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Imprinting
Kinds of Imprinting Terms modified by Imprinting Selected AbstractsCYTONUCLEAR INTERACTIONS CAN FAVOR THE EVOLUTION OF GENOMIC IMPRINTINGEVOLUTION, Issue 5 2009Jason B. Wolf Interactions between cytoplasmic (generally organelle) and nuclear genomes may be relatively common and could potentially have major fitness consequences. As in the case of within-genome epistasis, this cytonuclear epistasis can favor the evolutionary coadaptation of high-fitness combinations of nuclear and cytoplasmic alleles. Because cytoplasmic factors are generally uniparentally inherited, the cytoplasmic genome is inherited along with only one of the nuclear haplotypes, and therefore, coadaptation is expected to evolve through the interaction of these coinherited (usually maternally inherited) genomes. Here I show that, as a result of this coinheritance of the two genomes, cytonuclear epistasis can favor the evolution of genomic imprinting such that, when the cytoplasmic factor is maternally inherited, selection favors maternal expression of the nuclear locus and when the factor is paternally inherited selection favors paternal expression. Genomic imprinting evolves in this model because it leads to a pattern of gene expression in the nuclear haplotype that is coadapted with (i.e., adaptively coordinated with) gene expression in the coinherited cytoplasmic genome. [source] PERSPECTIVE: MATERNAL KIN GROUPS AND THE ORIGINS OF ASYMMETRIC GENETIC SYSTEMS,GENOMIC IMPRINTING, HAPLODIPLOIDY, AND PARTHENOGENESISEVOLUTION, Issue 4 2006Benjamin B. Normark Abstract The genetic systems of animals and plants are typically eumendelian. That is, an equal complement of autosomes is inherited from each of two parents, and at each locus, each parent's allele is equally likely to be expressed and equally likely to be transmitted. Genetic systems that violate any of these eumendelian symmetries are termed asymmetric and include parent-specific gene expression (PSGE), haplodiploidy, thelytoky, and related systems. Asymmetric genetic systems typically arise in lineages with close associations between kin (gregarious siblings, brooding, or viviparity). To date, different explanatory frameworks have been proposed to account for each of the different asymmetric genetic systems. Haig's kinship theory of genomic imprinting argues that PSGE arises when kinship asymmetries between interacting kin create conflicts between maternally and paternally derived alleles. Greater maternal than paternal relatedness within groups selects for more "abstemious" expression of maternally derived alleles and more "greedy" expression of paternally derived alleles. Here, I argue that this process may also underlie origins of haplodiploidy and many origins of thelytoky. The tendency for paternal alleles to be more "greedy" in maternal kin groups means that maternal-paternal conflict is not a zero-sum game: the maternal optimum will more closely correspond to the optimum for family groups and demes and for associated entities such as symbionts. Often in these circumstances, partial or complete suppression of paternal gene expression will evolve (haplodiploidy, thelytoky), or other features of the life cycle will evolve to minimize the conflict (monogamy, inbreeding). Maternally transmitted cytoplasmic elements and maternally imprinted nuclear alleles have a shared interest in minimizing agonistic interactions between female siblings and may cooperate to exclude the paternal genome. Eusociality is the most dramatic expression of the conflict-reducing effects of haplodiploidy, but its original and more widespread function may be suppression of intrafamilial cannibalism. In rare circumstances in which paternal gene products gain access to maternal physiology via a placenta, PSGE with greedy paternal gene expression can persist (e.g., in mammals). [source] Sensitive Biomimetic Sensor Based on Molecular Imprinting at Functionalized Indium Tin Oxide ElectrodesELECTROANALYSIS, Issue 16 2007Na Gao Abstract We initially report an electrochemical sensing platform based on molecularly imprinted polymers (MIPs) at functionalized Indium Tin Oxide Electrodes (ITO). In this research, aminopropyl-derivatized organosilane aminopropyltriethoxysilane (APTES), which plays the role of functional monomers for template recognition, was firstly self-assembled on an ITO electrode and then dopamine-imprinted sol was spin-coated on the modified surface. APTES which can interact with template dopamine (DA) through hydrogen bonds brought more binding sites located closely to the surface of the ITO electrode, thus made the prepared sensor more sensitive for DA detection. Potential scanning is presented to extract DA from the modified film, thus DA can rapidly and completely leach out. The affinity and selectivity of the resulting biomimetic sensor were characterized using cyclic voltammetry (CV). It exhibited an increased affinity for DA over that of structurally related molecules, the anodic current for DA oxidation depended on the concentration of DA in the linear range from 2×10,6 M to 0.8×10,3 M with a correlation coefficient of 0.9927. In contrast, DA-templated film prepared under identical conditions on a bare ITO showed obviously lower response toward dopamine in solution. It should be noted that potential scanning is a very effective approach for DA extraction, and surface modification of the electrochemical transducer with functional monomers is responsible for the development of MIPs-based highly sensitive biomimetic sensor. [source] Estimation of variance components due to imprinting effects with DFREML and VCE: results of a simulation studyJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 1 2002A. ESSL Treating gametes as homozygous diploid individuals, TIER and SÖLKNER (Theor. Appl. Genet. 