The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells

PubMed Central

McConnell, Kristopher H.; Dixon, Michael; Calvi, Brian R.

2012-01-01

DNA replication origin activity changes during development. Chromatin modifications are known to influence the genomic location of origins and the time during S phase that they initiate replication in different cells. However, how chromatin regulates origins in concert with cell differentiation remains poorly understood. Here, we use developmental gene amplification in Drosophila ovarian follicle cells as a model to investigate how chromatin modifiers regulate origins in a developmental context. We find that the histone acetyltransferase (HAT) Chameau (Chm) binds to amplicon origins and is partially required for their function. Depletion of Chm had relatively mild effects on origins during gene amplification and genomic replication compared with previous knockdown of its ortholog HBO1 in human cells, which has severe effects on origin function. We show that another HAT, CBP (Nejire), also binds amplicon origins and is partially required for amplification. Knockdown of Chm and CBP together had a more severe effect on nucleosome acetylation and amplicon origin activity than knockdown of either HAT alone, suggesting that these HATs collaborate in origin regulation. In addition to their local function at the origin, we show that Chm and CBP also globally regulate the developmental transition of follicle cells into the amplification stages of oogenesis. Our results reveal a complexity of origin epigenetic regulation by multiple HATs during development and suggest that chromatin modifiers are a nexus that integrates differentiation and DNA replication programs. PMID:22951641

Dynamic changes of genome-wide DNA methylation during soybean seed development

USDA-ARS?s Scientific Manuscript database

Seed development is programmed by expression of many genes in plants. Seed maturation is an important developmental process to soybean seed quality and yield. DNA methylation is a major epigenetic modification regulating gene expression. However, little is known about the dynamic nature of DNA me...

The ULT1 and ULT2 trxG genes play overlapping roles in Arabidopsis development and gene regulation

USDA-ARS?s Scientific Manuscript database

The epigenetic regulation of gene expression is critical for ensuring the proper deployment and stability of defined genome transcription programs at specific developmental stages. The cellular memory of stable gene expression states during animal and plant development is mediated by the opposing ac...

Developmentally Programmed 3′ CpG Island Methylation Confers Tissue- and Cell-Type-Specific Transcriptional Activation

PubMed Central

Yu, Da-Hai; Ware, Carol; Waterland, Robert A.; Zhang, Jiexin; Chen, Miao-Hsueh; Gadkari, Manasi; Kunde-Ramamoorthy, Govindarajan; Nosavanh, Lagina M.

2013-01-01

During development, a small but significant number of CpG islands (CGIs) become methylated. The timing of developmentally programmed CGI methylation and associated mechanisms of transcriptional regulation during cellular differentiation, however, remain poorly characterized. Here, we used genome-wide DNA methylation microarrays to identify epigenetic changes during human embryonic stem cell (hESC) differentiation. We discovered a group of CGIs associated with developmental genes that gain methylation after hESCs differentiate. Conversely, erasure of methylation was observed at the identified CGIs during subsequent reprogramming to induced pluripotent stem cells (iPSCs), further supporting a functional role for the CGI methylation. Both global gene expression profiling and quantitative reverse transcription-PCR (RT-PCR) validation indicated opposing effects of CGI methylation in transcriptional regulation during differentiation, with promoter CGI methylation repressing and 3′ CGI methylation activating transcription. By studying diverse human tissues and mouse models, we further confirmed that developmentally programmed 3′ CGI methylation confers tissue- and cell-type-specific gene activation in vivo. Importantly, luciferase reporter assays provided evidence that 3′ CGI methylation regulates transcriptional activation via a CTCF-dependent enhancer-blocking mechanism. These findings expand the classic view of mammalian CGI methylation as a mechanism for transcriptional silencing and indicate a functional role for 3′ CGI methylation in developmental gene regulation. PMID:23459939

OS082. CHIPS-Child: Testing the developmental origins hypothesis.

PubMed

Magee, L A; Synnes, A

2012-07-01

CHIPS-Child is a natural test of the Developmental Origins of Health and Disease hypothesis (DOHaD) [1,2]. Reduced fetal growth rate is associated with adult cardiovascular risk markers (e.g., obesity) and disease [3,4]. Evidence worldwide indicates that this relationship is independent of birth weight. The leading theory describes 'developmental programming'in utero leading to permanent alteration of the fetal genome. While those changes are adaptive in utero, they may be maladaptive postnatally. To directly test, for the first time in humans, whether differential blood pressure (BP) control in pregnancy has developmental programming effects, independent of birth weight. We predict that, like famine or protein malnutrition, 'tight' (vs. 'less tight') control of maternal BP will be associated with fetal under-nutrition and effects will be consistent with developmental programming. CHIPS-Child is a parallel, ancillary study to the CHIPS randomized controlled trial (RCT). CHIPS is designed to determine whether 'less tight' control [target diastolic BP (dBP) 100mmHg] or 'tight' control [target dBP 85mmHg] of non-proteinuric hypertension in pregnancy is better for the baby without increasing maternal risk. CHIPS-Child will examine offspring of CHIPS participants non-invasively at 12m corrected post-gestational age (±2m) for anthropometry, hair cortisol, buccal swabs for epigenetic testing and a maternal questionnaire about infant feeding practices and background. Annual contact will be maintained in years 2-5 and will include annual parental measurement of the child's height, weight and waist circumference. CHIPS will recruit 1028 women. We estimate that 80% of CHIPS centres will participate in CHIPS-Child, approximately 97% of babies will survive, and 90% of children will be followed to 12m resulting in a sample size of 626. Power will be >80% to detect a between-group difference of ⩾0.25 in 'change in z-score for weight' between birth and 12m (2-sided alpha=0.05, SD 1). Recruitment has begun. The primary outcome will be the between-group difference in early postnatal weight gain ('change in z score for weight') between birth and 12m (p<0.05). Secondary:outcomes are (i) hypothalamic pituitary adrenal axis function (hair cortisol for overall cortisol production); and (ii) between-groups differences in DNA methylation, using targeted (genes associated with growth, obesity, cardiovascular disease, and/or a developmental programming effect) and global (genome-wide microarray) methods. CHIPS-Child offers a unique opportunity to both clarify whether differential dBP control in pregnancy has developmental programming effects and contribute to our understanding of human biology and diversity in a way that a cross-sectional or other observational studies cannot. Copyright © 2012. Published by Elsevier B.V.

Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

PubMed Central

Vangestel, Carl; Mergeay, Joachim; Dawson, Deborah A.; Vandomme, Viki; Lens, Luc

2011-01-01

Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed. PMID:21747940

Conserved Gene Expression Programs in Developing Roots from Diverse Plants.

PubMed

Huang, Ling; Schiefelbein, John

2015-08-01

The molecular basis for the origin and diversification of morphological adaptations is a central issue in evolutionary developmental biology. Here, we defined temporal transcript accumulation in developing roots from seven vascular plants, permitting a genome-wide comparative analysis of the molecular programs used by a single organ across diverse species. The resulting gene expression maps uncover significant similarity in the genes employed in roots and their developmental expression profiles. The detailed analysis of a subset of 133 genes known to be associated with root development in Arabidopsis thaliana indicates that most of these are used in all plant species. Strikingly, this was also true for root development in a lycophyte (Selaginella moellendorffii), which forms morphologically different roots and is thought to have evolved roots independently. Thus, despite vast differences in size and anatomy of roots from diverse plants, the basic molecular mechanisms employed during root formation appear to be conserved. This suggests that roots evolved in the two major vascular plant lineages either by parallel recruitment of largely the same developmental program or by elaboration of an existing root program in the common ancestor of vascular plants. © 2015 American Society of Plant Biologists. All rights reserved.

Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology

PubMed Central

Leung, Maxwell C. K.; Williams, Phillip L.; Benedetto, Alexandre; Au, Catherine; Helmcke, Kirsten J.; Aschner, Michael; Meyer, Joel N.

2008-01-01

The nematode Caenorhabditis elegans has emerged as an important animal model in various fields including neurobiology, developmental biology, and genetics. Characteristics of this animal model that have contributed to its success include its genetic manipulability, invariant and fully described developmental program, well-characterized genome, ease of maintenance, short and prolific life cycle, and small body size. These same features have led to an increasing use of C. elegans in toxicology, both for mechanistic studies and high-throughput screening approaches. We describe some of the research that has been carried out in the areas of neurotoxicology, genetic toxicology, and environmental toxicology, as well as high-throughput experiments with C. elegans including genome-wide screening for molecular targets of toxicity and rapid toxicity assessment for new chemicals. We argue for an increased role for C. elegans in complementing other model systems in toxicological research. PMID:18566021

Genetics on the Fly: A Primer on the Drosophila Model System

PubMed Central

Hales, Karen G.; Korey, Christopher A.; Larracuente, Amanda M.; Roberts, David M.

2015-01-01

Fruit flies of the genus Drosophila have been an attractive and effective genetic model organism since Thomas Hunt Morgan and colleagues made seminal discoveries with them a century ago. Work with Drosophila has enabled dramatic advances in cell and developmental biology, neurobiology and behavior, molecular biology, evolutionary and population genetics, and other fields. With more tissue types and observable behaviors than in other short-generation model organisms, and with vast genome data available for many species within the genus, the fly’s tractable complexity will continue to enable exciting opportunities to explore mechanisms of complex developmental programs, behaviors, and broader evolutionary questions. This primer describes the organism’s natural history, the features of sequenced genomes within the genus, the wide range of available genetic tools and online resources, the types of biological questions Drosophila can help address, and historical milestones. PMID:26564900

Maternal adiposity in the absence of excessive gestational weight gain is associated with distinct changes in DNA methylation patterns in umbilical cords of infants

USDA-ARS?s Scientific Manuscript database

Maternal obesity has been hypothesized to lead to developmental programming of excessive weight and adiposity in offspring. In addition, excessive gestational weight gain (GWG) is also a demonstrated determinant of later-life adiposity. We examined genome-wide DNA methylation (Infinium® HumanMethyla...

Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome

PubMed Central

Hamilton, Eileen P; Kapusta, Aurélie; Huvos, Piroska E; Bidwell, Shelby L; Zafar, Nikhat; Tang, Haibao; Hadjithomas, Michalis; Krishnakumar, Vivek; Badger, Jonathan H; Caler, Elisabet V; Russ, Carsten; Zeng, Qiandong; Fan, Lin; Levin, Joshua Z; Shea, Terrance; Young, Sarah K; Hegarty, Ryan; Daza, Riza; Gujja, Sharvari; Wortman, Jennifer R; Birren, Bruce W; Nusbaum, Chad; Thomas, Jainy; Carey, Clayton M; Pritham, Ellen J; Feschotte, Cédric; Noto, Tomoko; Mochizuki, Kazufumi; Papazyan, Romeo; Taverna, Sean D; Dear, Paul H; Cassidy-Hanley, Donna M; Xiong, Jie; Miao, Wei; Orias, Eduardo; Coyne, Robert S

2016-01-01

The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymena’s germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum. DOI: http://dx.doi.org/10.7554/eLife.19090.001 PMID:27892853

Patterns of expression of position-dependent integrated transgenes in mouse embryo.

PubMed Central

Bonnerot, C; Grimber, G; Briand, P; Nicolas, J F

1990-01-01

The abilities to introduce foreign DNA into the genome of mice and to visualize gene expression at the single-cell level underlie a method for defining individual elements of a genetic program. We describe the use of an Escherichia coli lacZ reporter gene fused to the promoter of the gene for hypoxanthine phosphoribosyl transferase that is expressed in all tissues. Most transgenic mice (six of seven) obtained with this construct express the lacZ gene from the hypoxanthine phosphoribosyltransferase promoter. Unexpectedly, however, the expression is temporally and spatially regulated. Each transgenic line is characterized by a specific, highly reproducible pattern of lacZ expression. These results show that, for expression, the integrated construct must be complemented by elements of the genome. These elements exert dominant developmental control on the hypoxanthine phosphoribosyltransferase promoter. The expression patterns in some transgenic mice conform to a typological marker and in others to a subtle combination of typology and topography. These observations define discrete heterogeneities of cell types and of certain structures, particularly in the nervous system and in the mesoderm. This system opens opportunities for developmental studies by providing cellular, molecular, and genetic markers of cell types, cell states, and cells from developmental compartments. Finally this method illustrates that genes transduced or transposed to a different position in the genome acquire different spatiotemporal specificities, a result that has implications for evolution. Images PMID:1696727

The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes

PubMed Central

Malmstrøm, Martin; Britz, Ralf; Matschiner, Michael; Tørresen, Ole K; Hadiaty, Renny Kurnia; Yaakob, Norsham; Tan, Heok Hui; Jakobsen, Kjetill Sigurd; Salzburger, Walter; Rüber, Lukas

2018-01-01

Abstract The world’s smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development. PMID:29684203

Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila

PubMed Central

Cattenoz, Pierre B.; Popkova, Anna; Southall, Tony D.; Aiello, Giuseppe; Brand, Andrea H.; Giangrande, Angela

2016-01-01

High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain–containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades. PMID:26567182

Epigenomic Reprogramming of the Developing Reproductive Tract and Disease Susceptibility in Adulthood

PubMed Central

Walker, Cheryl Lyn

2014-01-01

During development, epigenetic programs are “installed” on the genome that direct differentiation and normal tissue and organ function in adulthood. Consequently, development is also a period of susceptibility to reprogramming of the epigenome. Developmental reprogramming occurs when an adverse stimulus or insult interrupts the proper “install” of epigenetic programs during development, reprogramming normal physiological responses in such a way as to promote disease later in life. Some of the best examples of developmental reprogramming involve the reproductive tract, where early life exposures to environmental estrogens can increase susceptibility to benign and malignant tumors in adulthood including leiomyoma (fibroids), endometrial and prostate cancer. Although specific mechanism(s) by which environmental estrogens reprogram the developing epigenome were unknown, both DNA and histone methylation were considered likely targets for epigenetic reprogramming. We have now identified a mechanism by which developmental exposures to environmental estrogens reprogram the epigenome by inducing inappropriate activation of nongenomic estrogen receptor (ER) signaling. Activation of non-genomic ER signaling via the PI3K pathway activates the kinase AKT/PKB in the developing reproductive tract, which phosphorylates the histone lysine methyltransferase (HKMT) EZH2, the key “installer” of epigenetic histone H3 lysine 27 trimethylation (H3K27me3). AKT phosphorylation inactivates EZH2, decreasing levels of H3K27 methylation, a repressive mark that inhibits gene expression, in the developing uterus. As a result of this developmental reprogramming, many estrogen-responsive genes become hypersensitive to estrogen in adulthood, exhibiting elevated expression throughout the estrus cycle, and resulting in a “hyper-estrogenized” phenotype in the adult uterus that promotes development of hormone dependent tumors. PMID:21656660

Pattern and process in the evolution of the sole dioecious member of Brassicaceae.

