Effect of sex, age, and breed on genetic recombination features in cattle

USDA-ARS?s Scientific Manuscript database

Meiotic recombination is a fundamental biological process which generates genetic diversity, affects fertility, and influences evolvability. Here we investigate the roles of sex, age, and breed in cattle recombination features, including recombination rate, location and crossover interference. Usin...

Disrupting evolutionary processes: the effect of habitat fragmentation on collared lizards in the Missouri Ozarks.

PubMed

Templeton, A R; Robertson, R J; Brisson, J; Strasburg, J

2001-05-08

Humans affect biodiversity at the genetic, species, community, and ecosystem levels. This impact on genetic diversity is critical, because genetic diversity is the raw material of evolutionary change, including adaptation and speciation. Two forces affecting genetic variation are genetic drift (which decreases genetic variation within but increases genetic differentiation among local populations) and gene flow (which increases variation within but decreases differentiation among local populations). Humans activities often augment drift and diminish gene flow for many species, which reduces genetic variation in local populations and prevents the spread of adaptive complexes outside their population of origin, thereby disrupting adaptive processes both locally and globally within a species. These impacts are illustrated with collared lizards (Crotaphytus collaris) in the Missouri Ozarks. Forest fire suppression has reduced habitat and disrupted gene flow in this lizard, thereby altering the balance toward drift and away from gene flow. This balance can be restored by managed landscape burns. Some have argued that, although human-induced fragmentation disrupts adaptation, it will also ultimately produce new species through founder effects. However, population genetic theory and experiments predict that most fragmentation events caused by human activities will facilitate not speciation, but local extinction. Founder events have played an important role in the macroevolution of certain groups, but only when ecological opportunities are expanding rather than contracting. The general impact of human activities on genetic diversity disrupts or diminishes the capacity for adaptation, speciation, and macroevolutionary change. This impact will ultimately diminish biodiversity at all levels.

Heritability of the neural response to emotional pictures: evidence from ERPs in an adult twin sample.

PubMed

Weinberg, Anna; Venables, Noah C; Proudfit, Greg Hajcak; Patrick, Christopher J

2015-03-01

Affect-modulated event-related potentials (ERPs) are increasingly used to study psychopathology and individual differences in emotion processing. Many have suggested that variation in these neural responses reflects genetically mediated risk. However, to date, no studies have demonstrated genetic contributions to affect-modulated ERPs. The present study therefore sought to examine the heritability of a range of ERPs elicited during affective picture viewing. One hundred and thirty monozygotic and 124 dizygotic twin pairs passively viewed 30 pleasant, 30 neutral and 30 unpleasant images for 6 s each. The early posterior negativity was scored for each subject; in addition, the P300/late positive potential (LPP) was scored in multiple time windows and sites. Results indicate that the centro-parietal P300 (occurring between 300 and 600 ms) is subject to substantial genetic contributions. Furthermore, variance in the P300 elicited by affective stimuli was moderately heritable even after controlling for the P300 elicited by neutral stimuli. Later and more frontal activation (i.e. between 1000 and 3000 ms) also showed evidence of heritablity. Early parietal, and perhaps later frontal portions of the P300/LPP complex, may therefore represent promising neurobehavioral markers of genetically influenced processing of emotional information. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Alexithymia, emotion perception, and social assertiveness in adult women with Noonan and Turner syndromes.

PubMed

Roelofs, Renée L; Wingbermühle, Ellen; Freriks, Kim; Verhaak, Chris M; Kessels, Roy P C; Egger, Jos I M

2015-04-01

Noonan syndrome (NS) and Turner syndrome (TS) are associated with cognitive problems and difficulties in affective information processing. While both phenotypes include short stature, facial dysmorphisms, and a webbed neck, genetic etiology and neuropsychological phenotype differ significantly. The present study examines putative differences in affective information processing and social assertiveness between adult women with NS and TS. Twenty-six women with NS, 40 women with TS, and 40 female controls were matched on age and intelligence, and subsequently compared on (1) alexithymia, measured by the Bermond-Vorst Alexithymia Questionnaire, (2) emotion perception, evaluated by the Emotion Recognition Task, and (3) social assertiveness and social discomfort, assessed by the Scale for Interpersonal Behavior. Women with TS showed higher levels of alexithymia than women with NS and controls (P-values < 0.001), whereas women with NS had more trouble recognizing angry facial expressions in comparison with controls (P = 0.01). No significant group differences were found for the frequency of social assertiveness and the level of social discomfort. Women with NS and TS demonstrated different patterns of impairment in affective information processing, in terms of alexithymia and emotion perception. The present findings suggest neuropsychological phenotyping to be helpful for the diagnosis of specific cognitive-affective deficits in genetic syndromes, for the enhancement of genetic counseling, and for the development of personalized treatment plans. © 2015 Wiley Periodicals, Inc.

Atypical Sensory Processing in Adolescents with an Autism Spectrum Disorder and Their Non-Affected Siblings

ERIC Educational Resources Information Center

De la Marche, Wouter; Steyaert, Jean; Noens, Ilse

2012-01-01

Atypical sensory processing is common in autism spectrum disorders (ASD). Specific profiles have been proposed in different age groups, but no study has focused specifically on adolescents. Identifying traits of ASD that are shared by individuals with ASD and their non-affected family members can shed light on the genetic underpinnings of ASD.…

Individual differences in cognition, affect, and performance: Behavioral, neuroimaging, and molecular genetic approaches

PubMed Central

Parasuraman, Raja; Jiang, Yang

2012-01-01

We describe the use of behavioral, neuroimaging, and genetic methods to examine individual differences in cognition and affect, guided by three criteria: (1) relevance to human performance in work and everyday settings; (2) interactions between working memory, decision-making, and affective processing; and (3) examination of individual differences. The results of behavioral, functional MRI (fMRI), event-related potential (ERP), and molecular genetic studies show that analyses at the group level often mask important findings associated with sub-groups of individuals. Dopaminergic/noradrenergic genes influencing prefrontal cortex activity contribute to inter-individual variation in working memory and decision behavior, including performance in complex simulations of military decision-making. The interactive influences of individual differences in anxiety, sensation seeking, and boredom susceptibility on evaluative decision-making can be systematically described using ERP and fMRI methods. We conclude that a multi-modal neuroergonomic approach to examining brain function (using both neuroimaging and molecular genetics) can be usefully applied to understanding individual differences in cognition and affect and has implications for human performance at work. PMID:21569853

Factors influencing parents' decision to donate their healthy infant's DNA for minimal-risk genetic research.

PubMed

Hatfield, Linda A; Pearce, Margaret M

2014-11-01

To examine factors that influence a parent's decision to donate their healthy infant's DNA for minimal-risk genetic research. Grounded theory, using semi-structured interviews conducted with 35 postpartum mother or mother-father dyads in an urban teaching hospital. Data were collected from July 2011 to January 2012. Audiorecorded semistructured interviews were conducted in private rooms with mothers or mother-father dyads 24 to 48 hr after the birth of their healthy, full-term infant. Data-driven content analysis using selected principles of grounded theory was performed. Parents' willingness to donate their healthy infant's DNA for minimal-risk pediatric genetic research emerged as a process involving three interacting components: the parents, the scientist, and the comfort of the child embedded within the context of benefit to the child. The purpose of the study and parents' perception of their commitment of time and resources determined their willingness to participate. The scientist's ability to communicate trust in the research process influenced parents' decisions. Physical discomfort of the child shaped parents' decision to donate DNA. Parental perception of a direct benefit to their child affected their willingness to discuss genetic research and its outcomes. Significant gaps and misunderstandings in parental knowledge of pediatric genetic research may affect parental willingness to donate their healthy child's DNA. Nurses knowledgeable about the decision-making process parents utilize to donate their healthy infant's DNA for minimal-risk genetic research and the factors influencing that decision are well positioned to educate parents about the role of genetics in health and illness and reassure potential research participants of the value and safeguards in pediatric genetic research. © 2014 Sigma Theta Tau International.

Genetic Variation in the MAPK/ERK Pathway Affects Contact Hypersensitivity Responses.

PubMed

Legrand, Julien M D; Roy, Edwige; Baz, Batoul; Mukhopadhyay, Pamela; Wong, Ho Yi; Ram, Ramesh; Morahan, Grant; Walker, Graeme; Khosrotehrani, Kiarash

2018-05-10

Using a genetic resource that enables rapid mapping of genes for complex traits, we demonstrate dramatic diversity between murine strains in response to immune challenge. We identified several candidate genes that point to the MAPK/ERK pathway as a key modulator of this process. Copyright © 2018. Published by Elsevier Inc.

Warpage improvement on wheel caster by optimizing the process parameters using genetic algorithm (GA)

NASA Astrophysics Data System (ADS)

Safuan, N. S.; Fathullah, M.; Shayfull, Z.; Nasir, S. M.; Hazwan, M. H. M.

2017-09-01

In injection moulding process, the defects will always encountered and affected the final product shape and functionality. This study is concerning on minimizing warpage and optimizing the process parameter of injection moulding part. Apart from eliminating product wastes, this project also giving out best recommended parameters setting. This research studied on five parameters. The optimization showed that warpage have been improved 42.64% from 0.6524 mm to 0.30879 mm in Autodesk Moldflow Insight (AMI) simulation result and Genetic Algorithm (GA) respectively.

Test- and behavior-specific genetic factors affect WKY hypoactivity in tests of emotionality.

PubMed

Baum, Amber E; Solberg, Leah C; Churchill, Gary A; Ahmadiyeh, Nasim; Takahashi, Joseph S; Redei, Eva E

2006-05-15

Inbred Wistar-Kyoto rats consistently display hypoactivity in tests of emotional behavior. We used them to test the hypothesis that the genetic factors underlying the behavioral decision-making process will vary in different environmental contexts. The contexts used were the open-field test (OFT), a novel environment with no explicit threats present, and the defensive-burying test (DB), a habituated environment into which a threat has been introduced. Rearing, a voluntary behavior was measured in both tests, and our study was the first to look for genetic loci affecting grooming, a relatively automatic, stress-responsive stereotyped behavior. Quantitative trait locus analysis was performed on a population of 486 F2 animals bred from reciprocal inter-crosses. The genetic architectures of DB and OFT rearing, and of DB and OFT grooming, were compared. There were no common loci affecting grooming behavior in both tests. These different contexts produced the stereotyped behavior via different pathways, and genetic factors seem to influence the decision-making pathways and not the expression of the behavior. Three loci were found that affected rearing behavior in both tests. However, in both contexts, other loci had greater effects on the behavior. Our results imply that environmental context's effects on decision-making vary depending on the category of behavior.

Altitudinal gradients, biogeographic history and microhabitat adaptation affect fine-scale spatial genetic structure in African and Neotropical populations of an ancient tropical tree species.

PubMed

Torroba-Balmori, Paloma; Budde, Katharina B; Heer, Katrin; González-Martínez, Santiago C; Olsson, Sanna; Scotti-Saintagne, Caroline; Casalis, Maxime; Sonké, Bonaventure; Dick, Christopher W; Heuertz, Myriam

2017-01-01

The analysis of fine-scale spatial genetic structure (FSGS) within populations can provide insights into eco-evolutionary processes. Restricted dispersal and locally occurring genetic drift are the primary causes for FSGS at equilibrium, as described in the isolation by distance (IBD) model. Beyond IBD expectations, spatial, environmental or historical factors can affect FSGS. We examined FSGS in seven African and Neotropical populations of the late-successional rain forest tree Symphonia globulifera L. f. (Clusiaceae) to discriminate the influence of drift-dispersal vs. landscape/ecological features and historical processes on FSGS. We used spatial principal component analysis and Bayesian clustering to assess spatial genetic heterogeneity at SSRs and examined its association with plastid DNA and habitat features. African populations (from Cameroon and São Tomé) displayed a stronger FSGS than Neotropical populations at both marker types (mean Sp = 0.025 vs. Sp = 0.008 at SSRs) and had a stronger spatial genetic heterogeneity. All three African populations occurred in pronounced altitudinal gradients, possibly restricting animal-mediated seed dispersal. Cyto-nuclear disequilibria in Cameroonian populations also suggested a legacy of biogeographic history to explain these genetic patterns. Conversely, Neotropical populations exhibited a weaker FSGS, which may reflect more efficient wide-ranging seed dispersal by Neotropical bats and other dispersers. The population from French Guiana displayed an association of plastid haplotypes with two morphotypes characterized by differential habitat preferences. Our results highlight the importance of the microenvironment for eco-evolutionary processes within persistent tropical tree populations.

Altitudinal gradients, biogeographic history and microhabitat adaptation affect fine-scale spatial genetic structure in African and Neotropical populations of an ancient tropical tree species

PubMed Central

Torroba-Balmori, Paloma; Budde, Katharina B.; Heer, Katrin; González-Martínez, Santiago C.; Olsson, Sanna; Scotti-Saintagne, Caroline; Sonké, Bonaventure; Dick, Christopher W.

2017-01-01

The analysis of fine-scale spatial genetic structure (FSGS) within populations can provide insights into eco-evolutionary processes. Restricted dispersal and locally occurring genetic drift are the primary causes for FSGS at equilibrium, as described in the isolation by distance (IBD) model. Beyond IBD expectations, spatial, environmental or historical factors can affect FSGS. We examined FSGS in seven African and Neotropical populations of the late-successional rain forest tree Symphonia globulifera L. f. (Clusiaceae) to discriminate the influence of drift-dispersal vs. landscape/ecological features and historical processes on FSGS. We used spatial principal component analysis and Bayesian clustering to assess spatial genetic heterogeneity at SSRs and examined its association with plastid DNA and habitat features. African populations (from Cameroon and São Tomé) displayed a stronger FSGS than Neotropical populations at both marker types (mean Sp = 0.025 vs. Sp = 0.008 at SSRs) and had a stronger spatial genetic heterogeneity. All three African populations occurred in pronounced altitudinal gradients, possibly restricting animal-mediated seed dispersal. Cyto-nuclear disequilibria in Cameroonian populations also suggested a legacy of biogeographic history to explain these genetic patterns. Conversely, Neotropical populations exhibited a weaker FSGS, which may reflect more efficient wide-ranging seed dispersal by Neotropical bats and other dispersers. The population from French Guiana displayed an association of plastid haplotypes with two morphotypes characterized by differential habitat preferences. Our results highlight the importance of the microenvironment for eco-evolutionary processes within persistent tropical tree populations. PMID:28771629

The epigenomic landscape of African rainforest hunter-gatherers and farmers.

PubMed

Fagny, Maud; Patin, Etienne; MacIsaac, Julia L; Rotival, Maxime; Flutre, Timothée; Jones, Meaghan J; Siddle, Katherine J; Quach, Hélène; Harmant, Christine; McEwen, Lisa M; Froment, Alain; Heyer, Evelyne; Gessain, Antoine; Betsem, Edouard; Mouguiama-Daouda, Patrick; Hombert, Jean-Marie; Perry, George H; Barreiro, Luis B; Kobor, Michael S; Quintana-Murci, Lluis

2015-11-30

The genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation--particularly that correlated with historical lifestyle--shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time.

Landscape attributes and life history variability shape genetic structure of trout populations in a stream network

USGS Publications Warehouse

Neville, H.M.; Dunham, J.B.; Peacock, M.M.

2006-01-01

Spatial and temporal landscape patterns have long been recognized to influence biological processes, but these processes often operate at scales that are difficult to study by conventional means. Inferences from genetic markers can overcome some of these limitations. We used a landscape genetics approach to test hypotheses concerning landscape processes influencing the demography of Lahontan cutthroat trout in a complex stream network in the Great Basin desert of the western US. Predictions were tested with population- and individual-based analyses of microsatellite DNA variation, reflecting patterns of dispersal, population stability, and local effective population sizes. Complementary genetic inferences suggested samples from migratory corridors housed a mixture of fish from tributaries, as predicted based on assumed migratory life histories in those habitats. Also as predicted, populations presumed to have greater proportions of migratory fish or from physically connected, large, or high quality habitats had higher genetic variability and reduced genetic differentiation from other populations. Populations thought to contain largely non-migratory individuals generally showed the opposite pattern, suggesting behavioral isolation. Estimated effective sizes were small, and we identified significant and severe genetic bottlenecks in several populations that were isolated, recently founded, or that inhabit streams that desiccate frequently. Overall, this work suggested that Lahontan cutthroat trout populations in stream networks are affected by a combination of landscape and metapopulation processes. Results also demonstrated that genetic patterns can reveal unexpected processes, even within a system that is well studied from a conventional ecological perspective. ?? Springer 2006.

Optimisation of shock absorber process parameters using failure mode and effect analysis and genetic algorithm

NASA Astrophysics Data System (ADS)

Mariajayaprakash, Arokiasamy; Senthilvelan, Thiyagarajan; Vivekananthan, Krishnapillai Ponnambal

2013-07-01

The various process parameters affecting the quality characteristics of the shock absorber during the process were identified using the Ishikawa diagram and by failure mode and effect analysis. The identified process parameters are welding process parameters (squeeze, heat control, wheel speed, and air pressure), damper sealing process parameters (load, hydraulic pressure, air pressure, and fixture height), washing process parameters (total alkalinity, temperature, pH value of rinsing water, and timing), and painting process parameters (flowability, coating thickness, pointage, and temperature). In this paper, the process parameters, namely, painting and washing process parameters, are optimized by Taguchi method. Though the defects are reasonably minimized by Taguchi method, in order to achieve zero defects during the processes, genetic algorithm technique is applied on the optimized parameters obtained by Taguchi method.

Genetic and environmental influences on growth from late childhood to adulthood: a longitudinal study of two Finnish twin cohorts.

PubMed

Jelenkovic, Aline; Ortega-Alonso, Alfredo; Rose, Richard J; Kaprio, Jaakko; Rebato, Esther; Silventoinen, Karri

2011-01-01

Human growth is a complex process that remains insufficiently understood. We aimed to analyze genetic and environmental influences on growth from late childhood to early adulthood. Two cohorts of monozygotic and dizygotic (same sex and opposite sex) Finnish twin pairs were studied longitudinally using self-reported height at 11-12, 14, and 17 years and adult age (FinnTwin12) and at 16, 17, and 18 years and adult age (FinnTwin16). Univariate and multivariate variance component models for twin data were used. From childhood to adulthood, genetic differences explained 72-81% of the variation of height in boys and 65-86% in girls. Environmental factors common to co-twins explained 5-23% of the variation of height, with the residual variation explained by environmental factors unique to each twin individual. Common environmental factors affecting height were highly correlated between the analyzed ages (0.72-0.99 and 0.91-1.00 for boys and girls, respectively). Genetic (0.58-0.99 and 0.70-0.99, respectively) and unique environmental factors (0.32-0.78 and 0.54-0.82, respectively) affecting height at different ages were more weakly, but still substantially, correlated. The genetic contribution to height is strong during adolescence. The high genetic correlations detected across the ages encourage further efforts to identify genes affecting growth. Common and unique environmental factors affecting height during adolescence are also important, and further studies are necessary to identify their nature and test whether they interact with genetic factors. Copyright © 2011 Wiley-Liss, Inc.

Environmental Factors Affecting Preschoolers' Motor Development

ERIC Educational Resources Information Center

Venetsanou, Fotini; Kambas, Antonis

2010-01-01

The process of development occurs according to the pattern established by the genetic potential and also by the influence of environmental factors. The aim of the present study was to focus on the main environmental factors affecting motor development. The review of the literature revealed that family features, such as socioeconomic status,…

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

PubMed Central

Goodman, A H

2000-01-01

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

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

PubMed

Goodman, A H

2000-11-01

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

The use of telephone in genetic counseling versus in-person counseling: a randomized study on counselees' outcome.

PubMed

Platten, Ulla; Rantala, Johanna; Lindblom, Annika; Brandberg, Yvonne; Lindgren, Gunilla; Arver, Brita

2012-09-01

Increased demand for genetic counseling services necessitates exploring alternatives to in-person counseling. Telephone counseling is a less time-consuming and more cost-effective alternative. So far there is insufficient evidence to support a pre-counseling telephone model. This randomized questionnaire study aims to evaluate the oncogenetic counseling process and to compare the impact of the initial part of the oncogenetic counseling, when conducted via telephone versus in-person. The aspects of evaluations were: patients' expectations, satisfaction and experiences of genetic counseling, worry for developing hereditary cancer and health related quality of life. A total of 215 participants representing several cancer syndromes were randomized to counseling via telephone or in-person. The questionnaires were completed before and after oncogenetic nurse counseling, and 1 year after the entire counseling process. Overall, a high satisfaction rate with the oncogenetic counseling process was found among the participants regardless of whether the oncogenetic nurse counseling was conducted by telephone or in-person. The results show that a considerable number of participants experienced difficulties with the process of creating a pedigree and dissatisfaction with information on surveillance and prevention. Affected participants reported lower levels in most SF-36 domains compared to non-affected and both groups reported lower levels as compared to a Swedish reference group. The results indicate that telephone pre-counseling works as well as in-person counseling. Emotional support during genetic counseling and information on recommended cancer prevention and surveillance should be improved.

Genetic sex determination and extinction.

PubMed

Hedrick, Philip W; Gadau, Jürgen; Page, Robert E

2006-02-01

Genetic factors can affect the probability of extinction either by increasing the effect of detrimental variants or by decreasing the potential for future adaptive responses. In a recent paper, Zayed and Packer demonstrate that low variation at a specific locus, the complementary sex determination (csd) locus in Hymenoptera (ants, bees and wasps), can result in a sharply increased probability of extinction. Their findings illustrate situations in which there is a feedback process between decreased genetic variation at the csd locus owing to genetic drift and decreased population growth, resulting in an extreme type of extinction vortex for these ecologically important organisms.

No genetic adaptation of the Mediterranean keystone shrub Cistus ladanifer in response to experimental fire and extreme drought.

PubMed

Torres, Iván; Parra, Antonio; Moreno, José M; Durka, Walter

2018-01-01

In Mediterranean ecosystems, climate change is projected to increase fire danger and summer drought, thus reducing post-fire recruitment of obligate seeder species, and possibly affecting the population genetic structure. We performed a genome-wide genetic marker study, using AFLP markers, on individuals from one Central Spain population of the obligate post-fire seeder Cistus ladanifer L. that established after experimental fire and survived during four subsequent years under simulated drought implemented with a rainout shelter system. We explored the effects of the treatments on marker diversity, spatial genetic structure and presence of outlier loci suggestive of selection. We found no effect of fire or drought on any of the genetic diversity metrics. Analysis of Molecular Variance showed very low genetic differentiation among treatments. Neither fire nor drought altered the small-scale spatial genetic structure of the population. Only one locus was significantly associated with the fire treatment, but inconsistently across outlier detection methods. Neither fire nor drought are likely to affect the genetic makeup of emerging C. ladanifer, despite reduced recruitment caused by drought. The lack of genetic change suggests that reduced recruitment is a random, non-selective process with no genome-wide consequences on this keystone, drought- and fire tolerant Mediterranean species.

Genetics and epigenetics of obesity.

PubMed

Herrera, Blanca M; Keildson, Sarah; Lindgren, Cecilia M

2011-05-01

Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40-70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these variants do not fully explain the heritability of obesity, other forms of variation, such as epigenetics marks, must be considered. Epigenetic marks, or "imprinting", affect gene expression without actually changing the DNA sequence. Failures in imprinting are known to cause extreme forms of obesity (e.g. Prader-Willi syndrome), but have also been convincingly associated with susceptibility to obesity. Furthermore, environmental exposures during critical developmental periods can affect the profile of epigenetic marks and result in obesity. We review the most recent evidence for genetic and epigenetic mechanisms involved in the susceptibility and development of obesity. Only a comprehensive understanding of the underlying genetic and epigenetic mechanisms, and the metabolic processes they govern, will allow us to manage, and eventually prevent, obesity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Genome instability: Linking ageing and brain degeneration.

PubMed

Barzilai, Ari; Schumacher, Björn; Shiloh, Yosef

2017-01-01

Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-associated decline of brain functionality and the detrimental effect of genome instability on brain functionality and development. This review discusses these similarities and differences and highlights cell classes whose role in these processes might have been underestimated-glia and microglia. Copyright © 2016. Published by Elsevier B.V.

Conservation genetics of managed ungulate populations

USGS Publications Warehouse

Scribner, Kim T.

1993-01-01

Natural populations of many species are increasingly impacted by human activities. Perturbations are particularly pronunced for large ungulates due in part to sport and commercial harvest, to reductions and fragmentation of native habitat, and as the result of reintroductions. These perturbations affect population size, sex and age composition, and population breeding structure, and as a consequence affect the levels and partitioning of genetic variation. Three case histories highlighting long-term ecological genetic research on mule deer Odocoileus hemionus (Rafinesque, 1817), white-tailed deer O. virginianus (Zimmermann, 1780), and Alpine ibex Capra i. ibex Linnaeus, 1758 are presented. Joint examinations of population ecological and genetic data from several populations of each species reveal: (1) that populations are not in genetic equilibrium, but that allele frequencies and heterozygosity change dramatically over time and among cohorts produced in successive years, (2) populations are genetically structured over short and large geographic distances reflecting local breeding structure and patterns of gene flow, respectively; however, this structure is quite dynamic over time, due in part to population exploitation, and (3) restocking programs are often undertaken with small numbers of founding individuals resulting in dramatic declines in levels of genetic variability and increasing levels of genetic differentiation among populations due to genetic drift. Genetic characteristics have and will continue to provide valuable indirect sources of information relating enviromental and human perturbations to changes in population processes.

Striatal Sensitivity during Reward Processing in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Paloyelis, Yannis; Mehta, Mitul A.; Faraone, Stephen V.; Asherson, Philip; Kuntsi, Jonna

2012-01-01

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been linked to deficits in the dopaminergic reward-processing circuitry; yet, existing evidence is limited, and the influence of genetic variation affecting dopamine signaling remains unknown. We investigated striatal responsivity to rewards in ADHD combined type (ADHD-CT) using…

A developmental and genetic classification for midbrain-hindbrain malformations

PubMed Central

Millen, Kathleen J.; Dobyns, William B.

2009-01-01

Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510

Genetic by environment interactions affect plant–soil linkages

PubMed Central

Pregitzer, Clara C; Bailey, Joseph K; Schweitzer, Jennifer A

2013-01-01

The role of plant intraspecific variation in plant–soil linkages is poorly understood, especially in the context of natural environmental variation, but has important implications in evolutionary ecology. We utilized three 18- to 21-year-old common gardens across an elevational gradient, planted with replicates of five Populus angustifolia genotypes each, to address the hypothesis that tree genotype (G), environment (E), and G × E interactions would affect soil carbon and nitrogen dynamics beneath individual trees. We found that soil nitrogen and carbon varied by over 50% and 62%, respectively, across all common garden environments. We found that plant leaf litter (but not root) traits vary by genotype and environment while soil nutrient pools demonstrated genotype, environment, and sometimes G × E interactions, while process rates (net N mineralization and net nitrification) demonstrated G × E interactions. Plasticity in tree growth and litter chemistry was significantly related to the variation in soil nutrient pools and processes across environments, reflecting tight plant–soil linkages. These data overall suggest that plant genetic variation can have differential affects on carbon storage and nitrogen cycling, with implications for understanding the role of genetic variation in plant–soil feedback as well as management plans for conservation and restoration of forest habitats with a changing climate. PMID:23919173

Evidence of opposing fitness effects of parental heterozygosity and relatedness in a critically endangered marine turtle?

PubMed

Phillips, K P; Jorgensen, T H; Jolliffe, K G; Richardson, D S

2017-11-01

How individual genetic variability relates to fitness is important in understanding evolution and the processes affecting populations of conservation concern. Heterozygosity-fitness correlations (HFCs) have been widely used to study this link in wild populations, where key parameters that affect both variability and fitness, such as inbreeding, can be difficult to measure. We used estimates of parental heterozygosity and genetic similarity ('relatedness') derived from 32 microsatellite markers to explore the relationship between genetic variability and fitness in a population of the critically endangered hawksbill turtle, Eretmochelys imbricata. We found no effect of maternal MLH (multilocus heterozygosity) on clutch size or egg success rate, and no single-locus effects. However, we found effects of paternal MLH and parental relatedness on egg success rate that interacted in a way that may result in both positive and negative effects of genetic variability. Multicollinearity in these tests was within safe limits, and null simulations suggested that the effect was not an artefact of using paternal genotypes reconstructed from large samples of offspring. Our results could imply a tension between inbreeding and outbreeding depression in this system, which is biologically feasible in turtles: female-biased natal philopatry may elevate inbreeding risk and local adaptation, and both processes may be disrupted by male-biased dispersal. Although this conclusion should be treated with caution due to a lack of significant identity disequilibrium, our study shows the importance of considering both positive and negative effects when assessing how variation in genetic variability affects fitness in wild systems. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Identification of cognitive profiles among women considering BRCA1/2 testing through the utilisation of cluster analytic techniques.

PubMed

Roussi, Pagona; Sherman, Kerry A; Miller, Suzanne M; Hurley, Karen; Daly, Mary B; Godwin, Andrew; Buzaglo, Joanne S; Wen, Kuang-Yi

2011-10-01

Based on the cognitive-social health information processing model, we identified cognitive profiles of women at risk for breast and ovarian cancer. Prior to genetic counselling, participants (N = 171) completed a study questionnaire concerning their cognitive and affective responses to being at genetic risk. Using cluster analysis, four cognitive profiles were generated: (a) high perceived risk/low coping; (b) low value of screening/high expectancy of cancer; (c) moderate perceived risk/moderate efficacy of prevention/low informativeness of test result; and (d) high efficacy of prevention/high coping. The majority of women in Clusters One, Two and Three had no personal history of cancer, whereas Cluster Four consisted almost entirely of women affected with cancer. Women in Cluster One had the highest number of affected relatives and experienced higher levels of distress than women in the other three clusters. These results highlight the need to consider the psychological profile of women undergoing genetic testing when designing counselling interventions and messages.

Rare Disease Mechanisms Identified by Genealogical Proteomics of Copper Homeostasis Mutant Pedigrees.

PubMed

Zlatic, Stephanie A; Vrailas-Mortimer, Alysia; Gokhale, Avanti; Carey, Lucas J; Scott, Elizabeth; Burch, Reid; McCall, Morgan M; Rudin-Rush, Samantha; Davis, John Bowen; Hartwig, Cortnie; Werner, Erica; Li, Lian; Petris, Michael; Faundez, Victor

2018-03-28

Rare neurological diseases shed light onto universal neurobiological processes. However, molecular mechanisms connecting genetic defects to their disease phenotypes are elusive. Here, we obtain mechanistic information by comparing proteomes of cells from individuals with rare disorders with proteomes from their disease-free consanguineous relatives. We use triple-SILAC mass spectrometry to quantify proteomes from human pedigrees affected by mutations in ATP7A, which cause Menkes disease, a rare neurodegenerative and neurodevelopmental disorder stemming from systemic copper depletion. We identified 214 proteins whose expression was altered in ATP7A -/y fibroblasts. Bioinformatic analysis of ATP7A-mutant proteomes identified known phenotypes and processes affected in rare genetic diseases causing copper dyshomeostasis, including altered mitochondrial function. We found connections between copper dyshomeostasis and the UCHL1/PARK5 pathway of Parkinson disease, which we validated with mitochondrial respiration and Drosophila genetics assays. We propose that our genealogical "omics" strategy can be broadly applied to identify mechanisms linking a genomic locus to its phenotypes. Copyright © 2018 Elsevier Inc. All rights reserved.

Demographic mechanisms underpinning genetic assimilation of remnant groups of a large carnivore

USGS Publications Warehouse

Mikle, Nathaniel; Graves, Tabitha A.; Kovach, Ryan P.; Kendall, Katherine C.; Macleod, Amy C.

2016-01-01

Current range expansions of large terrestrial carnivores are occurring following human-induced range contraction. Contractions are often incomplete, leaving small remnant groups in refugia throughout the former range. Little is known about the underlying ecological and evolutionary processes that influence how remnant groups are affected during range expansion. We used data from a spatially explicit, long-term genetic sampling effort of grizzly bears (Ursus arctos) in the Northern Continental Divide Ecosystem (NCDE), USA, to identify the demographic processes underlying spatial and temporal patterns of genetic diversity. We conducted parentage analysis to evaluate how reproductive success and dispersal contribute to spatio-temporal patterns of genetic diversity in remnant groups of grizzly bears existing in the southwestern (SW), southeastern (SE) and east-central (EC) regions of the NCDE. A few reproductively dominant individuals and local inbreeding caused low genetic diversity in peripheral regions that may have persisted for multiple generations before eroding rapidly (approx. one generation) during population expansion. Our results highlight that individual-level genetic and reproductive dynamics play critical roles during genetic assimilation, and show that spatial patterns of genetic diversity on the leading edge of an expansion may result from historical demographic patterns that are highly ephemeral.

Demographic mechanisms underpinning genetic assimilation of remnant groups of a large carnivore

PubMed Central

Kovach, Ryan; Kendall, Katherine C.; Macleod, Amy C.

2016-01-01

Current range expansions of large terrestrial carnivores are occurring following human-induced range contraction. Contractions are often incomplete, leaving small remnant groups in refugia throughout the former range. Little is known about the underlying ecological and evolutionary processes that influence how remnant groups are affected during range expansion. We used data from a spatially explicit, long-term genetic sampling effort of grizzly bears (Ursus arctos) in the Northern Continental Divide Ecosystem (NCDE), USA, to identify the demographic processes underlying spatial and temporal patterns of genetic diversity. We conducted parentage analysis to evaluate how reproductive success and dispersal contribute to spatio-temporal patterns of genetic diversity in remnant groups of grizzly bears existing in the southwestern (SW), southeastern (SE) and east-central (EC) regions of the NCDE. A few reproductively dominant individuals and local inbreeding caused low genetic diversity in peripheral regions that may have persisted for multiple generations before eroding rapidly (approx. one generation) during population expansion. Our results highlight that individual-level genetic and reproductive dynamics play critical roles during genetic assimilation, and show that spatial patterns of genetic diversity on the leading edge of an expansion may result from historical demographic patterns that are highly ephemeral. PMID:27655768

Testing the link between population genetic differentiation and clade diversification in Costa Rican orchids.

PubMed

Kisel, Yael; Moreno-Letelier, Alejandra C; Bogarín, Diego; Powell, Martyn P; Chase, Mark W; Barraclough, Timothy G

2012-10-01

Species population genetics could be an important factor explaining variation in clade species richness. Here, we use newly generated amplified fragment length polymorphism (AFLP) data to test whether five pairs of sister clades of Costa Rican orchids that differ greatly in species richness also differ in average neutral genetic differentiation within species, expecting that if the strength of processes promoting differentiation within species is phylogenetically heritable, then clades with greater genetic differentiation should diversify more. Contrary to expectation, neutral genetic differentiation does not correlate directly with total diversification in the clades studied. Neutral genetic differentiation varies greatly among species and shows no heritability within clades. Half of the variation in neutral genetic differentiation among populations can be explained by ecological variables, and species-level traits explain the most variation. Unexpectedly, we find no isolation by distance in any species, but genetic differentiation is greater between populations occupying different niches. This pattern corresponds with those observed for microscopic eukaryotes and could reflect effective widespread dispersal of tiny and numerous orchid seeds. Although not providing a definitive answer to whether population genetics processes affect clade diversification, this work highlights the potential for addressing new macroevolutionary questions using a comparative population genetic approach. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM families in an era of genetic non-discrimination acts.

PubMed

Geelen, Els; Horstman, Klasien; Marcelis, Carlo L M; Doevendans, Pieter A; Van Hoyweghen, Ine

2012-10-01

Since the 1990s, many countries in Europe and the United States have enacted genetic non-discrimination legislation to prevent people from deferring genetic tests for fear that insurers or employers would discriminate against them based on that information. Although evidence for genetic discrimination exists, little is known about the origins and backgrounds of fears of discrimination and how it affects decisions for uptake of genetic testing. The aim of this article is to gain a better understanding of these fears and its possible impact on the uptake of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a qualitative study, we followed six Dutch extended families involved in genetic testing for HCM for three-and-a-half years. Semi-structured interviews were conducted with 57 members of these families. Based on the narratives of the families, we suggest that fears of discrimination have to be situated in the broader social and life-course context of family and kin. We describe the processes in which families developed meaningful interpretations of genetic discrimination and how these interpretations affected family members' decisions to undergo genetic testing. Our findings show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members. These results help identify the possible limitations of genetic non-discrimination regulations and provide direction to clinicians supporting their clients as they confront issues of genetic testing and genetic discrimination.

Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM families in an era of genetic non-discrimination acts

PubMed Central

Geelen, Els; Horstman, Klasien; Marcelis, Carlo LM; Doevendans, Pieter A; Van Hoyweghen, Ine

2012-01-01

Since the 1990s, many countries in Europe and the United States have enacted genetic non-discrimination legislation to prevent people from deferring genetic tests for fear that insurers or employers would discriminate against them based on that information. Although evidence for genetic discrimination exists, little is known about the origins and backgrounds of fears of discrimination and how it affects decisions for uptake of genetic testing. The aim of this article is to gain a better understanding of these fears and its possible impact on the uptake of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a qualitative study, we followed six Dutch extended families involved in genetic testing for HCM for three-and-a-half years. Semi-structured interviews were conducted with 57 members of these families. Based on the narratives of the families, we suggest that fears of discrimination have to be situated in the broader social and life-course context of family and kin. We describe the processes in which families developed meaningful interpretations of genetic discrimination and how these interpretations affected family members' decisions to undergo genetic testing. Our findings show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members. These results help identify the possible limitations of genetic non-discrimination regulations and provide direction to clinicians supporting their clients as they confront issues of genetic testing and genetic discrimination. PMID:22453290

Retrospective reports of parental physical affection and parenting style: a study of Finnish twins.

PubMed

Harlaar, Nicole; Santtila, Pekka; Björklund, Johanna; Alanko, Katarina; Jern, Patrick; Varjonen, Markus; von der Pahlen, Bettina; Sandnabba, Kenneth

2008-08-01

Individual differences in parenting behaviors are due, in part, to genetic factors. In the present study, the authors sought to determine whether the degree of genetic influence varied according to the type of parental behavior under consideration. A population-based sample of 2,334 pairs of Finnish twins provided ratings on the physical affection, control, abusiveness, and indifference shown by their father and mother during childhood. Genetic influences, shared environmental influences, and nonshared environmental influences accounted for a small-to-medium proportion (17%-30%), a small-to-large proportion (22%-44%), and a medium-to-large proportion (37%-55%) of the variance in each parenting measure, respectively. There were no significant differences in effect sizes for mothers and fathers or across the 4 types of parental behavior. The genetic results may reflect characteristic styles with which parents respond to genetically influenced behaviors of individuals (gene-environment correlations) or individual perceptions of this relationship (gene-person correlation processes). The findings have implications for intervention and prevention work with families and for interpretation of evidence for interactions between genes and parenting behaviors.

Mate choice for genetic quality when environments vary: suggestions for empirical progress.

PubMed

Bussière, Luc F; Hunt, John; Stölting, Kai N; Jennions, Michael D; Brooks, Robert

2008-09-01

Mate choice for good-genes remains one of the most controversial evolutionary processes ever proposed. This is partly because strong directional choice should theoretically deplete the genetic variation that explains the evolution of this type of female mating preference (the so-called lek paradox). Moreover, good-genes benefits are generally assumed to be too small to outweigh opposing direct selection on females. Here, we review recent progress in the study of mate choice for genetic quality, focussing particularly on the potential for genotype by environment interactions (GEIs) to rescue additive genetic variation for quality, and thereby resolve the lek paradox. We raise five questions that we think will stimulate empirical progress in this field, and suggest directions for research in each area: (1) How is condition-dependence affected by environmental variation? (2) How important are GEIs for maintaining additive genetic variance in condition? (3) How much do GEIs reduce the signalling value of male condition? (4) How does GEI affect the multivariate version of the lek paradox? (5) Have mating biases for high-condition males evolved because of indirect benefits?

Introgression Makes Waves in Inferred Histories of Effective Population Size.

PubMed

Hawks, John

2017-01-01

Human populations have a complex history of introgression and of changing population size. Human genetic variation has been affected by both these processes, so inference of past population size depends upon the pattern of gene flow and introgression among past populations. One remarkable aspect of human population history as inferred from genetics is a consistent "wave" of larger effective population sizes, found in both African and non-African populations, that appears to reflect events prior to the last 100,000 years. I carried out a series of simulations to investigate how introgression and gene flow from genetically divergent ancestral populations affect the inference of ancestral effective population size. Both introgression and gene flow from an extinct, genetically divergent population consistently produce a wave in the history of inferred effective population size. The time and amplitude of the wave reflect the time of origin of the genetically divergent ancestral populations and the strength of introgression or gene flow. These results demonstrate that even small fractions of introgression or gene flow from ancient populations may have visible effects on the inference of effective population size.

Who is afraid of math? Two sources of genetic variance for mathematical anxiety.

PubMed

Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W; Lyons, Ian M; Petrill, Stephen A

2014-09-01

Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem solving and achievement. This study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and nonfamilial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics and may extend to other areas of academic achievement. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Who’s Afraid of Math? Two Sources of Genetic Variance for Mathematical Anxiety

PubMed Central

Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A.; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W.; Lyons, Ian M.; Petrill, Stephen A.

2015-01-01

Background Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem-solving and achievement. The present study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Methods Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Results Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and non-familial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. Conclusions The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics, and may extend to other areas of academic achievement. PMID:24611799

Communication of Information about Genetic Risks: Putting Families at the Center.

PubMed

Mendes, Álvaro; Metcalfe, Alison; Paneque, Milena; Sousa, Liliana; Clarke, Angus J; Sequeiros, Jorge

2017-07-16

Genetic information is a family affair. With the expansion of genomic technologies, many new causal genes and variants have been established and the potential for molecular diagnoses increased, with implications not only for patients but also their relatives. The need for genetic counseling and intrafamilial circulation of information on genetic risks grew accordingly. Also, the amount and, particularly, the complexity of the information to convey multiplied. Sharing information about genetic risks with family members, however, has never been an easy matter and often becomes a source of personal and familial conflicts and distress. Ethical requisites generally prevent healthcare professionals from directly contacting their consultands' relatives (affected or still at risk), who often feel unsupported throughout that process. We discuss here the communication of genetic risks to family members. We first consider genomic testing as a basis for family-centered health care, as opposed to a predominant focus on the individual. We reviewed the literature on sharing genetic risk information with family members, and the associated ethical issues for professionals. Some clinical cases are presented and discussed, and key issues for meeting the needs of individuals and families are addressed. We argue that genetic information is inextricably linked to the family and that communicating about genetic risks is a process grounded within the broader milieu of family relationships and functioning. We conclude for the need for a more family-centered approach and interventions that can promote sensitive attitudes to the provision of genetic information to and within the family, as well as its inclusion in educational and training programmes for genetic healthcare professionals. © 2017 Family Process Institute.

Is There a Right Time to Know? The Right Not to Know and Genetic Testing in Children.

PubMed

Borry, Pascal; Shabani, Mahsa; Howard, Heidi Carmen

2014-01-01

The increasing implementation of next-generation sequencing technologies in the clinical context and the expanding commercial offer of genetic tests directly-toconsumers has increased the availability of previously inaccessible genetic information. A particular concern in both situations is how the volume of novel information will affect the processing of genetic and genomic information from minors. For minors, it is argued that in the provision of genetic testing, their "right not to know" should be respected as much as possible. Testing a minor early in life eliminates the possibility for the minor to make use of his or her "right not to know." The article discusses the theoretical underpinnings of the right not know, analyzes reasons why various direct-to-consumer companies process samples from minors, and discusses the right not to know in relation to common complex disorders in a pediatric population. © 2014 American Society of Law, Medicine & Ethics, Inc.

Update on Leukodystrophies: A Historical Perspective and Adapted Definition.

PubMed

Kevelam, Sietske H; Steenweg, Marjan E; Srivastava, Siddharth; Helman, Guy; Naidu, Sakkubai; Schiffmann, Raphael; Blaser, Susan; Vanderver, Adeline; Wolf, Nicole I; van der Knaap, Marjo S

2016-12-01

Leukodystrophies were defined in the 1980s as progressive genetic disorders primarily affecting myelin of the central nervous system. At that time, a limited number of such disorders and no associated gene defects were known. The majority of the leukodystrophy patients remained without a specific diagnosis. In the following two decades, magnetic resonance imaging pattern recognition revolutionized the field, allowing the definition of numerous novel leukodystrophies. Their genetic defects were usually identified through genetic linkage studies. This process required substantial numbers of cases and many rare disorders remained unclarified. As recently as 2010, 50% of the leukodystrophy patients remained unclassified. Since 2011, whole-exome sequencing has resulted in an exponential increase in numbers of known, distinct, genetically determined, ultrarare leukodystrophies. We performed a retrospective study concerning three historical cohorts of unclassified leukodystrophy patients and found that currently at least 80% of the patients can be molecularly classified. Based on the original definition of the leukodystrophies, numerous defects in proteins important in myelin structure, maintenance, and function were expected. By contrast, a high percentage of the newly identified gene defects affect the housekeeping process of mRNA translation, shedding new light on white matter pathobiology and requiring adaptation of the leukodystrophy definition. Georg Thieme Verlag KG Stuttgart · New York.

Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture, Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (Genus Papio)

PubMed Central

Atkinson, Elizabeth G.; Rogers, Jeffrey; Mahaney, Michael C.; Cox, Laura A.; Cheverud, James M.

2015-01-01

Folding of the primate brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. The arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is thought to reflect the underlying neural network. Gyrification, an adaptive trait with a unique evolutionary history, is affected by genetic factors different from those affecting brain volume. Using a large pedigreed population of ∼1000 Papio baboons, we address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical–cortical connectivity, and gyrification’s potential for future evolution. Through Mantel testing and cluster analyses, we find that the baboon cortex is quite evolvable, with high integration between the genotype and phenotype. We further find significantly similar partitioning of variation between cortical development, anatomy, and connectivity, supporting the predictions of tension-based models for sulcal development. We identify a significant, moderate degree of genetic control over variation in sulcal length, with gyrus-shape features being more susceptible to environmental effects. Finally, through QTL mapping, we identify novel chromosomal regions affecting variation in brain folding. The most significant QTL contain compelling candidate genes, including gene clusters associated with Williams and Down syndromes. The QTL distribution suggests a complex genetic architecture for gyrification with both polygeny and pleiotropy. Our results provide a solid preliminary characterization of the genetic basis of primate brain folding, a unique and biomedically relevant phenotype with significant implications in primate brain evolution. PMID:25873632

Genetic diversity in Malus ×domestica (Rosaceae) through time in response to domestication.

PubMed

Gross, Briana L; Henk, Adam D; Richards, Christopher M; Fazio, Gennaro; Volk, Gayle M

2014-10-01

• Patterns of genetic diversity in domesticated plants are affected by geographic region of origin and cultivation, intentional artificial selection, and unintentional genetic bottlenecks. While bottlenecks are mainly associated with the initial domestication process, they can also affect diversity during crop improvement. Here, we investigate the impact of the improvement process on the genetic diversity of domesticated apple in comparison with other perennial and annual fruit crops.• Apple cultivars that were developed at various times (ranging from the 13th through the 20th century) and 11 of the 15 apple cultivars that are used for 90% of the apple production in the United States were surveyed for genetic diversity based on either 9 or 19 simple sequence repeats (SSRs). Diversity was compared using standard metrics and model-based approaches based on expected heterozygosity (He) at equilibrium. Improvement bottleneck data for fruit crops were also collected from the literature.• Domesticated apples showed no significant reduction in genetic diversity through time across the last eight centuries. Diversity was generally high, with an average He > 0.7 for apples from all centuries. However, diversity of the apples currently used for the bulk of commercial production was lower.• The improvement bottleneck in domesticated apples appears to be mild or nonexistent, in contrast to improvement bottlenecks in many annual and perennial fruit crops, as documented from the literature survey. The low diversity of the subset of cultivars used for commercial production, however, indicates that an improvement bottleneck may be in progress for this perennial crop. © 2014 Botanical Society of America, Inc.

Are languages really independent from genes? If not, what would a genetic bias affecting language diversity look like?

PubMed

Dediu, Dan

2011-04-01

It is generally accepted that the relationship between human genes and language is very complex and multifaceted. This has its roots in the “regular” complexity governing the interplay among genes and between genes and environment for most phenotypes, but with the added layer of supraontogenetic and supra-individual processes defining culture. At the coarsest level, focusing on the species, it is clear that human-specific--but not necessarily faculty-specific--genetic factors subtend our capacity for language and a currently very productive research program is aiming at uncovering them. At the other end of the spectrum, it is uncontroversial that individual-level variations in different aspects related to speech and language have an important genetic component and their discovery and detailed characterization have already started to revolutionize the way we think about human nature. However, at the intermediate, glossogenetic/population level, the relationship becomes controversial, partly due to deeply ingrained beliefs about language acquisition and universality and partly because of confusions with a different type of gene-languages correlation due to shared history. Nevertheless, conceptual, mathematical and computational models--and, recently, experimental evidence from artificial languages and songbirds--have repeatedly shown that genetic biases affecting the acquisition or processing of aspects of language and speech can be amplified by population-level intergenerational cultural processes and made manifest either as fixed “universal” properties of language or as structured linguistic diversity. Here, I review several such models as well as the recently proposed case of a causal relationship between the distribution of tone languages and two genes related to brain growth and development, ASPM and Microcephalin, and I discuss the relevance of such genetic biasing for language evolution, change, and diversity.

Pattern of genetic differentiation of an incipient speciation process: The case of the high Andean killifish Orestias

PubMed Central

Guerrero-Jiménez, Claudia Jimena; Peña, Fabiola; Morales, Pamela; Méndez, Marco; Sallaberry, Michel; Vila, Irma; Poulin, Elie

2017-01-01

During the Pleistocene and Holocene, the southwest Andean Altiplano (17°-22°S) was affected by repeated fluctuations in water levels, high volcanic activity and major tectonic movements. In the early Holocene the humid Tauca phase shifted to the arid conditions that have lasted until the present, producing endorheic rivers, lakes, lagoons and wetlands. The endemic fish Orestias (Cyprinodontidae) represents a good model to observe the genetic differentiation that characterizes an incipient speciation process in allopatry since the morphospecies described inhabit a restricted geographic area, with present habitat fragmentation. The genetic diversity and population structure of four endemic morphospecies of Orestias (Cyprinodontidae) found in the Lauca National Park (LNP) analyzed with mitochondrial markers (Control Region) and eight microsatellites, revealed the existence of genetic groups that matches the fragmentation of these systems. High values of genetic and phylogeographic differentiation indices were observed between Chungará Lake and Piacota lagoon. The group composed of the Lauca River, Copapujo and Chuviri wetlands sampling sites showed a clear signal of expansion, with a star-like haplotype network. Levels of genetic differentiation were lower than in Chungará and Piacota, suggesting that these localities would have differentiated after the bottlenecks linked to the collapse of Parinacota volcano. The Parinacota sample showed a population signal that differed from the other localities revealing greater genetic diversity and a disperse network, presenting haplotypes shared with other LNP localities. A mixing pattern of the different genetic groups was evident using the microsatellite markers. The chronology of the vicariance events in LNP may indicate that the partition process of the Orestias populations was gradual. Considering this, and in view of the genetic results, we may conclude that the morphospecies from LNP are populations in ongoing differentiation process. PMID:28245250

Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons.

PubMed

Specchia, Valeria; Piacentini, Lucia; Tritto, Patrizia; Fanti, Laura; D'Alessandro, Rosalba; Palumbo, Gioacchino; Pimpinelli, Sergio; Bozzetti, Maria P

2010-02-04

The canalization concept describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways, indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability. Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis.

Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward.

PubMed

Sanders, Amy Cecilia; Hussain, Ali J; Hen, René; Zhuang, Xiaoxi

2007-11-01

The therapeutic effects of chronic selective serotonin reuptake inhibitors (SSRIs) are well documented, yet the elementary behavioral processes that are affected by such treatment have not been fully investigated. We report here the effects of chronic fluoxetine treatment and genetic deletion of the serotonin transporter (SERT) on food reinforced behavior in three paradigms: the progressive ratio operant task, the concurrent choice operant task, and the Pavlovian-to-Instrumental transfer task. We consistently find that chronic pharmacological blockade or genetic deletion of SERT result in similar behavioral consequences: reduced operant responding for natural reward. This is in line with previous studies reporting declines in operant responding for drugs and intracranial self-stimulation with fluoxetine treatment, suggesting that the effect of SERT blockade can be generalized to different reward types. Detailed analyses of behavioral parameters indicate that this reduction in operant responding affect both goal-directed and non-goal-directed behaviors without affecting the Pavlovian cue-triggered excessive operant responding. In addition, both pharmacological and genetic manipulations reduce locomotor activity in the open field novel environment. Our data contrast with the effect of dopamine in increasing operant responding for natural reward specifically in goal-directed behaviors and in increasing Pavlovian cue-triggered excessive operant responding. Serotonin and dopamine have been proposed to serve opposing functions in motivational processes. Our data suggest that their interactions do not result in simple opponency. The fact that pharmacological blockade and genetic deletion of SERT have similar behavioral consequences reinforces the utility of the SERT null mice for investigation of the mechanisms underlying chronic SSRIs treatment.

Genetics Home Reference: maple syrup urine disease

MedlinePlus

... disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. It is also characterized ...

Knowledge and expectations of women undergoing cancer genetic risk assessment: a qualitative analysis of free-text questionnaire comments.

PubMed

Phelps, C; Wood, F; Bennett, P; Brain, K; Gray, J

2007-08-01

Individuals undergoing cancer genetic risk assessment have been found to have a poor understanding of the process, which may affect how well they cope with learning their risk. This paper reports free-text data from questionnaires completed by women undergoing a randomised controlled trial of a psychological intervention. Of the 268 women undergoing genetic assessment for familial breast/ovarian cancer risk who were invited to take part in the trial, 157 women returned research questionnaires. Of these, 97 women provided free-text comments upon referral to a cancer genetics clinic, 62 provided comments whilst waiting for risk information (average, moderate or high), and 36 women provided comments following notification of risk. This paper reports a thematic analysis of the free-text data. Themes reflected individuals' poor knowledge and uncertainty about genetic risk assessment. How well individuals responded to learning their risk depended upon whether expectations had been met. Regardless of risk, individuals undergoing cancer genetic risk assessment are likely to benefit from increased information about its process and timescales, and access to increased psychological support. Free-text comments can provide valuable data about individuals' expectations and knowledge of genetics services.

Tooth dentin defects reflect genetic disorders affecting bone mineralization

PubMed Central

Vital, S. Opsahl; Gaucher, C.; Bardet, C.; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

2012-01-01

Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID:22296718

Landscape-scale deforestation decreases gene flow distance of a keystone tropical palm, Euterpe edulis Mart (Arecaceae).

PubMed

Santos, Alesandro S; Cazetta, Eliana; Dodonov, Pavel; Faria, Deborah; Gaiotto, Fernanda A

2016-09-01

Habitat loss represents one of the main threats to tropical forests, which have reached extremely high rates of species extinction. Forest loss negatively impacts biodiversity, affecting ecological (e.g., seed dispersal) and genetic (e.g., genetic diversity and structure) processes. Therefore, understanding how deforestation influences genetic resources is strategic for conservation. Our aim was to empirically evaluate the effects of landscape-scale forest reduction on the spatial genetic structure and gene flow of Euterpe edulis Mart (Arecaceae), a palm tree considered a keystone resource for many vertebrate species. This study was carried out in nine forest remnants in the Atlantic Forest, northeastern Brazil, located in landscapes within a gradient of forest cover (19-83%). We collected leaves of 246 adults and 271 seedlings and performed genotyping using microsatellite markers. Our results showed that the palm populations had low spatial genetic structure, indicating that forest reduction did not influence this genetic parameter for neither seedlings nor adults. However, forest loss decreased the gene flow distance, which may negatively affect the genetic diversity of future generations by increasing the risk of local extinction of this keystone palm. For efficient strategies of genetic variability conservation and maintenance of gene flow in E. edulis , we recommend the maintenance of landscapes with intermediary to high levels of forest cover, that is, forest cover above 40%.

System-level analysis of genes and functions affecting survival during nutrient starvation in Saccharomyces cerevisiae.

PubMed

Gresham, David; Boer, Viktor M; Caudy, Amy; Ziv, Naomi; Brandt, Nathan J; Storey, John D; Botstein, David

2011-01-01

An essential property of all cells is the ability to exit from active cell division and persist in a quiescent state. For single-celled microbes this primarily occurs in response to nutrient deprivation. We studied the genetic requirements for survival of Saccharomyces cerevisiae when starved for either of two nutrients: phosphate or leucine. We measured the survival of nearly all nonessential haploid null yeast mutants in mixed populations using a quantitative sequencing method that estimates the abundance of each mutant on the basis of frequency of unique molecular barcodes. Starvation for phosphate results in a population half-life of 337 hr whereas starvation for leucine results in a half-life of 27.7 hr. To measure survival of individual mutants in each population we developed a statistical framework that accounts for the multiple sources of experimental variation. From the identities of the genes in which mutations strongly affect survival, we identify genetic evidence for several cellular processes affecting survival during nutrient starvation, including autophagy, chromatin remodeling, mRNA processing, and cytoskeleton function. In addition, we found evidence that mitochondrial and peroxisome function is required for survival. Our experimental and analytical methods represent an efficient and quantitative approach to characterizing genetic functions and networks with unprecedented resolution and identified genotype-by-environment interactions that have important implications for interpretation of studies of aging and quiescence in yeast.

Neurogenetics in Child Neurology: Redefining a Discipline in the Twenty-first Century.

PubMed

Kaufmann, Walter E

2016-12-01

Increasing knowledge on genetic etiology of pediatric neurologic disorders is affecting the practice of the specialty. I reviewed here the history of pediatric neurologic disorder classification and the role of genetics in the process. I also discussed the concept of clinical neurogenetics, with its role in clinical practice, education, and research. Finally, I propose a flexible model for clinical neurogenetics in child neurology in the twenty-first century. In combination with disorder-specific clinical programs, clinical neurogenetics can become a home for complex clinical issues, repository of genetic diagnostic advances, educational resource, and research engine in child neurology.

