. The tools applied include genome-wide association studies encompassing >200,000 individuals complemented by bioinformatic approaches, including...... identified. Furthermore, a total of 202 independent signals in 109 loci have achieved a false discovery rate (qgenetic risk scores that can improve risk prediction beyond conventional risk...... have led to a broader understanding of the genetic architecture of CAD and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on CAD risk. Despite this success, there has been...

A fast multilocus test with adaptive SNP selection for large-scale genetic-association studies

KAUST Repository

Zhang, Han

2013-09-11

As increasing evidence suggests that multiple correlated genetic variants could jointly influence the outcome, a multilocus test that aggregates association evidence across multiple genetic markers in a considered gene or a genomic region may be more powerful than a single-marker test for detecting susceptibility loci. We propose a multilocus test, AdaJoint, which adopts a variable selection procedure to identify a subset of genetic markers that jointly show the strongest association signal, and defines the test statistic based on the selected genetic markers. The P-value from the AdaJoint test is evaluated by a computationally efficient algorithm that effectively adjusts for multiple-comparison, and is hundreds of times faster than the standard permutation method. Simulation studies demonstrate that AdaJoint has the most robust performance among several commonly used multilocus tests. We perform multilocus analysis of over 26,000 genes/regions on two genome-wide association studies of pancreatic cancer. Compared with its competitors, AdaJoint identifies a much stronger association between the gene CLPTM1L and pancreatic cancer risk (6.0 × 10(-8)), with the signal optimally captured by two correlated single-nucleotide polymorphisms (SNPs). Finally, we show AdaJoint as a powerful tool for mapping cis-regulating methylation quantitative trait loci on normal breast tissues, and find many CpG sites whose methylation levels are jointly regulated by multiple SNPs nearby.

QSAR study of HCV NS5B polymerase inhibitors using the genetic algorithm-multiple linear regression (GA-MLR).

Science.gov (United States)

Rafiei, Hamid; Khanzadeh, Marziyeh; Mozaffari, Shahla; Bostanifar, Mohammad Hassan; Avval, Zhila Mohajeri; Aalizadeh, Reza; Pourbasheer, Eslam

2016-01-01

Quantitative structure-activity relationship (QSAR) study has been employed for predicting the inhibitory activities of the Hepatitis C virus (HCV) NS5B polymerase inhibitors . A data set consisted of 72 compounds was selected, and then different types of molecular descriptors were calculated. The whole data set was split into a training set (80 % of the dataset) and a test set (20 % of the dataset) using principle component analysis. The stepwise (SW) and the genetic algorithm (GA) techniques were used as variable selection tools. Multiple linear regression method was then used to linearly correlate the selected descriptors with inhibitory activities. Several validation technique including leave-one-out and leave-group-out cross-validation, Y-randomization method were used to evaluate the internal capability of the derived models. The external prediction ability of the derived models was further analyzed using modified r(2), concordance correlation coefficient values and Golbraikh and Tropsha acceptable model criteria's. Based on the derived results (GA-MLR), some new insights toward molecular structural requirements for obtaining better inhibitory activity were obtained.

Personality and language characteristics in parents from multiple-incidence autism families.

Science.gov (United States)

Piven, J; Palmer, P; Landa, R; Santangelo, S; Jacobi, D; Childress, D

1997-07-25

Several studies have suggested that the genetic liability for autism may be expressed in non-autistic relatives of autistic probands, in behavioral characteristics that are milder but qualitatively similar to the defining features of autism. We employ a variety of direct assessment approaches to examine both personality and language in parents ascertained through having two autistic children (multiple-incidence autism parents) and parents of Down syndrome probands. Multiple-incidence autism parents had higher rates of particular personality characteristics (rigidity, aloofness, hypersensitivity to criticism, and anxiousness), speech and pragmatic language deficits, and more limited friendships than parents in the comparison group. The implications of these findings for future genetic studies of autism are discussed.

Depression and genetic causal attribution of epilepsy in multiplex epilepsy families.

Science.gov (United States)

Sorge, Shawn T; Hesdorffer, Dale C; Phelan, Jo C; Winawer, Melodie R; Shostak, Sara; Goldsmith, Jeff; Chung, Wendy K; Ottman, Ruth

2016-10-01

Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients' psychological responses and coping strategies, but little is known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that among members of families containing multiple individuals with epilepsy, depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause. A self-administered survey was completed by 417 individuals in 104 families averaging 4 individuals with epilepsy per family. Current depression was measured with the Patient Health Questionnaire. Genetic causal attribution was assessed by three questions addressing the following: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual's epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biologic relatives without epilepsy, and 3.9% in 51 individuals married into the families. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biologic relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p = 0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in families containing

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England.

Science.gov (United States)

Bennett, Catherine L; Burke, Sarah E; Burton, Hilary; Farndon, Peter A

2010-05-14

As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can

Estimating the contribution of genetic variants to difference in incidence of disease between population groups

Science.gov (United States)

Moonesinghe, Ramal; Ioannidis, John PA; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

2012-01-01

Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene–environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal. PMID:22333905

Estimating the contribution of genetic variants to difference in incidence of disease between population groups.

Science.gov (United States)

Moonesinghe, Ramal; Ioannidis, John P A; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

2012-08-01

Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene-environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal.

Novel human multiple myeloma cell line UHKT-893

Czech Academy of Sciences Publication Activity Database

Uherková, L.; Vančurová, I.; Vyhlídalová, I.; Pleschnerová, M.; Špička, I.; Mihalová, R.; Březinová, J.; Hodný, Zdeněk; Čermáková, K.; Polanská, V.; Marinov, I.; Jedelský, P.L.; Kuželová, K.; Stöckbauer, P.

2013-01-01

Roč. 37, č. 3 (2013), s. 320-326 ISSN 0145-2126 Institutional support: RVO:68378050 Keywords : human myeloma cell line * human multiple myeloma * plasma cell * IL-6 dependence * immunoglobulin * free light chain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.692, year: 2013

Rapid Genetic Analysis in Congenital Hyperinsulinism

DEFF Research Database (Denmark)

Christesen, Henrik Thybo; Brusgaard, Klaus; Alm, Jan

2007-01-01

BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated...... with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation....... METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease...

Multivariate Methods for Meta-Analysis of Genetic Association Studies.

Science.gov (United States)

Dimou, Niki L; Pantavou, Katerina G; Braliou, Georgia G; Bagos, Pantelis G

2018-01-01

Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.

Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism

DEFF Research Database (Denmark)

Barthold, Julia Spencer; Reinhardt, Susanne; Thorup, Jorgen

2016-01-01

genetic risk, multiple susceptibility loci, and a role for the maternal environment. Epidemiologic studies have identified low birth weight or intrauterine growth retardation as factors most strongly associated with cryptorchidism, with additional evidence suggesting that maternal smoking and gestational...

Class II HLA interactions modulate genetic risk for multiple sclerosis

DEFF Research Database (Denmark)

Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H

2015-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17...

[Genetic and neuroendocrine aspects in autism spectrum disorder].

Science.gov (United States)

Oviedo, Norma; Manuel-Apolinar, Leticia; de la Chesnaye, Elsa; Guerra-Araiza, Christian

The autism spectrum disorder (ASD) was described in 1943 and is defined as a developmental disorder that affects social interaction and communication. It is usually identified in early stages of development from 18 months of age. Currently, autism is considered a neurological disorder with a spectrum covering cases of different degrees, which is associated with genetic factors, not genetic and environmental. Among the genetic factors, various syndromes have been described that are associated with this disorder. Also, the neurobiology of autism has been studied at the genetic, neurophysiological, neurochemical and neuropathological levels. Neuroimaging techniques have shown multiple structural abnormalities in these patients. There have also been changes in the serotonergic, GABAergic, catecholaminergic and cholinergic systems related to this disorder. This paper presents an update of the information presented in the genetic and neuroendocrine aspects of autism spectrum disorder. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Grain yield is a complex character representing a multiplicative end product of many yield attributes. However, understanding the genetics and inheritance that underlies yield and its component characters pose a prerequisite to attain the actual yieldpotential of any crop species. The knowledge pertaining to gene actions ...

Vitrified/warmed single blastocyst transfer in preimplantation genetic diagnosis/preimplantation genetic screening cycles.

Science.gov (United States)

Huang, Jin; Li, Rong; Lian, Ying; Chen, Lixue; Shi, Xiaodan; Qiao, Jie; Liu, Ping

2015-01-01

To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes.

Habitat degradation and seasonality affect physiological stress levels of Eulemur collaris in littoral forest fragments.

Directory of Open Access Journals (Sweden)

Michela Balestri

Full Text Available The littoral forest on sandy soil is among the most threatened habitats in Madagascar and, as such, it represents a hot-spot within a conservation hot-spot. Assessing the health of the resident lemur fauna is not only critical for the long-term viability of these populations, but also necessary for the future re-habilitation of this unique habitat. Since the Endangered collared brown lemur, Eulemur collaris, is the largest seed disperser of the Malagasy south-eastern littoral forest its survival in this habitat is crucial. In this study we compared fecal glucocorticoid metabolite (fGCM levels, a measure of physiological stress and potential early indicator of population health, between groups of collared brown lemurs living in a degraded forest fragment and groups occurring in a more preserved area. For this, we analysed 279 fecal samples collected year-round from 4 groups of collared brown lemurs using a validated 11-oxoetiocholanolone enzyme immunoassay and tested if fGCM levels were influenced by reproductive stages, phenological seasons, sex, and habitat degradation. The lemurs living in the degraded forest had significantly higher fGCM levels than those living in the more preserved area. In particular, the highest fGCM levels were found during the mating season in all animals and in females during gestation in the degraded forest. Since mating and gestation are both occurring during the lean season in the littoral forest, these results likely reflect a combination of ecological and reproductive pressures. Our findings provide a clear indication that habitat degradation has additive effects to the challenges found in the natural habitat. Since increased stress hormone output may have long-term negative effects on population health and reproduction, our data emphasize the need for and may add to the development of effective conservation plans for the species.