PubMed

Soza, Valerie L; Le Huynh, Vietnam; Di Stilio, Verónica S

2014-01-01

Lepidium sisymbrioides, a polyploid New Zealand endemic, is the sole dioecious species in Brassicaceae and therefore the closest dioecious relative of the model plant Arabidopsis thaliana. The attractiveness of developing this system for future studies on the genetics of sex determination prompted us to investigate historical and developmental factors surrounding the evolution of its unisexual flowers. Our goal was to determine the evolutionary pattern of polyploidization of L. sisymbrioides and the timing and process of flower reproductive organ abortion. To that end, we used a combination of phylogenetics to place this species within the complex history of polyploidization events in Lepidium and histology to compare its floral ontogeny to that of its closest hermaphroditic relatives and to A. thaliana. Using a nuclear locus (PISTILLATA), we reconstructed the gene tree among Lepidium taxa and applied a phylogenetic network analysis to identify ancestral genomes that contributed to the evolution of L. sisymbrioides. Combining this phylogenetic framework with cytological and genome size data, we estimated L. sisymbrioides as an allo-octoploid resulting from three hybridization events. Our investigations of flower development showed that unisexual flowers appear to abort reproductive organs by programmed cell death in female flowers and by developmental arrest in male flowers. This selective abortion occurs at the same floral developmental stage in both males and females, corresponding to Arabidopsis stage nine. Dioecy in Brassicaceae evolved once in L. sisymbrioides following several allopolyploidization events, by a process of selective abortion of reproductive organs at intermediate stages of flower development. Different developmental processes, but similar timing of abortions, affect male versus female flower development. An increased understanding of how and when reproductive organs abort in this species, combined with our estimates of ancestral genome contributions, ploidy and genome size, lay the foundation for future efforts to examine the genetic mechanisms involved in the evolution of unisexual flowers in the closest dioecious relative of the best studied model plant.

Protocorms and Protocorm-Like Bodies Are Molecularly Distinct from Zygotic Embryonic Tissues in Phalaenopsis aphrodite1[OPEN

PubMed Central

Chen, Jhun-Chen; Wei, Miao-Ju

2016-01-01

The distinct reproductive program of orchids provides a unique evolutionary model with pollination-triggered ovule development and megasporogenesis, a modified embryogenesis program resulting in seeds with immature embryos, and mycorrhiza-induced seed germination. However, the molecular mechanisms that have evolved to establish these unparalleled developmental programs are largely unclear. Here, we conducted comparative studies of genome-wide gene expression of various reproductive tissues and captured the molecular events associated with distinct reproductive programs in Phalaenopsis aphrodite. Importantly, our data provide evidence to demonstrate that protocorm-like body (PLB) regeneration (the clonal regeneration practice used in the orchid industry) does not follow the embryogenesis program. Instead, we propose that SHOOT MERISTEMLESS, a class I KNOTTED-LIKE HOMEOBOX gene, is likely to play a role in PLB regeneration. Our studies challenge the current understanding of the embryonic identity of PLBs. Taken together, the data obtained establish a fundamental framework for orchid reproductive development and provide a valuable new resource to enable the prediction of gene regulatory networks that is required for specialized developmental programs of orchid species. PMID:27338813

Comparative Genomics as a Foundation for Evo-Devo Studies in Birds.

PubMed

Grayson, Phil; Sin, Simon Y W; Sackton, Timothy B; Edwards, Scott V

2017-01-01

Developmental genomics is a rapidly growing field, and high-quality genomes are a useful foundation for comparative developmental studies. A high-quality genome forms an essential reference onto which the data from numerous assays and experiments, including ChIP-seq, ATAC-seq, and RNA-seq, can be mapped. A genome also streamlines and simplifies the development of primers used to amplify putative regulatory regions for enhancer screens, cDNA probes for in situ hybridization, microRNAs (miRNAs) or short hairpin RNAs (shRNA) for RNA interference (RNAi) knockdowns, mRNAs for misexpression studies, and even guide RNAs (gRNAs) for CRISPR knockouts. Finally, much can be gleaned from comparative genomics alone, including the identification of highly conserved putative regulatory regions. This chapter provides an overview of laboratory and bioinformatics protocols for DNA extraction, library preparation, library quantification, and genome assembly, from fresh or frozen tissue to a draft avian genome. Generating a high-quality draft genome can provide a developmental research group with excellent resources for their study organism, opening the doors to many additional assays and experiments.

Sporulation in Bacteria: Beyond the Standard Model.

PubMed

Hutchison, Elizabeth A; Miller, David A; Angert, Esther R

2014-10-01

Endospore formation follows a complex, highly regulated developmental pathway that occurs in a broad range of Firmicutes. Although Bacillus subtilis has served as a powerful model system to study the morphological, biochemical, and genetic determinants of sporulation, fundamental aspects of the program remain mysterious for other genera. For example, it is entirely unknown how most lineages within the Firmicutes regulate entry into sporulation. Additionally, little is known about how the sporulation pathway has evolved novel spore forms and reproductive schemes. Here, we describe endospore and internal offspring development in diverse Firmicutes and outline progress in characterizing these programs. Moreover, comparative genomics studies are identifying highly conserved sporulation genes, and predictions of sporulation potential in new isolates and uncultured bacteria can be made from these data. One surprising outcome of these comparative studies is that core regulatory and some structural aspects of the program appear to be universally conserved. This suggests that a robust and sophisticated developmental framework was already in place in the last common ancestor of all extant Firmicutes that produce internal offspring or endospores. The study of sporulation in model systems beyond B. subtilis will continue to provide key information on the flexibility of the program and provide insights into how changes in this developmental course may confer advantages to cells in diverse environments.

Molecular analysis of the replication program in unicellular model organisms.

PubMed

Raghuraman, M K; Brewer, Bonita J

2010-01-01

Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program of replication in particular. But what exactly is a temporal program of replication, and how might it arise? In this article, we explore this question, drawing again on the wealth of experimental information in unicellular model organisms.

Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation.

PubMed

Urushihara, Hideko; Kuwayama, Hidekazu; Fukuhara, Kensuke; Itoh, Takehiko; Kagoshima, Hiroshi; Shin-I, Tadasu; Toyoda, Atsushi; Ohishi, Kazuyo; Taniguchi, Tateaki; Noguchi, Hideki; Kuroki, Yoko; Hata, Takashi; Uchi, Kyoko; Mohri, Kurato; King, Jason S; Insall, Robert H; Kohara, Yuji; Fujiyama, Asao

2015-02-14

Social amoebae are lower eukaryotes that inhabit the soil. They are characterized by the construction of a starvation-induced multicellular fruiting body with a spore ball and supportive stalk. In most species, the stalk is filled with motile stalk cells, as represented by the model organism Dictyostelium discoideum, whose developmental mechanisms have been well characterized. However, in the genus Acytostelium, the stalk is acellular and all aggregated cells become spores. Phylogenetic analyses have shown that it is not an ancestral genus but has lost the ability to undergo cell differentiation. We performed genome and transcriptome analyses of Acytostelium subglobosum and compared our findings to other available dictyostelid genome data. Although A. subglobosum adopts a qualitatively different developmental program from other dictyostelids, its gene repertoire was largely conserved. Yet, families of polyketide synthase and extracellular matrix proteins have not expanded and a serine protease and ABC transporter B family gene, tagA, and a few other developmental genes are missing in the A. subglobosum lineage. Temporal gene expression patterns are astonishingly dissimilar from those of D. discoideum, and only a limited fraction of the ortholog pairs shared the same expression patterns, so that some signaling cascades for development seem to be disabled in A. subglobosum. The absence of the ability to undergo cell differentiation in Acytostelium is accompanied by a small change in coding potential and extensive alterations in gene expression patterns.

An assessment of time involved in pre-test case review and counseling for a whole genome sequencing clinical research program.

PubMed

Williams, Janet L; Faucett, W Andrew; Smith-Packard, Bethanny; Wagner, Monisa; Williams, Marc S

2014-08-01

Whole genome sequencing (WGS) is being used for evaluation of individuals with undiagnosed disease of suspected genetic origin. Implementing WGS into clinical practice will place an increased burden upon care teams with regard to pre-test patient education and counseling about results. To quantitate the time needed for appropriate pre-test evaluation of participants in WGS testing, we documented the time spent by our clinical research group on various activities related to program preparation, participant screening, and consent prior to WGS. Participants were children or young adults with autism, intellectual or developmental disability, and/or congenital anomalies, who have remained undiagnosed despite previous evaluation, and their biologic parents. Results showed that significant time was spent in securing allocation of clinical research space to counsel participants and families, and in acquisition and review of participant's medical records. Pre-enrollment chart review identified two individuals with existing diagnoses resulting in savings of $30,000 for the genome sequencing alone, as well as saving hours of personnel time for genome interpretation and communication of WGS results. New WGS programs should plan for costs associated with additional pre-test administrative planning and patient evaluation time that will be required to provide high quality care.

The Utility of Chromosomal Microarray Analysis in Developmental and Behavioral Pediatrics

ERIC Educational Resources Information Center

Beaudet, Arthur L.

2013-01-01

Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism…

Developmental pathways inferred from modularity, morphological integration and fluctuating asymmetry patterns in the human face.

PubMed

Quinto-Sánchez, Mirsha; Muñoz-Muñoz, Francesc; Gomez-Valdes, Jorge; Cintas, Celia; Navarro, Pablo; Cerqueira, Caio Cesar Silva de; Paschetta, Carolina; de Azevedo, Soledad; Ramallo, Virginia; Acuña-Alonzo, Victor; Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Hünemeier, Tábita; Everardo, Paola; de Avila, Francisco; Jaramillo, Claudia; Arias, Williams; Gallo, Carla; Poletti, Giovani; Bedoya, Gabriel; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Rosique, Javier; Ruiz-Linares, Andres; Gonzalez-Jose, Rolando

2018-01-17

Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes.

An imbalanced parental genome ratio affects the development of rice zygotes.

PubMed

Toda, Erika; Ohnishi, Yukinosuke; Okamoto, Takashi

2018-04-27

Upon double fertilization, one sperm cell fuses with the egg cell to form a zygote with a 1:1 maternal-to-paternal genome ratio (1m:1p), and another sperm cell fuses with the central cell to form a triploid primary endosperm cell with a 2m:1p ratio, resulting in formation of the embryo and the endosperm, respectively. The endosperm is known to be considerably sensitive to the ratio of the parental genomes. However, the effect of an imbalance of the parental genomes on zygotic development and embryogenesis has not been well studied, because it is difficult to reproduce the parental genome-imbalanced situation in zygotes and to monitor the developmental profile of zygotes without external effects from the endosperm. In this study, we produced polyploid zygotes with an imbalanced parental genome ratio by electro-fusion of isolated rice gametes and observed their developmental profiles. Polyploid zygotes with an excess maternal gamete/genome developed normally, whereas approximately half to three-quarters of polyploid zygotes with a paternal excess showed developmental arrests. These results indicate that paternal and maternal genomes synergistically serve zygote development with distinct functions, and that genes with monoallelic expression play important roles during zygotic development and embryogenesis.

Draft genome of the medaka fish: a comprehensive resource for medaka developmental genetics and vertebrate evolutionary biology.

PubMed

Takeda, Hiroyuki

2008-06-01

The medaka Oryzias latipes is a small egg-laying freshwater teleost, and has become an excellent model system for developmental genetics and evolutionary biology. The medaka genome is relatively small in size, approximately 800 Mb, and the genome sequencing project was recently completed by Japanese research groups, providing a high-quality draft genome sequence of the inbred Hd-rR strain of medaka. In this review, I present an overview of the medaka genome project including genome resources, followed by specific findings obtained with the medaka draft genome. In particular, I focus on the analysis that was done by taking advantage of the medaka system, such as the sex chromosome differentiation and the regional history of medaka species using single nucleotide polymorphisms as genomic markers.

Pdsg1 and Pdsg2, Novel Proteins Involved in Developmental Genome Remodelling in Paramecium

PubMed Central

Hoehener, Cristina; Singh, Aditi; Swart, Estienne C.; Nowacki, Mariusz

2014-01-01

The epigenetic influence of maternal cells on the development of their progeny has long been studied in various eukaryotes. Multicellular organisms usually provide their zygotes not only with nutrients but also with functional elements required for proper development, such as coding and non-coding RNAs. These maternally deposited RNAs exhibit a variety of functions, from regulating gene expression to assuring genome integrity. In ciliates, such as Paramecium these RNAs participate in the programming of large-scale genome reorganization during development, distinguishing germline-limited DNA, which is excised, from somatic-destined DNA. Only a handful of proteins playing roles in this process have been identified so far, including typical RNAi-derived factors such as Dicer-like and Piwi proteins. Here we report and characterize two novel proteins, Pdsg1 and Pdsg2 (Paramecium protein involved in Development of the Somatic Genome 1 and 2), involved in Paramecium genome reorganization. We show that these proteins are necessary for the excision of germline-limited DNA during development and the survival of sexual progeny. Knockdown of PDSG1 and PDSG2 genes affects the populations of small RNAs known to be involved in the programming of DNA elimination (scanRNAs and iesRNAs) and chromatin modification patterns during development. Our results suggest an association between RNA-mediated trans-generational epigenetic signal and chromatin modifications in the process of Paramecium genome reorganization. PMID:25397898

Pdsg1 and Pdsg2, novel proteins involved in developmental genome remodelling in Paramecium.