Developmental mechanisms underlying variation in craniofacial disease and evolution.

PubMed

Fish, Jennifer L

2016-07-15

Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children.

PubMed

Mrena, S; Savola, K; Kulmala, P; Reijonen, H; Ilonen, J; Akerblom, H K; Knip, M

2003-06-01

We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P < 0.001 for DQB1 genotypes according to the first classification), whereas there was a higher proportion of siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P < 0.001 according to the first classification). Autoantibodies alone were more sensitive in the prediction of future diabetes in siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P < 0.001 according to the first classification) and whether overt type 1 diabetes became manifest or not. Genetic susceptibility has an impact on both the initiation and progression of the autoimmune process leading to clinical diabetes in siblings of affected children.

River network architecture, genetic effective size and distributional patterns predict differences in genetic structure across species in a dryland stream fish community.

PubMed

Pilger, Tyler J; Gido, Keith B; Propst, David L; Whitney, James E; Turner, Thomas F

2017-05-01

Dendritic ecological network (DEN) architecture can be a strong predictor of spatial genetic patterns in theoretical and simulation studies. Yet, interspecific differences in dispersal capabilities and distribution within the network may equally affect species' genetic structuring. We characterized patterns of genetic variation from up to ten microsatellite loci for nine numerically dominant members of the upper Gila River fish community, New Mexico, USA. Using comparative landscape genetics, we evaluated the role of network architecture for structuring populations within species (pairwise F ST ) while explicitly accounting for intraspecific demographic influences on effective population size (N e ). Five species exhibited patterns of connectivity and/or genetic diversity gradients that were predicted by network structure. These species were generally considered to be small-bodied or habitat specialists. Spatial variation of N e was a strong predictor of pairwise F ST for two species, suggesting patterns of connectivity may also be influenced by genetic drift independent of network properties. Finally, two study species exhibited genetic patterns that were unexplained by network properties and appeared to be related to nonequilibrium processes. Properties of DENs shape community-wide genetic structure but effects are modified by intrinsic traits and nonequilibrium processes. Further theoretical development of the DEN framework should account for such cases. © 2017 John Wiley & Sons Ltd.

Habitat predictors of genetic diversity for two sympatric wetland-breeding amphibian species.

PubMed

McKee, Anna M; Maerz, John C; Smith, Lora L; Glenn, Travis C

2017-08-01

Population genetic diversity is widely accepted as important to the conservation and management of wildlife. However, habitat features may differentially affect evolutionary processes that facilitate population genetic diversity among sympatric species. We measured genetic diversity for two pond-breeding amphibian species (Dwarf salamanders, Eurycea quadridigitata ; and Southern Leopard frogs, Lithobates sphenocephalus ) to understand how habitat characteristics and spatial scale affect genetic diversity across a landscape. Samples were collected from wetlands on a longleaf pine reserve in Georgia. We genotyped microsatellite loci for both species to assess population structures and determine which habitat features were most closely associated with observed heterozygosity and rarefied allelic richness. Both species exhibited significant population genetic structure; however, structure in Southern Leopard frogs was driven primarily by one outlier site. Dwarf salamander allelic richness was greater at sites with less surrounding road area within 0.5 km and more wetland area within 1.0 and 2.5 km, and heterozygosity was greater at sites with more wetland area within 0.5 km. In contrast, neither measure of Southern Leopard frog genetic diversity was associated with any habitat features at any scale we evaluated. Genetic diversity in the Dwarf salamander was strongly associated with land cover variables up to 2.5 km away from breeding wetlands, and/or results suggest that minimizing roads in wetland buffers may be beneficial to the maintenance of population genetic diversity. This study suggests that patterns of genetic differentiation and genetic diversity have associations with different habitat features across different spatial scales for two syntopic pond-breeding amphibian species.

Co-segregation of social cognition, executive function and local processing style in children with ASD, their siblings and normal controls.

PubMed

Oerlemans, Anoek M; Droste, Katharina; van Steijn, Daphne J; de Sonneville, Leo M J; Buitelaar, Jan K; Rommelse, Nanda N J

2013-12-01

Cognitive research proposes that social cognition (SC), executive functions (EF) and local processing style (weak CC) may be fruitful areas for research into the familial-genetic underpinnings of Autism Spectrum Disorders (ASD). The performance of 140 children with ASD, 172 siblings and 127 controls on tasks measuring SC (face recognition, affective prosody, and facial emotion recognition), EF (inhibition, cognitive flexibility, and verbal working memory) and local processing style was assessed. Compelling evidence was found for the interrelatedness of SC and EF, but not local processing style, within individuals and within families, suggesting that these domains tend to co-segregate in ASD. Using the underlying shared variance of these constructs in genetic research may increase the power for detecting susceptibility genes for ASD.

The near demise and subsequent revival of classical genetics for investigating Caenorhabditis elegans embryogenesis: RNAi meets next-generation DNA sequencing.

PubMed

Bowerman, Bruce

2011-10-01

Molecular genetic investigation of the early Caenorhabditis elegans embryo has contributed substantially to the discovery and general understanding of the genes, pathways, and mechanisms that regulate and execute developmental and cell biological processes. Initially, worm geneticists relied exclusively on a classical genetics approach, isolating mutants with interesting phenotypes after mutagenesis and then determining the identity of the affected genes. Subsequently, the discovery of RNA interference (RNAi) led to a much greater reliance on a reverse genetics approach: reducing the function of known genes with RNAi and then observing the phenotypic consequences. Now the advent of next-generation DNA sequencing technologies and the ensuing ease and affordability of whole-genome sequencing are reviving the use of classical genetics to investigate early C. elegans embryogenesis.

Inbreeding and disease resistance in a social insect: effects of heterozygosity on immunocompetence in the termite Zootermopsis angusticollis

PubMed Central

Calleri, Daniel V; McGrail Reid, Ellen; Rosengaus, Rebeca B; Vargo, Edward L; Traniello, James F.A

2006-01-01

Recent research has shown that low genetic variation in individuals can increase susceptibility to infection and group living may exacerbate pathogen transmission. In the eusocial diploid termites, cycles of outbreeding and inbreeding characterizing basal species can reduce genetic variation within nestmates during the life of a colony, but the relationship of genetic heterogeneity to disease resistance is poorly understood. Here we show that, one generation of inbreeding differentially affects the survivorship of isolated and grouped termites (Zootermopsis angusticollis) depending on the nature of immune challenge and treatment. Inbred and outbred isolated and grouped termites inoculated with a bacterial pathogen, exposed to a low dose of fungal pathogen or challenged with an implanted nylon monofilament had similar levels of immune defence. However, inbred grouped termites exposed to a relatively high concentration of fungal conidia had significantly greater mortality than outbred grouped termites. Inbred termites also had significantly higher cuticular microbial loads, presumably due to less effective grooming by nestmates. Genetic analyses showed that inbreeding significantly reduced heterozygosity and allelic diversity. Decreased heterozygosity thus appeared to increase disease susceptibility by affecting social behaviour or some other group-level process influencing infection control rather than affecting individual immune physiology. PMID:17002949

Fine-Scale Ecological and Genetic Population Structure of Two Whitefish (Coregoninae) Species in the Vicinity of Industrial Thermal Emissions.

PubMed

Graham, Carly F; Eberts, Rebecca L; Morgan, Thomas D; Boreham, Douglas R; Lance, Stacey L; Manzon, Richard G; Martino, Jessica A; Rogers, Sean M; Wilson, Joanna Y; Somers, Christopher M

2016-01-01

Thermal pollution from industrial processes can have negative impacts on the spawning and development of cold-water fish. Point sources of thermal effluent may need to be managed to avoid affecting discrete populations. Correspondingly, we examined fine-scale ecological and genetic population structure of two whitefish species (Coregonus clupeaformis and Prosopium cylindraceum) on Lake Huron, Canada, in the immediate vicinity of thermal effluent from nuclear power generation. Niche metrics using δ13C and δ15N stable isotopes showed high levels of overlap (48.6 to 94.5%) in resource use by adult fish captured in areas affected by thermal effluent compared to nearby reference locations. Isotopic niche size, a metric of resource use diversity, was 1.3- to 2.8-fold higher than reference values in some thermally affected areas, indicative of fish mixing. Microsatellite analyses of genetic population structure (Fst, STRUCTURE and DAPC) indicated that fish captured at all locations in the vicinity of the power plant were part of a larger population extending beyond the study area. In concert, ecological and genetic markers do not support the presence of an evolutionarily significant unit in the vicinity of the power plant. Thus, future research should focus on the potential impacts of thermal emissions on development and recruitment.

Fine-Scale Ecological and Genetic Population Structure of Two Whitefish (Coregoninae) Species in the Vicinity of Industrial Thermal Emissions

PubMed Central

Graham, Carly F.; Eberts, Rebecca L.; Morgan, Thomas D.; Boreham, Douglas R.; Lance, Stacey L.; Manzon, Richard G.; Martino, Jessica A.; Rogers, Sean M.; Wilson, Joanna Y.; Somers, Christopher M.

2016-01-01

Thermal pollution from industrial processes can have negative impacts on the spawning and development of cold-water fish. Point sources of thermal effluent may need to be managed to avoid affecting discrete populations. Correspondingly, we examined fine-scale ecological and genetic population structure of two whitefish species (Coregonus clupeaformis and Prosopium cylindraceum) on Lake Huron, Canada, in the immediate vicinity of thermal effluent from nuclear power generation. Niche metrics using δ13C and δ15N stable isotopes showed high levels of overlap (48.6 to 94.5%) in resource use by adult fish captured in areas affected by thermal effluent compared to nearby reference locations. Isotopic niche size, a metric of resource use diversity, was 1.3- to 2.8-fold higher than reference values in some thermally affected areas, indicative of fish mixing. Microsatellite analyses of genetic population structure (Fst, STRUCTURE and DAPC) indicated that fish captured at all locations in the vicinity of the power plant were part of a larger population extending beyond the study area. In concert, ecological and genetic markers do not support the presence of an evolutionarily significant unit in the vicinity of the power plant. Thus, future research should focus on the potential impacts of thermal emissions on development and recruitment. PMID:26807722

Genomic regions with a history of divergent selection affect fitness of hybrids between two butterfly species.

PubMed

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

2012-07-01

Speciation is the process by which reproductively isolated lineages arise, and is one of the fundamental means by which the diversity of life increases. Whereas numerous studies have documented an association between ecological divergence and reproductive isolation, relatively little is known about the role of natural selection in genome divergence during the process of speciation. Here, we use genome-wide DNA sequences and Bayesian models to test the hypothesis that loci under divergent selection between two butterfly species (Lycaeides idas and L. melissa) also affect fitness in an admixed population. Locus-specific measures of genetic differentiation between L. idas and L. melissa and genomic introgression in hybrids varied across the genome. The most differentiated genetic regions were characterized by elevated L. idas ancestry in the admixed population, which occurs in L. idas-like habitat, consistent with the hypothesis that local adaptation contributes to speciation. Moreover, locus-specific measures of genetic differentiation (a metric of divergent selection) were positively associated with extreme genomic introgression (a metric of hybrid fitness). Interestingly, concordance of differentiation and introgression was only partial. We discuss multiple, complementary explanations for this partial concordance. © 2012 The Author(s).

Evolutionary response of landraces to climate change in centers of crop diversity

PubMed Central

Mercer, Kristin L; Perales, Hugo R

2010-01-01

Landraces cultivated in centers of crop diversity result from past and contemporary patterns of natural and farmer-mediated evolutionary forces. Successful in situ conservation of crop genetic resources depends on continuity of these evolutionary processes. Climate change is projected to affect agricultural production, yet analyses of impacts on in situ conservation of crop genetic diversity and farmers who conserve it have been absent. How will crop landraces respond to alterations in climate? We review the roles that phenotypic plasticity, evolution, and gene flow might play in sustaining production, although we might expect erosion of genetic diversity if landrace populations or entire races lose productivity. For example, highland maize landraces in southern Mexico do not express the plasticity necessary to sustain productivity under climate change, but may evolve in response to altered conditions. The outcome for any given crop in a given region will depend on the distribution of genetic variation that affects fitness and patterns of climate change. Understanding patterns of neutral and adaptive diversity from the population to the landscape scale is essential to clarify how landraces conserved in situ will continue to evolve and how to minimize genetic erosion of this essential natural resource. PMID:25567941

Evolutionary response of landraces to climate change in centers of crop diversity.

PubMed

Mercer, Kristin L; Perales, Hugo R

2010-09-01

Landraces cultivated in centers of crop diversity result from past and contemporary patterns of natural and farmer-mediated evolutionary forces. Successful in situ conservation of crop genetic resources depends on continuity of these evolutionary processes. Climate change is projected to affect agricultural production, yet analyses of impacts on in situ conservation of crop genetic diversity and farmers who conserve it have been absent. How will crop landraces respond to alterations in climate? We review the roles that phenotypic plasticity, evolution, and gene flow might play in sustaining production, although we might expect erosion of genetic diversity if landrace populations or entire races lose productivity. For example, highland maize landraces in southern Mexico do not express the plasticity necessary to sustain productivity under climate change, but may evolve in response to altered conditions. The outcome for any given crop in a given region will depend on the distribution of genetic variation that affects fitness and patterns of climate change. Understanding patterns of neutral and adaptive diversity from the population to the landscape scale is essential to clarify how landraces conserved in situ will continue to evolve and how to minimize genetic erosion of this essential natural resource.

The genetics of normal and defective color vision

PubMed Central

Neitz, Jay; Neitz, Maureen

2011-01-01

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25 years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectrum of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. PMID:21167193

Evidence that disease-induced population decline changes genetic structure and alters dispersal patterns in the Tasmanian devil

PubMed Central

Lachish, S; Miller, K J; Storfer, A; Goldizen, A W; Jones, M E

2011-01-01

Infectious disease has been shown to be a major cause of population declines in wild animals. However, there remains little empirical evidence on the genetic consequences of disease-mediated population declines, or how such perturbations might affect demographic processes such as dispersal. Devil facial tumour disease (DFTD) has resulted in the rapid decline of the Tasmanian devil, Sarcophilus harrisii, and threatens to cause extinction. Using 10 microsatellite DNA markers, we compared genetic diversity and structure before and after DFTD outbreaks in three Tasmanian devil populations to assess the genetic consequences of disease-induced population decline. We also used both genetic and demographic data to investigate dispersal patterns in Tasmanian devils along the east coast of Tasmania. We observed a significant increase in inbreeding (FIS pre/post-disease −0.030/0.012, P<0.05; relatedness pre/post-disease 0.011/0.038, P=0.06) in devil populations after just 2–3 generations of disease arrival, but no detectable change in genetic diversity. Furthermore, although there was no subdivision apparent among pre-disease populations (θ=0.005, 95% confidence interval (CI) −0.003 to 0.017), we found significant genetic differentiation among populations post-disease (θ=0.020, 0.010–0.027), apparently driven by a combination of selection and altered dispersal patterns of females in disease-affected populations. We also show that dispersal is male-biased in devils and that dispersal distances follow a typical leptokurtic distribution. Our results show that disease can result in genetic and demographic changes in host populations over few generations and short time scales. Ongoing management of Tasmanian devils must now attempt to maintain genetic variability in this species through actions designed to reverse the detrimental effects of inbreeding and subdivision in disease-affected populations. PMID:20216571

The impact of transposable elements on mammalian development

PubMed Central

Garcia-Perez, Jose L.; Widmann, Thomas J.; Adams, Ian R.

2018-01-01

Summary Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that significantly impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and how the somatic activity of TEs can influence gene regulatory networks. PMID:27875251

Genetic manipulation and monitoring of autophagy in Drosophila.

PubMed

Neufeld, Thomas P

2008-01-01

Drosophila melanogaster provides a model system useful for many aspects of the study of autophagy in vivo. These include testing and validation of genes potentially involved in autophagy, discovery of novel genes through genetic screening for mutations that affect autophagy, and analysis of potential roles of autophagy in specific developmental or physiological processes. In recent years, a number of techniques and transgenic and mutant fly strains have been developed to facilitate autophagy analysis in this system. Here, protocols are described for activating or inhibiting autophagy in Drosophila, and for examining the progression of autophagy in vivo through imaging-based assays. The goal of this chapter is to provide a resource both for autophagy investigators with limited familiarity with fly genetics, as well as for experienced Drosophila biologists who wish to test for connections between autophagy and a given gene, pathway or process.

Gendering Genetics: Biological Contingencies in the Protective Effects of Social Integration for Men and Women.

PubMed

Perry, Brea L

2016-05-01

Evidence that social and biological processes are intertwined in producing health and human behavior is rapidly accumulating. Using a feminist approach, this research explores how gender moderates the interaction between biological processes and men's and women's behavioral and emotional responses to similar social environments. Using data from the Collaborative Study on the Genetics of Alcoholism, the influence of gender, social integration, and genetic risk on nicotine and alcohol dependence is examined. Three-way interaction models reveal gender-specific moderation of interactions between genetic risk score and social integration. Namely, being currently married and reporting positive social psychological integration are predictive of reduced risk of nicotine dependence among men with genetic susceptibility to strong nicotine cravings in the presence of social cues like stress. In contrast, the protective effects of marital status and social integration are substantially attenuated and absent, respectively, among women with high-risk genotypes. This pattern reflects the dualism (i.e., simultaneous costs and benefits) inherent in social integration for women, which may disproportionately affect those with a genetic sensitivity to stress. These findings contest the notion of genotype as static biological hardwiring that is independent from social and cultural systems of gender difference.

Preferences of newborn mice for odours indicating closer genetic relatedness: is experience necessary?

PubMed

Todrank, Josephine; Busquet, Nicolas; Baudoin, Claude; Heth, Giora

2005-10-07

Evidence from studies with adult rodents indicates that individual recognition enables distinctions between familiar individuals irrespective of relatedness (but including close kin) and a separate mechanism enables discriminations based on genetic relatedness without prior familiarity. For example, adult mice could assess the extent of their genetic relatedness to unfamiliar individuals using perceptual similarities between their individual odours. The ontogeny of this genetic relatedness assessment mechanism, however, had not been investigated. Here, in two-choice tests, newborn mice differentially preferred odours of more genetically similar lactating females (paternal aunts to unrelated conspecific and conspecific to heterospecific) even without prior direct exposure to adults with the tested genotypes. The results provide a direct demonstration of genetic relatedness assessment abilities in newborns and show that experience with parental odours is not necessary for genetic relatedness distinctions. Future studies will be necessary to determine whether exposure to odours of other foetuses in the womb or littermates shortly after birth affects this genetic relatedness assessment process.

Preferences of newborn mice for odours indicating closer genetic relatedness: is experience necessary?

PubMed Central

Todrank, Josephine; Busquet, Nicolas; Baudoin, Claude; Heth, Giora

2005-01-01

Evidence from studies with adult rodents indicates that individual recognition enables distinctions between familiar individuals irrespective of relatedness (but including close kin) and a separate mechanism enables discriminations based on genetic relatedness without prior familiarity. For example, adult mice could assess the extent of their genetic relatedness to unfamiliar individuals using perceptual similarities between their individual odours. The ontogeny of this genetic relatedness assessment mechanism, however, had not been investigated. Here, in two-choice tests, newborn mice differentially preferred odours of more genetically similar lactating females (paternal aunts to unrelated conspecific and conspecific to heterospecific) even without prior direct exposure to adults with the tested genotypes. The results provide a direct demonstration of genetic relatedness assessment abilities in newborns and show that experience with parental odours is not necessary for genetic relatedness distinctions. Future studies will be necessary to determine whether exposure to odours of other foetuses in the womb or littermates shortly after birth affects this genetic relatedness assessment process. PMID:16191620

Insights in the Fruit Flesh Browning Mechanisms in Solanum melongena Genetic Lines with Opposite Postcut Behavior.

PubMed

Docimo, T; Francese, G; De Palma, M; Mennella, D; Toppino, L; Lo Scalzo, R; Mennella, G; Tucci, M

2016-06-08

Color, taste, flavor, nutritional value, and shelf life are important factors determining quality and healthiness of food and vegetables. These factors are strongly affected by browning processes, occurring after fruit or vegetable cutting. Characterization of ten eggplant genotypes for chlorogenic acid (CGA) content, total phenols (TP), polyphenoloxidase (PPO) activity, and browning tendency corroborated a lack of significant correlations between biochemical factors and fruit flesh browning. Further in-depth molecular and biochemical analyses of two divergent eggplant genetic lines, AM199 (high browning) and AM086 (low browning), within 30 min from cutting, highlighted differences in the physiological mechanisms underlying the browning process. qRT-PCR analysis revealed distinct activation mechanisms of CGA biosynthetic and PPO genes in the two genetic lines. Metabolic data on CGA, sugars, and ascorbic acid contents confirmed that their different browning tendency matched with different metabolic responses to cutting. Our findings suggest that the complex mechanism of flesh browning in the two eggplant genetic lines might be mediated by multiple specific factors.

Genetic and epigenetic mechanisms in the pathogenesis of neurofibromatosis type I

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

Metheny, L.J.; Amedeo, M.S.; Cappione, J.

Neurofibromatosis type I (NF1) is a common genetic disease which leads to a variety of clinical features affecting cells of neural crest origin. In the period since the NF1 gene was isolated 1991, our understanding of the genetics of NF1 has increased remarkably. One of the most striking aspects of NF1 genetics is its complexity, both in terms of gene organization and expression. The gene is large and, when mutated, gives rise to diverse manifestations. A growing body of data suggests that mutations in the NF1 gene alone may not be responsible for all of the features of this disease.more » Epigenetic mechanisms, those which affect the NF1 transcript, play a role in the normal expression of the NF1 gene. Therefore, aberrations in those epigenetic processes are most likely pathogenic. Herein we summarize salient aspects of the vast body of NF1 literature and provide some insights into the myriad of regulatory mechanisms that may go awry in the genesis of this common but complex disease. 58 refs., 3 figs.« less

Genetic screens for mutations affecting development of Xenopus tropicalis.

PubMed

Goda, Tadahiro; Abu-Daya, Anita; Carruthers, Samantha; Clark, Matthew D; Stemple, Derek L; Zimmerman, Lyle B

2006-06-01

We present here the results of forward and reverse genetic screens for chemically-induced mutations in Xenopus tropicalis. In our forward genetic screen, we have uncovered 77 candidate phenotypes in diverse organogenesis and differentiation processes. Using a gynogenetic screen design, which minimizes time and husbandry space expenditures, we find that if a phenotype is detected in the gynogenetic F2 of a given F1 female twice, it is highly likely to be a heritable abnormality (29/29 cases). We have also demonstrated the feasibility of reverse genetic approaches for obtaining carriers of mutations in specific genes, and have directly determined an induced mutation rate by sequencing specific exons from a mutagenized population. The Xenopus system, with its well-understood embryology, fate map, and gain-of-function approaches, can now be coupled with efficient loss-of-function genetic strategies for vertebrate functional genomics and developmental genetics.

The capture of heritable variation for genetic quality through social competition.

PubMed

Wolf, Jason B; Harris, W Edwin; Royle, Nick J

2008-09-01

In theory, females of many species choose mates based on traits that are indicators of male genetic quality. A fundamental question in evolutionary biology is why genetic variation for such indicator traits persists despite strong persistent selection imposed by female preference, which is known as the lek paradox. One potential solution to the lek paradox suggests that the traits that are targets of mate choice should evolve condition-dependent expression and that condition should have a large genetic variance. Condition is expected to exhibit high genetic variance because it is affected by a large number of physiological processes and hence, condition-dependent traits should 'capture' variation contributed by a large number of loci. We suggest that a potentially important cause of variation in condition is competition for limited resources. Here, we discuss a pair of models to analyze the evolutionary genetics of traits affected by success in social competition for resources. We show that competition can contribute to genetic variation of 'competition-dependent' traits that have fundamentally different evolutionary properties than other sources of variation. Competition dependence can make traits honest indicators of genetic quality by revealing the relative competitive ability of males, can provide a component of heritable variation that does not contribute to trait evolution, and can help maintain heritable variation under directional selection. Here we provide a general introduction to the concept of competition dependence and briefly introduce two models to demonstrate the potential evolutionary consequences of competition-dependent trait expression.

A neutral theory for interpreting correlations between species and genetic diversity in communities.

PubMed

Laroche, Fabien; Jarne, Philippe; Lamy, Thomas; David, Patrice; Massol, Francois

2015-01-01

Spatial patterns of biological diversity have been extensively studied in ecology and population genetics, because they reflect the forces acting on biodiversity. A growing number of studies have found that genetic (within-species) and species diversity can be correlated in space (the so-called species-gene diversity correlation [SGDC]), which suggests that they are controlled by nonindependent processes. Positive SGDCs are generally assumed to arise from parallel responses of genetic and species diversity to variation in site size and connectivity. However, this argument implicitly assumes a neutral model that has yet to be developed. Here, we build such a model to predict SGDC in a metacommunity. We describe how SGDC emerges from competition within sites and variation in connectivity and carrying capacity among sites. We then introduce the formerly ignored mutation process, which affects genetic but not species diversity. When mutation rate is low, our model confirms that variation in the number of migrants among sites creates positive SGDCs. However, when considering high mutation rates, interactions between mutation, migration, and competition can produce negative SGDCs. Neutral processes thus do not always contribute positively to SGDCs. Our approach provides empirical guidelines for interpreting these novel patterns in natura with respect to evolutionary and ecological forces shaping metacommunities.

The behavioral genetics of nonhuman primates: Status and prospects.

PubMed

Rogers, Jeffrey

2018-01-01

The complexity and diversity of primate behavior have long attracted the attention of ethologists, psychologists, behavioral ecologists, and neuroscientists. Recent studies have advanced our understanding of the nature of genetic influences on differences in behavior among individuals within species. A number of analyses have focused on the genetic analysis of behavioral reactions to specific experimental tests, providing estimates of the degree of genetic control over reactivity, and beginning to identify the genes involved. Substantial progress is also being made in identifying genetic factors that influence the structure and function of the primate brain. Most of the published studies on these topics have examined either cercopithecines or chimpanzees, though a few studies have addressed these questions in other primate species. One potentially important line of research is beginning to identify the epigenetic processes that influence primate behavior, thus revealing specific cellular and molecular mechanisms by which environmental experiences can influence gene expression or gene function relevant to behavior. This review summarizes many of these studies of non-human primate behavioral genetics. The primary focus is on analyses that address the nature of the genes and genetic processes that affect differences in behavior among individuals within non-human primate species. Analyses of between species differences and potential avenues for future research are also discussed. © 2018 American Association of Physical Anthropologists.

Interdependence between transcription and mRNP processing and export, and its impact on genetic stability.

PubMed

Luna, Rosa; Jimeno, Sonia; Marín, Mercedes; Huertas, Pablo; García-Rubio, María; Aguilera, Andrés

2005-06-10

The conserved eukaryotic THO-TREX complex acts at the interface between transcription and mRNA export and affects transcription-associated recombination. To investigate the interdependence of nuclear mRNA processes and their impact on genomic integrity, we analyzed transcript accumulation and recombination of 40 selected mutants covering representative steps of the biogenesis and export of the messenger ribonucleoprotein particle (mRNP). None of the mutants analyzed shared the strong transcript-accumulation defect and hyperrecombination of THO mutants. Nevertheless, mutants in 3' end cleavage/polyadenylation, nuclear exosome, and mRNA export showed a weak but significant effect on recombination and transcript accumulation. Mutants of the nuclear exosome (rrp6) and 3' end processing factors (rna14 and rna15) showed inefficient transcription elongation and genetic interactions with THO. The results suggest a tight interdependence among mRNP biogenesis steps and transcription and an unexpected effect of the nuclear exosome and the cleavage/polyadenylation factors on transcription elongation and genetic integrity.

Community specificity: life and afterlife effects of genes.

PubMed

Whitham, Thomas G; Gehring, Catherine A; Lamit, Louis J; Wojtowicz, Todd; Evans, Luke M; Keith, Arthur R; Smith, David Solance

2012-05-01

Community-level genetic specificity results when individual genotypes or populations of the same species support different communities. Our review of the literature shows that genetic specificity exhibits both life and afterlife effects; it is a widespread phenomenon occurring in diverse taxonomic groups, aquatic to terrestrial ecosystems, and species-poor to species-rich systems. Such specificity affects species interactions, evolution, ecosystem processes and leads to community feedbacks on the performance of the individuals expressing the traits. Thus, genetic specificity by communities appears to be fundamentally important, suggesting that specificity is a major driver of the biodiversity and stability of the world's ecosystems. Copyright © 2012. Published by Elsevier Ltd.

Mechanisms and Modifiers of Methylmercury-Induced Neurotoxicity

PubMed Central

Fretham, Stephanie JB; Caito, Samuel; Martinez-Finley, Ebany J; Aschner, Michael

2016-01-01

The neurotoxic consequences of methylmercury (MeHg) exposure have long been known, however a complete understanding of the mechanisms underlying this toxicity is elusive. Recent epidemiological and experimental studies have provided many mechanistic insights, particularly into the contribution of genetic and environmental factors that interact with MeHg to modify toxicity. This review will outline cellular processes directly and indirectly affected by MeHg, including oxidative stress, cellular signaling and gene expression, and discuss genetic, environmental and nutritional factors capable of modifying MeHg toxicity. PMID:27795823

Hybridization affects life-history traits and host specificity in Diorhabda spp

USDA-ARS?s Scientific Manuscript database

Hybridization is an influential evolutionary process that has been viewed alternatively as an evolutionary dead-end or as an important creative evolutionary force. In colonizing species, such as introduced biological control agents, hybridization can negate the effects of bottlenecks and genetic dri...

Bidirectional genetic and environmental influences on mother and child behavior: the family system as the unit of analyses.

PubMed

Mills-Koonce, W Roger; Propper, Cathi B; Gariepy, Jean-Louis; Blair, Clancy; Garrett-Peters, Patricia; Cox, Martha J

2007-01-01

Family systems theory proposes that an individual's functioning depends on interactive processes within the self and within the context of dyadic family subsystems. Previous research on these processes has focused largely on behavioral, cognitive, and psychophysiological properties of the individual and the dyad. The goals of this study were to explore genetic and environmental interactions within the family system by examining how the dopamine receptor D2 gene (DRD2) A1+ polymorphism in mothers and children relates to maternal sensitivity, how maternal and child characteristics might mediate those effects, and whether maternal sensitivity moderates the association between DRD2 A1+ and child affective problems. Evidence is found for an evocative effect of child polymorphism on parenting behavior, and for a moderating effect of child polymorphism on the association between maternal sensitivity and later child affective problems. Findings are discussed from a family systems perspective, highlighting the role of the family as a context for gene expression in both mothers and children.

Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome.

PubMed

Shefi, Shai; Raviv, Gil; Rienstein, Shlomit; Barkai, Gad; Aviram-Goldring, Ayala; Levron, Jacob

2009-07-01

To report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order to diagnose embryos affected by DiGeorge syndrome. Case report. Academic referral center. A 32 year-old female affected by DiGeorge syndrome. History and physical examination, karyotyping, amniocentesis, preimplantation genetic diagnosis, fluorescence in-situ hybridization. Avoidance of pregnancy with embryo affected by DiGeorge syndrome. Termination of pregnancy with an affected embryo followed by fluorescence in-situ hybridization based preimplantation genetic diagnosis and delivery of healthy offspring. The combination of preimplantation genetic diagnosis with fluorescence in-situ hybridization is recommended to prevent pregnancies with DiGeorge syndrome affected embryos in properly selected patients.

The impact of transposable elements on mammalian development.

PubMed

Garcia-Perez, Jose L; Widmann, Thomas J; Adams, Ian R

2016-11-15

Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that have a significant impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and discuss how the somatic activity of TEs can influence gene regulatory networks. © 2016. Published by The Company of Biologists Ltd.

The broad footprint of climate change from genes to biomes to people.

PubMed

Scheffers, Brett R; De Meester, Luc; Bridge, Tom C L; Hoffmann, Ary A; Pandolfi, John M; Corlett, Richard T; Butchart, Stuart H M; Pearce-Kelly, Paul; Kovacs, Kit M; Dudgeon, David; Pacifici, Michela; Rondinini, Carlo; Foden, Wendy B; Martin, Tara G; Mora, Camilo; Bickford, David; Watson, James E M

2016-11-11

Most ecological processes now show responses to anthropogenic climate change. In terrestrial, freshwater, and marine ecosystems, species are changing genetically, physiologically, morphologically, and phenologically and are shifting their distributions, which affects food webs and results in new interactions. Disruptions scale from the gene to the ecosystem and have documented consequences for people, including unpredictable fisheries and crop yields, loss of genetic diversity in wild crop varieties, and increasing impacts of pests and diseases. In addition to the more easily observed changes, such as shifts in flowering phenology, we argue that many hidden dynamics, such as genetic changes, are also taking place. Understanding shifts in ecological processes can guide human adaptation strategies. In addition to reducing greenhouse gases, climate action and policy must therefore focus equally on strategies that safeguard biodiversity and ecosystems. Copyright © 2016, American Association for the Advancement of Science.

Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

PubMed

Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

2011-02-01

Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

Interatomic Coulombic Decay Effects in Theoretical DNA Recombination Systems Involving Protein Interaction Sites

NASA Astrophysics Data System (ADS)

Vargas, E. L.; Rivas, D. A.; Duot, A. C.; Hovey, R. T.; Andrianarijaona, V. M.

2015-03-01

DNA replication is the basis for all biological reproduction. A strand of DNA will ``unzip'' and bind with a complimentary strand, creating two identical strands. In this study, we are considering how this process is affected by Interatomic Coulombic Decay (ICD), specifically how ICD affects the individual coding proteins' ability to hold together. ICD mainly deals with how the electron returns to its original state after excitation and how this affects its immediate atomic environment, sometimes affecting the connectivity between interaction sites on proteins involved in the DNA coding process. Biological heredity is fundamentally controlled by DNA and its replication therefore it affects every living thing. The small nature of the proteins (within the range of nanometers) makes it a good candidate for research of this scale. Understanding how ICD affects DNA molecules can give us invaluable insight into the human genetic code and the processes behind cell mutations that can lead to cancer. Authors wish to give special thanks to Pacific Union College Student Senate in Angwin, California, for their financial support.

Genetic variation in social environment construction influences the development of aggressive behavior in Drosophila melanogaster

PubMed Central

Saltz, J B

2017-01-01

Individuals are not merely subject to their social environments; they choose and create them, through a process called social environment (or social niche) construction. When genotypes differ in social environment-constructing behaviors, different genotypes are expected to experience different social environments. As social experience often affects behavioral development, quantitative genetics and psychology theories predict that genetic variation in social environment construction should have an important role in determining phenotypic variation; however, this hypothesis has not been tested directly. I identify multiple mechanisms of social environment construction that differ among natural genotypes of Drosophila melanogaster and investigate their consequences for the development of aggressive behavior. Male genotypes differed in the group sizes that they preferred and in their aggressive behavior; both of these behaviors influenced social experience, demonstrating that these behaviors function as social environment-constructing traits. Further, the effects of social experience—as determined in part by social environment construction—carried over to affect focal male aggression at a later time and with a new opponent. These results provide manipulative experimental support for longstanding hypotheses in psychology, that genetic variation in social environment construction has a causal role in behavioral development. More broadly, these results imply that studies of the genetic basis of complex traits should be expanded to include mechanisms by which genetic variation shapes the environments that individuals experience. PMID:27848947

Agricultural management affects evolutionary processes in a migratory songbird

USGS Publications Warehouse

Perlut, N.G.; Freeman-Gallant, C. R.; Strong, A.M.; Donovan, T.M.; Kilpatrick, C.W.; Zalik, N.J.

2008-01-01

Hay harvests have detrimental ecological effects on breeding songbirds, as harvesting results in nest failure. Importantly, whether harvesting also affects evolutionary processes is not known. We explored how hay harvest affected social and genetic mating patterns, and thus, the overall opportunity for sexual selection and evolutionary processes for a ground-nesting songbird, the Savannah sparrow (Passerculus sandwichensis). On an unharvested field, 55% of females were in polygynous associations, and social polygyny was associated with greater rates of extra-pair paternity (EPP). In this treatment, synchrony explained variation in EPP rates, as broods by more synchronous females had more EPP than broods by asynchronous females. In contrast, on a harvested field, simultaneous nest failure caused by haying dramatically decreased the overall incidence of EPP by increasing the occurrence of social monogamy and, apparently, the ability of polygynous males to maintain paternity in their own nests. Despite increased social and genetic monogamy, these haying-mediated changes in mating systems resulted in greater than twofold increase in the opportunity for sexual selection. This effect arose, in part, from a 30% increase in the variance associated with within-pair fertilization success, relative to the unharvested field. This effect was caused by a notable increase (+110%) in variance associated with the quality of social mates following simultaneous nest failure. Because up to 40% of regional habitat is harvested by early June, these data may demonstrate a strong population-level effect on mating systems, sexual selection, and consequently, evolutionary processes. ?? 2008 The Authors.

Fine-scale ecological and genetic population structure of two whitefish (Coregoninae) species in the vicinity of industrial thermal emissions

DOE PAGES

Graham, Carly F.; Eberts, Rebecca L.; Morgan, Thomas D.; ...

2016-01-25

Thermal pollution from industrial processes can have negative impacts on the spawning and development of cold-water fish. Point sources of thermal effluent may need to be managed to avoid affecting discrete populations. Correspondingly, we examined fine-scale ecological and genetic population structure of two whitefish species ( Coregonus clupeaformis and Prosopium cylindraceum) on Lake Huron, Canada, in the immediate vicinity of thermal effluent from nuclear power generation. Niche metrics using δ 13C and δ 15N stable isotopes showed high levels of overlap (48.6 to 94.5%) in resource use by adult fish captured in areas affected by thermal effluent compared to nearbymore » reference locations. Isotopic niche size, a metric of resource use diversity, was 1.3- to 2.8-fold higher than reference values in some thermally affected areas, indicative of fish mixing. Microsatellite analyses of genetic population structure (F st, STRUCTURE and DAPC) indicated that fish captured at all locations in the vicinity of the power plant were part of a larger population extending beyond the study area. In concert, ecological and genetic markers do not support the presence of an evolutionarily significant unit in the vicinity of the power plant. Furthermore, future research should focus on the potential impacts of thermal emissions on development and recruitment.« less

Fine-scale ecological and genetic population structure of two whitefish (Coregoninae) species in the vicinity of industrial thermal emissions

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

Graham, Carly F.; Eberts, Rebecca L.; Morgan, Thomas D.

Thermal pollution from industrial processes can have negative impacts on the spawning and development of cold-water fish. Point sources of thermal effluent may need to be managed to avoid affecting discrete populations. Correspondingly, we examined fine-scale ecological and genetic population structure of two whitefish species ( Coregonus clupeaformis and Prosopium cylindraceum) on Lake Huron, Canada, in the immediate vicinity of thermal effluent from nuclear power generation. Niche metrics using δ 13C and δ 15N stable isotopes showed high levels of overlap (48.6 to 94.5%) in resource use by adult fish captured in areas affected by thermal effluent compared to nearbymore » reference locations. Isotopic niche size, a metric of resource use diversity, was 1.3- to 2.8-fold higher than reference values in some thermally affected areas, indicative of fish mixing. Microsatellite analyses of genetic population structure (F st, STRUCTURE and DAPC) indicated that fish captured at all locations in the vicinity of the power plant were part of a larger population extending beyond the study area. In concert, ecological and genetic markers do not support the presence of an evolutionarily significant unit in the vicinity of the power plant. Furthermore, future research should focus on the potential impacts of thermal emissions on development and recruitment.« less

Contemporary and historic factors influence differently genetic differentiation and diversity in a tropical palm

PubMed Central

da Silva Carvalho, C; Ribeiro, M C; Côrtes, M C; Galetti, M; Collevatti, R G

2015-01-01

Population genetics theory predicts loss in genetic variability because of drift and inbreeding in isolated plant populations; however, it has been argued that long-distance pollination and seed dispersal may be able to maintain gene flow, even in highly fragmented landscapes. We tested how historical effective population size, historical migration and contemporary landscape structure, such as forest cover, patch isolation and matrix resistance, affect genetic variability and differentiation of seedlings in a tropical palm (Euterpe edulis) in a human-modified rainforest. We sampled 16 sites within five landscapes in the Brazilian Atlantic forest and assessed genetic variability and differentiation using eight microsatellite loci. Using a model selection approach, none of the covariates explained the variation observed in inbreeding coefficients among populations. The variation in genetic diversity among sites was best explained by historical effective population size. Allelic richness was best explained by historical effective population size and matrix resistance, whereas genetic differentiation was explained by matrix resistance. Coalescence analysis revealed high historical migration between sites within landscapes and constant historical population sizes, showing that the genetic differentiation is most likely due to recent changes caused by habitat loss and fragmentation. Overall, recent landscape changes have a greater influence on among-population genetic variation than historical gene flow process. As immediate restoration actions in landscapes with low forest amount, the development of more permeable matrices to allow the movement of pollinators and seed dispersers may be an effective strategy to maintain microevolutionary processes. PMID:25873150

Imaging-Genetics in Dyslexia: Connecting risk genetic variants to brain neuroimaging and ultimately to reading impairments

PubMed Central

Eicher, John D.; Gruen, Jeffrey R.

2013-01-01

Dyslexia is a common pediatric disorder that affects 5-17% of schoolchildren in the United States. It is marked by unexpected difficulties in fluent reading despite adequate intelligence, opportunity, and instruction. Classically, neuropsychologists have studied dyslexia using a variety of neurocognitive batteries to gain insight into the specific deficits and impairments in affected children. Since dyslexia is a complex genetic trait with high heritability, analyses conditioned on performance on these neurocognitive batteries have been used to try to identify associated genes. This has led to some successes in identifying contributing genes, although much of the heritability remains unexplained. Additionally, the lack of relevant human brain tissue for analysis and the challenges of modeling a uniquely human trait in animals are barriers to advancing our knowledge of the underlying pathophysiology. In vivo imaging technologies, however, present new opportunities to examine dyslexia and reading skills in a clearly relevant context in human subjects. Recent investigations have started to integrate these imaging data with genetic data in attempts to gain a more complete and complex understanding of reading processes. In addition to bridging the gap from genetic risk variant to a discernible neuroimaging phenotype and ultimately to the clinical impairments in reading performance, the use of neuroimaging phenotypes will reveal novel risk genes and variants. In this article, we briefly discuss the genetic and imaging investigations and take an in-depth look at the recent imaging-genetics investigations of dyslexia. PMID:23916419

Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making.

PubMed

Gao, Xiaoxue; Liu, Jinting; Gong, Pingyuan; Wang, Junhui; Fang, Wan; Yan, Hongming; Zhu, Lusha; Zhou, Xiaolin

2017-09-01

The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making. © The Author (2017). Published by Oxford University Press.

Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making

PubMed Central

Gao, Xiaoxue; Liu, Jinting; Gong, Pingyuan; Wang, Junhui; Fang, Wan; Yan, Hongming; Zhu, Lusha

2017-01-01

Abstract The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making. PMID:28431168

The genetics of normal and defective color vision.

PubMed

Neitz, Jay; Neitz, Maureen

2011-04-13

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectra of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. Copyright © 2010 Elsevier Ltd. All rights reserved.

Megakaryocyte- and megakaryocyte precursor–related gene therapies

PubMed Central

2016-01-01

Hematopoietic stem cells (HSCs) can be safely collected from the body, genetically modified, and re-infused into a patient with the goal to express the transgene product for an individual’s lifetime. Hematologic defects that can be corrected with an allogeneic bone marrow transplant can theoretically also be treated with gene replacement therapy. Because some genetic disorders affect distinct cell lineages, researchers are utilizing HSC gene transfer techniques using lineage-specific endogenous gene promoters to confine transgene expression to individual cell types (eg, ITGA2B for inherited platelet defects). HSCs appear to be an ideal target for platelet gene therapy because they can differentiate into megakaryocytes which are capable of forming several thousand anucleate platelets that circulate within blood vessels to establish hemostasis by repairing vascular injury. Platelets play an essential role in other biological processes (immune response, angiogenesis) as well as diseased states (atherosclerosis, cancer, thrombosis). Thus, recent advances in genetic manipulation of megakaryocytes could lead to new and improved therapies for treating a variety of disorders. In summary, genetic manipulation of megakaryocytes has progressed to the point where clinically relevant strategies are being developed for human trials for genetic disorders affecting platelets. Nevertheless, challenges still need to be overcome to perfect this field; therefore, strategies to increase the safety and benefit of megakaryocyte gene therapy will be discussed. PMID:26787735

Genetic, Physiological, and Environmental Factors Affecting Acrylamide Concentration in Fried Potato Products

USDA-ARS?s Scientific Manuscript database

The discovery of acrylamide in processed potato products has brought increased interest in the controlling Maillard reaction precursors (reducing sugars and amino acids) in potato tubers. Because of their effects on nonenzymatic browning of fried potato products, reducing sugars and amino acids have...

Changes in composition of cuticular biochemicals of the facultatively polygynous ant Petalomyrmex phylax during range expansion in Cameroon with respect to social, spatial and genetic variation.

PubMed

Dalecky, Ambroise; Renucci, Marielle; Tirard, Alain; Debout, Gabriel; Roux, Maurice; Kjellberg, Finn; Provost, Erick

2007-09-01

In social insects, biochemicals found at the surface of the cuticle are involved in the recognition process and in protection against desiccation and pathogens. However, the relative contribution of evolutionary forces in shaping diversity of these biochemicals remains largely unresolved in ants. We determined the composition of epicuticular biochemicals for workers sampled in 12 populations of the ant Petalomyrmex phylax from Cameroon. Genetic variation at 12 microsatellite markers was used to infer population history and to provide null expectations under the neutrality hypothesis. Genetic data suggest a recent southward range expansion of this ant species. Furthermore, there is a decline southward in the numbers of queens present in mature colonies. Here, we contrast the pattern of biochemical variation against genetic, social and spatial parameters. We thus provide the first estimates of the relative contribution of neutral and selective processes on variation of ant cuticular profile. Populations in migration-drift disequilibrium showed reduction of within-population variation for genetic markers as well as for cuticular profiles. In these populations, the cuticular profile became biased towards a limited number of high molecular weight molecules. Within- and among-population biochemical variation was explained by both genetic and social variation and by the spatial distribution of populations. We therefore propose that during range expansion of P. phylax, the composition of epicuticular compounds has been affected by a combination of neutral processes - genetic drift and spatially limited dispersal - and spatially varying selection, social organization and environmental effects.

Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli.

PubMed

Redlich, Ronny; Stacey, David; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Kugel, Harald; Heindel, Walter; Arolt, Volker; Baune, Bernhard T; Dannlowski, Udo

2015-12-01

Since numerous studies have found that exposure to early life stress leads to increased peripheral inflammation and psychiatric disease, it is thought that peripheral immune activation precedes and possibly mediates the onset of stress-associated psychiatric disease. Despite early studies, IFNγ has received little attention relative to other inflammatory cytokines in the context of the pathophysiology of affective disorders. Neuroimaging endophenotypes have emerged recently as a promising means of elucidating these types of complex relationships including the modeling of the interaction between environmental factors and genetic predisposition. Here we investigate the GxE relationship between early-life stress and genetic variants of IFNγ on emotion processing. To investigate the impact of the relationship between genetic variants of IFNγ (rs1861494, rs2069718, rs2430561) and early life stress on emotion processing, a sample of healthy adults (n=409) undergoing an emotional faces paradigm in an fMRI study were genotyped and analysed. Information on early life stress was obtained via Childhood Trauma Questionnaire (CTQ). A positive association between early life stress and amygdala reactivity was found. Specifically, the main effect of genotype of rs1861494 on amygdala reactivity indicates a higher neural response in C allele carriers compared to T homozygotes, while we did not find main effects of rs2069718 and rs2430561. Importantly, interaction analyses revealed a specific interaction between IFNγ genotype (rs1861494) and early life stress affecting amygdala reactivity to emotional faces, resulting from a positive association between CTQ scores and amygdala reactivity in C allele carriers while this association was absent in T homozygotes. Our findings indicate that firstly the genetic variant of IFNγ (rs1861494) is involved with the regulation of amygdala reactivity to emotional stimuli and secondly, that this genetic variant moderates effects of early life stress on emotion processing. These findings reiterate the importance that inflammatory genes play in the interaction with early life stress and the regulation of emotion processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drift, selection, or migration? Processes affecting genetic differentiation and variation along a latitudinal gradient in an amphibian.

PubMed

Cortázar-Chinarro, Maria; Lattenkamp, Ella Z; Meyer-Lucht, Yvonne; Luquet, Emilien; Laurila, Anssi; Höglund, Jacob

2017-08-14

Past events like fluctuations in population size and post-glacial colonization processes may influence the relative importance of genetic drift, migration and selection when determining the present day patterns of genetic variation. We disentangle how drift, selection and migration shape neutral and adaptive genetic variation in 12 moor frog populations along a 1700 km latitudinal gradient. We studied genetic differentiation and variation at a MHC exon II locus and a set of 18 microsatellites. Using outlier analyses, we identified the MHC II exon 2 (corresponding to the β-2 domain) locus and one microsatellite locus (RCO8640) to be subject to diversifying selection, while five microsatellite loci showed signals of stabilizing selection among populations. STRUCTURE and DAPC analyses on the neutral microsatellites assigned populations to a northern and a southern cluster, reflecting two different post-glacial colonization routes found in previous studies. Genetic variation overall was lower in the northern cluster. The signature of selection on MHC exon II was weaker in the northern cluster, possibly as a consequence of smaller and more fragmented populations. Our results show that historical demographic processes combined with selection and drift have led to a complex pattern of differentiation along the gradient where some loci are more divergent among populations than predicted from drift expectations due to diversifying selection, while other loci are more uniform among populations due to stabilizing selection. Importantly, both overall and MHC genetic variation are lower at northern latitudes. Due to lower evolutionary potential, the low genetic variation in northern populations may increase the risk of extinction when confronted with emerging pathogens and climate change.

Evaluation of fire recurrence effect on genetic diversity in maritime pine (Pinus pinaster Ait.) stands using Inter-Simple Sequence Repeat profiles.

PubMed

Lucas-Borja, M E; Ahrazem, O; Candel-Pérez, D; Moya, D; Fonseca, T; Hernández Tecles, E; De Las Heras, J; Gómez-Gómez, L

2016-12-01

The management of maritime pine in fire-prone habitats is a challenging task and fine-scale population genetic analyses are necessary to check if different fire recurrences affect genetic variability. The objective of this study was to assess the effect of fire recurrence on maritime pine genetic diversity using inter-simple sequence repeat markers (ISSR). Three maritime pine (Pinus pinaster Ait.) populations from Northern Portugal were chosen to characterize the genetic variability among populations. In relation to fire recurrence, Seirós population was affected by fire both in 1990 and 2005 whereas Vila Seca-2 population was affected by fire just in 2005. The Vila Seca-1 population has been never affected by fire. Our results showed the highest Nei's genetic diversity (He=0.320), Shannon information index (I=0.474) and polymorphic loci (PPL=87.79%) among samples from twice burned populations (Seirós site). Thus, fire regime plays an important role affecting genetic diversity in the short-term, although not generating maritime pine genetic erosion. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptation and colonization history affect the evolution of clines in two introduced species.

PubMed

Keller, Stephen R; Sowell, Dexter R; Neiman, Maurine; Wolfe, Lorne M; Taylor, Douglas R

2009-08-01

Phenotypic and genetic clines have long been synonymous with adaptive evolution. However, other processes (for example, migration, range expansion, invasion) may generate clines in traits or loci across geographical and environmental gradients. It is therefore important to distinguish between clines that represent adaptive evolution and those that result from selectively neutral demographic or genetic processes. We tested for the differentiation of phenotypic traits along environmental gradients using two species in the genus Silene, whilst statistically controlling for colonization history and founder effects. We sampled seed families from across the native and introduced ranges, genotyped individuals and estimated phenotypic differentiation in replicated common gardens. The results suggest that post-glacial expansion of S. vulgaris and S. latifolia involved both neutral and adaptive genetic differentiation (clines) of life history traits along major axes of environmental variation in Europe and North America. Phenotypic clines generally persisted when tested against the neutral expectation, although some clines disappeared (and one cline emerged) when the effects of genetic ancestry were statistically removed. Colonization history, estimated using genetic markers, is a useful null model for tests of adaptive trait divergence, especially during range expansion and invasion when selection and gene flow may not have reached equilibrium.

Genetic and flow anomalies in congenital heart disease.

PubMed

Rugonyi, Sandra

2016-01-01

Congenital heart defects are the most common malformations in humans, affecting approximately 1% of newborn babies. While genetic causes of congenital heart disease have been studied, only less than 20% of human cases are clearly linked to genetic anomalies. The cause for the majority of the cases remains unknown. Heart formation is a finely orchestrated developmental process and slight disruptions of it can lead to severe malformations. Dysregulation of developmental processes leading to heart malformations are caused by genetic anomalies but also environmental factors including blood flow. Intra-cardiac blood flow dynamics plays a significant role regulating heart development and perturbations of blood flow lead to congenital heart defects in animal models. Defects that result from hemodynamic alterations, however, recapitulate those observed in human babies, even those due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental events, such as valve formation and septation, occur under blood flow conditions while the heart is pumping, blood flow regulation of cardiac formation might be a critical factor determining cardiac phenotype. The contribution of flow to cardiac phenotype, however, is frequently ignored. More research is needed to determine how blood flow influences cardiac development and the extent to which flow may determine cardiac phenotype.

Influence of COMT genotype and affective distractors on the processing of self-generated thought.

PubMed

Kilford, Emma J; Dumontheil, Iroise; Wood, Nicholas W; Blakemore, Sarah-Jayne

2015-06-01

The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val(158)Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function. © The Author (2014). Published by Oxford University Press.

Effects of sample size, number of markers, and allelic richness on the detection of spatial genetic pattern

USGS Publications Warehouse

Landguth, Erin L.; Gedy, Bradley C.; Oyler-McCance, Sara J.; Garey, Andrew L.; Emel, Sarah L.; Mumma, Matthew; Wagner, Helene H.; Fortin, Marie-Josée; Cushman, Samuel A.

2012-01-01

The influence of study design on the ability to detect the effects of landscape pattern on gene flow is one of the most pressing methodological gaps in landscape genetic research. To investigate the effect of study design on landscape genetics inference, we used a spatially-explicit, individual-based program to simulate gene flow in a spatially continuous population inhabiting a landscape with gradual spatial changes in resistance to movement. We simulated a wide range of combinations of number of loci, number of alleles per locus and number of individuals sampled from the population. We assessed how these three aspects of study design influenced the statistical power to successfully identify the generating process among competing hypotheses of isolation-by-distance, isolation-by-barrier, and isolation-by-landscape resistance using a causal modelling approach with partial Mantel tests. We modelled the statistical power to identify the generating process as a response surface for equilibrium and non-equilibrium conditions after introduction of isolation-by-landscape resistance. All three variables (loci, alleles and sampled individuals) affect the power of causal modelling, but to different degrees. Stronger partial Mantel r correlations between landscape distances and genetic distances were found when more loci were used and when loci were more variable, which makes comparisons of effect size between studies difficult. Number of individuals did not affect the accuracy through mean equilibrium partial Mantel r, but larger samples decreased the uncertainty (increasing the precision) of equilibrium partial Mantel r estimates. We conclude that amplifying more (and more variable) loci is likely to increase the power of landscape genetic inferences more than increasing number of individuals.

Effects of sample size, number of markers, and allelic richness on the detection of spatial genetic pattern

USGS Publications Warehouse

Landguth, E.L.; Fedy, B.C.; Oyler-McCance, S.J.; Garey, A.L.; Emel, S.L.; Mumma, M.; Wagner, H.H.; Fortin, M.-J.; Cushman, S.A.

2012-01-01

The influence of study design on the ability to detect the effects of landscape pattern on gene flow is one of the most pressing methodological gaps in landscape genetic research. To investigate the effect of study design on landscape genetics inference, we used a spatially-explicit, individual-based program to simulate gene flow in a spatially continuous population inhabiting a landscape with gradual spatial changes in resistance to movement. We simulated a wide range of combinations of number of loci, number of alleles per locus and number of individuals sampled from the population. We assessed how these three aspects of study design influenced the statistical power to successfully identify the generating process among competing hypotheses of isolation-by-distance, isolation-by-barrier, and isolation-by-landscape resistance using a causal modelling approach with partial Mantel tests. We modelled the statistical power to identify the generating process as a response surface for equilibrium and non-equilibrium conditions after introduction of isolation-by-landscape resistance. All three variables (loci, alleles and sampled individuals) affect the power of causal modelling, but to different degrees. Stronger partial Mantel r correlations between landscape distances and genetic distances were found when more loci were used and when loci were more variable, which makes comparisons of effect size between studies difficult. Number of individuals did not affect the accuracy through mean equilibrium partial Mantel r, but larger samples decreased the uncertainty (increasing the precision) of equilibrium partial Mantel r estimates. We conclude that amplifying more (and more variable) loci is likely to increase the power of landscape genetic inferences more than increasing number of individuals. ?? 2011 Blackwell Publishing Ltd.

Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

PubMed Central

Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

2008-01-01

Background Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, ~4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. Results As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. Conclusion We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s). PMID:19055778

Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis.

PubMed

Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

2008-12-03

Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, approximately 4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s).

Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study

PubMed Central

Powers, Sara J.; Wang, Yingying; Beach, Sara D.; Sideridis, Georgios D.; Gaab, Nadine

2016-01-01

Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n=29) and without (FHD−, n=21) a family history of developmental dyslexia. We controlled for socio-economic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior/middle frontal and right fusiform gyri in FHD− compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHD− children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models. PMID:27550556

Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study.

PubMed

Powers, Sara J; Wang, Yingying; Beach, Sara D; Sideridis, Georgios D; Gaab, Nadine

2016-10-01

Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here, we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n = 29) and without (FHD-, n = 21) a family history of developmental dyslexia. We further controlled for socioeconomic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior/middle frontal and right fusiform gyri in FHD- compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHD- children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models.

Genetic variability in captive populations of the stingless bee Tetragonisca angustula.