Habitat degradation and seasonality affect physiological stress levels of Eulemur collaris in littoral forest fragments.

Science.gov (United States)

Balestri, Michela; Barresi, Marta; Campera, Marco; Serra, Valentina; Ramanamanjato, Jean Baptiste; Heistermann, Michael; Donati, Giuseppe

2014-01-01

The littoral forest on sandy soil is among the most threatened habitats in Madagascar and, as such, it represents a hot-spot within a conservation hot-spot. Assessing the health of the resident lemur fauna is not only critical for the long-term viability of these populations, but also necessary for the future re-habilitation of this unique habitat. Since the Endangered collared brown lemur, Eulemur collaris, is the largest seed disperser of the Malagasy south-eastern littoral forest its survival in this habitat is crucial. In this study we compared fecal glucocorticoid metabolite (fGCM) levels, a measure of physiological stress and potential early indicator of population health, between groups of collared brown lemurs living in a degraded forest fragment and groups occurring in a more preserved area. For this, we analysed 279 fecal samples collected year-round from 4 groups of collared brown lemurs using a validated 11-oxoetiocholanolone enzyme immunoassay and tested if fGCM levels were influenced by reproductive stages, phenological seasons, sex, and habitat degradation. The lemurs living in the degraded forest had significantly higher fGCM levels than those living in the more preserved area. In particular, the highest fGCM levels were found during the mating season in all animals and in females during gestation in the degraded forest. Since mating and gestation are both occurring during the lean season in the littoral forest, these results likely reflect a combination of ecological and reproductive pressures. Our findings provide a clear indication that habitat degradation has additive effects to the challenges found in the natural habitat. Since increased stress hormone output may have long-term negative effects on population health and reproduction, our data emphasize the need for and may add to the development of effective conservation plans for the species.

Association analysis of multiple traits by an approach of combining ...

Indian Academy of Sciences (India)

Lili Chen

diseases. Joint analysis of multiple traits can increase statistical power of association analysis and uncover the underlying genetic ... genthaler and Thilly 2007), the combined multivariate and ... Because of using reverse regression model, our.

Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

Science.gov (United States)

Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

2008-12-23

As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

Improved genetic manipulation of human embryonic stem cells.

NARCIS (Netherlands)

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

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

Science.gov (United States)

Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

Whole genome amplification in preimplantation genetic diagnosis*

Science.gov (United States)

Zheng, Ying-ming; Wang, Ning; Li, Lei; Jin, Fan

2011-01-01

Preimplantation genetic diagnosis (PGD) refers to a procedure for genetically analyzing embryos prior to implantation, improving the chance of conception for patients at high risk of transmitting specific inherited disorders. This method has been widely used for a large number of genetic disorders since the first successful application in the early 1990s. Polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) are the two main methods in PGD, but there are some inevitable shortcomings limiting the scope of genetic diagnosis. Fortunately, different whole genome amplification (WGA) techniques have been developed to overcome these problems. Sufficient DNA can be amplified and multiple tasks which need abundant DNA can be performed. Moreover, WGA products can be analyzed as a template for multi-loci and multi-gene during the subsequent DNA analysis. In this review, we will focus on the currently available WGA techniques and their applications, as well as the new technical trends from WGA products. PMID:21194180

Strong population genetic structuring in an annual fish, Nothobranchius furzeri, suggests multiple savannah refugia in southern Mozambique.

Science.gov (United States)

Bartáková, Veronika; Reichard, Martin; Janko, Karel; Polačik, Matej; Blažek, Radim; Reichwald, Kathrin; Cellerino, Alessandro; Bryja, Josef

2013-09-12

Intraspecific genetic variation of African fauna has been significantly affected by pronounced climatic fluctuations in Plio-Pleistocene, but, with the exception of large mammals, very limited empirical data on diversity of natural populations are available for savanna-dwelling animals. Nothobranchius furzeri is an annual fish from south-eastern Africa, inhabiting discrete temporary savannah pools outside main river alluvia. Their dispersal is limited and population processes affecting its genetic structure are likely a combination of those affecting terrestrial and aquatic taxa. N. furzeri is a model taxon in ageing research and several populations of known geographical origin are used in laboratory studies. Here, we analysed the genetic structure, diversity, historical demography and temporal patterns of divergence in natural populations of N. furzeri across its entire distribution range. Genetic structure and historical demography of N. furzeri were analysed using a combination of mitochondrial (partial cytochrome b sequences, 687 bp) and nuclear (13 microsatellites) markers in 693 fish from 36 populations. Genetic markers consistently demonstrated strong population structuring and suggested two main genetic groups associated with river basins. The split was dated to the Pliocene (>2 Mya). The northern group inhabits savannah pools across the basin of the intermittent river Chefu in south-western Mozambique and eastern Zimbabwe. The southern group (from southernmost Mozambique) is subdivided, with the River Limpopo forming a barrier (maximum divergence time 1 Mya). A strong habitat fragmentation (isolated temporary pools) is reflected in significant genetic structuring even between adjacent pools, with a major influence of genetic drift and significant isolation-by-distance. Analysis of historical demography revealed that the expansion of both groups is ongoing, supported by frequent founder effects in marginal parts of the range and evidence of secondary

Patterns of gut bacterial colonization in three primate species.

Directory of Open Access Journals (Sweden)

Erin A McKenney

Full Text Available Host fitness is impacted by trillions of bacteria in the gastrointestinal tract that facilitate development and are inextricably tied to life history. During development, microbial colonization primes the gut metabolism and physiology, thereby setting the stage for adult nutrition and health. However, the ecological rules governing microbial succession are poorly understood. In this study, we examined the relationship between host lineage, captive diet, and life stage and gut microbiota characteristics in three primate species (infraorder, Lemuriformes. Fecal samples were collected from captive lemur mothers and their infants, from birth to weaning. Microbial DNA was extracted and the v4 region of 16S rDNA was sequenced on the Illumina platform using protocols from the Earth Microbiome Project. Here, we show that colonization proceeds along different successional trajectories in developing infants from species with differing dietary regimes and ecological profiles: frugivorous (fruit-eating Varecia variegata, generalist Lemur catta, and folivorous (leaf-eating Propithecus coquereli. Our analyses reveal community membership and succession patterns consistent with previous studies of human infants, suggesting that lemurs may serve as a useful model of microbial ecology in the primate gut. Each lemur species exhibits distinct species-specific bacterial diversity signatures correlating to life stages and life history traits, implying that gut microbial community assembly primes developing infants at species-specific rates for their respective adult feeding strategies.

Genetic optimization of steam multi-turbines system

International Nuclear Information System (INIS)

Olszewski, Pawel

2014-01-01

Optimization analysis of partially loaded cogeneration, multiple-stages steam turbines system was numerically investigated by using own-developed code (C++). The system can be controlled by following variables: fresh steam temperature, pressure, and flow rates through all stages in steam turbines. Five various strategies, four thermodynamics and one economical, which quantify system operation, were defined and discussed as an optimization functions. Mathematical model of steam turbines calculates steam properties according to the formulation proposed by the International Association for the Properties of Water and Steam. Genetic algorithm GENOCOP was implemented as a solving engine for non–linear problem with handling constrains. Using formulated methodology, example solution for partially loaded system, composed of five steam turbines (30 input variables) with different characteristics, was obtained for five strategies. The genetic algorithm found multiple solutions (various input parameters sets) giving similar overall results. In real application it allows for appropriate scheduling of machine operation that would affect equable time load of every system compounds. Also based on these results three strategies where chosen as the most complex: the first thermodynamic law energy and exergy efficiency maximization and total equivalent energy minimization. These strategies can be successfully used in optimization of real cogeneration applications. - Highlights: • Genetic optimization model for a set of five various steam turbines was presented. • Four various thermodynamic optimization strategies were proposed and discussed. • Operational parameters (steam pressure, temperature, flow) influence was examined. • Genetic algorithm generated optimal solutions giving the best estimators values. • It has been found that similar energy effect can be obtained for various inputs

Targeting a heterologous protein to multiple plant organelles via rationally designed 5? mRNA tags

NARCIS (Netherlands)

Voges, M.J.; Silver, P.A.; Way, J.C.; Mattozzi, M.D.

2013-01-01

Background Plant bioengineers require simple genetic devices for predictable localization of heterologous proteins to multiple subcellular compartments. Results We designed novel hybrid signal sequences for multiple-compartment localization and characterize their function when fused to GFP in

Coffee, Genetic Variants, and Parkinson's Disease: Gene–Environment Interactions

OpenAIRE

Yamada-Fowler, Naomi; Söderkvist, Peter

2015-01-01

Studies of gene–environment interactions may help us to understand the disease mechanisms of common and complex diseases such as Parkinson's disease (PD). Sporadic PD, the common form of PD, is thought to be a multifactorial disorder caused by combinations of multiple genetic factors and environmental or life-style exposures. Since one of the most extensively studied life-style factors in PD is coffee/caffeine intake, here, the studies of genetic polymorphisms with life-style interactions of ...