PubMed

Arambasic, Miroslav; Sandoval, Pamela Y; Hoehener, Cristina; Singh, Aditi; Swart, Estienne C; Nowacki, Mariusz

2014-01-01

The epigenetic influence of maternal cells on the development of their progeny has long been studied in various eukaryotes. Multicellular organisms usually provide their zygotes not only with nutrients but also with functional elements required for proper development, such as coding and non-coding RNAs. These maternally deposited RNAs exhibit a variety of functions, from regulating gene expression to assuring genome integrity. In ciliates, such as Paramecium these RNAs participate in the programming of large-scale genome reorganization during development, distinguishing germline-limited DNA, which is excised, from somatic-destined DNA. Only a handful of proteins playing roles in this process have been identified so far, including typical RNAi-derived factors such as Dicer-like and Piwi proteins. Here we report and characterize two novel proteins, Pdsg1 and Pdsg2 (Paramecium protein involved in Development of the Somatic Genome 1 and 2), involved in Paramecium genome reorganization. We show that these proteins are necessary for the excision of germline-limited DNA during development and the survival of sexual progeny. Knockdown of PDSG1 and PDSG2 genes affects the populations of small RNAs known to be involved in the programming of DNA elimination (scanRNAs and iesRNAs) and chromatin modification patterns during development. Our results suggest an association between RNA-mediated trans-generational epigenetic signal and chromatin modifications in the process of Paramecium genome reorganization.

Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

PubMed Central

2007-01-01

Background The usage of synonymous codons shows considerable variation among mammalian genes. How and why this usage is non-random are fundamental biological questions and remain controversial. It is also important to explore whether mammalian genes that are selectively expressed at different developmental stages bear different molecular features. Results In two models of mouse stem cell differentiation, we established correlations between codon usage and the patterns of gene expression. We found that the optimal codons exhibited variation (AT- or GC-ending codons) in different cell types within the developmental hierarchy. We also found that genes that were enriched (developmental-pivotal genes) or specifically expressed (developmental-specific genes) at different developmental stages had different patterns of codon usage and local genomic GC (GCg) content. Moreover, at the same developmental stage, developmental-specific genes generally used more GC-ending codons and had higher GCg content compared with developmental-pivotal genes. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons. In addition, our data show that after human-mouse divergence, the influence of selective constraints is still detectable. Conclusion Our findings suggest that developmental stage-related patterns of gene expression are correlated with codon usage (GC3) and GCg content in stem cell hierarchies. Moreover, this paper provides evidence for the influence of natural selection at synonymous sites in the mouse genome and novel clues for linking the molecular features of genes to their patterns of expression during mammalian ontogenesis. PMID:17349061

Contrasting Transcriptional Programs Control Postharvest Development of Apples (Malus x domestica Borkh.) Submitted to Cold Storage and Ethylene Blockage.

PubMed

Storch, Tatiane Timm; Finatto, Taciane; Bruneau, Maryline; Orsel-Baldwin, Mathilde; Renou, Jean-Pierre; Rombaldi, Cesar Valmor; Quecini, Vera; Laurens, François; Girardi, César Luis

2017-09-06

Apple is commercially important worldwide. Favorable genomic contexts and postharvest technologies allow year-round availability. Although ripening is considered a unidirectional developmental process toward senescence, storage at low temperatures, alone or in combination with ethylene blockage, is effective in preserving apple properties. Quality traits and genome wide expression were integrated to investigate the mechanisms underlying postharvest changes. Development and conservation techniques were responsible for transcriptional reprogramming and distinct programs associated with quality traits. A large portion of the differentially regulated genes constitutes a program involved in ripening and senescence, whereas a smaller module consists of genes associated with reestablishment and maintenance of juvenile traits after harvest. Ethylene inhibition was associated with a reversal of ripening by transcriptional induction of anabolic pathways. Our results demonstrate that the blockage of ethylene perception and signaling leads to upregulation of genes in anabolic pathways. We also associated complex phenotypes to subsets of differentially regulated genes.

The SUMO Pathway Is Developmentally Regulated and Required for Programmed DNA Elimination in Paramecium tetraurelia† ‡

PubMed Central

Matsuda, Atsushi; Forney, James D.

2006-01-01

Extensive genome-wide remodeling occurs during the formation of the somatic macronuclei from the germ line micronuclei in ciliated protozoa. This process is limited to sexual reproduction and includes DNA amplification, chromosome fragmentation, and the elimination of internal segments of DNA. Our efforts to define the pathways regulating these events revealed a gene encoding a homologue of ubiquitin activating enzyme 2 (UBA2) that is upregulated at the onset of macronuclear development in Paramecium tetraurelia. Uba2 enzymes are known to activate the protein called small ubiquitin-related modifier (SUMO) that is covalently attached to target proteins. Consistent with this relationship, Northern analysis showed increased abundance of SUMO transcripts during sexual reproduction in Paramecium. RNA interference (RNAi) against UBA2 or SUMO during vegetative growth had little effect on cell survival or fission rates. In contrast, RNAi of mating cells resulted in failure to form a functional macronucleus. Despite normal amplification of the genome, excision of internal eliminated sequences was completely blocked. Additional experiments showed that the homologous UBA2 and SUMO genes in Tetrahymena thermophila are also upregulated during conjugation. These results provide evidence for the developmental regulation of the SUMO pathway in ciliates and suggest a key role for the pathway in controlling genome remodeling. PMID:16682458

Reptile genomes open the frontier for comparative analysis of amniote development and regeneration.

PubMed

Tollis, Marc; Hutchins, Elizabeth D; Kusumi, Kenro

2014-01-01

Developmental genetic studies of vertebrates have focused primarily on zebrafish, frog and mouse models, which have clear application to medicine and well-developed genomic resources. In contrast, reptiles represent the most diverse amniote group, but have only recently begun to gather the attention of genome sequencing efforts. Extant reptilian groups last shared a common ancestor ?280 million years ago and include lepidosaurs, turtles and crocodilians. This phylogenetic diversity is reflected in great morphological and behavioral diversity capturing the attention of biologists interested in mechanisms regulating developmental processes such as somitogenesis and spinal patterning, regeneration, the evolution of "snake-like" morphology, the formation of the unique turtle shell, and the convergent evolution of the four-chambered heart shared by mammals and archosaurs. The complete genome of the first non-avian reptile, the green anole lizard, was published in 2011 and has provided insights into the origin and evolution of amniotes. Since then, the genomes of multiple snakes, turtles, and crocodilians have also been completed. Here we will review the current diversity of available reptile genomes, with an emphasis on their evolutionary relationships, and will highlight how these genomes have and will continue to facilitate research in developmental and regenerative biology.

Clinical utility of an array comparative genomic hybridization analysis for Williams syndrome.

PubMed

Yagihashi, Tatsuhiko; Torii, Chiharu; Takahashi, Reiko; Omori, Mikimasa; Kosaki, Rika; Yoshihashi, Hiroshi; Ihara, Masahiro; Minagawa-Kawai, Yasuyo; Yamamoto, Junichi; Takahashi, Takao; Kosaki, Kenjiro

2014-11-01

To reveal the relation between intellectual disability and the deleted intervals in Williams syndrome, we performed an array comparative genomic hybridization analysis and standardized developmental testing for 11 patients diagnosed as having Williams syndrome based on fluorescent in situ hybridization testing. One patient had a large 4.2-Mb deletion spanning distally beyond the common 1.5-Mb intervals observed in 10/11 patients. We formulated a linear equation describing the developmental age of the 10 patients with the common deletion; the developmental age of the patient with the 4.2-Mb deletion was significantly below the expectation (developmental age = 0.51 × chronological age). The large deletion may account for the severe intellectual disability; therefore, the use of array comparative genomic hybridization may provide practical information regarding individuals with Williams syndrome. © 2014 Japanese Teratology Society.

Homologous recombination and non-homologous end-joining repair pathways in bovine embryos with different developmental competence

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

Henrique Barreta, Marcos; Laboratorio de Biotecnologia e Reproducao Animal-BioRep, Universidade Federal de Santa Maria, Santa Maria, RS; Garziera Gasperin, Bernardo

2012-10-01

This study investigated the expression of genes controlling homologous recombination (HR), and non-homologous end-joining (NHEJ) DNA-repair pathways in bovine embryos of different developmental potential. It also evaluated whether bovine embryos can respond to DNA double-strand breaks (DSBs) induced with ultraviolet irradiation by regulating expression of genes involved in HR and NHEJ repair pathways. Embryos with high, intermediate or low developmental competence were selected based on the cleavage time after in vitro insemination and were removed from in vitro culture before (36 h), during (72 h) and after (96 h) the expected period of embryonic genome activation. All studied genes weremore » expressed before, during and after the genome activation period regardless the developmental competence of the embryos. Higher mRNA expression of 53BP1 and RAD52 was found before genome activation in embryos with low developmental competence. Expression of 53BP1, RAD51 and KU70 was downregulated at 72 h and upregulated at 168 h post-insemination in response to DSBs induced by ultraviolet irradiation. In conclusion, important genes controlling HR and NHEJ DNA-repair pathways are expressed in bovine embryos, however genes participating in these pathways are only regulated after the period of embryo genome activation in response to ultraviolet-induced DSBs.« less

Sex in the brain: hormones and sex differences.

PubMed

Marrocco, Jordan; McEwen, Bruce S

2016-12-01

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

Deep developmental transcriptome sequencing uncovers numerous new genes and enhances gene annotation in the sponge Amphimedon queenslandica.

PubMed

Fernandez-Valverde, Selene L; Calcino, Andrew D; Degnan, Bernard M

2015-05-15

The demosponge Amphimedon queenslandica is amongst the few early-branching metazoans with an assembled and annotated draft genome, making it an important species in the study of the origin and early evolution of animals. Current gene models in this species are largely based on in silico predictions and low coverage expressed sequence tag (EST) evidence. Amphimedon queenslandica protein-coding gene models are improved using deep RNA-Seq data from four developmental stages and CEL-Seq data from 82 developmental samples. Over 86% of previously predicted genes are retained in the new gene models, although 24% have additional exons; there is also a marked increase in the total number of annotated 3' and 5' untranslated regions (UTRs). Importantly, these new developmental transcriptome data reveal numerous previously unannotated protein-coding genes in the Amphimedon genome, increasing the total gene number by 25%, from 30,060 to 40,122. In general, Amphimedon genes have introns that are markedly smaller than those in other animals and most of the alternatively spliced genes in Amphimedon undergo intron-retention; exon-skipping is the least common mode of alternative splicing. Finally, in addition to canonical polyadenylation signal sequences, Amphimedon genes are enriched in a number of unique AT-rich motifs in their 3' UTRs. The inclusion of developmental transcriptome data has substantially improved the structure and composition of protein-coding gene models in Amphimedon queenslandica, providing a more accurate and comprehensive set of genes for functional and comparative studies. These improvements reveal the Amphimedon genome is comprised of a remarkably high number of tightly packed genes. These genes have small introns and there is pervasive intron retention amongst alternatively spliced transcripts. These aspects of the sponge genome are more similar unicellular opisthokont genomes than to other animal genomes.

A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

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

Ren, J.; Pei-Chen Lin, C.; Pathak, M. C.

2016-07-06

Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumedmore » during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.« less

A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

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

Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.

2014-07-11

Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumedmore » during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.« less

Developmental Programming and Endocrine Disruptor Effects on Reproductive Neuroendocrine Systems

PubMed Central

Gore, Andrea C.

2009-01-01

The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted. PMID:18394690

Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data.

PubMed

Wright, Caroline F; Fitzgerald, Tomas W; Jones, Wendy D; Clayton, Stephen; McRae, Jeremy F; van Kogelenberg, Margriet; King, Daniel A; Ambridge, Kirsty; Barrett, Daniel M; Bayzetinova, Tanya; Bevan, A Paul; Bragin, Eugene; Chatzimichali, Eleni A; Gribble, Susan; Jones, Philip; Krishnappa, Netravathi; Mason, Laura E; Miller, Ray; Morley, Katherine I; Parthiban, Vijaya; Prigmore, Elena; Rajan, Diana; Sifrim, Alejandro; Swaminathan, G Jawahar; Tivey, Adrian R; Middleton, Anna; Parker, Michael; Carter, Nigel P; Barrett, Jeffrey C; Hurles, Matthew E; FitzPatrick, David R; Firth, Helen V

2015-04-04

Human genome sequencing has transformed our understanding of genomic variation and its relevance to health and disease, and is now starting to enter clinical practice for the diagnosis of rare diseases. The question of whether and how some categories of genomic findings should be shared with individual research participants is currently a topic of international debate, and development of robust analytical workflows to identify and communicate clinically relevant variants is paramount. The Deciphering Developmental Disorders (DDD) study has developed a UK-wide patient recruitment network involving over 180 clinicians across all 24 regional genetics services, and has performed genome-wide microarray and whole exome sequencing on children with undiagnosed developmental disorders and their parents. After data analysis, pertinent genomic variants were returned to individual research participants via their local clinical genetics team. Around 80,000 genomic variants were identified from exome sequencing and microarray analysis in each individual, of which on average 400 were rare and predicted to be protein altering. By focusing only on de novo and segregating variants in known developmental disorder genes, we achieved a diagnostic yield of 27% among 1133 previously investigated yet undiagnosed children with developmental disorders, whilst minimising incidental findings. In families with developmentally normal parents, whole exome sequencing of the child and both parents resulted in a 10-fold reduction in the number of potential causal variants that needed clinical evaluation compared to sequencing only the child. Most diagnostic variants identified in known genes were novel and not present in current databases of known disease variation. Implementation of a robust translational genomics workflow is achievable within a large-scale rare disease research study to allow feedback of potentially diagnostic findings to clinicians and research participants. Systematic recording of relevant clinical data, curation of a gene-phenotype knowledge base, and development of clinical decision support software are needed in addition to automated exclusion of almost all variants, which is crucial for scalable prioritisation and review of possible diagnostic variants. However, the resource requirements of development and maintenance of a clinical reporting system within a research setting are substantial. Health Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the UK Department of Health. Copyright © 2015 Wright et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data

PubMed Central

Wright, Caroline F; Fitzgerald, Tomas W; Jones, Wendy D; Clayton, Stephen; McRae, Jeremy F; van Kogelenberg, Margriet; King, Daniel A; Ambridge, Kirsty; Barrett, Daniel M; Bayzetinova, Tanya; Bevan, A Paul; Bragin, Eugene; Chatzimichali, Eleni A; Gribble, Susan; Jones, Philip; Krishnappa, Netravathi; Mason, Laura E; Miller, Ray; Morley, Katherine I; Parthiban, Vijaya; Prigmore, Elena; Rajan, Diana; Sifrim, Alejandro; Swaminathan, G Jawahar; Tivey, Adrian R; Middleton, Anna; Parker, Michael; Carter, Nigel P; Barrett, Jeffrey C; Hurles, Matthew E; FitzPatrick, David R; Firth, Helen V