PubMed

Santiago, Leandro R; Francisco, Flávio O; Jaffé, Rodolfo; Arias, Maria C

2016-08-01

Low genetic variability has normally been considered a consequence of animal husbandry and a major contributing factor to declining bee populations. Here, we performed a molecular analysis of captive and wild populations of the stingless bee Tetragonisca angustula, one of the most commonly kept species across South America. Microsatellite analyses showed similar genetic variability between wild and captive populations However, captive populations showed lower mitochondrial genetic variability. Male-mediated gene flow, transport and division of nests are suggested as the most probable explanations for the observed patterns of genetic structure. We conclude that increasing the number of colonies kept through nest divisions does not negatively affect nuclear genetic variability, which seems to be maintained by small-scale male dispersal and human-mediated nest transport. However, the transport of nests from distant localities should be practiced with caution given the high genetic differentiation observed between samples from western and eastern areas. The high genetic structure verified is the result of a long-term evolutionary process, and bees from distant localities may represent unique evolutionary lineages.

Assessing Multivariate Constraints to Evolution across Ten Long-Term Avian Studies

PubMed Central

Teplitsky, Celine; Tarka, Maja; Møller, Anders P.; Nakagawa, Shinichi; Balbontín, Javier; Burke, Terry A.; Doutrelant, Claire; Gregoire, Arnaud; Hansson, Bengt; Hasselquist, Dennis; Gustafsson, Lars; de Lope, Florentino; Marzal, Alfonso; Mills, James A.; Wheelwright, Nathaniel T.; Yarrall, John W.; Charmantier, Anne

2014-01-01

Background In a rapidly changing world, it is of fundamental importance to understand processes constraining or facilitating adaptation through microevolution. As different traits of an organism covary, genetic correlations are expected to affect evolutionary trajectories. However, only limited empirical data are available. Methodology/Principal Findings We investigate the extent to which multivariate constraints affect the rate of adaptation, focusing on four morphological traits often shown to harbour large amounts of genetic variance and considered to be subject to limited evolutionary constraints. Our data set includes unique long-term data for seven bird species and a total of 10 populations. We estimate population-specific matrices of genetic correlations and multivariate selection coefficients to predict evolutionary responses to selection. Using Bayesian methods that facilitate the propagation of errors in estimates, we compare (1) the rate of adaptation based on predicted response to selection when including genetic correlations with predictions from models where these genetic correlations were set to zero and (2) the multivariate evolvability in the direction of current selection to the average evolvability in random directions of the phenotypic space. We show that genetic correlations on average decrease the predicted rate of adaptation by 28%. Multivariate evolvability in the direction of current selection was systematically lower than average evolvability in random directions of space. These significant reductions in the rate of adaptation and reduced evolvability were due to a general nonalignment of selection and genetic variance, notably orthogonality of directional selection with the size axis along which most (60%) of the genetic variance is found. Conclusions These results suggest that genetic correlations can impose significant constraints on the evolution of avian morphology in wild populations. This could have important impacts on evolutionary dynamics and hence population persistence in the face of rapid environmental change. PMID:24608111

Implementing meta-analysis from genome-wide association studies for pork quality traits

USDA-ARS?s Scientific Manuscript database

Pork quality plays an important role in the meat processing industry, thus different methodologies have been implemented to elucidate the genetic architecture of traits affecting meat quality. One of the most common and widely used approaches is to perform genome-wide association (GWA) studies. Howe...

Molecular, physiological and morphological analysis of waterlogging tolerance in clonal genotypes of Theobroma cacao

USDA-ARS?s Scientific Manuscript database

In soil, hypoxia and anoxia conditions generated by waterlogging induce changes in genetic morphological, physiological processes, and as well as altering the growth and development of plant The mass propagation of cacao (Theobroma cacao) cuttings-to produce plantlets (clones) is affected by waterlo...

Who Is Afraid of Math? Two Sources of Genetic Variance for Mathematical Anxiety

ERIC Educational Resources Information Center

Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A.; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W.; Lyons, Ian M.; Petrill, Stephen A.

2014-01-01

Background: Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem solving…

Teaching Evolution through Inquiry-Based Lessons of Uncontroversial Science

ERIC Educational Resources Information Center

DeSantis, Larisa R. G.

2009-01-01

Antibiotic resistance, genetically modified produce, avian flu, and invasive species persistence are just a few scientific issues pulled from the headlines that affect society on a daily basis. Understanding these issues requires knowledge of evolutionary processes. Educating students about evolution may never have been as necessary as it is…

Rare Muscular Dystrophies: Congenital, Distal, Emery-Dreifuss and Oculopharyngeal Muscular Dystrophies

MedlinePlus

... although EDMD and OPMD can have more than one genetic cause). In most cases of muscular dystrophy, muscle mass in the affected ... categories. Many of these diseases can vary from one person to the next, and in some cases, research- ers are still in the process of ...

Donor Conception and "Passing," or; Why Australian Parents of Donor-Conceived Children Want Donors Who Look Like Them.

PubMed

Wong, Karen-Anne

2017-03-01

This article explores the processes through which Australian recipients select unknown donors for use in assisted reproductive technologies and speculates on how those processes may affect the future life of the donor-conceived person. I will suggest that trust is an integral part of the exchange between donors, recipients, and gamete agencies in donor conception and heavily informs concepts of relatedness, race, ethnicity, kinship, class, and visibility. The decision to be transparent (or not) about a child's genetic parentage affects recipient parents' choices of donor, about who is allowed to "know" children's genetic backgrounds, and how important it is to be able to "pass" as an unassisted conception. In this way, recipients must trust the process, institutions, and individuals involved in their treatment, as well as place trust in the future they imagine for their child. The current market for donor gametes reproduces normative conceptions of the nuclear family, kinship, and relatedness by facilitating "matching" donors to recipients by phenotype and cultural affinities. Recipient parents who choose not to prioritize "matching," and actively disclose the process of children's conceptions, may embark on a project of queering heteronormative family structures and place great trust in both their own children and changing social attitudes to reduce stigma and generate acceptance for non-traditional families.

Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency.

PubMed

Fliegauf, Manfred; Bryant, Vanessa L; Frede, Natalie; Slade, Charlotte; Woon, See-Tarn; Lehnert, Klaus; Winzer, Sandra; Bulashevska, Alla; Scerri, Thomas; Leung, Euphemia; Jordan, Anthony; Keller, Baerbel; de Vries, Esther; Cao, Hongzhi; Yang, Fang; Schäffer, Alejandro A; Warnatz, Klaus; Browett, Peter; Douglass, Jo; Ameratunga, Rohan V; van der Meer, Jos W M; Grimbacher, Bodo

2015-09-03

Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ∼90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-κB pathway). The altered protein bearing an internal deletion (p.Asp191_Lys244delinsGlu; p105ΔEx8) is degraded, but is not processed to p50ΔEx8. Altered NF-κB1 proteins were also undetectable in a German CVID-affected family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50—translated from the non-mutated alleles—were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genetic interaction analysis of point mutations enables interrogation of gene function at a residue-level resolution

PubMed Central

Braberg, Hannes; Moehle, Erica A.; Shales, Michael; Guthrie, Christine; Krogan, Nevan J.

2014-01-01

We have achieved a residue-level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. PMID:24842270

A Genetically Informed Cross-lagged Analysis of Autistic-Like Traits and Affective Problems in Early Childhood

PubMed Central

Micalizzi, Lauren; Ronald, Angelica; Saudino, Kimberly J.

2015-01-01

A genetically informed cross-lagged model was applied to twin data to explore etiological links between autistic-like traits and affective problems in early childhood. The sample comprised 310 same-sex twin pairs (143 monozygotic and 167 dizygotic; 53% male). Autistic-like traits and affective problems were assessed at ages 2 and 3 using parent ratings. Both constructs were related within and across age (r = .30−.53) and showed moderate stability (r = .45−.54). Autistic-like traits and affective problems showed genetic and environmental influences at both ages. Whereas at age 2, the covariance between autistic-like traits and affective problems was entirely due to environmental influences (shared and nonshared), at age 3, genetic factors also contributed to the covariance between constructs. The stability paths, but not the cross-lagged paths, were significant, indicating that there is stability in both autistic-like traits and affective problems but they do not mutually influence each other across age. Stability effects were due to genetic, shared, and nonshared environmental influences. Substantial novel genetic and nonshared environmental influences emerge at age 3 and suggest change in the etiology of these constructs over time. During early childhood, autistic-like traits tend to occur alongside affective problems and partly overlapping genetic and environmental influences explain this association. PMID:26456961

Nuclear Genetic Diversity in Human Lice (Pediculus humanus) Reveals Continental Differences and High Inbreeding among Worldwide Populations

PubMed Central

Ascunce, Marina S.; Toups, Melissa A.; Kassu, Gebreyes; Fane, Jackie; Scholl, Katlyn; Reed, David L.

2013-01-01

Understanding the evolution of parasites is important to both basic and applied evolutionary biology. Knowledge of the genetic structure of parasite populations is critical for our ability to predict how an infection can spread through a host population and for the design of effective control methods. However, very little is known about the genetic structure of most human parasites, including the human louse (Pediculus humanus). This species is composed of two ecotypes: the head louse (Pediculus humanus capitis De Geer), and the clothing (body) louse (Pediculus humanus humanus Linnaeus). Hundreds of millions of head louse infestations affect children every year, and this number is on the rise, in part because of increased resistance to insecticides. Clothing lice affect mostly homeless and refugee-camp populations and although they are less prevalent than head lice, the medical consequences are more severe because they vector deadly bacterial pathogens. In this study we present the first assessment of the genetic structure of human louse populations by analyzing the nuclear genetic variation at 15 newly developed microsatellite loci in 93 human lice from 11 sites in four world regions. Both ecotypes showed heterozygote deficits relative to Hardy–Weinberg equilibrium and high inbreeding values, an expected pattern given their parasitic life history. Bayesian clustering analyses assigned lice to four distinct genetic clusters that were geographically structured. The low levels of gene flow among louse populations suggested that the evolution of insecticide resistance in lice would most likely be affected by local selection pressures, underscoring the importance of tailoring control strategies to population-specific genetic makeup and evolutionary history. Our panel of microsatellite markers provides powerful data to investigate not only ecological and evolutionary processes in lice, but also those in their human hosts because of the long-term coevolutionary association between lice and humans. PMID:23460886

Nuclear genetic diversity in human lice (Pediculus humanus) reveals continental differences and high inbreeding among worldwide populations.

PubMed

Ascunce, Marina S; Toups, Melissa A; Kassu, Gebreyes; Fane, Jackie; Scholl, Katlyn; Reed, David L

2013-01-01

Understanding the evolution of parasites is important to both basic and applied evolutionary biology. Knowledge of the genetic structure of parasite populations is critical for our ability to predict how an infection can spread through a host population and for the design of effective control methods. However, very little is known about the genetic structure of most human parasites, including the human louse (Pediculus humanus). This species is composed of two ecotypes: the head louse (Pediculus humanus capitis De Geer), and the clothing (body) louse (Pediculus humanus humanus Linnaeus). Hundreds of millions of head louse infestations affect children every year, and this number is on the rise, in part because of increased resistance to insecticides. Clothing lice affect mostly homeless and refugee-camp populations and although they are less prevalent than head lice, the medical consequences are more severe because they vector deadly bacterial pathogens. In this study we present the first assessment of the genetic structure of human louse populations by analyzing the nuclear genetic variation at 15 newly developed microsatellite loci in 93 human lice from 11 sites in four world regions. Both ecotypes showed heterozygote deficits relative to Hardy-Weinberg equilibrium and high inbreeding values, an expected pattern given their parasitic life history. Bayesian clustering analyses assigned lice to four distinct genetic clusters that were geographically structured. The low levels of gene flow among louse populations suggested that the evolution of insecticide resistance in lice would most likely be affected by local selection pressures, underscoring the importance of tailoring control strategies to population-specific genetic makeup and evolutionary history. Our panel of microsatellite markers provides powerful data to investigate not only ecological and evolutionary processes in lice, but also those in their human hosts because of the long-term coevolutionary association between lice and humans.

Human niche construction in interdisciplinary focus

PubMed Central

Kendal, Jeremy; Tehrani, Jamshid J.; Odling-Smee, John

2011-01-01

Niche construction is an endogenous causal process in evolution, reciprocal to the causal process of natural selection. It works by adding ecological inheritance, comprising the inheritance of natural selection pressures previously modified by niche construction, to genetic inheritance in evolution. Human niche construction modifies selection pressures in environments in ways that affect both human evolution, and the evolution of other species. Human ecological inheritance is exceptionally potent because it includes the social transmission and inheritance of cultural knowledge, and material culture. Human genetic inheritance in combination with human cultural inheritance thus provides a basis for gene–culture coevolution, and multivariate dynamics in cultural evolution. Niche construction theory potentially integrates the biological and social aspects of the human sciences. We elaborate on these processes, and provide brief introductions to each of the papers published in this theme issue. PMID:21320894

Genetics Home Reference: Jacobsen syndrome

MedlinePlus

... varies among affected individuals, with most affected people missing 5 million to 16 million DNA building blocks ( ... translocation can have a chromosomal rearrangement with some missing genetic material and some extra genetic material. Individuals ...

Effects of multiple founder populations on spatial genetic structure of reintroduced American martens.

PubMed

Williams, Bronwyn W; Scribner, Kim T

2010-01-01

Reintroductions and translocations are increasingly used to repatriate or increase probabilities of persistence for animal and plant species. Genetic and demographic characteristics of founding individuals and suitability of habitat at release sites are commonly believed to affect the success of these conservation programs. Genetic divergence among multiple source populations of American martens (Martes americana) and well documented introduction histories permitted analyses of post-introduction dispersion from release sites and development of genetic clusters in the Upper Peninsula (UP) of Michigan <50 years following release. Location and size of spatial genetic clusters and measures of individual-based autocorrelation were inferred using 11 microsatellite loci. We identified three genetic clusters in geographic proximity to original release locations. Estimated distances of effective gene flow based on spatial autocorrelation varied greatly among genetic clusters (30-90 km). Spatial contiguity of genetic clusters has been largely maintained with evidence for admixture primarily in localized regions, suggesting recent contact or locally retarded rates of gene flow. Data provide guidance for future studies of the effects of permeabilities of different land-cover and land-use features to dispersal and of other biotic and environmental factors that may contribute to the colonization process and development of spatial genetic associations.

Genetic diversity is largely unpredictable but scales with museum occurrences in a species-rich clade of Australian lizards

PubMed Central

Huang, Huateng; Title, Pascal O.; Donnellan, Stephen C.; Holmes, Iris; Rabosky, Daniel L.

2017-01-01

Genetic diversity is a fundamental characteristic of species and is affected by many factors, including mutation rate, population size, life history and demography. To better understand the processes that influence levels of genetic diversity across taxa, we collected genome-wide restriction-associated DNA data from more than 500 individuals spanning 76 nominal species of Australian scincid lizards in the genus Ctenotus. To avoid potential biases associated with variation in taxonomic practice across the group, we used coalescent-based species delimitation to delineate 83 species-level lineages within the genus for downstream analyses. We then used these genetic data to infer levels of within-population genetic diversity. Using a phylogenetically informed approach, we tested whether variation in genetic diversity could be explained by population size, environmental heterogeneity or historical demography. We find that the strongest predictor of genetic diversity is a novel proxy for census population size: the number of vouchered occurrences in museum databases. However, museum occurrences only explain a limited proportion of the variance in genetic diversity, suggesting that genetic diversity might be difficult to predict at shallower phylogenetic scales. PMID:28469025

Genetic diversity is largely unpredictable but scales with museum occurrences in a species-rich clade of Australian lizards.

PubMed

Singhal, Sonal; Huang, Huateng; Title, Pascal O; Donnellan, Stephen C; Holmes, Iris; Rabosky, Daniel L

2017-05-17

Genetic diversity is a fundamental characteristic of species and is affected by many factors, including mutation rate, population size, life history and demography. To better understand the processes that influence levels of genetic diversity across taxa, we collected genome-wide restriction-associated DNA data from more than 500 individuals spanning 76 nominal species of Australian scincid lizards in the genus Ctenotus To avoid potential biases associated with variation in taxonomic practice across the group, we used coalescent-based species delimitation to delineate 83 species-level lineages within the genus for downstream analyses. We then used these genetic data to infer levels of within-population genetic diversity. Using a phylogenetically informed approach, we tested whether variation in genetic diversity could be explained by population size, environmental heterogeneity or historical demography. We find that the strongest predictor of genetic diversity is a novel proxy for census population size: the number of vouchered occurrences in museum databases. However, museum occurrences only explain a limited proportion of the variance in genetic diversity, suggesting that genetic diversity might be difficult to predict at shallower phylogenetic scales. © 2017 The Author(s).

Community Involvement in Developing Policies for Genetic Testing: Assessing the Interests and Experiences of Individuals Affected by Genetic Conditions

PubMed Central

Gollust, Sarah E.; Apse, Kira; Fuller, Barbara P.; Miller, Paul Steven; Biesecker, Barbara B.

2005-01-01

Because the introduction of genetic testing into clinical medicine and public health creates concerns for the welfare of individuals affected with genetic conditions, those individuals should have a role in policy decisions about testing. Mechanisms for promoting participation range from membership on advisory committees to community dialogues to surveys that provide evidence for supporting practice guidelines. Surveys can assess the attitudes and the experiences of members of an affected group and thus inform discussions about that community’s concerns regarding the appropriate use of a genetic test. Results of a survey of individuals affected with inherited dwarfism show how data can be used in policy and clinical-practice contexts. Future research of affected communities’ interests should be pursued so that underrepresented voices can be heard. PMID:15623855

Whole genome sequences of two octogenarians with sustained cognitive abilities

PubMed Central

Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar; Isobe, Noriko; Miller, Bruce L.; Baranzini, Sergio E.; Kramer, Joel H.; Oksenberg, Jorge R.

2014-01-01

Although numerous genetic variants affecting aging and mortality have been identified, e.g. APOE ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of two female octogenarians. We provide the repertoire of genomic variants that the two octogenarians have in common. We also describe the overlap with the previously reported genomes of two supercentenarians - individuals aged ≥ 110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the two octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased lifespan. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies. PMID:25618617

Whole genome sequences of 2 octogenarians with sustained cognitive abilities.

PubMed

Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar; Isobe, Noriko; Miller, Bruce L; Baranzini, Sergio E; Kramer, Joel H; Oksenberg, Jorge R

2015-03-01

Although numerous genetic variants affecting aging and mortality have been identified, for example, apolipoprotein E ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of 2 female octogenarians. We provide the repertoire of genomic variants that the 2 octogenarians have in common. We also describe the overlap with the previously reported genomes of 2 supercentenarians—individuals aged ≥110 years. We assessed the genetic disease propensities of the octogenarians and non-aged control genomes and could not find support for the hypothesis that long-lived healthy individuals might exhibit greater genetic fitness than the general population. Furthermore, there is no evidence for an accumulation of previously described variants promoting longevity in the 2 octogenarians. These findings suggest that genetic fitness, as currently defined, is not the sole factor enabling an increased life span. We identified a number of healthy-cognitive-aging candidate genetic loci awaiting confirmation in larger studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapy of a couple with a bipolar spouse.

PubMed

Witusik, Andrzej; Pietras, Tadeusz

2017-10-23

Qualitative analysis of therapy of a couple with a partner who has bipolar disorder is an important research paradigm in contemporary psychotherapy of mental disorders.The qualitative method of the study is important both from the cognitive point of view and for the evaluation of the therapeutic efficacy in the individual, idiographical aspect. The aim of the study is a qualitative analysis of the therapeutic process of a couple in which one partner suffers from bipolar affective disorder. The study of the couple therapy process utilized the qualitative research methodology using variouspsychotherapeutic paradigms indicating the interrelationships that exist between relapses of the disease and functioning of the couple. The importance of triangulation processes, inheritance of transgenerational myths and dysfunctional cognitive patterns in the functional destabilization of a couple with one partner suffering from bipolar affective disorder was indicated. The study of the couple therapy process utilized the qualitative research methodology using variouspsychotherapeutic paradigms indicating the interrelationships that exist between relapses of the disease and functioning of the couple. The importance of triangulation processes, inheritance of transgenerational myths and dysfunctional cognitive patterns in the functional destabilization of a couple with one partner suffering from bipolar affective disorder was indicated. The dysfunctionality of the discussed couple is largely due to the effects of bipolar disorder and related disturbances on marital functioning. The spectrum of autism in the child is probably related both to the genetic strain of predisposition to psychiatric disorders and to the dysfunctionality of the parental dyad. The presence of bipolar affective disorder in the partner's family is also a genetic burden. The wife's aggression represents probably a syndrome of adaptation to disease in the family. Aggression plays a morphostatic role in the couple integrity.In both families of origin of the spouses, the transgeneration myth placed the woman in the position of a strong and family-oriented person.

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

PubMed

Bruce, H A; Kochunov, P; Paciga, S A; Hyde, C L; Chen, X; Xie, Z; Zhang, B; Xi, H S; O'Donnell, P; Whelan, C; Schubert, C R; Bellon, A; Ament, S A; Shukla, D K; Du, X; Rowland, L M; O'Neill, H; Hong, L E

2017-06-01

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Demographic History and Reproductive Output Correlates with Intraspecific Genetic Variation in Seven Species of Indo-Pacific Mangrove Crabs

PubMed Central

Fratini, Sara; Ragionieri, Lapo; Cannicci, Stefano

2016-01-01

The spatial distribution and the amount of intraspecific genetic variation of marine organisms are strongly influenced by many biotic and abiotic factors. Comparing biological and genetic data characterizing species living in the same habitat can help to elucidate the processes driving these variation patterns. Here, we present a comparative multispecies population genetic study on seven mangrove crabs co-occurring in the West Indian Ocean characterized by planktotrophic larvae with similar pelagic larval duration. Our main aim was to investigate whether a suite of biological, behavioural and ecological traits could affect genetic diversities of the study species in combination with historical demographic parameters. As possible current explanatory factors, we used the intertidal micro-habitat colonised by adult populations, various parameters of individual and population fecundity, and the timing of larval release. As the genetic marker, we used partial sequences of cytochrome oxidase subunit I gene. Genetic and ecological data were collected by the authors and/or gathered from primary literature. Permutational multiple regression models and ANOVA tests showed that species density and their reproductive output in combination with historical demographic parameters could explain the intraspecific genetic variation indexes across the seven species. In particular, species producing consistently less eggs per spawning event showed higher values of haplotype diversity. Moreover, Tajima’s D parameters well explained the recorded values for haplotype diversity and average γst. We concluded that current intraspecific gene diversities in crabs inhabiting mangrove forests were affected by population fecundity as well as past demographic history. The results were also discussed in terms of management and conservation of fauna in the Western Indian Ocean mangroves. PMID:27379532

Demographic History and Reproductive Output Correlates with Intraspecific Genetic Variation in Seven Species of Indo-Pacific Mangrove Crabs.

PubMed

Fratini, Sara; Ragionieri, Lapo; Cannicci, Stefano

2016-01-01

The spatial distribution and the amount of intraspecific genetic variation of marine organisms are strongly influenced by many biotic and abiotic factors. Comparing biological and genetic data characterizing species living in the same habitat can help to elucidate the processes driving these variation patterns. Here, we present a comparative multispecies population genetic study on seven mangrove crabs co-occurring in the West Indian Ocean characterized by planktotrophic larvae with similar pelagic larval duration. Our main aim was to investigate whether a suite of biological, behavioural and ecological traits could affect genetic diversities of the study species in combination with historical demographic parameters. As possible current explanatory factors, we used the intertidal micro-habitat colonised by adult populations, various parameters of individual and population fecundity, and the timing of larval release. As the genetic marker, we used partial sequences of cytochrome oxidase subunit I gene. Genetic and ecological data were collected by the authors and/or gathered from primary literature. Permutational multiple regression models and ANOVA tests showed that species density and their reproductive output in combination with historical demographic parameters could explain the intraspecific genetic variation indexes across the seven species. In particular, species producing consistently less eggs per spawning event showed higher values of haplotype diversity. Moreover, Tajima's D parameters well explained the recorded values for haplotype diversity and average γst. We concluded that current intraspecific gene diversities in crabs inhabiting mangrove forests were affected by population fecundity as well as past demographic history. The results were also discussed in terms of management and conservation of fauna in the Western Indian Ocean mangroves.

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Ethical issues in dementia

PubMed Central

Whitehouse, Peter J.

2000-01-01

The growing number of individuals affected by dementia will intensify the ethical issues that emerge in clinical practice and research, issues early in disease relate to genetic testing, use of medications in mildly affected persons, and diagnostic disclosure. Research issues relate to appropriate informed consent processes, conflict of interests, and research design issues, such as the use of placebos and the use of biological tissues, in the later stages of disease concern about appropriate therapeutic goals and end-of-life care is appropriate. PMID:22033828

Focus on: epigenetics and fetal alcohol spectrum disorders.

PubMed

Kobor, Michael S; Weinberg, Joanne

2011-01-01

Epigenetic changes-stable but potentially reversible alterations in a cell's genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence-may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol's adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine-homocysteine cycle.

Focus On: Epigenetics and Fetal Alcohol Spectrum Disorders

PubMed Central

Kobor, Michael S.; Weinberg, Joanne

2011-01-01

Epigenetic changes—stable but potentially reversible alterations in a cell’s genetic information that result in changes in gene expression but do not involve changes in the underlying DNA sequence—may mediate some of the detrimental effects of prenatal alcohol exposure and contribute to the deficits and abnormalities associated with fetal alcohol spectrum disorders. These epigenetic processes are linked to the chromatin (i.e., DNA, histone proteins, and other associated proteins) and commonly involve chemical modifications (e.g., methylation) of these molecules, which may result in altered expression of the affected genes. Even alcohol exposure prior to conception appears to be able to induce epigenetic changes in the parental genetic material that can be passed on to the offspring and affect offspring outcome. Similarly, epigenetic processes may occur as a result of maternal alcohol consumption during the period between fertilization of the egg and implantation in the uterus. The period most sensitive to alcohol’s adverse effects appears to be gastrulation, which corresponds to prenatal weeks 3 to 8 in the human and prenatal days 7 to 14 in the mouse, when cells are differentiating to form organs. One way in which alcohol exposure may induce epigenetic changes, particularly abnormal DNA methylation, is by affecting a set of biochemical reactions called the methionine–homocysteine cycle. PMID:23580038

Genetics Home Reference: chronic atrial and intestinal dysrhythmia

MedlinePlus

... for This Condition CAID cohesinopathy affecting heart and gut rhythm Related Information How are genetic conditions and ... SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nat Genet. 2014 Nov;46(11):1245- ...

Growth

Treesearch

John R. Jones; George A. Schier

1985-01-01

This chapter considers aspen growth as a process, and discusses some characteristics of the growth and development of trees and stands. For the most part, factors affecting growth are discussed elsewhere, particularly in the GENETICS AND VARIATION chapter and in chapters in PART 11. ECOLOGY. Aspen growth as it relates to wood production is examined in the WOOD RESOURCE...

Relative contributions of neutral and non-neutral processes to clinal variation in calyx lobe length in the series Sakawanum (Asarum: Aristolochiaceae).

PubMed

Takahashi, Daiki; Teramine, Tsutomu; Sakaguchi, Shota; Setoguchi, Hiroaki

2018-01-25

Clines, the gradual variation in measurable traits along a geographical axis, play a major role in evolution and can contribute to our understanding of the relative roles of selective and neutral process in trait variation. Using genetic and morphological analyses, the relative contributions of neutral and non-neutral processes were explored to infer the evolutionary history of species of the series Sakawanum (genus Asarum), which shows significant clinal variation in calyx lobe length. A total of 27 populations covering the natural geographical distribution of the series Sakawanum were sampled. Six nuclear microsatellite markers were used to investigate genetic structure and genetic diversity. The lengths of calyx lobes of multiple populations were measured to quantify their geographical and taxonomic differentiation. To detect the potential impact of selective pressure, morphological differentiation was compared with genetic differentiation (QCT-FST comparison). Average calyx lobe length of A. minamitanianum was 124.11 mm, while that of A. costatum was 13.80 mm. Though gradually changing along the geographical axis within series, calyx lobe lengths were significantly differentiated among the taxa. Genetic differentiation between taxa was low (FST = 0.099), but a significant geographical structure along the morphological cline was detected. Except for one taxon pair, pairwise QCT values were significantly higher than the neutral genetic measures of FST and G'ST. Divergent selection may have driven the calyx lobe length variation in series Sakawanum taxa, although the underlying mechanism is still not clear. The low genetic differentiation indicates recent divergence and/or gene flows between geographically close taxa. These neutral processes would also affect the clinal variation in calyx lobe lengths. Overall, this study implies the roles of population history and divergent selection in shaping the current cline of a flower trait in the series Sakawanum. © The Author(s) 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic selection for temperament affects behaviour and the secretion of adrenal and reproductive hormones in sheep subjected to stress.

PubMed

Hawken, P A R; Luckins, N; Tilbrook, A; Fiol, C; Martin, G B; Blache, D

2013-01-01

We investigated the effect of genetic selection for temperament on the way that stressors affect the behaviour and the adrenal and reproductive axes of sheep. We tested three hypotheses: (i) isolation would increase cortisol secretion and decrease luteinising hormone (LH) secretion more in nervous sheep than in calm sheep; (ii) isolation combined with simulated human presence would increase cortisol secretion and decrease LH secretion more in nervous sheep than in calm sheep and (iii) isolation combined with stressors that were not specific to the selection process (i.e. non-selection stressors) would increase cortisol secretion and decrease LH secretion equally in calm and nervous sheep. Isolation alone increased cortisol secretion and decreased LH secretion in nervous sheep but not in calm sheep. Compared to calm sheep, nervous sheep were more agitated during the first 2 h of isolation but not during the second 2 h of isolation. Exposure to non-selection stressors increased cortisol secretion, decreased LH pulse amplitude and the mean plasma concentrations of LH in both calm and nervous sheep. We conclude that genetic selection for temperament affects the behavioural expression of the stress response and the secretion of adrenal and reproductive hormones during isolation, but has less impact on their reactivity to non-selection stressors.

Communication of Psychiatric Risk in 22q11.2 Deletion Syndrome: A Pilot Project.

PubMed

Hart, Sarah J; Schoch, Kelly; Shashi, Vandana; Callanan, Nancy

2016-02-01

Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an increased chance of developing a psychiatric disorder. While parents of children affected by 22q11.2DS typically receive counseling about risk for non-psychiatric health concerns, genetic counselors may be reluctant to discuss psychiatric risk. Further education of genetic counselors may be necessary to encourage discussion of psychiatric risk with these families. The goal of this project was to develop recommendations for genetic counselors to provide psychiatric risk information to families affected by 22q11.2DS. The recommendations were developed by synthesizing resources in the literature about risk communication. These recommendations were refined following an online focus group meeting with five health care professionals who were recruited for participation from 22q11.2DS clinics across the U.S.A. The focus group data revealed three themes related to discussion of psychiatric risk: 1) Stepwise approach, 2) Discussing treatment options and reducing risks, and 3) Addressing stigma. These recommendations may be used as a foundation for a future clinical protocol to encourage discussion about the risk for psychiatric illness at an earlier point in the diagnostic process for 22q11.2DS and to provide improved information, support and resources to affected families.

[Expansive development of the French regulation of the genetic print files after the recent reforms (Part I)].

PubMed

Etxeberria Guridi, José Francisco

2003-01-01

French regulations related to "genetic prints" and its later incorporation to an automatized file in the frame of the penal process, initially deserved (1998) a positive judgement due to the guarantees surrounding such techniques, considering that with its use an interference was made with the freedom and rights of the individual. This primary regulation is watching a legislative evolution that brings serious doubts about the current guarantee system. A couple of legal reforms with security as their main axis (2001 and 2003) give more importance to the "genetic print" file by extending the causes in which it starts functioning going against the proportionality that must be observed when freedoms and rights of the individual can be affected.

Regulating preimplantation genetic diagnosis in Australia: Disability and parental choice.

PubMed

de Souza, Michelle

2015-06-01

Preimplantation genetic diagnosis (PGD) is the process by which an early in vitro embryo is screened for a genetic condition. As the name suggests, the procedure is undertaken prior to the embryo being implanted into a woman and therefore affected embryos can be discarded. This article argues that the objections previously put forward opposing the use of PGD to select against disability are flawed. It also argues that permitting parents to act in a procreatively beneficent manner and to preserve their child's right to an open future are good reasons for parents to have the freedom to select against disability. In light of this, are there any sound reasons to limit the use of PGD to selection against serious disabilities?

Our retroviral heritage.

PubMed

Patience, C; Wilkinson, D A; Weiss, R A

1997-03-01

Darwin could not have foretold that we are descended from viruses as well as from apes. While there is clear evidence that viral diseases, such as polio and rabies, affected ancient civilizations, viruses were not defined until the early years of this century, shortly after the rediscovery of mendelian genetics. That retroviral genomes can oscillate between infectious and genetic modes of transmission seemed preposterous before the discovery of reverse transcription in 1970. Those of us who had earlier provided mendelian evidence for germ-line transmission of retroviruses were subject of friendly ridicule. Today, the shunting of genetic elements between chromosomes and RNA, and the generation of processed pseudogenes, seems commonplace. It is timely, however, to revisit the topic of human endogenous retroviruses-the subject of this article.

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

PubMed

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 contact between Chefu and Limpopo populations. We demonstrated: (1) ancient (pre-Pleistocene) divergence between the two main N. furzeri lineages, their recent secondary contact and lack of reproductive isolation; (2) important genetic structuring attributed to the fragmented nature of their environment and isolation-by-distance, suggesting that dispersal is limited, occurs over short distances and is not directly associated with river routes; (3) an apparent role of the River Limpopo as a barrier to dispersal and gene flow.

Genetic and environmental factors affecting early rooting of six Populus genomic groups: implications for tree improvement

Treesearch

Ronald S., Jr. Zalesny

2006-01-01

Genetic and environmental factors affect the early rooting of Populus planted as unrooted hardwood cuttings. Populus genotypes of six genomic groups were tested in numerous studies for the quantitative genetics of rooting, along with effects of preplanting treatments and soil temperature. Genetics data (e.g. heritabilities,...

Functional variation in a disease resistance gene in populations of Arabidopsis thaliana.

PubMed

Jorgensen, T H; Emerson, B C

2008-11-01

Analyses of functional genetic diversity in natural populations may provide important new insights into gene function and are necessary to understand the evolutionary processes maintaining diversity itself. The importance of including diversity within and between local populations in such studies is often ignored although many of the processes affecting genetic diversity act on this scale. Here we examine the molecular diversity in RPW8 (Recognition of Powdery Mildew), a gene conferring broad-spectrum resistance to powdery mildews in Arabidopsis thaliana stock-center accessions. Our eight UK study populations of the weedy A. thaliana were from locations judged to be subject to a minimum of anthropogenic disturbance and potentially long established. The majority of populations comprised considerable variation both in disease phenotype and RPW8 genotype. Although resistant individuals shared a major RPW8 genotype, no single allele was uniquely associated with resistance. It is concluded that RPW8 is an essential component of resistance to powdery mildews in A. thaliana, but not the only genetic factor involved in this process. No signature of selection was detected at RPW8 with a microsatellite multilocus test using an empirical null model. Unlike many previous studies of this model plant species, we found high levels of genetic diversity and relatively low differentiation (F(ST) = 0.31) between populations at 14 microsatellite markers. This is judged to be due to our sampling being aimed at potentially long established populations and highlights the importance of population choice for studies of genetic diversity within this species.

A twin study of the genetics of fear conditioning.

PubMed

Hettema, John M; Annas, Peter; Neale, Michael C; Kendler, Kenneth S; Fredrikson, Mats

2003-07-01

Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample. Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning. All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli. Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.

Lower urinary tract development and disease

PubMed Central

Rasouly, Hila Milo; Lu, Weining

2013-01-01

Congenital Anomalies of the Lower Urinary Tract (CALUT) are a family of birth defects of the ureter, the bladder and the urethra. CALUT includes ureteral anomalies such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUV). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, bladder, and urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, bladder and urethra and associated gene mutations are also presented. As we are entering the post-genomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. PMID:23408557

Testing for Neuropsychological Endophenotypes in Siblings Discordant for ADHD

PubMed Central

Bidwell, L. Cinnamon; Willcutt, Erik G.; DeFries, John C.; Pennington, Bruce F.

2007-01-01

Objective Neurocognitive deficits associated with attention deficit-hyperactivity disorder (ADHD) may be useful intermediate endophenotypes for determining specific genetic pathways that contribute to ADHD. Methods This study administered 17 measures from prominent neuropsychological theories of ADHD (executive function, processing speed, arousal regulation and motivation/delay aversion) in dizygotic (DZ) twin pairs discordant for ADHD and control twin pairs (ages 8–18) in order to compare performance between twins affected with ADHD (n = 266), their unaffected co-twins (n = 228), and control children from twin pairs without ADHD or learning difficulties (n = 332). Results ADHD subjects show significant impairment on executive function, processing speed, and response variability measures compared to control subjects. Unaffected cotwins of ADHD subjects are significantly impaired on nearly all the same measures as their ADHD siblings, even when subclinical symptoms of ADHD are controlled. Conclusion Executive function, processing speed, and response variability deficits may be useful endophenotypes for genetic studies of ADHD. PMID:17585884

A de novo variant in the ASPRV1 gene in a dog with ichthyosis.

PubMed

Bauer, Anina; Waluk, Dominik P; Galichet, Arnaud; Timm, Katrin; Jagannathan, Vidhya; Sayar, Beyza S; Wiener, Dominique J; Dietschi, Elisabeth; Müller, Eliane J; Roosje, Petra; Welle, Monika M; Leeb, Tosso

2017-03-01

Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding "aspartic peptidase, retroviral-like 1", which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.

Spatial heterogeneity and the evolution of sex in diploids.

PubMed

Agrawal, Aneil F

2009-07-01

Much of the theoretical work on the evolution of sex has focused on the effects of recombination. In diploids, segregation also occurs during sexual reproduction. Segregation breaks down some types of genetic associations that are not affected by recombination and thus influences the evolution of sex in ways that are not apparent from studying the evolution of recombination as a surrogate for sex. Here I examine the evolution of sex in diploids experiencing spatially heterogeneous selection. If divergent selection causes genetic differentiation, then migration can be a powerful force generating genetic associations that may not be favored by selection. An advantage to sex can arise from breaking down these associations. By examining modifiers of both sex and recombination, the model allows for a direct comparison of the forces acting on these related but different processes, illuminating the role of segregation. The model also includes inbreeding, which has been shown to be important for both segregation and recombination. I find that inbreeding affects the evolution of sex through segregation, not recombination. Several suggestions for empirical experiments are given.

Insight into podocyte differentiation from the study of human genetic disease: nail-patella syndrome and transcriptional regulation in podocytes.

PubMed

Morello, Roy; Lee, Brendan

2002-05-01

In recent years, our understanding of the molecular basis of kidney development has benefited from the study of rare genetic diseases affecting renal function. This has especially been the case with the differentiation of the highly specialized podocyte in the pathogenesis of human disorders and mouse phenotypes affecting the renal filtration barrier. This filtration barrier represents the end product of a complex series of signaling events that produce a tripartite structure consisting of interdigitating podocyte foot processes with intervening slit diaphragms, the glomerular basement membrane, and the fenestrated endothelial cell. Dysregulation of unique cytoskeletal and extracellular matrix proteins in genetic forms of nephrotic syndrome has shown how specific structural proteins contribute to podocyte function and differentiation. However, much less is known about the transcriptional determinants that both specify and maintain this differentiated cell. Our studies of a skeletal malformation syndrome, nail-patella syndrome, have shown how the LIM homeodomain transcription factor, Lmx1b, contributes to transcriptional regulation of glomerular basement membrane collagen expression by podocytes. Moreover, they raise intriguing questions about more global transcriptional regulation of podocyte morphogenesis.

The Arabidopsis DELAY OF GERMINATION 1 gene affects ABSCISIC ACID INSENSITIVE 5 (ABI5) expression and genetically interacts with ABI3 during Arabidopsis seed development.

PubMed

Dekkers, Bas J W; He, Hanzi; Hanson, Johannes; Willems, Leo A J; Jamar, Diaan C L; Cueff, Gwendal; Rajjou, Loïc; Hilhorst, Henk W M; Bentsink, Leónie

2016-02-01

The seed expressed gene DELAY OF GERMINATION (DOG) 1 is absolutely required for the induction of dormancy. Next to a non-dormant phenotype, the dog1-1 mutant is also characterized by a reduced seed longevity suggesting that DOG1 may affect additional seed processes as well. This aspect however, has been hardly studied and is poorly understood. To uncover additional roles of DOG1 in seeds we performed a detailed analysis of the dog1 mutant using both transcriptomics and metabolomics to investigate the molecular consequences of a dysfunctional DOG1 gene. Further, we used a genetic approach taking advantage of the weak aba insensitive (abi) 3-1 allele as a sensitized genetic background in a cross with dog1-1. DOG1 affects the expression of hundreds of genes including LATE EMBRYOGENESIS ABUNDANT and HEAT SHOCK PROTEIN genes which are affected by DOG1 partly via control of ABI5 expression. Furthermore, the content of a subset of primary metabolites, which normally accumulate during seed maturation, was found to be affected in the dog1-1 mutant. Surprisingly, the abi3-1 dog1-1 double mutant produced green seeds which are highly ABA insensitive, phenocopying severe abi3 mutants, indicating that dog1-1 acts as an enhancer of the weak abi3-1 allele and thus revealing a genetic interaction between both genes. Analysis of the dog1 and dog1 abi3 mutants revealed additional seed phenotypes and therefore we hypothesize that DOG1 function is not limited to dormancy but that it is required for multiple aspects of seed maturation, in part by interfering with ABA signalling components. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Ethical dilemmas in genetic testing: examples from the Cuban program for predictive diagnosis of hereditary ataxias.

PubMed

Mariño, Tania Cruz; Armiñán, Rubén Reynaldo; Cedeño, Humberto Jorge; Mesa, José Miguel Laffita; Zaldivar, Yanetza González; Rodríguez, Raúl Aguilera; Santos, Miguel Velázquez; Mederos, Luis Enrique Almaguer; Herrera, Milena Paneque; Pérez, Luis Velázquez

2011-06-01

Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series of five cases involving predictive testing for hereditary ataxias in Cuba. The examples herein present evidence of the deeply controversial situations faced by both individuals at risk and professionals in charge of these predictive studies, suggesting a need for expanded guidelines to address such complexities.

The double-edged sword of genetic accounts of criminality: causal attributions from genetic ascriptions affect legal decision making.

PubMed

Cheung, Benjamin Y; Heine, Steven J

2015-12-01

Much debate exists surrounding the applicability of genetic information in the courtroom, making the psychological processes underlying how people consider this information important to explore. This article addresses how people think about different kinds of causal explanations in legal decision-making contexts. Three studies involving a total of 600 Mechanical Turk and university participants found that genetic, versus environmental, explanations of criminal behavior lead people to view the applicability of various defense claims differently, perceive the perpetrator's mental state differently, and draw different causal attributions. Moreover, mediation and path analyses highlight the double-edged nature of genetic attributions-they simultaneously reduce people's perception of the perpetrator's sense of control while increasing people's tendencies to attribute the cause to internal factors and to expect the perpetrator to reoffend. These countervailing relations, in turn, predict sentencing in opposite directions, although no overall differences in sentencing or ultimate verdicts were found. © 2015 by the Society for Personality and Social Psychology, Inc.

Community acquired pneumonia: genetic variants influencing systemic inflammation.

PubMed

Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

2014-01-01

The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

The emergence of overlapping scale-free genetic architecture in digital organisms.

PubMed

Gerlee, P; Lundh, T

2008-01-01

We have studied the evolution of genetic architecture in digital organisms and found that the gene overlap follows a scale-free distribution, which is commonly found in metabolic networks of many organisms. Our results show that the slope of the scale-free distribution depends on the mutation rate and that the gene development is driven by expansion of already existing genes, which is in direct correspondence to the preferential growth algorithm that gives rise to scale-free networks. To further validate our results we have constructed a simple model of gene development, which recapitulates the results from the evolutionary process and shows that the mutation rate affects the tendency of genes to cluster. In addition we could relate the slope of the scale-free distribution to the genetic complexity of the organisms and show that a high mutation rate gives rise to a more complex genetic architecture.

Genetic and cellular mechanisms of the formation of Esophageal Atresia and Tracheoesophageal Fistula

PubMed Central

Jacobs, Ian J.; Que, Jianwen

2015-01-01

Foregut separation involves dynamic changes in the activities of signaling pathways and transcription factors. Recent mouse genetic studies demonstrate that some of these pathways interact with each other to form a complex network, leading to a unique dorsal-ventral patterning in the early foregut. In this review we will discuss how this unique dorsal-ventral patterning is set prior to the foregut separation and how disruption of this patterning affects the separation process. We will further discuss the roles of downstream targets of these pathways in regulating separation at cellular and molecular levels. Understanding the mechanism of normal separation process will provide us insights into the pathobiology of a relatively common birth defect Esophageal Atresia (EA) with/without Tracheo-esophageal Fistula (TEF). PMID:23679023

Rangewide landscape genetics of an endemic Pacific northwestern salamander.

PubMed

Trumbo, Daryl R; Spear, Stephen F; Baumsteiger, Jason; Storfer, Andrew

2013-03-01

A species' genetic structure often varies in response to ecological and landscape processes that differ throughout the species' geographic range, yet landscape genetics studies are rarely spatially replicated. The Cope's giant salamander (Dicamptodon copei) is a neotenic, dispersal-limited amphibian with a restricted geographic range in the Pacific northwestern USA. We investigated which landscape factors affect D. copei gene flow in three regions spanning the species' range, which vary in climate, landcover and degree of anthropogenic disturbance. Least cost paths and Circuitscape resistance analyses revealed that gene flow patterns vary across the species' range, with unique combinations of landscape variables affecting gene flow in different regions. Populations in the northern coastal portions of the range had relatively high gene flow, largely facilitated by stream and river networks. Near the southeastern edge of the species' range, gene flow was more restricted overall, with relatively less facilitation by streams and more limitation by heat load index and fragmented forest cover. These results suggested that the landscape is more difficult for individuals to disperse through at the southeastern edge of the species' range, with terrestrial habitat desiccation factors becoming more limiting to gene flow. We suggest that caution be used when attempting to extrapolate landscape genetic models and conservation measures from one portion of a species' range to another. © 2013 Blackwell Publishing Ltd.

Transcription as a source of genome instability

PubMed Central

Kim, Nayun; Jinks-Robertson, Sue

2012-01-01

Alterations in genome sequence and structure contribute to somatic disease, affect the fitness of subsequent generations and drive evolutionary processes. The critical roles of highly accurate replication and efficient repair in maintaining overall genome integrity are well known, but the more localized stability costs associated with transcribing DNA into RNA molecules are less appreciated. Here we review the diverse ways that the essential process of transcription alters the underlying DNA template and thereby modifies the genetic landscape. PMID:22330764

An example of demographic anthropology, the study of matrimonial exchanges--endogamy, choice of spouse and preferential marriage.

PubMed

Cazes, Marie-Hélène

2006-09-01

The development of demographic studies in anthropology is directly linked to the success of population genetics. The anthropodemographic or anthropogenetic approach is thus underpinned by questions of genetics. While demographers focus on population dynamics and renewal in quantitative terms, population geneticists refer not to individuals but to the sets of genes carried by individuals in a population. Their aim is to detect the factors and processes which influence the genetic evolution of a group, i.e. which modify gene frequencies from one generation to the next. Among them are the factors which affect modes of reproduction. To illustrate the association of these three approaches, i.e. demographic, anthropological and genetic, I use here the example of matrimonial exchanges--which lie at the heart of the population renewal process--among the Dogon of Boni, a Malian ethnic group living in the southern Sahel. We can see how successive analyses--starting with endogamy at macroscopic level and moving down to the individual with choice of spouse and preferential marriage-- combining both quantitative and qualitative approaches, can be used to obtain a detailed description of matrimonial exchanges which shed light upon and complement the three different viewpoints.

Interaction between DRD2 variation and sound environment on mood and emotion-related brain activity.

PubMed

Quarto, T; Fasano, M C; Taurisano, P; Fazio, L; Antonucci, L A; Gelao, B; Romano, R; Mancini, M; Porcelli, A; Masellis, R; Pallesen, K J; Bertolino, A; Blasi, G; Brattico, E

2017-01-26

Sounds, like music and noise, are capable of reliably affecting individuals' mood and emotions. However, these effects are highly variable across individuals. A putative source of variability is genetic background. Here we explored the interaction between a functional polymorphism of the dopamine D2 receptor gene (DRD2 rs1076560, G>T, previously associated with the relative expression of D2S/L isoforms) and sound environment on mood and emotion-related brain activity. Thirty-eight healthy subjects were genotyped for DRD2 rs1076560 (G/G=26; G/T=12) and underwent functional magnetic resonance imaging (fMRI) during performance of an implicit emotion-processing task while listening to music or noise. Individual variation in mood induction was assessed before and after the task. Results showed mood improvement after music exposure in DRD2GG subjects and mood deterioration after noise exposure in GT subjects. Moreover, the music, as opposed to noise environment, decreased the striatal activity of GT subjects as well as the prefrontal activity of GG subjects while processing emotional faces. These findings suggest that genetic variability of dopamine receptors affects sound environment modulations of mood and emotion processing. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Metabolic rate and climatic fluctuations shape continental wide pattern of genetic divergence and biodiversity in fishes.

PubMed

April, Julien; Hanner, Robert H; Mayden, Richard L; Bernatchez, Louis

2013-01-01

Taxonomically exhaustive and continent wide patterns of genetic divergence within and between species have rarely been described and the underlying evolutionary causes shaping biodiversity distribution remain contentious. Here, we show that geographic patterns of intraspecific and interspecific genetic divergence among nearly all of the North American freshwater fish species (>750 species) support a dual role involving both the late Pliocene-Pleistocene climatic fluctuations and metabolic rate in determining latitudinal gradients of genetic divergence and very likely influencing speciation rates. Results indicate that the recurrent glacial cycles caused global reduction in intraspecific diversity, interspecific genetic divergence, and species richness at higher latitudes. At the opposite, longer geographic isolation, higher metabolic rate increasing substitution rate and possibly the rapid accumulation of genetic incompatibilities, led to an increasing biodiversity towards lower latitudes. This indicates that both intrinsic and extrinsic factors similarly affect micro and macro evolutionary processes shaping global patterns of biodiversity distribution. These results also indicate that factors favouring allopatric speciation are the main drivers underlying the diversification of North American freshwater fishes.

Metabolic Rate and Climatic Fluctuations Shape Continental Wide Pattern of Genetic Divergence and Biodiversity in Fishes

PubMed Central

April, Julien; Hanner, Robert H.; Mayden, Richard L.; Bernatchez, Louis

2013-01-01

Taxonomically exhaustive and continent wide patterns of genetic divergence within and between species have rarely been described and the underlying evolutionary causes shaping biodiversity distribution remain contentious. Here, we show that geographic patterns of intraspecific and interspecific genetic divergence among nearly all of the North American freshwater fish species (>750 species) support a dual role involving both the late Pliocene-Pleistocene climatic fluctuations and metabolic rate in determining latitudinal gradients of genetic divergence and very likely influencing speciation rates. Results indicate that the recurrent glacial cycles caused global reduction in intraspecific diversity, interspecific genetic divergence, and species richness at higher latitudes. At the opposite, longer geographic isolation, higher metabolic rate increasing substitution rate and possibly the rapid accumulation of genetic incompatibilities, led to an increasing biodiversity towards lower latitudes. This indicates that both intrinsic and extrinsic factors similarly affect micro and macro evolutionary processes shaping global patterns of biodiversity distribution. These results also indicate that factors favouring allopatric speciation are the main drivers underlying the diversification of North American freshwater fishes. PMID:23922969

[Genetic predisposition to breast and ovarian cancer: importance of test results].

PubMed

Julian-Reynier, Claire

2011-01-01

Oncogenetic consultations and predictive BRCA1/2 testing are intertwined processes and the specific impact of these genetic tests if performed alone through direct-to-consumer offers remains unknown. Noteworthy, the expectations of patients vary with their own status, whether they are affected or not by breast cancer at the time genetic testing is performed. The prescription of genetic tests for BCRA mutations has doubled in France between 2003 and 2009. There is a consensus on the fact that genetic results disclosure led to a significant increase in the knowledge and understanding that the patients have of the genetic risk and also changed the medical follow-up of these patients. Evaluating the psychological burden of tests disclosure did not reveal any major distress in patients who are followed by high-quality multidisciplinary teams. Longitudinal cohorts studies have now evaluated the perception and behaviour of these patients, and observed sociodemographic as well as geographic and psychosocial differences both in the acceptation of prophylactic strategies such as surgery, and time to surgery. © 2011 médecine/sciences - Inserm / SRMS.

Congenital prosopagnosia is associated with a genetic variation in the oxytocin receptor (OXTR) gene: An exploratory study.

PubMed

Cattaneo, Zaira; Daini, Roberta; Malaspina, Manuela; Manai, Federico; Lillo, Mariarita; Fermi, Valentina; Schiavi, Susanna; Suchan, Boris; Comincini, Sergio

2016-12-17

Face-recognition deficits, referred to with the term prosopagnosia (i.e., face blindness), may manifest during development in the absence of any brain injury (from here the term congenital prosopagnosia, CP). It has been estimated that approximately 2.5% of the population is affected by face-processing deficits not depending on brain lesions, and varying a lot in severity. The genetic bases of this disorder are not known. In this study we tested for genetic association between single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) and CP in a restricted cohort of Italian participants. We found evidence of an association between the common genetic variants rs53576 and rs2254298 OXTR SNPs and prosopagnosia. This association was also found when including an additional group of German individuals classified as prosopagnosic in the analysis. Our preliminary data provide initial support for the involvement of genetic variants of OXTR in a relevant cognitive impairment, whose genetic bases are still largely unexplored. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Genetic variation in vitamin B-12 content of bovine milk and its association with SNP along the bovine genome.

PubMed

Rutten, Marc J M; Bouwman, Aniek C; Sprong, R Corinne; van Arendonk, Johan A M; Visker, Marleen H P W

2013-01-01

Vitamin B-12 (also called cobalamin) is essential for human health and current intake levels of vitamin B-12 are considered to be too low. Natural enrichment of the vitamin B-12 content in milk, an important dietary source of vitamin B-12, may help to increase vitamin B-12 intake. Natural enrichment of the milk vitamin B-12 content could be achieved through genetic selection, provided there is genetic variation between cows with respect to the vitamin B-12 content in their milk. A substantial amount of genetic variation in vitamin B-12 content was detected among raw milk samples of 544 first-lactation Dutch Holstein Friesian cows. The presence of genetic variation between animals in vitamin B-12 content in milk indicates that the genotype of the cow affects the amount of vitamin B-12 that ends up in her milk and, consequently, that the average milk vitamin B-12 content of the cow population can be increased by genetic selection. A genome-wide association study revealed significant association between 68 SNP and vitamin B-12 content in raw milk of 487 first-lactation Dutch Holstein Friesian cows. This knowledge facilitates genetic selection for milk vitamin B-12 content. It also contributes to the understanding of the biological mechanism responsible for the observed genetic variation in vitamin B-12 content in milk. None of the 68 significantly associated SNP were in or near known candidate genes involved in transport of vitamin B-12 through the gastrointestinal tract, uptake by ileum epithelial cells, export from ileal cells, transport through the blood, uptake from the blood, intracellular processing, or reabsorption by the kidneys. Probably, associations relate to genes involved in alternative pathways of well-studied processes or to genes involved in less well-studied processes such as ruminal production of vitamin B-12 or secretion of vitamin B-12 by the mammary gland.

Domesticated, Genetically Engineered, and Wild Plant Relatives Exhibit Unintended Phenotypic Differences: A Comparative Meta-Analysis Profiling Rice, Canola, Maize, Sunflower, and Pumpkin

PubMed Central

Hernández-Terán, Alejandra; Wegier, Ana; Benítez, Mariana; Lira, Rafael; Escalante, Ana E.

2017-01-01

Agronomic management of plants is a powerful evolutionary force acting on their populations. The management of cultivated plants is carried out by the traditional process of human selection or plant breeding and, more recently, by the technologies used in genetic engineering (GE). Even though crop modification through GE is aimed at specific traits, it is possible that other non-target traits can be affected by genetic modification due to the complex regulatory processes of plant metabolism and development. In this study, we conducted a meta-analysis profiling the phenotypic consequences of plant breeding and GE, and compared modified cultivars with wild relatives in five crops of global economic and cultural importance: rice, maize, canola, sunflower, and pumpkin. For these five species, we analyzed the literature with documentation of phenotypic traits that are potentially related to fitness for the same species in comparable conditions. The information was analyzed to evaluate whether the different processes of modification had influenced the phenotype in such a way as to cause statistical differences in the state of specific phenotypic traits or grouping of the organisms depending on their genetic origin [wild, domesticated with genetic engineering (domGE), and domesticated without genetic engineering (domNGE)]. In addition, we tested the hypothesis that, given that transgenic plants are a construct designed to impact, in many cases, a single trait of the plant (e.g., lepidopteran resistance), the phenotypic differences between domGE and domNGE would be either less (or inexistent) than between the wild and domesticated relatives (either domGE or domNGE). We conclude that (1) genetic modification (either by selective breeding or GE) can be traced phenotypically when comparing wild relatives with their domesticated relatives (domGE and domNGE) and (2) the existence and the magnitude of the phenotypic differences between domGE and domNGE of the same crop suggest consequences of genetic modification beyond the target trait(s). PMID:29259610

Juvenile myopia progression, risk factors and interventions.

PubMed

Myrowitz, Elliott H

2012-07-01

The development and progression of early onset myopia is actively being investigated. While myopia is often considered a benign condition it should be considered a public health problem for its visual, quality of life, and economic consequences. Nearly half of the visually impaired population in the world has uncorrected refractive errors, with myopia a high percent of that group. Uncorrected visual acuity should be screened for and treated in order to improve academic performance, career opportunities and socio-economic status. Genetic and environmental factors contribute to the onset and progression of myopia. Twin studies have supported genetic factors and research continues to identify myopia genetic loci. While multiple myopia genetic loci have been identified establishing myopia as a common complex disorder, there is not yet a genetic model explaining myopia progression in populations. Environmental factors include near work, education levels, urban compared to rural location, and time spent outdoors. In this field of study where there continues to be etiology controversies, there is recent agreement that children who spend more time outdoors are less likely to become myopic. Worldwide population studies, some completed and some in progress, with a common protocol are gathering both genetic and environmental cohort data of great value. There have been rapid population changes in prevalence rates supporting an environmental influence. Interventions to prevent juvenile myopia progression include pharmacologic agents, glasses and contact lenses. Pharmacological interventions over 1-2 year trials have shown benefits. Peripheral vision defocus has been found to affect the emmetropization process and may be affected by wearing glasses or contacts. Accommodation accuracy also has been implicated in myopia progression. Further research will aim to assess both the role and interaction of environmental influences and genetic factors.