Multiple sclerosis and herpesvirus interaction

Directory of Open Access Journals (Sweden)

Guilherme Sciascia do Olival

2013-09-01

Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

Science.gov (United States)

Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

2010-01-01

The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

Species specificity in major urinary proteins by parallel evolution.

Directory of Open Access Journals (Sweden)

Darren W Logan

Full Text Available Species-specific chemosignals, pheromones, regulate social behaviors such as aggression, mating, pup-suckling, territory establishment, and dominance. The identity of these cues remains mostly undetermined and few mammalian pheromones have been identified. Genetically-encoded pheromones are expected to exhibit several different mechanisms for coding 1 diversity, to enable the signaling of multiple behaviors, 2 dynamic regulation, to indicate age and dominance, and 3 species-specificity. Recently, the major urinary proteins (Mups have been shown to function themselves as genetically-encoded pheromones to regulate species-specific behavior. Mups are multiple highly related proteins expressed in combinatorial patterns that differ between individuals, gender, and age; which are sufficient to fulfill the first two criteria. We have now characterized and fully annotated the mouse Mup gene content in detail. This has enabled us to further analyze the extent of Mup coding diversity and determine their potential to encode species-specific cues.Our results show that the mouse Mup gene cluster is composed of two subgroups: an older, more divergent class of genes and pseudogenes, and a second class with high sequence identity formed by recent sequential duplications of a single gene/pseudogene pair. Previous work suggests that truncated Mup pseudogenes may encode a family of functional hexapeptides with the potential for pheromone activity. Sequence comparison, however, reveals that they have limited coding potential. Similar analyses of nine other completed genomes find Mup gene expansions in divergent lineages, including those of rat, horse and grey mouse lemur, occurring independently from a single ancestral Mup present in other placental mammals. Our findings illustrate that increasing genomic complexity of the Mup gene family is not evolutionarily isolated, but is instead a recurring mechanism of generating coding diversity consistent with a species

Combined genetic algorithm and multiple linear regression (GA-MLR) optimizer: Application to multi-exponential fluorescence decay surface.

Science.gov (United States)

Fisz, Jacek J

2006-12-07

The optimization approach based on the genetic algorithm (GA) combined with multiple linear regression (MLR) method, is discussed. The GA-MLR optimizer is designed for the nonlinear least-squares problems in which the model functions are linear combinations of nonlinear functions. GA optimizes the nonlinear parameters, and the linear parameters are calculated from MLR. GA-MLR is an intuitive optimization approach and it exploits all advantages of the genetic algorithm technique. This optimization method results from an appropriate combination of two well-known optimization methods. The MLR method is embedded in the GA optimizer and linear and nonlinear model parameters are optimized in parallel. The MLR method is the only one strictly mathematical "tool" involved in GA-MLR. The GA-MLR approach simplifies and accelerates considerably the optimization process because the linear parameters are not the fitted ones. Its properties are exemplified by the analysis of the kinetic biexponential fluorescence decay surface corresponding to a two-excited-state interconversion process. A short discussion of the variable projection (VP) algorithm, designed for the same class of the optimization problems, is presented. VP is a very advanced mathematical formalism that involves the methods of nonlinear functionals, algebra of linear projectors, and the formalism of Fréchet derivatives and pseudo-inverses. Additional explanatory comments are added on the application of recently introduced the GA-NR optimizer to simultaneous recovery of linear and weakly nonlinear parameters occurring in the same optimization problem together with nonlinear parameters. The GA-NR optimizer combines the GA method with the NR method, in which the minimum-value condition for the quadratic approximation to chi(2), obtained from the Taylor series expansion of chi(2), is recovered by means of the Newton-Raphson algorithm. The application of the GA-NR optimizer to model functions which are multi

Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars

NARCIS (Netherlands)

Shahin, A.; Smulders, M.J.M.; Tuyl, van J.M.; Arens, P.F.P.; Bakker, F.T.

2014-01-01

Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from

Risk of Multiple Sclerosis in Patients with Psoriasis

DEFF Research Database (Denmark)

Egeberg, Alexander; Mallbris, Lotus; Gislason, Gunnar Hilmar

2016-01-01

Psoriasis and multiple sclerosis (MS) are inflammatory disorders with similarities in genetic risk variants and inflammatory pathways. Limited evidence is available on the relationship between the two diseases. We therefore investigated the risk of incident (new-onset) MS in patients with mild...

Rare germline alterations in cancer-related genes associated with the risk of multiple primary tumor development

DEFF Research Database (Denmark)

Villacis, Rolando A. R.; Basso, Tatiane R; Canto, Luisa M

2017-01-01

Multiple primary tumors (MPT) have been described in carriers of inherited cancer predisposition genes. However, the genetic etiology of a large proportion of MPT cases remains unclear. We reviewed 267 patients with hereditary cancer predisposition syndromes (HCPS) that underwent genetic counseli...

Genetically engineered nanocarriers for drug delivery

Directory of Open Access Journals (Sweden)

Shi P

2014-03-01

Full Text Available Pu Shi, Joshua A Gustafson, J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USAAbstract: Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.Keywords: polymeric drug carrier, non-polymeric drug carrier, gene delivery, GE drug carriers

Identification of a new mutation in an Iranian family with hereditary multiple osteochondromas

Directory of Open Access Journals (Sweden)

Akbaroghli S

2016-12-01

Full Text Available Susan Akbaroghli,1,* Maryam Balali,2,* Behnam Kamalidehghan,3,4 Siamak Saber,4 Omid Aryani,5 Goh Yong Meng,6 Massoud Houshmand4 1Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, 2ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences (IUMS, 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, 4Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology, 5Department of Neuroscience, Iran Medical University, Tehran, Iran; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM, Serdang, Malaysia *These authors contributed equally to this work Background: Hereditary multiple osteochondromas (HMO, previously named hereditary multiple exostoses (HME, is an autosomal dominant skeletal disorder characterized by the growth of multiple osteochondromas and is associated with bony deformity, skeletal growth reduction, nerve compression, restriction of joint motion, and premature osteoarthrosis. HMO is genetically heterogeneous, localized on at least three chromosomal loci including 8q24.1 (EXT1, 11p11-p13 (EXT2, and 19p (EXT3. The median age of diagnosis is 3 years; almost all affected individuals are diagnosed by age 12. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk of malignant degeneration is low (~1%.Methods and results: This study was performed on an Iranian family with nine affected individuals from three consecutive generations. Here, the proband was an affected woman who received genetic counseling prior to pregnancy. All exons of the three genes were examined in the proband using polymerase chain reaction and sequencing methods (the last member of this family is a male with severe deformities and lesions, especially around his large joints. Exon 4 of EXT1 (c.1235 G>A was changed in affected

Landscape genetics of the nonnative red fox of California.

Science.gov (United States)

Sacks, Benjamin N; Brazeal, Jennifer L; Lewis, Jeffrey C

2016-07-01

Invasive mammalian carnivores contribute disproportionately to declines in global biodiversity. In California, nonnative red foxes (Vulpes vulpes) have significantly impacted endangered ground-nesting birds and native canids. These foxes derive primarily from captive-reared animals associated with the fur-farming industry. Over the past five decades, the cumulative area occupied by nonnative red fox increased to cover much of central and southern California. We used a landscape-genetic approach involving mitochondrial DNA (mtDNA) sequences and 13 microsatellites of 402 nonnative red foxes removed in predator control programs to investigate source populations, contemporary connectivity, and metapopulation dynamics. Both markers indicated high population structuring consistent with origins from multiple introductions and low subsequent gene flow. Landscape-genetic modeling indicated that population connectivity was especially low among coastal sampling sites surrounded by mountainous wildlands but somewhat higher through topographically flat, urban and agricultural landscapes. The genetic composition of populations tended to be stable for multiple generations, indicating a degree of demographic resilience to predator removal programs. However, in two sites where intensive predator control reduced fox abundance, we observed increases in immigration, suggesting potential for recolonization to counter eradication attempts. These findings, along with continued genetic monitoring, can help guide localized management of foxes by identifying points of introductions and routes of spread and evaluating the relative importance of reproduction and immigration in maintaining populations. More generally, the study illustrates the utility of a landscape-genetic approach for understanding invasion dynamics and metapopulation structure of one of the world's most destructive invasive mammals, the red fox.

[Arboviroses in the region of Nosy-Bé, Madagascar. Serologic and entomologic data].

Science.gov (United States)

Fontenille, D; Mathiot, C; Rodhain, F; Coulanges, P

1988-01-01

Since 1977, the Pasteur Institute of Madagascar has been studying, during six surveys, the arboviruses of Nosy-Be area, in the north-west of Madagascar. 47.2% out of 271 human sera and 11.3% out of 151 sera of Lemurs, tested for antibodies to 16 arboviruses by the haemagglutination inhibition test, are positive. The results show an important prevalence of Flaviviruses. West Nile and Dengue 1 viruses were probably circulating some years before the surveys. Antibodies against Sindbis and Rift Valley Fever viruses, were found only in few subjects. Bunyamwera and California groups of virus are absent. The rate of positive Lemurs is weak, particularly in Lemur macaco macaco. Flaviviruses are the most frequent. 12,262 haematophagous diptera (11,965 Culicidae belonging to 40 species) were caught. Aedes aegypti and Aedes albopictus are both present. Arbovirus isolation attempts from 394 mosquito pools failed; only Mengo virus was isolated from four pools of Eretmapodites quinquevittatus and one pool of Aedes (Skusea) sp.