2015-01-01

Summary Background Human genome sequencing has transformed our understanding of genomic variation and its relevance to health and disease, and is now starting to enter clinical practice for the diagnosis of rare diseases. The question of whether and how some categories of genomic findings should be shared with individual research participants is currently a topic of international debate, and development of robust analytical workflows to identify and communicate clinically relevant variants is paramount. Methods The Deciphering Developmental Disorders (DDD) study has developed a UK-wide patient recruitment network involving over 180 clinicians across all 24 regional genetics services, and has performed genome-wide microarray and whole exome sequencing on children with undiagnosed developmental disorders and their parents. After data analysis, pertinent genomic variants were returned to individual research participants via their local clinical genetics team. Findings Around 80 000 genomic variants were identified from exome sequencing and microarray analysis in each individual, of which on average 400 were rare and predicted to be protein altering. By focusing only on de novo and segregating variants in known developmental disorder genes, we achieved a diagnostic yield of 27% among 1133 previously investigated yet undiagnosed children with developmental disorders, whilst minimising incidental findings. In families with developmentally normal parents, whole exome sequencing of the child and both parents resulted in a 10-fold reduction in the number of potential causal variants that needed clinical evaluation compared to sequencing only the child. Most diagnostic variants identified in known genes were novel and not present in current databases of known disease variation. Interpretation Implementation of a robust translational genomics workflow is achievable within a large-scale rare disease research study to allow feedback of potentially diagnostic findings to clinicians and research participants. Systematic recording of relevant clinical data, curation of a gene–phenotype knowledge base, and development of clinical decision support software are needed in addition to automated exclusion of almost all variants, which is crucial for scalable prioritisation and review of possible diagnostic variants. However, the resource requirements of development and maintenance of a clinical reporting system within a research setting are substantial. Funding Health Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the UK Department of Health. PMID:25529582

Genomewide Analysis of Aryl Hydrocarbon Receptor Binding Targets Reveals an Extensive Array of Gene Clusters that Control Morphogenetic and Developmental Programs

PubMed Central

Sartor, Maureen A.; Schnekenburger, Michael; Marlowe, Jennifer L.; Reichard, John F.; Wang, Ying; Fan, Yunxia; Ma, Ci; Karyala, Saikumar; Halbleib, Danielle; Liu, Xiangdong; Medvedovic, Mario; Puga, Alvaro

2009-01-01

Background The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. The naive receptor is believed to reside in an inactive cytosolic complex that translocates to the nucleus and induces transcription of xenobiotic detoxification genes after activation by ligand. Objectives We conducted an integrative genomewide analysis of AHR gene targets in mouse hepatoma cells and determined whether AHR regulatory functions may take place in the absence of an exogenous ligand. Methods The network of AHR-binding targets in the mouse genome was mapped through a multipronged approach involving chromatin immunoprecipitation/chip and global gene expression signatures. The findings were integrated into a prior functional knowledge base from Gene Ontology, interaction networks, Kyoto Encyclopedia of Genes and Genomes pathways, sequence motif analysis, and literature molecular concepts. Results We found the naive receptor in unstimulated cells bound to an extensive array of gene clusters with functions in regulation of gene expression, differentiation, and pattern specification, connecting multiple morphogenetic and developmental programs. Activation by the ligand displaced the receptor from some of these targets toward sites in the promoters of xenobiotic metabolism genes. Conclusions The vertebrate AHR appears to possess unsuspected regulatory functions that may be potential targets of environmental injury. PMID:19654925

Highly Precise and Developmentally Programmed Genome Assembly in Paramecium Requires Ligase IV–Dependent End Joining

PubMed Central

Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D.; Malinsky, Sophie; Bétermier, Mireille

2011-01-01

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5′ overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi–mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5′-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3′ ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a “cut-and-close” mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics. PMID:21533177

Highly precise and developmentally programmed genome assembly in Paramecium requires ligase IV-dependent end joining.

PubMed

Kapusta, Aurélie; Matsuda, Atsushi; Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D; Malinsky, Sophie; Bétermier, Mireille

2011-04-01

During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5' overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi-mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5'-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3' ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a "cut-and-close" mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms involved in genome dynamics.

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

HpBase: A genome database of a sea urchin, Hemicentrotus pulcherrimus.

PubMed

Kinjo, Sonoko; Kiyomoto, Masato; Yamamoto, Takashi; Ikeo, Kazuho; Yaguchi, Shunsuke

2018-04-01

To understand the mystery of life, it is important to accumulate genomic information for various organisms because the whole genome encodes the commands for all the genes. Since the genome of Strongylocentrotus purpratus was sequenced in 2006 as the first sequenced genome in echinoderms, the genomic resources of other North American sea urchins have gradually been accumulated, but no sea urchin genomes are available in other areas, where many scientists have used the local species and reported important results. In this manuscript, we report a draft genome of the sea urchin Hemincentrotus pulcherrimus because this species has a long history as the target of developmental and cell biology in East Asia. The genome of H. pulcherrimus was assembled into 16,251 scaffold sequences with an N50 length of 143 kbp, and approximately 25,000 genes were identified in the genome. The size of the genome and the sequencing coverage were estimated to be approximately 800 Mbp and 100×, respectively. To provide these data and information of annotation, we constructed a database, HpBase (http://cell-innovation.nig.ac.jp/Hpul/). In HpBase, gene searches, genome browsing, and blast searches are available. In addition, HpBase includes the "recipes" for experiments from each lab using H. pulcherrimus. These recipes will continue to be updated according to the circumstances of individual scientists and can be powerful tools for experimental biologists and for the community. HpBase is a suitable dataset for evolutionary, developmental, and cell biologists to compare H. pulcherrimus genomic information with that of other species and to isolate gene information. © 2018 Japanese Society of Developmental Biologists.

fluff: exploratory analysis and visualization of high-throughput sequencing data

PubMed Central

Georgiou, Georgios

2016-01-01

Summary. In this article we describe fluff, a software package that allows for simple exploration, clustering and visualization of high-throughput sequencing data mapped to a reference genome. The package contains three command-line tools to generate publication-quality figures in an uncomplicated manner using sensible defaults. Genome-wide data can be aggregated, clustered and visualized in a heatmap, according to different clustering methods. This includes a predefined setting to identify dynamic clusters between different conditions or developmental stages. Alternatively, clustered data can be visualized in a bandplot. Finally, fluff includes a tool to generate genomic profiles. As command-line tools, the fluff programs can easily be integrated into standard analysis pipelines. The installation is straightforward and documentation is available at http://fluff.readthedocs.org. Availability. fluff is implemented in Python and runs on Linux. The source code is freely available for download at https://github.com/simonvh/fluff. PMID:27547532

Pervasive, Coordinated Protein-Level Changes Driven by Transcript Isoform Switching during Meiosis.

PubMed

Cheng, Ze; Otto, George Maxwell; Powers, Emily Nicole; Keskin, Abdurrahman; Mertins, Philipp; Carr, Steven Alfred; Jovanovic, Marko; Brar, Gloria Ann

2018-02-22

To better understand the gene regulatory mechanisms that program developmental processes, we carried out simultaneous genome-wide measurements of mRNA, translation, and protein through meiotic differentiation in budding yeast. Surprisingly, we observed that the levels of several hundred mRNAs are anti-correlated with their corresponding protein products. We show that rather than arising from canonical forms of gene regulatory control, the regulation of at least 380 such cases, or over 8% of all measured genes, involves temporally regulated switching between production of a canonical, translatable transcript and a 5' extended isoform that is not efficiently translated into protein. By this pervasive mechanism for the modulation of protein levels through a natural developmental program, a single transcription factor can coordinately activate and repress protein synthesis for distinct sets of genes. The distinction is not based on whether or not an mRNA is induced but rather on the type of transcript produced. Copyright © 2018 Elsevier Inc. All rights reserved.

Coordination of flower development by homeotic master regulators.

PubMed

Ito, Toshiro

2011-02-01

Floral homeotic genes encode transcription factors and act as master regulators of flower development. The homeotic protein complex is expressed in a specific whorl of the floral primordium and determines floral organ identity by the combinatorial action. Homeotic proteins continue to be expressed until late in flower development to coordinate growth and organogenesis. Recent genomic studies have shown that homeotic proteins bind thousands of target sites in the genome and regulate the expression of transcription factors, chromatin components and various proteins involved in hormone biosynthesis and signaling and other physiological activities. Further, homeotic proteins program chromatin to direct the developmental coordination of stem cell maintenance and differentiation in shaping floral organs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Use of a Drosophila Genome-Wide Conserved Sequence Database to Identify Functionally Related cis-Regulatory Enhancers

PubMed Central

Brody, Thomas; Yavatkar, Amarendra S; Kuzin, Alexander; Kundu, Mukta; Tyson, Leonard J; Ross, Jermaine; Lin, Tzu-Yang; Lee, Chi-Hon; Awasaki, Takeshi; Lee, Tzumin; Odenwald, Ward F

2012-01-01

Background: Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs. Results: We have generated a Drosophila genome-wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis-Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function. To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization. Conclusions: cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process. Developmental Dynamics 241:169–189, 2012. © 2011 Wiley Periodicals, Inc. Key findings A genome-wide catalog of Drosophila conserved DNA sequence clusters. cis-Decoder discovers functionally related enhancers. Functionally related enhancers share balanced sequence element copy numbers. Many enhancers function during multiple phases of development. PMID:22174086

Developmental Pathways Are Blueprints for Designing Successful Crops

PubMed Central

Trevaskis, Ben

2018-01-01

Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene–gene or gene–environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted. PMID:29922318

Developmental Pathways Are Blueprints for Designing Successful Crops.

PubMed

Trevaskis, Ben

2018-01-01

Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene-gene or gene-environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted.

An Approach to Using Toxicogenomic Data in US EPA Human ...

EPA Pesticide Factsheets

This draft report is a description of an approach to evaluate genomic data for use in risk assessment and a case study to illustrate the approach. The dibutyl phthalate (DBP) case study example focuses on male reproductive developmental effects and the qualitative application of the available genomic data. The case study presented in this draft document is a separate activity from any of the ongoing IRIS human health assessments for the phthalates. This draft report is a description of an approach to evaluate genomic data for use in risk assessment and a case study to illustrate the approach. The dibutyl phthalate (DBP) case study example focuses on male reproductive developmental effects and the qualitative application of the available genomic data.

Flow cytometry sorting of nuclei enables the first global characterization of Paramecium germline DNA and transposable elements.

PubMed

Guérin, Frédéric; Arnaiz, Olivier; Boggetto, Nicole; Denby Wilkes, Cyril; Meyer, Eric; Sperling, Linda; Duharcourt, Sandra

2017-04-26

DNA elimination is developmentally programmed in a wide variety of eukaryotes, including unicellular ciliates, and leads to the generation of distinct germline and somatic genomes. The ciliate Paramecium tetraurelia harbors two types of nuclei with different functions and genome structures. The transcriptionally inactive micronucleus contains the complete germline genome, while the somatic macronucleus contains a reduced genome streamlined for gene expression. During development of the somatic macronucleus, the germline genome undergoes massive and reproducible DNA elimination events. Availability of both the somatic and germline genomes is essential to examine the genome changes that occur during programmed DNA elimination and ultimately decipher the mechanisms underlying the specific removal of germline-limited sequences. We developed a novel experimental approach that uses flow cell imaging and flow cytometry to sort subpopulations of nuclei to high purity. We sorted vegetative micronuclei and macronuclei during development of P. tetraurelia. We validated the method by flow cell imaging and by high throughput DNA sequencing. Our work establishes the proof of principle that developing somatic macronuclei can be sorted from a complex biological sample to high purity based on their size, shape and DNA content. This method enabled us to sequence, for the first time, the germline DNA from pure micronuclei and to identify novel transposable elements. Sequencing the germline DNA confirms that the Pgm domesticated transposase is required for the excision of all ~45,000 Internal Eliminated Sequences. Comparison of the germline DNA and unrearranged DNA obtained from PGM-silenced cells reveals that the latter does not provide a faithful representation of the germline genome. We developed a flow cytometry-based method to purify P. tetraurelia nuclei to high purity and provided quality control with flow cell imaging and high throughput DNA sequencing. We identified 61 germline transposable elements including the first Paramecium retrotransposons. This approach paves the way to sequence the germline genomes of P. aurelia sibling species for future comparative genomic studies.

A Genome-Wide Screen Indicates Correlation between Differentiation and Expression of Metabolism Related Genes

PubMed Central

Shende, Akhilesh; Singh, Anupama; Meena, Anil; Ghosal, Ritika; Ranganathan, Madhav; Bandyopadhyay, Amitabha

2013-01-01

Differentiated tissues may be considered as materials with distinct properties. The differentiation program of a given tissue ensures that it acquires material properties commensurate with its function. It may be hypothesized that some of these properties are acquired through production of tissue-specific metabolites synthesized by metabolic enzymes. To establish correlation between metabolism and organogenesis we have carried out a genome-wide expression study of metabolism related genes by RNA in-situ hybridization. 23% of the metabolism related genes studied are expressed in a tissue-restricted but not tissue-exclusive manner. We have conducted the screen on whole mount chicken (Gallus gallus) embryos from four distinct developmental stages to correlate dynamic changes in expression patterns of metabolic enzymes with spatio-temporally unique developmental events. Our data strongly suggests that unique combinations of metabolism related genes, and not specific metabolic pathways, are upregulated during differentiation. Further, expression of metabolism related genes in well established signaling centers that regulate different aspects of morphogenesis indicates developmental roles of some of the metabolism related genes. The database of tissue-restricted expression patterns of metabolism related genes, generated in this study, should serve as a resource for systematic identification of these genes with tissue-specific functions during development. Finally, comprehensive understanding of differentiation is not possible unless the downstream genes of a differentiation cascade are identified. We propose, metabolic enzymes constitute a significant portion of these downstream target genes. Thus our study should help elucidate different aspects of tissue differentiation. PMID:23717462

A genome-wide screen indicates correlation between differentiation and expression of metabolism related genes.