Using Memes and Memetic Processes to Explain Social and Conceptual Influences on Student Understanding about Complex Socio-Scientific Issues

ERIC Educational Resources Information Center

Yoon, Susan

2008-01-01

This study investigated seventh grade learners' decision making about genetic engineering concepts and applications. A social network analyses supported by technology tracked changes in student understanding with a focus on social and conceptual influences. Results indicated that several social and conceptual mechanisms potentially affected how…

Factors Influencing the Decision-Making Process and Long-Term Interpersonal Outcomes for Parents Who Undergo Preimplantation Genetic Diagnosis for Fanconi Anemia: a Qualitative Investigation.

PubMed

Haude, K; McCarthy Veach, P; LeRoy, B; Zierhut, H

2017-06-01

Fanconi anemia (FA) is characterized by congenital malformations, progressive bone marrow failure, and predisposition to malignancy. Hematopoietic stem cell transplantation is used to treat FA, and best results are attained with sibling donors who are human leukocyte antigen (HLA) identical matches. Preimplantation genetic diagnosis (PGD) offers parents of an affected child the opportunity to have an unaffected child who is an HLA match. While some research has investigated parents' experiences during the PGD process, no published studies specifically address factors influencing their decision-making process and long-term interpersonal outcomes. The aims of this study are to: (1) examine parents' expectations and the influence of media, bioethics, and religion on their decision to undergo PGD; (2) examine parents' social support and emotional experiences during their PGD process; and (3) characterize long-term effects of PGD on relationship dynamics (partner, family, friends), others' attitudes, and parental regret. Nine parents participated in semi-structured interviews. Thematic analysis revealed their decision to use PGD was variously influenced by media, bioethics, and religion, in particular, affecting parents' initial confidence levels. Moreover, the PGD process was emotionally complex, with parents desiring varying amounts and types of support from different sources at different times. Parents reported others' attitudes towards them were similar or no different than before PGD. Parental regret regarding PGD was negligible. Results of this study will promote optimization of long-term care for FA families.

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

PubMed

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

2016-03-01

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

Attitudes toward prenatal genetic testing for Treacher Collins syndrome among affected individuals and families.

PubMed

Wu, Rebecca L; Lawson, Cathleen S; Jabs, Ethylin Wang; Sanderson, Saskia C

2012-07-01

Treacher Collins syndrome (TCS) is a craniofacial syndrome that is both phenotypically variable and heterogeneous, caused by mutations in the TCOF1, POLR1C, and POLR1D genes. We examined attitudes towards TCS prenatal genetic testing among affected families using a telephone questionnaire. Participants were 31 affected adults and relatives recruited primarily through families cared for in the mid-Atlantic region. Nineteen participants (65%) reported that they would take a TCS prenatal genetic test which could not predict degree of disease severity. Interest in TCS genetic testing was associated with higher income, higher concern about having a child with TCS, lower religiosity, lower concern about genetic testing procedures, and having a sporadic rather than familial mutation. Over half reported that their decision to have TCS genetic testing would be influenced a great deal by their desire to relieve anxiety and attitudes toward abortion. Ten participants (32%) reported that they would be likely to end the pregnancy upon receiving a positive test result; this was lower amongst TCS affected individuals and higher amongst participants with children with TCS. Genetics healthcare providers need to be aware of affected individuals' and families' attitudes and interest in prenatal genetic testing for TCS, and the possible implications for other craniofacial disorders, so that patients' information needs can be met. Copyright © 2012 Wiley Periodicals, Inc.

Great influence of geographic isolation on the genetic differentiation of Myriophyllum spicatum under a steep environmental gradient

PubMed Central

Wu, Zhigang; Yu, Dan; Wang, Zhong; Li, Xing; Xu, Xinwei

2015-01-01

Understanding how natural processes affect population genetic structures is an important issue in evolutionary biology. One effective method is to assess the relative importance of environmental and geographical factors in the genetic structure of populations. In this study, we examined the spatial genetic variation of thirteen Myriophyllum spicatum populations from the Qinghai-Tibetan Plateau (QTP) and adjacent highlands (Yunnan-Guizhou Plateau, YGP) by using microsatellite loci and environmental and geographical factors. Bioclim layers, hydrological properties and elevation were considered as environmental variables and reduced by principal component analysis. The genetic isolation by geographic distance (IBD) was tested by Mantel tests and the relative importance of environmental variables on population genetic differentiation was determined by a partial Mantel test and multiple matrix regression with randomization (MMRR). Two genetic clusters corresponding to the QTP and YGP were identified. Both tests and MMRR revealed a significant and strong correlation between genetic divergence and geographic isolation under the influence of environmental heterogeneity at the overall and finer spatial scales. Our findings suggested the dominant role of geography on the evolution of M. spicatum under a steep environmental gradient in the alpine landscape as a result of dispersal limitation and genetic drift. PMID:26494202

The effects of learning about one's own genetic susceptibility to alcoholism: a randomized experiment.

PubMed

Dar-Nimrod, Ilan; Zuckerman, Miron; Duberstein, Paul R

2013-02-01

Increased accessibility of direct-to-consumer personalized genetic reports raises the question: how are people affected by information about their own genetic predispositions? Participants were led to believe that they had entered a study on the genetics of alcoholism and sleep disorders. Participants provided a saliva sample purportedly to be tested for the presence of relevant genes. While awaiting the results, they completed a questionnaire assessing their emotional state. They subsequently received a bogus report about their genetic susceptibility and completed a questionnaire about their emotional state and items assessing perceived control over drinking, relevant future drinking-related intentions, and intervention-related motivation and behavior. Participants who were led to believe that they had a gene associated with alcoholism showed an increase in negative affect, decrease in positive affect, and reduced perceived personal control over drinking. Reported intentions for alcohol consumption in the near future were not affected; however, individuals were more likely to enroll in a "responsible drinking" workshop after learning of their alleged genetic susceptibility. The first complete randomized experiment to examine the psychological and behavioral effects of receiving personalized genetic susceptibility information indicates some potential perils and benefits of direct-to-consumer genetic tests.

Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.

PubMed

Glahn, David C; Almasy, Laura; Barguil, Marcela; Hare, Elizabeth; Peralta, Juan Manuel; Kent, Jack W; Dassori, Albana; Contreras, Javier; Pacheco, Adriana; Lanzagorta, Nuria; Nicolini, Humberto; Raventós, Henriette; Escamilla, Michael A

2010-02-01

Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes. To adjudicate neurocognitive endophenotypes for bipolar disorder. All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status. Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas. Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia. Neurocognitive test performance. Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory. This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.

Geographic distance affects dispersal of the patchy distributed greater long-tailed hamster (Tscherskia triton).

PubMed

Xue, Huiliang; Zhong, Min; Xu, Jinhui; Xu, Laixiang

2014-01-01

Dispersal is a fundamental process in ecology influencing the genetic structure and the viability of populations. Understanding how variable factors influence the dispersal of the population is becoming an important question in animal ecology. To date, geographic distance and geographic barriers are often considered as main factors impacting dispersal, but their effects are variable depending on different conditions. In general, geographic barriers affect more significantly than geographic distance on dispersal. In rapidly expanding populations, however, geographic barriers have less effect on dispersal than geographic distance. The effects of both geographic distance and geographic barriers in low-density populations with patchy distributions are poorly understood. By using a panel of 10 microsatellite loci we investigated the genetic structure of three patchy-distributed populations of the Greater long-tailed hamster (Tscherskia triton) from Raoyang, Guan and Shunyi counties of the North China Plain. The results showed that (i) high genetic diversity and differentiation exist in three geographic populations with patchy distributions; (ii) gene flow occurs among these three populations with physical barriers of Beijing city and Hutuo River, which potentially restricted the dispersal of the animal; (iii) the gene flow is negatively correlated with the geographic distance, while the genetic distance shows the positive correlation. Our results suggest that the effect of the physical barriers is conditional-dependent, including barrier capacity or individual potentially dispersal ability. Geographic distance also acts as an important factor affecting dispersal for the patchy distributed geographic populations. So, gene flow is effective, even at relatively long distances, in balancing the effect of geographic barrier in this study.

Lost in Translation: Bioinformatic Analysis of Variations Affecting the Translation Initiation Codon in the Human Genome.

PubMed

Abad, Francisco; de la Morena-Barrio, María Eugenia; Fernández-Breis, Jesualdo Tomás; Corral, Javier

2018-06-01

Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (> 0:01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11,261 genetic variations affecting the initiation AUG codon of 7,205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. jfernand@um.es. Supplementary data are available at Bioinformatics online.

Behavioural and cognitive profiles of mouse models for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Isles, Anthony R

2013-03-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with aspects of psychiatric illness caused by genetic mutations at chromosome 15q11-q13. In addition to causing PWS, this interval is also thought to be of importance more generally in the development of autism and psychotic illness. The PWS genetic interval is conserved in mammals, and consequently mice carrying genetic manipulations affecting one or all of the genes in the region of conserved synteny have been generated and used in neurobehavioural studies. Here we give an overview of these models and describe the behavioural and neurobiological analyses that have been performed, many of which have provide new insights into the molecular and neural processes influenced by genes within the PWS interval. Copyright © 2011 Elsevier Inc. All rights reserved.

High gene flow in epiphytic ferns despite habitat loss and fragmentation.

PubMed

Winkler, Manuela; Koch, Marcus; Hietz, Peter

2011-01-01

Tropical montane forests suffer from increasing fragmentation and replacement by other types of land-use such as coffee plantations. These processes are known to affect gene flow and genetic structure of plant populations. Epiphytes are particularly vulnerable because they depend on their supporting trees for their entire life-cycle. We compared population genetic structure and genetic diversity derived from AFLP markers of two epiphytic fern species differing in their ability to colonize secondary habitats. One species, Pleopeltis crassinervata , is a successful colonizer of shade trees and isolated trees whereas the other species, Polypodium rhodopleuron , is restricted to forests with anthropogenic separation leading to significant isolation between populations. By far most genetic variation was distributed within rather than among populations in both species, and a genetic admixture analysis did not reveal any clustering. Gene flow exceeded by far the benchmark of one migrant per generation to prevent genetic divergence between populations in both species. Though populations are threatened by habitat loss, long-distance dispersal is likely to support gene flow even between distant populations, which efficiently delays genetic isolation. Consequently, populations may rather be threatened by ecological consequences of habitat loss and fragmentation.

Empathy as a “Risky Strength”: A Multilevel Examination of Empathy and Risk for Internalizing Disorders

PubMed Central

Tone, Erin B.; Tully, Erin C.

2015-01-01

Learning to respond to others’ distress with well-regulated empathy is an important developmental task linked to positive health outcomes and moral achievements. However, this important interpersonal skill set may also, paradoxically, confer risk for depression and anxiety when present at extreme levels and in combination with certain individual characteristics or within particular contexts. The purpose of this review is to describe an empirically-grounded theoretical rationale for the hypothesis that empathic tendencies can be “risky strengths”. We propose a model in which typical development of affective and cognitive empathy can be influenced by complex interplay among intraindividual and interindividual moderators that increase risk for empathic personal distress and excessive interpersonal guilt. These intermediate states, in turn, precipitate internalizing problems that map onto empirically-derived fear/arousal and anhedonia/misery subfactors of internalizing disorders. The intraindividual moderators include a genetically-influenced propensity toward physiological hyperarousal, which is proposed to interact with genetic propensity to empathic sensitivity to contribute to neurobiological processes that underlie personal distress responses others’ pain or unhappiness. This empathic personal distress then increases risk for internalizing problems, particularly fear/arousal symptoms. Similarly, interactions between genetic propensities toward negative thinking processes and empathic sensitivity are hypothesized to contribute to excess interpersonal guilt in response to others’ distress. In turn, this interpersonal guilt increases risk for internalizing problems, especially anhedonia/misery symptoms. Interindividual moderators, such as maladaptive parenting or chronic exposure to parents’ negative affect, further interact with these genetic liabilities to amplify risk for personal distress and interpersonal guilt, as well as for consequent internalizing problems. Age-related increases in the heritability of depression, anxiety, and empathy-related constructs are consistent with developmental shifts toward greater influence of intraindividual moderators throughout childhood and adolescence, with interindividual moderators exerting their greatest influence during early childhood. Efforts to modulate neurobiological and behavioral expressions of genetic dysregulation liabilities and to promote adaptive empathic skills must thus begin early in development. PMID:25422978

Empathy as a "risky strength": a multilevel examination of empathy and risk for internalizing disorders.

PubMed

Tone, Erin B; Tully, Erin C

2014-11-01

Learning to respond to others' distress with well-regulated empathy is an important developmental task linked to positive health outcomes and moral achievements. However, this important interpersonal skill set may also confer risk for depression and anxiety when present at extreme levels and in combination with certain individual characteristics or within particular contexts. The purpose of this review is to describe an empirically grounded theoretical rationale for the hypothesis that empathic tendencies can be "risky strengths." We propose a model in which typical development of affective and cognitive empathy can be influenced by complex interplay among intraindividual and interindividual moderators that increase risk for empathic personal distress and excessive interpersonal guilt. These intermediate states in turn precipitate internalizing problems that map onto empirically derived fear/arousal and anhedonia/misery subfactors of internalizing disorders. The intraindividual moderators include a genetically influenced propensity toward physiological hyperarousal, which is proposed to interact with genetic propensity to empathic sensitivity to contribute to neurobiological processes that underlie personal distress responses to others' pain or unhappiness. This empathic personal distress then increases risk for internalizing problems, particularly fear/arousal symptoms. In a similar fashion, interactions between genetic propensities toward negative thinking processes and empathic sensitivity are hypothesized to contribute to excess interpersonal guilt in response to others' distress. This interpersonal guilt then increases the risk for internalizing problems, especially anhedonia/misery symptoms. Interindividual moderators, such as maladaptive parenting or chronic exposure to parents' negative affect, further interact with these genetic liabilities to amplify risk for personal distress and interpersonal guilt as well as for consequent internalizing problems. Age-related increases in the heritability of depression, anxiety, and empathy-related constructs are consistent with developmental shifts toward greater influence of intraindividual moderators throughout childhood and adolescence, with interindividual moderators exerting their greatest influence during early childhood. Efforts to modulate neurobiological and behavioral expressions of genetic dysregulation liabilities and to promote adaptive empathic skills must thus begin early in development.

Decision-making process of women carrying a BRCA1 or BRCA2 mutation who have chosen prophylactic mastectomy.

PubMed

McQuirter, Megan; Castiglia, Luisa Luciani; Loiselle, Carmen G; Wong, Nora

2010-05-01

To explore the decision-making process of women with a BRCA1 or BRCA2 gene mutation who have chosen to undergo prophylactic mastectomy. Cross-sectional, qualitative, descriptive design. Participants were recruited from an outpatient cancer prevention center in the oncology and medical genetics departments of a large university-affiliated hospital in Montreal, Quebec, Canada. 10 women carrying a BRCA1 or BRCA2 mutation; 8 previously had had a prophylactic mastectomy and 2 were scheduled for surgery at the time of study. Semistructured, in-depth interviews were conducted. Field notes were written and audiotapes were transcribed verbatim. The textual data were coded and analyzed. Decision-making process for prophylactic mastectomy. Two broad findings emerged. First, several intrapersonal and contextual factors interacted throughout the process to move women either closer to choosing a prophylactic mastectomy or further from the decision. Second, all women reported experiencing a "pivotal point," an emotionally charged event when the decision to have a prophylactic mastectomy became definitive. Pivotal points for patients included either receiving a positive result for a genetic mutation or a breast cancer diagnosis for herself or a family member in the context of positive mutation status. Decision making about prophylactic mastectomy was an affective and intuitive process incorporating contexts and their relations rather than a rational, straight-forward process of weighing pros and cons. Supportive interventions for women in this population should explicitly address the individual and the inter-relationships of contextual factors that shape decision making about prophylactic mastectomy while recognizing important affective components involved.

Best practice guidelines for the molecular genetic diagnosis of Type 1 (HFE-related) hereditary haemochromatosis

PubMed Central

King, Caitriona; Barton, David E

2006-01-01

Background Hereditary haemochromatosis (HH) is a recessively-inherited disorder of iron over-absorption prevalent in Caucasian populations. Affected individuals for Type 1 HH are usually either homozygous for a cysteine to tyrosine amino acid substitution at position 282 (C282Y) of the HFE gene, or compound heterozygotes for C282Y and for a histidine to aspartic acid change at position 63 (H63D). Molecular genetic testing for these two mutations has become widespread in recent years. With diverse testing methods and reporting practices in use, there was a clear need for agreed guidelines for haemochromatosis genetic testing. The UK Clinical Molecular Genetics Society has elaborated a consensus process for the development of disease-specific best practice guidelines for genetic testing. Methods A survey of current practice in the molecular diagnosis of haemochromatosis was conducted. Based on the results of this survey, draft guidelines were prepared using the template developed by UK Clinical Molecular Genetics Society. A workshop was held to develop the draft into a consensus document. The consensus document was then posted on the Clinical Molecular Genetics Society website for broader consultation and amendment. Results Consensus or near-consensus was achieved on all points in the draft guidelines. The consensus and consultation processes worked well, and outstanding issues were documented in an appendix to the guidelines. Conclusion An agreed set of best practice guidelines were developed for diagnostic, predictive and carrier testing for hereditary haemochromatosis and for reporting the results of such testing. PMID:17134494

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

PubMed Central

Li, Wenzhu; Yi, Jia; Agbu, Pamela; Zhou, Zheng; Kelley, Richard L.; Jia, Songtao

2017-01-01

The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance. We show that replication stresses, due to either hydroxyurea treatment or various forms of genetic lesions of the replication machinery, reduce the inheritance accuracy of CENP-A/Cnp1 nucleosome positioning within centromere. Mechanistically, we demonstrate that excessive formation of single-stranded DNA, a common molecular abnormality under these conditions, might have correlation with the reduction in fidelity of centromeric chromatin duplication. Furthermore, we show that replication stress broadly changes chromatin structure at various loci in the genome, such as telomere heterochromatin expanding and mating type locus heterochromatin spreading out of the boundaries. Interestingly, the levels of inheritable expanding at sub-telomeric heterochromatin regions are highly variable among independent cell populations. Finally, we show that HU treatment of the multi-cellular organisms C. elegans and D. melanogaster affects epigenetically programmed development and PEV, illustrating the evolutionary conservation of the phenomenon. Replication stress, in addition to its demonstrated role in genetic instability, promotes variable epigenetic instability throughout the epigenome. PMID:28749973

Genetic variation affecting host-parasite interactions: major-effect quantitative trait loci affect the transmission of sigma virus in Drosophila melanogaster.

PubMed

Bangham, Jenny; Knott, Sara A; Kim, Kang-Wook; Young, Robert S; Jiggins, Francis M

2008-09-01

In natural populations, genetic variation affects resistance to disease. Whether that genetic variation comprises lots of small-effect polymorphisms or a small number of large-effect polymorphisms has implications for adaptation, selection and how genetic variation is maintained in populations. Furthermore, how much genetic variation there is, and the genes that underlie this variation, affects models of co-evolution between parasites and their hosts. We are studying the genetic variation that affects the resistance of Drosophila melanogaster to its natural pathogen--the vertically transmitted sigma virus. We have carried out three separate quantitative trait locus mapping analyses to map gene variants on the second chromosome that cause variation in the rate at which males transmit the infection to their offspring. All three crosses identified a locus in a similar chromosomal location that causes a large drop in the rate at which the virus is transmitted. We also found evidence for an additional smaller-effect quantitative trait locus elsewhere on the chromosome. Our data, together with previous experiments on the sigma virus and parasitoid wasps, indicate that the resistance of D. melanogaster to co-evolved pathogens is controlled by a limited number of major-effect polymorphisms.

Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene.

PubMed

Chiao, Joan Y; Blizinsky, Katherine D

2010-02-22

Culture-gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism-collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture-gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism-collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture-gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism-collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture-gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed.

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

PubMed

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

2013-06-01

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

Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC).

PubMed

Hilner, Joan E; Perdue, Letitia H; Sides, Elizabeth G; Pierce, June J; Wägner, Ana M; Aldrich, Alan; Loth, Amanda; Albret, Lotte; Wagenknecht, Lynne E; Nierras, Concepcion; Akolkar, Beena

2010-01-01

The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. T1DGC implemented a distributed, regional network structure to reach ASP recruitment targets. The infrastructure proved robust and flexible enough to accommodate additional recruitment. T1DGC has established significant resources that provide a basis for future discovery in the study of type 1 diabetes genetics.

Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets

PubMed Central

Olsson, Anders H.; Volkov, Petr; Bacos, Karl; Dayeh, Tasnim; Hall, Elin; Nilsson, Emma A.; Ladenvall, Claes; Rönn, Tina; Ling, Charlotte

2014-01-01

Genetic and epigenetic mechanisms may interact and together affect biological processes and disease development. However, most previous studies have investigated genetic and epigenetic mechanisms independently, and studies examining their interactions throughout the human genome are lacking. To identify genetic loci that interact with the epigenome, we performed the first genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human pancreatic islets. We related 574,553 single nucleotide polymorphisms (SNPs) with genome-wide DNA methylation data of 468,787 CpG sites targeting 99% of RefSeq genes in islets from 89 donors. We identified 67,438 SNP-CpG pairs in cis, corresponding to 36,783 SNPs (6.4% of tested SNPs) and 11,735 CpG sites (2.5% of tested CpGs), and 2,562 significant SNP-CpG pairs in trans, corresponding to 1,465 SNPs (0.3% of tested SNPs) and 383 CpG sites (0.08% of tested CpGs), showing significant associations after correction for multiple testing. These include reported diabetes loci, e.g. ADCY5, KCNJ11, HLA-DQA1, INS, PDX1 and GRB10. CpGs of significant cis-mQTLs were overrepresented in the gene body and outside of CpG islands. Follow-up analyses further identified mQTLs associated with gene expression and insulin secretion in human islets. Causal inference test (CIT) identified SNP-CpG pairs where DNA methylation in human islets is the potential mediator of the genetic association with gene expression or insulin secretion. Functional analyses further demonstrated that identified candidate genes (GPX7, GSTT1 and SNX19) directly affect key biological processes such as proliferation and apoptosis in pancreatic β-cells. Finally, we found direct correlations between DNA methylation of 22,773 (4.9%) CpGs with mRNA expression of 4,876 genes, where 90% of the correlations were negative when CpGs were located in the region surrounding transcription start site. Our study demonstrates for the first time how genome-wide genetic and epigenetic variation interacts to influence gene expression, islet function and potential diabetes risk in humans. PMID:25375650

Does indirect speech promote nondirective genetic counseling? Results of a sociolinguistic investigation.

PubMed

Benkendorf, J L; Prince, M B; Rose, M A; De Fina, A; Hamilton, H E

2001-01-01

To date, research examining adherence to genetic counseling principles has focused on specific counseling activities such as the giving or withholding of information and responding to client requests for advice. We audiotaped 43 prenatal genetic counseling sessions and used data-driven, qualitative, sociolinguistic methodologies to investigate how language choices facilitate or hinder the counseling process. Transcripts of each session were prepared for sociolinguistic analysis of the emergent discourse that included studying conversational style, speaker-listener symmetry, directness, and other interactional patterns. Analysis of our data demonstrates that: 1) indirect speech, marked by the use of hints, hedges, and other politeness strategies, facilitates rapport and mitigates the tension between a client-centered relationship and a counselor-driven agenda; 2) direct speech, or speaking literally, is an effective strategy for providing information and education; and 3) confusion exists between the use of indirect speech and the intent to provide nondirective counseling, especially when facilitating client decision-making. Indirect responses to client questions, such as those that include the phrases "some people" or "most people," helped to maintain counselor neutrality; however, this well-intended indirectness, used to preserve client autonomy, may have obstructed direct explorations of client needs. We argue that the genetic counseling process requires increased flexibility in the use of direct and indirect speech and provide new insights into how "talk" affects the work of genetic counselors.

Role of Genomic Typing in Taxonomy, Evolutionary Genetics, and Microbial Epidemiology

PubMed Central

van Belkum, Alex; Struelens, Marc; de Visser, Arjan; Verbrugh, Henri; Tibayrenc, Michel

2001-01-01

Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing data for discrimination between genotypes. Apart from being an essential component of these fundamental sciences, microbial typing clearly affects several areas of applied microbiogical research. The epidemiological investigation of outbreaks of infectious diseases and the measurement of genetic diversity in relation to relevant biological properties such as pathogenicity, drug resistance, and biodegradation capacities are obvious examples. The diversity among nucleic acid molecules provides the basic information for all fields described above. However, researchers in various disciplines tend to use different vocabularies, a wide variety of different experimental methods to monitor genetic variation, and sometimes widely differing modes of data processing and interpretation. The aim of the present review is to summarize the technological and fundamental concepts used in microbial taxonomy, evolutionary genetics, and epidemiology. Information on the nomenclature used in the different fields of research is provided, descriptions of the diverse genetic typing procedures are presented, and examples of both conceptual and technological research developments for Escherichia coli are included. Recommendations for unification of the different fields through standardization of laboratory techniques are made. PMID:11432813

Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development

PubMed Central

Lopez-Escamez, Jose A.; Bibas, Thanos; Cima, Rilana F. F.; Van de Heyning, Paul; Knipper, Marlies; Mazurek, Birgit; Szczepek, Agnieszka J.; Cederroth, Christopher R.

2016-01-01

Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus. PMID:27594824

The prospects of selection for social genetic effects to improve welfare and productivity in livestock

PubMed Central

Ellen, Esther D.; Rodenburg, T. Bas; Albers, Gerard A. A.; Bolhuis, J. Elizabeth; Camerlink, Irene; Duijvesteijn, Naomi; Knol, Egbert F.; Muir, William M.; Peeters, Katrijn; Reimert, Inonge; Sell-Kubiak, Ewa; van Arendonk, Johan A. M.; Visscher, Jeroen; Bijma, Piter

2014-01-01

Social interactions between individuals living in a group can have both positive and negative effects on welfare, productivity, and health of these individuals. Negative effects of social interactions in livestock are easier to observe than positive effects. For example, laying hens may develop feather pecking, which can cause mortality due to cannibalism, and pigs may develop tail biting or excessive aggression. Several studies have shown that social interactions affect the genetic variation in a trait. Genetic improvement of socially-affected traits, however, has proven to be difficult until relatively recently. The use of classical selection methods, like individual selection, may result in selection responses opposite to expected, because these methods neglect the effect of an individual on its group mates (social genetic effects). It has become clear that improvement of socially-affected traits requires selection methods that take into account not only the direct effect of an individual on its own phenotype but also the social genetic effects, also known as indirect genetic effects, of an individual on the phenotypes of its group mates. Here, we review the theoretical and empirical work on social genetic effects, with a focus on livestock. First, we present the theory of social genetic effects. Subsequently, we evaluate the evidence for social genetic effects in livestock and other species, by reviewing estimates of genetic parameters for direct and social genetic effects. Then we describe the results of different selection experiments. Finally, we discuss issues concerning the implementation of social genetic effects in livestock breeding programs. This review demonstrates that selection for socially-affected traits, using methods that target both the direct and social genetic effects, is a promising, but sometimes difficult to use in practice, tool to simultaneously improve production and welfare in livestock. PMID:25426136

The prospects of selection for social genetic effects to improve welfare and productivity in livestock.

PubMed

Ellen, Esther D; Rodenburg, T Bas; Albers, Gerard A A; Bolhuis, J Elizabeth; Camerlink, Irene; Duijvesteijn, Naomi; Knol, Egbert F; Muir, William M; Peeters, Katrijn; Reimert, Inonge; Sell-Kubiak, Ewa; van Arendonk, Johan A M; Visscher, Jeroen; Bijma, Piter

2014-01-01

Social interactions between individuals living in a group can have both positive and negative effects on welfare, productivity, and health of these individuals. Negative effects of social interactions in livestock are easier to observe than positive effects. For example, laying hens may develop feather pecking, which can cause mortality due to cannibalism, and pigs may develop tail biting or excessive aggression. Several studies have shown that social interactions affect the genetic variation in a trait. Genetic improvement of socially-affected traits, however, has proven to be difficult until relatively recently. The use of classical selection methods, like individual selection, may result in selection responses opposite to expected, because these methods neglect the effect of an individual on its group mates (social genetic effects). It has become clear that improvement of socially-affected traits requires selection methods that take into account not only the direct effect of an individual on its own phenotype but also the social genetic effects, also known as indirect genetic effects, of an individual on the phenotypes of its group mates. Here, we review the theoretical and empirical work on social genetic effects, with a focus on livestock. First, we present the theory of social genetic effects. Subsequently, we evaluate the evidence for social genetic effects in livestock and other species, by reviewing estimates of genetic parameters for direct and social genetic effects. Then we describe the results of different selection experiments. Finally, we discuss issues concerning the implementation of social genetic effects in livestock breeding programs. This review demonstrates that selection for socially-affected traits, using methods that target both the direct and social genetic effects, is a promising, but sometimes difficult to use in practice, tool to simultaneously improve production and welfare in livestock.

Examining the etiological associations among higher-order temperament dimensions

PubMed Central

Allan, Nicholas P.; Mikolajewski, Amy J.; Lonigan, Christopher J.; Hart, Sara A.; Taylor, Jeanette

2014-01-01

A multivariate independent pathway model was used to examine the shared and unique genetic and environmental influences of Positive Affect (PA), Negative Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age = 10.07, SD = 1.74). There were common genetic influences and nonshared environmental influences shared across all three temperament dimensions and shared environmental influences in common to NA and EC. There were also significant independent genetic influences unique to PA and NA and significant independent shared environmental influences unique to PA. This study demonstrates that there are genetic and environmental influences that affect the covariance among temperament dimensions as well as unique genetic and environmental influences that influence the dimensions independently. PMID:24729641

Therapeutic Genome Editing: Prospects and Challenges

PubMed Central

Cox, David Benjamin Turitz; Platt, Randall Jeffrey; Zhang, Feng

2015-01-01

Recent advances in the development of genome editing technologies based on programmable nucleases have significantly improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress towards developing programmable nuclease-based therapies as well as future prospects and challenges. PMID:25654603

Health Orientation, Knowledge, and Attitudes toward Genetic Testing and Personalized Genomic Services: Preliminary Data from an Italian Sample.

PubMed

Oliveri, Serena; Masiero, Marianna; Arnaboldi, Paola; Cutica, Ilaria; Fioretti, Chiara; Pravettoni, Gabriella

2016-01-01

Objective . The study aims at assessing personality tendencies and orientations that could be closely correlated with knowledge, awareness, and interest toward undergoing genetic testing. Methods. A sample of 145 subjects in Italy completed an online survey, investigating demographic data, health orientation, level of perceived knowledge about genetic risk, genetic screening, and personal attitudes toward direct to consumer genetic testing (DTCGT). Results . Results showed that respondents considered genetic assessment to be helpful for disease prevention, but they were concerned that results could affect their life planning with little clinical utility. Furthermore, a very high percentage of respondents (67%) had never heard about genetic testing directly available to the public. Data showed that personality tendencies, such as personal health consciousness, health internal control, health esteem, and confidence, motivation to avoid unhealthiness and motivation for healthiness affected the uptake of genetic information and the interest in undergoing genetic testing. Conclusions . Public knowledge and attitudes toward genetic risk and genetic testing among European countries, along with individual personality and psychological tendencies that could affect these attitudes, remain unexplored. The present study constitutes one of the first attempts to investigate how such personality tendencies could motivation to undergo genetic testing and engagement in lifestyle changes.

Health Orientation, Knowledge, and Attitudes toward Genetic Testing and Personalized Genomic Services: Preliminary Data from an Italian Sample

PubMed Central

Arnaboldi, Paola; Cutica, Ilaria; Fioretti, Chiara

2016-01-01

Objective. The study aims at assessing personality tendencies and orientations that could be closely correlated with knowledge, awareness, and interest toward undergoing genetic testing. Methods. A sample of 145 subjects in Italy completed an online survey, investigating demographic data, health orientation, level of perceived knowledge about genetic risk, genetic screening, and personal attitudes toward direct to consumer genetic testing (DTCGT). Results. Results showed that respondents considered genetic assessment to be helpful for disease prevention, but they were concerned that results could affect their life planning with little clinical utility. Furthermore, a very high percentage of respondents (67%) had never heard about genetic testing directly available to the public. Data showed that personality tendencies, such as personal health consciousness, health internal control, health esteem, and confidence, motivation to avoid unhealthiness and motivation for healthiness affected the uptake of genetic information and the interest in undergoing genetic testing. Conclusions. Public knowledge and attitudes toward genetic risk and genetic testing among European countries, along with individual personality and psychological tendencies that could affect these attitudes, remain unexplored. The present study constitutes one of the first attempts to investigate how such personality tendencies could motivation to undergo genetic testing and engagement in lifestyle changes. PMID:28105428

Exploring the Relationship between Negative Urgency and Dysregulated Eating: Etiologic Associations and the Role of Negative Affect

PubMed Central

Racine, Sarah E.; Keel, Pamela K.; Burt, S. Alexandra; Sisk, Cheryl L.; Neale, Michael; Boker, Steven; Klump, Kelly L.

2013-01-01

Negative urgency (i.e., the tendency to engage in rash action in response to negative affect) has emerged as a critical personality trait contributing to individual differences in binge eating. However, studies investigating the extent to which genetic and/or environmental influences underlie the effects of negative urgency on binge eating are lacking. Moreover, it remains unclear whether negative urgency-binge eating associations are simply due to the well-established role of negative affect in the development/maintenance of binge eating. The current study addresses these gaps by examining phenotypic and etiologic associations between negative urgency, negative affect, and dysregulated eating (i.e., binge eating, emotional eating) in a sample of 222 same-sex female twin pairs from the Michigan State Twin Registry. Negative urgency was significantly associated with both dysregulated eating symptoms, even after controlling for the effects of negative affect. Genetic factors accounted for the majority (62–77%) of this phenotypic association, although a significant proportion of this genetic covariation was due to genetic influences in common with negative affect. Non-shared environmental factors accounted for a relatively smaller (23–38%) proportion of the association, but these non-shared environmental effects were independent of negative affect. Findings suggest that the presence of emotion-based rash action, combined with high levels of negative affect, may significantly increase genetic risk for dysregulated eating. PMID:23356217

Exploring the relationship between negative urgency and dysregulated eating: etiologic associations and the role of negative affect.

PubMed

Racine, Sarah E; Keel, Pamela K; Burt, S Alexandra; Sisk, Cheryl L; Neale, Michael; Boker, Steven; Klump, Kelly L

2013-05-01

Negative urgency (i.e., the tendency to engage in rash action in response to negative affect) has emerged as a critical personality trait contributing to individual differences in binge eating. However, studies investigating the extent to which genetic and/or environmental influences underlie the effects of negative urgency on binge eating are lacking. Moreover, it remains unclear whether negative urgency-binge eating associations are simply a result of the well-established role of negative affect in the development/maintenance of binge eating. The current study addresses these gaps by examining phenotypic and etiologic associations between negative urgency, negative affect, and dysregulated eating (i.e., binge eating, emotional eating) in a sample of 222 same-sex female twin pairs from the Michigan State University Twin Registry. Negative urgency was significantly associated with both dysregulated eating symptoms, even after controlling for the effects of negative affect. Genetic factors accounted for the majority (62-77%) of this phenotypic association, although a significant proportion of this genetic covariation was due to genetic influences in common with negative affect. Nonshared environmental factors accounted for a relatively smaller (23-38%) proportion of the association, but these nonshared environmental effects were independent of negative affect. Findings suggest that the presence of emotion-based rash action, combined with high levels of negative affect, may significantly increase genetic risk for dysregulated eating. © 2013 American Psychological Association

Encephaloceles

MedlinePlus

... and seizures. Some affected children may have normal intelligence. There is a genetic component to the condition; ... and seizures. Some affected children may have normal intelligence. There is a genetic component to the condition; ...

Effects of genetic, processing, or product formulation changes on efficacy and safety of probiotics.

PubMed

Sanders, Mary Ellen; Klaenhammer, Todd R; Ouwehand, Arthur C; Pot, Bruno; Johansen, Eric; Heimbach, James T; Marco, Maria L; Tennilä, Julia; Ross, R Paul; Franz, Charles; Pagé, Nicolas; Pridmore, R David; Leyer, Greg; Salminen, Seppo; Charbonneau, Duane; Call, Emma; Lenoir-Wijnkoop, Irene

2014-02-01

Commercial probiotic strains for food or supplement use can be altered in different ways for a variety of purposes. Production conditions for the strain or final product may be changed to address probiotic yield, functionality, or stability. Final food products may be modified to improve flavor and other sensory properties, provide new product formats, or respond to market opportunities. Such changes can alter the expression of physiological traits owing to the live nature of probiotics. In addition, genetic approaches may be used to improve strain attributes. This review explores whether genetic or phenotypic changes, by accident or design, might affect the efficacy or safety of commercial probiotics. We highlight key issues important to determining the need to re-confirm efficacy or safety after strain improvement, process optimization, or product formulation changes. Research pinpointing the mechanisms of action for probiotic function and the development of assays to measure them are greatly needed to better understand if such changes have a substantive impact on probiotic efficacy. © 2014 New York Academy of Sciences.

Genetic instability in budding and fission yeast—sources and mechanisms

PubMed Central

Skoneczna, Adrianna; Kaniak, Aneta; Skoneczny, Marek

2015-01-01

Cells are constantly confronted with endogenous and exogenous factors that affect their genomes. Eons of evolution have allowed the cellular mechanisms responsible for preserving the genome to adjust for achieving contradictory objectives: to maintain the genome unchanged and to acquire mutations that allow adaptation to environmental changes. One evolutionary mechanism that has been refined for survival is genetic variation. In this review, we describe the mechanisms responsible for two biological processes: genome maintenance and mutation tolerance involved in generations of genetic variations in mitotic cells of both Saccharomyces cerevisiae and Schizosaccharomyces pombe. These processes encompass mechanisms that ensure the fidelity of replication, DNA lesion sensing and DNA damage response pathways, as well as mechanisms that ensure precision in chromosome segregation during cell division. We discuss various factors that may influence genome stability, such as cellular ploidy, the phase of the cell cycle, transcriptional activity of a particular region of DNA, the proficiency of DNA quality control systems, the metabolic stage of the cell and its respiratory potential, and finally potential exposure to endogenous or environmental stress. PMID:26109598

Genetic instability in budding and fission yeast-sources and mechanisms.

PubMed

Skoneczna, Adrianna; Kaniak, Aneta; Skoneczny, Marek

2015-11-01

Cells are constantly confronted with endogenous and exogenous factors that affect their genomes. Eons of evolution have allowed the cellular mechanisms responsible for preserving the genome to adjust for achieving contradictory objectives: to maintain the genome unchanged and to acquire mutations that allow adaptation to environmental changes. One evolutionary mechanism that has been refined for survival is genetic variation. In this review, we describe the mechanisms responsible for two biological processes: genome maintenance and mutation tolerance involved in generations of genetic variations in mitotic cells of both Saccharomyces cerevisiae and Schizosaccharomyces pombe. These processes encompass mechanisms that ensure the fidelity of replication, DNA lesion sensing and DNA damage response pathways, as well as mechanisms that ensure precision in chromosome segregation during cell division. We discuss various factors that may influence genome stability, such as cellular ploidy, the phase of the cell cycle, transcriptional activity of a particular region of DNA, the proficiency of DNA quality control systems, the metabolic stage of the cell and its respiratory potential, and finally potential exposure to endogenous or environmental stress. © FEMS 2015.

Applications of graph theory to landscape genetics

PubMed Central

Garroway, Colin J; Bowman, Jeff; Carr, Denis; Wilson, Paul J

2008-01-01

We investigated the relationships among landscape quality, gene flow, and population genetic structure of fishers (Martes pennanti) in ON, Canada. We used graph theory as an analytical framework considering each landscape as a network node. The 34 nodes were connected by 93 edges. Network structure was characterized by a higher level of clustering than expected by chance, a short mean path length connecting all pairs of nodes, and a resiliency to the loss of highly connected nodes. This suggests that alleles can be efficiently spread through the system and that extirpations and conservative harvest are not likely to affect their spread. Two measures of node centrality were negatively related to both the proportion of immigrants in a node and node snow depth. This suggests that central nodes are producers of emigrants, contain high-quality habitat (i.e., deep snow can make locomotion energetically costly) and that fishers were migrating from high to low quality habitat. A method of community detection on networks delineated five genetic clusters of nodes suggesting cryptic population structure. Our analyses showed that network models can provide system-level insight into the process of gene flow with implications for understanding how landscape alterations might affect population fitness and evolutionary potential. PMID:25567802

Intraspecific competition and light effect on reproduction of Ligularia virgaurea, an invasive native alpine grassland clonal herb

PubMed Central

Xie, Tian-peng; Zhang, Ge-fei; Zhao, Zhi-gang; Du, Guo-zhen; He, Gui-yong

2014-01-01

The relationship between sexual reproduction and clonal growth in clonal plants often shows up at the ramet level. However, only a few studies focus on the relationship at the genet level, which could finally account for evolution. The sexual reproduction and clonal growth of Ligularia virgaurea, a perennial herb widely distributed in the alpine grasslands of the Qinghai-Tibetan Plateau of China, were studied under different competition intensities and light conditions at the genet level through a potted experiment. The results showed that: (1) sexual reproduction did not depend on density or light, and increasing clonal growth with decreasing density and increasing light intensity indicated that intraspecific competition and light intensity may affect the clonal life history of L. virgaurea; (2) both sexual reproduction and clonal growth show a positive linear relationship with genet size under different densities and light conditions; (3) a threshold size is required for sexual reproduction and no evidence of a threshold size for clonal growth under different densities and light conditions; (4) light level affected the allocation of total biomass to clonal and sexual structures, with less allocation to clonal structures and more allocation to sexual structures in full sunlight than in shade; (5) light determined the onset of sexual reproduction, and the genets in the shade required a smaller threshold size for sexual reproduction to occur than the plants in full sunlight; and (6) no evidence was found of trade-offs between clonal growth and sexual reproduction under different densities and light conditions at the genet level, and the positive correlation between two reproductive modes indicated that these are two integrated processes. Clonal growth in this species may be viewed as a growth strategy that tends to maximize genet fitness. PMID:24683463

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

PubMed Central

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

2016-01-01

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

Stuck in traffic: an emerging theme in diseases of the nervous system.

PubMed

Neefjes, Jacques; van der Kant, Rik

2014-02-01

The past decade has seen an explosion of DNA sequencing activities and many mutations and genetic variances underlying neurological and neurodegenerative diseases have been determined. This wealth of genetic data is now placed in molecular pathways revealing the nodes that underlie the disrupted processes. Many mutations in neurological diseases affect proteins controlling endosomal/lysosomal transport. Although the age of onset of these diseases range from juvenile [i.e., Niemann-Pick type C (NPC) and Charcot-Marie-Tooth (CMT) disease] to late onset (Parkinson's and Alzheimer's disease), deregulation of endosomal transport is a common theme. This review summarizes how elucidating the genetic basis for the various neurological diseases has advanced our understanding of the endo-lysosomal system and why the various mutations all translate into similar disease phenotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

When the face says it all: dysmorphology in identifying syndromic causes of epilepsy.

PubMed

Dixit, Abhijit; Suri, Mohnish

2016-04-01

Identifying the underlying cause of epilepsy often helps in choosing the appropriate management, suggests the long-term prognosis and clarifies the risk of the same condition in relatives. Epilepsy has many causes and a small but significant proportion of affected people have an identifiable genetic cause. Here, we discuss the role of genetic testing in adults with epilepsy, focusing on dysmorphic features noticeable on physical examination that might provide a strong clue to a specific genetic syndrome. We give illustrative examples of recognisable facial 'gestalt'. An astute clinician can recognise such clues and significantly shorten the process of making the underlying diagnosis in their patient. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Combinatorial optimization problem solution based on improved genetic algorithm

NASA Astrophysics Data System (ADS)

Zhang, Peng

2017-08-01

Traveling salesman problem (TSP) is a classic combinatorial optimization problem. It is a simplified form of many complex problems. In the process of study and research, it is understood that the parameters that affect the performance of genetic algorithm mainly include the quality of initial population, the population size, and crossover probability and mutation probability values. As a result, an improved genetic algorithm for solving TSP problems is put forward. The population is graded according to individual similarity, and different operations are performed to different levels of individuals. In addition, elitist retention strategy is adopted at each level, and the crossover operator and mutation operator are improved. Several experiments are designed to verify the feasibility of the algorithm. Through the experimental results analysis, it is proved that the improved algorithm can improve the accuracy and efficiency of the solution.

New insights into the endophenotypic status of cognition in bipolar disorder: genetic modelling study of twins and siblings.

PubMed

Georgiades, Anna; Rijsdijk, Fruhling; Kane, Fergus; Rebollo-Mesa, Irene; Kalidindi, Sridevi; Schulze, Katja K; Stahl, Daniel; Walshe, Muriel; Sahakian, Barbara J; McDonald, Colm; Hall, Mei-Hua; Murray, Robin M; Kravariti, Eugenia

2016-06-01

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder. To quantify the shared genetic variability between bipolar disorder and cognitive measures. Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder. Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|-|1.00|), which remained significant after covarying for affective symptoms. Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder. © The Royal College of Psychiatrists 2016.

Fine-scale genetic structure arises during range expansion of an invasive gecko.

PubMed

Short, Kristen Harfmann; Petren, Kenneth

2011-01-01

Processes of range expansion are increasingly important in light of current concerns about invasive species and range shifts due to climate change. Theoretical studies suggest that genetic structuring may occur during range expansion. Ephemeral genetic structure can have important evolutionary implications, such as propagating genetic changes along the wave front of expansion, yet few studies have shown evidence of such structure. We tested the hypothesis that genetic structure arises during range expansion in Hemidactylus mabouia, a nocturnal African gecko recently introduced to Florida, USA. Twelve highly variable microsatellite loci were used to screen 418 individuals collected from 43 locations from four sampling sites across Florida, representing a gradient from earlier (∼1990s) to very recent colonization. We found earlier colonized locations had little detectable genetic structure and higher allelic richness than more recently colonized locations. Genetic structuring was pronounced among locations at spatial scales of tens to hundreds of meters near the leading edge of range expansion. Despite the rapid pace of range expansion in this introduced gecko, dispersal is limited among many suitable habitat patches. Fine-scale genetic structure is likely the result of founder effects during colonization of suitable habitat patches. It may be obscured over time and by scale-dependent modes of dispersal. Further studies are needed to determine if such genetic structure affects adaptation and trait evolution in range expansions and range shifts.

Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Phillips, Charles A; Langston, Michael A; Ragan, Mark A

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k ) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k . Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k .

Biological pathways and genetic mechanisms involved in social functioning.

PubMed

Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

2013-08-01

To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

Genetic effects on mating success and partner choice in a social mammal

PubMed Central

Tung, Jenny; Charpentier, Marie JE; Mukherjee, Sayan; Altmann, Jeanne; Alberts, Susan C

2012-01-01

Mating behavior has profound consequences for two phenomena – individual reproductive success and the maintenance of species boundaries – that contribute to evolutionary processes. Studies of mating behavior in relation to individual reproductive success are common in many species, but studies of mating behavior in relation to genetic variation and species boundaries are less commonly conducted in socially complex species. Here, we leveraged extensive observations of a wild yellow baboon (Papio cynocephalus) population that has experienced recent gene flow from a close sister taxon, the anubis baboon (Papio anubis), to examine how admixture-related genetic background affects mating behavior. We identified novel effects of genetic background on mating patterns, including an advantage accruing to anubis-like males and assortative mating among both yellow-like and anubis-like pairs. These genetic effects acted alongside social dominance rank, inbreeding avoidance, and age to produce highly nonrandom mating patterns. Our results suggest that this population may be undergoing admixture-related evolutionary change, driven in part by nonrandom mating. However, the strength of the genetic effects is mediated by behavioral plasticity and social interactions, emphasizing the strong influence of social context on mating behavior in socially complex species. PMID:22673655

Cousin marriage and premarital carrier matching in a Bedouin community in Israel: attitudes, service development and educational intervention.

PubMed

Raz, Aviad E; Atar, Marcela

2004-01-01

Premarital carrier matching is a form of genetic counselling in which two individuals are told, if both are carriers, that they have a 25% risk at each pregnancy of having a child affected by the disease for which they were tested. If only one individual is a carrier this information is not disclosed. This scheme is offered to a consanguineous Bedouin community characterised by high prevalence of genetic diseases and a religious ban on abortion. To elicit attitudes of community members concerning cousin marriage and genetic counselling. Semi-structured interviews were conducted with Bedouin respondents (n = 49). Interviews revealed that a majority of Bedouin respondents confirmed the traditional and social role of cousin marriage. The main reasons given in this context were clan solidarity, interpersonal compatibility, preservation of family property, parental authority and social protection for women. A majority of the respondents also associated cousin marriage with genetic diseases. Regarding genetic testing, the majority of respondents preferred the option of premarital carrier matching, which was supposed to reduce stigmatisation, especially of women. Prenatal genetic testing was rejected on religious grounds. The result of this community-based and culture-sensitive process was a focus on premarital carrier matching.

Neurocognitive Endophenotypes for Bipolar Disorder Identified in Multiplex Multigenerational Families

PubMed Central

Glahn, David C.; Almasy, Laura; Barguil, Marcela; Hare, Elizabeth; Peralta, Juan Manuel; Kent, Jack W.; Dassori, Alabana; Contreras, Javier; Pacheco, Adriana; Lanzagorta, Nuria; Nicolini, Humberto; Raventós, Henriette; Escamilla, Michael A.

2012-01-01

Context Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, one strategy for identifying risk genes is the use of quantitative endophenotypes. Objective The goal of the current study is to adjudicate neurocognitive endophenotypes for bipolar disorder. Design, Setting, and Participants 709 Latino individuals from the central valley of Costa Rica, Mexico City, Mexico, or San Antonio, Texas participated in the study. 660 of these persons were members of extended pedigrees with at least two siblings diagnosed with bipolar disorder (n=230). The remaining subjects were community controls drawn from each site and without personal or family history of bipolar disorder or schizophrenia. All subjects received psychodiagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which tests are impaired in affected individuals, sensitive to genetic liability for the illness and genetically correlated with affection status. Main Outcome Measures The main outcome measure was neurocognitive test performance. Results Two of the 21 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 of these cognitive measures compared to non-related healthy subjects. Non-bipolar first-degree relatives were impaired on five of these and three tests were genetically correlated with affection status: digit symbol coding, object delayed response, and immediate facial memory. Conclusions This large-scale extended pedigree study of cognitive functioning in bipolar disorder identified measures of processing speed, working memory and declarative (facial) memory as candidate endophenotypes for bipolar disorder. PMID:20124116

Leigh syndrome: Resolving the clinical and genetic heterogeneity paves the way for treatment options.

PubMed

Gerards, Mike; Sallevelt, Suzanne C E H; Smeets, Hubert J M

2016-03-01

Leigh syndrome is a progressive neurodegenerative disorder, affecting 1 in 40,000 live births. Most patients present with symptoms between the ages of three and twelve months, but adult onset Leigh syndrome has also been described. The disease course is characterized by a rapid deterioration of cognitive and motor functions, in most cases resulting in death due to respiratory failure. Despite the high genetic heterogeneity of Leigh syndrome, patients present with identical, symmetrical lesions in the basal ganglia or brainstem on MRI, while additional clinical manifestations and age of onset varies from case to case. To date, mutations in over 60 genes, both nuclear and mitochondrial DNA encoded, have been shown to cause Leigh syndrome, still explaining only half of all cases. In most patients, these mutations directly or indirectly affect the activity of the mitochondrial respiratory chain or pyruvate dehydrogenase complex. Exome sequencing has accelerated the discovery of new genes and pathways involved in Leigh syndrome, providing novel insights into the pathophysiological mechanisms. This is particularly important as no general curative treatment is available for this devastating disorder, although several recent studies imply that early treatment might be beneficial for some patients depending on the gene or process affected. Timely, gene-based personalized treatment may become an important strategy in rare, genetically heterogeneous disorders like Leigh syndrome, stressing the importance of early genetic diagnosis and identification of new genes/pathways. In this review, we provide a comprehensive overview of the most important clinical manifestations and genes/pathways involved in Leigh syndrome, and discuss the current state of therapeutic interventions in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Variable Gene Dispersal Conditions and Spatial Deforestation Patterns Can Interact to Affect Tropical Tree Conservation Outcomes

PubMed Central

Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H.

2015-01-01

Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with ‘Near’ distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal regimens will be a likely outcome of fragmentation. Conservation implications include possible manual interventions (manual manipulations of offspring dispersers and/or pollinators) in forest fragments to increase population recovery and genetic diversity retention. PMID:26000951

Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

PubMed

Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H

2015-01-01

Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal regimens will be a likely outcome of fragmentation. Conservation implications include possible manual interventions (manual manipulations of offspring dispersers and/or pollinators) in forest fragments to increase population recovery and genetic diversity retention.

How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis.

PubMed

Deth, Richard; Muratore, Christina; Benzecry, Jorge; Power-Charnitsky, Verna-Ann; Waly, Mostafa

2008-01-01

Recently higher rates of autism diagnosis suggest involvement of environmental factors in causing this developmental disorder, in concert with genetic risk factors. Autistic children exhibit evidence of oxidative stress and impaired methylation, which may reflect effects of toxic exposure on sulfur metabolism. We review the metabolic relationship between oxidative stress and methylation, with particular emphasis on adaptive responses that limit activity of cobalamin and folate-dependent methionine synthase. Methionine synthase activity is required for dopamine-stimulated phospholipid methylation, a unique membrane-delimited signaling process mediated by the D4 dopamine receptor that promotes neuronal synchronization and attention, and synchrony is impaired in autism. Genetic polymorphisms adversely affecting sulfur metabolism, methylation, detoxification, dopamine signaling and the formation of neuronal networks occur more frequently in autistic subjects. On the basis of these observations, a "redox/methylation hypothesis of autism" is described, in which oxidative stress, initiated by environment factors in genetically vulnerable individuals, leads to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks.

A Conceptual Framework for Pharmacodynamic Genome-wide Association Studies in Pharmacogenomics

PubMed Central

Wu, Rongling; Tong, Chunfa; Wang, Zhong; Mauger, David; Tantisira, Kelan; Szefler, Stanley J.; Chinchilli, Vernon M.; Israel, Elliot

2013-01-01

Summary Genome-wide association studies (GWAS) have emerged as a powerful tool to identify loci that affect drug response or susceptibility to adverse drug reactions. However, current GWAS based on a simple analysis of associations between genotype and phenotype ignores the biochemical reactions of drug response, thus limiting the scope of inference about its genetic architecture. To facilitate the inference of GWAS in pharmacogenomics, we sought to undertake the mathematical integration of the pharmacodynamic process of drug reactions through computational models. By estimating and testing the genetic control of pharmacodynamic and pharmacokinetic parameters, this mechanistic approach does not only enhance the biological and clinical relevance of significant genetic associations, but also improve the statistical power and robustness of gene detection. This report discusses the general principle and development of pharmacodynamics-based GWAS, highlights the practical use of this approach in addressing various pharmacogenomic problems, and suggests that this approach will be an important method to study the genetic architecture of drug responses or reactions. PMID:21920452

Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

PubMed Central

Iyer, Janani; Wang, Qingyu; Le, Thanh; Pizzo, Lucilla; Grönke, Sebastian; Ambegaokar, Surendra S.; Imai, Yuzuru; Srivastava, Ashutosh; Troisí, Beatriz Llamusí; Mardon, Graeme; Artero, Ruben; Jackson, George R.; Isaacs, Adrian M.; Partridge, Linda; Lu, Bingwei; Kumar, Justin P.; Girirajan, Santhosh

2016-01-01

About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions. PMID:26994292

Genetic structure in striped skunks (Mephitis mephitis) on the southern high plains of Texas

USGS Publications Warehouse

Hansen, L.A.; Mathews, N.E.; Hansen, R.W.; Vander Lee, B. A.; Scott, Lutz R.

2003-01-01

Genetic variation within populations reflects population-level social and demographic processes and influences how a population behaves as an evolutionary unit. We examined partitioning of genetic variation in striped skunks (Mephitis mephitis) from the Southern High Plains of Texas during 1994-1995. Sixty-nine male and 35 female skunks were sampled on four 12.8-km2 study plots. Plot centers ranged from 17.6 to 61.6 km apart. We used multi-locus DNA fingerprinting with 2 probes, pV47 and CTTxAGG, to test 3 hypotheses: (1) females are more genetically similar to other females than males are to other males on the same plot (indicating greater female philopatry than male philopatry), (2) genetic similarity is greater within plots than among plots (indicating partitioning of genetic variation in space), and (3) genetic similarity of males decreases as the distance separating males increases (indicating geographic distance affects rates of gene flow). In general, males on a plot had lower average genetic similarity than females. Genetic similarity within plots was not different from genetic similarity among plots for males or for females. Genetic similarity of males did not decrease with increasing distance among plots. The lack of geographical genetic structure in striped skunks suggests at the scale of this study (<60 km) that gene flow of biparentally inherited genes is not distance-mediated. However, the higher similarity values for females than for males on the same plot supports an effect of male-biased dispersal and female philopatry on partitioning of genetic variation between sexes.

'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

PubMed

Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

2013-12-01

The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Understanding GINA and How GINA Affects Nurses.