[Arbovirus infections on the island of Nosy-Be; serologic and entomologic findings].

Science.gov (United States)

Fontenille, D; Mathiot, C; Rodhain, F; Coulanges, P

1988-01-01

Since 1977, the Pasteur Institute of madagascar has been studying, during six surveys, the arboviruses of Nosy-Be area, in the north-west of Madagascar. 47.2 p. 100 out of 271 human sera and 11.3 p. 100 out of 150 animal sera (mostly from Lemurs), tested for antibodies to 16 arboviruses by the haemagglutination inhibition test, are positive. The results show an important prevalence of Flaviviruses. West-Nile and Dengue 1 viruses were probably circulating some years before the surveys. Antibodies against Sindbis and Rift Valley Fever viruses, were found only in few subjects. Bunyamwera and Tahyna viruses are absent. The rate of positive Lemurs is weak, particularly in Lemur macaco species. Flaviviruses are the most frequent. 12262 haematophagous diptera (11965 Culicidae belonging to 40 species) were caught . Aedes aegypti and Aedes albopictus are both present. Arbovirus isolation attempts from 394 mosquito pools failed; only Mengo virus was isolated from four pools of Erethmapodites quinquevittatus and one pool of Aedes (Skusea) sp.

Encephalomyocarditis virus infection in an Italian zoo

Directory of Open Access Journals (Sweden)

Pascotto Ernesto

2010-03-01

Full Text Available Abstract A fatal Encephalomyocarditis virus (EMCV infection epidemic involving fifteen primates occurred between October 2006 and February 2007 at the Natura Viva Zoo. This large open-field zoo park located near Lake Garda in Northern Italy hosts one thousand animals belonging to one hundred and fifty different species, including various lemur species. This lemur collection is the most relevant and rich in Italy. A second outbreak between September and November 2008 involved three lemurs. In all cases, the clinical signs were sudden deaths generally without any evident symptoms or only with mild unspecific clinical signs. Gross pathologic changes were characterized by myocarditis (diffuse or focal pallor of the myocardium, pulmonary congestion, emphysema, oedema and thoracic fluid. The EMCV was isolated and recognized as the causative agent of both outbreaks. The first outbreak in particular was associated with a rodent plague, confirming that rats are an important risk factor for the occurrence of the EMCV infection.

Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

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Necla Keskin

2013-08-01

Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

QTL identification of grain protein concentration and its genetic ...

Indian Academy of Sciences (India)

culated using the statistical software package SPSS 12.0. (SPSS, Chicago, USA). ... Joint QTL analysis for PC and GWP/SC was carried out according to the multiple interval ..... testing for epistasis: an application in maize. Theor. Appl. Genet.

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England

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Burton Hilary

2010-05-01

Full Text Available Abstract Background As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Methods Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Results Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots

Multiple neoplasms, single primaries, and patient survival

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Amer MH

2014-03-01

clinical behavior with longer survival rates, possibly related to genetic predisposition. Keywords: genetic susceptibility, incidence study, hereditary, multiple primary neoplasms, survival analysis, prognosis

Sporadic inclusion body myositis: the genetic contributions to the pathogenesis

Science.gov (United States)

2014-01-01

Sporadic inclusion body myositis (sIBM) is the commonest idiopathic inflammatory muscle disease in people over 50 years old. It is characterized by slowly progressive muscle weakness and atrophy, with typical pathological changes of inflammation, degeneration and mitochondrial abnormality in affected muscle fibres. The cause(s) of sIBM are still unknown, but are considered complex, with the contribution of multiple factors such as environmental triggers, ageing and genetic susceptibility. This review summarizes the current understanding of the genetic contributions to sIBM and provides some insights for future research in this mysterious disease with the advantage of the rapid development of advanced genetic technology. An international sIBM genetic study is ongoing and whole-exome sequencing will be applied in a large cohort of sIBM patients with the aim of unravelling important genetic risk factors for sIBM. PMID:24948216

Nevoid basal cell carcinoma syndrome—case report and genetic study

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Yu-Feng Huang

2010-09-01

Full Text Available Nevoid basal cell carcinoma syndrome (also named Gorlin-Goltz syndrome is a rare disease. Commonly seen features include multiple odontogenic keratocysts (OKCs, nevus-like basal cell carcinoma, and bifid ribs. Genetic alterations of the PTCH1 gene are associated with the disease. Herein, we report the case of a 15-year-old girl who presented with multiple OKCs, a bifid rib, ectopic calcification of the falx cer-ebri, and an arachnoid cyst of the cerebrum. No basal cell carcinoma was identified. In addition, a search for genetic alterations was performed on the patient. We identified a genetic mutation of C→T in exon 12 (c.1686 bp and a G→C mutation in intron 13 (g.91665 bp of the PTCH1 gene. Although a similar mutation in exon 12 was reported in a literature search, the mutation in intron 13 has not previously been reported. The patient has continued to be followed-up almost 3 years after the surgery with no recurrence of the OKCs or development of basal cell carcinoma.

Males and females contribute unequally to offspring genetic diversity in the polygynandrous mating system of wild boar.

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Javier Pérez-González

Full Text Available The maintenance of genetic diversity across generations depends on both the number of reproducing males and females. Variance in reproductive success, multiple paternity and litter size can all affect the relative contributions of male and female parents to genetic variation of progeny. The mating system of the wild boar (Sus scrofa has been described as polygynous, although evidence of multiple paternity in litters has been found. Using 14 microsatellite markers, we evaluated the contribution of males and females to genetic variation in the next generation in independent wild boar populations from the Iberian Peninsula and Hungary. Genetic contributions of males and females were obtained by distinguishing the paternal and maternal genetic component inherited by the progeny. We found that the paternally inherited genetic component of progeny was more diverse than the maternally inherited component. Simulations showed that this finding might be due to a sampling bias. However, after controlling for the bias by fitting both the genetic diversity in the adult population and the number of reproductive individuals in the models, paternally inherited genotypes remained more diverse than those inherited maternally. Our results suggest new insights into how promiscuous mating systems can help maintain genetic variation.

Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

DEFF Research Database (Denmark)

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...

Regeneration and Agrobacterium-mediated transformation of multiple lily cultivars

NARCIS (Netherlands)

Wang, Yue; Kronenburg-van de Ven, van B.C.E.; Menzel, T.R.; Maliepaard, C.A.; Shen, X.; Krens, F.A.

2012-01-01

To pursue genetic improvement of lily, efficiency of both regeneration and transformation from callus cultures induced from different explants were evaluated in multiple cultivars. Thirty-five callus lines induced from filaments or styles and one control callus line derived from bulb scales of in

Testing the structure of a hydrological model using Genetic Programming

Science.gov (United States)

Selle, Benny; Muttil, Nitin

2011-01-01

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

Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

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Robin Lemmens

2011-01-01

Full Text Available Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

Is the Experience of Thermal Pain Genetics Dependent?

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Emilia Horjales-Araujo

2015-01-01

Full Text Available It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown. It is suggested that the genetic contributions to pain perception vary across pain modalities. For example, it has been suggested that more than 60% of the variance in cold pressor responses can be explained by genetic factors; in comparison, only 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some of the genetic variations that have previously been associated with different experimental thermal pain models.

Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations.

Science.gov (United States)

Haber, Marc; Mezzavilla, Massimo; Bergström, Anders; Prado-Martinez, Javier; Hallast, Pille; Saif-Ali, Riyadh; Al-Habori, Molham; Dedoussis, George; Zeggini, Eleftheria; Blue-Smith, Jason; Wells, R Spencer; Xue, Yali; Zalloua, Pierre A; Tyler-Smith, Chris

2016-12-01

Understanding human genetic diversity in Africa is important for interpreting the evolution of all humans, yet vast regions in Africa, such as Chad, remain genetically poorly investigated. Here, we use genotype data from 480 samples from Chad, the Near East, and southern Europe, as well as whole-genome sequencing from 19 of them, to show that many populations today derive their genomes from ancient African-Eurasian admixtures. We found evidence of early Eurasian backflow to Africa in people speaking the unclassified isolate Laal language in southern Chad and estimate from linkage-disequilibrium decay that this occurred 4,750-7,200 years ago. It brought to Africa a Y chromosome lineage (R1b-V88) whose closest relatives are widespread in present-day Eurasia; we estimate from sequence data that the Chad R1b-V88 Y chromosomes coalesced 5,700-7,300 years ago. This migration could thus have originated among Near Eastern farmers during the African Humid Period. We also found that the previously documented Eurasian backflow into Africa, which occurred ∼3,000 years ago and was thought to be mostly limited to East Africa, had a more westward impact affecting populations in northern Chad, such as the Toubou, who have 20%-30% Eurasian ancestry today. We observed a decline in heterozygosity in admixed Africans and found that the Eurasian admixture can bias inferences on their coalescent history and confound genetic signals from adaptation and archaic introgression. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Testing the Structure of Hydrological Models using Genetic Programming

Science.gov (United States)

Selle, B.; Muttil, N.

2009-04-01

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

A genetic ensemble approach for gene-gene interaction identification

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Ho Joshua WK

2010-10-01

Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

Reproduction in Leishmania: A focus on genetic exchange.