PubMed

Roy, Priti; Kumar, Brijesh; Shende, Akhilesh; Singh, Anupama; Meena, Anil; Ghosal, Ritika; Ranganathan, Madhav; Bandyopadhyay, Amitabha

2013-01-01

Differentiated tissues may be considered as materials with distinct properties. The differentiation program of a given tissue ensures that it acquires material properties commensurate with its function. It may be hypothesized that some of these properties are acquired through production of tissue-specific metabolites synthesized by metabolic enzymes. To establish correlation between metabolism and organogenesis we have carried out a genome-wide expression study of metabolism related genes by RNA in-situ hybridization. 23% of the metabolism related genes studied are expressed in a tissue-restricted but not tissue-exclusive manner. We have conducted the screen on whole mount chicken (Gallus gallus) embryos from four distinct developmental stages to correlate dynamic changes in expression patterns of metabolic enzymes with spatio-temporally unique developmental events. Our data strongly suggests that unique combinations of metabolism related genes, and not specific metabolic pathways, are upregulated during differentiation. Further, expression of metabolism related genes in well established signaling centers that regulate different aspects of morphogenesis indicates developmental roles of some of the metabolism related genes. The database of tissue-restricted expression patterns of metabolism related genes, generated in this study, should serve as a resource for systematic identification of these genes with tissue-specific functions during development. Finally, comprehensive understanding of differentiation is not possible unless the downstream genes of a differentiation cascade are identified. We propose, metabolic enzymes constitute a significant portion of these downstream target genes. Thus our study should help elucidate different aspects of tissue differentiation.

Obituary: John Sulston (1942-2018).

PubMed

White, John

2018-05-08

John Sulston, a pioneer in the developmental studies of the nematode C. elegans who went on to spearhead the sequencing of the genome of this organism and ultimately the human genome, died on 6th March 2018, shortly after being diagnosed with stomach cancer. Here, I reflect on John's life and work, with a particular focus on his time working on the developmental genetics and lineage of C. elegans . © 2018. Published by The Company of Biologists Ltd.

A review of fundamental principles for animal models of DOHaD research: an Australian perspective.

PubMed

Dickinson, H; Moss, T J; Gatford, K L; Moritz, K M; Akison, L; Fullston, T; Hryciw, D H; Maloney, C A; Morris, M J; Wooldridge, A L; Schjenken, J E; Robertson, S A; Waddell, B J; Mark, P J; Wyrwoll, C S; Ellery, S J; Thornburg, K L; Muhlhausler, B S; Morrison, J L

2016-10-01

Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

How Can Genomics Inform Education?

ERIC Educational Resources Information Center

Grigorenko, Elena L.

2007-01-01

This article offers some thoughts on possible connections between genomics and education. Genomics is already revolutionizing the way medical care is delivered and distributed; it will inevitably affect children's developmental trajectories by introducing more pharmacological and behavioral therapies. Educators should be prepared to understand the…

The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

PubMed Central

Guerra, Daniel J.

2011-01-01

Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD. PMID:22937247

Array comparative genomic hybridization and computational genome annotation in constitutional cytogenetics: suggesting candidate genes for novel submicroscopic chromosomal imbalance syndromes.

PubMed

Van Vooren, Steven; Coessens, Bert; De Moor, Bart; Moreau, Yves; Vermeesch, Joris R

2007-09-01

Genome-wide array comparative genomic hybridization screening is uncovering pathogenic submicroscopic chromosomal imbalances in patients with developmental disorders. In those patients, imbalances appear now to be scattered across the whole genome, and most patients carry different chromosomal anomalies. Screening patients with developmental disorders can be considered a forward functional genome screen. The imbalances pinpoint the location of genes that are involved in human development. Because most imbalances encompass regions harboring multiple genes, the challenge is to (1) identify those genes responsible for the specific phenotype and (2) disentangle the role of the different genes located in an imbalanced region. In this review, we discuss novel tools and relevant databases that have recently been developed to aid this gene discovery process. Identification of the functional relevance of genes will not only deepen our understanding of human development but will, in addition, aid in the data interpretation and improve genetic counseling.

A Gestational High Protein Diet Affects the Abundance of Muscle Transcripts Related to Cell Cycle Regulation throughout Development in Porcine Progeny

PubMed Central

Oster, Michael; Murani, Eduard; Metges, Cornelia C.; Ponsuksili, Siriluck; Wimmers, Klaus

2012-01-01

Background In various animal models pregnancy diets have been shown to affect offspring phenotype. Indeed, the underlying programming of development is associated with modulations in birth weight, body composition, and continual diet-dependent modifications of offspring metabolism until adulthood, producing the hypothesis that the offspring's transcriptome is permanently altered depending on maternal diet. Methodology/Principal Findings To assess alterations of the offspring's transcriptome due to gestational protein supply, German Landrace sows were fed isoenergetic diets containing protein levels of either 30% (high protein - HP) or 12% (adequate protein - AP) throughout their pregnancy. Offspring muscle tissue (M. longissimus dorsi) was collected at 94 days post conception (dpc), and 1, 28, and 188 days post natum (dpn) for use with Affymetrix GeneChip Porcine Genome Arrays and subsequent statistical and Ingenuity pathway analyses. Numerous transcripts were found to have altered abundance at 94 dpc and 1 dpn; at 28 dpn no transcripts were altered, and at 188 dpn only a few transcripts showed a different abundance between diet groups. However, when assessing transcriptional changes across developmental time points, marked differences were obvious among the dietary groups. Depending on the gestational dietary exposure, short- and long-term effects were observed for mRNA expression of genes related to cell cycle regulation, energy metabolism, growth factor signaling pathways, and nucleic acid metabolism. In particular, the abundance of transcripts related to cell cycle remained divergent among the groups during development. Conclusion Expression analysis indicates that maternal protein supply induced programming of the offspring's genome; early postnatal compensation of the slight growth retardation obvious at birth in HP piglets resulted, as did a permanently different developmental alteration and responsiveness to the common environment of the transcriptome. The transcriptome modulations are interpreted as the molecular equivalent of developmental plasticity of the offspring that necessitates adaptation and maintenance of the organismal phenotype. PMID:22496824

The NR3B subgroup: an ovERRview

PubMed Central

Tremblay, Annie M.; Giguère, Vincent

2007-01-01

Members of the NR3B group of the nuclear receptor superfamily, known as the estrogen-related receptors (ERRs), were the first orphan receptors to be identified two decades ago. Despite the fact that a natural ligand has yet to be associated with the ERRs, considerable knowledge about their mode of action and biological functions has emerged through extensive biochemical, genetic and functional genomics studies. This review describes our current understanding of how the ERRs work as transcription factors and as such, how they control diverse developmental and physiological programs. PMID:18174917

Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men.

PubMed

Hammoud, Saher Sue; Nix, David A; Hammoud, Ahmad O; Gibson, Mark; Cairns, Bradley R; Carrell, Douglas T

2011-09-01

The sperm chromatin of fertile men retains a small number of nucleosomes that are enriched at developmental gene promoters and imprinted gene loci. This unique chromatin packaging at certain gene promoters provides these genomic loci the ability to convey instructive epigenetic information to the zygote, potentially expanding the role and significance of the sperm epigenome in embryogenesis. We hypothesize that changes in chromatin packaging may be associated with poor reproductive outcome. Seven patients with reproductive dysfunction were recruited: three had unexplained poor embryogenesis during IVF and four were diagnosed with male infertility and previously shown to have altered protamination. Genome-wide analysis of the location of histones and histone modifications was analyzed by isolation and purification of DNA bound to histones and protamines. The histone-bound fraction of DNA was analyzed using high-throughput sequencing, both initially and following chromatin immunoprecipitation. The protamine-bound fraction was hybridized to agilent arrays. DNA methylation was examined using bisulfite sequencing. Unlike fertile men, five of seven infertile men had non-programmatic (randomly distributed) histone retention genome-wide. Interestingly, in contrast to the total histone pool, the localization of H3 Lysine 4 methylation (H3K4me) or H3 Lysine 27 methylation (H3K27me) was highly similar in the gametes of infertile men compared with fertile men. However, there was a reduction in the amount of H3K4me or H3K27me retained at developmental transcription factors and certain imprinted genes. Finally, the methylation status of candidate developmental promoters and imprinted loci were altered in a subset of the infertile men. This initial genome-wide analysis of epigenetic markings in the sperm of infertile men demonstrates differences in composition and epigenetic markings compared with fertile men, especially at certain imprinted and developmental loci. Although no single locus displays a complete change in chromatin packaging or DNA modification, the data suggest that moderate changes throughout the genome exist and may have a cumulative detrimental effect on fecundity.

Making new genetic diagnoses with old data: iterative reanalysis and reporting from genome-wide data in 1,133 families with developmental disorders.

PubMed

Wright, Caroline F; McRae, Jeremy F; Clayton, Stephen; Gallone, Giuseppe; Aitken, Stuart; FitzGerald, Tomas W; Jones, Philip; Prigmore, Elena; Rajan, Diana; Lord, Jenny; Sifrim, Alejandro; Kelsell, Rosemary; Parker, Michael J; Barrett, Jeffrey C; Hurles, Matthew E; FitzPatrick, David R; Firth, Helen V

2018-01-11

PurposeGiven the rapid pace of discovery in rare disease genomics, it is likely that improvements in diagnostic yield can be made by systematically reanalyzing previously generated genomic sequence data in light of new knowledge.MethodsWe tested this hypothesis in the United Kingdom-wide Deciphering Developmental Disorders study, where in 2014 we reported a diagnostic yield of 27% through whole-exome sequencing of 1,133 children with severe developmental disorders and their parents. We reanalyzed existing data using improved variant calling methodologies, novel variant detection algorithms, updated variant annotation, evidence-based filtering strategies, and newly discovered disease-associated genes.ResultsWe are now able to diagnose an additional 182 individuals, taking our overall diagnostic yield to 454/1,133 (40%), and another 43 (4%) have a finding of uncertain clinical significance. The majority of these new diagnoses are due to novel developmental disorder-associated genes discovered since our original publication.ConclusionThis study highlights the importance of coupling large-scale research with clinical practice, and of discussing the possibility of iterative reanalysis and recontact with patients and health professionals at an early stage. We estimate that implementing parent-offspring whole-exome sequencing as a first-line diagnostic test for developmental disorders would diagnose >50% of patients.GENETICS in MEDICINE advance online publication, 11 January 2018; doi:10.1038/gim.2017.246.

Getting to the root of plant biology: impact of the Arabidopsis genome sequence on root research

PubMed Central

Benfey, Philip N.; Bennett, Malcolm; Schiefelbein, John

2010-01-01

Summary Prior to the availability of the genome sequence, the root of Arabidopsis had attracted a small but ardent group of researchers drawn to its accessibility and developmental simplicity. Roots are easily observed when grown on the surface of nutrient agar media, facilitating analysis of responses to stimuli such as gravity and touch. Developmental biologists were attracted to the simple radial organization of primary root tissues, which form a series of concentric cylinders around the central vascular tissue. Equally attractive was the mode of propagation, with stem cells at the tip giving rise to progeny that were confined to cell files. These properties of root development reduced the normal four-dimensional problem of development (three spatial dimensions and time) to a two-dimensional problem, with cell type on the radial axis and developmental time along the longitudinal axis. The availability of the complete Arabidopsis genome sequence has dramatically accelerated traditional genetic research on root biology, and has also enabled entirely new experimental strategies to be applied. Here we review examples of the ways in which availability of the Arabidopsis genome sequence has enhanced progress in understanding root biology. PMID:20409273

Genome-wide and caste-specific DNA methylomes of the ants Camponotus floridanus and Harpegnathos saltator

PubMed Central

Bonasio, Roberto; Li, Qiye; Lian, Jinmin; Mutti, Navdeep S.; Jin, Lijun; Zhao, Hongmei; Zhang, Pei; Wen, Ping; Xiang, Hui; Ding, Yun; Jin, Zonghui; Shen, Steven S.; Wang, Zongji; Wang, Wen; Wang, Jun; Berger, Shelley L.; Liebig, Jürgen; Zhang, Guojie; Reinberg, Danny

2012-01-01

SUMMARY Background Ant societies comprise individuals belonging to different castes characterized by specialized morphologies and behaviors. Because ant embryos can follow different developmental trajectories, epigenetic mechanisms must play a role in caste determination. Ants have a full set of DNA methyltransferase and their genomes contain methylcytosine. To determine the relationship between DNA methylation and phenotypic plasticity in ants, we obtained and compared the genome-wide methylomes of different castes and developmental stages of Camponotus floridanus and Harpegnathos saltator. Results In the ant genomes, methylcytosines are found both in CpG and non-CpG contexts and are strongly enriched at exons of active genes. Changes in exonic DNA methylation correlate with alternative splicing events such as exon skipping and alternative splice site selection. Several genes exhibit caste-specific and developmental changes in DNA methylation that are conserved between the two species, including genes involved in reproduction, telomere maintenance, and noncoding RNA metabolism. Several loci are methylated and expressed monoallelically, and in some cases the choice of methylated allele depends on the caste. Conclusions These first ant methylomes and their intra- and inter-species comparison reveal an exonic methylation pattern that points to a connection between DNA methylation and splicing. The presence of monoallelic DNA methylation and the methylation of non-CpG sites in all samples suggest roles in genome regulation in these social insects, including the intriguing possibility of parental or caste-specific genomic imprinting. PMID:22885060

The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus

PubMed Central

2013-01-01

Background The barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites. Results The draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules. Conclusions The draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders. PMID:23985341

Genome-wide chromatin state transitions associated with developmental and environmental cues.