85: 868,872, 1993) proposed a method which manages the use of available computer programs with a common animal model to estimate variance components caused by imprinting effects. Despite some relevant model restrictions, this approach has already been used in some field data analyses by an adapted version of the widely used DFREML computer program, subsequently indicated by DFREMLa. The main objective of this study was to ascertain the properties of DFREMLa by computer simulation and to examine other alternative estimation approaches. The most important results may be summarized as follows: (1) Treating gametes as homozygous diploid individuals has the consequence that one-half of the actually realized gametic effect is totally abstracted in variance component estimation. Thus, an additional adjustment of the phenotypic variance calculated by DFREMLa is necessary to get correct values of estimated variance component ratios. (2) Adjusted DFREMLa estimates yielded correct results when animals were unselected and only maternal or paternal imprinting (not both simultaneously) occurred. (3) When the model did not adequately account for the additive genetic component within a maternal lineage, significant upward biases for the cytoplasmic component were observed. (4) The use of a simple dam and sire model with appropriate relationship matrices can be recommended when only the difference of maternal and paternal imprinting effects is of primary interest and the covariance between maternal halfsibs is not substantially increased by common environmental effects. (5) An adequate estimation of variance components for all possible imprinting situations requires the use of an animal model augmented by both maternal and paternal gametic effects. Unfortunately, a computer program on the basis of such a model does not yet exist. Schätzung von Varianzkomponenten für Imprintingeffekte mittels DFREML und VCE: Ergebnisse einer Simulationsstudie TIER and SÖLKNER (Theor. Appl. Genet. 85: 868,872, 1993) schlugen eine Methode zur Schätzung von imprintingbedingten Varianzkomponenten vor, die mit einem einfach zu adaptierenden Computerprogramm auf der Basis eines üblichen Tiermodells vorgenommen werden kann, indem sie Gameten wie homozygot diploide Individuen behandelten. Obwohl dieser Ansatz einige praxisrelevante Einschränkungen hat, wurde er bereits bei einigen Felddatenanalysen verwendet. Für diesen Zweck wurde eine entsprechend adaptierte Version des häufig verwendeten Computerprogrammes DFREML eingesetzt, die im folgenden mit DFREMLa bezeichnet wird. Das Ziel der vorliegen Untersuchung lag darin, die Eigenschaften von DFREMLa bei verschiedenen Imprintingsituationen zu überprüfen und weiters die Brauchbarkeit anderer möglicher Schätzansätze zu überprüfen. (1) Werden Gameten wie diploide homozygote Individuen aufgefaßt, dann geht bei der Schätzung von Varianzkomponenten mit DFREMLa eine Hälfte des tatsächlich wirksamen Gameteneffektes völlig verloren. Das heißt, die von DFREMLa ausgewiesenen Ergebnisse müssen nachträglich entsprechend adjustiert werden, um korrekte Schätzergebnisse für alle jene Quotienten von Varianzkomponenten zu erhalten, bei denen die gesamte phänotypische Varianz im Nenner steht. (2) Die adjustierten DFREMLa Schätzwerte lieferten in all jenen Fällen korrekte Ergebnisse, wo keine Selektion der Tiere erfolgte und entweder nur maternales oder paternales Imprinting (nicht beide gleichzeitig) auftrat. (3) Alle Modelle, bei denen die additiv genetische Komponente innerhalb einer Kuhfamilie keine adäquate Berücksichtigung fand, führten zu einer systematischen Überschätzung der zytoplasmatischen Varianzkomponente. (4) Ist nur jene Varianzkomponente von Interesse, die durch unterschiedlich starkes maternales bzw. paternales Imprinting erklärt werden kann, dann kann auch die Verwendung einfacher Vater-bzw. Muttermodelle empfohlen werden. Voraussetzung hierfür ist allerdings, daß die Kovarianz zwischen mütterlichen Halbgeschwistern durch keine gemeinsame Umwelt erhöht ist. (5) Eine für alle Imprintingsituationen problemadäquate Schätzung von Varianzkomponenten verlangt die Anwendung eines Tiermodelles, erweitert um beide imprintingbedingten Gameteneffekte. Leider fehlt gegenwärtig hierfür noch ein entsprechendes Computerprogramm. [source] Neuroendocrinology Briefings 16: Genomic Imprinting, Hormones and BehaviourJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2002Article first published