PubMed

Delk, Kayla L

2015-11-01

The Genetic Information Nondiscrimination Act (GINA) is a federal law that became fully effective in 2009 and is intended to prevent employers and health insurers from discriminating against individuals based on their genetic or family history. The article discusses the sections of GINA, what information constitutes genetic information, who enforces GINA, and scenarios in which GINA does not apply. Also discussed are the instances in which an employer may request genetic information from employees, including wellness or genetic monitoring programs. Finally, the article offers a look at how GINA affects nurses who are administering wellness or genetic monitoring programs on behalf of employers. © 2015 The Author(s).

Effects of land-use management on soil microbes to degrade organic matter through captured metagenomics and metatranscriptomics

NASA Astrophysics Data System (ADS)

Manoharan, Lokeshwaran; Ahren, Dag; Urich, Tim; Hedlund, Katarina

2017-04-01

The role of microbial communities in different soil ecosystem processes has been hard to determine in the past due to their vast diversity both in terms of taxonomy and functions. Molecular methods such as high-throughput sequencing of environmental communities have made it easier to delve into these diverse ecosystems and understand their functions. Trait-based approaches through quantification of functional genes and their expression have shown to be much more meaningful in explaining ecosystem functioning than the taxonomy based approaches. One such approach is the "captured metagenomics" technique where only the genetic regions of functional enzymes involved in a particular ecosystem process such as carbon metabolism is targeted from the genetic pool and sequenced. This allows focused investigations of ecosystem processes through functional genes in complex environments such as soils. In our study, we have implemented this method to look into the effects of land-use management on the functional genetic diversity of microbial communities to degrade soil organic matter (SOM). Soils from different agricultural and grassland fields in southern Sweden were chosen in this study. Oligonucleotide probes were generated based on the genetic sequences of enzymes involved in organic matter degradation from public databases. On the DNA level, there was a significant shift in the functional genetic diversity of microbes to degrade SOM due to land-use management. Grasslands had a higher abundance and diversity of genes coding for enzymes involved in SOM degradation than agricultural soils. The amount of nitrogen was the main factor that affected the functional diversity of the microbes that degrade SOM in these soils. Interestingly, there was no correlation between the functional diversity of microbes to their taxonomic diversity measured through traditional ribosomal sequencing. In addition, for the first time the capture method was used in large scale, targeting many genes coding for SOM degrading enzymes coupled with RNA/cDNA from the soils to quantify their expressions. For this, the soils from different land-use managements were treated with straw, while the microbial growth rates in these soils were also monitored for a month. RNA was extracted from at three different time points from both treated and untreated soils from different land-use managements. Agricultural soils with straw addition had higher relative microbial growth rates and higher abundance of gene sequences captured compared to the control and grassland soils. Land-use management seems to be the most significant factor in affecting the expression of SOM degrading genes in these soils. Additional analyses of the generated data are expected to provide valuable insights on how land-use management affects the microbial responses during addition of organic matter in soils.

Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

PubMed Central

Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

2016-01-01

Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students’ ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding. PMID:27909016

Effects of pathogen exposure on life history variation in the gypsy moth (Lymantria dispar)

PubMed Central

Páez, David J.; Fleming-Davies, Arietta E.; Dwyer, Greg

2015-01-01

Investment in host defenses against pathogens may lead to tradeoffs with host fecundity. When such tradeoffs arise from genetic correlations, rates of phenotypic change by natural selection may be affected. However, genetic correlations between host survival and fecundity are rarely quantified. To understand tradeoffs between immune responses to baculovirus exposure and fecundity in the gypsy moth (Lymantria dispar), we estimated genetic correlations between survival probability and traits related to fecundity, such as pupal weight. In addition, we tested whether different virus isolates have different effects on male and female pupal weight. To estimate genetic correlations, we exposed individuals of known relatedness to a single baculovirus isolate. To then evaluate the effect of virus isolate on pupal weight, we exposed a single gypsy moth strain to 16 baculovirus isolates. We found a negative genetic correlation between survival and pupal weight. In addition, virus exposure caused late-pupating females to be identical in weight to males, whereas unexposed females were 2–3 times as large as unexposed males. Finally, we found that female pupal weight is a quadratic function of host mortality across virus isolates, which is likely due to tradeoffs and compensatory growth processes acting at high and low mortality levels, respectively. Overall, our results suggest that fecundity costs may strongly affect the response to selection for disease resistance. In nature, baculoviruses contribute to the regulation of gypsy moth outbreaks, as pathogens often do in forest-defoliating insects. We therefore argue that tradeoffs between host life-history traits may help explain outbreak dynamics. PMID:26201381

Biotechnological advancement in genetic improvement of broccoli (Brassica oleracea L. var. italica), an important vegetable crop.

PubMed

Kumar, Pankaj; Srivastava, Dinesh Kumar

2016-07-01

With the advent of molecular biotechnology, plant genetic engineering techniques have opened an avenue for the genetic improvement of important vegetable crops. Vegetable crop productivity and quality are seriously affected by various biotic and abiotic stresses which destabilize rural economies in many countries. Moreover, absence of proper post-harvest storage and processing facilities leads to qualitative and quantitative losses. In the past four decades, conventional breeding has significantly contributed to the improvement of vegetable yields, quality, post-harvest life, and resistance to biotic and abiotic stresses. However, there are many constraints in conventional breeding, which can only be overcome by advancements made in modern biology. Broccoli (Brassica oleracea L. var. italica) is an important vegetable crop, of the family Brassicaceae; however, various biotic and abiotic stresses cause enormous crop yield losses during the commercial cultivation of broccoli. Thus, genetic engineering can be used as a tool to add specific characteristics to existing cultivars. However, a pre-requisite for transferring genes into plants is the availability of efficient regeneration and transformation techniques. Recent advances in plant genetic engineering provide an opportunity to improve broccoli in many aspects. The goal of this review is to summarize genetic transformation studies on broccoli to draw the attention of researchers and scientists for its further genetic advancement.

Being fruitful: genetics of reproduction in Arabidopsis.

PubMed

Preuss, D

1995-04-01

Reproduction in flowering plants requires a series of interactions between the haploid and diploid phases of the life cycle of the plant. Mutations that affect these interactions have been identified in Arabidopsis, thus giving insight into the processes of gamete development and pollination. These studies promise to yield new information on diverse topics in plant biology, from cell-cell recognition to the evolution of mating interactions.

Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

ERIC Educational Resources Information Center

Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

2016-01-01

Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon…

Examining the Relationship between Home Literacy Environment and Neural Correlates of Phonological Processing in Beginning Readers with and without a Familial Risk for Dyslexia: An fMRI Study

ERIC Educational Resources Information Center

Powers, Sara J.; Wang, Yingying; Beach, Sara D.; Sideridis, Georgios D.; Gaab, Nadine

2016-01-01

Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy…

Predicting Silk Fiber Mechanical Properties through Multiscale Simulation and Protein Design.

PubMed

Rim, Nae-Gyune; Roberts, Erin G; Ebrahimi, Davoud; Dinjaski, Nina; Jacobsen, Matthew M; Martín-Moldes, Zaira; Buehler, Markus J; Kaplan, David L; Wong, Joyce Y

2017-08-14

Silk is a promising material for biomedical applications, and much research is focused on how application-specific, mechanical properties of silk can be designed synthetically through proper amino acid sequences and processing parameters. This protocol describes an iterative process between research disciplines that combines simulation, genetic synthesis, and fiber analysis to better design silk fibers with specific mechanical properties. Computational methods are used to assess the protein polymer structure as it forms an interconnected fiber network through shearing and how this process affects fiber mechanical properties. Model outcomes are validated experimentally with the genetic design of protein polymers that match the simulation structures, fiber fabrication from these polymers, and mechanical testing of these fibers. Through iterative feedback between computation, genetic synthesis, and fiber mechanical testing, this protocol will enable a priori prediction capability of recombinant material mechanical properties via insights from the resulting molecular architecture of the fiber network based entirely on the initial protein monomer composition. This style of protocol may be applied to other fields where a research team seeks to design a biomaterial with biomedical application-specific properties. This protocol highlights when and how the three research groups (simulation, synthesis, and engineering) should be interacting to arrive at the most effective method for predictive design of their material.

Systematic Analysis of the Genetic Variability That Impacts SUMO Conjugation and Their Involvement in Human Diseases

NASA Astrophysics Data System (ADS)

Xu, Hao-Dong; Shi, Shao-Ping; Chen, Xiang; Qiu, Jian-Ding

2015-07-01

Protein function has been observed to rely on select essential sites instead of requiring all sites to be indispensable. Small ubiquitin-related modifier (SUMO) conjugation or sumoylation, which is a highly dynamic reversible process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified, has shown to be especially valuable in cellular biology. Motivated by the significance of SUMO conjugation in biological processes, we report here on the first exploratory assessment whether sumoylation related genetic variability impacts protein functions as well as the occurrence of diseases related to SUMO. Here, we defined the SUMOAMVR as sumoylation related amino acid variations that affect sumoylation sites or enzymes involved in the process of connectivity, and categorized four types of potential SUMOAMVRs. We detected that 17.13% of amino acid variations are potential SUMOAMVRs and 4.83% of disease mutations could lead to SUMOAMVR with our system. More interestingly, the statistical analysis demonstrates that the amino acid variations that directly create new potential lysine sumoylation sites are more likely to cause diseases. It can be anticipated that our method can provide more instructive guidance to identify the mechanisms of genetic diseases.

Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population.

PubMed

Karaca, Sefayet; Erge, Sema; Cesuroglu, Tomris; Polimanti, Renato

2016-06-01

Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic Factors That Might Lead to Different Responses in Individuals Exposed to Perchlorate

PubMed Central

Scinicariello, Franco; Murray, H. Edward; Smith, Lester; Wilbur, Sharon; Fowler, Bruce A.

2005-01-01

Perchlorate has been detected in groundwater in many parts of the United States, and recent detection in vegetable and dairy food products indicates that contamination by perchlorate is more widespread than previously thought. Perchlorate is a competitive inhibitor of the sodium iodide symporter, the thyroid cell–surface protein responsible for transporting iodide from the plasma into the thyroid. An estimated 4.3% of the U.S. population is subclinically hypothyroid, and 6.9% of pregnant women may have low iodine intake. Congenital hypothyroidism affects 1 in 3,000 to 1 in 4,000 infants, and 15% of these cases have been attributed to genetic defects. Our objective in this review is to identify genetic biomarkers that would help define subpopulations sensitive to environmental perchlorate exposure. We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification. Furthermore, we summarize relevant studies of perchlorate in humans. Because of perchlorate inhibition of iodide uptake, it is biologically plausible that chronic ingestion of perchlorate through contaminated sources may cause some degree of iodine discharge in populations that are genetically susceptible to defects in the iodination process of the thyroid hormone synthesis, thus deteriorating their conditions. We conclude that future studies linking human disease and environmental perchlorate exposure should consider the genetic makeup of the participants, actual perchlorate exposure levels, and individual iodine intake/excretion levels. PMID:16263499

Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency

PubMed Central

Argente, Jesús; Flores, Raquel; Gutiérrez-Arumí, Armand; Verma, Bhupendra; Martos-Moreno, Gabriel Á; Cuscó, Ivon; Oghabian, Ali; Chowen, Julie A; Frilander, Mikko J; Pérez-Jurado, Luis A

2014-01-01

The molecular basis of a significant number of cases of isolated growth hormone deficiency remains unknown. We describe three sisters affected with severe isolated growth hormone deficiency and pituitary hypoplasia caused by biallelic mutations in the RNPC3 gene, which codes for a minor spliceosome protein required for U11/U12 small nuclear ribonucleoprotein (snRNP) formation and splicing of U12-type introns. We found anomalies in U11/U12 di-snRNP formation and in splicing of multiple U12-type introns in patient cells. Defective transcripts include preprohormone convertases SPCS2 and SPCS3 and actin-related ARPC5L genes, which are candidates for the somatotroph-restricted dysfunction. The reported novel mechanism for familial growth hormone deficiency demonstrates that general mRNA processing defects of the minor spliceosome can lead to very narrow tissue-specific consequences. Subject Categories Genetics, Gene Therapy ' Genetic Disease; Metabolism PMID:24480542

Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans.

PubMed

Rodrigues, Sarina M; Saslow, Laura R; Garcia, Natalia; John, Oliver P; Keltner, Dacher

2009-12-15

Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the "Reading the Mind in the Eyes" Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles.

Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans

PubMed Central

Rodrigues, Sarina M.; Saslow, Laura R.; Garcia, Natalia; John, Oliver P.; Keltner, Dacher

2009-01-01

Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the “Reading the Mind in the Eyes” Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles. PMID:19934046

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper.

PubMed

Randall, Leslie M; Pothuri, Bhavana; Swisher, Elizabeth M; Diaz, John P; Buchanan, Adam; Witkop, Catherine T; Bethan Powell, C; Smith, Ellen Blair; Robson, Mark E; Boyd, Jeff; Coleman, Robert L; Lu, Karen

2017-08-01

To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care. Copyright © 2017. Published by Elsevier Inc.

Genetic landscape and deregulated pathways in B-cell lymphoid malignancies.

PubMed

Rosenquist, R; Beà, S; Du, M-Q; Nadel, B; Pan-Hammarström, Q

2017-11-01

With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma. We will detail recurrent alterations affecting important signalling pathways, that is the B-cell receptor/NF-κB pathway, NOTCH signalling, JAK-STAT signalling, p53/DNA damage response, apoptosis and cell cycle regulation, as well as other perhaps unexpected cellular processes, such as immune regulation, cell migration, epigenetic regulation and RNA processing. Whilst many of these pathways/processes are commonly altered in different lymphoid tumors, albeit at varying frequencies, others are preferentially targeted in selected B-cell malignancies. Some of these genetic lesions are either involved in disease ontogeny or linked to the evolution of each disease and/or specific clinicobiological features, and some of them have been demonstrated to have prognostic and even predictive impact. Future work is especially needed to understand the therapy-resistant disease, particularly in patients treated with targeted therapy, and to identify novel targets and therapeutic strategies in order to realize true precision medicine in this clinically heterogeneous patient group. © 2017 The Association for the Publication of the Journal of Internal Medicine.

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

PubMed

Wereszczuk, Anna; Leblois, Raphaël; Zalewski, Andrzej

2017-12-22

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

Present spatial diversity patterns of Theobroma cacao L. in the neotropics reflect genetic differentiation in pleistocene refugia followed by human-influenced dispersal.

PubMed

Thomas, Evert; van Zonneveld, Maarten; Loo, Judy; Hodgkin, Toby; Galluzzi, Gea; van Etten, Jacob

2012-01-01

Cacao (Theobroma cacao L.) is indigenous to the Amazon basin, but is generally believed to have been domesticated in Mesoamerica for the production of chocolate beverage. However, cacao's distribution of genetic diversity in South America is also likely to reflect pre-Columbian human influences that were superimposed on natural processes of genetic differentiation. Here we present the results of a spatial analysis of the intra-specific diversity of cacao in Latin America, drawing on a dataset of 939 cacao trees genotypically characterized by means of 96 SSR markers. To assess continental diversity patterns we performed grid-based calculations of allelic richness, Shannon diversity and Nei gene diversity, and distinguished different spatially coherent genetic groups by means of cluster analysis. The highest levels of genetic diversity were observed in the Upper Amazon areas from southern Peru to the Ecuadorian Amazon and the border areas between Colombia, Peru and Brazil. On the assumption that the last glaciation (22,000-13,000 BP) had the greatest pre-human impact on the current distribution and diversity of cacao, we modeled the species' Pleistocene niche suitability and overlaid this with present-day diversity maps. The results suggest that cacao was already widely distributed in the Western Amazon before the onset of glaciation. During glaciations, cacao populations were likely to have been restricted to several refugia where they probably underwent genetic differentiation, resulting in a number of genetic clusters which are representative for, or closest related to, the original wild cacao populations. The analyses also suggested that genetic differentiation and geographical distribution of a number of other clusters seem to have been significantly affected by processes of human management and accompanying genetic bottlenecks. We discuss the implications of these results for future germplasm collection and in situ, on farm and ex situ conservation of cacao.

Present Spatial Diversity Patterns of Theobroma cacao L. in the Neotropics Reflect Genetic Differentiation in Pleistocene Refugia Followed by Human-Influenced Dispersal

PubMed Central

Thomas, Evert; van Zonneveld, Maarten; Loo, Judy; Hodgkin, Toby; Galluzzi, Gea; van Etten, Jacob

2012-01-01

Cacao (Theobroma cacao L.) is indigenous to the Amazon basin, but is generally believed to have been domesticated in Mesoamerica for the production of chocolate beverage. However, cacao’s distribution of genetic diversity in South America is also likely to reflect pre-Columbian human influences that were superimposed on natural processes of genetic differentiation. Here we present the results of a spatial analysis of the intra-specific diversity of cacao in Latin America, drawing on a dataset of 939 cacao trees genotypically characterized by means of 96 SSR markers. To assess continental diversity patterns we performed grid-based calculations of allelic richness, Shannon diversity and Nei gene diversity, and distinguished different spatially coherent genetic groups by means of cluster analysis. The highest levels of genetic diversity were observed in the Upper Amazon areas from southern Peru to the Ecuadorian Amazon and the border areas between Colombia, Peru and Brazil. On the assumption that the last glaciation (22,000–13,000 BP) had the greatest pre-human impact on the current distribution and diversity of cacao, we modeled the species’ Pleistocene niche suitability and overlaid this with present-day diversity maps. The results suggest that cacao was already widely distributed in the Western Amazon before the onset of glaciation. During glaciations, cacao populations were likely to have been restricted to several refugia where they probably underwent genetic differentiation, resulting in a number of genetic clusters which are representative for, or closest related to, the original wild cacao populations. The analyses also suggested that genetic differentiation and geographical distribution of a number of other clusters seem to have been significantly affected by processes of human management and accompanying genetic bottlenecks. We discuss the implications of these results for future germplasm collection and in situ, on farm and ex situ conservation of cacao. PMID:23112832

Annual research review: Rare genotypes and childhood psychopathology--uncovering diverse developmental mechanisms of ADHD risk.

PubMed

Scerif, Gaia; Baker, Kate

2015-03-01

Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional-behavioural disturbance has theoretical and practical utility. We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses - attention deficit hyperactivity disorder (ADHD) - in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within genotype-defined groups. Crucially, as genetic predispositions modify interaction dynamics from the outset, longitudinal research is required to understand the multi-level developmental processes that mediate symptom evolution. © 2014 Association for Child and Adolescent Mental Health.

Phylogenetic congruence of lichenised fungi and algae is affected by spatial scale and taxonomic diversity.

PubMed

Buckley, Hannah L; Rafat, Arash; Ridden, Johnathon D; Cruickshank, Robert H; Ridgway, Hayley J; Paterson, Adrian M

2014-01-01

The role of species' interactions in structuring biological communities remains unclear. Mutualistic symbioses, involving close positive interactions between two distinct organismal lineages, provide an excellent means to explore the roles of both evolutionary and ecological processes in determining how positive interactions affect community structure. In this study, we investigate patterns of co-diversification between fungi and algae for a range of New Zealand lichens at the community, genus, and species levels and explore explanations for possible patterns related to spatial scale and pattern, taxonomic diversity of the lichens considered, and the level sampling replication. We assembled six independent datasets to compare patterns in phylogenetic congruence with varied spatial extent of sampling, taxonomic diversity and level of specimen replication. For each dataset, we used the DNA sequences from the ITS regions of both the fungal and algal genomes from lichen specimens to produce genetic distance matrices. Phylogenetic congruence between fungi and algae was quantified using distance-based redundancy analysis and we used geographic distance matrices in Moran's eigenvector mapping and variance partitioning to evaluate the effects of spatial variation on the quantification of phylogenetic congruence. Phylogenetic congruence was highly significant for all datasets and a large proportion of variance in both algal and fungal genetic distances was explained by partner genetic variation. Spatial variables, primarily at large and intermediate scales, were also important for explaining genetic diversity patterns in all datasets. Interestingly, spatial structuring was stronger for fungal than algal genetic variation. As the spatial extent of the samples increased, so too did the proportion of explained variation that was shared between the spatial variables and the partners' genetic variation. Different lichen taxa showed some variation in their phylogenetic congruence and spatial genetic patterns and where greater sample replication was used, the amount of variation explained by partner genetic variation increased. Our results suggest that the phylogenetic congruence pattern, at least at small spatial scales, is likely due to reciprocal co-adaptation or co-dispersal. However, the detection of these patterns varies among different lichen taxa, across spatial scales and with different levels of sample replication. This work provides insight into the complexities faced in determining how evolutionary and ecological processes may interact to generate diversity in symbiotic association patterns at the population and community levels. Further, it highlights the critical importance of considering sample replication, taxonomic diversity and spatial scale in designing studies of co-diversification.

Genetic and Environmental Influences on Adult Mental Health: Evidence for Gene-Environment Interplay as a Function of Maternal and Paternal Discipline and Affection.

PubMed

South, Susan C; Jarnecke, Amber M

2015-07-01

Researchers have long theorized that genetic influence on mental health may differ as a function of environmental risk factors. One likely moderator of genetic and environmental influences on psychopathological symptoms is parenting behavior, as phenotypic research shows that negative aspects of parent-child relationships are associated with greater likelihood of mental illness in adulthood. The current study examined whether levels of reported parental discipline and affection experienced in childhood act as a trigger, or buffer, for adult mental health problems. Results from a nationwide twin sample suggest level of father's discipline and affection, as reported by now-adult twins, moderated genetic and environmental influences on internalizing symptoms in adulthood, such that heritability was greatest at the highest levels of discipline and affection. Father's affection also moderated the etiological influences on alcohol use problems, with greater heritability at the lowest levels of affection. No moderating effect was found for mothers. Findings suggest relationships with fathers in childhood can have long-lasting effects on the etiological influences on adult mental health outcomes.

Culture–gene coevolution of individualism–collectivism and the serotonin transporter gene

PubMed Central

Chiao, Joan Y.; Blizinsky, Katherine D.

2010-01-01

Culture–gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism–collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture–gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism–collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture–gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism–collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture–gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed. PMID:19864286

Looking on the bright side: biased attention and the human serotonin transporter gene.

PubMed

Fox, Elaine; Ridgewell, Anna; Ashwin, Chris

2009-05-22

Humans differ in terms of biased attention for emotional stimuli and these biases can confer differential resilience and vulnerability to emotional disorders. Selective processing of positive emotional information, for example, is associated with enhanced sociability and well-being while a bias for negative material is associated with neuroticism and anxiety. A tendency to selectively avoid negative material might also be associated with mental health and well-being. The neurobiological mechanisms underlying these cognitive phenotypes are currently unknown. Here we show for the first time that allelic variation in the promotor region of the serotonin transporter gene (5-HTTLPR) is associated with differential biases for positive and negative affective pictures. Individuals homozygous for the long allele (LL) showed a marked bias to selectively process positive affective material alongside selective avoidance of negative affective material. This potentially protective pattern was absent among individuals carrying the short allele (S or SL). Thus, allelic variation on a common genetic polymorphism was associated with the tendency to selectively process positive or negative information. The current study is important in demonstrating a genotype-related alteration in a well-established processing bias, which is a known risk factor in determining both resilience and vulnerability to emotional disorders.

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging.

PubMed

Afornali, Alessandro; Vecchi, Rodrigo de; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; Oliveira, Luciana Lima de; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

2013-01-01

The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.

Beyond Serial Founder Effects: The Impact of Admixture and Localized Gene Flow on Patterns of Regional Genetic Diversity.

PubMed

Hunley, Keith L; Cabana, Graciela S

2016-07-01

Geneticists have argued that the linear decay in within-population genetic diversity with increasing geographic distance from East Africa is best explained by a phylogenetic process of repeated founder effects, growth, and isolation. However, this serial founder effect (SFE) process has not yet been adequately vetted against other evolutionary processes that may also affect geospatial patterns of diversity. Additionally, studies of the SFE process have been largely based on a limited 52-population sample. Here, we assess the effects of founder effect, admixture, and localized gene flow processes on patterns of global and regional diversity using a published data set of 645 autosomal microsatellite genotypes from 5,415 individuals in 248 widespread populations. We used a formal tree-fitting approach to explore the role of founder effects. The approach involved fitting global and regional population trees to extant patterns of gene diversity and then systematically examining the deviations in fit. We also informally tested the SFE process using linear models of gene diversity versus waypoint geographic distances from Africa. We tested the role of localized gene flow using partial Mantel correlograms of gene diversity versus geographic distance controlling for the confounding effects of treelike genetic structure. We corroborate previous findings that global patterns of diversity, both within and between populations, are the product of an out-of-Africa SFE process. Within regions, however, diversity within populations is uncorrelated with geographic distance from Africa. Here, patterns of diversity have been largely shaped by recent interregional admixture and secondary range expansions. Our detailed analyses of the pattern of diversity within and between populations reveal that the signatures of different evolutionary processes dominate at different geographic scales. These findings have important implications for recent publications on the biology of race.

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

PubMed Central

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

2013-01-01

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

Pedigree construction and disease confirmation: a pilot study in Wales exploring the role of nonclinical personnel.

PubMed

Tempest, Vanessa; Iredale, Rachel; Gray, Jonathon; France, Liz; Anstey, Sally; Steward, John

2005-09-01

Pedigree construction and disease confirmation are the means by which reported family histories are translated into a verified clinical tool informing risk assessment and management decisions by clinical genetics staff. In this study, we hypothesised that pedigree generation data processes do not generally require the clinical expertise of genetic counsellors and that they could be successfully transferred to nonclinical data administrators. We made a pragmatic comparison of two processes of pedigree generation by different personnel from 14 consecutive family history questionnaires containing 88 living and decease affected individuals. The pedigrees generated by the genetic counsellor and the data administrator were compared; discrepancies were quantified and their source determined. The information gathered by the data administrator mirrored that of the genetic counsellors in 89% of cases. Time was saved by permitting direct access to cancer registry and local oncology centre databases. Constructing a pedigree is not always a case of transferring clear-cut data. Decisions need to be made about which cancers to confirm. Notable differences emerged in the number of pieces of information not transferred. Ambiguous information was often interpreted differently, suggesting the need for clinical staff to review pedigrees after their initial plotting by the data administrator. This study demonstrates a good degree of concordance between pedigrees constructed by a nonclinical data administrator and those of experienced genetic counsellors. However, the redirection of all pedigree activity to nonclinical personnel up to the point of risk review is not possible at present.

Imaging epigenetics in Alzheimer's disease.

PubMed

Lista, Simone; Garaci, Francesco G; Toschi, Nicola; Hampel, Harald

2013-01-01

Sporadic Alzheimer's disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and behavioral decline. This decline includes reductions in the activities of daily living, quality of life, independence, and life expectancy. Evolving lines of research suggest that epigenetic mechanisms may play a crucial role during AD development and progression. Epigenetics designates molecular mechanisms that alter gene expression without modifications of the genetic code. This topic includes modifications on DNA and histone proteins, the primary elements of chromatin structure. Accumulating evidence has revealed the relevant processes that mediate epigenetic modifications and has begun to elucidate how these processes are apparently dysregulated in AD. This evidence has led to the clarification of the roles of specific classes of therapeutic compounds that affect epigenetic pathways and characteristics of the epigenome. This insight is accompanied by the development of new methods for studying the global patterns of DNA methylation and chromatin alterations. In particular, high-throughput sequencing approaches, such as next-generation DNA sequencing techniques, are beginning to drive the field into the next stage of development. In parallel, genetic imaging is beginning to answer additional questions through its ability to uncover genetic variants, with or without genome-wide significance, that are related to brain structure, function and metabolism, which impact disease risk and fundamental network-based cognitive processes. Neuroimaging measures can further be used to define AD systems and endophenotypes. The integration of genetic neuroimaging methods with epigenetic markers in humans appears promising. This evolving development may lead to a new research discipline - imaging epigenetics - that will provide deeper insight into the causative pathogenetic and pathophysiological pathways through which genes and environment interrelate during life and impact human brain development, physiology, aging and disease. This knowledge may open doors for the development of novel biomarkers and preventive and disease-modifying treatments.

Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.

PubMed

Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

2017-01-01

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity ( MPL, JAK2, CALR ) and loss-of-function (LOF) activity of negative regulators ( CBL, LNK ) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of MPL leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF THPO or MPL mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.

Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis

PubMed Central

Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

2017-01-01

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity (MPL, JAK2, CALR) and loss-of-function (LOF) activity of negative regulators (CBL, LNK) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of MPL leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF THPO or MPL mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production. PMID:28955303

[HLA genetic markers and auto-antibody profile in a Mapuche family with a case affected of type 1 diabetes].

PubMed

Asenjo, Sylvia; Gleisner, Andrea; Pérez, Francisco

2004-01-01

Type 1 diabetes (DM1) is caused by an autoimmune process that destroys beta cells of pancreas. Not all carriers of susceptible HLA genes and positive for autoantibodies develop the disease. Environmental factors play a role in triggering the autoimmune process. To analyze an exceptional case of DM1 in a Mapuche family in the context of genetic, immunological and environmental factors. A study of a family with an affected female child was carried out in a Mapuche community in Southern Chile (VIII region). This is an unique and sporadic DM1 case with Mapuche heritage. Nutritional and viral infections data were collected by interview and clinical records. A genetic analysis by PCR was done to detect class I and II HLA genes by reverse dot blot. The proband, her mother and sister had positive islet cell antibodies (ICA). Her father and brother were negative. All thefamily was positive for anti glutamic decarboxylase antibodies (GAD65). All subjects had HLA-DRB1 0407/0407 and HLA-DQB1 0302/0302 alleles. The index case and her father were homozygotes for the HLA-A1:A*68012/A*68012 allele. Mean breastfeeding lapse was 18 months in all children. No evidences for viral infections such as rubella, mumps or measles were found in this family. There was an altered profile of autoantibodies in the family of the index case. All genotypes were comparable with the European population where the diabetogenic combination DR4/DQB1*0302 is the most prevalent. No environmental factors could be incriminated as triggers of the disease.

Locally adapted fish populations maintain small-scale genetic differentiation despite perturbation by a catastrophic flood event

PubMed Central

2010-01-01

Background Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification of P. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood. Results Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre. Conclusions The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary perturbations, as adaptations to physico-chemical stressors may directly affect the survival probability in divergent habitat types. PMID:20731863

Locally adapted fish populations maintain small-scale genetic differentiation despite perturbation by a catastrophic flood event.

PubMed

Plath, Martin; Hermann, Bernd; Schröder, Christiane; Riesch, Rüdiger; Tobler, Michael; García de León, Francisco J; Schlupp, Ingo; Tiedemann, Ralph

2010-08-23

Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification of P. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood. Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre. The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary perturbations, as adaptations to physico-chemical stressors may directly affect the survival probability in divergent habitat types.

Intelligent Modeling Combining Adaptive Neuro Fuzzy Inference System and Genetic Algorithm for Optimizing Welding Process Parameters

NASA Astrophysics Data System (ADS)

Gowtham, K. N.; Vasudevan, M.; Maduraimuthu, V.; Jayakumar, T.

2011-04-01

Modified 9Cr-1Mo ferritic steel is used as a structural material for steam generator components of power plants. Generally, tungsten inert gas (TIG) welding is preferred for welding of these steels in which the depth of penetration achievable during autogenous welding is limited. Therefore, activated flux TIG (A-TIG) welding, a novel welding technique, has been developed in-house to increase the depth of penetration. In modified 9Cr-1Mo steel joints produced by the A-TIG welding process, weld bead width, depth of penetration, and heat-affected zone (HAZ) width play an important role in determining the mechanical properties as well as the performance of the weld joints during service. To obtain the desired weld bead geometry and HAZ width, it becomes important to set the welding process parameters. In this work, adaptative neuro fuzzy inference system is used to develop independent models correlating the welding process parameters like current, voltage, and torch speed with weld bead shape parameters like depth of penetration, bead width, and HAZ width. Then a genetic algorithm is employed to determine the optimum A-TIG welding process parameters to obtain the desired weld bead shape parameters and HAZ width.

The Legal Past, Present and Future of Prenatal Genetic Testing: Professional Liability and Other Legal Challenges Affecting Patient Access to Services.

PubMed

Pergament, Deborah; Ilijic, Katie

2014-12-15

This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments.

The Legal Past, Present and Future of Prenatal Genetic Testing: Professional Liability and Other Legal Challenges Affecting Patient Access to Services

PubMed Central

Pergament, Deborah; Ilijic, Katie

2014-01-01

This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments. PMID:26237611

Genetic and Environmental Contributions to the Development of Positive Affect in Infancy

PubMed Central

Planalp, Elizabeth M.; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Goldsmith, H. Hill

2016-01-01

We studied developmental changes in infant positive affect from 6 to 12 months of age, a time marked by increasing use of positive vocalizations, laughter, and social smiles. We estimated the magnitude of genetic and environmental influences on observed and parent reported infant positive affect across development. Participants were drawn from a longitudinal twin study of infancy and toddlerhood (N=536 twin pairs). Mothers and fathers reported on infant temperament and infants were videotaped during two observational tasks assessing positive affect. Parents also reported on their own affect and emotional expression within the family. Biometric models examined genetic and environmental influences that contribute to the developmental continuity of positive affect. Infant positive affect was associated with increased parent positive affect and family expressions of positive affect although not with family expressions of negative affect. In addition, the shared environment accounted for a large portion of variation in infant positive affect and continuity over time. These findings highlight the importance of the family environment in relation to infant positive emotional development. PMID:27797564

Genetic and environmental contributions to the development of positive affect in infancy.

PubMed

Planalp, Elizabeth M; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Goldsmith, H Hill

2017-04-01

We studied developmental changes in infant positive affect from 6 to 12 months of age, a time marked by increasing use of positive vocalizations, laughter, and social smiles. We estimated the magnitude of genetic and environmental influences on observed and parent reported infant positive affect across development. Participants were drawn from a longitudinal twin study of infancy and toddlerhood (N = 536 twin pairs). Mothers and fathers reported on infant temperament and infants were videotaped during 2 observational tasks assessing positive affect. Parents also reported on their own affect and emotional expression within the family. Biometric models examined genetic and environmental influences that contribute to the developmental continuity of positive affect. Infant positive affect was associated with increased parent positive affect and family expressions of positive affect although not with family expressions of negative affect. In addition, the shared environment accounted for a large portion of variation in infant positive affect and continuity over time. These findings highlight the importance of the family environment in relation to infant positive emotional development. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genetic and epigenetic effects in sex determination.

PubMed

Gunes, Sezgin Ozgur; Metin Mahmutoglu, Asli; Agarwal, Ashok

2016-12-01

Sex determination is a complex and dynamic process with multiple genetic and environmental causes, in which germ and somatic cells receive various sex-specific features. During the fifth week of fetal life, the bipotential embryonic gonad starts to develop in humans. In the bipotential gonadal tissue, certain cell groups start to differentiate to form the ovaries or testes. Despite considerable efforts and advances in identifying the mechanisms playing a role in sex determination and differentiation, the underlying mechanisms of the exact functions of many genes, gene-gene interactions, and epigenetic modifications that are involved in different stages of this cascade are not completely understood. This review aims at discussing current data on the genetic effects via genes and epigenetic mechanisms that affect the regulation of sex determination. Birth Defects Research (Part C) 108:321-336, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Sex ratio dynamics and fluctuating selection on personality.

PubMed

Del Giudice, Marco

2012-03-21

Fluctuating selection has often been proposed as an explanation for the maintenance of genetic variation in personality. Here I argue that the temporal dynamics of the sex ratio can be a powerful source of fluctuating selection on personality traits, and develop this hypothesis with respect to humans. First, I review evidence that sex ratios modulate a wide range of social processes related to mating and parenting. Since most personality traits affect mating and parenting behavior, changes in the sex ratio can be expected to result in variable selection on personality. I then show that the temporal dynamics of the sex ratio are intrinsically characterized by fluctuations at various timescales. Finally, I address a number of evolutionary genetic challenges to the hypothesis. I conclude that the sex ratio hypothesis is a plausible explanation of genetic variation in human personality, and may be fruitfully applied to other species as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

The response of transgenic Brassica species to salt stress: a review.

PubMed

Shah, Nadil; Anwar, Sumera; Xu, Jingjing; Hou, Zhaoke; Salah, Akram; Khan, Shahbaz; Gong, Jianfang; Shang, Zhengwei; Qian, Li; Zhang, Chunyu

2018-06-01

Salt stress is considered one of the main abiotic factors to limit crop growth and productivity by affecting morpho-physiological and biochemical processes. Genetically, a number of salt tolerant Brassica varieties have been developed and introduced, but breeding of such varieties is time consuming. Therefore, current focus is on transgenic technology, which plays an important role in the development of salt tolerant varieties. Various salt tolerant genes have been characterized and incorporated into Brassica. Therefore, such genetic transformation of Brassica species is a significant step for improvement of crops, as well as conferring salt stress resistance qualities to Brassica species. Complete genome sequencing has made the task of genetically transforming Brassica species easier, by identifying desired candidate genes. The present review discusses relevant information about the principles which should be employed to develop transgenic Brassica species, and also will recommend tools for improved tolerance to salinity.

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

PubMed

Beattie, Peter

2017-01-01

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

A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family.

PubMed

Tian, Qi; Li, Yunping; Kousar, Rizwana; Guo, Hui; Peng, Fenglan; Zheng, Yu; Yang, Xiaohua; Long, Zhigao; Tian, Runyi; Xia, Kun; Lin, Haiying; Pan, Qian

2017-01-07

Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males. Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype. Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein. The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.

Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures.

PubMed

Monnereau, Claire; Vogelezang, Suzanne; Kruithof, Claudia J; Jaddoe, Vincent W V; Felix, Janine F

2016-08-18

Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. We used data from a population-based prospective cohort study among 3,975 children with a mean age of 6 years. Genetic risk scores were constructed based on the 97 SNPs associated with adult BMI previously identified with GWAS and on 28 BMI related biological pathways based on subsets of these 97 SNPs. Outcomes were infant peak weight velocity, BMI at adiposity peak and age at adiposity peak, and childhood BMI, total fat mass percentage, android/gynoid fat ratio, and preperitoneal fat area. Analyses were performed using linear regression models. A higher overall adult BMI risk score was associated with infant BMI at adiposity peak and childhood BMI, total fat mass, android/gynoid fat ratio, and preperitoneal fat area (all p-values < 0.05). Analyses focused on specific biological pathways showed that the membrane proteins genetic risk score was associated with infant peak weight velocity, and the genetic risk scores related to neuronal developmental processes, hypothalamic processes, cyclicAMP, WNT-signaling, membrane proteins, monogenic obesity and/or energy homeostasis, glucose homeostasis, cell cycle, and muscle biology pathways were associated with childhood adiposity measures (all p-values <0.05). None of the pathways were associated with childhood preperitoneal fat area. A genetic risk score based on 97 SNPs related to adult BMI was associated with peak weight velocity during infancy and general and abdominal fat measurements at the age of 6 years. Risk scores based on genetic variants linked to specific biological pathways, including central nervous system and hypothalamic processes, influence body fat development from early life onwards.

Molecular Genetics of Root Thigmoresponsiveness in Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Masson, Patrick H.

2002-01-01

The molecular mechanisms that allow plant roots to use gravity and touch as growth guides are investigated. We are using a molecular genetic strategy in Arabidopsis thaliana to study these processes. When Arabidopsis thaliana seedlings grow on tilted hard-agar surfaces, their roots develop a wavy pattern of growth which appears to derive from a succession of left-handed and right-handed circumnutation-like processes triggered by gravity and touch stimulation (Okada and Shimura, 1990; Rutherford et al., 1998; Rutherford and Masson, 1996). Interestingly, mutations that affect root waving on tilted hard-agar surfaces can be identified and characterized. Some of these mutations affect root gravitropism, while others appear to be responsible for the production of abnormal waves (no waves, compressed or square waves, coils) without affecting gravitropism. The specific objectives of this project were to functionally characterize two genes (WVD2 and WVD6) which are required for root waving on tilted agar surfaces, but not for root gravitropism. Specific objectives included a physiological and cytological analysis of the mutants, and molecular cloning and characterization of the corresponding genes. As summarized in this paper, we have reached these objectives. We have also identified and partially characterized other mutations that affect root skewing on hard-agar surfaces (sku5-1 and ago1), and have completed our work on the root-wave phenotype associated with mutations in genes of the tryptophan biosynthesis pathway (Lynn et al., 1999; Rutherford et al., 1998; Sedbrook et al., 2000, 2002). We briefly describe our progress on the cloning and characterization of WVD6, WVD2 and SKU5, and provide a list of papers (published, or in preparation) that derived from this grant. We also discuss the biological implications of our findings, with special emphasis on the analysis of WVD2.

The Voltage-Sensing Domain of K(v)7.2 Channels as a Molecular Target for Epilepsy-Causing Mutations and Anticonvulsants.

PubMed

Miceli, Francesco; Soldovieri, Maria Virginia; Iannotti, Fabio Arturo; Barrese, Vincenzo; Ambrosino, Paolo; Martire, Maria; Cilio, Maria Roberta; Taglialatela, Maurizio

2011-01-01

Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs) has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically determined channelopathies affecting heart rhythm (arrhythmias), neuronal excitability (epilepsy, pain), or skeletal muscle contraction (periodic paralysis). Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function. In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K(+) channels encoded by the K(v)7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by K(v)7.2-K(v)7.5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically determined alterations in K(v)7.2 and K(v)7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of K(v)7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in K(v)7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability.

The Voltage-Sensing Domain of Kv7.2 Channels as a Molecular Target for Epilepsy-Causing Mutations and Anticonvulsants

PubMed Central

Miceli, Francesco; Soldovieri, Maria Virginia; Iannotti, Fabio Arturo; Barrese, Vincenzo; Ambrosino, Paolo; Martire, Maria; Cilio, Maria Roberta; Taglialatela, Maurizio

2010-01-01

Understanding the molecular mechanisms underlying voltage-dependent gating in voltage-gated ion channels (VGICs) has been a major effort over the last decades. In recent years, changes in the gating process have emerged as common denominators for several genetically determined channelopathies affecting heart rhythm (arrhythmias), neuronal excitability (epilepsy, pain), or skeletal muscle contraction (periodic paralysis). Moreover, gating changes appear as the main molecular mechanism by which several natural toxins from a variety of species affect ion channel function. In this work, we describe the pathophysiological and pharmacological relevance of the gating process in voltage-gated K+ channels encoded by the Kv7 gene family. After reviewing the current knowledge on the molecular mechanisms and on the structural models of voltage-dependent gating in VGICs, we describe the physiological relevance of these channels, with particular emphasis on those formed by Kv7.2–Kv7.5 subunits having a well-established role in controlling neuronal excitability in humans. In fact, genetically determined alterations in Kv7.2 and Kv7.3 genes are responsible for benign familial neonatal convulsions, a rare seizure disorder affecting newborns, and the pharmacological activation of Kv7.2/3 channels can exert antiepileptic activity in humans. Both mutation-triggered channel dysfunction and drug-induced channel activation can occur by impeding or facilitating, respectively, channel sensitivity to membrane voltage and can affect overlapping molecular sites within the voltage-sensing domain of these channels. Thus, understanding the molecular steps involved in voltage-sensing in Kv7 channels will allow to better define the pathogenesis of rare human epilepsy, and to design innovative pharmacological strategies for the treatment of epilepsies and, possibly, other human diseases characterized by neuronal hyperexcitability. PMID:21687499

Parents' communication with siblings of children affected by an inherited genetic condition.

PubMed

Plumridge, Gillian; Metcalfe, Alison; Coad, Jane; Gill, Paramjit

2011-08-01

The objective of this study was to explore parents' communication about risk with siblings of children affected by an inherited genetic condition, and to ascertain what level of support, if any, is required from health professionals. Semi-structured interviews were conducted with affected and unaffected children and their parents. Families were affected by one of six genetic conditions representing different patterns of inheritance and variations in age of onset, life expectancy and impact on families. Interviews were analysed using constructivist grounded theory and informed by models which focused on three different aspects of family communication. Interviews with 33 families showed that siblings' information and support needs go largely unrecognized by health professionals and sometimes by parents. Some siblings were actively informed about the genetic condition by parents, others were left to find out and assimilate information by themselves. Siblings were given information about the current symptoms and management of the genetic condition but were less likely to know about its hereditary nature and their own potential risk. When siblings were fully informed about the condition and included in family discussion, they had a better understanding of their role within their family, and family relationships were reported to be more harmonious. The information and support needs of siblings can be overlooked. Parents with the responsibility for caring for a child affected by a genetic condition may require support from health professionals to understand and respond to their unaffected children's need for more information about the genetic condition and its implications for the children's own future health and reproductive decision-making.

Smoking at the workplace: Effects of genetic and environmental causal accounts on attitudes towards smoking employees and restrictive policies

PubMed Central

Dar-Nimrod, Ilan; Zuckerman, Miron; Duberstein, Paul

2014-01-01

People hold diverse beliefs regarding the etiologies of individual and group differences in behaviors which, in turn, might affect their attitudes and behaviors. It is important to establish how perceived etiologies for smoking might affect the effectiveness of policy initiatives and prevention efforts. The present study assessed whether exposure to genetic vs. environmental accounts for smoking affects attitudes towards a) workplace-related smoking policies and b) smokers at the workplace. Results indicate that exposure to a genetic explanation led to stronger objections to a smoking restrictive policy compared with a non-genetic explanation. Additionally, participants in the genetic condition were more accepting of a smoker in the workplace than in the environmental condition. Evidently, beliefs about the etiology of smoking influence a range of attitudes related to smokers and smoking related policies. PMID:25530710

Quantification of the genetic change in the transition of Rhodnius pallescens Barber, 1932 (Hemiptera: Reduviidae) from field to laboratory.

PubMed

Gómez-Sucerquia, Leysa Jackeline; Triana-Chávez, Omar; Jaramillo-Ocampo, Nicolás

2009-09-01

Previous studies have reported genetic differences between wild-caught sylvatic, domestic and laboratory pop-ulations of several Triatominae species. The differences between sylvatic and laboratory colonies parallel are similar to the differences observed between sylvatic and domestic populations. Laboratory colonies are frequently used as references for field populations, but the consequences of founder events on the genetic makeup of laboratory or domestic populations are rarely quantified. Our goal was to quantify the genetic change in Rhodnius pallescens populations artificially submitted to founder effects via laboratory colonization. We compared the genetic makeup of two sylvatic populations and their laboratory descendants using a panel of 10 microsatellite markers. Both sylvatic populations were initially collected from palm trees, but the colonies differed in the number of founder insects and amount of time kept in the laboratory. We evaluated allelic polymorphism, differences between expected and observed heterozygosity, estimates of population differentiation (Fst) and inbreeding (Fis, Fit) and cluster analyses based on Nei's distances. We found a unique genetic structure for each sample population, with significant differentiation between the field insects and each of the laboratory generations. These analyses showed strong founder effects and showed that genetic drift had led to a genetic equilibrium over several generations of isolation. Our results suggest that laboratory colonies of R. pallescens have a different genetic structure than their wild relatives and similar processes likely affect other Triatominae laboratory stocks.

Genetic influences on the cognitive biases associated with anxiety and depression symptoms in adolescents.

PubMed

Zavos, Helena M S; Rijsdijk, Frühling V; Gregory, Alice M; Eley, Thalia C

2010-07-01

There is a substantial overlap between genes affecting anxiety and depression. Both anxiety and depression are associated with cognitive biases such as anxiety sensitivity and attributional style. Little, however, is known about the relationship between these variables and whether these too are genetically correlated. Self-reports of anxiety sensitivity, anxiety symptoms, attributional style and depression symptoms were obtained for over 1300 adolescent twin and sibling pairs at two time points. The magnitude of genetic and environmental influences on the measures was examined. Strongest associations were found between anxiety sensitivity and anxiety ratings at both measurement times (r=.70, .72) and between anxiety and depression (r=.62 at both time points). Correlations between the cognitive biases were modest at time 1 (r=-.12) and slightly larger at time 2 (r=-.31). All measures showed moderate genetic influence. Generally genetic correlations reflected phenotypic correlations. Thus the highest genetic correlations were between anxiety sensitivity and anxiety ratings (.86, .87) and between anxiety and depression ratings (.77, .71). Interestingly, depression ratings also showed a high genetic correlation with anxiety sensitivity (.70, .76). Genetic correlations between the cognitive bias measures were moderate (-.31, -.46). The sample consists primarily of twins, there are limitations associated with the twin design. Cognitive biases associated with depression and anxiety are not as genetically correlated as anxiety and depression ratings themselves. Further research into the cognitive processes related to anxiety and depression will facilitate understanding of the relationship between bias and symptoms.

Solid lipid nanoparticles release DNA upon endosomal acidification in human embryonic kidney cells.

PubMed

Radaic, A; de Jesus, M B

2018-08-03

Nanotechnology can produce materials with unique features compared to their bulk counterparts, which can be useful for medical applications (i.e. nanomedicine). Among the therapeutic agents used in nanomedicine, small molecules or biomacromolecules, such as proteins or genetic materials, can be designed for disease diagnostics and treatment. To transport these biomacromolecules to the target cells, nanomedicine requires nanocarriers. Solid lipid nanoparticles (SLNs) are among the promising nanocarriers available, because they can be made from biocompatible materials and present high stability (over one year). In addition, upon the binding genetic material, SLNs form SLNplexes. However, little is yet known about how cells process these SLNplexes-in particular, how internalization and endosome acidification affects the transfection mediated by SLNplexes. Therefore, we aim to investigate how these processes affect SLNplex transfection in HEK293T cells. We find that the SLNplex is mainly internalized by clathrin-mediated endocytosis, which is a fast and reliable pathway to transfection, leading to approximately 60% transfection efficiency. Interestingly, upon acidification (below pH 5.0), the SLN seems to release its DNA content, which can be an essential step for SLNplex transfection. The underlying mechanisms described in this work may help improve SLNplex formulations and transfection efficiency. Moreover, these advances can improve the field of nanomedical research and bring new ways to cure diseases.

Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) affected by environmental factors.

PubMed

Wang, Qiuxia; Liu, Huitao; Gao, Ainong; Yang, Xinming; Liu, Weihua; Li, Xiuquan; Li, Lihui

2012-01-01

Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

Intergenomic Rearrangements after Polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) Affected by Environmental Factors

PubMed Central

Wang, Qiuxia; Liu, Huitao; Gao, Ainong; Yang, Xinming; Liu, Weihua; Li, Xiuquan; Li, Lihui

2012-01-01

Polyploidization is a major evolutionary process. Approximately 70–75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution. PMID:22363542

Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

NASA Technical Reports Server (NTRS)

Norga, Koenraad K.; Gurganus, Marjorie C.; Dilda, Christy L.; Yamamoto, Akihiko; Lyman, Richard F.; Patel, Prajal H.; Rubin, Gerald M.; Hoskins, Roger A.; Mackay, Trudy F.; Bellen, Hugo J.

2003-01-01

BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

Tailored HIV-1 vectors for genetic modification of primary human dendritic cells and monocytes.

PubMed

Durand, Stéphanie; Nguyen, Xuan-Nhi; Turpin, Jocelyn; Cordeil, Stephanie; Nazaret, Nicolas; Croze, Séverine; Mahieux, Renaud; Lachuer, Joël; Legras-Lachuer, Catherine; Cimarelli, Andrea

2013-01-01

Monocyte-derived dendritic cells (MDDCs) play a key role in the regulation of the immune system and are the target of numerous gene therapy applications. The genetic modification of MDDCs is possible with human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LVs) but requires high viral doses to bypass their natural resistance to viral infection, and this in turn affects their physiological properties. To date, a single viral protein is able to counter this restrictive phenotype, Vpx, a protein derived from members of the HIV-2/simian immunodeficiency virus SM lineage that counters at least two restriction factors present in myeloid cells. By tagging Vpx with a short heterologous membrane-targeting domain, we have obtained HIV-1 LVs incorporating high levels of this protein (HIV-1-Src-Vpx). These vectors efficiently transduce differentiated MDDCs and monocytes either as previously purified populations or as populations within unsorted peripheral blood mononuclear cells (PBMCs). In addition, these vectors can be efficiently pseudotyped with receptor-specific envelopes, further restricting their cellular tropism almost uniquely to MDDCs. Compared to conventional HIV-1 LVs, these novel vectors allow for an efficient genetic modification of MDDCs and, more importantly, do not cause their maturation or affect their survival, which are unwanted side effects of the transduction process. This study describes HIV-1-Src-Vpx LVs as a novel potent tool for the genetic modification of differentiated MDDCs and of circulating monocyte precursors with strong potential for a wide range of gene therapy applications.

Genetics Home Reference: Boucher-Neuhäuser syndrome

MedlinePlus

... the cerebellum ). Affected individuals have an unsteady walking style (gait) and frequent falls. Another key feature of ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: ...

Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention.

PubMed

Post, Robert M

2016-06-01

The process of sensitization (increased responsivity) to the recurrence of stressors, affective episodes, and bouts of substance abuse that can drive illness progression in the recurrent affective disorders requires a memory of and increased reactivity to the prior exposures. A wealth of studies now supports the postulate that epigenetic mechanisms underlie both normal and pathological memory processes. We selectively reviewed the literature pertinent to the role of epigenetics in behavioral sensitization phenomena and discuss its clinical implications. Epigenetics means above genetics and refers to environmental effects on the chemistry of DNA, histones (around which DNA is wound), and microRNA that change how easily genes are turned on and off. The evidence supports that sensitization to repeated stressor, affective episodes, and substance is likely based on epigenetic mechanisms and that these environmentally based processes can then become targets for prevention, early intervention, and ongoing treatment. Sensitization processes are remediable or preventable risk factors for a poor illness outcome and deserve increased clinical, public health, and research attention in the hopes of making the recurrent unipolar and bipolar affective disorders less impairing, disabling, and lethal by suicide and increased medical mortality. The findings that epigenetic chemical marks, which change in the most fundamental way how genes are regulated, mediate the long-term increased responsivity to recurrent stressors, mood episodes, and bouts of substance abuse should help change how the affective disorders are conceptualized and move treatment toward earlier, more comprehensive, and sustained pharmacoprophylaxis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

PubMed

Bakker, J M; Lieverse, R; Menne-Lothmann, C; Viechtbauer, W; Pishva, E; Kenis, G; Geschwind, N; Peeters, F; van Os, J; Wichers, M

2014-04-22

Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the μ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

Empathy in early childhood: genetic, environmental, and affective contributions.

PubMed

Knafo, Ariel; Zahn-Waxler, Carolyn; Davidov, Maayan; Van Hulle, Carol; Robinson, JoAnn L; Rhee, Soo Hyun

2009-06-01

We investigated the genetic and environmental origins of children's empathy toward a distress victim and its correlates with emotional symptoms and affective knowledge. The cognitive (hypothesis testing) and affective (empathic concern) empathy of 122 twin pairs in response to simulated pain by an adult examiner was observed at 3.5 years of age. Moderate (0.19 to 0.44) heritabilities were estimated for individual differences in empathy, and the nonshared environment and error accounted for the rest of the variance. Hypothesis testing and empathic concern were moderately correlated, mainly through overlapping genetic effects. Although children's affective knowledge did not correlate with their empathy, affective knowledge interacted with mother-rated emotional symptoms in predicting empathy; knowledge about emotions was associated with greater empathy in children low in emotional symptoms. In contrast, among children with high degrees of emotional symptoms, those with better affective knowledge tended to show lower empathy.

Update on Genetic Conditions Affecting the Skin and the Kidneys

PubMed Central

Reimer, Antonia; He, Yinghong; Has, Cristina

2018-01-01

Genetic conditions affecting the skin and kidney are clinically and genetically heterogeneous, and target molecular components present in both organs. The molecular pathology involves defects of cell–matrix adhesion, metabolic or signaling pathways, as well as tumor suppressor genes. This article gives a clinically oriented overview of this group of disorders, highlighting entities which have been recently described, as well as the progress made in understanding well-known entities. The genetic bases as well as molecular cell biological mechanisms are described, with therapeutic applications. PMID:29552546

Sewage treatment plant associated genetic differentiation in the blue mussel from the Baltic Sea and Swedish west coast

PubMed Central

Lönn, Mikael; Lind, Emma E.; Świeżak, Justyna; Smolarz, Katarzyna; Grahn, Mats

2016-01-01

Human-derived environmental pollutants and nutrients that reach the aquatic environment through sewage effluents, agricultural and industrial processes are constantly contributing to environmental changes that serve as drivers for adaptive responses and evolutionary changes in many taxa. In this study, we examined how two types of point sources of aquatic environmental pollution, harbors and sewage treatment plants, affect gene diversity and genetic differentiation in the blue mussel in the Baltic Sea area and off the Swedish west coast (Skagerrak). Reference sites (REF) were geographically paired with sites from sewage treatments plant (STP) and harbors (HAR) with a nested sampling scheme, and genetic differentiation was evaluated using a high-resolution marker amplified fragment length polymorphism (AFLP). This study showed that genetic composition in the Baltic Sea blue mussel was associated with exposure to sewage treatment plant effluents. In addition, mussel populations from harbors were genetically divergent, in contrast to the sewage treatment plant populations, suggesting that there is an effect of pollution from harbors but that the direction is divergent and site specific, while the pollution effect from sewage treatment plants on the genetic composition of blue mussel populations acts in the same direction in the investigated sites. PMID:27812424

Pharmacogenetics of drug response in Parkinson's disease.

PubMed

Džoljić, Eleonora; Novaković, Ivana; Krajinovic, Maja; Grbatinić, Ivan; Kostić, Vladimir

2015-01-01

Parkinson's disease (PD) is a debilitating, demoralizing and financially devastating condition affecting 1% of population at the age of 60 years. Thus, very important issue to address is individual therapy optimization. Recent results have shown evidence that variable efficacy of treatment and risk of motor and mental complications could have genetic origin. Significant roles in that process play (pharmaco)genomic/genetic studies of PD. Variability in genes coding for drug-metabolizing enzymes, drug receptors and proteins involved in drug pathway signaling is an important factor determining inter-individual variability in drug responses. Interpersonal differences in drug responses are clearly documented although individualized treatment of PD is not widely known. Treatment with antiparkinsonian drugs is associated with the development of complications, such as L-DOPA-induced dyskinesia (LID), hallucinations and excessive daytime sleepiness. Carriers of specific genetic polymorphisms are particularly susceptible to development of some of these drug adverse effects. Pharmacogenomics aims to understand the relationship between genetic factors and inter-individual variations in drug responses, and to translate this information in therapy tailored to individual patient genetics. Relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. Thus, many genetic variations and polymorphisms in myriad of different proteins can influence individual response to anti-PD drugs.