Science.gov (United States)

Rougeron, V; De Meeûs, T; Bañuls, A-L

2017-06-01

One key process of the life cycle of pathogens is their mode of reproduction. Indeed, this fundamental biological process conditions the multiplication and the transmission of genes and thus the propagation of diseases in the environment. Reproductive strategies of protozoan parasites have been a subject of debate for many years, principally due to the difficulty in making direct observations of sexual reproduction (i.e. genetic recombination). Traditionally, these parasites were considered as characterized by a preeminent clonal structure. Nevertheless, with the development of elaborate culture experiments, population genetics and evolutionary and population genomics, several studies suggested that most of these pathogens were also characterized by constitutive genetic recombination events. In this opinion, we focused on Leishmania parasites, pathogens responsible of leishmaniases, a major public health issue. We first discuss the evolutionary advantages of a mixed mating reproductive strategy, then we review the evidence of genetic exchange, and finally we detail available tools to detect naturally occurring genetic recombination in Leishmania parasites and more generally in protozoan parasites. Copyright © 2016. Published by Elsevier B.V.

Interlaboratory study of DNA extraction from multiple ground samples, multiplex real-time PCR, and multiplex qualitative PCR for individual kernel detection system of genetically modified maize.

Science.gov (United States)

Akiyama, Hiroshi; Sakata, Kozue; Makiyma, Daiki; Nakamura, Kosuke; Teshima, Reiko; Nakashima, Akie; Ogawa, Asako; Yamagishi, Toru; Futo, Satoshi; Oguchi, Taichi; Mano, Junichi; Kitta, Kazumi

2011-01-01

In many countries, the labeling of grains, feed, and foodstuff is mandatory if the genetically modified (GM) organism content exceeds a certain level of approved GM varieties. We previously developed an individual kernel detection system consisting of grinding individual kernels, DNA extraction from the individually ground kernels, GM detection using multiplex real-time PCR, and GM event detection using multiplex qualitative PCR to analyze the precise commingling level and varieties of GM maize in real sample grains. We performed the interlaboratory study of the DNA extraction with multiple ground samples, multiplex real-time PCR detection, and multiplex qualitative PCR detection to evaluate its applicability, practicality, and ruggedness for the individual kernel detection system of GM maize. DNA extraction with multiple ground samples, multiplex real-time PCR, and multiplex qualitative PCR were evaluated by five laboratories in Japan, and all results from these laboratories were consistent with the expected results in terms of the commingling level and event analysis. Thus, the DNA extraction with multiple ground samples, multiplex real-time PCR, and multiplex qualitative PCR for the individual kernel detection system is applicable and practicable in a laboratory to regulate the commingling level of GM maize grain for GM samples, including stacked GM maize.

Multiple cavernous malformations presenting in a patient with Poland syndrome: A case report

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De Salles Antonio AF

2011-09-01

Full Text Available Abstract Introduction Poland syndrome is a congenital disorder related to chest and hand anomalies on one side of the body. Its etiology remains unclear, with an ipsilateral vascular alteration (of unknown origin to the subclavian artery in early embryogenesis being the currently accepted theory. Cavernous malformations are vascular hamartomas, which have been linked to a genetic etiology, particularly in familial cases, which commonly present with multiple lesions. Our case report is the first to describe multiple cavernous malformations associated with Poland syndrome, further supporting the vascular etiology theory, but pointing to a genetic rather than a mechanistic factor disrupting blood flow in the corresponding vessels. Case presentation A 41-year-old Caucasian man with Poland syndrome on the right side of his body presented to our hospital with a secondary generalized seizure and was found to have multiple cavernous malformations distributed in his brain, cerebellum, and brain stem, with a predominance of lesions in the left hemisphere. Conclusion The distribution of cavernous malformations in the left hemisphere and the right-sided Poland syndrome in our patient could not be explained by a mechanistic disruption of one of the subclavian arteries. A genetic alteration, as in familial cavernous malformations, would be a more appropriate etiologic diagnosis of Poland syndrome in our patient. Further genetic and pathological studies of the involved blood vessels in patients with Poland syndrome could lead to a better understanding of the disease.

Temporal genetic population structure and interannual variation in migration behavior of Pacific Lamprey Entosphenus tridentatus

Science.gov (United States)

Clemens, Benjamin J.; Wyss, Lance A.; McCoun, Rebecca; Courter, Ian; Schwabe, Lawrence; Peery, Christopher; Schreck, Carl B.; Spice, Erin K.; Docker, Margaret F.

2017-01-01

Studies using neutral loci suggest that Pacific lamprey, Entosphenus tridentatus, lack strong spatial genetic population structure. However, it is unknown whether temporal genetic population structure exists. We tested whether adult Pacific lamprey: (1) show temporal genetic population structure; and (2) migrate different distances between years. We non-lethally sampled lamprey for DNA in 2009 and 2010 and used eight microsatellite loci to test for genetic population structure. We used telemetry to record the migration behaviors of these fish. Lamprey were assignable to three moderately differentiated genetic clusters (FST = 0.16–0.24 for all pairwise comparisons): one cluster was composed of individuals from 2009, and the other two contained individuals from 2010. The FST value between years was 0.13 and between genetic clusters within 2010 was 0.20. A total of 372 (72.5%) fish were detected multiple times during their migrations. Most fish (69.9%) remained in the mainstem Willamette River; the remaining 30.1% migrated into tributaries. Eighty-two lamprey exhibited multiple back-and-forth movements among tributaries and the mainstem, which may indicate searching behaviors. All migration distances were significantly greater in 2010, when the amplitude of river discharge was greater. Our data suggest genetic structuring between and within years that may reflect different cohorts.

Joint Identification of Genetic Variants for Physical Activity in Korean Population

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Jayoun Kim

2014-07-01

Full Text Available There has been limited research on genome-wide association with physical activity (PA. This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA.

Past climate-driven range shifts and population genetic diversity in arctic plants

DEFF Research Database (Denmark)

Pellissier, Loïc; Eidesen, Pernille Bronken; Ehrich, Dorothee

2016-01-01

High intra-specific genetic diversity is necessary for species adaptation to novel environments under climate change, but species tracking suitable conditions are losing alleles through successive founder events during range shift. Here, we investigated the relationship between range shift since ...... the Last Glacial Maximum (LGM) and extant population genetic diversity across multiple plant species to understand variability in species responses...

Exploiting Genetic Interference for Antiviral Therapy.

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Elizabeth J Tanner

2016-05-01

Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

The interaction between smoking and HLA genes in multiple sclerosis

DEFF Research Database (Denmark)

Hedström, Anna Karin; Katsoulis, Michail; Hössjer, Ola

2017-01-01

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We us...

Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

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Donald P. Knowles

2013-06-01

Full Text Available Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus and goats (caprine arthritis encephalitis virus [CAEV]. Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions.

Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

Science.gov (United States)

White, Stephen N.; Knowles, Donald P.

2013-01-01

Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions. PMID:23771240

Genetic parameters and genetic trends in the Chinese × European Tiameslan composite pig line. II. Genetic trends

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Legault Christian

2000-01-01

Full Text Available Abstract The Tiameslan line was created between 1983 and 1985 by mating Meishan × Jiaxing crossbred Chinese boars with sows from the Laconie composite male line. The Tiameslan line has been selected since then on an index combining average backfat thickness (ABT and days from 20 to 100 kg (DT. Direct and correlated responses to 11 years of selection were estimated using BLUP methodology applied to a multiple trait animal model. A total of 11 traits were considered, i.e.: ABT, DT, body weight at 4 (W4w, 8 (W8w and 22 (W22w weeks of age, teat number (TEAT, number of good teats (GTEAT, total number of piglets born (TNB, born alive (NBA and weaned (NW per litter, and birth to weaning survival rate (SURV. Performance data from a total of 4 881 males and 4 799 females from 1 341 litters were analysed. The models included both direct and maternal effects for ABT, W4w and W8w. Male and female performances were considered as different traits for W22w, DT and ABT. Genetic parameters estimated in another paper (Zhang et al., Genet. Sel. Evol. 32 (2000 41-56 were used to perform the analyses. Favourable phenotypic (ΔP and direct genetic trends (ΔGd were obtained for post-weaning growth traits and ABT. Trends for maternal effects were limited. Phenotypic and genetic trends were larger in females than in males for ABT (e.g. ΔGd = -0.48 vs. -0.38 mm/year, were larger in males for W22w (ΔGd = 0.90 vs. 0.58 kg/year and were similar in both sexes for DT (ΔGd = -0.54 vs. -0.55 day/year. Phenotypic and genetic trends were slightly favourable for W4w, W8w, TEAT and GTEAT and close to zero for reproductive traits.

Review:Whole genome amplification in preimplantation genetic diagnosis

Institute of Scientific and Technical Information of China (English)

Ying-ming ZHENG; Ning WANG; Lei LI; Fan JIN

2011-01-01

Preimplantation genetic diagnosis(PGD)refers to a procedure for genetically analyzing embryos prior to implantation,improving the chance of conception for patients at high risk of transmitting specific inherited disorders.This method has been widely used for a large number of genetic disorders since the first successful application in the early 1990s.Polymerase chain reaction(PCR)and fluorescent in situ hybridization(FISH)are the two main methods in PGD,but there are some inevitable shortcomings limiting the scope of genetic diagnosis.Fortunately,different whole genome amplification(WGA)techniques have been developed to overcome these problems.Sufficient DNA can be amplified and multiple tasks which need abundant DNA can be performed.Moreover,WGA products can be analyzed as a template for multi-loci and multi-gene during the subsequent DNA analysis.In this review,we will focus on the currently available WGA techniques and their applications,as well as the new technical trends from WGA products.