online: 9 OCT 200 First page of article [source] Imprinting on chromosome 20: Tissue-specific imprinting and imprinting mutations in the GNAS locus,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010Gavin Kelsey Abstract The GNAS locus on chromosome 20q13.11 is the archetypal complex imprinted locus. It comprises a bewildering array of alternative transcripts determined by differentially imprinted promoters which encode distinct proteins. It also provides the classic example of tissue-specific imprinted gene expression, in which the canonical GNAS transcript coding for Gs, is expressed predominantly from the maternal allele in a set of seemingly unrelated tissues. Functionally, this rather obscure imprinting is nevertheless of considerable clinical significance, as it dictates the nature of the disease caused by inactivating mutations in Gs,, with end organ hormone resistance specifically on maternal transmission (pseudohypoparathyroidism type 1a, PHP1a). In addition, there is a bona fide imprinting disorder, PHP1b, which is caused specifically by DNA methylation defects in the differentially methylated regions (DMRs) that determine tissue-specific monoallelic expression of GNAS. Although the genetic defect in PHP1a and the disrupted imprinting in PHP1b both essentially result in profound reduction of Gs, activity in tissues with monoallelic GNAS expression, and despite a growing awareness of the overlap in these two conditions, there are important pathophysiological differences between the two whose basis is not fully understood. PHP1b is one of the only imprinted gene syndromes in which cis -acting mutations have been discovered that disrupt methylation of germline-derived imprint marks; such imprinting mutations in GNAS are helping to provide important new insights into the mechanisms of imprinting establishment generally. © 2010 Wiley-Liss, Inc. [source] Private Sector Imprinting: An Examination of the Impacts of Private Sector Job Experience on Public Manager's Work AttitudesPUBLIC ADMINISTRATION REVIEW, Issue 1 2010Craig Boardman What are the attitudes of public managers who have had full-time private sector work experience? Public managers with private sector work experience report different perspectives when compared to their counterparts who have spent their entire careers in the public sector. Though private sector work experience negatively correlates with job satisfaction, it only does so for the "new switcher," whose last job was in the private sector. As careers advance, the negative impact seems to wane, leaving a public sector workforce that, in part as a result of their private sector work experience, are relatively more intrinsically motivated and involved in their jobs. We conclude with discussion of implications for human resources management. [source] The Essence of Linkage-based Imprinting Detection: Comparing Power, Type 1 Error, and the Effects of Confounders in Two Different Analysis ApproachesANNALS OF HUMAN GENETICS, Issue 3 2010David A. Greenberg Summary Imprinting is critical to understanding disease expression. It can be detected using linkage information, but the effects of potential confounders (heterogeneity, sex-specific penetrance, and sex-biased ascertainment) have not been explored. We examine power and confounders in two imprinting detection approaches, and we explore imprinting-linkage interaction. One method (PP) models imprinting by maximising lod scores w.r.t. parent-specific penetrances. The second (DRF) approximates imprinting by maximising lods over differential male-female recombination fractions. We compared power, type 1 error, and confounder effects in these two methods, using computer-simulated data. We varied heterogeneity, penetrance, family and dataset size, and confounders that might mimic imprinting. Without heterogeneity, PP had more imprinting-detecting power than DRF. PP's power increased when parental affectedness status was ignored, but decreased with heterogeneity. With heterogeneity, type 1 error increased dramatically for both methods. However, DRF's power also increased under heterogeneity, more than was attributable to inflated type 1 error. Sex-specific penetrance could increase false positives for PP but not for DRF. False positives did not increase on ascertainment through an affected "mother". For PP, non-penetrant individuals increased information, arguing against using affecteds-only methods. The high type 1 error levels under some circumstances means these methods must be used cautiously. [source] Imprinting and looping: epigenetic marks control interactions between regulatory elementsBIOESSAYS, Issue 1 2005Yuzuru Kato Gene regulation involves various cis -regulatory elements that can act at a distance. They may physically interact each other or with their target genes to exert their effects. Such interactions are beginning to be uncovered in the imprinted Igf2/H19 domain.1 The differentially methylated regions (DMRs), containing insulators, silencers and activators, were shown to have physical contacts between them. The interactions were changeable depending on their epigenetic state, presumably enabling