Species differentiation on a dynamic landscape: shifts in metapopulation genetic structure using the chronology of the Hawaiian Archipelago

USGS Publications Warehouse

Roderick, George K.; Croucher, Peter J.P.; Vandergast, Amy G.; Gillespie, Rosemary G.

2012-01-01

Species formation during adaptive radiation often occurs in the context of a changing environment. The establishment and arrangement of populations, in space and time, sets up ecological and genetic processes that dictate the rate and pattern of differentiation. Here, we focus on how a dynamic habitat can affect genetic structure, and ultimately, differentiation among populations. We make use of the chronology and geographical history provided by the Hawaiian archipelago to examine the initial stages of population establishment and genetic divergence. We use data from a set of 6 spider lineages that differ in habitat affinities, some preferring low elevation habitats with a longer history of connection, others being more specialized for high elevation and/or wet forest, some with more general habitat affinities. We show that habitat preferences associated with lineages are important in ecological and genetic structuring. Lineages that have more restricted habitat preferences are subject to repeated episodes of isolation and fragmentation as a result of lava flows and vegetation succession. The initial dynamic set up by the landscape translates over time into discrete lineages. Further work is needed to understand how genetic changes interact with a changing set of ecological interactions amongst a shifting mosaic of landscapes to achieve species formation.

The impact of translocations on neutral and functional genetic diversity within and among populations of the Seychelles warbler.

PubMed

Wright, David J; Spurgin, Lewis G; Collar, Nigel J; Komdeur, Jan; Burke, Terry; Richardson, David S

2014-05-01

Translocations are an increasingly common tool in conservation. The maintenance of genetic diversity through translocation is critical for both the short- and long-term persistence of populations and species. However, the relative spatio-temporal impacts of translocations on neutral and functional genetic diversity, and how this affects genetic structure among the conserved populations overall, have received little investigation. We compared the impact of translocating different numbers of founders on both microsatellite and major histocompatibility complex (MHC) class I diversity over a 23-year period in the Seychelles warbler (Acrocephalus sechellensis). We found low and stable microsatellite and MHC diversity in the source population and evidence for only a limited loss of either type of diversity in the four new populations. However, we found evidence of significant, but low to moderate, genetic differentiation between populations, with those populations established with fewer founders clustering separately. Stochastic genetic capture (as opposed to subsequent drift) was the main determinant of translocated population diversity. Furthermore, a strong correlation between microsatellite and MHC differentiation suggested that neutral processes outweighed selection in shaping MHC diversity in the new populations. These data provide important insights into how to optimize the use of translocation as a conservation tool. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

The impact of translocations on neutral and functional genetic diversity within and among populations of the Seychelles warbler

PubMed Central

Wright, David J; Spurgin, Lewis G; Collar, Nigel J; Komdeur, Jan; Burke, Terry; Richardson, David S

2014-01-01

Translocations are an increasingly common tool in conservation. The maintenance of genetic diversity through translocation is critical for both the short- and long-term persistence of populations and species. However, the relative spatio-temporal impacts of translocations on neutral and functional genetic diversity, and how this affects genetic structure among the conserved populations overall, have received little investigation. We compared the impact of translocating different numbers of founders on both microsatellite and major histocompatibility complex (MHC) class I diversity over a 23-year period in the Seychelles warbler (Acrocephalus sechellensis). We found low and stable microsatellite and MHC diversity in the source population and evidence for only a limited loss of either type of diversity in the four new populations. However, we found evidence of significant, but low to moderate, genetic differentiation between populations, with those populations established with fewer founders clustering separately. Stochastic genetic capture (as opposed to subsequent drift) was the main determinant of translocated population diversity. Furthermore, a strong correlation between microsatellite and MHC differentiation suggested that neutral processes outweighed selection in shaping MHC diversity in the new populations. These data provide important insights into how to optimize the use of translocation as a conservation tool. PMID:24689851

Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease.

PubMed

Gan-Or, Ziv; Dion, Patrick A; Rouleau, Guy A

2015-01-01

Parkinson disease (PD), once considered as a prototype of a sporadic disease, is now known to be considerably affected by various genetic factors, which interact with environmental factors and the normal process of aging, leading to PD. Large studies determined that the hereditary component of PD is at least 27%, and in some populations, single genetic factors are responsible for more than 33% of PD patients. Interestingly, many of these genetic factors, such as LRRK2, GBA, SMPD1, SNCA, PARK2, PINK1, PARK7, SCARB2, and others, are involved in the autophagy-lysosome pathway (ALP). Some of these genes encode lysosomal enzymes, whereas others correspond to proteins that are involved in transport to the lysosome, mitophagy, or other autophagic-related functions. Is it possible that all these factors converge into a single pathway that causes PD? In this review, we will discuss these genetic findings and the role of the ALP in the pathogenesis of PD and will try to answer this question. We will suggest a novel hypothesis for the pathogenic mechanism of PD that involves the lysosome and the different autophagy pathways.

Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease

PubMed Central

Gan-Or, Ziv; Dion, Patrick A; Rouleau, Guy A

2015-01-01

Parkinson disease (PD), once considered as a prototype of a sporadic disease, is now known to be considerably affected by various genetic factors, which interact with environmental factors and the normal process of aging, leading to PD. Large studies determined that the hereditary component of PD is at least 27%, and in some populations, single genetic factors are responsible for more than 33% of PD patients. Interestingly, many of these genetic factors, such as LRRK2, GBA, SMPD1, SNCA, PARK2, PINK1, PARK7, SCARB2, and others, are involved in the autophagy-lysosome pathway (ALP). Some of these genes encode lysosomal enzymes, whereas others correspond to proteins that are involved in transport to the lysosome, mitophagy, or other autophagic-related functions. Is it possible that all these factors converge into a single pathway that causes PD? In this review, we will discuss these genetic findings and the role of the ALP in the pathogenesis of PD and will try to answer this question. We will suggest a novel hypothesis for the pathogenic mechanism of PD that involves the lysosome and the different autophagy pathways. PMID:26207393

Genetics Home Reference: adiposis dolorosa

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes The cause of adiposis dolorosa is unknown. The condition is thought to have a genetic component because a few families with multiple affected family members have been reported. ...

Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF

PubMed Central

Cong, Yingnan; Chan, Yao-ban; Phillips, Charles A.; Langston, Michael A.; Ragan, Mark A.

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k. Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k. PMID:28154557

DR-GAS: a database of functional genetic variants and their phosphorylation states in human DNA repair systems.

PubMed

Sehgal, Manika; Singh, Tiratha Raj

2014-04-01

We present DR-GAS(1), a unique, consolidated and comprehensive DNA repair genetic association studies database of human DNA repair system. It presents information on repair genes, assorted mechanisms of DNA repair, linkage disequilibrium, haplotype blocks, nsSNPs, phosphorylation sites, associated diseases, and pathways involved in repair systems. DNA repair is an intricate process which plays an essential role in maintaining the integrity of the genome by eradicating the damaging effect of internal and external changes in the genome. Hence, it is crucial to extensively understand the intact process of DNA repair, genes involved, non-synonymous SNPs which perhaps affect the function, phosphorylated residues and other related genetic parameters. All the corresponding entries for DNA repair genes, such as proteins, OMIM IDs, literature references and pathways are cross-referenced to their respective primary databases. DNA repair genes and their associated parameters are either represented in tabular or in graphical form through images elucidated by computational and statistical analyses. It is believed that the database will assist molecular biologists, biotechnologists, therapeutic developers and other scientific community to encounter biologically meaningful information, and meticulous contribution of genetic level information towards treacherous diseases in human DNA repair systems. DR-GAS is freely available for academic and research purposes at: http://www.bioinfoindia.org/drgas. Copyright © 2014 Elsevier B.V. All rights reserved.

Nature versus nurture in determining athletic ability.

PubMed

Brutsaert, Tom D; Parra, Esteban J

2009-01-01

This chapter provides an overview of the truism that both nature and nurture determine human athletic ability. The major thesis developed is that environmental effects work through the process of growth and development and interact with an individual's genetic background to produce a specific adult phenotype, i.e. an athletic or nonathletic phenotype. On the nature side (genetics), a brief historical review is provided with emphasis on several areas that are likely to command future attention including the rise of genome-wide association as a mapping strategy, the problem of false positives using association approaches, as well as the relatively unknown effects of gene-gene interaction(epistasis), gene-environment interaction, and genome structure on complex trait variance. On the nurture side (environment), common environmental effects such as training-level and sports nutrition are largely ignored in favor of developmental environmental effects that are channeled through growth and development processes. Developmental effects are difficult to distinguish from genetic effects as phenotypic plasticity in response to early life environmental perturbation can produce lasting effects into adulthood. In this regard, the fetal programming (FP) hypothesis is reviewed in some detail as FP provides an excellent example of how developmental effects work and also interact with genetics. In general, FP has well-documented effects on adult body composition and the risk for adult chronic disease, but there is emerging evidence that FP affects human athletic performance as well. 2009 S. Karger AG, Basel

Testing Domestication Scenarios of Lima Bean (Phaseolus lunatus L.) in Mesoamerica: Insights from Genome-Wide Genetic Markers

PubMed Central

Chacón-Sánchez, María I.; Martínez-Castillo, Jaime

2017-01-01

Plant domestication can be seen as a long-term process that involves a complex interplay among demographic processes and evolutionary forces. Previous studies have suggested two domestication scenarios for Lima bean in Mesoamerica: two separate domestication events, one from gene pool MI in central-western Mexico and another one from gene pool MII in the area Guatemala-Costa Rica, or a single domestication from gene pool MI in central-western Mexico followed by post-domestication gene flow with wild populations. In this study we evaluated the genetic structure of the wild gene pool and tested these two competing domestication scenarios of Lima bean in Mesoamerica by applying an ABC approach to a set of genome-wide SNP markers. The results confirm the existence of three gene pools in wild Lima bean, two Mesoamerican gene pools (MI and MII) and the Andean gene pool (AI), and suggest the existence of another gene pool in central Colombia. The results indicate that although both domestication scenarios may be supported by genetic data, higher statistical support was given to the single domestication scenario in central-western Mexico followed by admixture with wild populations. Domestication would have involved strong founder effects reflected in loss of genetic diversity and increased LD levels in landraces. Genomic regions affected by selection were detected and these may harbor candidate genes related to domestication. PMID:28955351

Genetic manipulations in aquaculture: a review of stock improvement by classical and modern technologies.

PubMed

Hulata, G

2001-01-01

The aim of this review was to highlight the extent to which the genetic technologies are implemented by the aquaculture industry. The review shows that some of the modern genetic technologies are already extensively applied by the diverse aquaculture industries, though not to the same extent for all important aquacultured species (according to FAO 1998 figures). Some species (common carp, Atlantic salmon, rainbow trout, channel catfish, Nile tilapia, and the Pacific oyster) received concentrated breeding efforts, while other major cultured species (Chinese and Indian carps and the giant tiger shrimp) received, so far, relatively limited attention, and a few species (Yesso scallop, blue mussel, white Amur bream, and milkfish) have, apparently, not been genetically improved at all. Most of the genetically improved strains reaching the aquaculture industry were developed through traditional selective breeding (selection, crossbreeding, and hybridization). Emerging, more modern technologies for genetic manipulation seem to take 10-20 years from being established experimentally until applications affect the industry. Thus, chromosome-set and sex manipulations started to affect the industry during the 1980's and 1990's. DNA marker technology and gene manipulations have yet hardly affected the industry. The former have not matured yet, but hold much promise. The latter could have affected the industry already had it not been restricted by public concern.

Familial Hypercholesterolemia: A Systematic Review of Guidelines on Genetic Testing and Patient Management.

PubMed

Migliara, Giuseppe; Baccolini, Valentina; Rosso, Annalisa; D'Andrea, Elvira; Massimi, Azzurra; Villari, Paolo; De Vito, Corrado

2017-01-01

Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in premature coronary heart disease and, if untreated, death. Recent studies have shown its prevalence to be higher than previously considered, which has important implications for the mortality and morbidity of associated cardiovascular disease (CVD). Several clinical tools are used worldwide to help physicians diagnose FH, but nevertheless most patients remain undetected. This systematic review of guidelines aims to assess the role of genetic testing in the screening, diagnosis, and management of patients affected by heterozygous or homozygous FH and to identify related health-care pathways. We performed a systematic review of the literature; inclusion criteria were English or Italian guidelines focusing on genetic testing. The guidelines were included and evaluated for their content and development process using the Appraisal of Guidelines for Research and Evaluation II instrument. Ten guidelines were considered eligible, and all were judged to be of good quality, with slight differences among them. The most common indications for performing genetic tests were high levels of cholesterol, or physical findings consistent with lipid disorder, in the subject or in the family history. Subsequent screening of family members was indicated when a mutation had been identified in the index patient. Regarding patient management, the various guidelines agreed that intensive treatment with lipid-lowering medications should begin as quickly as possible and that lifestyle modifications should be an integral part of the therapy. Since the early detection of affected patients is beneficial for effective prevention of CVD, genetic testing is particularly useful for identifying family members via cascade screening and for distinguishing between heterozygous and homozygous individuals, the latter of which require more extreme therapeutic intervention.

Subliminal (latent) processing of pain and its evolution to conscious awareness

PubMed Central

Borsook, David; Youssef, Andrew M.; Barakat, Nadia; Sieberg, Christine B.; Elman, Igor

2018-01-01

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, re-organization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic status) contribute to enhancing or inhibiting the presentation of pain awareness. Here we put forward the notion that for many patients, ongoing sub-conscious changes in brain function are significant players in the eventual manifestation of chronic pain. In this review, we provide clinical examples of nascent or what we term pre-pain processes and the neurobiological mechanisms of how these changes may contribute to pain, but also potential opportunities to define the process for early therapeutic interventions. PMID:29476771

Subliminal (latent) processing of pain and its evolution to conscious awareness.

PubMed

Borsook, David; Youssef, Andrew M; Barakat, Nadia; Sieberg, Christine B; Elman, Igor

2018-05-01

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, reorganization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic status) contribute to enhancing or inhibiting the presentation of pain awareness. Here we put forward the notion that for many patients, ongoing sub-conscious changes in brain function are significant players in the eventual manifestation of chronic pain. In this review, we provide clinical examples of nascent or what we term pre-pain processes and the neurobiological mechanisms of how these changes may contribute to pain, but also potential opportunities to define the process for early therapeutic interventions. Copyright © 2018. Published by Elsevier Ltd.

Chemical genomics: characterizing target pathways for bioactive compounds using the endomembrane trafficking network.

PubMed

Rodriguez-Furlán, Cecilia; Hicks, Glenn R; Norambuena, Lorena

2014-01-01

The plant endomembrane trafficking system is a highly complex set of processes. This complexity presents a challenge for its study. Classical plant genetics often struggles with loss-of-function lethality and gene redundancy. Chemical genomics allows overcoming many of these issues by using small molecules of natural or synthetic origin to inhibit specific trafficking proteins thereby affecting the processes in a tunable and reversible manner. Bioactive chemicals identified by high-throughput phenotype screens must be characterized in detail starting with understanding of the specific trafficking pathways affected. Here, we describe approaches to characterize bioactive compounds that perturb vesicle trafficking. This should equip researchers with practical knowledge on how to identify endomembrane-specific trafficking pathways that may be perturbed by specific compounds and will help to eventually identify molecular targets for these small molecules.

Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re-introduced Asiatic wild ass.

PubMed

Renan, Sharon; Greenbaum, Gili; Shahar, Naama; Templeton, Alan R; Bouskila, Amos; Bar-David, Shirli

2015-04-01

Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re-introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re-introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re-introduced population's genetic diversity could have significant consequences for the long-term persistence of the population in the Negev. The stochastic modelling approach and the use of allele-frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited. © 2015 John Wiley & Sons Ltd.

Low but significant genetic differentiation underlies biologically meaningful phenotypic divergence in a large Atlantic salmon population.

PubMed

Aykanat, Tutku; Johnston, Susan E; Orell, Panu; Niemelä, Eero; Erkinaro, Jaakko; Primmer, Craig R

2015-10-01

Despite decades of research assessing the genetic structure of natural populations, the biological meaning of low yet significant genetic divergence often remains unclear due to a lack of associated phenotypic and ecological information. At the same time, structured populations with low genetic divergence and overlapping boundaries can potentially provide excellent models to study adaptation and reproductive isolation in cases where high-resolution genetic markers and relevant phenotypic and life history information are available. Here, we combined single nucleotide polymorphism (SNP)-based population inference with extensive phenotypic and life history data to identify potential biological mechanisms driving fine-scale subpopulation differentiation in Atlantic salmon (Salmo salar) from the Teno River, a major salmon river in Europe. Two sympatrically occurring subpopulations had low but significant genetic differentiation (FST  = 0.018) and displayed marked differences in the distribution of life history strategies, including variation in juvenile growth rate, age at maturity and size within age classes. Large, late-maturing individuals were virtually absent from one of the two subpopulations, and there were significant differences in juvenile growth rates and size at age after oceanic migration between individuals in the respective subpopulations. Our findings suggest that different evolutionary processes affect each subpopulation and that hybridization and subsequent selection may maintain low genetic differentiation without hindering adaptive divergence. © 2015 John Wiley & Sons Ltd.

Matching genetics with oceanography: directional gene flow in a Mediterranean fish species.

PubMed

Schunter, C; Carreras-Carbonell, J; Macpherson, E; Tintoré, J; Vidal-Vijande, E; Pascual, A; Guidetti, P; Pascual, M

2011-12-01

Genetic connectivity and geographic fragmentation are two opposing mechanisms determining the population structure of species. While the first homogenizes the genetic background across populations the second one allows their differentiation. Therefore, knowledge of processes affecting dispersal of marine organisms is crucial to understand their genetic distribution patterns and for the effective management of their populations. In this study, we use genetic analyses of eleven microsatellites in combination with oceanographic satellite and dispersal simulation data to determine distribution patterns for Serranus cabrilla, a ubiquitous demersal broadcast spawner, in the Mediterranean Sea. Pairwise population F(ST) values ranged between -0.003 and 0.135. Two genetically distinct clusters were identified, with a clear division located between the oceanographic discontinuities at the Ibiza Channel (IC) and the Almeria-Oran Front (AOF), revealing an admixed population in between. The Balearic Front (BF) also appeared to dictate population structure. Directional gene flow on the Spanish coast was observed as S. cabrilla dispersed from west to east over the AOF, from north to south on the IC and from south of the IC towards the Balearic Islands. Correlations between genetic and oceanographic data were highly significant. Seasonal changes in current patterns and the relationship between ocean circulation patterns and spawning season may also play an important role in population structure around oceanographic fronts. © 2011 Blackwell Publishing Ltd.

Reduced Genetic Diversity and Increased Dispersal in Guigna (Leopardus guigna) in Chilean Fragmented Landscapes.

PubMed

Napolitano, Constanza; Díaz, Diego; Sanderson, Jim; Johnson, Warren E; Ritland, Kermit; Ritland, Carol E; Poulin, Elie

2015-01-01

Landscape fragmentation is often a major cause of species extinction as it can affect a wide variety of ecological processes. The impact of fragmentation varies among species depending on many factors, including their life-history traits and dispersal abilities. Felids are one of the groups most threatened by fragmented landscapes because of their large home ranges, territorial behavior, and low population densities. Here, we model the impacts of habitat fragmentation on patterns of genetic diversity in the guigna (Leopardus guigna), a small felid that is closely associated with the heavily human-impacted temperate rainforests of southern South America. We assessed genetic variation in 1798 base pairs of mitochondrial DNA sequences, 15 microsatellite loci, and 2 sex chromosome genes and estimated genetic diversity, kinship, inbreeding, and dispersal in 38 individuals from landscapes with differing degrees of fragmentation on Chiloé Island in southern Chile. Increased fragmentation was associated with reduced genetic diversity, but not with increased kinship or inbreeding. However, in fragmented landscapes, there was a weaker negative correlation between pairwise kinship and geographic distance, suggesting increased dispersal distances. These results highlight the importance of biological corridors to maximize connectivity in fragmented landscapes and contribute to our understanding of the broader genetic consequences of habitat fragmentation, especially for forest-specialist carnivores. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Micro-evolution due to pollution: possible consequences for ecosystem responses to toxic stress.

PubMed

Medina, Matías H; Correa, Juan A; Barata, Carlos

2007-05-01

Polluting events can change community structure and ecosystem functioning. Selection of genetically inherited tolerance on exposed populations, here referred as micro-evolution due to pollution, has been recognized as one of the causes of these changes. However, there is a gap between studies addressing this process and those assessing effects at higher levels of biological organization. In this review we attempt to address these evolutionary considerations into the ecological risk assessment (ERA) of polluting events and to trigger the discussion about the consequences of this process for the ecosystem response to toxic stress. We provide clear evidence that pollution drives micro-evolutionary processes in several species. When this process occurs, populations inhabiting environments that become polluted may persist. However, due to the existence of ecological costs derived from the loss of genetic variability, negative pleiotropy with fitness traits and/or from physiological alterations, micro-evolution due to pollution may alter different properties of the affected populations. Despite the existence of empirical evidence showing that safety margins currently applied in the ERA process may account for pollution-induced genetic changes in tolerance, information regarding long-term ecological consequences at higher levels of biological organization due to ecological costs is not explicitly considered in these procedures. In relation to this, we present four testable hypotheses considering that micro-evolution due to pollution acts upon the variability of functional response traits of the exposed populations and generates changes on their functional effect traits, therefore, modifying the way species exploit their ecological niches and participate in the overall ecosystem functioning.

Facial affect recognition deficit as a marker of genetic vulnerability to schizophrenia.

PubMed

Alfimova, Margarita V; Abramova, Lilia I; Barhatova, Aleksandra I; Yumatova, Polina E; Lyachenko, Galina L; Golimbet, Vera E

2009-05-01

The aim of this study was to investigate the possibility that affect recognition impairments are associated with genetic liability to schizophrenia. In a group of 55 unaffected relatives of schizophrenia patients (parents and siblings) we examined the capacity to detect facially expressed emotions and its relationship to schizotypal personality, neurocognitive functioning, and the subject's actual emotional state. The relatives were compared with 103 schizophrenia patients and 99 healthy subjects without any family history of psychoses. Emotional stimuli were nine black-and-white photos of actors, who portrayed six basic emotions as well as interest, contempt, and shame. The results evidenced the affect recognition deficit in relatives, though milder than that in patients themselves. No correlation between the deficit and schizotypal personality measured with SPQ was detected in the group of relatives. Neither cognitive functioning, including attention, verbal memory and linguistic ability, nor actual emotional states accounted for their affect recognition impairments. The results suggest that the facial affect recognition deficit in schizophrenia may be related to genetic predisposition to the disorder and may serve as an endophenotype in molecular-genetic studies.

The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans

PubMed Central

Zheng, Ming; Zhang, Haili; Dill, David L.; Clark, J. David; Tu, Susan; Yablonovitch, Arielle L.; Tan, Meng How; Zhang, Rui; Rujescu, Dan; Wu, Manhong; Tessarollo, Lino; Vieira, Wilfred; Gottesman, Michael M.; Deng, Suhua; Eberlin, Livia S.; Zare, Richard N.; Billard, Jean-Martin; Gillet, Jean-Pierre; Li, Jin Billy; Peltz, Gary

2015-01-01

Background We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study. Methods and Findings A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered. Conclusions ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity. PMID:25647612

Familial Renal Cancer: Molecular Genetics and Surgical Management

PubMed Central

Barrisford, Glen W.; Singer, Eric A.; Rosner, Inger L.; Linehan, W. Marston; Bratslavsky, Gennady

2011-01-01

Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer. PMID:22312516

How spatio-temporal habitat connectivity affects amphibian genetic structure.

PubMed

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

2015-01-01

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

Neutral null models for diversity in serial transfer evolution experiments.

PubMed

Harpak, Arbel; Sella, Guy

2014-09-01

Evolution experiments with microorganisms coupled with genome-wide sequencing now allow for the systematic study of population genetic processes under a wide range of conditions. In learning about these processes in natural, sexual populations, neutral models that describe the behavior of diversity and divergence summaries have played a pivotal role. It is therefore natural to ask whether neutral models, suitably modified, could be useful in the context of evolution experiments. Here, we introduce coalescent models for polymorphism and divergence under the most common experimental evolution assay, a serial transfer experiment. This relatively simple setting allows us to address several issues that could affect diversity patterns in evolution experiments, whether selection is operating or not: the transient behavior of neutral polymorphism in an experiment beginning from a single clone, the effects of randomness in the timing of cell division and noisiness in population size in the dilution stage. In our analyses and discussion, we emphasize the implications for experiments aimed at measuring diversity patterns and making inferences about population genetic processes based on these measurements. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Optimization of Straight Cylindrical Turning Using Artificial Bee Colony (ABC) Algorithm

NASA Astrophysics Data System (ADS)

Prasanth, Rajanampalli Seshasai Srinivasa; Hans Raj, Kandikonda

2017-04-01

Artificial bee colony (ABC) algorithm, that mimics the intelligent foraging behavior of honey bees, is increasingly gaining acceptance in the field of process optimization, as it is capable of handling nonlinearity, complexity and uncertainty. Straight cylindrical turning is a complex and nonlinear machining process which involves the selection of appropriate cutting parameters that affect the quality of the workpiece. This paper presents the estimation of optimal cutting parameters of the straight cylindrical turning process using the ABC algorithm. The ABC algorithm is first tested on four benchmark problems of numerical optimization and its performance is compared with genetic algorithm (GA) and ant colony optimization (ACO) algorithm. Results indicate that, the rate of convergence of ABC algorithm is better than GA and ACO. Then, the ABC algorithm is used to predict optimal cutting parameters such as cutting speed, feed rate, depth of cut and tool nose radius to achieve good surface finish. Results indicate that, the ABC algorithm estimated a comparable surface finish when compared with real coded genetic algorithm and differential evolution algorithm.

Screening mosaic F1 females for mutations affecting zebrafish heart induction and patterning.

PubMed

Alexander, J; Stainier, D Y; Yelon, D

1998-01-01

The genetic pathways underlying the induction and anterior-posterior patterning of the heart are poorly understood. The recent emergence of the zebrafish model system now allows a classical genetic approach to such challenging problems in vertebrate development. Two large-scale screens for mutations affecting zebrafish embryonic development have recently been completed; among the hundreds of mutations identified were several that affect specific aspects of cardiac morphogenesis, differentiation, and function. However, very few mutations affecting induction and/or anterior-posterior patterning of the heart were identified. We hypothesize that a directed approach utilizing molecular markers to examine these particular steps of heart development will uncover additional such mutations. To test this hypothesis, we are conducting two parallel screens for mutations that affect either the induction or the anterior-posterior patterning of the zebrafish heart. As an indicator of cardiac induction, we examine expression of nkx2.5, the earliest known marker of precardiac mesoderm; to assess anterior-posterior patterning, we distinguish ventricle from atrium with antibodies that recognize different myosin heavy chain isoforms. In order to expedite the examination of a large number of mutations, we are screening the haploid progeny of mosaic F1 females. In these ongoing screens, we have identified four mutations that affect nkx2.5 expression as well as 21 that disrupt either ventricular or atrial development and thus far have recovered several of these mutations, demonstrating the value of our approach. Future analysis of these and other cardiac mutations will provide further insight into the processes of induction and anterior-posterior patterning of the heart.

[Environmental factors of longevity].

PubMed

Christen, Yves

2003-03-01

A PROBABLE ROLE: The great increase in life expectancy over the past decades and too short a time lapse for any major genetic mutations to intervene, are arguments in favour of the intervention of environmental factors in longevity. A FAIRLY LONG LIST: Various environmental factors can be envisaged: prenatal environment, pollution, radiation and oncogenic agents, notably tobacco, food (quantitatively and qualitatively), medicinal products, stress, education and socio-professional life style, isolation, number of children and sexual activity, sports and exercising, etc. It is highly likely that all these factors, or at least some of them, have a real effect on longevity, although this is difficult to demonstrate directly. A COMBINED EFFECT: The basic idea of this paper is that these environmental factors should be seen as agents, the effects of which would be combined with those of genetic factors, considered as agents of radically different nature. We suggest that, in order to have any real effect, these environmental factors have to work on the same cell mechanisms as those that affect the genetic process, notably the mechanisms related to oxidative stress and genetic expression.

Denoising of genetic switches based on Parrondo's paradox

NASA Astrophysics Data System (ADS)

Fotoohinasab, Atiyeh; Fatemizadeh, Emad; Pezeshk, Hamid; Sadeghi, Mehdi

2018-03-01

Random decision making in genetic switches can be modeled as tossing a biased coin. In other word, each genetic switch can be considered as a game in which the reactive elements compete with each other to increase their molecular concentrations. The existence of a very small number of reactive element molecules has caused the neglect of effects of noise to be inevitable. Noise can lead to undesirable cell fate in cellular differentiation processes. In this paper, we study the robustness to noise in genetic switches by considering another switch to have a new gene regulatory network (GRN) in which both switches have been affected by the same noise and for this purpose, we will use Parrondo's paradox. We introduce two networks of games based on possible regulatory relations between genes. Our results show that the robustness to noise can increase by combining these noisy switches. We also describe how one of the switches in network II can model lysis/lysogeny decision making of bacteriophage lambda in Escherichia coli and we change its fate by another switch.

A cognitive characterization of dyscalculia in Turner syndrome.

PubMed

Bruandet, Marie; Molko, Nicolas; Cohen, Laurent; Dehaene, Stanislas

2004-01-01

Current theories of number processing postulate that the human abilities for arithmetic are based on cerebral circuits that are partially laid down under genetic control and later modified by schooling and education. This view predicts the existence of genetic diseases that interfere specifically with components of the number system. Here, we investigate whether Turner syndrome (TS) corresponds to this definition. TS is a genetic disorder which affects one woman in 2500 and is characterized by partial or complete absence of one X chromosome. In addition to well-characterized physical and hormonal dysfunction, TS patients exhibit cognitive deficits including dyscalculia. We tested 12 women with Turner syndrome and 13 control subjects on a cognitive battery including arithmetical tests (addition, subtraction, multiplication, division) as well as tests of the understanding of numerosity and quantity (cognitive estimation, estimation, comparison, bisection, subitizing/counting). Impairments were observed in cognitive estimation, subitizing, and calculation. We examine whether these deficits can be attributed to a single source, and discuss the possible implications of hormonal and genetic factors in the neuropsychological profile of TS patients.

Research on prediction of agricultural machinery total power based on grey model optimized by genetic algorithm

NASA Astrophysics Data System (ADS)

Xie, Yan; Li, Mu; Zhou, Jin; Zheng, Chang-zheng

2009-07-01

Agricultural machinery total power is an important index to reflex and evaluate the level of agricultural mechanization. It is the power source of agricultural production, and is the main factors to enhance the comprehensive agricultural production capacity expand production scale and increase the income of the farmers. Its demand is affected by natural, economic, technological and social and other "grey" factors. Therefore, grey system theory can be used to analyze the development of agricultural machinery total power. A method based on genetic algorithm optimizing grey modeling process is introduced in this paper. This method makes full use of the advantages of the grey prediction model and characteristics of genetic algorithm to find global optimization. So the prediction model is more accurate. According to data from a province, the GM (1, 1) model for predicting agricultural machinery total power was given based on the grey system theories and genetic algorithm. The result indicates that the model can be used as agricultural machinery total power an effective tool for prediction.

The genomic era and serious mental illness: a potential application for psychiatric genetic counseling.

PubMed

Austin, Jehannine C; Honer, William G

2007-02-01

Genetic counseling is an important clinical service that is routinely offered to families affected by genetic disorders or by complex disorders for which genetic testing is available. It is not yet routinely offered to individuals with serious mental illnesses and their families, but recent findings that beliefs about the cause of mental illness can affect an individual's adaptation to the illness suggest that genetic counseling may be a useful intervention for this population. In a genetic counseling session the counselor discusses genetic and environmental contributors to disease pathogenesis; helps individuals explore conceptions, fears, and adaptive strategies; and provides nondirective support for decision making. Expected outcomes may include reductions in fear, stigma, and guilt associated with a psychiatric diagnosis; improvements in adherence to prescribed medications; declines in risk behaviors; and reductions in misconceptions about the illness. The authors endorse a multidisciplinary approach in which a psychiatrist and genetic counselor collaborate to provide comprehensive psychiatric genetic counseling.

Parents' perceptions of autism spectrum disorder etiology and recurrence risk and effects of their perceptions on family planning: Recommendations for genetic counselors.

PubMed

Selkirk, Christina G; McCarthy Veach, Patricia; Lian, Fengqin; Schimmenti, Lisa; LeRoy, Bonnie S

2009-10-01

Knowledge about the etiology of Autism Spectrum Disorders (ASDs) is increasing, but causes remain elusive for most cases. Genetic counselors are positioned to help families that have children with ASDs despite uncertainty regarding etiology. To determine how genetic counselors might best provide services, an anonymous survey was conducted with 255 parents whose children were diagnosed on the autism spectrum. Questions concerned: 1) their perceptions of ASD cause(s) and 2) recurrence risk, 3) whether perceived risk affected family planning decisions, 4) whether parents had received genetic services, and 5) how genetic counselors might assist families. The most prevalent perceived cause was genetic influences (72.6%). Most parents' recurrence risk perceptions were inaccurately high and significantly affected family planning. Only 10% had seen a genetic professional related to an ASD. Parents provided several suggestions for genetic counselor best practices. Findings indicate the importance of genetic counselor awareness of parent perceptions in order to best help families who have children with ASDs.

Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease

PubMed Central

Ghosh, Sujoy; Vivar, Juan; Nelson, Christopher P; Willenborg, Christina; Segrè, Ayellet V; Mäkinen, Ville-Petteri; Nikpay, Majid; Erdmann, Jeannette; Blankenberg, Stefan; O'Donnell, Christopher; März, Winfried; Laaksonen, Reijo; Stewart, Alexandre FR; Epstein, Stephen E; Shah, Svati H; Granger, Christopher B; Hazen, Stanley L; Kathiresan, Sekar; Reilly, Muredach P; Yang, Xia; Quertermous, Thomas; Samani, Nilesh J; Schunkert, Heribert; Assimes, Themistocles L; McPherson, Ruth

2016-01-01

Objective Genome-wide association (GWA) studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Approaches and Results Employing pathways (gene sets) from Reactome, we carried out a two-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CADGWAS data sets (9,889 cases/11,089 controls), nominally significant gene-sets were tested for replication in a meta-analysis of 9 additional studies (15,502 cases/55,730 controls) from the CARDIoGRAM Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication p<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix integrity, innate immunity, axon guidance, and signaling by PDRF, NOTCH, and the TGF-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (e.g. semaphorin regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared to random networks (p<0.001). Network centrality analysis (‘degree’ and ‘betweenness’) further identified genes (e.g. NCAM1, FYN, FURIN etc.) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. Conclusions These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. PMID:25977570

Heterotrophic cultivation of microalgae for production of biodiesel.

PubMed

Mohamed, Mohd Shamzi; Wei, Lai Zee; Ariff, Arbakariya B

2011-08-01

High cell density cultivation of microalgae via heterotrophic growth mechanism could effectively address the issues of low productivity and operational constraints presently affecting the solar driven biodiesel production. This paper reviews the progress made so far in the development of commercial-scale heterotrophic microalgae cultivation processes. The review also discusses on patentable concepts and innovations disclosed in the past four years with regards to new approaches to microalgal cultivation technique, improvisation on the process flow designs to economically produced biodiesel and genetic manipulation to confer desirable traits leading to much valued high lipid-bearing microalgae strains.

The Genetic and Environmental Factors Underlying Hypospadias

PubMed Central

Pask, Andrew; Heloury, Yves; Sinclair, Andrew H.

2016-01-01

Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200–300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgen erational epigenetic impacts. PMID:26613581

Longevity and aging. Mechanisms and perspectives.

PubMed

Labat-Robert, J; Robert, L

2015-12-01

Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not "coded" in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2016-11-01

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

Ethics and Neuropsychiatric Genetics: A Review of Major Issues

PubMed Central

Hoge, Steven K.; Appelbaum, Paul S.

2012-01-01

Advances in neuropsychiatric genetics hold great hopes for improved prevention, diagnosis, and treatment. However, the power of genetic testing to identify individuals at increased risk for disorders and to convey information about relatives creates a set of complex ethical issues. Public attitudes are inevitably affected by the shadow of eugenics, with its history of distorting scientific findings to serve socio-political ends. Nonetheless, the growing availability of genetic tests means that more patients will seek genetic information, and physicians must manage the process of informed consent to allow meaningful decisions. Patients should be helped to understand the often-limited predictive power of current knowledge, potential psychological impact, risks of stigma and discrimination, and possible implications for family members. Decisions for predictive testing of children raise additional concerns, including distortions of family dynamics and negative effects on children’s self-image; testing is best deferred until adulthood unless preventive interventions exist. Pharmacogenomic testing, part of personalized medicine, may bring collateral susceptibility information for which patients should be prepared. The implications of genetic findings for families raise the question of whether physicians have duties to inform family members of implications for their health. Finally, participation in research in neuropsychiatric genetics evokes a broad range of ethical concerns, including the contentious issue of the extent to which results should be returned to individual subjects. As genetic science becomes more widely applied, the public will become more sophisticated and will be likely to demand a greater role in determining social policy on these issues. PMID:22272758

Genetic and Epigenetic Variations Induced by Wheat-Rye 2R and 5R Monosomic Addition Lines

PubMed Central

Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

2013-01-01

Background Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. Methodology/Principal Findings In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. Conclusions/Significance The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat. PMID:23342073

Genetic and epigenetic variations induced by wheat-rye 2R and 5R monosomic addition lines.

PubMed

Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

2013-01-01

Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat.

Genetic Disorders

MedlinePlus

... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

Past, present, and future of a freshwater fish metapopulation in a threatened landscape.

PubMed

Vera-Escalona, Iván; Senthivasan, Shreeram; Habit, Evelyn; Ruzzante, Daniel E

2018-02-12

It is well documented that hydropower plants can affect the dynamics of fish populations through landscape alterations and the creation of new barriers. Less emphasis has been placed on the examination of the genetic consequences for fish populations of the construction of dams. The relatively few studies that focus on genetics often do not consider colonization history and even fewer tend to use this information for conservation purposes. As a case study, we used a 3-pronged approach to study the influence of historical processes, contemporary landscape features, and potential future anthropogenic changes in landscape on the genetic diversity of a fish metapopulation. Our goal was to identify the metapopulation's main attributes, detect priority areas for conservation, and assess the consequences of the construction of hydropower plants for the persistence of the metapopulation. We used microsatellite markers and coalescent approaches to examine historical colonization processes, traditional population genetics, and simulations of future populations under alternate scenarios of population size reduction and gene flow. Historical gene flow appeared to have declined relatively recently and contemporary populations appeared highly susceptible to changes in landscape. Gene flow is critical for population persistence. We found that hydropower plants could lead to a rapid reduction in number of alleles and to population extirpation 50-80 years after their construction. More generally, our 3-pronged approach for the analyses of empirical genetic data can provide policy makers with information on the potential impacts of landscape changes and thus lead to more robust conservation efforts. © 2018 Society for Conservation Biology.

Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.

PubMed

Banin, Eyal; Bandah-Rozenfeld, Dikla; Obolensky, Alexey; Cideciyan, Artur V; Aleman, Tomas S; Marks-Ohana, Devora; Sela, Malka; Boye, Sanford; Sumaroka, Alexander; Roman, Alejandro J; Schwartz, Sharon B; Hauswirth, William W; Jacobson, Samuel G; Hemo, Itzhak; Sharon, Dror

2010-12-01

The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.

Microsatellite based genetic diversity and population structure of the endangered Spanish Guadarrama goat breed

PubMed Central

Serrano, Magdalena; Calvo, Jorge H; Martínez, Marta; Marcos-Carcavilla, Ane; Cuevas, Javier; González, Carmen; Jurado, Juan J; de Tejada, Paloma Díez

2009-01-01

Background Assessing genetic biodiversity and population structure of minor breeds through the information provided by neutral molecular markers, allows determination of their extinction risk and to design strategies for their management and conservation. Analysis of microsatellite loci is known to be highly informative in the reconstruction of the historical processes underlying the evolution and differentiation of animal populations. Guadarrama goat is a threatened Spanish breed which actual census (2008) consists of 3057 females and 203 males distributed in 22 populations more or less isolated. The aim of this work is to study the genetic status of this breed through the analysis of molecular data from 10 microsatellites typed in historic and actual live animals. Results The mean expected heterozygosity across loci within populations ranged from 0.62 to 0.77. Genetic differentiation measures were moderate, with a mean FST of 0.074, GST of 0.081 and RST of 0.085. Percentages of variation among and within populations were 7.5 and 92.5, respectively. Bayesian clustering analyses pointed out a population subdivision in 16 clusters, however, no correlation between geographical distances and genetic differences was found. Management factors such as the limited exchange of animals between farmers (estimated gene flow Nm = 3.08) mostly due to sanitary and social constraints could be the major causes affecting Guadarrama goat population subdivision. Conclusion Genetic diversity measures revealed a good status of biodiversity in the Guadarrama goat breed. Since diseases are the first cause affecting the census in this breed, population subdivision would be an advantage for its conservation. However, to maintain private alleles present at low frequencies in such small populations minimizing the inbreeding rate, it would necessitate some mating designs of animals carrying such alleles among populations. The systematic use of molecular markers will facilitate the comprehensive management of these populations, which in combination with the actual breeding program to increase milk yield, will constitute a good strategy to preserve the breed. PMID:19785776

Toward diagnostic and phenotype markers for genetically transmitted speech delay.

PubMed

Shriberg, Lawrence D; Lewis, Barbara A; Tomblin, J Bruce; McSweeny, Jane L; Karlsson, Heather B; Scheer, Alison R

2005-08-01

Converging evidence supports the hypothesis that the most common subtype of childhood speech sound disorder (SSD) of currently unknown origin is genetically transmitted. We report the first findings toward a set of diagnostic markers to differentiate this proposed etiological subtype (provisionally termed speech delay-genetic) from other proposed subtypes of SSD of unknown origin. Conversational speech samples from 72 preschool children with speech delay of unknown origin from 3 research centers were selected from an audio archive. Participants differed on the number of biological, nuclear family members (0 or 2+) classified as positive for current and/or prior speech-language disorder. Although participants in the 2 groups were found to have similar speech competence, as indexed by their Percentage of Consonants Correct scores, their speech error patterns differed significantly in 3 ways. Compared with children who may have reduced genetic load for speech delay (no affected nuclear family members), children with possibly higher genetic load (2+ affected members) had (a) a significantly higher proportion of relative omission errors on the Late-8 consonants; (b) a significantly lower proportion of relative distortion errors on these consonants, particularly on the sibilant fricatives /s/, /z/, and //; and (c) a significantly lower proportion of backed /s/ distortions, as assessed by both perceptual and acoustic methods. Machine learning routines identified a 3-part classification rule that included differential weightings of these variables. The classification rule had diagnostic accuracy value of 0.83 (95% confidence limits = 0.74-0.92), with positive and negative likelihood ratios of 9.6 (95% confidence limits = 3.1-29.9) and 0.40 (95% confidence limits = 0.24-0.68), respectively. The diagnostic accuracy findings are viewed as promising. The error pattern for this proposed subtype of SSD is viewed as consistent with the cognitive-linguistic processing deficits that have been reported for genetically transmitted verbal disorders.

Parental smoking and children's attention to smoking cues.

PubMed

Lochbuehler, Kirsten; Otten, Roy; Voogd, Hubert; Engels, Rutger C M E

2012-07-01

Research has shown that children with smoking parents are more likely to initiate smoking than children with non-smoking parents. So far, these effects have been explained through genetic factors, modelling and norm-setting processes. However, it is also possible that parental smoking affects smoking initiation through automatic cognitive processes. Therefore, we examined whether children with a smoking parent focus longer, faster and more often on smoking cues. The children were given two movie clips to watch, during which their attention to smoking cues was assessed with eye-tracking technology. Results showed that children with a smoking parent focused more often and longer on smoking cues compared with children with non-smoking parents. No correlations between attentional bias and explicit smoking cognitions were found. In conclusion, results suggest that parental smoking affects children's attention to smoking cues. These findings may indicate that parental smoking instigates automatic cognitive processes in children who have not experimented with smoking, and possibly even before explicit smoking cognitions become more favourable.

Infrared thermal facial image sequence registration analysis and verification

NASA Astrophysics Data System (ADS)

Chen, Chieh-Li; Jian, Bo-Lin

2015-03-01

To study the emotional responses of subjects to the International Affective Picture System (IAPS), infrared thermal facial image sequence is preprocessed for registration before further analysis such that the variance caused by minor and irregular subject movements is reduced. Without affecting the comfort level and inducing minimal harm, this study proposes an infrared thermal facial image sequence registration process that will reduce the deviations caused by the unconscious head shaking of the subjects. A fixed image for registration is produced through the localization of the centroid of the eye region as well as image translation and rotation processes. Thermal image sequencing will then be automatically registered using the two-stage genetic algorithm proposed. The deviation before and after image registration will be demonstrated by image quality indices. The results show that the infrared thermal image sequence registration process proposed in this study is effective in localizing facial images accurately, which will be beneficial to the correlation analysis of psychological information related to the facial area.

The clinical content of preconception care: genetics and genomics.

PubMed

Solomon, Benjamin D; Jack, Brian W; Feero, W Gregory

2008-12-01

The prevalence of paternal and maternal genetic conditions that affect pregnancy varies according to many factors that include parental age, medical history, and family history. Although some genetic conditions that affect pregnancy are identified easily early in life, other conditions are not and may require additional diagnostic testing. A complete 3-generation family medical history that includes ethnicity information about both sides of the family is arguably the single best genetic "test" that is applicable to preconception care. Assessment of genetic risk by an experienced professional has been shown to improve the detection rate of identifiable risk factors. Learning about possible genetic issues in the preconception period is ideal, because knowledge permits patients to make informed reproductive decisions. Options that are available to couples before conception include adoption, surrogacy, use of donor sperm, in vitro fertilization after preimplantation genetic diagnosis, and avoidance of pregnancy. Future technologic advances will increase the choices that are available to couples.

The Clinical Content of Preconception Care: Genetics and Genomics

PubMed Central

SOLOMON, Benjamin D.; JACK, Brian; FEERO, W. Gregory

2008-01-01

The prevalence of paternal and maternal genetic conditions that affect pregnancy varies according to many factors, including parental age, medical history, and family history. While some genetic conditions that affect pregnancy are easily identified early in life, others are not and may require additional diagnostic testing. A complete three-generation family medical history that includes ethnicity information about both sides of the family is arguably the single best genetic “test” applicable to preconception care. Assessment of genetic risk by an experienced professional has been shown to improve the detection rate of identifiable risk factors. Learning about possible genetic issues in the pre-conception period is ideal, as knowledge permits patients to make informed reproductive decisions. Options available to couples before conception include adoption, surrogacy, use of donor sperm, in vitro fertilization after pre-implantation genetic diagnosis, and avoidance of pregnancy. Future technological advances will increase the choices available to couples. PMID:19081428

When to suspect a genetic syndrome.

PubMed

Solomon, Benjamin D; Muenke, Maximilian

2012-11-01

Family physicians should be able to recognize findings on physical examination and history that suggest the presence of a genetic syndrome to aid in the diagnosis and treatment of potentially affected patients, as well as subspecialty referral. General themes that can alert family physicians to the presence of genetic conditions include dysmorphic features that are evident on physical examination; multiple anomalies in one patient; unexplained neurocognitive impairment; and a family history that is suggestive of a hereditary disease. The presence of one obvious malformation should not limit the full evaluation, because additional, subtler findings will often be important in the differential diagnosis. Taking an accurate three-generation family history is invaluable when considering a genetic syndrome. Important elements include the age and sex of family members; when family members were affected by disease or when they died; the ethnic background; and if there is consanguinity. Genetic subspecialists can assist family physicians in diagnosis, suggest additional testing and referrals if warranted, help direct medical care, and provide counseling for affected patients and their families.

Reasonable Foreseeability and Liability in Relation to Genetically Modified Organisms

ERIC Educational Resources Information Center

Khoury, Lara; Smyth, Stuart

2007-01-01

This article examines problems that may arise when addressing liability resulting from the genetic modification of microbes, animals, and plants. More specifically, it evaluates how uncertainties relating to the outcomes of these biotechnological innovations affect--or may affect--the courts' application of the reasonable foreseeability…

Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns.

PubMed

Enge, Martin; Arda, H Efsun; Mignardi, Marco; Beausang, John; Bottino, Rita; Kim, Seung K; Quake, Stephen R

2017-10-05

As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Oncogenomic disruptions in arsenic-induced carcinogenesis

PubMed Central

Ng, Kevin W.; Stewart, Greg L.; Dummer, Trevor J.B.; Lam, Wan L.; Martinez, Victor D

2017-01-01

Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process. PMID:28179585

Environmental-stress-induced Chromatin Regulation and its Heritability

PubMed Central

Fang, Lei; Wuptra, Kenly; Chen, Danqi; Li, Hongjie; Huang, Shau-Ku; Jin, Chunyuan; Yokoyama, Kazunari K

2014-01-01

Chromatin is subject to proofreading and repair mechanisms during the process of DNA replication, as well as repair to maintain genetic and epigenetic information and genome stability. The dynamic structure of chromatin modulates various nuclear processes, including transcription and replication, by altering the accessibility of the DNA to regulatory factors. Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodeling of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by controlling stochastic switching of chromatin structure and dynamics in response to the environmental disruptors and endogenous stresses. The dynamic chromatin remodeling can, therefore, serve as a sensor, through which environmental and/or metabolic agents can alter gene expression, leading to global cellular changes involving multiple interactive networks. Furthermore its recent evidence also suggests that the epigenetic changes are heritable during the development. This review will discuss the environmental sensing system for chromatin regulation and genetic and epigenetic controls from developmental perspectives. PMID:25045581

Dissecting genomic imprinting and genetic conflict from a game theory prospective. Comment on: ;Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition; by Qian Wang et al.

NASA Astrophysics Data System (ADS)

Cui, Yuehua; Yang, Haitao

2017-03-01

Epigenetics typically refers to changes in the structure of a chromosome that affect gene activity and expression. Genomic imprinting is a special type of epigenetic phenomenon in which the expression of an allele depends on its parental origin. When an allele inherited from the mother (or father) is imprinted (i.e., silent), it is termed as maternal (or paternal) imprinting. Imprinting is often resulted from DNA methylation and tends to cluster together in the genome [1]. It has been shown to play a key role in many genetic disorders in humans [2]. Imprinting is heritable and undergoes a reprogramming process in gametes before and after fertilization [1]. Sometimes the reprogramming process is not reversible, leading to the loss of imprinting [3]. Although efforts have been made to experimentally or computationally infer imprinting genes, the underlying molecular mechanism that leads to unbalanced allelic expression is still largely unknown.

Genetic effects on gene expression across human tissues

PubMed Central

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease. PMID:29022597

Genetic effects on gene expression across human tissues.

PubMed

Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

2017-10-11

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging *

PubMed Central

Afornali, Alessandro; de Vecchi, Rodrigo; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; de Oliveira, Luciana Lima; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

2013-01-01

BACKGROUND The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. PMID:24474102

Perspective on the Genetic Response to Antiparasitics: A Review Article

PubMed Central

ALARCON-VALDES, Patricia; ORTIZ-REYNOSO, Mariana; SANTILLAN-BENITEZ, Jonnathan

2017-01-01

Background: Drugs’ pharmacokinetics and pharmacodynamics can be affected by diverse genetic variations, within which simple nucleotide polymorphisms (SNPs) are the most common. Genetic variability is one of the factors that could explain questions like why a given drug does not have the desired effect or why do adverse drug reactions arise. Methods: In this retrospective observational study, literature search limits were set within PubMed database as well as the epidemiological bulletins published by the Mexican Ministry of Health, from Jan 1st 2001 to Mar 31st 2017 (16 years). Results: Metabolism of antiparasitic drugs and their interindividual responses are mainly modified by variations in cytochrome P450 enzymes. These enzymes show high frequencies of polymorphic variability thus affecting the expression of CYP2C, CYP2A, CYP2A6, CYP2D6, CYP2E6 and CYP2A6 isoforms. Research in this field opens the door to new personalized treatment approaches in medicine. Conclusion: Clinical and pharmacological utility yield by applying pharmacogenetics to antiparasitic treatments is not intended as a mean to improve the prescription process, but to select or exclude patients that could present adverse drug reactions as well as to evaluate genetic alterations which result in a diversity of responses, ultimately seeking to provide a more effective and safe treatment; therefore choosing a proper dose for the appropriate patient and the optimal treatment duration. Furthermore, pharmacogenetics assists in the development of vaccines. In other words, the aim of this discipline is to find therapeutic targets allowing personalized treatments. PMID:29317871

Pharmacogenetics and Imaging-Pharmacogenetics of Antidepressant Response: Towards Translational Strategies.

PubMed

Lett, Tristram A; Walter, Henrik; Brandl, Eva J

2016-12-01

Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment. The purpose of this article is to provide a comprehensive review of the advances made in the field of pharmacogenetics of antidepressant efficacy and side effects, imaging findings of antidepressant response, and the latest results in the expanding field of imaging-pharmacogenetics studies. We suggest there is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. The most promising imaging-pharmacogenetics findings exist for the SCL6A4 gene, with converging associations with antidepressant response, frontolimbic predictors of affective symptoms, and normalization of frontolimbic activity following antidepressant treatment. More research is required before imaging-pharmacogenetics informed personalized medicine can be applied to antidepressant treatment; nevertheless, inroads have been made towards assessing genetic and neuroanatomical liability and potential clinical application.

Rapid contemporary evolution and clonal food web dynamics

PubMed Central

Jones, Laura E.; Becks, Lutz; Ellner, Stephen P.; Hairston, Nelson G.; Yoshida, Takehito; Fussmann, Gregor F.

2009-01-01

Character evolution that affects ecological community interactions often occurs contemporaneously with temporal changes in population size, potentially altering the very nature of those dynamics. Such eco-evolutionary processes may be most readily explored in systems with short generations and simple genetics. Asexual and cyclically parthenogenetic organisms such as microalgae, cladocerans and rotifers, which frequently dominate freshwater plankton communities, meet these requirements. Multiple clonal lines can coexist within each species over extended periods, until either fixation occurs or a sexual phase reshuffles the genetic material. When clones differ in traits affecting interspecific interactions, within-species clonal dynamics can have major effects on the population dynamics. We first consider a simple predator–prey system with two prey genotypes, parametrized with data from a well-studied experimental system, and explore how the extent of differences in defence against predation within the prey population determine dynamic stability versus instability of the system. We then explore how increased potential for evolution affects the community dynamics in a more general community model with multiple predator and multiple prey genotypes. These examples illustrate how microevolutionary ‘details’ that enhance or limit the potential for heritable phenotypic change can have significant effects on contemporaneous community-level dynamics and the persistence and coexistence of species. PMID:19414472

Human genetics and sleep behavior.

PubMed

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

2017-06-01

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

Genetic Brain Disorders

MedlinePlus

A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form ... mutation is a change in a gene. Genetic brain disorders affect the development and function of the ...

Genetic profile for five common variants associated with age-related macular degeneration in densely affected families: a novel analytic approach

PubMed Central

Sobrin, Lucia; Maller, Julian B; Neale, Benjamin M; Reynolds, Robyn C; Fagerness, Jesen A; Daly, Mark J; Seddon, Johanna M

2010-01-01

About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes. PMID:19844262

How spatio-temporal habitat connectivity affects amphibian genetic structure

PubMed Central

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

2015-01-01

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

How spatio-temporal habitat connectivity affects amphibian genetic structure

USGS Publications Warehouse

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

2015-01-01

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

Genetic Improvement of Switchgrass and Other Herbaceous Plants for Use as Biomass Fuel Feedstock

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

Vogel, K.P.

2001-01-11

It should be highly feasible to genetically modify the feedstock quality of switchgrass and other herbaceous plants using both conventional and molecular breeding techniques. Effectiveness of breeding to modify herbages of switchgrass and other perennial and annual herbaceous species has already been demonstrated. The use of molecular markers and transformation technology will greatly enhance the capability of breeders to modify the plant structure and cell walls of herbaceous plants. It will be necessary to monitor gene flow to remnant wild populations of plants and have strategies available to curtail gene flow if it becomes a potential problem. It also willmore » be necessary to monitor plant survival and long-term productivity as affected by genetic changes that improve forage quality. Information on the conversion processes that will be used and the biomass characteristics that affect conversion efficiency and rate is absolutely essential as well as information on the relative economic value of specific traits. Because most forage or biomass quality characteristics are highly affected by plant maturity, it is suggested that plant material of specific maturity stages be used in research to determining desirable feedstock quality characteristics. Plant material could be collected at various stages of development from an array of environments and storage conditions that could be used in conversion research. The same plant material could be used to develop NIRS calibrations that could be used by breeders in their selection programs and also to develop criteria for a feedstock quality assessment program. Breeding for improved feedstock quality will likely affect the rate of improvement of biomass production per acre. If the same level of resources are used, multi-trait breeding simply reduces the selection pressure and hence the breeding progress that can be made for a single trait unless all the traits are highly correlated. Since desirable feedstock traits are likely to be similar to IVDMD, it is likely that they will not be highly positively correlated with yield. Hence to achieve target yields and improve specific quality traits, it will likely be necessary to increase the resources available to plant breeders. Marker assisted selection will be extremely useful in breeding for quality traits, particularly for traits that can be affected by modifying a few genes. Genetic markers are going to be needed for monitoring gene flow to wild populations. Transformation will be a very useful tool for determining the affects of specific genes on biomass feedstock quality.« less

A comprehensive assessment of cognitive function in the common genetic generalized epilepsy syndromes.