PubMed

Zhu, Jiang; Adli, Mazhar; Zou, James Y; Verstappen, Griet; Coyne, Michael; Zhang, Xiaolan; Durham, Timothy; Miri, Mohammad; Deshpande, Vikram; De Jager, Philip L; Bennett, David A; Houmard, Joseph A; Muoio, Deborah M; Onder, Tamer T; Camahort, Ray; Cowan, Chad A; Meissner, Alexander; Epstein, Charles B; Shoresh, Noam; Bernstein, Bradley E

2013-01-31

Differences in chromatin organization are key to the multiplicity of cell states that arise from a single genetic background, yet the landscapes of in vivo tissues remain largely uncharted. Here, we mapped chromatin genome-wide in a large and diverse collection of human tissues and stem cells. The maps yield unprecedented annotations of functional genomic elements and their regulation across developmental stages, lineages, and cellular environments. They also reveal global features of the epigenome, related to nuclear architecture, that also vary across cellular phenotypes. Specifically, developmental specification is accompanied by progressive chromatin restriction as the default state transitions from dynamic remodeling to generalized compaction. Exposure to serum in vitro triggers a distinct transition that involves de novo establishment of domains with features of constitutive heterochromatin. We describe how these global chromatin state transitions relate to chromosome and nuclear architecture, and discuss their implications for lineage fidelity, cellular senescence, and reprogramming. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Liphardt, Jan

In April 1953, Watson and Crick largely defined the program of 20th century biology: obtaining the blueprint of life encoded in the DNA. Fifty years later, in 2003, the sequencing of the human genome was completed. Like any major scientific breakthrough, the sequencing of the human genome raised many more questions than it answered. I'll brief you on some of the big open problems in cell and developmental biology, and I'll explain why approaches, tools, and ideas from the physical sciences are currently reshaping biological research. Super-resolution light microscopies are revealing the intricate spatial organization of cells, single-molecule methods showmore » how molecular machines function, and new probes are clarifying the role of mechanical forces in cell and tissue function. At the same time, Physics stands to gain beautiful new problems in soft condensed matter, quantum mechanics, and non-equilibrium thermodynamics.« less

The Intersection of Physics and Biology

ScienceCinema

Liphardt, Jan

2017-12-22

In April 1953, Watson and Crick largely defined the program of 20th century biology: obtaining the blueprint of life encoded in the DNA. Fifty years later, in 2003, the sequencing of the human genome was completed. Like any major scientific breakthrough, the sequencing of the human genome raised many more questions than it answered. I'll brief you on some of the big open problems in cell and developmental biology, and I'll explain why approaches, tools, and ideas from the physical sciences are currently reshaping biological research. Super-resolution light microscopies are revealing the intricate spatial organization of cells, single-molecule methods show how molecular machines function, and new probes are clarifying the role of mechanical forces in cell and tissue function. At the same time, Physics stands to gain beautiful new problems in soft condensed matter, quantum mechanics, and non-equilibrium thermodynamics.

StereoGene: rapid estimation of genome-wide correlation of continuous or interval feature data.

PubMed

Stavrovskaya, Elena D; Niranjan, Tejasvi; Fertig, Elana J; Wheelan, Sarah J; Favorov, Alexander V; Mironov, Andrey A

2017-10-15

Genomics features with similar genome-wide distributions are generally hypothesized to be functionally related, for example, colocalization of histones and transcription start sites indicate chromatin regulation of transcription factor activity. Therefore, statistical algorithms to perform spatial, genome-wide correlation among genomic features are required. Here, we propose a method, StereoGene, that rapidly estimates genome-wide correlation among pairs of genomic features. These features may represent high-throughput data mapped to reference genome or sets of genomic annotations in that reference genome. StereoGene enables correlation of continuous data directly, avoiding the data binarization and subsequent data loss. Correlations are computed among neighboring genomic positions using kernel correlation. Representing the correlation as a function of the genome position, StereoGene outputs the local correlation track as part of the analysis. StereoGene also accounts for confounders such as input DNA by partial correlation. We apply our method to numerous comparisons of ChIP-Seq datasets from the Human Epigenome Atlas and FANTOM CAGE to demonstrate its wide applicability. We observe the changes in the correlation between epigenomic features across developmental trajectories of several tissue types consistent with known biology and find a novel spatial correlation of CAGE clusters with donor splice sites and with poly(A) sites. These analyses provide examples for the broad applicability of StereoGene for regulatory genomics. The StereoGene C ++ source code, program documentation, Galaxy integration scripts and examples are available from the project homepage http://stereogene.bioinf.fbb.msu.ru/. favorov@sensi.org. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Systems biology of embryonic development: Prospects for a complete understanding of the Caenorhabditis elegans embryo.

PubMed

Murray, John Isaac

2018-05-01

The convergence of developmental biology and modern genomics tools brings the potential for a comprehensive understanding of developmental systems. This is especially true for the Caenorhabditis elegans embryo because its small size, invariant developmental lineage, and powerful genetic and genomic tools provide the prospect of a cellular resolution understanding of messenger RNA (mRNA) expression and regulation across the organism. We describe here how a systems biology framework might allow large-scale determination of the embryonic regulatory relationships encoded in the C. elegans genome. This framework consists of two broad steps: (a) defining the "parts list"-all genes expressed in all cells at each time during development and (b) iterative steps of computational modeling and refinement of these models by experimental perturbation. Substantial progress has been made towards defining the parts list through imaging methods such as large-scale green fluorescent protein (GFP) reporter analysis. Imaging results are now being augmented by high-resolution transcriptome methods such as single-cell RNA sequencing, and it is likely the complete expression patterns of all genes across the embryo will be known within the next few years. In contrast, the modeling and perturbation experiments performed so far have focused largely on individual cell types or genes, and improved methods will be needed to expand them to the full genome and organism. This emerging comprehensive map of embryonic expression and regulatory function will provide a powerful resource for developmental biologists, and would also allow scientists to ask questions not accessible without a comprehensive picture. This article is categorized under: Invertebrate Organogenesis > Worms Technologies > Analysis of the Transcriptome Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics. © 2018 Wiley Periodicals, Inc.

Molecular developmental mechanism in polypterid fish provides insight into the origin of vertebrate lungs

PubMed Central

Tatsumi, Norifumi; Kobayashi, Ritsuko; Yano, Tohru; Noda, Masatsugu; Fujimura, Koji; Okada, Norihiro; Okabe, Masataka

2016-01-01

The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods. Moreover, we found a Tbx4 core lung mesenchyme-specific enhancer (C-LME) in the genomes of bichir and coelacanth (Latimeria chalumnae) and experimentally confirmed that these were functional in tetrapods. These findings provide the first molecular evidence that the developmental program for lung was already established in the common ancestor of actinopterygians and sarcopterygians. PMID:27466206

Molecular developmental mechanism in polypterid fish provides insight into the origin of vertebrate lungs.

PubMed

Tatsumi, Norifumi; Kobayashi, Ritsuko; Yano, Tohru; Noda, Masatsugu; Fujimura, Koji; Okada, Norihiro; Okabe, Masataka

2016-07-28

The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods. Moreover, we found a Tbx4 core lung mesenchyme-specific enhancer (C-LME) in the genomes of bichir and coelacanth (Latimeria chalumnae) and experimentally confirmed that these were functional in tetrapods. These findings provide the first molecular evidence that the developmental program for lung was already established in the common ancestor of actinopterygians and sarcopterygians.

Impact of Maternal Diet on the Epigenome during In Utero Life and the Developmental Programming of Diseases in Childhood and Adulthood

PubMed Central

Lee, Ho-Sun

2015-01-01

Exposure to environmental factors in early life can influence developmental processes and long-term health in humans. Early life nutrition and maternal diet are well-known examples of conditions shown to influence the risk of developing metabolic diseases, including type 2 diabetes mellitus and cardiovascular diseases, in adulthood. It is increasingly accepted that environmental compounds, including nutrients, can produce changes in the genome activity that, in spite of not altering the DNA sequence, can produce important, stable and, in some instances, transgenerational alterations in the phenotype. Epigenetics refers to changes in gene function that cannot be explained by changes in the DNA sequence, with DNA methylation patterns/histone modifications that can make important contributions to epigenetic memory. The epigenome can be considered as an interface between the genome and the environment that is central to the generation of phenotypes and their stability throughout the life course. To better understand the role of maternal health and nutrition in the initiation and progression of diseases in childhood and adulthood, it is necessary to identify the physiological and/or pathological roles of specific nutrients on the epigenome and how dietary interventions in utero and early life could modulate disease risk through epigenomic alteration. PMID:26593940

The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development

PubMed Central

Akhter, Shamima; Lam, Yung C.; Chang, Sandy; Legerski, Randy J.

2013-01-01

Summary Conserved metallo β-Lactamase and β-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice. PMID:20854421

Perspectives on the history of evo-devo and the contemporary research landscape in the genomics era.

PubMed

Tickle, Cheryll; Urrutia, Araxi O

2017-02-05

A fundamental question in biology is how the extraordinary range of living organisms arose. In this theme issue, we celebrate how evolutionary studies on the origins of morphological diversity have changed over the past 350 years since the first publication of the Philosophical Transactions of The Royal Society Current understanding of this topic is enriched by many disciplines, including anatomy, palaeontology, developmental biology, genetics and genomics. Development is central because it is the means by which genetic information of an organism is translated into morphology. The discovery of the genetic basis of development has revealed how changes in form can be inherited, leading to the emergence of the field known as evolutionary developmental biology (evo-devo). Recent approaches include imaging, quantitative morphometrics and, in particular, genomics, which brings a new dimension. Articles in this issue illustrate the contemporary evo-devo field by considering general principles emerging from genomics and how this and other approaches are applied to specific questions about the evolution of major transitions and innovations in morphology, diversification and modification of structures, intraspecific morphological variation and developmental plasticity. Current approaches enable a much broader range of organisms to be studied, thus building a better appreciation of the origins of morphological diversity.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'. © 2016 The Author(s).

Nuclease-mediated genome editing: At the front-line of functional genomics technology.

PubMed

Sakuma, Tetsushi; Woltjen, Knut

2014-01-01

Genome editing with engineered endonucleases is rapidly becoming a staple method in developmental biology studies. Engineered nucleases permit random or designed genomic modification at precise loci through the stimulation of endogenous double-strand break repair. Homology-directed repair following targeted DNA damage is mediated by co-introduction of a custom repair template, allowing the derivation of knock-out and knock-in alleles in animal models previously refractory to classic gene targeting procedures. Currently there are three main types of customizable site-specific nucleases delineated by the source mechanism of DNA binding that guides nuclease activity to a genomic target: zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR). Among these genome engineering tools, characteristics such as the ease of design and construction, mechanism of inducing DNA damage, and DNA sequence specificity all differ, making their application complementary. By understanding the advantages and disadvantages of each method, one may make the best choice for their particular purpose. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

76 FR 2399 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-13

...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Neurotransporters, Receptors...- 1198. [email protected] . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group.... (301) 435-1045. [email protected] . Name of Committee: Molecular, Cellular and Developmental...

DNA Repair and Genome Maintenance in Bacillus subtilis

PubMed Central

Lenhart, Justin S.; Schroeder, Jeremy W.; Walsh, Brian W.

2012-01-01

Summary: From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis. PMID:22933559

Shifting from clonal to sexual reproduction in aphids: physiological and developmental aspects.

PubMed

Le Trionnaire, Gaël; Hardie, Jim; Jaubert-Possamai, Stéphanie; Simon, Jean-Christophe; Tagu, Denis

2008-08-01

Developmental biology is one of the fastest growing and fascinating research fields in life sciences. Among the wide range of embryonic development, a fundamental difference exists between organisms with sexual or asexual development. Aphids are unusual organisms which display alternative pathways of sexual and asexual development, the orientation of the pathway being determined by environmental conditions. These insects offer an adapted system in which to study developmental plasticity, because a side-by-side comparison of sexual and asexual development can be made in individuals with the same genotype. In this review, we describe the developmental mechanisms that have evolved in aphids for alternative sexual and asexual reproduction. In particular, we discuss how environmental cues orientate the reproductive mode of aphids from signal perception to endocrine regulation, and propose a comparative analysis of sexual and asexual gametogenesis and embryogenesis, which has been possible due to the development of molecular methods. As a result of the recent development of genomic resources in aphids, we expect these species will permit major advances in the study of the genomic basis underlying the choice of developmental fate and multiple reproduction strategies.

Developmental history and application of CRISPR in human disease.

PubMed

Liang, Puping; Zhang, Xiya; Chen, Yuxi; Huang, Junjiu

2017-06-01

Genome-editing tools are programmable artificial nucleases, mainly including zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeat (CRISPR). By recognizing and cleaving specific DNA sequences, genome-editing tools make it possible to generate site-specific DNA double-strand breaks (DSBs) in the genome. DSBs will then be repaired by either error-prone nonhomologous end joining or high-fidelity homologous recombination mechanisms. Through these two different mechanisms, endogenous genes can be knocked out or precisely repaired/modified. Rapid developments in genome-editing tools, especially CRISPR, have revolutionized human disease models generation, for example, various zebrafish, mouse, rat, pig, monkey and human cell lines have been constructed. Here, we review the developmental history of CRISPR and its application in studies of human diseases. In addition, we also briefly discussed the therapeutic application of CRISPR in the near future. Copyright © 2017 John Wiley & Sons, Ltd.

Tripolar mitosis and partitioning of the genome arrests human preimplantation development in vitro.

PubMed

Ottolini, Christian S; Kitchen, John; Xanthopoulou, Leoni; Gordon, Tony; Summers, Michael C; Handyside, Alan H

2017-08-29

Following in vitro fertilisation (IVF), only about half of normally fertilised human embryos develop beyond cleavage and morula stages to form a blastocyst in vitro. Although many human embryos are aneuploid and genomically imbalanced, often as a result of meiotic errors inherited in the oocyte, these aneuploidies persist at the blastocyst stage and the reasons for the high incidence of developmental arrest remain unknown. Here we use genome-wide SNP genotyping and meiomapping of both polar bodies to identify maternal meiotic errors and karyomapping to fingerprint the parental chromosomes in single cells from disaggregated arrested embryos and excluded cells from blastocysts. Combined with time lapse imaging of development in culture, we demonstrate that tripolar mitoses in early cleavage cause chromosome dispersal to clones of cells with identical or closely related sub-diploid chromosome profiles resulting in intercellular partitioning of the genome. We hypothesise that following zygotic genome activation (ZGA), the combination of genomic imbalance and partial genome loss disrupts the normal pattern of embryonic gene expression blocking development at the morula-blastocyst transition. Failure to coordinate the cell cycle in early cleavage and regulate centrosome duplication is therefore a major cause of human preimplantation developmental arrest in vitro.

Molluscan Evolutionary Genomics

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

Simison, W. Brian; Boore, Jeffrey L.

2005-12-01

In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the earlymore » 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.« less

Are we Genomic Mosaics? Variations of the Genome of Somatic Cells can Contribute to Diversify our Phenotypes.