Igf2 to move between an active and a silent chromatin domain. The study gives us a novel view on how regulatory elements influence gene expression and how epigenetic modifications modulate their long-range effects. BioEssays 27:1,4, 2005. © 2004 Wiley Periodicals, Inc. [source] EPIGENETIK: Genomic Imprinting in SäugetierenBIOLOGIE IN UNSERER ZEIT (BIUZ), Issue 2 2007Article first published online: 11 APR 200 Die Epigenetik beschäftigt sich mit der Weitergabe von Eigenschaften auf die Nachkommen, die nicht auf Abweichungen in der DNA-Sequenz beruhen. Prominente Beispiele für epigenetische Modifikationen des Chromatins sind die Addition von Acetyl- oder Methylgruppen , auf unserem Titelbild symbolisiert durch den kleinen Turner in der Doppelhelix. Mehr zum Thema lesen Sie ab Seite 86. Bild: Linda Bucklin , FOTOLIA. [source] Quantifying Genomic Imprinting in the Presence of LinkageBIOMETRICS, Issue 4 2006Quentin Vincent Summary Genomic imprinting decreases the power of classical linkage analysis, in which paternal and maternal transmissions of marker alleles are equally weighted. Several methods have been proposed for taking genomic imprinting into account in the model-free linkage analysis of binary traits. However, none of these methods are suitable for the formal identification and quantification of genomic imprinting in the presence of linkage. In addition, the available methods are designed for use with pure sib-pairs, requiring artificial decomposition in cases of larger sibships, leading to a loss of power. We propose here the maximum likelihood binomial method adaptive for imprinting (MLB-I), which is a unified analytic framework giving rise to specific tests in sibships of any size for (i) linkage adaptive to imprinting, (ii) genomic imprinting in the presence of linkage, and (iii) partial versus complete genomic imprinting. In addition, we propose an original measure for quantifying genomic imprinting. We have derived and validated the distribution of the three tests under their respective null hypotheses for various genetic models, and have assessed the power of these tests in simulations. This method can readily be applied to genome-wide scanning, as illustrated here for leprosy sibships. Our approach provides a novel tool for dissecting genomic imprinting in model-free linkage analysis, and will be of considerable value for identifying and evaluating the contribution of imprinted genes to complex diseases. [source] From 3D to 2D: A Review of the Molecular Imprinting of ProteinsBIOTECHNOLOGY PROGRESS, Issue 6 2006Nicholas W. Turner Molecular imprinting is a generic technology that allows for the introduction of sites of specific molecular affinity into otherwise homogeneous polymeric matrices. Commonly this technique has been shown to be effective when targeting small molecules of molecular weight <1500, while extending the technique to larger molecules such as proteins has proven difficult. A number of key inherent problems in protein imprinting have been identified, including permanent entrapment, poor mass transfer, denaturation, and heterogeneity in binding pocket affinity, which have been addressed using a variety of approaches. This review focuses on protein imprinting in its various forms, ranging from conventional bulk techniques to novel thin film and monolayer surface imprinting approaches. [source] ChemInform Abstract: Synthesis of Heterogeneous Palladium Catalyst Assemblies by Molecular Imprinting.CHEMINFORM, Issue 16 2002Andrew N. Cammidge Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Imprinting Status of G,S, NESP55, and XL,s in Cell Cultures Derived from Human Embryonic Germ Cells: GNAS Imprinting in Human Embryonic Germ CellsCLINICAL AND TRANSLATIONAL SCIENCE, Issue 5 2009Janet L. Crane M.D. Abstract GNAS is a complex gene that through use of alternative first exons encodes signaling proteins G,s and XL,s plus neurosecretory protein NESP55. Tissue-specific expression of these proteins is regulated through reciprocal genomic imprinting in fully differentiated and developed tissue. Mutations in GNAS account for several human disorders, including McCune-Albright syndrome and Albright hereditary osteodystrophy, and further knowledge of GNAS imprinting may provide insights into variable phenotypes of these disorders. We therefore analyzed expression of G,s, NESP55, and XL,s prior to tissue differentiation in cell cultures derived from human primordia germ cells. We found that the expression of G,s was biallelic (maternal allele: 52.6%± 2.5%; paternal allele: 47.2%± 2.5%; p= 0.07), whereas NESP55 was expressed preferentially from the maternal allele (maternal allele: 81.9%± 10%; paternal allele: 18.1%± 10%; p= 0.002) and XL,s was preferentially expressed from the paternal allele (maternal allele: 2.7%± 0.3%; paternal allele: 97.3%± 0.3%; p= 0.007). These results demonstrate that imprinting of NESP55 occurs very early in development, although complete imprinting appears to take place later than 5,11 weeks postfertilization, and that imprinting of XL,s occurs very early postfertilization. By contrast, mprinting of G,s most likely occurs after 11 weeks