PubMed

Loughman, A; Bowden, S C; D'Souza, W J

2017-03-01

Considered to be benign conditions, the common genetic generalized epilepsy (GGE) syndromes are now known to be frequently accompanied by cognitive dysfunction. However, unresolved issues impede clinical management of this common comorbidity, including which cognitive abilities are most affected, whether there are differences between syndromes and how seizure type and mood symptoms affect cognitive dysfunction. We provide a detailed description of cognitive ability and evaluate factors contributing to cognitive dysfunction. A total of 76 adults with GGE were assessed with the Woodcock Johnson III Tests of Cognitive Abilities. Scores on tests of overall cognitive ability, acquired knowledge, long-term retrieval and speed of information processing were significantly below the normative mean. Long-term retrieval was a pronounced weakness with a large reduction in scores (d = 0.84). GGE syndrome, seizure type and the presence of recent psychopathology symptoms were not significantly associated with cognitive function. This study confirms previous meta-analytic findings with a prospective study, offers new insights into the cognitive comorbidity of these common epilepsy syndromes and reinforces the need for cognitive interventions in people with GGE. © 2016 EAN.

The evolutionary and ecological consequences of animal social networks: emerging issues.

PubMed

Kurvers, Ralf H J M; Krause, Jens; Croft, Darren P; Wilson, Alexander D M; Wolf, Max

2014-06-01

The first generation of research on animal social networks was primarily aimed at introducing the concept of social networks to the fields of animal behaviour and behavioural ecology. More recently, a diverse body of evidence has shown that social fine structure matters on a broader scale than initially expected, affecting many key ecological and evolutionary processes. Here, we review this development. We discuss the effects of social network structure on evolutionary dynamics (genetic drift, fixation probabilities, and frequency-dependent selection) and social evolution (cooperation and between-individual behavioural differences). We discuss how social network structure can affect important coevolutionary processes (host-pathogen interactions and mutualisms) and population stability. We also discuss the potentially important, but poorly studied, role of social network structure on dispersal and invasion. Throughout, we highlight important areas for future research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of behavioral genetic evidence on the adjudication of criminal behavior.

PubMed

Appelbaum, Paul S; Scurich, Nicholas

2014-01-01

Recent advances in behavioral genetics suggest a modest relationship among certain gene variants, early childhood experiences, and criminal behavior. Although scientific research examining this link is still at an early stage, genetic data are already being introduced in criminal trials. However, the extent to which such evidence is likely to affect jurors' decisions has not been explored. In the present study, a representative sample of the U.S. population (n = 250) received a vignette describing an apparently impulsive homicide, accompanied by one of four explanations of the defendant's impulsivity: childhood abuse, genetic predisposition, childhood abuse and genetic predisposition, or simple impulsive behavior. The participants were asked to identify the crime that the defendant had committed and to select an appropriate sentence range. Evidence of genetic predisposition did not affect the crime of which the defendant was convicted or the sentence. However, participants who received the abuse or genetic + abuse explanation imposed longer prison sentences. Paradoxically, the genetic and genetic + abuse conditions engendered the greatest fear of the defendant. These findings should allay concerns that genetic evidence in criminal adjudications will be overly persuasive to jurors, but should raise questions about the impact of genetic attributions on perceptions of dangerousness.

Impact of Behavioral Genetic Evidence on the Adjudication of Criminal Behavior

PubMed Central

Appelbaum, Paul S.; Scurich, Nicholas

2013-01-01

Recent advances in behavioral genetics suggest a modest relationship among certain gene variants, early childhood experiences, and criminal behavior. Although scientific research examining this link is still at an early stage, genetic data are already being introduced in criminal trials. However, the extent to which such evidence is likely to affect jurors’ decisions has not previously been explored. In the present study, a representative sample of the U.S. population (n=250) received a vignette describing an apparently impulsive homicide, accompanied by one of four explanations of the defendant’s impulsivity: childhood abuse; genetic predisposition; childhood abuse and genetic predisposition; or simple impulsive behavior. Participants were asked to identify the crime that the defendant had committed and to select an appropriate sentence range. Evidence of genetic predisposition did not affect the crime of which the defendant was convicted or the sentence. However, participants who received the abuse or genetic + abuse explanation imposed longer prison sentences. Paradoxically, the genetic and genetic + abuse conditions engendered the greatest fear of the defendant. These findings should allay concerns that genetic evidence in criminal adjudications will be overly persuasive to jurors, but raise questions about the impact of genetic attributions on perceptions of dangerousness. PMID:24618524

Provision of Genetic Services for Autism and Its Impact on Spanish Families

ERIC Educational Resources Information Center

Codina-Solà, Marta; Pérez-Jurado, Luis A.; Cuscó, Ivon; Serra-Juhé, Clara

2017-01-01

Although a genetic evaluation can identify the etiology in 15-30% of individuals with autism spectrum disorder, several studies show an underuse of genetic services by affected families. We have explored the access to genetic services and perception of genetics and recurrence risk in parents of autistic children in Spain. Despite the high interest…

75 FR 68321 - Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

...] Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready Alfalfa... Inspection Service has received a supplemental request for ``partial deregulation'' from Forage Genetics... affected persons of the availability of the documents submitted to the Agency from Forage Genetics...

In Utero Alcohol Exposure, Epigenetic Changes, and Their Consequences

PubMed Central

Ungerer, Michelle; Knezovich, Jaysen; Ramsay, Michele

2013-01-01

Exposure to alcohol has serious consequences for the developing fetus, leading to a range of conditions collectively known as fetal alcohol spectrum disorders (FASD). Most importantly, alcohol exposure affects the development of the brain during critical periods of differentiation and growth, leading to cognitive and behavioral deficits. The molecular mechanisms and processes underlying the teratogenic effects of alcohol exposure remain poorly understood and are complex, because the specific effects depend on the timing, amount, and duration of exposure as well as genetic susceptibility. Accumulating evidence from studies on DNA methylation and histone modification that affect chromatin structure, as well as on the role of microRNAs in regulating mRNA levels supports the contribution of epigenetic mechanisms to the development of FASD. These epigenetic effects are difficult to study, however, because they often are cell-type specific and transient in nature. Rodent models play an important role in FASD research. Although recent studies using these models have yielded some insight into epigenetic mechanisms affecting brain development, they have generated more questions than they have provided definitive answers. Researchers are just beginning to explore the intertwined roles of different epigenetic mechanisms in neurogenesis and how this process is affected by exposure to alcohol, causing FASD. PMID:24313163

The role of latitudinal, genetic and temperature variation in the induction of diapause of Papilio glaucus (Lepidoptera: Papilionidae).

PubMed

Ryan, Sean F; Valella, Patti; Thivierge, Gabrielle; Aardema, Matthew L; Scriber, J Mark

2018-04-01

A key adaptation in insects for dealing with variable environmental conditions is the ability to diapause. The tiger swallowtail butterflies, Papilio glaucus and P. canadensis are ideal species to explore the genetic causes and population genetic consequences of diapause because divergence in this trait is believed to be a salient factor in maintaining a hybrid zone between these species. Yet little is known about the factors that influence diapause induction in this system. Here we explored how spatial (latitudinal), environmental (temperature) and genetic (hybridization) factors affect diapause induction in this system. Specifically, a series of growth chamber experiments using wild caught individuals from across the eastern United States were performed to: (1) evaluate how critical photoperiod varies with latitude, (2) isolate the stage in which induction occurs, (3) test whether changes in temperature affected rates of diapause induction, and (4) explore how the incidence of diapause is affected in hybrid offspring. We find that induction occurs in the larval stage, is not sensitive to a relatively broad range of temperatures, appears to have a complex genetic basis (i.e., is not simply a dominant trait following a Mendelian inheritance pattern) and that the critical photoperiod increases by 0.4 h with each increasing degree in latitude. This work deepens our understanding of how spatial, environmental and genetic variation influences a key seasonal adaptation (diapause induction) in a well-developed ecological model system and will make possible future studies that explore how climatic variation affects the population dynamics and genetics of this system. © 2016 Institute of Zoology, Chinese Academy of Sciences.

A world without pain or tears.

PubMed

Axelrod, Felicia B

2006-04-01

The world of the child with familial dysautonomia (FD), a genetic disorder affecting development of the sensory and autonomic nervous system, is not idyllic. However, over the last 35 years advances in supportive treatments have improved morbidity and mortality. Recent genetic breakthroughs have further expanded thinking about this disorder and suggested innovative approaches to modifying genetic expression. This article reviews the current supportive treatment modalities and their rationale, as well as the suggested new treatments that may alter the function and prognosis of an individual affected with FD.

Patterns of Genetic Variation across Altitude in Three Plant Species of Semi-Dry Grasslands

PubMed Central

Hahn, Thomas; Kettle, Chris J.; Ghazoul, Jaboury; Frei, Esther R.; Matter, Philippe; Pluess, Andrea R.

2012-01-01

Background Environmental gradients caused by altitudinal gradients may affect genetic variation within and among plant populations and inbreeding within populations. Populations in the upper range periphery of a species may be important source populations for range shifts to higher altitude in response to climate change. In this study we investigate patterns of population genetic variation at upper peripheral and lower more central altitudes in three common plant species of semi-dry grasslands in montane landscapes. Methodology/Principal Findings In Briza media, Trifolium montanum and Ranunculus bulbosus genetic diversity, inbreeding and genetic relatedness of individuals within populations and genetic differentiation among populations was characterized using AFLP markers. Populations were sampled in the Swiss Alps at 1800 (upper periphery of the study organisms) and at 1200 m a.s.l. Genetic diversity was not affected by altitude and only in B. media inbreeding was greater at higher altitudes. Genetic differentiation was slightly greater among populations at higher altitudes in B. media and individuals within populations were more related to each other compared to individuals in lower altitude populations. A similar but less strong pattern of differentiation and relatedness was observed in T. montanum, while in R. bulbosus there was no effect of altitude. Estimations of population size and isolation of populations were similar, both at higher and lower altitudes. Conclusions/Significance Our results suggest that altitude does not affect genetic diversity in the grassland species under study. Genetic differentiation of populations increased only slightly at higher elevation, probably due to extensive (historic) gene flow among altitudes. Potentially pre-adapted genes might therefore spread easily across altitudes. Our study indicates that populations at the upper periphery are not genetically depauperate or isolated and thus may be important source populations for migration under climate change. PMID:22870236

Autosomal genetic diversity in non-breed horses from eastern Eurasia provides insights into historical population movements.

PubMed

Warmuth, Vera; Manica, Andrea; Eriksson, Anders; Barker, Graeme; Bower, Mim

2013-02-01

Many events in the history of eastern Eurasia, including the process of domestication itself, the initial spread of domestic horses and subsequent movements, are believed to have affected the genetic structure of domestic horse populations in this area. We investigated levels of within- and between-population genetic diversity in 'non-breed horses' (working horses sampled in remote areas) from 17 locations in Asia and parts of Eastern Europe, using 26 autosomal microsatellite loci. Non-breed horses have not been subject to the same intensity of artificial selection and closed breeding as have most breed animals and are thus expected to better reflect the population history of domestic horses. Despite geographic distances of between 300 and 7000 km between sampling locations, pairwise F (ST) was very low (range: <0.001 to -0.033), suggesting historically high levels of gene flow. Our analyses of non-breed horses revealed a pattern of isolation by distance and a significant decline in genetic diversity (expected heterozygosity and allelic richness) from east to west, consistent with a westward expansion of horses out of East Asia. Although the timing of this putative expansion is unclear, our results highlight the benefit of studying animals that do not belong to particular breeds when investigating aspects of a population's history. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder.

PubMed

Dezhina, Zalina; Ranlund, Siri; Kyriakopoulos, Marinos; Williams, Steve C R; Dima, Danai

2018-05-10

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.

Beyond mean allelic effects: A locus at the major color gene MC1R associates also with differing levels of phenotypic and genetic (co)variance for coloration in barn owls.

PubMed

San-Jose, Luis M; Ducret, Valérie; Ducrest, Anne-Lyse; Simon, Céline; Roulin, Alexandre

2017-10-01

The mean phenotypic effects of a discovered variant help to predict major aspects of the evolution and inheritance of a phenotype. However, differences in the phenotypic variance associated to distinct genotypes are often overlooked despite being suggestive of processes that largely influence phenotypic evolution, such as interactions between the genotypes with the environment or the genetic background. We present empirical evidence for a mutation at the melanocortin-1-receptor gene, a major vertebrate coloration gene, affecting phenotypic variance in the barn owl, Tyto alba. The white MC1R allele, which associates with whiter plumage coloration, also associates with a pronounced phenotypic and additive genetic variance for distinct color traits. Contrarily, the rufous allele, associated with a rufous coloration, relates to a lower phenotypic and additive genetic variance, suggesting that this allele may be epistatic over other color loci. Variance differences between genotypes entailed differences in the strength of phenotypic and genetic associations between color traits, suggesting that differences in variance also alter the level of integration between traits. This study highlights that addressing variance differences of genotypes in wild populations provides interesting new insights into the evolutionary mechanisms and the genetic architecture underlying the phenotype. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Genetic counselors’ implicit racial attitudes and their relationship to communication

PubMed Central

Schaa, Kendra L; Roter, Debra L; Biesecker, Barbara B; Cooper, Lisa A; Erby, Lori H

2015-01-01

Objective Implicit racial attitudes are thought to shape interpersonal interactions and may contribute to health care disparities. This study explored the relationship between genetic counselors’ implicit racial attitudes and their communication during simulated genetic counseling sessions. Methods A nationally representative sample of genetic counselors completed a web-based survey that included the Race Implicit Association Test (IAT). A subset of these counselors (n=67) had participated in an earlier study in which they were video recorded counseling Black, Hispanic and non-Hispanic White simulated clients (SC) about their prenatal or cancer risks. The counselors’ IAT scores were related to their session communication through robust regression modeling. Results Genetic counselors showed a moderate to strong pro-White bias on the Race IAT (M=0.41, SD=0.35). Counselors with stronger pro-White bias were rated as displaying lower levels of positive affect (p<.05) and tended to use less emotionally responsive communication (p<.10) when counseling minority SCs. When counseling White SCs, pro-White bias was associated with lower levels of verbal dominance during sessions (p<.10). Stronger pro-White bias was also associated with more positive ratings of counselors’ nonverbal effectiveness by White SCs. Conclusions Implicit racial bias is associated with negative markers of communication in minority client sessions and may contribute to racial disparities in processes of care related to genetic services. PMID:25622081

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

PubMed

Peter, Beattie J D

2017-01-01

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

A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

PubMed

Nikpay, Majid; Goel, Anuj; Won, Hong-Hee; Hall, Leanne M; Willenborg, Christina; Kanoni, Stavroula; Saleheen, Danish; Kyriakou, Theodosios; Nelson, Christopher P; Hopewell, Jemma C; Webb, Thomas R; Zeng, Lingyao; Dehghan, Abbas; Alver, Maris; Armasu, Sebastian M; Auro, Kirsi; Bjonnes, Andrew; Chasman, Daniel I; Chen, Shufeng; Ford, Ian; Franceschini, Nora; Gieger, Christian; Grace, Christopher; Gustafsson, Stefan; Huang, Jie; Hwang, Shih-Jen; Kim, Yun Kyoung; Kleber, Marcus E; Lau, King Wai; Lu, Xiangfeng; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Mihailov, Evelin; Morrison, Alanna C; Pervjakova, Natalia; Qu, Liming; Rose, Lynda M; Salfati, Elias; Saxena, Richa; Scholz, Markus; Smith, Albert V; Tikkanen, Emmi; Uitterlinden, Andre; Yang, Xueli; Zhang, Weihua; Zhao, Wei; de Andrade, Mariza; de Vries, Paul S; van Zuydam, Natalie R; Anand, Sonia S; Bertram, Lars; Beutner, Frank; Dedoussis, George; Frossard, Philippe; Gauguier, Dominique; Goodall, Alison H; Gottesman, Omri; Haber, Marc; Han, Bok-Ghee; Huang, Jianfeng; Jalilzadeh, Shapour; Kessler, Thorsten; König, Inke R; Lannfelt, Lars; Lieb, Wolfgang; Lind, Lars; Lindgren, Cecilia M; Lokki, Marja-Liisa; Magnusson, Patrik K; Mallick, Nadeem H; Mehra, Narinder; Meitinger, Thomas; Memon, Fazal-Ur-Rehman; Morris, Andrew P; Nieminen, Markku S; Pedersen, Nancy L; Peters, Annette; Rallidis, Loukianos S; Rasheed, Asif; Samuel, Maria; Shah, Svati H; Sinisalo, Juha; Stirrups, Kathleen E; Trompet, Stella; Wang, Laiyuan; Zaman, Khan S; Ardissino, Diego; Boerwinkle, Eric; Borecki, Ingrid B; Bottinger, Erwin P; Buring, Julie E; Chambers, John C; Collins, Rory; Cupples, L Adrienne; Danesh, John; Demuth, Ilja; Elosua, Roberto; Epstein, Stephen E; Esko, Tõnu; Feitosa, Mary F; Franco, Oscar H; Franzosi, Maria Grazia; Granger, Christopher B; Gu, Dongfeng; Gudnason, Vilmundur; Hall, Alistair S; Hamsten, Anders; Harris, Tamara B; Hazen, Stanley L; Hengstenberg, Christian; Hofman, Albert; Ingelsson, Erik; Iribarren, Carlos; Jukema, J Wouter; Karhunen, Pekka J; Kim, Bong-Jo; Kooner, Jaspal S; Kullo, Iftikhar J; Lehtimäki, Terho; Loos, Ruth J F; Melander, Olle; Metspalu, Andres; März, Winfried; Palmer, Colin N; Perola, Markus; Quertermous, Thomas; Rader, Daniel J; Ridker, Paul M; Ripatti, Samuli; Roberts, Robert; Salomaa, Veikko; Sanghera, Dharambir K; Schwartz, Stephen M; Seedorf, Udo; Stewart, Alexandre F; Stott, David J; Thiery, Joachim; Zalloua, Pierre A; O'Donnell, Christopher J; Reilly, Muredach P; Assimes, Themistocles L; Thompson, John R; Erdmann, Jeanette; Clarke, Robert; Watkins, Hugh; Kathiresan, Sekar; McPherson, Ruth; Deloukas, Panos; Schunkert, Heribert; Samani, Nilesh J; Farrall, Martin

2015-10-01

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

Remembrance of things past retrieved from the Paramecium genome.

PubMed

Sperling, Linda

2011-01-01

Paramecium and other ciliates are the only unicellular eukaryotes that separate germinal and somatic functions. A germline micronucleus transmits the genetic information to sexual progeny, while a somatic macronucleus expresses the genetic information during vegetative growth to determine the phenotype. At each sexual generation, a new macronucleus develops from the zygotic nucleus through programmed rearrangements of the germline genome. Paramecium tetraurelia somatic genome sequencing, reviewed here, has provided insight into the organization and evolution of the genome. A series of at least 3 whole genome duplications was detected in the Paramecium lineage and selective pressures that determine the fate of the gene duplicates analyzed. Variability in the somatic DNA was characterized and could be attributed to the genome rearrangement processes. Since, in Paramecium, alternative genome rearrangement patterns can be inherited across sexual generations by homology-dependent epigenetic mechanisms and can affect phenotype, I discuss the possibility that ciliate nuclear dimorphism buffers genetic variation hidden in the germline. Copyright © 2011 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics.

PubMed

Trigueros Genao, M; Torres, R J

2014-11-01

Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

PubMed

Dichter, Gabriel S; Damiano, Cara A; Allen, John A

2012-07-06

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

PubMed Central

2012-01-01

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies. PMID:22958744

Cole Disease Results from Mutations in ENPP1.

PubMed

Eytan, Ori; Morice-Picard, Fanny; Sarig, Ofer; Ezzedine, Khaled; Isakov, Ofer; Li, Qiaoli; Ishida-Yamamoto, Akemi; Shomron, Noam; Goldsmith, Tomer; Fuchs-Telem, Dana; Adir, Noam; Uitto, Jouni; Orlow, Seth J; Taieb, Alain; Sprecher, Eli

2013-10-03

The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A physico-genetic module for the polarisation of auxin efflux carriers PIN-FORMED (PIN)

NASA Astrophysics Data System (ADS)

Hernández-Hernández, Valeria; Barrio, Rafael A.; Benítez, Mariana; Nakayama, Naomi; Romero-Arias, José Roberto; Villarreal, Carlos

2018-05-01

Intracellular polarisation of auxin efflux carriers is crucial for understanding how auxin gradients form in plants. The polarisation dynamics of auxin efflux carriers PIN-FORMED (PIN) depends on both biomechanical forces as well as chemical, molecular and genetic factors. Biomechanical forces have shown to affect the localisation of PIN transporters to the plasma membrane. We propose a physico-genetic module of PIN polarisation that integrates biomechanical, molecular, and cellular processes as well as their non-linear interactions. The module was implemented as a discrete Boolean model and then approximated to a continuous dynamic system, in order to explore the relative contribution of the factors mediating PIN polarisation at the scale of single cell. Our models recovered qualitative behaviours that have been experimentally observed and enable us to predict that, in the context of PIN polarisation, the effects of the mechanical forces can predominate over the activity of molecular factors such as the GTPase ROP6 and the ROP-INTERACTIVE CRIB MOTIF-CONTAINING PROTEIN RIC1.

Cancer genomics: technology, discovery, and translation.

PubMed

Tran, Ben; Dancey, Janet E; Kamel-Reid, Suzanne; McPherson, John D; Bedard, Philippe L; Brown, Andrew M K; Zhang, Tong; Shaw, Patricia; Onetto, Nicole; Stein, Lincoln; Hudson, Thomas J; Neel, Benjamin G; Siu, Lillian L

2012-02-20

In recent years, the increasing awareness that somatic mutations and other genetic aberrations drive human malignancies has led us within reach of personalized cancer medicine (PCM). The implementation of PCM is based on the following premises: genetic aberrations exist in human malignancies; a subset of these aberrations drive oncogenesis and tumor biology; these aberrations are actionable (defined as having the potential to affect management recommendations based on diagnostic, prognostic, and/or predictive implications); and there are highly specific anticancer agents available that effectively modulate these targets. This article highlights the technology underlying cancer genomics and examines the early results of genome sequencing and the challenges met in the discovery of new genetic aberrations. Finally, drawing from experiences gained in a feasibility study of somatic mutation genotyping and targeted exome sequencing led by Princess Margaret Hospital-University Health Network and the Ontario Institute for Cancer Research, the processes, challenges, and issues involved in the translation of cancer genomics to the clinic are discussed.

Genetic responses to rapid change in the environment during the anthropocene

USGS Publications Warehouse

Tallmon, David A.; Kovach, Ryan

2017-01-01

Humans have greatly affected the genetic composition of many different organisms during the Anthropocene. Humans cause genetic changes by affecting the direction and magnitude of evolutionary forces that act to create the Earth's biota. In many cases, we expect the outcome of human actions to be extinction and hybridization of existing species, but other outcomes, such as adaptation, also occur. Given the reach of humans throughout the globe, and recent biotechnology advances that make it possible to move individual genes between species or to remove them, it is likely that human influence on the genetic composition of other organisms will become even more widespread as the Anthropocene progresses.

Genetic autonomic disorders.

PubMed

Axelrod, Felicia B

2013-03-01

Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

Diversity and uniformity in genetic responsibility: moral attitudes of patients, relatives and lay people in Germany and Israel.

PubMed

Raz, Aviad E; Schicktanz, Silke

2009-11-01

The professional and institutional responsibility for handling genetic knowledge is well discussed; less attention has been paid to how lay people and particularly people who are affected by genetic diseases perceive and frame such responsibilities. In this exploratory study we qualitatively examine the attitudes of lay people, patients and relatives of patients in Germany and Israel towards genetic testing. These attitudes are further examined in the national context of Germany and Israel, which represent opposite regulatory approaches and bioethical debates concerning genetic testing. Three major themes of responsibility emerged from the inter-group and cross-cultural comparison: self-responsibility, responsibility for kin, and responsibility of society towards its members. National contrast was apparent in the moral reasoning of lay respondents concerning, for example, the right not to know versus the duty to know (self-responsibility) and the moral conflict concerning informing kin versus the moral duty to inform (responsibility for kin). Attitudes of respondents affected by genetic diseases were, however, rather similar in both countries. We conclude by discussing how moral discourses of responsibility are embedded within cultural (national, religious) as well as phenomenological (being affected) narratives, and the role of public engagement in bioethical discourse.

Loss of Sexual Reproduction and Dwarfing in a Small Metazoan

PubMed Central

Stelzer, Claus-Peter; Schmidt, Johanna; Wiedlroither, Anneliese; Riss, Simone

2010-01-01

Background Asexuality has major theoretical advantages over sexual reproduction, yet newly formed asexual lineages rarely endure. The success, or failure, of such lineages is affected by their mechanism of origin, because it determines their initial genetic makeup and variability. Most previously described mechanisms imply that asexual lineages are randomly frozen subsamples of a sexual population. Methodology/Principal Findings We found that transitions to obligate parthenogenesis (OP) in the rotifer Brachionus calyciflorus, a small freshwater invertebrate which normally reproduces by cyclical parthenogenesis, were controlled by a simple Mendelian inheritance. Pedigree analysis suggested that obligate parthenogens were homozygous for a recessive allele, which caused inability to respond to the chemical signals that normally induce sexual reproduction in this species. Alternative mechanisms, such as ploidy changes, could be ruled out on the basis of flow cytometric measurements and genetic marker analysis. Interestingly, obligate parthenogens were also dwarfs (approximately 50% smaller than cyclical parthenogens), indicating pleiotropy or linkage with genes that strongly affect body size. We found no adverse effects of OP on survival or fecundity. Conclusions/Significance This mechanism of inheritance implies that genes causing OP may evolve within sexual populations and remain undetected in the heterozygous state long before they get frequent enough to actually cause a transition to asexual reproduction. In this process, genetic variation at other loci might become linked to OP genes, leading to non-random associations between asexuality and other phenotypic traits. PMID:20862222

Molecular factors in migraine

PubMed Central

Kowalska, Marta; Prendecki, Michał; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

2016-01-01

Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID:27191890

Copy number variations of genes involved in stress responses reflect the redox state and DNA damage in brewing yeasts.

PubMed

Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Natkanska, Urszula; Kwiatkowska, Aleksandra; Rawska, Ewa; Potocki, Leszek; Kuna, Ewelina; Panek, Anita; Lewinska, Anna; Wnuk, Maciej

2016-09-01

The yeast strains of the Saccharomyces sensu stricto complex involved in beer production are a heterogeneous group whose genetic and genomic features are not adequately determined. Thus, the aim of the present study was to provide a genetic characterization of selected group of commercially available brewing yeasts both ale top-fermenting and lager bottom-fermenting strains. Molecular karyotyping revealed that the diversity of chromosome patterns and four strains with the most accented genetic variabilities were selected and subjected to genome-wide array-based comparative genomic hybridization (array-CGH) analysis. The differences in the gene copy number were found in five functional gene categories: (1) maltose metabolism and transport, (2) response to toxin, (3) siderophore transport, (4) cellular aldehyde metabolic process, and (5) L-iditol 2-dehydrogenase activity (p < 0.05). In the Saflager W-34/70 strain (Fermentis) with the most affected array-CGH profile, loss of aryl-alcohol dehydrogenase (AAD) gene dosage correlated with an imbalanced redox state, oxidative DNA damage and breaks, lower levels of nucleolar proteins Nop1 and Fob1, and diminished tolerance to fermentation-associated stress stimuli compared to other strains. We suggest that compromised stress response may not only promote oxidant-based changes in the nucleolus state that may affect fermentation performance but also provide novel directions for future strain improvement.

Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood.

PubMed

Boecker-Schlier, Regina; Holz, Nathalie E; Buchmann, Arlette F; Blomeyer, Dorothea; Plichta, Michael M; Jennen-Steinmetz, Christine; Wolf, Isabella; Baumeister, Sarah; Treutlein, Jens; Rietschel, Marcella; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2016-05-15

Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurobiology of autism gene products: towards pathogenesis and drug targets.

PubMed

Kleijer, Kristel T E; Schmeisser, Michael J; Krueger, Dilja D; Boeckers, Tobias M; Scheiffele, Peter; Bourgeron, Thomas; Brose, Nils; Burbach, J Peter H

2014-03-01

The genetic heterogeneity of autism spectrum disorders (ASDs) is enormous, and the neurobiology of proteins encoded by genes associated with ASD is very diverse. Revealing the mechanisms on which different neurobiological pathways in ASD pathogenesis converge may lead to the identification of drug targets. The main objective is firstly to outline the main molecular networks and neuronal mechanisms in which ASD gene products participate and secondly to answer the question how these converge. Finally, we aim to pinpoint drug targets within these mechanisms. Literature review of the neurobiological properties of ASD gene products with a special focus on the developmental consequences of genetic defects and the possibility to reverse these by genetic or pharmacological interventions. The regulation of activity-dependent protein synthesis appears central in the pathogenesis of ASD. Through sequential consequences for axodendritic function, neuronal disabilities arise expressed as behavioral abnormalities and autistic symptoms in ASD patients. Several known ASD gene products have their effect on this central process by affecting protein synthesis intrinsically, e.g., through enhancing the mammalian target of rapamycin (mTOR) signal transduction pathway or through impairing synaptic function in general. These are interrelated processes and can be targeted by compounds from various directions: inhibition of protein synthesis through Lovastatin, mTOR inhibition using rapamycin, or mGluR-related modulation of synaptic activity. ASD gene products may all feed into a central process of translational control that is important for adequate glutamatergic regulation of dendritic properties. This process can be modulated by available compounds but may also be targeted by yet unexplored routes.

Advances in ecological genomics in forest trees and applications to genetic resources conservation and breeding.

PubMed

Holliday, Jason A; Aitken, Sally N; Cooke, Janice E K; Fady, Bruno; González-Martínez, Santiago C; Heuertz, Myriam; Jaramillo-Correa, Juan-Pablo; Lexer, Christian; Staton, Margaret; Whetten, Ross W; Plomion, Christophe

2017-02-01

Forest trees are an unparalleled group of organisms in their combined ecological, economic and societal importance. With widespread distributions, predominantly random mating systems and large population sizes, most tree species harbour extensive genetic variation both within and among populations. At the same time, demographic processes associated with Pleistocene climate oscillations and land-use change have affected contemporary range-wide diversity and may impinge on the potential for future adaptation. Understanding how these adaptive and neutral processes have shaped the genomes of trees species is therefore central to their management and conservation. As for many other taxa, the advent of high-throughput sequencing methods is expected to yield an understanding of the interplay between the genome and environment at a level of detail and depth not possible only a few years ago. An international conference entitled 'Genomics and Forest Tree Genetics' was held in May 2016, in Arcachon (France), and brought together forest geneticists with a wide range of research interests to disseminate recent efforts that leverage contemporary genomic tools to probe the population, quantitative and evolutionary genomics of trees. An important goal of the conference was to discuss how such data can be applied to both genome-enabled breeding and the conservation of forest genetic resources under land use and climate change. Here, we report discoveries presented at the meeting and discuss how the ecological genomic toolkit can be used to address both basic and applied questions in tree biology. © 2016 John Wiley & Sons Ltd.

Reaction time, inhibition, working memory and ‘delay aversion’ performance: genetic influences and their interpretation

PubMed Central

KUNTSI, JONNA; ROGERS, HANNAH; SWINARD, GREER; BÖRGER, NORBERT; van der MEERE, JAAP; RIJSDIJK, FRUHLING; ASHERSON, PHILIP

2013-01-01

Background For candidate endophenotypes to be useful for psychiatric genetic research, they first of all need to show significant genetic influences. To address the relative lack of previous data, we set to investigate the extent of genetic and environmental influences on performance in a set of theoretically driven cognitive-experimental tasks in a large twin sample. We further aimed to illustrate how test–retest reliability of the measures affects the estimates. Method Four-hundred 7- to 9-year-old twin pairs were assessed individually on tasks measuring reaction time, inhibition, working memory and ‘delay aversion’ performance. Test–retest reliability data on some of the key measures were available from a previous study. Results Several key measures of reaction time, inhibition and working-memory performance indicated a moderate degree of genetic influence. Combining data across theoretically related tasks increased the heritability estimates, as illustrated by the heritability estimates of 60% for mean reaction time and 50% for reaction-time variability. Psychometric properties (reliability or ceiling effects) had a substantial influence on the estimates for some measures. Conclusions The data support the usefulness of several of the variables for endophenotype studies that aim to link genes to cognitive and motivational processes. Importantly, the data also illustrate specific conditions under which the true extent of genetic influences may be underestimated and hence the usefulness for genetic mapping studies compromised, and suggest ways to address this. PMID:16882357

When the topic is you: genetic counselor responses to prenatal patients' requests for self-disclosure.

PubMed

Balcom, Jessica R; Veach, Patricia McCarthy; Bemmels, Heather; Redlinger-Grosse, Krista; LeRoy, Bonnie S

2013-06-01

A limited amount of research indicates patient requests play a major role in genetic counselors' self-disclosure decisions and that disclosure and non-disclosure responses to patient requests may differentially affect genetic counseling processes. Studies further suggest patient requests may be more common in prenatal settings, particularly when counselors are pregnant. Empirical evidence is limited however, concerning the nature of patient requests. This study explored genetic counselors' experiences of prenatal patients' requests for self-disclosure. Four major research questions were: (1) What types of questions do prenatal patients ask that invite self-disclosure?; (2) Do pregnant genetic counselors have unique experiences with prenatal patient disclosure requests?; (3) How do genetic counselors typically respond to disclosure requests?; and (4) What strategies are effective and ineffective in responding to disclosure requests? One hundred seventy-six genetic counselors completed an online survey and 40 also participated in telephone interviews. Inductive analysis of 21 interviews revealed patient questions vary, although questions about counselor demographics are most common, and patients are more likely to ask pregnant counselors questions about their personal pregnancy decisions. Participants reported greater discomfort with self-disclosure requests during pregnancy, yet also disclosing more frequently during pregnancy. Counselor responses included personal self-disclosure, professional self-disclosure, redirection, and declining to disclose. Factors perceived as influencing disclosure included: topic, patient motivations, timing of request, quality of counseling relationship, patient characteristics, and ethical/legal responsibilities. Disclosure practices changed over time for most counselors. Additional findings, practice implications, and research recommendations are discussed.

Parental decision-making after ultrasound diagnosis of a serious foetal abnormality.

PubMed

Bijma, Hilmar H; Wildschut, Hajo I J; van der Heide, Agnes; Passchier, Jan; Wladimiroff, Juriy W; van der Maas, Paul J

2005-01-01

The purpose of this article is to provide clinicians who are involved in the field of foetal medicine with a comprehensive overview of theories that are relevant for the parental decision-making process after ultrasound diagnosis of a serious foetal abnormality. Since little data are available of parental decision-making after ultrasound diagnosis of foetal abnormality, we reviewed the literature on parental decision-making in genetic counselling of couples at increased genetic risk together with the literature on general decision-making theories. The findings were linked to the specific situation of parental decision-making after an ultrasound diagnosis of foetal abnormality. Based on genetic counselling studies, several cognitive mechanisms play a role in parental decision-making regarding future pregnancies. Parents often have a binary perception of risk. Probabilistic information is translated into two options: the child will or will not be affected. The graduality of chance seems to be of little importance in this process. Instead, the focus shifts to the possible consequences for future family life. General decision-making theories often focus on rationality and coherence of the decision-making process. However, studies of both the influence of framing and the influence of stress indicate that emotional mechanisms can have an important and beneficial function in the decision-making process. Cognitive mechanisms that are elicited by emotions and that are not necessarily rational can have an important and beneficial function in parental decision-making after ultrasound diagnosis of a foetal abnormality. Consequently, the process of parental decision-making should not solely be assessed on the basis of its rationality, but also on the basis of the parental emotional outcome. Copyright (c) 2005 S. Karger AG, Basel.

[Application of Epigenetics in Perinatal Nursing Care].

PubMed

Chou, Hsueh-Fen; Kao, Chien-Huei; Gau, Meei-Ling

2017-04-01

Epigenetics is a field of biomedicine that expanded tremendously during the 1980s. Epigenetics is the study of heritable changes in gene expression independent of underlying DNA (DeoxyriboNucleic Acid) sequence, which not only affect this generation but will be passed to subsequent generations. Although conception is the critical moment for making decisions regarding gene mapping and fetal health, studies have shown that perinatal nursing care practices also affect the genetic remodeling processes and the subsequent health of the mother and her offspring. To optimize maternal-infant and the offspring health, it is important to ensure that the new mother get adequate nutrition, reduce stress levels, adopt gentle birth practices, facilitate exclusive breastfeeding, and avoid contacting toxic substances.

Prediction of laser cutting heat affected zone by extreme learning machine

NASA Astrophysics Data System (ADS)

Anicic, Obrad; Jović, Srđan; Skrijelj, Hivzo; Nedić, Bogdan

2017-01-01

Heat affected zone (HAZ) of the laser cutting process may be developed based on combination of different factors. In this investigation the HAZ forecasting, based on the different laser cutting parameters, was analyzed. The main goal was to predict the HAZ according to three inputs. The purpose of this research was to develop and apply the Extreme Learning Machine (ELM) to predict the HAZ. The ELM results were compared with genetic programming (GP) and artificial neural network (ANN). The reliability of the computational models were accessed based on simulation results and by using several statistical indicators. Based upon simulation results, it was demonstrated that ELM can be utilized effectively in applications of HAZ forecasting.

Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder

PubMed Central

Hill, S. Kristian; Harris, Margret S. H.; Herbener, Ellen S.; Pavuluri, Mani; Sweeney, John A.

2008-01-01

Psychiatric disorders are genetically complex and represent the end product of multiple biological and social factors. Links between genes and disorder-related abnormalities can be effectively captured via assessment of phenotypes that are both associated with genetic effects and potentially contributory to behavioral abnormalities. Identifying intermediate or allied phenotypes as a strategy for clarifying genetic contributions to disorders has been successful in other areas of medicine and is a promising strategy for identifying susceptibility genes in complex psychiatric disorders. There is growing evidence that schizophrenia and bipolar disorder, rather than being wholly distinct disorders, share genetic risk at several loci. Further, there is growing evidence of similarity in the pattern of cognitive and neurobiological deficits in these groups, which may be the result of the effects of these common genetic factors. This review was undertaken to identify patterns of performance on neurocognitive and affective tasks across probands with schizophrenia and bipolar disorder as well as unaffected family members, which warrant further investigation as potential intermediate trait markers. Available evidence indicates that measures of attention regulation, working memory, episodic memory, and emotion processing offer potential for identifying shared and illness-specific allied neurocognitive phenotypes for schizophrenia and bipolar disorder. However, very few studies have evaluated neurocognitive dimensions in bipolar probands or their unaffected relatives, and much work in this area is needed. PMID:18448479

Segregation in a mycorrhizal fungus alters rice growth and symbiosis-specific gene transcription.

PubMed

Angelard, Caroline; Colard, Alexandre; Niculita-Hirzel, Hélène; Croll, Daniel; Sanders, Ian R

2010-07-13

Arbuscular mycorrhizal fungi (AMF) form symbioses with the majority of plants, improving plant nutrition and diversity. Evidence exists suggesting that AMF contain populations of genetically different nucleotypes coexisting in a common cytoplasm. This potentially has two important consequences for their genetics. First, by random distribution of nuclei at spore formation, new offspring of an AMF could receive different complements of nucleotypes compared to the parent or siblings-we consider this as segregation. Second, genetic exchange between AMF would allow the mixing of nuclei, altering nucleotype diversity in new spores. Because segregation was assumed not to occur and genetic exchange has only recently been demonstrated, no attempts have been made to test whether this affects the symbiosis with plants. Here, we show that segregation occurs in the AMF Glomus intraradices and can enhance the growth of rice up to five times, even though neither parental nor crossed AMF lines induced a positive growth response. This process also resulted in an alteration of symbiosis-specific gene transcription in rice. Our results demonstrate that manipulation of AMF genetics has important consequences for the symbiotic effects on plants and could be used to enhance the growth of globally important crops. Copyright 2010 Elsevier Ltd. All rights reserved.

Genetic consequences of sequential founder events by an island-colonizing bird.

PubMed

Clegg, Sonya M; Degnan, Sandie M; Kikkawa, Jiro; Moritz, Craig; Estoup, Arnaud; Owens, Ian P F

2002-06-11

The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documented, natural colonization events by the silvereye species-complex (Zosterops lateralis), a group used to illustrate the process of island colonization in the original founder effect model. Our results indicate that single founder events do not affect levels of heterozygosity or allelic diversity, nor do they result in immediate genetic differentiation between populations. Instead, four to five successive founder events are required before indices of diversity and divergence approach that seen in evolutionarily old forms. A Bayesian analysis based on computer simulation allows inferences to be made on the number of effective founders and indicates that founder effects are weak because island populations are established from relatively large flocks. Indeed, statistical support for a founder event model was not significantly higher than for a gradual-drift model for all recently colonized islands. Taken together, these results suggest that single colonization events in this species complex are rarely accompanied by severe founder effects, and multiple founder events and/or long-term genetic drift have been of greater consequence for neutral genetic diversity.

Developmental Changes in Morphology of the Middle and Posterior External Cranial Base in Modern Homo sapiens.

PubMed

Dalal, Deepal H; Smith, Heather F

2015-01-01

The basicranium has been described as phylogenetically informative, developmentally stable, and minimally affected by external factors and consequently plays an important role in cranial size and shape in subadult humans. Here basicranial variation of subadults from several modern human populations was investigated and the impact of genetic relatedness on basicranial morphological similarities was investigated. Three-dimensional landmark data were digitized from subadult basicrania from seven populations. Published molecular data on short tandem repeats were statistically compared to morphological data from three ontogenetic stages. Basicranial and temporal bone morphology both reflect genetic distances in childhood and adolescence (5-18 years), but not in infancy (<5 years). The occipital bone reflects genetic distances only in adolescence (13-18 years). The sphenoid bone does not reflect genetic distances at any ontogenetic stage but was the most diagnostic region evaluated, resulting in high rates of correct classification among populations. These results suggest that the ontogenetic processes driving basicranial development are complex and cannot be succinctly summarized across populations or basicranial regions. However, the fact that certain regions reflect genetic distances suggests that the morphology of these regions may be useful in reconstructing population history in specimens for which direct DNA evidence is unavailable, such as archaeological sites.

African genetic diversity provides novel insights into evolutionary history and local adaptations.

PubMed

Choudhury, Ananyo; Aron, Shaun; Sengupta, Dhriti; Hazelhurst, Scott; Ramsay, Michèle

2018-05-08

Genetic variation and susceptibility to disease are shaped by human demographic history. We can now study the genomes of extant Africans and uncover traces of population migration, admixture, assimilation and selection by applying sophisticated computational algorithms. There are four major ethnolinguistic divisions among present day Africans: Hunter-gatherer populations in southern and central Africa; Nilo-Saharan speakers from north and northeast Africa; Afro-Asiatic speakers from east Africa; and Niger-Congo speakers who are the predominant ethnolinguistic group spread across most of sub-Saharan Africa. The enormous ethnolinguistic diversity in sub-Saharan African populations is largely paralleled by extensive genetic diversity and until a decade ago, little was known about the origins and divergence of these groups. Results from large-scale population genetic studies, and more recently whole genome sequence data, are unraveling the critical role of events like migration and admixture and environment factors including diet, infectious diseases and climatic conditions in shaping current population diversity. It is now possible to start providing quantitative estimates of divergence times, population size and dynamic processes that have affected populations and their genetic risk for disease. Finally, the availability of ancient genomes from Africa is providing historical insights of unprecedented depth. In this review, we highlight some key interpretations that have emerged from recent African genome studies.

Ethical issues in genetic counselling with special reference to haemoglobinopathies.

PubMed

Muthuswamy, Vasantha

2011-10-01

Genetic counselling is provided in places where genetic tests are carried out. The process involves pre-test counselling as well as post-test counselling to enable the individuals to face the situation and take appropriate decisions with the right frame of mind. Major ethical principles which govern the attitudes and actions of counsellors include: respect for patient autonomy, non-maleficence, beneficence, or taking action to help benefit others and prevent harm, both physical and mental, and justice, which requires that services be distributed fairly to those in need. Other moral issues include veracity, the duty to disclose information or to be truthful, and respect for patient confidentiality. Nondirective counselling, a hallmark of this profession, is in accordance with the principle of individual autonomy. High prevalence of haemoglobinopathies with availability of good and sensitive carrier detection tests and prenatal diagnostic techniques makes these good candidates for population screening of carriers along with genetic counselling for primary prevention of the disease. Screening of the extended family members of the affected child, high risk communities and general population screening including antenatal women are the main target groups for planning a Haemoglobinopathy control programme. A critical mass of trained genetic counsellors who have understanding of the ethical issues and its appropriate handling with the required sensitivity is needed in India.

Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study

PubMed Central

Pellegrini, Silvia; Palumbo, Sara; Iofrida, Caterina; Melissari, Erika; Rota, Giuseppina; Mariotti, Veronica; Anastasio, Teresa; Manfrinati, Andrea; Rumiati, Rino; Lotto, Lorella; Sarlo, Michela; Pietrini, Pietro

2017-01-01

Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment. Moreover, while it is well-known that responses to the same moral dilemmas differ across individuals, to what extent this variability may be rooted in genetics still remains to be understood. As dopamine is a key modulator of neural processes underlying executive functions, we questioned whether genetic polymorphisms associated with decision-making and dopaminergic neurotransmission modulation would contribute to the observed variability in moral judgment. To this aim, we genotyped five genetic variants of the dopaminergic pathway [rs1800955 in the dopamine receptor D4 (DRD4) gene, DRD4 48 bp variable number of tandem repeat (VNTR), solute carrier family 6 member 3 (SLC6A3) 40 bp VNTR, rs4680 in the catechol-O-methyl transferase (COMT) gene, and rs1800497 in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene] in 200 subjects, who were requested to answer 56 moral dilemmas. As these variants are all located in genes belonging to the dopaminergic pathway, they were combined in multilocus genetic profiles for the association analysis. While no individual variant showed any significant effects on moral dilemma responses, the multilocus genetic profile analysis revealed a significant gender-specific influence on human moral acceptability. Specifically, those genotype combinations that improve dopaminergic signaling selectively increased moral acceptability in females, by making their responses to moral dilemmas more similar to those provided by males. As females usually give more emotionally-based answers and engage the “emotional brain” more than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process. PMID:28900390

The classical pink-eyed dilution mutation affects angiogenic responsiveness.

PubMed

Rogers, Michael S; Boyartchuk, Victor; Rohan, Richard M; Birsner, Amy E; Dietrich, William F; D'Amato, Robert J

2012-01-01

Angiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations, including humans and mice, harbor genetic variations that alter angiogenesis. Angiogenesis-regulating gene variants can result in increased susceptibility to multiple angiogenesis-dependent diseases in humans. Our efforts to dissect the complexity of the genetic diversity that regulates angiogenesis have used laboratory animals due to the availability of genome sequence for many species and the ability to perform high volume controlled breeding. Using the murine corneal micropocket assay, we have observed more than ten-fold difference in angiogenic responsiveness among various mouse strains. This degree of difference is observed with either bFGF or VEGF induced corneal neovascularization. Ongoing mapping studies have identified multiple loci that affect angiogenic responsiveness in several mouse models. In this study, we used F2 intercrosses between C57BL/6J and the 129 substrains 129P1/ReJ and 129P3/J, as well as the SJL/J strain, where we have identified new QTLs that affect angiogenic responsiveness. In the case of AngFq5, on chromosome 7, congenic animals were used to confirm the existence of this locus and subcongenic animals, combined with a haplotype-based mapping approach that identified the pink-eyed dilution mutation as a candidate polymorphism to explain AngFq5. The ability of mutations in the pink-eyed dilution gene to affect angiogenic response was demonstrated using the p-J allele at the same locus. Using this allele, we demonstrate that pink-eyed dilution mutations in Oca2 can affect both bFGF and VEGF-induced corneal angiogenesis.

Genetic evolutionary taboo search for optimal marker placement in infrared patient setup

NASA Astrophysics Data System (ADS)

Riboldi, M.; Baroni, G.; Spadea, M. F.; Tagaste, B.; Garibaldi, C.; Cambria, R.; Orecchia, R.; Pedotti, A.

2007-09-01

In infrared patient setup adequate selection of the external fiducial configuration is required for compensating inner target displacements (target registration error, TRE). Genetic algorithms (GA) and taboo search (TS) were applied in a newly designed approach to optimal marker placement: the genetic evolutionary taboo search (GETS) algorithm. In the GETS paradigm, multiple solutions are simultaneously tested in a stochastic evolutionary scheme, where taboo-based decision making and adaptive memory guide the optimization process. The GETS algorithm was tested on a group of ten prostate patients, to be compared to standard optimization and to randomly selected configurations. The changes in the optimal marker configuration, when TRE is minimized for OARs, were specifically examined. Optimal GETS configurations ensured a 26.5% mean decrease in the TRE value, versus 19.4% for conventional quasi-Newton optimization. Common features in GETS marker configurations were highlighted in the dataset of ten patients, even when multiple runs of the stochastic algorithm were performed. Including OARs in TRE minimization did not considerably affect the spatial distribution of GETS marker configurations. In conclusion, the GETS algorithm proved to be highly effective in solving the optimal marker placement problem. Further work is needed to embed site-specific deformation models in the optimization process.

Exploring lateral genetic transfer among microbial genomes using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Ragan, Mark A

2016-07-25

Many microbes can acquire genetic material from their environment and incorporate it into their genome, a process known as lateral genetic transfer (LGT). Computational approaches have been developed to detect genomic regions of lateral origin, but typically lack sensitivity, ability to distinguish donor from recipient, and scalability to very large datasets. To address these issues we have introduced an alignment-free method based on ideas from document analysis, term frequency-inverse document frequency (TF-IDF). Here we examine the performance of TF-IDF on three empirical datasets: 27 genomes of Escherichia coli and Shigella, 110 genomes of enteric bacteria, and 143 genomes across 12 bacterial and three archaeal phyla. We investigate the effect of k-mer size, gap size and delineation of groups on the inference of genomic regions of lateral origin, finding an interplay among these parameters and sequence divergence. Because TF-IDF identifies donor groups and delineates regions of lateral origin within recipient genomes, aggregating these regions by gene enables us to explore, for the first time, the mosaic nature of lateral genes including the multiplicity of biological sources, ancestry of transfer and over-writing by subsequent transfers. We carry out Gene Ontology enrichment tests to investigate which biological processes are potentially affected by LGT.

Multiple levels of redundant processes inhibit Caenorhabditis elegans vulval cell fates.

PubMed

Andersen, Erik C; Saffer, Adam M; Horvitz, H Robert

2008-08-01

Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms.

Multiple Levels of Redundant Processes Inhibit Caenorhabditis elegans Vulval Cell Fates

PubMed Central

Andersen, Erik C.; Saffer, Adam M.; Horvitz, H. Robert

2008-01-01

Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms. PMID:18689876

Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk

PubMed Central

Holmes, Avram J.; Lee, Phil H.; Hollinshead, Marisa O.; Bakst, Leah; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.

2013-01-01

Individual differences in affective and social processes may arise from variability in amygdala-medial prefrontal (mPFC) circuitry and related genetic heterogeneity. To explore this possibility in humans, we examined the structural correlates of trait negative affect in a sample of 1050 healthy young adults with no history of psychiatric illness. Analyses revealed that heightened negative affect was associated with increased amygdala volume and reduced thickness in a left mPFC region encompassing the subgenual and rostral anterior cingulate cortex. The most extreme individuals displayed an inverse correlation between amygdala volume and mPFC thickness, suggesting that imbalance between these structures is linked to negative affect in the general population. Subgroups of participants were further evaluated on social (n = 206) and emotional (n = 533) functions. Individuals with decreased mPFC thickness exhibited the poorest social cognition and were least able to correctly identify facial emotion. Given prior links between disrupted amygdala–mPFC circuitry and the presence of major depressive disorder (MDD), we explored whether the individual differences in anatomy observed here in healthy young adults were associated with polygenic risk for MDD (n = 438) using risk scores derived from a large genome-wide association analysis (n = 18,759). Analyses revealed associations between increasing polygenic burden for MDD and reduced cortical thickness in the left mPFC. These collective findings suggest that, within the healthy population, there is significant variability in amygdala–mPFC circuitry that is associated with poor functioning across affective and social domains. Individual differences in this circuitry may arise, in part, from common genetic variability that contributes to risk for MDD. PMID:23238724

Turner Syndrome: Genetic and Hormonal Factors Contributing to a Specific Learning Disability Profile

ERIC Educational Resources Information Center

Rovet, Joanne

2004-01-01

Turner Syndrome (TS) is a genetic disorder affecting primarily females. It arises from a loss of X-chromosome material, most usually one of the two X chromosomes. Affected individuals have a number of distinguishing somatic features, including short stature and ovarian dysgenesis. Individuals with TS show a distinct neurocognitive profile…

Retrieval of Dry Snow Parameters from Radiometric Data Using a Dense Medium Model and Genetic Algorithms

NASA Technical Reports Server (NTRS)

Tedesco, Marco; Kim, Edward J.

2005-01-01

In this paper, GA-based techniques are used to invert the equations of an electromagnetic model based on Dense Medium Radiative Transfer Theory (DMRT) under the Quasi Crystalline Approximation with Coherent Potential to retrieve snow depth, mean grain size and fractional volume from microwave brightness temperatures. The technique is initially tested on both noisy and not-noisy simulated data. During this phase, different configurations of genetic algorithm parameters are considered to quantify how their change can affect the algorithm performance. A configuration of GA parameters is then selected and the algorithm is applied to experimental data acquired during the NASA Cold Land Process Experiment. Snow parameters retrieved with the GA-DMRT technique are then compared with snow parameters measured on field.

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

Volkow, N.D.; Wang, G.; Volkow, N.D.

A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors,more » developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.« less

Genetic structure and demographic inference of the regular sea urchin Sterechinus neumayeri (Meissner, 1900) in the Southern Ocean: The role of the last glaciation.

PubMed

Díaz, Angie; Gérard, Karin; González-Wevar, Claudio; Maturana, Claudia; Féral, Jean-Pierre; David, Bruno; Saucède, Thomas; Poulin, Elie

2018-01-01

One of the most relevant characteristics of the extant Southern Ocean fauna is its resiliency to survive glacial processes of the Quaternary. These climatic events produced catastrophic habitat reductions and forced some marine benthic species to move, adapt or go extinct. The marine benthic species inhabiting the Antarctic upper continental shelf faced the Quaternary glaciations with different strategies that drastically modified population sizes and thus affected the amount and distribution of intraspecific genetic variation. Here we present new genetic information for the most conspicuous regular sea urchin of the Antarctic continental shelf, Sterechinus neumayeri. We studied the patterns of genetic diversity and structure in this broadcast-spawner across three Antarctic regions: Antarctic Peninsula, the Weddell Sea and Adélie Land in East Antarctica. Genetic analyses based on mitochondrial and nuclear markers suggested that S. neumayeri is a single genetic unit around the Antarctic continent. The species is characterized by low levels of genetic diversity and exhibits a typical star-like haplotype genealogy that supports the hypothesis of a single in situ refugium. Based on two mutation rates standardized for this genus, the Bayesian Skyline plot analyses detected a rapid demographic expansion after the Last Glacial Maximum. We propose a scenario of rapid postglacial expansion and recolonization of Antarctic shallow areas from a less ice-impacted refugium where the species survived the LGM. Considering the patterns of genetic diversity and structure recorded in the species, this refugium was probably located in East Antarctica.

Effects of complex life cycles on genetic diversity: cyclical parthenogenesis

PubMed Central

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

2016-01-01

Neutral patterns of population genetic diversity in species with complex life cycles are difficult to anticipate. Cyclical parthenogenesis (CP), in which organisms undergo several rounds of clonal reproduction followed by a sexual event, is one such life cycle. Many species, including crop pests (aphids), human parasites (trematodes) or models used in evolutionary science (Daphnia), are cyclical parthenogens. It is therefore crucial to understand the impact of such a life cycle on neutral genetic diversity. In this paper, we describe distributions of genetic diversity under conditions of CP with various clonal phase lengths. Using a Markov chain model of CP for a single locus and individual-based simulations for two loci, our analysis first demonstrates that strong departures from full sexuality are observed after only a few generations of clonality. The convergence towards predictions made under conditions of full clonality during the clonal phase depends on the balance between mutations and genetic drift. Second, the sexual event of CP usually resets the genetic diversity at a single locus towards predictions made under full sexuality. However, this single recombination event is insufficient to reshuffle gametic phases towards full-sexuality predictions. Finally, for similar levels of clonality, CP and acyclic partial clonality (wherein a fixed proportion of individuals are clonally produced within each generation) differentially affect the distribution of genetic diversity. Overall, this work provides solid predictions of neutral genetic diversity that may serve as a null model in detecting the action of common evolutionary or demographic processes in cyclical parthenogens (for example, selection or bottlenecks). PMID:27436524

Impact of presymptomatic genetic testing on young adults: a systematic review.

PubMed

Godino, Lea; Turchetti, Daniela; Jackson, Leigh; Hennessy, Catherine; Skirton, Heather

2016-04-01

Presymptomatic and predictive genetic testing should involve a considered choice, which is particularly true when testing is undertaken in early adulthood. Young adults are at a key life stage as they may be developing a career, forming partnerships and potentially becoming parents: presymptomatic testing may affect many facets of their future lives. The aim of this integrative systematic review was to assess factors that influence young adults' or adolescents' choices to have a presymptomatic genetic test and the emotional impact of those choices. Peer-reviewed papers published between January 1993 and December 2014 were searched using eight databases. Of 3373 studies identified, 29 were reviewed in full text: 11 met the inclusion criteria. Thematic analysis was used to identify five major themes: period before testing, experience of genetic counselling, parental involvement in decision-making, impact of test result communication, and living with genetic risk. Many participants grew up with little or no information concerning their genetic risk. The experience of genetic counselling was either reported as an opportunity for discussing problems or associated with feelings of disempowerment. Emotional outcomes of disclosure did not directly correlate with test results: some mutation carriers were relieved to know their status, however, the knowledge they may have passed on the mutation to their children was a common concern. Parents appeared to have exerted pressure on their children during the decision-making process about testing and risk reduction surgery. Health professionals should take into account all these issues to effectively assist young adults in making decisions about presymptomatic genetic testing.

A General Population Genetic Framework for Antagonistic Selection That Accounts for Demography and Recurrent Mutation

PubMed Central

Connallon, Tim; Clark, Andrew G.