PubMed

Astolfi, P A; Salamini, F; Sgaramella, V

2010-09-01

Theoretical and experimental evidences support the hypothesis that the genomes and the epigenomes may be different in the somatic cells of complex organisms. In the genome, the differences range from single base substitutions to chromosome number; in the epigenome, they entail multiple postsynthetic modifications of the chromatin. Somatic genome variations (SGV) may accumulate during development in response both to genetic programs, which may differ from tissue to tissue, and to environmental stimuli, which are often undetected and generally irreproducible. SGV may jeopardize physiological cellular functions, but also create novel coding and regulatory sequences, to be exposed to intraorganismal Darwinian selection. Genomes acknowledged as comparatively poor in genes, such as humans', could thus increase their pristine informational endowment. A better understanding of SGV will contribute to basic issues such as the "nature vs nurture" dualism and the inheritance of acquired characters. On the applied side, they may explain the low yield of cloning via somatic cell nuclear transfer, provide clues to some of the problems associated with transdifferentiation, and interfere with individual DNA analysis. SGV may be unique in the different cells types and in the different developmental stages, and thus explain the several hundred gaps persisting in the human genomes "completed" so far. They may compound the variations associated to our epigenomes and make of each of us an "(epi)genomic" mosaic. An ensuing paradigm is the possibility that a single genome (the ephemeral one assembled at fertilization) has the capacity to generate several different brains in response to different environments.

Functional genetics for all: engineered nucleases, CRISPR and the gene editing revolution.

PubMed

Gilles, Anna F; Averof, Michalis

2014-01-01

Developmental biology, as all experimental science, is empowered by technological advances. The availability of genetic tools in some species - designated as model organisms - has driven their use as major platforms for understanding development, physiology and behavior. Extending these tools to a wider range of species determines whether (and how) we can experimentally approach developmental diversity and evolution. During the last two decades, comparative developmental biology (evo-devo) was marked by the introduction of gene knockdown and deep sequencing technologies that are applicable to a wide range of species. These approaches allowed us to test the developmental role of specific genes in diverse species, to study biological processes that are not accessible in established models and, in some cases, to conduct genome-wide screens that overcome the limitations of the candidate gene approach. The recent discovery of CRISPR/Cas as a means of precise alterations into the genome promises to revolutionize developmental genetics. In this review we describe the development of gene editing tools, from zinc-finger nucleases to TALENs and CRISPR, and examine their application in gene targeting, their limitations and the opportunities they present for evo-devo. We outline their use in gene knock-out and knock-in approaches, and in manipulating gene functions by directing molecular effectors to specific sites in the genome. The ease-of-use and efficiency of CRISPR in diverse species provide an opportunity to close the technology gap that exists between established model organisms and emerging genetically-tractable species.

Developmental biology of Streptomyces from the perspective of 100 actinobacterial genome sequences

PubMed Central

Chandra, Govind; Chater, Keith F

2014-01-01

To illuminate the evolution and mechanisms of actinobacterial complexity, we evaluate the distribution and origins of known Streptomyces developmental genes and the developmental significance of actinobacteria-specific genes. As an aid, we developed the Actinoblast database of reciprocal blastp best hits between the Streptomyces coelicolor genome and more than 100 other actinobacterial genomes (http://streptomyces.org.uk/actinoblast/). We suggest that the emergence of morphological complexity was underpinned by special features of early actinobacteria, such as polar growth and the coupled participation of regulatory Wbl proteins and the redox-protecting thiol mycothiol in transducing a transient nitric oxide signal generated during physiologically stressful growth transitions. It seems that some cell growth and division proteins of early actinobacteria have acquired greater importance for sporulation of complex actinobacteria than for mycelial growth, in which septa are infrequent and not associated with complete cell separation. The acquisition of extracellular proteins with structural roles, a highly regulated extracellular protease cascade, and additional regulatory genes allowed early actinobacterial stationary phase processes to be redeployed in the emergence of aerial hyphae from mycelial mats and in the formation of spore chains. These extracellular proteins may have contributed to speciation. Simpler members of morphologically diverse clades have lost some developmental genes. PMID:24164321

45 CFR 1388.2 - Program criteria-purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

... inclusion of individuals with developmental disabilities. Compliance with the program criteria is a..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM THE UNIVERSITY AFFILIATED PROGRAMS § 1388.2 Program criteria—purpose. The program criteria...

75 FR 994 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-07

..., Genomes, and Genetics Integrated Review Group; Molecular Genetics C Study Section. Date: February 4-5...: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Neural Oxidative Metabolism [email protected] . Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review...

Can Nucleoli Be Markers of Developmental Potential in Human Zygotes?

PubMed

Fulka, Helena; Kyogoku, Hirohisa; Zatsepina, Olga; Langerova, Alena; Fulka, Josef

2015-11-01

In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental genome restructuring after fertilization, and that interfering with this process may lead to developmental failure. These studies thus support the Tesarik-Greco evaluation as a potentially useful method for selecting high-quality embryos in human assisted reproductive technologies. In this opinion article we discuss recent evidence linking nucleoli to parental genome reprogramming, and ask whether nucleoli can mirror or be used as representative markers of embryonic parameters such as chromosome content or DNA fragmentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of the pre- and post-natal environment in developmental programming of health and productivity.

PubMed

Reynolds, Lawrence P; Caton, Joel S

2012-05-06

The concept that developmental insults (for example, poor pre- or postnatal nutrition) can have long-term consequences on health and well-being of the offspring has been termed developmental programming. In livestock, developmental programming affects production traits, including growth, body composition, and reproduction. Although low birth weight was used as a proxy for compromised fetal development in the initial epidemiological studies, based on controlled studies using livestock and other animal models in the last two decades we now know that developmental programming can occur independently of any effects on birth weight. Studies in humans, rodents, and livestock also have confirmed the critical role of the placenta in developmental programming. In addition, the central role of epigenetic regulation in developmental programming has been confirmed. Lastly, relatively simple therapeutic/management strategies designed to 'rescue' placental development and function are being developed to minimize the effects of developmental programming on health and productivity of humans, livestock, and other mammals. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Sequence-specific epigenetic effects of the maternal somatic genome on developmental rearrangements of the zygotic genome in Paramecium primaurelia.

PubMed Central

Meyer, E; Butler, A; Dubrana, K; Duharcourt, S; Caron, F

1997-01-01

In ciliates, the germ line genome is extensively rearranged during the development of the somatic macronucleus from a mitotic product of the zygotic nucleus. Germ line chromosomes are fragmented in specific regions, and a large number of internal sequence elements are eliminated. It was previously shown that transformation of the vegetative macronucleus of Paramecium primaurelia with a plasmid containing a subtelomeric surface antigen gene can affect the processing of the homologous germ line genomic region during development of a new macronucleus in sexual progeny of transformed clones. The gene and telomere-proximal flanking sequences are deleted from the new macronuclear genome, although the germ line genome remains wild type. Here we show that plasmids containing nonoverlapping segments of the same genomic region are able to induce similar terminal deletions; the locations of deletion end points depend on the particular sequence used. Transformation of the maternal macronucleus with a sequence internal to a macronuclear chromosome also causes the occurrence of internal deletions between short direct repeats composed of alternating thymines and adenines. The epigenetic influence of maternal macronuclear sequences on developmental rearrangements of the zygotic genome thus appears to be both sequence specific and general, suggesting that this trans-nucleus effect is mediated by pairing of homologous sequences. PMID:9199294

Seeing chordate evolution through the Ciona genome sequence

PubMed Central

Cañestro, Cristian; Bassham, Susan; Postlethwait, John H

2003-01-01

A draft sequence of the compact genome of the sea squirt Ciona intestinalis, a non-vertebrate chordate that diverged very early from other chordates, including vertebrates, illuminates how chordates originated and how vertebrate developmental innovations evolved. PMID:12620098

Implications of long-term culture for mesenchymal stem cells: genetic defects or epigenetic regulation?

PubMed Central

2012-01-01

Mesenchymal stem cells change dramatically during culture expansion. Long-term culture has been suspected to evoke oncogenic transformation: overall, the genome appears to be relatively stable throughout culture but transient clonal aneuploidies have been observed. Oncogenic transformation does not necessarily entail growth advantage in vitro and, therefore, the available methods - such as karyotypic analysis or genomic profiling - cannot exclude this risk. On the other hand, long-term culture is associated with specific senescence-associated DNA methylation (SA-DNAm) changes, particularly in developmental genes. SA-DNAm changes are highly reproducible and can be used to monitor the state of senescence for quality control. Notably, neither telomere attrition nor SA-DNAm changes occur in pluripotent stem cells, which can evade the 'Hayflick limit'. Long-term culture of mesenchymal stem cells seems to involve a tightly regulated epigenetic program. These epigenetic modifications may counteract dominant clones, which are more prone to transformation. PMID:23257053

Implications of long-term culture for mesenchymal stem cells: genetic defects or epigenetic regulation?

PubMed

Wagner, Wolfgang

2012-12-20

Mesenchymal stem cells change dramatically during culture expansion. Long-term culture has been suspected to evoke oncogenic transformation: overall, the genome appears to be relatively stable throughout culture but transient clonal aneuploidies have been observed. Oncogenic transformation does not necessarily entail growth advantage in vitro and, therefore, the available methods - such as karyotypic analysis or genomic profiling - cannot exclude this risk. On the other hand, long-term culture is associated with specific senescence-associated DNA methylation (SA-DNAm) changes, particularly in developmental genes. SA-DNAm changes are highly reproducible and can be used to monitor the state of senescence for quality control. Notably, neither telomere attrition nor SA-DNAm changes occur in pluripotent stem cells, which can evade the 'Hayflick limit'. Long-term culture of mesenchymal stem cells seems to involve a tightly regulated epigenetic program. These epigenetic modifications may counteract dominant clones, which are more prone to transformation.

Insights into neural crest development and evolution from genomic analysis

PubMed Central

Simões-Costa, Marcos; Bronner, Marianne E.

2013-01-01

The neural crest is an excellent model system for the study of cell type diversification during embryonic development due to its multipotency, motility, and ability to form a broad array of derivatives ranging from neurons and glia, to cartilage, bone, and melanocytes. As a uniquely vertebrate cell population, it also offers important clues regarding vertebrate origins. In the past 30 yr, introduction of recombinant DNA technology has facilitated the dissection of the genetic program controlling neural crest development and has provided important insights into gene regulatory mechanisms underlying cell migration and differentiation. More recently, new genomic approaches have provided a platform and tools that are changing the depth and breadth of our understanding of neural crest development at a “systems” level. Such advances provide an insightful view of the regulatory landscape of neural crest cells and offer a new perspective on developmental as well as stem cell and cancer biology. PMID:23817048

The intellectual developmental disorders Mexico study: situational diagnosis, burden, genomics and intervention proposal.

PubMed

Lazcano-Ponce, Eduardo; Katz, Gregorio; Rodríguez-Valentín, Rocío; Castro, Filipa de; Allen-Leigh, Betania; Márquez-Caraveo, María Elena; Ramírez-García, Miguel Ángel; Arroyo-García, Eduardo; Medina-Mora, María Elena; Ángeles, Gustavo; Urquieta-Salomón, José Edmundo; Salvador-Carulla, Luis

2016-01-01

This study aims to generate evidence on intellectual development disorders (IDD) in Mexico. IDD disease burden will be estimated with a probabilistic model, using population-based surveys. Direct and indirect costs of catastrophic expenses of families with a member with an IDD will be evaluated. Genomic characterization of IDD will include: sequencing participant exomes and performing bioinformatics analyses to identify de novo or inherited variants through trio analysis; identifying genetic variants associated with IDD, and validating randomly selected variants by polymerase chain reaction (PCR) and sequencing or real-time quantitative PCR (qPCR). Delphi surveys will be done on best practices for IDD diagnosis and management. An external evaluation will employ qualitative case studies of two social and labor inclusion programs for people with IDD. The results will constitute scientific evidence for the design, promotion and evaluation of public policies, which are currently absent on IDD.

Discovery of the First Germline-Restricted Gene by Subtractive Transcriptomic Analysis in the Zebra Finch, Taeniopygia guttata.

PubMed

Biederman, Michelle K; Nelson, Megan M; Asalone, Kathryn C; Pedersen, Alyssa L; Saldanha, Colin J; Bracht, John R

2018-05-21

Developmentally programmed genome rearrangements are rare in vertebrates, but have been reported in scattered lineages including the bandicoot, hagfish, lamprey, and zebra finch (Taeniopygia guttata) [1]. In the finch, a well-studied animal model for neuroendocrinology and vocal learning [2], one such programmed genome rearrangement involves a germline-restricted chromosome, or GRC, which is found in germlines of both sexes but eliminated from mature sperm [3, 4]. Transmitted only through the oocyte, it displays uniparental female-driven inheritance, and early in embryonic development is apparently eliminated from all somatic tissue in both sexes [3, 4]. The GRC comprises the longest finch chromosome at over 120 million base pairs [3], and previously the only known GRC-derived sequence was repetitive and non-coding [5]. Because the zebra finch genome project was sourced from male muscle (somatic) tissue [6], the remaining genomic sequence and protein-coding content of the GRC remain unknown. Here we report the first protein-coding gene from the GRC: a member of the α-soluble N-ethylmaleimide sensitive fusion protein (NSF) attachment protein (α-SNAP) family hitherto missing from zebra finch gene annotations. In addition to the GRC-encoded α-SNAP, we find an additional paralogous α-SNAP residing in the somatic genome (a somatolog)-making the zebra finch the first example in which α-SNAP is not a single-copy gene. We show divergent, sex-biased expression for the paralogs and also that positive selection is detectable across the bird α-SNAP lineage, including the GRC-encoded α-SNAP. This study presents the identification and evolutionary characterization of the first protein-coding GRC gene in any organism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents.

PubMed

Gilbert, Scott F; Bosch, Thomas C G; Ledón-Rettig, Cristina

2015-10-01

The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.

The genome of the sea urchin Strongylocentrotus purpuratus.