postfertilization and after tissue differentiation. [source] Epigenetic control of skeletal muscle fibre typeACTA PHYSIOLOGICA, Issue 4 2010K. Baar Abstract Adult muscle is extremely plastic. However, the muscle precursor cells associated with those fibres show stable and heritable differences in gene expression indicative of epigenetic imprinting. Epigenetic processes in the development of skeletal muscle have been appreciated for over a decade; however, there are a paucity of studies looking at whether epigenetics determines the phenotype of adult and/or ageing skeletal muscle. This review presents the evidence that epigenetics plays a role in determining adult muscle function and a series of unanswered questions that would greatly increase our understanding of how epigenetics works in adult muscle. With the increased interest in epigenetics, over the next few years this field will begin to unfold in unimaginable directions. [source] Turner syndrome: Neuroimaging findings: Structural and functionalDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2009Ronan Mullaney Abstract Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including the parietal lobe; cerebellum, amygdala, hippocampus; and basal ganglia; and perhaps differences in "connectivity" between frontal and parieto-occipital regions. Finally, there is preliminary evidence that genomic imprinting, sex hormones and growth hormone have significant modulatory effects on brain maturation in TS. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:279,283. [source] Indiscriminate nursing in communal breeders: a role for genomic imprintingECOLOGY LETTERS, Issue 3 2003Alexandre Roulin Abstract In several communally nesting mammal species, females indiscriminately nurse each others' offspring. Previous hypotheses have suggested that the inability to recognize one's own young during lactation is the result of costs incurred from recognition errors. Here, we propose an alternative hypothesis based on sexual conflict theory and genomic imprinting. In polygynous species, males copulate with several females that may later breed communally. Under such conditions, males benefit from indiscriminate nursing of all their offspring and the reduced risk of female infanticide. This may have selected for paternally expressed genes that suppress kin recognition during lactation. [source] Removal of high-abundance proteins for nuclear subproteome studies in rice (Oryza sativa) endospermELECTROPHORESIS, Issue 3 2008Guosheng Li Abstract Endosperm is a highly specialized storage organ with three sets of genomes. It is one of the most economically important organs in plants. Endosperm development involves parental imprinting and endoreduplication. A thorough study of the endosperm proteome, particularly the nuclear proteome, may provide critical insight into the regulation of seed development. Unfortunately, endosperm is extremely rich in starch grains and protein bodies of different sizes, making proteome studies on nonstorage proteins, particularly the low-abundance proteins, very challenging. Here we have developed a chromatographic method to remove large starch grains and an electrophoresis method to recover low-abundance proteins, respectively. Using these methods, we have identified 468 proteins from the nuclear enriched fraction of rice endosperm, including transcription factors, histone modification proteins, kinetochore proteins, centromere/microtubule binding proteins, and transposon proteins. Among the 468 proteins, 208 (44%) are hypothetical proteins, indicating that the endosperm proteome is poorly explored. In addition, analyses of the MS/MS data using BioWorks 3.1 have identified 59 putative acetylated proteins and 40 putative methylated proteins. Our studies have developed a method to remove starch grains and recover low-abundance proteins, respectively. The methods should be applicable to other organisms. [source] Molecularly imprinted polymers as a tool for separation in CECELECTROPHORESIS, Issue 1-2 2007Zhao-Sheng Liu Dr. Abstract Molecularly imprinted polymers (MIPs) are synthesized in the presence of a template which results in the formation of specific recognition cavities complementary to the template in shape and chemical functionality. One of the most successful application areas of MIPs is chromatographic sorbents, which are tailor-made synthetic polymers for a given analyte. However, low efficiency of MIP columns is often observed because of slow kinetics of the template. CEC-based MIPs are thought to improve efficiency of MIP-based separation due to the enhanced flow dynamics of CEC. Another attractive feature is the miniaturized format of CEC, so that fewer templates or monomers for the molecular imprinting are consumed, a characteristic desired for ,green chemistry'. The small dimensions of a capillary demand the development of novel polymer formats that can be applied to a miniaturized system. This review discusses the various formats, i.e., the micro- or nanoparticle, the coating and the monolith, for application in CEC as well as the use in MIP syntheses and characteristics. [source] Assessing human