2012-01-01

Antagonistic selection—where alleles at a locus have opposing effects on male and female fitness (“sexual antagonism”) or between components of fitness (“antagonistic pleiotropy”)—might play an important role in maintaining population genetic variation and in driving phylogenetic and genomic patterns of sexual dimorphism and life-history evolution. While prior theory has thoroughly characterized the conditions necessary for antagonistic balancing selection to operate, we currently know little about the evolutionary interactions between antagonistic selection, recurrent mutation, and genetic drift, which should collectively shape empirical patterns of genetic variation. To fill this void, we developed and analyzed a series of population genetic models that simultaneously incorporate these processes. Our models identify two general properties of antagonistically selected loci. First, antagonistic selection inflates heterozygosity and fitness variance across a broad parameter range—a result that applies to alleles maintained by balancing selection and by recurrent mutation. Second, effective population size and genetic drift profoundly affect the statistical frequency distributions of antagonistically selected alleles. The “efficacy” of antagonistic selection (i.e., its tendency to dominate over genetic drift) is extremely weak relative to classical models, such as directional selection and overdominance. Alleles meeting traditional criteria for strong selection (Nes >> 1, where Ne is the effective population size, and s is a selection coefficient for a given sex or fitness component) may nevertheless evolve as if neutral. The effects of mutation and demography may generate population differences in overall levels of antagonistic fitness variation, as well as molecular population genetic signatures of balancing selection. PMID:22298707

A general population genetic framework for antagonistic selection that accounts for demography and recurrent mutation.

PubMed

Connallon, Tim; Clark, Andrew G

2012-04-01

Antagonistic selection--where alleles at a locus have opposing effects on male and female fitness ("sexual antagonism") or between components of fitness ("antagonistic pleiotropy")--might play an important role in maintaining population genetic variation and in driving phylogenetic and genomic patterns of sexual dimorphism and life-history evolution. While prior theory has thoroughly characterized the conditions necessary for antagonistic balancing selection to operate, we currently know little about the evolutionary interactions between antagonistic selection, recurrent mutation, and genetic drift, which should collectively shape empirical patterns of genetic variation. To fill this void, we developed and analyzed a series of population genetic models that simultaneously incorporate these processes. Our models identify two general properties of antagonistically selected loci. First, antagonistic selection inflates heterozygosity and fitness variance across a broad parameter range--a result that applies to alleles maintained by balancing selection and by recurrent mutation. Second, effective population size and genetic drift profoundly affect the statistical frequency distributions of antagonistically selected alleles. The "efficacy" of antagonistic selection (i.e., its tendency to dominate over genetic drift) is extremely weak relative to classical models, such as directional selection and overdominance. Alleles meeting traditional criteria for strong selection (N(e)s > 1, where N(e) is the effective population size, and s is a selection coefficient for a given sex or fitness component) may nevertheless evolve as if neutral. The effects of mutation and demography may generate population differences in overall levels of antagonistic fitness variation, as well as molecular population genetic signatures of balancing selection.

Genetic structure and demographic inference of the regular sea urchin Sterechinus neumayeri (Meissner, 1900) in the Southern Ocean: The role of the last glaciation

PubMed Central

Gérard, Karin; González-Wevar, Claudio; Maturana, Claudia; Féral, Jean-Pierre; David, Bruno; Saucède, Thomas; Poulin, Elie

2018-01-01

One of the most relevant characteristics of the extant Southern Ocean fauna is its resiliency to survive glacial processes of the Quaternary. These climatic events produced catastrophic habitat reductions and forced some marine benthic species to move, adapt or go extinct. The marine benthic species inhabiting the Antarctic upper continental shelf faced the Quaternary glaciations with different strategies that drastically modified population sizes and thus affected the amount and distribution of intraspecific genetic variation. Here we present new genetic information for the most conspicuous regular sea urchin of the Antarctic continental shelf, Sterechinus neumayeri. We studied the patterns of genetic diversity and structure in this broadcast-spawner across three Antarctic regions: Antarctic Peninsula, the Weddell Sea and Adélie Land in East Antarctica. Genetic analyses based on mitochondrial and nuclear markers suggested that S. neumayeri is a single genetic unit around the Antarctic continent. The species is characterized by low levels of genetic diversity and exhibits a typical star-like haplotype genealogy that supports the hypothesis of a single in situ refugium. Based on two mutation rates standardized for this genus, the Bayesian Skyline plot analyses detected a rapid demographic expansion after the Last Glacial Maximum. We propose a scenario of rapid postglacial expansion and recolonization of Antarctic shallow areas from a less ice-impacted refugium where the species survived the LGM. Considering the patterns of genetic diversity and structure recorded in the species, this refugium was probably located in East Antarctica. PMID:29874287

Genetic Testing for Hereditary Breast Cancer: The Decision to Decline.

PubMed

White, V Brook; Walsh, Kendall K; Foss, Kimberly Showers; Amacker-North, Lisa; Lenarcic, Stacy; McNeely, Lindsay; White, Richard L

2018-01-01

Genetic testing is important for comprehensive cancer care. Commercial analysis of the BRCA1/2 genes has been available since 1996, and testing for hereditary breast and ovarian cancer syndrome is well established. The National Comprehensive Cancer Network (NCCN) guidelines identify individuals for whom BRCA1/2 analysis is appropriate and define management recommendations for mutation carriers. Despite recommendations, not all who meet NCCN criteria undergo genetic testing. We assess the frequency that individuals meeting NCCN criteria decline BRCA1/2 analysis, as well as factors that affect the decision-making process. A retrospective chart review was performed from September 2013 through August 2014 of individuals who received genetic counseling at the Levine Cancer Institute. A total of 1082 individuals identified through the retrospective chart review met NCCN criteria for BRCA1/2 analysis. Of these, 267 (24.7%) did not pursue genetic testing. Of the Nontested cohort, 59 (22.1%) were disinterested in testing and 108 (40.4%) were advised to gather additional genetic or medical information about their relatives before testing. The remaining 100 (37.5%) individuals were insured and desired to undergo genetic testing but were prohibited by the expense. Eighty five of these 100 patients were responsible for the total cost of the test, whereas the remaining 15 faced a prohibitive copay expense. Financial concerns are a major deterrent to the pursuit of BRCA1/2 analysis among those who meet NCNN criteria, especially in patients diagnosed with breast or ovarian cancer. These findings highlight the need to address financial concerns for genetic testing in this high-risk population.

What can microbial genetics teach sociobiology?

PubMed Central

Foster, Kevin R.; Parkinson, Katie; Thompson, Christopher R.L.

2009-01-01

Progress in our understanding of sociobiology has occurred with little knowledge of the genetic mechanisms that underlie social traits. However, several recent studies have described microbial genes that affect social traits, thereby bringing genetics to sociobiology. A key finding is that simple genetic changes can have marked social consequences, and mutations that affect cheating and recognition behaviors have been discovered. The study of these mutants confirms a central theoretical prediction of social evolution: that genetic relatedness promotes cooperation. Microbial genetics also provides an important new perspective: that the genome-to-phenome mapping of social organisms might be organized to constrain the evolution of social cheaters. This constraint can occur both through pleiotropic genes that link cheating to a personal cost and through the existence of phoenix genes, which rescue cooperative systems from selfish and destructive strategies. These new insights show the power of studying microorganisms to improve our understanding of the evolution of cooperation. PMID:17207887

Urban habitat fragmentation and genetic population structure of bobcats in coastal southern California

USGS Publications Warehouse

Ruell, E.W.; Riley, S.P.D.; Douglas, M.R.; Antolin, M.F.; Pollinger, J.R.; Tracey, J.A.; Lyren, L.M.; Boydston, E.E.; Fisher, R.N.; Crooks, K.R.

2012-01-01

Although habitat fragmentation is recognized as a primary threat to biodiversity, the effects of urban development on genetic population structure vary among species and landscapes and are not yet well understood. Here we use non-invasive genetic sampling to compare the effects of fragmentation by major roads and urban development on levels of dispersal, genetic diversity, and relatedness between paired bobcat populations in replicate landscapes in coastal southern California. We hypothesized that bobcat populations in sites surrounded by urbanization would experience reduced functional connectivity relative to less isolated nearby populations. Our results show that bobcat genetic population structure is affected by roads and development but not always as predicted by the degree that these landscape features surround fragments. Instead, we suggest that urban development may affect functional connectivity between bobcat populations more by limiting the number and genetic diversity of source populations of migrants than by creating impermeable barriers to dispersal.

Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans

PubMed Central

Bendesky, Andres; Pitts, Jason; Rockman, Matthew V.; Chen, William C.; Tan, Man-Wah; Kruglyak, Leonid; Bargmann, Cornelia I.

2012-01-01

Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%–8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation. PMID:23284308

[Polyvalence of bacteriophages isolated from fruit trees, affected by bacterial fire blight].

PubMed

Tovkach, F I; Moroz, S N; Korol', N A; Faĭdiuk, Iu V; Kushkina, A I

2013-01-01

Phage populations appearing as a result of a pathogenic process caused by Erwinia amylovora have been discovered and described. They accompany bacterial fire blight development in the process of quince, pear and apple trees vegetation in Zakarpattya region of Ukraine. Phage isolates of the affected pear and quince include polyvalent virulent phages able to develop on bacterial strains associated with plants--E. amylovora. E. "horticola" and Pantoea agglomerans. E. amylovora isolated from the plant tissues affected by the fire blight and detected at the same time as phages proved to be resistant to the viral infection. It is hard to explain now this characteristic however it was noticed that resistance to phages can change drastically in case of dissociation, lysogenization and mutagenesis of erwinia in laboratory conditions. Phage population study shows that they are heterogeneous and can obviously include not only polyvalent but also specific viruses. Further studies of biology and molecular genetics of pure lines of isolated phages will help to get closer to understanding the place and role of bacteriophages in the complicated network of relations between bacterial pathogens and plants.

A genetic stochastic process model for genome-wide joint analysis of biomarker dynamics and disease susceptibility with longitudinal data.

PubMed

He, Liang; Zhbannikov, Ilya; Arbeev, Konstantin G; Yashin, Anatoliy I; Kulminski, Alexander M

2017-11-01

Unraveling the underlying biological mechanisms or pathways behind the effects of genetic variations on complex diseases remains one of the major challenges in the post-GWAS (where GWAS is genome-wide association study) era. To further explore the relationship between genetic variations, biomarkers, and diseases for elucidating underlying pathological mechanism, a huge effort has been placed on examining pleiotropic and gene-environmental interaction effects. We propose a novel genetic stochastic process model (GSPM) that can be applied to GWAS and jointly investigate the genetic effects on longitudinally measured biomarkers and risks of diseases. This model is characterized by more profound biological interpretation and takes into account the dynamics of biomarkers during follow-up when investigating the hazards of a disease. We illustrate the rationale and evaluate the performance of the proposed model through two GWAS. One is to detect single nucleotide polymorphisms (SNPs) having interaction effects on type 2 diabetes (T2D) with body mass index (BMI) and the other is to detect SNPs affecting the optimal BMI level for protecting from T2D. We identified multiple SNPs that showed interaction effects with BMI on T2D, including a novel SNP rs11757677 in the CDKAL1 gene (P = 5.77 × 10 -7 ). We also found a SNP rs1551133 located on 2q14.2 that reversed the effect of BMI on T2D (P = 6.70 × 10 -7 ). In conclusion, the proposed GSPM provides a promising and useful tool in GWAS of longitudinal data for interrogating pleiotropic and interaction effects to gain more insights into the relationship between genes, quantitative biomarkers, and risks of complex diseases. © 2017 WILEY PERIODICALS, INC.

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature.

PubMed

Wit, Jan M; Oostdijk, Wilma; Losekoot, Monique; van Duyvenvoorde, Hermine A; Ruivenkamp, Claudia A L; Kant, Sarina G

2016-04-01

The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFκB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in ∼3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders. © 2016 European Society of Endocrinology.

God and Genes in the Caring Professions: Clinician and Clergy Perceptions of Religion and Genetics

PubMed Central

Bartlett, Virginia L; Johnson, Rolanda L

2013-01-01

Little is known about how care providers’ perceptions of religion and genetics affect interactions with patients/parishioners. This study investigates clinicians’ and clergy’s perceptions of and experiences with religion and genetics in their clinical and pastoral interactions. An exploratory qualitative study designed to elicit care providers’ descriptions of experiences with religion and genetics in clinical or pastoral interactions. Thirteen focus groups were conducted with members of the caring professions: physicians, nurses, and genetics counselors (clinicians), ministers and chaplains (clergy). Preliminary analysis of qualitative data is presented here. Preliminary analysis highlights four positions in professional perceptions of the relationship between science and faith. Further, differences among professional perceptions appear to influence perceptions of needed or available resources for interactions with religion and genetics. Clinicians’ and clergy’s perceptions of how religion and genetics relate are not defined solely by professional affiliation. These non-role-defined perceptions may affect clinical and pastoral interactions, especially regarding resources for patients and parishioners. PMID:19170091

MKLN1 splicing defect in dogs with lethal acrodermatitis

PubMed Central

Bauer, Anina; McEwan, Neil A.; Cadieu, Edouard; André, Catherine; Roosje, Petra; Mellersh, Cathryn; Casal, Margret L.

2018-01-01

Lethal acrodermatitis (LAD) is a genodermatosis with monogenic autosomal recessive inheritance in Bull Terriers and Miniature Bull Terriers. The LAD phenotype is characterized by poor growth, immune deficiency, and skin lesions, especially at the paws. Utilizing a combination of genome wide association study and haplotype analysis, we mapped the LAD locus to a critical interval of ~1.11 Mb on chromosome 14. Whole genome sequencing of an LAD affected dog revealed a splice region variant in the MKLN1 gene that was not present in 191 control genomes (chr14:5,731,405T>G or MKLN1:c.400+3A>C). This variant showed perfect association in a larger combined Bull Terrier/Miniature Bull Terrier cohort of 46 cases and 294 controls. The variant was absent from 462 genetically diverse control dogs of 62 other dog breeds. RT-PCR analysis of skin RNA from an affected and a control dog demonstrated skipping of exon 4 in the MKLN1 transcripts of the LAD affected dog, which leads to a shift in the MKLN1 reading frame. MKLN1 encodes the widely expressed intracellular protein muskelin 1, for which diverse functions in cell adhesion, morphology, spreading, and intracellular transport processes are discussed. While the pathogenesis of LAD remains unclear, our data facilitate genetic testing of Bull Terriers and Miniature Bull Terriers to prevent the unintentional production of LAD affected dogs. This study may provide a starting point to further clarify the elusive physiological role of muskelin 1 in vivo. PMID:29565995

Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan.

PubMed

Akuta, Norio; Kawamura, Yusuke; Arase, Yasuji; Suzuki, Fumitaka; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Ikeda, Kenji; Kumada, Hiromitsu

2016-05-23

It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.

Identification of Aortic Arch-Specific Quantitative Trait Loci for Atherosclerosis by an Intercross of DBA/2J and 129S6 Apolipoprotein E-Deficient Mice

PubMed Central

Kayashima, Yukako; Makhanova, Natalia A.; Matsuki, Kota; Tomita, Hirofumi; Bennett, Brian J.; Maeda, Nobuyo

2015-01-01

The genetic background of apolipoprotein E (apoE) deficient mice influences atherosclerotic plaque development. We previously reported three quantitative trait loci (QTL), Aath1–Aath3, that affect aortic arch atherosclerosis independently of those in the aortic root in a cross between C57BL6 apoEKO mice (B6-apoE) and 129S6 apoEKO mice (129-apoE). To gain further insight into genetic factors that influence atherosclerosis at different vascular locations, we analyzed 335 F2 mice from an intercross between 129-apoE and apoEKO mice on a DBA/2J genetic background (DBA-apoE). The extent of atherosclerosis in the aortic arch was very similar in the two parental strains. Nevertheless, a genome-wide scan identified two significant QTL for plaque size in the aortic arch: Aath4 on Chromosome (Chr) 2 at 137 Mb and Aath5 on Chr 10 at 51 Mb. The DBA alleles of Aath4 and Aath5 respectively confer susceptibility and resistance to aortic arch atherosclerosis over 129 alleles. Both QTL are also independent of those affecting plaque size at the aortic root. Genome analysis suggests that athero-susceptibility of Aath4 in DBA may be contributed by multiple genes, including Mertk and Cd93, that play roles in phagocytosis of apoptotic cells and modulate inflammation. A candidate gene for Aath5 is Stab2, the DBA allele of which is associated with 10 times higher plasma hyaluronan than the 129 allele. Overall, our identification of two new QTL that affect atherosclerosis in an aortic arch-specific manner further supports the involvement of distinct pathological processes at different vascular locations. PMID:25689165

Clinical Significance of Epigenetic Alterations in Human Hepatocellular Carcinoma and Its Association with Genetic Mutations.

PubMed

Nishida, Naoshi; Kudo, Masatoshi

Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development. In addition, genetic mutations in histone modulators and chromatin regulators would be critical for the acceleration of epigenetic alteration. It is also possible that major genetic mutations of HCC, such as TP53 and CNTTB1 mutations, are associated with the disturbance of epigenetic integrity. For example, specific TP53 mutations frequently induced by aflatoxin B1 exposure might affect histone modifiers and nucleosome remodelers. Generally, epigenetic alteration is reversible, because of which dysregulation of transcription takes place, without affecting protein structure. Therefore, differentiation therapy is one of the potential approaches for HCC with advanced epigenetic alterations. On the other hand, a tumor carrying an accumulation of genetic mutations would result in many abnormal proteins that could be recognized as non-self and could be targets for immune reactions; thus, immune-checkpoint blockers should be effective for HCCs with genetic hypermutation. Although the emergence of genetic and epigenetic alterations could be linked to each other and there could be some crossover or convergence between these cancer pathways, characterization of the mutation spectrum of genetic and epigenetic alterations could influence future HCC treatment. © 2016 S. Karger AG, Basel.

GENETICS OF WHITE MATTER DEVELOPMENT: A DTI STUDY OF 705 TWINS AND THEIR SIBLINGS AGED 12 TO 29

PubMed Central

Chiang, Ming-Chang; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Hickie, Ian; Toga, Arthur W.; Wright, Margaret J.; Thompson, Paul M.

2011-01-01

White matter microstructure is under strong genetic control, yet it is largely unknown how genetic influences change from childhood into adulthood. In one of the largest brain mapping studies ever performed, we determined whether the genetic control over white matter architecture depends on age, sex, socioeconomic status (SES), and intelligence quotient (IQ). We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4-Tesla), in 705 twins and their siblings (age range 12–29; 290 M/415 F). White matter integrity was quantified using a widely accepted measure, fractional anisotropy (FA). We fitted gene-environment interaction models pointwise, to visualize brain regions where age, sex, SES and IQ modulate heritability of fiber integrity. We hypothesized that environmental factors would start to outweigh genetic factors during late childhood and adolescence. Genetic influences were greater in adolescence versus adulthood, and greater in males than in females. Socioeconomic status significantly interacted with genes that affect fiber integrity: heritability was higher in those with higher SES. In people with above-average IQ, genetic factors explained over 800% of the observed FA variability in the thalamus, genu, posterior internal capsule, and superior corona radiata. In those with below-average IQ, however, only around 40% FA variability in the same regions was attributable to genetic factors. Genes affect fiber integrity, but their effects vary with age, sex, SES and IQ. Gene-environment interactions are vital to consider in the search for specific genetic polymorphisms that affect brain integrity and connectivity. PMID:20950689

Genetic and non-genetic factors affecting morphometry of Sirohi goats

PubMed Central

Dudhe, S. D.; Yadav, S. B. S.; Nagda, R. K.; Pannu, Urmila; Gahlot, G. C.

2015-01-01

Aim: The aim was to estimate genetic and non-genetic factors affecting morphometric traits of Sirohi goats under field condition. Materials and Methods: The detailed information of all animals on body measurements at birth, 3, 6, 9, and 12 months of age was collected from farmer’s flock under field condition born during 2007-2013 to analyze the effect of genetic and non-genetic factors. The least squares maximum likelihood program was used to estimate genetic and non-genetic parameters affecting morphometric traits. Results and Discussion: Effect of sire, cluster, year of birth, and sex was found to be highly significant (p<0.01) on all three morphometric traits, parity was highly significant (p<0.01) for body height (BH) and body girth (BG) at birth. The h2 estimates for morphometric traits ranged among 0.528±0.163 to 0.709±0.144 for BH, 0.408±0.159 to 0.605±0.192 for body length (BL), and 0.503±0.197 to 0.695±0.161 for BG. Conclusion: The effect of sire was highly significant (p<0.01) and also h² estimate of all morphometric traits were medium to high; therefore, it could be concluded on the basis of present findings that animals with higher body measurements at initial phases of growth will perform better with respect to even body weight traits at later stages of growth. PMID:27047043

Genetics Home Reference: neuromyelitis optica

MedlinePlus

... are some genetic conditions more common in particular ethnic groups? Genetic Changes No genes associated with neuromyelitis optica have been identified. However, a small percentage of people with this condition have a family member who is also affected, which indicates that ...

The role of interindividual variation in human carcinogenesis.

PubMed

Lai, C; Shields, P G

1999-02-01

The process of chemical carcinogenesis is a complex multistage process initiated by DNA damage in growth control genes. Carcinogens enter the body from a variety of sources, but most require metabolic activation before they can damage DNA. There are multiple protective processes that include detoxification and conjugation, DNA repair and programmed cell death. Most of these functions exhibit wide interindividual variation in the population and thus are thought to affect cancer risk. The role of gene-environment interactions is being explored, and current data indicate that genetic susceptibilities can modify carcinogen exposures from the diet and tobacco smoking, although much more data exist for the latter. This review addresses the relationships of human carcinogenesis to these interindividual differences of phase I, phase II and DNA repair enzymes.

Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility.

PubMed

Sang, Qing; Li, Bin; Kuang, Yanping; Wang, Xueqian; Zhang, Zhihua; Chen, Biaobang; Wu, Ling; Lyu, Qifeng; Fu, Yonglun; Yan, Zheng; Mao, Xiaoyan; Xu, Yao; Mu, Jian; Li, Qiaoli; Jin, Li; He, Lin; Wang, Lei

2018-04-05

Fertilization is a fundamental process of development and is a prerequisite for successful human reproduction. In mice, although several receptor proteins have been shown to play important roles in the process of fertilization, only three genes have been shown to cause fertilization failure and infertility when deleted in vivo. In clinical practice, some infertility case subjects suffer from recurrent failure of in vitro fertilization and intracytoplasmic sperm injection attempts due to fertilization failure, but the genetic basis of fertilization failure in humans remains largely unknown. Wee2 is a key oocyte-specific kinase involved in the control of meiotic arrest in mice, but WEE2 has not been associated with any diseases in humans. In this study, we identified homozygous mutations in WEE2 that are responsible for fertilization failure in humans. All four independent affected individuals had homozygous loss-of-function missense mutations or homozygous frameshift protein-truncating mutations, and the phenotype of fertilization failure was shown to follow a Mendelian recessive inheritance pattern. All four mutations significantly decreased the amount of WEE2 protein in vitro and in affected individuals' oocytes in vivo, and they all led to abnormal serine phosphorylation of WEE2 and reduced tyrosine 15 phosphorylation of Cdc2 in vitro. In addition, injection of WEE2 cRNA into affected individuals' oocytes rescued the fertilization failure phenotype and led to the formation of blastocysts in vitro. This work presents a novel gene responsible for human fertilization failure and has implications for future therapeutic treatments for infertility cases. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The translocator protein gene is associated with symptom severity and cerebral pain processing in fibromyalgia.

PubMed

Kosek, Eva; Martinsen, Sofia; Gerdle, Björn; Mannerkorpi, Kaisa; Löfgren, Monika; Bileviciute-Ljungar, Indre; Fransson, Peter; Schalling, Martin; Ingvar, Martin; Ernberg, Malin; Jensen, Karin B

2016-11-01

The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n=126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n=24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p=0.016) and fibromyalgia symptoms (p=0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p<0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

An empirical evaluation of genetic distance statistics using microsatellite data from bear (Ursidae) populations.

PubMed

Paetkau, D; Waits, L P; Clarkson, P L; Craighead, L; Strobeck, C

1997-12-01

A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago. At the finest scale, while some distance measures performed extremely well, statistics developed specifically to accommodate the mutational processes of microsatellites performed relatively poorly, presumably because of the relatively higher variance of these statistics. At the other extreme, no statistic was able to resolve the close sister relationship of polar bears and brown bears from more distantly related pairs of species. This failure is most likely due to constraints on allele distributions at microsatellite loci. At intermediate scales, both within continuous distributions and in comparisons to insular populations of late Pleistocene origin, it was not possible to define the point where linearity was lost for each of the statistics, except that it is clearly lost after relatively short periods of independent evolution. All of the statistics were affected by the amount of genetic diversity within the populations being compared, significantly complicating the interpretation of genetic distance data.

An Empirical Evaluation of Genetic Distance Statistics Using Microsatellite Data from Bear (Ursidae) Populations

PubMed Central

Paetkau, D.; Waits, L. P.; Clarkson, P. L.; Craighead, L.; Strobeck, C.

1997-01-01

A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago. At the finest scale, while some distance measures performed extremely well, statistics developed specifically to accommodate the mutational processes of microsatellites performed relatively poorly, presumably because of the relatively higher variance of these statistics. At the other extreme, no statistic was able to resolve the close sister relationship of polar bears and brown bears from more distantly related pairs of species. This failure is most likely due to constraints on allele distributions at microsatellite loci. At intermediate scales, both within continuous distributions and in comparisons to insular populations of late Pleistocene origin, it was not possible to define the point where linearity was lost for each of the statistics, except that it is clearly lost after relatively short periods of independent evolution. All of the statistics were affected by the amount of genetic diversity within the populations being compared, significantly complicating the interpretation of genetic distance data. PMID:9409849

The population genetics of mutations: good, bad and indifferent

PubMed Central

Loewe, Laurence; Hill, William G.

2010-01-01

Population genetics is fundamental to our understanding of evolution, and mutations are essential raw materials for evolution. In this introduction to more detailed papers that follow, we aim to provide an oversight of the field. We review current knowledge on mutation rates and their harmful and beneficial effects on fitness and then consider theories that predict the fate of individual mutations or the consequences of mutation accumulation for quantitative traits. Many advances in the past built on models that treat the evolution of mutations at each DNA site independently, neglecting linkage of sites on chromosomes and interactions of effects between sites (epistasis). We review work that addresses these limitations, to predict how mutations interfere with each other. An understanding of the population genetics of mutations of individual loci and of traits affected by many loci helps in addressing many fundamental and applied questions: for example, how do organisms adapt to changing environments, how did sex evolve, which DNA sequences are medically important, why do we age, which genetic processes can generate new species or drive endangered species to extinction, and how should policy on levels of potentially harmful mutagens introduced into the environment by humans be determined? PMID:20308090

Easy calculations of lod scores and genetic risks on small computers.

PubMed Central

Lathrop, G M; Lalouel, J M

1984-01-01

A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed. An illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy. PMID:6585139

Use of molecular genetic markers in forest management

Treesearch

Craig S. Echt

1997-01-01

When managing forests for biodiversity or sustainability, attention must be given to how silvicultural practices affect genetic diversity. A new generation of DNA-based markers affords a greater detail of genetic analysis than previously possible. These new markers, SSRs or microsatellites, have been used to demonstrate genetic diversity and infer evolutionary history...

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.

PubMed

Sirugo, Giorgio; Hennig, Branwen J; Adeyemo, Adebowale A; Matimba, Alice; Newport, Melanie J; Ibrahim, Muntaser E; Ryckman, Kelli K; Tacconelli, Alessandra; Mariani-Costantini, Renato; Novelli, Giuseppe; Soodyall, Himla; Rotimi, Charles N; Ramesar, Raj S; Tishkoff, Sarah A; Williams, Scott M

2008-07-01

Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease.

Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation.

PubMed

Yang, Ye; Christensen, Ole F; Sorensen, Daniel

2011-02-01

Over recent years, statistical support for the presence of genetic factors operating at the level of the environmental variance has come from fitting a genetically structured heterogeneous variance model to field or experimental data in various species. Misleading results may arise due to skewness of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box-Cox transformations. Litter size data in rabbits and pigs that had previously been analysed in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box-Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected by the presence of asymmetry in the distribution of data. We recommend that to avoid one important source of spurious inferences, future work seeking support for a genetic component acting on environmental variation using a parametric approach based on normality assumptions confirms that these are met.

Secrets from immortal worms: What can we learn about biological ageing from the planarian model system?

PubMed

Sahu, Sounak; Dattani, Anish; Aboobaker, A Aziz

2017-10-01

Understanding how some animals are immortal and avoid the ageing process is important. We currently know very little about how they achieve this. Research with genetic model systems has revealed the existence of conserved genetic pathways and molecular processes that affect longevity. Most of these established model organisms have relatively short lifespans. Here we consider the use of planarians, with an immortal life-history that is able to entirely avoid the ageing process. These animals are capable of profound feats of regeneration fueled by a population of adult stem cells called neoblasts. These cells are capable of indefinite self-renewal that has underpinned the evolution of animals that reproduce only by fission, having disposed of the germline, and must therefore be somatically immortal and avoid the ageing process. How they do this is only now starting to be understood. Here we suggest that the evidence so far supports the hypothesis that the lack of ageing is an emergent property of both being highly regenerative and the evolution of highly effective mechanisms for ensuring genome stability in the neoblast stem cell population. The details of these mechanisms could prove to be very informative in understanding how the causes of ageing can be avoided, slowed or even reversed. Copyright © 2017 Elsevier Ltd. All rights reserved.

From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families

NASA Astrophysics Data System (ADS)

Santos, Silvana; Bizzo, Nelio

2005-07-01

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

Morphometric magnetic resonance imaging and genetic testing in cerebellar abiotrophy in Arabian horses

PubMed Central

2013-01-01

Background Cerebellar abiotrophy (CA) is a rare but significant disease in Arabian horses caused by progressive death of the Purkinje cells resulting in cerebellar ataxia characterized by a typical head tremor, jerky head movements and lack of menace response. The specific role of magnetic resonance imaging (MRI) to support clinical diagnosis has been discussed. However, as yet MR imaging has only been described in one equine CA case. The role of MR morphometry in this regard is currently unknown. Due to the hereditary nature of the disease, genetic testing can support the diagnosis of CA. Therefore, the objective of this study was to perform MR morphometric analysis and genetic testing in four CA-affected Arabian horses and one German Riding Pony with purebred Arabian bloodlines in the third generation. Results CA was diagnosed pathohistologically in the five affected horses (2 months - 3 years) supported by clinical signs, necropsy, and genetic testing which confirmed the TOE1:g.2171G>A SNP genotype A/A in all CA-affected horses. On MR images morphometric analysis of the relative cerebellar size and relative cerebellar cerebrospinal fluid (CSF) space were compared to control images of 15 unaffected horses. It was demonstrated that in MR morphometric analyses, CA affected horses displayed a relatively smaller cerebellum compared to the entire brain mass than control animals (P = 0.0088). The relative cerebellar CSF space was larger in affected horses (P = 0.0017). Using a cut off value of 11.0% for relative cerebellar CSF space, the parameter differentiated between CA-affected horses and controls with a sensitivity of 100% and a specificity of 93.3%. Conclusions In conclusion, morphometric MRI and genetic analysis could be helpful to support the diagnosis of CA in vivo. PMID:23702154

Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig.

PubMed

Jégou, Maëva; Gondret, Florence; Vincent, Annie; Tréfeu, Christine; Gilbert, Hélène; Louveau, Isabelle

2016-01-01

The molecular mechanisms underlying feed efficiency need to be better understood to improve animal efficiency, a research priority to support a competitive and sustainable livestock production. This study was undertaken to determine whether pig blood transcriptome was affected by differences in feed efficiency and by ingested nutrients. Growing pigs from two lines divergently selected for residual feed intake (RFI) and fed isoproteic and isocaloric diets contrasted in energy source and nutrients were considered. Between 74 and 132 days of age, pigs (n = 12 by diet and by line) received a regular diet rich in cereals and low in fat (LF) or a diet where cereals where partially substituted by lipids and fibers (HF). At the end of the feeding trial, the total number of white blood cells was not affected by the line or by the diet, whereas the red blood cell number was higher (P<0.001) in low RFI than in high RFI pigs. Analysis of the whole blood transcriptome using a porcine microarray reveals a higher number of probes differentially expressed (DE) between RFI lines than between diets (2,154 versus 92 probes DE, P<0.01). This corresponds to 528 overexpressed genes and 477 underexpressed genes in low RFI pigs compared with high RFI pigs, respectively. Overexpressed genes were predominantly associated with translational elongation. Underexpressed genes were mainly involved in the immune response, regulation of inflammatory response, anti-apoptosis process, and cell organization. These findings suggest that selection for RFI has affected the immune status and defense mechanisms of pigs. Genes DE between diets were mainly related to the immune system and lipid metabolism. Altogether, this study demonstrates the usefulness of the blood transcriptome to identify the main biological processes affected by genetic selection and feeding strategies.

Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig

PubMed Central

Jégou, Maëva; Gondret, Florence; Vincent, Annie; Tréfeu, Christine; Gilbert, Hélène; Louveau, Isabelle

2016-01-01

The molecular mechanisms underlying feed efficiency need to be better understood to improve animal efficiency, a research priority to support a competitive and sustainable livestock production. This study was undertaken to determine whether pig blood transcriptome was affected by differences in feed efficiency and by ingested nutrients. Growing pigs from two lines divergently selected for residual feed intake (RFI) and fed isoproteic and isocaloric diets contrasted in energy source and nutrients were considered. Between 74 and 132 days of age, pigs (n = 12 by diet and by line) received a regular diet rich in cereals and low in fat (LF) or a diet where cereals where partially substituted by lipids and fibers (HF). At the end of the feeding trial, the total number of white blood cells was not affected by the line or by the diet, whereas the red blood cell number was higher (P<0.001) in low RFI than in high RFI pigs. Analysis of the whole blood transcriptome using a porcine microarray reveals a higher number of probes differentially expressed (DE) between RFI lines than between diets (2,154 versus 92 probes DE, P<0.01). This corresponds to 528 overexpressed genes and 477 underexpressed genes in low RFI pigs compared with high RFI pigs, respectively. Overexpressed genes were predominantly associated with translational elongation. Underexpressed genes were mainly involved in the immune response, regulation of inflammatory response, anti-apoptosis process, and cell organization. These findings suggest that selection for RFI has affected the immune status and defense mechanisms of pigs. Genes DE between diets were mainly related to the immune system and lipid metabolism. Altogether, this study demonstrates the usefulness of the blood transcriptome to identify the main biological processes affected by genetic selection and feeding strategies. PMID:26752050

Resolving a genetic paradox throughout preimplantation genetic diagnosis for autosomal dominant severe congenital neutropenia.

PubMed

Malcov, Mira; Reches, Adi; Ben-Yosef, Dalit; Cohen, Tania; Amit, Ami; Dgany, Orly; Tamary, Hannah; Yaron, Yuval

2010-03-01

Severe congenital neutropenia is an inherited disease characterized by low peripheral blood neutrophils, amenable to bone marrow transplantation. Genetic analysis in the family here described detected a ELA2 splice-site mutation in the affected child and also in his asymptomatic father. The parents requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to obtain a suitable bone marrow donor for the affected child. A PGD protocol was developed, based on multiplex nested PCR for direct analysis of the ELA2 mutation, flanking polymorphic markers and HLA typing. The amplification efficiency of the mutation was > 90% in single leukocytes from the affected child but only 67% in the father. Analysis of single haploid sperm cells from the father demonstrated three different sperm-cell populations: (1) sperm cells harboring the ELA2 mutation on the 'affected' haplotype, (2) sperm cells without the ELA2 mutation on the 'normal' haplotype, and (3) sperm cells without the ELA2 mutation on the 'affected' haplotype. These data demonstrate that the ELA2 mutation in the father occurred de novo during his embryonic development, resulting in somatic as well as germ-line mosaicism. This conclusion was also taken into consideration when PGD was performed. Copyright (c) 2010 John Wiley & Sons, Ltd.

Toward a therapy for mitochondrial disease

PubMed Central

Viscomi, Carlo

2016-01-01

Mitochondrial disorders are a group of genetic diseases affecting the energy-converting process of oxidative phosphorylation. The extreme variability of symptoms, organ involvement, and clinical course represent a challenge to the development of effective therapeutic interventions. However, new possibilities have recently been emerging from studies in model organisms and awaiting verification in humans. I will discuss here the most promising experimental approaches and the challenges we face to translate them into the clinics. The current clinical trials will also be briefly reviewed. PMID:27911730

Summing up the noise in gene networks

NASA Astrophysics Data System (ADS)

Paulsson, Johan

2004-01-01

Random fluctuations in genetic networks are inevitable as chemical reactions are probabilistic and many genes, RNAs and proteins are present in low numbers per cell. Such `noise' affects all life processes and has recently been measured using green fluorescent protein (GFP). Two studies show that negative feedback suppresses noise, and three others identify the sources of noise in gene expression. Here I critically analyse these studies and present a simple equation that unifies and extends both the mathematical and biological perspectives.

ADHD and Poor Motor Performance from a Family Genetic Perspective

ERIC Educational Resources Information Center

Fliers, Ellen; Vermeulen, Sita; Rijsdijk, Fruhling; Altink, Marieke; Buschgens, Cathelijne; Rommelse, Nanda; Faraone, Stephen; Sergeant, Joseph; Buitelaar, Jan; Franke, Barbara

2009-01-01

Analysis of the data from a genetics study of children with attention-deficit/hyperactivity disorder (ADHD) and their affected or unaffected siblings finds that ADHD-affected children had significantly more motor problems than their unaffected siblings. It is concluded that there is a common basis between ADHD and motor problems that may be due to…

Psychological Factors Associated with Genetic Test Decision-Making among Parents of Children with Autism Spectrum Disorders in Taiwan

ERIC Educational Resources Information Center

Xu, Lei; Richman, Alice R.

2015-01-01

Making decisions to undergo Autism Spectrum Disorders (ASD) genetic testing can be challenging. It is important to understand how the perceptions of affected individuals might influence testing decision-making. Although evidence has shown that psychological factors are important in predicting testing decisions, affect-type variables have been…

Mastitis of periparturient Holstein cattle: a phenotypic and genetic study.

PubMed

Detilleux, J C; Kehrli, M E; Freeman, A E; Fox, L K; Kelley, D H

1995-10-01

Environmental and genetic factors affecting somatic cell scores, clinical mastitis, and IMI by minor and major pathogens were studied on 137 periparturient Holstein cows selected for milk production. Environmental effects were obtained by generalized least squares and logistic regression. Genetic parameters were from BLUP and threshold animal models. Lactation number affected the number of quarters with clinical mastitis and the number of quarters infected with minor pathogens. The DIM affected somatic cell score and number of quarters infected with major pathogens. Heritabilities for all mastitis indicators averaged 10%, but differences occurred among the indicators. Correlations between breeding values of the number of quarters infected with minor pathogens and the number infected with major pathogens were antagonistic and statistically significant.

Effect of the Iberian pig line on dry-cured ham characteristics.

PubMed

Carrapiso, Ana I; García, Carmen

2008-10-01

The purpose of this study was to compare the characteristics (chemical composition, instrumental colour, sensory characteristics and acceptance) of dry-cured hams obtained form three genetic lines of Iberian pig (Censyra, Torbiscal and Entrepelado). The instrumental colour of fat was affected by the genetic line (b(∗), p=0.008; and h°, p=0.024), the Censyra group having the largest values. The genetic line did not affect the chemical composition of the subcutaneous fat and lean of the dry-cured hams or the instrumental colour of the lean. Data from a descriptive analysis showed that the only characteristic significantly affected was the toasted flavour (p=0.004), and juiciness and sweetness were slightly affected (p=0.062 and 0.061, respectively). In spite of the slight effect on the physical-chemical and sensory characteristics, acceptance was significantly different, Torbiscal hams having the highest scores.

When teams shift among processes: insights from simulation and optimization.

PubMed

Kennedy, Deanna M; McComb, Sara A

2014-09-01

This article introduces process shifts to study the temporal interplay among transition and action processes espoused in the recurring phase model proposed by Marks, Mathieu, and Zacarro (2001). Process shifts are those points in time when teams complete a focal process and change to another process. By using team communication patterns to measure process shifts, this research explores (a) when teams shift among different transition processes and initiate action processes and (b) the potential of different interventions, such as communication directives, to manipulate process shift timing and order and, ultimately, team performance. Virtual experiments are employed to compare data from observed laboratory teams not receiving interventions, simulated teams receiving interventions, and optimal simulated teams generated using genetic algorithm procedures. Our results offer insights about the potential for different interventions to affect team performance. Moreover, certain interventions may promote discussions about key issues (e.g., tactical strategies) and facilitate shifting among transition processes in a manner that emulates optimal simulated teams' communication patterns. Thus, we contribute to theory regarding team processes in 2 important ways. First, we present process shifts as a way to explore the timing of when teams shift from transition to action processes. Second, we use virtual experimentation to identify those interventions with the greatest potential to affect performance by changing when teams shift among processes. Additionally, we employ computational methods including neural networks, simulation, and optimization, thereby demonstrating their applicability in conducting team research. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology.

PubMed

Wesseldijk, Laura W; Fedko, Iryna O; Bartels, Meike; Nivard, Michel G; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; Middeldorp, Christel M

2017-04-01

The assessment of children's psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child's problems (r 0.60-0.75). The heritability was estimated over 55% for maternal and paternal ratings for all scales, except for conduct problems (44-46%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13%), oppositional (13%), and conduct problems (37%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child's psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Genetic analysis of gravity signal transduction in roots

NASA Astrophysics Data System (ADS)

Masson, Patrick; Strohm, Allison; Baldwin, Katherine

To grow downward into the soil, roots use gravity as a guide. Specialized cells, named stato-cytes, enable this directional growth response by perceiving gravity. Located in the columella region of the cap, these cells sense a reorientation of the root within the gravity field through the sedimentation of, and/or tension/pressure exerted by, dense amyloplasts. This process trig-gers a gravity signal transduction pathway that leads to a fast alkalinization of the cytoplasm and a change in the distribution of the plasma membrane-associated auxin-efflux carrier PIN3. The latter protein is uniformly distributed within the plasma membrane on all sides of the cell in vertically oriented roots. However, it quickly accumulates at the bottom side upon gravis-timulation. This process correlates with a preferential transport of auxin to the bottom side of the root cap, resulting in a lateral gradient across the tip. This gradient is then transported to the elongation zone where it promotes differential cellular elongation, resulting in downward curvature. We isolated mutations that affect gravity signal transduction at a step that pre-cedes cytoplasmic alkalinization and/or PIN3 relocalization and lateral auxin transport across the cap. arg1 and arl2 mutations identify a common genetic pathway that is needed for all three gravity-induced processes in the cap statocytes, indicating these genes function early in the pathway. On the other hand, adk1 affects gravity-induced PIN3 relocalization and lateral auxin transport, but it does not interfere with cytoplasmic alkalinization. ARG1 and ARL2 encode J-domain proteins that are associated with membranes of the vesicular trafficking path-way whereas ADK1 encodes adenosine kinase, an enzyme that converts adenosine derived from nucleic acid metabolism and the AdoMet cycle into AMP, thereby alleviating feedback inhibi-tion of this important methyl-donor cycle. Because mutations in ARG1 (and ARL2) do not completely eliminate gravitropism, we sought genetic enhancers of arg1 as a way to identify new gravity signal transducers. Two of these modifiers, named mar1 and mar2, were found to affect genes that encode two subunits of the plastidic outer-membrane protein import complex, TOC75 and TOC132, respectively. mar2 did not affect the ultrastructure of amyloplasts in the statocytes nor did it alter their ability to sediment in response to gravistimulation, suggesting a role for the outer membrane of the amyloplasts in gravity signal transduction (reviewed in Stanga et al., 2009, Plant Signal Behavior 4(10): 1-9). The contribution of TOC132 in gravity signal transduction is being investigated by analyzing the regions of this protein that are needed for the pathway, and investigating the contribution of a putative TOC132-interacting protein in gravity signal transduction. We have also isolated additional putative enhancers of arg1-2 in the hope of identifying new plastid-associated gravity signal transducers, and have initiated a screen for genetic enhancers of mar2 to seek new transducers in the ARG1 branch of the pathway.

The Emergence of Primary Anoetic Consciousness in Episodic Memory

PubMed Central

Vandekerckhove, Marie; Bulnes, Luis Carlo; Panksepp, Jaak

2014-01-01

Based on an interdisciplinary perspective, we discuss how primary-process, anoetic forms of consciousness emerge into higher forms of awareness such as knowledge-based episodic knowing and self-aware forms of higher-order consciousness like autonoetic awareness. Anoetic consciousness is defined as the rudimentary state of affective, homeostatic, and sensory-perceptual mental experiences. It can be considered as the autonomic flow of primary-process phenomenal experiences that reflects a fundamental form of first-person “self-experience,” a vastly underestimated primary form of phenomenal consciousness. We argue that this anoetic form of evolutionarily refined consciousness constitutes a critical antecedent that is foundational for all forms of knowledge acquisition via learning and memory, giving rise to a knowledge-based, or noetic, consciousness as well as higher forms of “awareness” or “knowing consciousness” that permits “time-travel” in the brain-mind. We summarize the conceptual advantages of such a multi-tiered neuroevolutionary approach to psychological issues, namely from genetically controlled primary (affective) and secondary (learning and memory), to higher tertiary (developmentally emergent) brain-mind processes, along with suggestions about how affective experiences become more cognitive and object-oriented, allowing the developmental creation of more subtle higher mental processes such as episodic memory which allows the possibility of autonoetic consciousness, namely looking forward and backward at one’s life and its possibilities within the “mind’s eye.” PMID:24427125

Genetic Counseling as an Educational Process.

ERIC Educational Resources Information Center

Eddy, James M.; St. Pierre, Richard

Historically genetic counseling programs have not included strong educational components or sound educational foundations. This paper deals with some of the drawbacks of current genetic counseling programs and the implications for education in the genetic counseling process. The author adopts a broad definition of genetic counseling which…

Impact of genetic risk information and type of disease on perceived risk, anticipated affect, and expected consequences of genetic tests.

PubMed

Cameron, Linda D; Sherman, Kerry A; Marteau, Theresa M; Brown, Paul M

2009-05-01

Genetic tests vary in their prediction of disease occurrence, with some mutations conferring relatively low risk and others indicating near certainty. The authors assessed how increments in absolute risk of disease influence risk perceptions, interest, and expected consequences of genetic tests for diseases of varying severity. Adults (N = 752), recruited from New Zealand, Australia, and the United Kingdom for an online analogue study, were randomly assigned to receive information about a test of genetic risk for diabetes, heart disease, colon cancer, or lung cancer. The lifetime risk varied across conditions by 10% increments, from 20% to 100%. Participants completed measures of perceived likelihood of disease for individuals with mutations, risk-related affect, interest, and testing consequences. Analyses revealed two increment clusters yielding differences in likelihood perceptions: A "moderate-risk" cluster (20%-70%), and a "high-risk" cluster (80%-100%). Risk increment influenced anticipated worry, feelings of risk, testing-induced distress, and family obligations, with nonlinear patterns including disproportionately high responses for the 50% increment. Risk increment did not alter testing interest or perceived benefits. These patterns of effects held across the four diseases. Magnitude of risk from genetic testing has a nonlinear influence on risk-related appraisals and affect but is unrelated to test interest.

Personality and divorce: a genetic analysis.

PubMed

Jocklin, V; McGue, M; Lykken, D T

1996-08-01

M. McGue and D.T. Lykken (1992) found that divorce risk was, to a substantial degree, genetically mediated; prior research has identified numerous social and psychological factors that affect divorce risk (G.C. Kitson, K.B. Barbi, & M.J. Roach, 1985). The present study attempted to link these domains by examining the extent to which genetic influences on one such psychological factor, personality, explain divorce risk heritability. A sample of adult twins from the Minnesota Twin Registry completed a marital history questionnaire and the Multidimensional Personality Questionnaire (A. Tellegen, 1982). Positive Emotionality and Negative Emotionality factors were positively related to divorce risk, whereas Constraint was negatively related. In women and men, respectively, 30% and 42% of the heritability of divorce risk consisted of genetic factors affecting personality and divorce risk correlated largely as a result of these common genetic influences.

Natural variation in stomatal abundance of Arabidopsis thaliana includes cryptic diversity for different developmental processes

PubMed Central

Delgado, Dolores; Alonso-Blanco, Carlos; Fenoll, Carmen; Mena, Montaña

2011-01-01

Background and Aims Current understanding of stomatal development in Arabidopsis thaliana is based on mutations producing aberrant, often lethal phenotypes. The aim was to discover if naturally occurring viable phenotypes would be useful for studying stomatal development in a species that enables further molecular analysis. Methods Natural variation in stomatal abundance of A. thaliana was explored in two collections comprising 62 wild accessions by surveying adaxial epidermal cell-type proportion (stomatal index) and density (stomatal and pavement cell density) traits in cotyledons and first leaves. Organ size variation was studied in a subset of accessions. For all traits, maternal effects derived from different laboratory environments were evaluated. In four selected accessions, distinct stomatal initiation processes were quantitatively analysed. Key Results and Conclusions Substantial genetic variation was found for all six stomatal abundance-related traits, which were weakly or not affected by laboratory maternal environments. Correlation analyses revealed overall relationships among all traits. Within each organ, stomatal density highly correlated with the other traits, suggesting common genetic bases. Each trait correlated between organs, supporting supra-organ control of stomatal abundance. Clustering analyses identified accessions with uncommon phenotypic patterns, suggesting differences among genetic programmes controlling the various traits. Variation was also found in organ size, which negatively correlated with cell densities in both organs and with stomatal index in the cotyledon. Relative proportions of primary and satellite lineages varied among the accessions analysed, indicating that distinct developmental components contribute to natural diversity in stomatal abundance. Accessions with similar stomatal indices showed different lineage class ratios, revealing hidden developmental phenotypes and showing that genetic determinants of primary and satellite lineage initiation combine in several ways. This first systematic, comprehensive natural variation survey for stomatal abundance in A. thaliana reveals cryptic developmental genetic variation, and provides relevant relationships amongst stomatal traits and extreme or uncommon accessions as resources for the genetic dissection of stomatal development. PMID:21447490

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

PubMed Central

Conway, Christopher C.; Slavich, George M.; Hammen, Constance

2016-01-01

Despite decades of research examining diathesis-stress models of emotional disorders, it remains unclear whether dysfunctional attitudes interact with stressful experiences to shape affect on a daily basis and, if so, how clinical and genetic factors influence these associations. To address these issues, we conducted a multi-level daily diary study that examined how dysfunctional attitudes and stressful events relate to daily fluctuations in negative and positive affect in 104 young adults. Given evidence that clinical and genetic factors underlie stress sensitivity, we also examined how daily affect is influenced by internalizing and externalizing symptoms and brain-derived neurotrophic factor (BDNF) genotype, which have been shown to influence neural, endocrine, and affective responses to stress. In multivariate models, internalizing symptoms and BDNF Val66Met genotype independently predicted heightened negative affect on stressful days, but dysfunctional attitudes did not. Specifically, the BDNF Met allele and elevated baseline internalizing symptomatology predicted greater increases in negative affect in stressful circumstances. These data are the first to demonstrate that BDNF genotype and stress are jointly associated with daily fluctuations in negative affect, and they challenge the assumption that maladaptive beliefs play a strong independent role in determining affective responses to everyday stressors. The results may thus inform the development of new multi-level theories of psychopathology and guide future research on predictors of affective lability. PMID:27041782

Social and spatial effects on genetic variation between foraging flocks in a wild bird population.

PubMed

Radersma, Reinder; Garroway, Colin J; Santure, Anna W; de Cauwer, Isabelle; Farine, Damien R; Slate, Jon; Sheldon, Ben C

2017-10-01

Social interactions are rarely random. In some instances, animals exhibit homophily or heterophily, the tendency to interact with similar or dissimilar conspecifics, respectively. Genetic homophily and heterophily influence the evolutionary dynamics of populations, because they potentially affect sexual and social selection. Here, we investigate the link between social interactions and allele frequencies in foraging flocks of great tits (Parus major) over three consecutive years. We constructed co-occurrence networks which explicitly described the splitting and merging of 85,602 flocks through time (fission-fusion dynamics), at 60 feeding sites. Of the 1,711 birds in those flocks, we genotyped 962 individuals at 4,701 autosomal single nucleotide polymorphisms (SNPs). By combining genomewide genotyping with repeated field observations of the same individuals, we were able to investigate links between social structure and allele frequencies at a much finer scale than was previously possible. We explicitly accounted for potential spatial effects underlying genetic structure at the population level. We modelled social structure and spatial configuration of great tit fission-fusion dynamics with eigenvector maps. Variance partitioning revealed that allele frequencies were strongly affected by group fidelity (explaining 27%-45% of variance) as individuals tended to maintain associations with the same conspecifics. These conspecifics were genetically more dissimilar than expected, shown by genomewide heterophily for pure social (i.e., space-independent) grouping preferences. Genomewide homophily was linked to spatial configuration, indicating spatial segregation of genotypes. We did not find evidence for homophily or heterophily for putative socially relevant candidate genes or any other SNP markers. Together, these results demonstrate the importance of distinguishing social and spatial processes in determining population structure. © 2017 John Wiley & Sons Ltd.

Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples.

PubMed

Mandage, Rajendra; Telford, Marco; Rodríguez, Juan Antonio; Farré, Xavier; Layouni, Hafid; Marigorta, Urko M; Cundiff, Caitlin; Heredia-Genestar, Jose Maria; Navarro, Arcadi; Santpere, Gabriel

2017-01-01

Epstein-Barr virus (EBV), human herpes virus 4, has been classically associated with infectious mononucleosis, multiple sclerosis and several types of cancers. Many of these diseases show marked geographical differences in prevalence, which points to underlying genetic and/or environmental factors. Those factors may include a different susceptibility to EBV infection and viral copy number among human populations. Since EBV is commonly used to transform B-cells into lymphoblastoid cell lines (LCLs) we hypothesize that differences in EBV copy number among individual LCLs may reflect differential susceptibility to EBV infection. To test this hypothesis, we retrieved whole-genome sequenced EBV-mapping reads from 1,753 LCL samples derived from 19 populations worldwide that were sequenced within the context of the 1000 Genomes Project. An in silico methodology was developed to estimate the number of EBV copy number in LCLs and validated these estimations by real-time PCR. After experimentally confirming that EBV relative copy number remains stable over cell passages, we performed a genome wide association analysis (GWAS) to try detecting genetic variants of the host that may be associated with EBV copy number. Our GWAS has yielded several genomic regions suggestively associated with the number of EBV genomes per cell in LCLs, unraveling promising candidate genes such as CAND1, a known inhibitor of EBV replication. While this GWAS does not unequivocally establish the degree to which genetic makeup of individuals determine viral levels within their derived LCLs, for which a larger sample size will be needed, it potentially highlighted human genes affecting EBV-related processes, which constitute interesting candidates to follow up in the context of EBV related pathologies.

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project.

PubMed

Cutting, Elizabeth M; Overby, Casey L; Banchero, Meghan; Pollin, Toni; Kelemen, Mark; Shuldiner, Alan R; Beitelshees, Amber L

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease.

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project

PubMed Central

Cutting, Elizabeth M.; Overby, Casey L.; Banchero, Meghan; Pollin, Toni; Kelemen, Mark; Shuldiner, Alan R.; Beitelshees, Amber L.

2015-01-01

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease. PMID:26958179

Regulatory effects of cotranscriptional RNA structure formation and transitions.

PubMed

Liu, Sheng-Rui; Hu, Chun-Gen; Zhang, Jin-Zhi

2016-09-01

RNAs, which play significant roles in many fundamental biological processes of life, fold into sophisticated and precise structures. RNA folding is a dynamic and intricate process, which conformation transition of coding and noncoding RNAs form the primary elements of genetic regulation. The cellular environment contains various intrinsic and extrinsic factors that potentially affect RNA folding in vivo, and experimental and theoretical evidence increasingly indicates that the highly flexible features of the RNA structure are affected by these factors, which include the flanking sequence context, physiochemical conditions, cis RNA-RNA interactions, and RNA interactions with other molecules. Furthermore, distinct RNA structures have been identified that govern almost all steps of biological processes in cells, including transcriptional activation and termination, transcriptional mutagenesis, 5'-capping, splicing, 3'-polyadenylation, mRNA export and localization, and translation. Here, we briefly summarize the dynamic and complex features of RNA folding along with a wide variety of intrinsic and extrinsic factors that affect RNA folding. We then provide several examples to elaborate RNA structure-mediated regulation at the transcriptional and posttranscriptional levels. Finally, we illustrate the regulatory roles of RNA structure and discuss advances pertaining to RNA structure in plants. WIREs RNA 2016, 7:562-574. doi: 10.1002/wrna.1350 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Penicillium purpurogenum cultures under ethanol-induced stress and its correlation with fungal adhesion and biodegrading ability.

PubMed

Gomaa, Ola M; Husseiny, Sherif M; Abd El Kareem, Hussein; Talaat, Riham

2016-10-01

Fungi are known to be affected by external environmental stimuli, resulting in different stress response effects, which in turn could be used to enhance its biodegrading ability. In a previous study, ethanol was used to manipulate cell-cell and cell-surface interaction to prevent cell loss and maximize the usage of Penicillium purpurogenum cells in the media, a correlation was drawn between ethanol oxidative stress, surface-bound proteins and fungal adhesion. The present study focuses on a more detailed study of the effect of ethanol on the same fungus. The results show that the presence of Yap1p gene and the detection of an oxidized form of glutathione (GSSG) suggest that a stress response might be involved in the adhesion process. The process of adhesion could be described as a signaling process and it is affected by the germ tube formation as an initial step in adhesion. Protein profile showed polymorphism in surface-bound proteins for cultures amended with ethanol when compared to control cultures. Ethanol also affected the DNA polymorphic profile of DNA, rendering the fungus genetically variable. P. purpurogenum produced phenol oxidase enzyme and could be used to degrade total phenols in olive mill waste water without the formation of biofilm on the surface of the containers.