Present status of understanding on the genetic etiology of polycystic ovary syndrome.

Science.gov (United States)

Dasgupta, S; Reddy, B Mohan

2008-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age with a prevalence of approximately 7-10% worldwide. PCOS reflects multiple potential aetiologies and variable clinical manifestations. This syndrome is characterized by serious health implications such as diabetes, coronary heart diseases and cancer and also leads to infertility. PCOS can be viewed as a heterogeneous androgen excess disorder with varying degrees of reproductive and metabolic abnormalities determined by the interaction of multiple genetic and environmental factors. In this paper, we have attempted a comprehensive review of primarily molecular genetic studies done so far on PCOS. We have also covered the studies focusing on the environmental factors and impact of ethnicity on the presentation of this syndrome. A large number of studies have been attempted to understand the aetiological mechanisms behind PCOS both at the clinical and molecular genetic levels. In the Indian context, majority of the PCOS studies have been confined to the clinical dimensions. However, a concrete genetic mechanism behind the manifestation of PCOS is yet to be ascertained. Understanding of this complex disorder requires comprehensive studies incorporating relatively larger homogenous samples for genetic analysis and taking into account the ethnicity and the environmental conditions of the population/cohort under study. Research focused on these aspects may provide better understanding on the genetic etiology and the interaction between genes and environment, which may help develop new treatment methods and possible prevention of the syndrome.

Present status of understanding on the genetic etiology of polycystic ovary syndrome

Directory of Open Access Journals (Sweden)

Dasgupta S

2008-01-01

Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrinopathy in women of reproductive age with a prevalence of approximately 7-10% worldwide. PCOS reflects multiple potential aetiologies and variable clinical manifestations. This syndrome is characterized by serious health implications such as diabetes, coronary heart diseases and cancer and also leads to infertility. PCOS can be viewed as a heterogeneous androgen excess disorder with varying degrees of reproductive and metabolic abnormalities determined by the interaction of multiple genetic and environmental factors. In this paper, we have attempted a comprehensive review of primarily molecular genetic studies done so far on PCOS. We have also covered the studies focusing on the environmental factors and impact of ethnicity on the presentation of this syndrome. A large number of studies have been attempted to understand the aetiological mechanisms behind PCOS both at the clinical and molecular genetic levels. In the Indian context, majority of the PCOS studies have been confined to the clinical dimensions. However, a concrete genetic mechanism behind the manifestation of PCOS is yet to be ascertained. Understanding of this complex disorder requires comprehensive studies incorporating relatively larger homogenous samples for genetic analysis and taking into account the ethnicity and the environmental conditions of the population/cohort under study. Research focused on these aspects may provide better understanding on the genetic etiology and the interaction between genes and environment, which may help develop new treatment methods and possible prevention of the syndrome.

Genetics of Vitiligo

Science.gov (United States)

Spritz, Richard; Andersen, Genevieve

2016-01-01

Synopsis Vitiligo is “complex disorder” (also termed polygenic and multifactorial), reflecting simultaneous contributions of multiple genetic risk factors and environmental triggers. Large-scale genome-wide association studies, principally in European-derived whites and in Chinese, have discovered approximately 50 different genetic loci that contribute to vitiligo risk, some of which also contribute to other autoimmune diseases that are epidemiologically associated with vitiligo. At many of these vitiligo susceptibility loci the corresponding relevant genes have now been identified, and for some of these genes the specific DNA sequence variants that contribute to vitiligo risk are also now known. A large fraction of these genes encode proteins involved in immune regulation, a number of others play roles in cellular apoptosis, and still others are involved in regulating functions of melanocytes. For this last group, there appears to be an opposite relationship between susceptibility to vitiligo and susceptibility to melanoma, suggesting that vitiligo may engage a normal mechanism of immune surveillance for melanoma. While many of the specific biologic mechanisms through which these genetic factors operate to cause vitiligo remain to be elucidated, it is now clear that vitiligo is an autoimmune disease involving a complex relationship between programming and function of the immune system, aspects of the melanocyte autoimmune target, and dysregulation of the immune response. PMID:28317533

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

Science.gov (United States)

Banda, Yambazi; Kvale, Mark N; Hoffmann, Thomas J; Hesselson, Stephanie E; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A; Dispensa, Brad P; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P; Van Den Eeden, Stephen K; Walter, Lawrence; Whitmer, Rachel A; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2015-08-01

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. Copyright © 2015 by the Genetics Society of America.

Recurrent and multiple bladder tumors show conserved expression profiles

International Nuclear Information System (INIS)

Lindgren, David; Fioretos, Thoas; Månsson, Wiking; Höglund, Mattias; Gudjonsson, Sigurdur; Jee, Kowan Ja; Liedberg, Fredrik; Aits, Sonja; Andersson, Anna; Chebil, Gunilla; Borg, Åke; Knuutila, Sakari

2008-01-01

Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors

Multiple genetic variants associated with posttransplantation diabetes mellitus in Chinese Han populations.

Science.gov (United States)

Chen, Jie; Li, Lixin; An, Yunfei; Zhang, Junlong; Liao, Yun; Li, Yi; Wang, Lanlan

2018-03-01

Posttransplantation diabetes mellitus (PTDM) is a major complication after solid organ transplantation. This study is to investigate the association of nine genetic variant factors and PTDM in Chinese Han patients. HLA-DP (rs3077, rs9277535), HLA-DQ (rs7453920), signal transducer and activator of transcription 4 (STAT4) (rs7574865), IL-28B (rs12979860, rs8099917, and rs12980275), and IL-18 (rs1946518 and rs187238) were investigated in 260 liver transplant recipients (PTDM vs non-PTDM) by high-resolution melting curve analysis. Serum interleukin (IL)-1β, IL-6, IL-8, IL-17, interferon-γ, inducible protein-10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1b were analyzed by a Bio-Plex suspension array system (Bio-Plex Multiplex Immunoassays, Bio-Rad, Hercules, CA, USA). Signal transducer and activator of transcription 4 (rs7574865) T allele and IL-18 (rs1946518) A allele increase the risk for insulin resistance and PTDM. Recipients with STAT4 (rs7574865) T allele are associated with an increased concentration of IL-1β, interferon-γ, monocyte chemoattractant protein, and macrophage inflammatory protein-1b. The genetic variants of STAT4 (rs7574865) and IL-18 (rs1946518) may be new important markers for PTDM. © 2017 Wiley Periodicals, Inc.

Results of Evolution Supervised by Genetic Algorithms

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Lorentz JÄNTSCHI

2010-09-01

Full Text Available The efficiency of a genetic algorithm is frequently assessed using a series of operators of evolution like crossover operators, mutation operators or other dynamic parameters. The present paper aimed to review the main results of evolution supervised by genetic algorithms used to identify solutions to agricultural and horticultural hard problems and to discuss the results of using a genetic algorithms on structure-activity relationships in terms of behavior of evolution supervised by genetic algorithms. A genetic algorithm had been developed and implemented in order to identify the optimal solution in term of estimation power of a multiple linear regression approach for structure-activity relationships. Three survival and three selection strategies (proportional, deterministic and tournament were investigated in order to identify the best survival-selection strategy able to lead to the model with higher estimation power. The Molecular Descriptors Family for structure characterization of a sample of 206 polychlorinated biphenyls with measured octanol-water partition coefficients was used as case study. Evolution using different selection and survival strategies proved to create populations of genotypes living in the evolution space with different diversity and variability. Under a series of criteria of comparisons these populations proved to be grouped and the groups were showed to be statistically different one to each other. The conclusions about genetic algorithm evolution according to a number of criteria were also highlighted.

Earthquake—explosion discrimination using genetic algorithm-based boosting approach

Science.gov (United States)

Orlic, Niksa; Loncaric, Sven

2010-02-01

An important and challenging problem in seismic data processing is to discriminate between natural seismic events such as earthquakes and artificial seismic events such as explosions. Many automatic techniques for seismogram classification have been proposed in the literature. Most of these methods have a similar approach to seismogram classification: a predefined set of features based on ad-hoc feature selection criteria is extracted from the seismogram waveform or spectral data and these features are used for signal classification. In this paper we propose a novel approach for seismogram classification. A specially formulated genetic algorithm has been employed to automatically search for a near-optimal seismogram feature set, instead of using ad-hoc feature selection criteria. A boosting method is added to the genetic algorithm when searching for multiple features in order to improve classification performance. A learning set of seismogram data is used by the genetic algorithm to discover a near-optimal feature set. The feature set identified by the genetic algorithm is then used for seismogram classification. The described method is developed to classify seismograms in two groups, whereas a brief overview of method extension for multiple group classification is given. For method verification, a learning set consisting of 40 local earthquake seismograms and 40 explosion seismograms was used. The method was validated on seismogram set consisting of 60 local earthquake seismograms and 60 explosion seismograms, with correct classification of 85%.

Profile of genetic disorders prevalent in northeast region of Cairo ...