germ-cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2007Andrew J. Wyrobek Abstract Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ,5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multiple-endpoint studies. Additional studies could involve the examination of transgenerational effects associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germ-cell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis. Environ. Mol. Mutagen., 2007. Published 2007 Wiley-Liss, Inc. [source] DNA methylation controls Foxp3 gene expressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Julia Abstract Compelling evidence suggests that Foxp3-expressing CD25+CD4+ regulatory T cells (Treg) are generated within the thymus as a separate lineage. However, Foxp3+CD4+ Treg can also be generated de novo in a TGF-,-dependent process from naive T cells by TCR triggering. Recently, we have shown that naturally occurring, but not in vitro TGF-,-induced Foxp3+ Treg display stable Foxp3 expression that was associated with selective demethylation of an evolutionarily conserved element within the Foxp3 locus named TSDR (Treg-specific demethylated region). Here, we report that inhibition of DNA methylation by azacytidine, even in absence of exogenous TGF-,, not only promoted de novo induction of Foxp3 expression during priming, but also conferred stability of Foxp3 expression upon restimulation. Most notably, such stable Foxp3 expression was found only for cells displaying enhanced TSDR demethylation. In contrast, in vitro TSDR methylation diminished its transcriptional activity. Foxp3+ Treg generated in vivo by DEC-205-mediated targeting of agonist ligands to dendritic cells showed long-term survival in the absence of the inducing antigen and exhibited efficient TSDR demethylation. Together, our data suggest that TSDR is an important methylation-sensitive element regulating Foxp3 expression and demonstrate that epigenetic imprinting in this region is critical for establishment of a stable Treg lineage. Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/38105_s.pdf [source] Long-term maternal imprinting of the specific B cell repertoire by maternal antibodiesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Katja Fink Abstract Maternal antibodies protect newborns whilst they are immunologically immature. This study shows that maternal antibodies can also shape the B cell repertoire of the offspring long after the maternal antibodies themselves become undetectable. VHDJH gene-targeted (VI10) mice expressing a heavy chain specific for vesicular stomatitis virus (VSV) produce a 20-fold increased spontaneous titer of VSV-neutralizing antibodies. When transferred from mother to offspring, these antibodies prevented accumulation of Ag-specific transitional type,2 and marginal zone B cells with an activated phenotype and favored selection to the B cell follicles. This effect was B cell-intrinsic and lasted up to adulthood. The pups nursed by mothers producing specific antibodies developed higher endogenous antibody titers of this specificity which perpetuated the effects of specific B cell selection into the mature follicular compartment, presumably by blocking auto-Ag-dependent development of transitional type,2 B cells in the spleen. This repertoire change was functional, as following infection of adult mice with VSV, those pups that had received specific maternal antibodies as neonates had increased pre-immune titers and mounted strong early IgG neutralizing antibodies. [source] HERITABILITY OF AND EARLY ENVIRONMENT EFFECTS ON VARIATION IN MATING PREFERENCESEVOLUTION, Issue 4 2010Holger Schielzeth Many species show substantial between-individual variation in mating preferences, but studying the causes of such variation remains a challenge. For example, the relative importance of heritable variation versus shared early environment effects (like sexual imprinting) on mating preferences has never been quantified in a population of animals. Here, we estimate the heritability of and early rearing effects on mate choice decisions in zebra finches based on the similarity of choices between pairs of genetic sisters raised apart and pairs of unrelated foster sisters. We found a low and nonsignificant heritability of preferences and no significant shared early rearing effects. A literature review shows that a low heritability of preferences is rather typical, whereas empirical tests for the relevance of sexual imprinting within populations are currently limited to very few studies. Although effects on preference functions (i.e., which male to prefer) were weak, we found strong individual consistency in choice behavior and part of this variation was heritable. It seems likely that variation in choice behavior (choosiness, responsiveness, sampling behavior) would produce patterns of nonrandom mating and this might be the more important source of between-individual differences in mating patterns. [source] RELATIVE CONTRIBUTION OF ADDITIVE, DOMINANCE, AND IMPRINTING EFFECTS TO PHENOTYPIC VARIATION IN BODY SIZE AND GROWTH BETWEEN DIVERGENT SELECTION LINES OF MICEEVOLUTION, Issue 5 2009Reinmar Hager Epigenetic effects attributed to genomic imprinting are increasingly recognized as an important source of variation in quantitative traits. However, little is known about their relative contribution to phenotypic variation compared to those of additive and dominance effects, and almost nothing about their role in phenotypic evolution. Here we address these questions by investigating the relative contribution of additive, dominance, and imprinting effects of quantitative trait loci (QTL) to variation in "early" and "late" body weight in an intercross of mice selected for divergent adult body weight. We identified 18 loci on 13 chromosomes; additive effects accounted for most of the phenotypic variation throughout development, and imprinting effects were always small. Genetic effects on early weight showed more dominance, less additive, and, surprisingly, less imprinting variation than that of late weight. The predominance of additivity of QTL effects on body weight follows the expectation that additive effects account for the evolutionary divergence between selection lines. We hypothesize that the appearance of more imprinting effects on late body weight may be a consequence of divergent selection on adult body weight, which may have indirectly selected for alleles showing partial imprinting effects due to their associated additive effects, highlighting a potential role of genomic imprinting in the response to selection. [source] CYTONUCLEAR INTERACTIONS CAN FAVOR THE EVOLUTION OF GENOMIC IMPRINTINGEVOLUTION, Issue 5 2009Jason B. Wolf Interactions between cytoplasmic (generally organelle) and nuclear genomes may be relatively common and could potentially have major fitness consequences. As in the case of within-genome epistasis, this cytonuclear epistasis can favor the evolutionary coadaptation of high-fitness combinations of nuclear and cytoplasmic alleles. Because cytoplasmic factors are generally uniparentally inherited, the cytoplasmic genome is inherited along with only one of the nuclear haplotypes, and therefore, coadaptation is expected to evolve through the interaction of these coinherited (usually maternally inherited) genomes. Here I show that, as a result of this coinheritance of the two genomes, cytonuclear epistasis can favor the evolution of genomic imprinting such that, when the cytoplasmic factor is maternally inherited, selection favors maternal expression of the nuclear locus and when the factor is paternally inherited selection favors paternal expression. Genomic imprinting evolves in this model because it leads to a pattern of gene expression in the nuclear haplotype that is coadapted with (i.e., adaptively coordinated with) gene expression in the coinherited cytoplasmic genome. [source] Turner syndrome and the evolution of human sexual dimorphismEVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 3 2008Bernard Crespi Abstract Turner syndrome is caused by loss of all or part of an X chromosome in females. A series of recent studies has characterized phenotypic differences between Turner females retaining the intact maternally inherited versus paternally inherited X chromosome, which have been interpreted as evidence for effects of X-linked imprinted genes. In this study I demonstrate that the differences between Turner females with a maternal X and a paternal X broadly parallel the differences between males and normal females for a large suite of traits, including lipid profile and visceral fat, response to growth hormone, sensorineural hearing loss, congenital heart and kidney malformations, neuroanatomy (sizes of the cerebellum, hippocampus, caudate nuclei and superior temporal gyrus), and aspects of cognition. This pattern indicates that diverse aspects of human sex differences are mediated in part by X-linked genes, via genomic imprinting of such genes, higher rates of mosaicism in Turner females with an intact X chromosome of paternal origin, karyotypic differences between Turner females with a maternal versus paternal X chromosome, or some combination of these phenomena. Determining the relative contributions of genomic imprinting, karyotype and mosaicism to variation in Turner syndrome phenotypes has important implications for both clinical treatment of individuals with this syndrome, and hypotheses for the evolution and development of human sexual dimorphism. [source] Genetic evidence for Dnmt3a-dependent imprinting during oocyte growth obtained by conditional knockout with Zp3 -Cre and complete exclusion of Dnmt3b by chimera formationGENES TO CELLS, Issue 3 2010Masahiro Kaneda In the male and female germ-lines of mice, both of the two de novo DNA methyltransferases Dnmt3a and Dnmt3b are expressed. By the conditional knockout experiments using the Tnap -Cre gene, we previously showed that deletion of Dnmt3a in primordial germ cells disrupts paternal and maternal imprinting, however, Dnmt3b mutants did not show any defect. Here, we have knocked out Dnmt3a after birth in growing oocytes by using the Zp3 -Cre gene and obtained genetic evidence that de novo methylation by Dnmt3a during the oocyte growth stage is indispensable for maternal imprinting. We also carried