African Journals Online (AJOL)

Rabah M. Shawky

2012-02-04

Feb 4, 2012 ... syndromes, multiple genetic disorders in the same individual or same family and homozygosity ...... array of hereditary eye disorders has been identified. These in- ..... of ED, decreased sweating was present in 92%, dry skin in.

Multiple introductions of the dengue vector, Aedes aegypti, into California.

Science.gov (United States)

Pless, Evlyn; Gloria-Soria, Andrea; Evans, Benjamin R; Kramer, Vicki; Bolling, Bethany G; Tabachnick, Walter J; Powell, Jeffrey R

2017-08-01

The yellow fever mosquito Aedes aegypti inhabits much of the tropical and subtropical world and is a primary vector of dengue, Zika, and chikungunya viruses. Breeding populations of A. aegypti were first reported in California (CA) in 2013. Initial genetic analyses using 12 microsatellites on collections from Northern CA in 2013 indicated the South Central US region as the likely source of the introduction. We expanded genetic analyses of CA A. aegypti by: (a) examining additional Northern CA samples and including samples from Southern CA, (b) including more southern US populations for comparison, and (c) genotyping a subset of samples at 15,698 SNPs. Major results are: (1) Northern and Southern CA populations are distinct. (2) Northern populations are more genetically diverse than Southern CA populations. (3) Northern and Southern CA groups were likely founded by two independent introductions which came from the South Central US and Southwest US/northern Mexico regions respectively. (4) Our genetic data suggest that the founding events giving rise to the Northern CA and Southern CA populations likely occurred before the populations were first recognized in 2013 and 2014, respectively. (5) A Northern CA population analyzed at multiple time-points (two years apart) is genetically stable, consistent with permanent in situ breeding. These results expand previous work on the origin of California A. aegypti with the novel finding that this species entered California on multiple occasions, likely some years before its initial detection. This work has implications for mosquito surveillance and vector control activities not only in California but also in other regions where the distribution of this invasive mosquito is expanding.

Multiple introductions of the dengue vector, Aedes aegypti, into California.

Directory of Open Access Journals (Sweden)

Evlyn Pless

2017-08-01

Full Text Available The yellow fever mosquito Aedes aegypti inhabits much of the tropical and subtropical world and is a primary vector of dengue, Zika, and chikungunya viruses. Breeding populations of A. aegypti were first reported in California (CA in 2013. Initial genetic analyses using 12 microsatellites on collections from Northern CA in 2013 indicated the South Central US region as the likely source of the introduction. We expanded genetic analyses of CA A. aegypti by: (a examining additional Northern CA samples and including samples from Southern CA, (b including more southern US populations for comparison, and (c genotyping a subset of samples at 15,698 SNPs. Major results are: (1 Northern and Southern CA populations are distinct. (2 Northern populations are more genetically diverse than Southern CA populations. (3 Northern and Southern CA groups were likely founded by two independent introductions which came from the South Central US and Southwest US/northern Mexico regions respectively. (4 Our genetic data suggest that the founding events giving rise to the Northern CA and Southern CA populations likely occurred before the populations were first recognized in 2013 and 2014, respectively. (5 A Northern CA population analyzed at multiple time-points (two years apart is genetically stable, consistent with permanent in situ breeding. These results expand previous work on the origin of California A. aegypti with the novel finding that this species entered California on multiple occasions, likely some years before its initial detection. This work has implications for mosquito surveillance and vector control activities not only in California but also in other regions where the distribution of this invasive mosquito is expanding.

Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

Science.gov (United States)

Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

2014-01-01

Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

The incidence of genetic disorders in children and young adults

International Nuclear Information System (INIS)

Anderson, T.W.; Baird, P.A.; Lowry, R.B.; Newcombe, H.B.

1987-11-01

Current estimates of the genetic risks from exposure to ionizing radiation are based on two kinds of data: a) incidence rates in humans for the genetic diseases that are believed to be present in the population due to mutations of natural origin, and b) radiation induced mutation rates. One necessary prerequisite before any possible increase in genetic load from mutagens can be estimated is baseline information on the magnitude of genetically-caused ill health already present in the population. The present study utilizes the data base of an ongoing population-based Registry with multiple sources of ascertainment to estimate the present population load from genetic disease. It was found that 4.9% of liveborn individuals below 25 can be expected to have genetic or partly genetic diseases. This was composed of single-gene disorders (autosomal dominant, autosomal recessive and X-linked recessive), chromosomal anomalies and multifactorial disorders (including those present at birth and those later in onset). Since previous studies have usually considered all congenital anomalies (ICD 740-759) as part of the genetic load, data are also presented separately for this category to facilitate comparison with earlier studies. These new data should represent a better estimate of the genetic load in the population than previous studies

Genetic components to caste allocation in a multiple-queen ant species

NARCIS (Netherlands)

Libbrecht, Romain; Schwander, Tanja; Keller, Laurent

2011-01-01

Reproductive division of labor and the coexistence of distinct castes are hallmarks of insect societies. In social insect species with multiple queens per colony, the fitness of nestmate queens directly depends on the process of caste allocation (i.e., the relative investment in queen, sterile

Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

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Qiong Yang

2012-01-01

Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

Science.gov (United States)

Banda, Yambazi; Kvale, Mark N.; Hoffmann, Thomas J.; Hesselson, Stephanie E.; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A.; Dispensa, Brad P.; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H.; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P.; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C.; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P.; Van Den Eeden, Stephen K.; Walter, Lawrence; Whitmer, Rachel A.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2015-01-01

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian–European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent–child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent–child pairs was largely due to intermarriage. The parent–child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. PMID:26092716

Multiple sclerosis - etiology and diagnostic potential.

Science.gov (United States)

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Multiple sclerosis - etiology and diagnostic potential

Directory of Open Access Journals (Sweden)

Joanna Kamińska

2017-06-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Toward genetics-based virus taxonomy: comparative analysis of a genetics-based classification and the taxonomy of picornaviruses.

Science.gov (United States)

Lauber, Chris; Gorbalenya, Alexander E

2012-04-01

Virus taxonomy has received little attention from the research community despite its broad relevance. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3890-3904, 2012), we have introduced a quantitative approach to hierarchically classify viruses of a family using pairwise evolutionary distances (PEDs) as a measure of genetic divergence. When applied to the six most conserved proteins of the Picornaviridae, it clustered 1,234 genome sequences in groups at three hierarchical levels (to which we refer as the "GENETIC classification"). In this study, we compare the GENETIC classification with the expert-based picornavirus taxonomy and outline differences in the underlying frameworks regarding the relation of virus groups and genetic diversity that represent, respectively, the structure and content of a classification. To facilitate the analysis, we introduce two novel diagrams. The first connects the genetic diversity of taxa to both the PED distribution and the phylogeny of picornaviruses. The second depicts a classification and the accommodated genetic diversity in a standardized manner. Generally, we found striking agreement between the two classifications on species and genus taxa. A few disagreements concern the species Human rhinovirus A and Human rhinovirus C and the genus Aphthovirus, which were split in the GENETIC classification. Furthermore, we propose a new supergenus level and universal, level-specific PED thresholds, not reached yet by many taxa. Since the species threshold is approached mostly by taxa with large sampling sizes and those infecting multiple hosts, it may represent an upper limit on divergence, beyond which homologous recombination in the six most conserved genes between two picornaviruses might not give viable progeny.

The relation between multilocus population genetics and social evolution theory.

Science.gov (United States)

Gardner, Andy; West, Stuart A; Barton, Nicholas H

2007-02-01

Evolution at multiple gene positions is complicated. Direct selection on one gene disturbs the evolutionary dynamics of associated genes. Recent years have seen the development of a multilocus methodology for modeling evolution at arbitrary numbers of gene positions with arbitrary dominance and epistatic relations, mode of inheritance, genetic linkage, and recombination. We show that the approach is conceptually analogous to social evolutionary methodology, which focuses on selection acting on associated individuals. In doing so, we (1) make explicit the links between the multilocus methodology and the foundations of social evolution theory, namely, Price's theorem and Hamilton's rule; (2) relate the multilocus approach to levels-of-selection and neighbor-modulated-fitness approaches in social evolution; (3) highlight the equivalence between genetical hitchhiking and kin selection; (4) demonstrate that the multilocus methodology allows for social evolutionary analyses involving coevolution of multiple traits and genetical associations between nonrelatives, including individuals of different species; (5) show that this methodology helps solve problems of dynamic sufficiency in social evolution theory; (6) form links between invasion criteria in multilocus systems and Hamilton's rule of kin selection; (7) illustrate the generality and exactness of Hamilton's rule, which has previously been described as an approximate, heuristic result.

MAC Protocol for Ad Hoc Networks Using a Genetic Algorithm

Science.gov (United States)

Elizarraras, Omar; Panduro, Marco; Méndez, Aldo L.