out DNA methylation analysis in the mutant oocytes and embryos and found that hypomethylation of imprinted genes in Dnmt3a -deficient oocytes was directly inherited to the embryos, but repetitive elements were re-methylated during development. Furthermore, we show that Dnmt3b -deficient cells can contribute to the male and female germ-lines in chimeric mice and can produce normal progeny, establishing that Dnmt3b is dispensable for mouse gametogenesis and imprinting. Finally, Dnmt3-related protein Dnmt3L is not only essential for methylation of imprinted genes but also enhances de novo methylation of repetitive elements in growing oocytes. [source] Spontaneous Lamellar Alignment in Thickness-Modulated Block Copolymer FilmsADVANCED FUNCTIONAL MATERIALS, Issue 16 2009Bong Hoon Kim Abstract Here, spontaneous lamellar alignment in a thickness-modulated block copolymer film is presented as a facile, scalable, and general approach for creating a highly aligned lamellar morphology. Thickness-modulated block copolymer films are prepared on neutral surfaces by various methods, such as solution dropping, dewetting-induced self-organized patterning, and thermal imprinting. Regardless of the film preparation method, the self-assembled lamellar domains become spontaneously aligned along the thickness gradient after sufficient thermal annealing. Real-time AFM imaging reveals that spontaneous alignment occurs through the directional growth of well-ordered domains along the thickness gradient, which is accompanied by defect dynamics, with vertical linear defects moving from thicker parts of the film towards the thinner ones, reducing their length and thus the associated energy. The mechanism underlying this interesting self-aligning behavior is provided by a ,geometric anchoring' phenomenon, originally envisioned to account for the liquid crystal alignment under a non-flat geometry of confinement. This novel self-aligning principle offers a valuable opportunity to control nanoscale alignment in block copolymer films by manipulating the, much larger, microscale morphology. [source] Genetic evidence for a maternal effect locus controlling genomic imprinting and growthGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 4 2005Amanda R. Duselis Abstract Crosses between two species of deer mouse (Peromyscus) yield dramatic parent-of-origin effects. Female P. maniculatus (BW) crossed with male P. polionotus (PO) produce animals smaller than either parent. PO females crossed with BW males yield lethal overgrowth that has been associated with loss-of-imprinting (LOI). Previously, we mapped two loci influencing fetal growth. These two loci, however, do not account for the LOI, nor for the dysmorphic phenotypes. Here we report that maternal genetic background strongly influences the LOI. Analyses of crosses wherein maternal genetic background is varied suggest that this effect is likely due to the action of a small number of loci. We have termed these putative loci Meil. Estimation of Meil loci number was confounded by skewed allelic ratios in the intercross line employed. We show that the Meil loci are not identical to any of the DNA methyltransferases shown to be involved in regulation of genomic imprinting. genesis 43:155,165, 2005. © 2005 Wiley-Liss, Inc. [source] Power calculations for likelihood ratio tests for offspring genotype risks, maternal effects, and parent-of-origin (POO) effects in the presence of missing parental genotypes when unaffected siblings are availableGENETIC EPIDEMIOLOGY, Issue 1 2007E. Rampersaud Abstract Genotype-based likelihood-ratio tests (LRT) of association that examine maternal and parent-of-origin effects have been previously developed in the framework of log-linear and conditional logistic regression models. In the situation where parental genotypes are missing, the expectation-maximization (EM) algorithm has been incorporated in the log-linear approach to allow incomplete triads to contribute to the LRT. We present an extension to this model which we call the Combined_LRT that incorporates additional information from the genotypes of unaffected siblings to improve assignment of incompletely typed families to mating type categories, thereby improving inference of missing parental data. Using simulations involving a realistic array of family structures, we demonstrate the validity of the Combined_LRT under the null hypothesis of no association and provide power comparisons under varying levels of missing data and using sibling genotype data. We demonstrate the improved power of the Combined_LRT compared with the family-based association test (FBAT), another widely used association test. Lastly, we apply the Combined_LRT to a candidate gene analysis in Autism families, some of which have missing parental genotypes. We conclude that the proposed log-linear model will be an important tool for future candidate gene studies, for many complex diseases where unaffected siblings can often be ascertained and where epigenetic factors such as imprinting may play a role in disease etiology. Genet. Epidemiol. © 2006 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||||||||