2014-01-01

The problem of obtaining the transmission rate in an ad hoc network consists in adjusting the power of each node to ensure the signal to interference ratio (SIR) and the energy required to transmit from one node to another is obtained at the same time. Therefore, an optimal transmission rate for each node in a medium access control (MAC) protocol based on CSMA-CDMA (carrier sense multiple access-code division multiple access) for ad hoc networks can be obtained using evolutionary optimization. This work proposes a genetic algorithm for the transmission rate election considering a perfect power control, and our proposition achieves improvement of 10% compared with the scheme that handles the handshaking phase to adjust the transmission rate. Furthermore, this paper proposes a genetic algorithm that solves the problem of power combining, interference, data rate, and energy ensuring the signal to interference ratio in an ad hoc network. The result of the proposed genetic algorithm has a better performance (15%) compared to the CSMA-CDMA protocol without optimizing. Therefore, we show by simulation the effectiveness of the proposed protocol in terms of the throughput. PMID:25140339

MAC Protocol for Ad Hoc Networks Using a Genetic Algorithm

Directory of Open Access Journals (Sweden)

Omar Elizarraras

2014-01-01

Full Text Available The problem of obtaining the transmission rate in an ad hoc network consists in adjusting the power of each node to ensure the signal to interference ratio (SIR and the energy required to transmit from one node to another is obtained at the same time. Therefore, an optimal transmission rate for each node in a medium access control (MAC protocol based on CSMA-CDMA (carrier sense multiple access-code division multiple access for ad hoc networks can be obtained using evolutionary optimization. This work proposes a genetic algorithm for the transmission rate election considering a perfect power control, and our proposition achieves improvement of 10% compared with the scheme that handles the handshaking phase to adjust the transmission rate. Furthermore, this paper proposes a genetic algorithm that solves the problem of power combining, interference, data rate, and energy ensuring the signal to interference ratio in an ad hoc network. The result of the proposed genetic algorithm has a better performance (15% compared to the CSMA-CDMA protocol without optimizing. Therefore, we show by simulation the effectiveness of the proposed protocol in terms of the throughput.

Genetic structure of the tiger mosquito, Aedes albopictus, in Cameroon (Central Africa.

Directory of Open Access Journals (Sweden)

Basile Kamgang

Full Text Available Aedes albopictus (Skuse, 1884 (Diptera: Culicidae, a mosquito native to Asia, has recently invaded all five continents. In Central Africa it was first reported in the early 2000s, and has since been implicated in the emergence of arboviruses such as dengue and chikungunya in this region. Recent genetic studies of invasive species have shown that multiple introductions are a key factor for successful expansion in new areas. As a result, phenotypic characters such as vector competence and insecticide susceptibility may vary within invasive pest species, potentially affecting vector efficiency and pest management. Here we assessed the genetic variability and population genetics of Ae. albopictus isolates in Cameroon (Central Africa, thereby deducing their likely geographic origin.Mosquitoes were sampled in 2007 in 12 localities in southern Cameroon and analyzed for polymorphism at six microsatellite loci and in two mitochondrial DNA regions (ND5 and COI. All the microsatellite markers were successfully amplified and were polymorphic, showing moderate genetic structureamong geographic populations (F(ST  = 0.068, P < 0.0001. Analysis of mtDNA sequences revealed four haplotypes each for the COI and ND5 genes, with a dominant haplotype shared by all Cameroonian samples. The weak genetic variation estimated from the mtDNA genes is consistent with the recent arrival of Ae. albopictus in Cameroon. Phylogeographic analysis based on COI polymorphism indicated that Ae. albopictus populations from Cameroon are related to tropical rather than temperate or subtropical outgroups.The moderate genetic diversity observed among Cameroonian Ae. albopictus isolates is in keeping with recent introduction and spread in this country. The genetic structure of natural populations points to multiple introductions from tropical regions.

Invited review: Genetic and genomic mouse models for livestock research

Directory of Open Access Journals (Sweden)

D. Arends

2018-02-01

Full Text Available Knowledge about the function and functioning of single or multiple interacting genes is of the utmost significance for understanding the organism as a whole and for accurate livestock improvement through genomic selection. This includes, but is not limited to, understanding the ontogenetic and environmentally driven regulation of gene action contributing to simple and complex traits. Genetically modified mice, in which the functions of single genes are annotated; mice with reduced genetic complexity; and simplified structured populations are tools to gain fundamental knowledge of inheritance patterns and whole system genetics and genomics. In this review, we briefly describe existing mouse resources and discuss their value for fundamental and applied research in livestock.

Sparse redundancy analysis of high-dimensional genetic and genomic data

NARCIS (Netherlands)

Csala, Attila; Voorbraak, Frans P. J. M.; Zwinderman, Aeilko H.; Hof, Michel H.

2017-01-01

Motivation: Recent technological developments have enabled the possibility of genetic and genomic integrated data analysis approaches, where multiple omics datasets from various biological levels are combined and used to describe (disease) phenotypic variations. The main goal is to explain and

Drag reduction of a car model by linear genetic programming control

Science.gov (United States)

Li, Ruiying; Noack, Bernd R.; Cordier, Laurent; Borée, Jacques; Harambat, Fabien

2017-08-01

We investigate open- and closed-loop active control for aerodynamic drag reduction of a car model. Turbulent flow around a blunt-edged Ahmed body is examined at ReH≈ 3× 105 based on body height. The actuation is performed with pulsed jets at all trailing edges (multiple inputs) combined with a Coanda deflection surface. The flow is monitored with 16 pressure sensors distributed at the rear side (multiple outputs). We apply a recently developed model-free control strategy building on genetic programming in Dracopoulos and Kent (Neural Comput Appl 6:214-228, 1997) and Gautier et al. (J Fluid Mech 770:424-441, 2015). The optimized control laws comprise periodic forcing, multi-frequency forcing and sensor-based feedback including also time-history information feedback and combinations thereof. Key enabler is linear genetic programming (LGP) as powerful regression technique for optimizing the multiple-input multiple-output control laws. The proposed LGP control can select the best open- or closed-loop control in an unsupervised manner. Approximately 33% base pressure recovery associated with 22% drag reduction is achieved in all considered classes of control laws. Intriguingly, the feedback actuation emulates periodic high-frequency forcing. In addition, the control identified automatically the only sensor which listens to high-frequency flow components with good signal to noise ratio. Our control strategy is, in principle, applicable to all multiple actuators and sensors experiments.

A Primer on the Genetics of Comorbid Eating Disorders and Substance Use Disorders.

Science.gov (United States)

Munn-Chernoff, Melissa A; Baker, Jessica H

2016-03-01

Eating disorders (EDs) and substance use disorders (SUDs) frequently co-occur; however, the reasons for this are unclear. We review the current literature on genetic risk for EDs and SUDs, as well as preliminary findings exploring whether these classes of disorders have overlapping genetic risk. Overall, genetic factors contribute to individual differences in liability to multiple EDs and SUDs. Although initial family studies concluded that no shared familial (which includes genetic) risk between EDs and SUDs exists, twin studies suggest a moderate proportion of shared variance is attributable to overlapping genetic factors, particularly for those EDs characterized by binge eating and/or inappropriate compensatory behaviours. No adoption or molecular genetic studies have examined shared genetic risk between these classes of disorders. Research investigating binge eating and inappropriate compensatory behaviours using emerging statistical genetic methods, as well as examining gene-environment interplay, will provide important clues into the aetiology of comorbid EDs and SUDs. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida.

Science.gov (United States)

Vadaparampil, S T; Scherr, C L; Cragun, D; Malo, T L; Pal, T

2015-05-01

Genetic counseling and testing for hereditary breast and ovarian cancer now includes practitioners from multiple healthcare professions, specialties, and settings. This study examined whether non-genetics professionals (NGPs) perform guideline-based patient intake and informed consent before genetic testing. NGPs offering BRCA testing services in Florida (n = 386) were surveyed about clinical practices. Among 81 respondents (response rate = 22%), approximately half reported: sometimes scheduling a separate session for pre-test counseling lasting 11-30 min prior to testing, discussing familial implications of testing, benefits and limitations of risk management options, and discussing the potential psychological impact and insurance-related issues. Few constructed a three-generation pedigree, discussed alternative hereditary cancer syndromes, or the meaning of a variant result. This lack of adherence to guideline-based practice may result in direct harm to patients and their family members. NGPs who are unable to deliver guideline adherent cancer genetics services should focus on identification and referral of at-risk patients to in person or telephone services provided by genetics professionals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a Caucasian family.

Science.gov (United States)

De Summa, Simona; Guida, Michele; Tommasi, Stefania; Strippoli, Sabino; Pellegrini, Cristina; Fargnoli, Maria Concetta; Pilato, Brunella; Natalicchio, Iole; Guida, Gabriella; Pinto, Rosamaria

2017-05-02

Multiple primary melanoma (MPM) is a rare condition, whose genetic basis has not yet been clarified. Only 8-12% of MPM are due to germline mutations of CDKN2A. However, other genes (POT1, BRCA1/2, MC1R, MGMT) have been demonstrated to be involved in predisposition to this pathology.To our knowledge, this is the first family study based on two siblings with the rare coexistence of MPM and oculocutaneous albinism (OCA), an autosomal recessive disease characterized by the absence or decrease in pigmentation in the skin, hair, and eyes.In this study, we evaluated genes involved in melanoma predisposition (CDKN2A, CDK4, MC1R, MITF, POT1, RB1, MGMT, BRCA1, BRCA2), pathogenesis (BRAF, NRAS, PIK3CA, KIT, PTEN), skin/hair pigmentation (MC1R, MITF) and in immune pathways (CTLA4) to individuate alterations able to explain the rare onset of MPM and OCA in indexes and the transmission in their pedigree.From the analysis of the pedigree, we were able to identify a "protective" haplotype with respect to MPM, including MGMT p.I174V alteration. The second generation offspring is under strict follow up as some of them have a higher risk of developing MPM according to our model.

Fractional populations in multiple gene inheritance.

Science.gov (United States)

Chung, Myung-Hoon; Kim, Chul Koo; Nahm, Kyun