PubMed

Sodergren, Erica; Weinstock, George M; Davidson, Eric H; Cameron, R Andrew; Gibbs, Richard A; Angerer, Robert C; Angerer, Lynne M; Arnone, Maria Ina; Burgess, David R; Burke, Robert D; Coffman, James A; Dean, Michael; Elphick, Maurice R; Ettensohn, Charles A; Foltz, Kathy R; Hamdoun, Amro; Hynes, Richard O; Klein, William H; Marzluff, William; McClay, David R; Morris, Robert L; Mushegian, Arcady; Rast, Jonathan P; Smith, L Courtney; Thorndyke, Michael C; Vacquier, Victor D; Wessel, Gary M; Wray, Greg; Zhang, Lan; Elsik, Christine G; Ermolaeva, Olga; Hlavina, Wratko; Hofmann, Gretchen; Kitts, Paul; Landrum, Melissa J; Mackey, Aaron J; Maglott, Donna; Panopoulou, Georgia; Poustka, Albert J; Pruitt, Kim; Sapojnikov, Victor; Song, Xingzhi; Souvorov, Alexandre; Solovyev, Victor; Wei, Zheng; Whittaker, Charles A; Worley, Kim; Durbin, K James; Shen, Yufeng; Fedrigo, Olivier; Garfield, David; Haygood, Ralph; Primus, Alexander; Satija, Rahul; Severson, Tonya; Gonzalez-Garay, Manuel L; Jackson, Andrew R; Milosavljevic, Aleksandar; Tong, Mark; Killian, Christopher E; Livingston, Brian T; Wilt, Fred H; Adams, Nikki; Bellé, Robert; Carbonneau, Seth; Cheung, Rocky; Cormier, Patrick; Cosson, Bertrand; Croce, Jenifer; Fernandez-Guerra, Antonio; Genevière, Anne-Marie; Goel, Manisha; Kelkar, Hemant; Morales, Julia; Mulner-Lorillon, Odile; Robertson, Anthony J; Goldstone, Jared V; Cole, Bryan; Epel, David; Gold, Bert; Hahn, Mark E; Howard-Ashby, Meredith; Scally, Mark; Stegeman, John J; Allgood, Erin L; Cool, Jonah; Judkins, Kyle M; McCafferty, Shawn S; Musante, Ashlan M; Obar, Robert A; Rawson, Amanda P; Rossetti, Blair J; Gibbons, Ian R; Hoffman, Matthew P; Leone, Andrew; Istrail, Sorin; Materna, Stefan C; Samanta, Manoj P; Stolc, Viktor; Tongprasit, Waraporn; Tu, Qiang; Bergeron, Karl-Frederik; Brandhorst, Bruce P; Whittle, James; Berney, Kevin; Bottjer, David J; Calestani, Cristina; Peterson, Kevin; Chow, Elly; Yuan, Qiu Autumn; Elhaik, Eran; Graur, Dan; Reese, Justin T; Bosdet, Ian; Heesun, Shin; Marra, Marco A; Schein, Jacqueline; Anderson, Michele K; Brockton, Virginia; Buckley, Katherine M; Cohen, Avis H; Fugmann, Sebastian D; Hibino, Taku; Loza-Coll, Mariano; Majeske, Audrey J; Messier, Cynthia; Nair, Sham V; Pancer, Zeev; Terwilliger, David P; Agca, Cavit; Arboleda, Enrique; Chen, Nansheng; Churcher, Allison M; Hallböök, F; Humphrey, Glen W; Idris, Mohammed M; Kiyama, Takae; Liang, Shuguang; Mellott, Dan; Mu, Xiuqian; Murray, Greg; Olinski, Robert P; Raible, Florian; Rowe, Matthew; Taylor, John S; Tessmar-Raible, Kristin; Wang, D; Wilson, Karen H; Yaguchi, Shunsuke; Gaasterland, Terry; Galindo, Blanca E; Gunaratne, Herath J; Juliano, Celina; Kinukawa, Masashi; Moy, Gary W; Neill, Anna T; Nomura, Mamoru; Raisch, Michael; Reade, Anna; Roux, Michelle M; Song, Jia L; Su, Yi-Hsien; Townley, Ian K; Voronina, Ekaterina; Wong, Julian L; Amore, Gabriele; Branno, Margherita; Brown, Euan R; Cavalieri, Vincenzo; Duboc, Véronique; Duloquin, Louise; Flytzanis, Constantin; Gache, Christian; Lapraz, François; Lepage, Thierry; Locascio, Annamaria; Martinez, Pedro; Matassi, Giorgio; Matranga, Valeria; Range, Ryan; Rizzo, Francesca; Röttinger, Eric; Beane, Wendy; Bradham, Cynthia; Byrum, Christine; Glenn, Tom; Hussain, Sofia; Manning, Gerard; Miranda, Esther; Thomason, Rebecca; Walton, Katherine; Wikramanayke, Athula; Wu, Shu-Yu; Xu, Ronghui; Brown, C Titus; Chen, Lili; Gray, Rachel F; Lee, Pei Yun; Nam, Jongmin; Oliveri, Paola; Smith, Joel; Muzny, Donna; Bell, Stephanie; Chacko, Joseph; Cree, Andrew; Curry, Stacey; Davis, Clay; Dinh, Huyen; Dugan-Rocha, Shannon; Fowler, Jerry; Gill, Rachel; Hamilton, Cerrissa; Hernandez, Judith; Hines, Sandra; Hume, Jennifer; Jackson, Laronda; Jolivet, Angela; Kovar, Christie; Lee, Sandra; Lewis, Lora; Miner, George; Morgan, Margaret; Nazareth, Lynne V; Okwuonu, Geoffrey; Parker, David; Pu, Ling-Ling; Thorn, Rachel; Wright, Rita

2006-11-10

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.

Genome-wide expression profiling in pediatric septic shock

PubMed Central

Wong, Hector R.

2013-01-01

For nearly a decade, our research group has had the privilege of developing and mining a multi-center, microarray-based, genome-wide expression database of critically ill children (≤ 10 years of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which will be reviewed. Fundamental observations include wide spread repression of gene programs corresponding to the adaptive immune system, and biologically significant differential patterns of gene expression across developmental age groups. The data have also identified gene expression-based subclasses of pediatric septic shock having clinically relevant phenotypic differences. The data have also been leveraged for the discovery of novel therapeutic targets, and for the discovery and development of novel stratification and diagnostic biomarkers. Almost a decade of genome-wide expression profiling in pediatric septic shock is now demonstrating tangible results. The studies have progressed from an initial discovery-oriented and exploratory phase, to a new phase where the data are being translated and applied to address several areas of clinical need. PMID:23329198

Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates

PubMed Central

Kikuta, Hiroshi; Laplante, Mary; Navratilova, Pavla; Komisarczuk, Anna Z.; Engström, Pär G.; Fredman, David; Akalin, Altuna; Caccamo, Mario; Sealy, Ian; Howe, Kerstin; Ghislain, Julien; Pezeron, Guillaume; Mourrain, Philippe; Ellingsen, Staale; Oates, Andrew C.; Thisse, Christine; Thisse, Bernard; Foucher, Isabelle; Adolf, Birgit; Geling, Andrea; Lenhard, Boris; Becker, Thomas S.

2007-01-01

We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated “bystander” genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs. PMID:17387144

The Long Noncoding RNA Transcriptome of Dictyostelium discoideum Development.

PubMed

Rosengarten, Rafael D; Santhanam, Balaji; Kokosar, Janez; Shaulsky, Gad

2017-02-09

Dictyostelium discoideum live in the soil as single cells, engulfing bacteria and growing vegetatively. Upon starvation, tens of thousands of amoebae enter a developmental program that includes aggregation, multicellular differentiation, and sporulation. Major shifts across the protein-coding transcriptome accompany these developmental changes. However, no study has presented a global survey of long noncoding RNAs (ncRNAs) in D. discoideum To characterize the antisense and long intergenic noncoding RNA (lncRNA) transcriptome, we analyzed previously published developmental time course samples using an RNA-sequencing (RNA-seq) library preparation method that selectively depletes ribosomal RNAs (rRNAs). We detected the accumulation of transcripts for 9833 protein-coding messenger RNAs (mRNAs), 621 lncRNAs, and 162 putative antisense RNAs (asRNAs). The noncoding RNAs were interspersed throughout the genome, and were distinct in expression level, length, and nucleotide composition. The noncoding transcriptome displayed a temporal profile similar to the coding transcriptome, with stages of gradual change interspersed with larger leaps. The transcription profiles of some noncoding RNAs were strongly correlated with known differentially expressed coding RNAs, hinting at a functional role for these molecules during development. Examining the mitochondrial transcriptome, we modeled two novel antisense transcripts. We applied yet another ribosomal depletion method to a subset of the samples to better retain transfer RNA (tRNA) transcripts. We observed polymorphisms in tRNA anticodons that suggested a post-transcriptional means by which D. discoideum compensates for codons missing in the genomic complement of tRNAs. We concluded that the prevalence and characteristics of long ncRNAs indicate that these molecules are relevant to the progression of molecular and cellular phenotypes during development. Copyright © 2017 Rosengarten et al.

45 CFR 1388.7 - Program criteria-dissemination.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., productivity, integration and inclusion of individuals with developmental disabilities and their families. (b... SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM THE UNIVERSITY AFFILIATED PROGRAMS § 1388.7 Program criteria—dissemination...

Global gene expression during early differentiation of Xenopus (Silurana) tropicalis gonad tissues

EPA Science Inventory

African clawed frog Xenopus sp. has been used extensively for developmental biology and toxicology research. Xenopus (Silurana) tropicalis has been coveted more recently for genomics research because its diploid genome has been sequenced. Amid concerns of environmental pollutants...

Genomic Sequence and Experimental Tractability of a New Decapod Shrimp Model, Neocaridina denticulata

PubMed Central

Kenny, Nathan J.; Sin, Yung Wa; Shen, Xin; Zhe, Qu; Wang, Wei; Chan, Ting Fung; Tobe, Stephen S.; Shimeld, Sebastian M.; Chu, Ka Hou; Hui, Jerome H. L.

2014-01-01

The speciose Crustacea is the largest subphylum of arthropods on the planet after the Insecta. To date, however, the only publically available sequenced crustacean genome is that of the water flea, Daphnia pulex, a member of the Branchiopoda. While Daphnia is a well-established ecotoxicological model, previous study showed that one-third of genes contained in its genome are lineage-specific and could not be identified in any other metazoan genomes. To better understand the genomic evolution of crustaceans and arthropods, we have sequenced the genome of a novel shrimp model, Neocaridina denticulata, and tested its experimental malleability. A library of 170-bp nominal fragment size was constructed from DNA of a starved single adult and sequenced using the Illumina HiSeq2000 platform. Core eukaryotic genes, the mitochondrial genome, developmental patterning genes (such as Hox) and microRNA processing pathway genes are all present in this animal, suggesting it has not undergone massive genomic loss. Comparison with the published genome of Daphnia pulex has allowed us to reveal 3750 genes that are indeed specific to the lineage containing malacostracans and branchiopods, rather than Daphnia-specific (E-value: 10−6). We also show the experimental tractability of N. denticulata, which, together with the genomic resources presented here, make it an ideal model for a wide range of further aquacultural, developmental, ecotoxicological, food safety, genetic, hormonal, physiological and reproductive research, allowing better understanding of the evolution of crustaceans and other arthropods. PMID:24619275

A genome-wide approach to children's aggressive behavior: The EAGLE consortium.

PubMed

Pappa, Irene; St Pourcain, Beate; Benke, Kelly; Cavadino, Alana; Hakulinen, Christian; Nivard, Michel G; Nolte, Ilja M; Tiesler, Carla M T; Bakermans-Kranenburg, Marian J; Davies, Gareth E; Evans, David M; Geoffroy, Marie-Claude; Grallert, Harald; Groen-Blokhuis, Maria M; Hudziak, James J; Kemp, John P; Keltikangas-Järvinen, Liisa; McMahon, George; Mileva-Seitz, Viara R; Motazedi, Ehsan; Power, Christine; Raitakari, Olli T; Ring, Susan M; Rivadeneira, Fernando; Rodriguez, Alina; Scheet, Paul A; Seppälä, Ilkka; Snieder, Harold; Standl, Marie; Thiering, Elisabeth; Timpson, Nicholas J; Veenstra, René; Velders, Fleur P; Whitehouse, Andrew J O; Smith, George Davey; Heinrich, Joachim; Hypponen, Elina; Lehtimäki, Terho; Middeldorp, Christel M; Oldehinkel, Albertine J; Pennell, Craig E; Boomsma, Dorret I; Tiemeier, Henning

2016-07-01

Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest sample exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed sample and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total sample. GCTA quantified variance tagged by common SNPs (10-54%). The meta-analysis of the total sample identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P = 5.30 × 10(-8) ). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Developmental Versus Remedial: Does a Confusion of Terms Exist in Higher Education Reading Programs?

ERIC Educational Resources Information Center

Nist, Sherrie L.

1985-01-01

Examines the differences between remedial and developmental reading programs and their places in higher education. Finds a consistency among definitions of remedial reading but no clear consensus for developmental reading. Sees a clear delineation between remedial and developmental students. Offers guidelines for programs and instruction…

Developmental Summer Bridge Programs. What Works Clearinghouse™ Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

Developmental summer bridge programs are designed to reduce the need for developmental education in college by providing students with accelerated instruction in areas where additional knowledge and skills are needed to help them succeed in higher education. The WWC identified one study of developmental summer bridge programs that meets WWC…

Identification and evaluation of candidate genes associated with susceptibility to PCB-126 induced developmental toxicity: a genome-wide analysis

EPA Science Inventory

Dioxin-like compounds (DLCs) are potent teratogens that persist in the environment and pose significant risk to ecological health. Variability in risk of developmental cardiotoxicity caused by DLCs has been demonstrated within and among several vertebrate species. Beyond our know...

Incorporating "omics" in the study of reproduction and development: Virtual Tissue Models in Developmental Toxicity Research

EPA Science Inventory

In recent years, ground breaking research in genomic applications in the area of reproductive and developmental toxicology have been successful in linking changes in the expression of specific genes and their higher-level biological processes to effects induced by drugs or chemic...

The extended evolutionary synthesis: its structure, assumptions and predictions

PubMed Central

Laland, Kevin N.; Uller, Tobias; Feldman, Marcus W.; Sterelny, Kim; Müller, Gerd B.; Moczek, Armin; Jablonka, Eva; Odling-Smee, John

2015-01-01

Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the ‘extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism–environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology. PMID:26246559

The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development.

PubMed

Akhter, Shamima; Lam, Yung C; Chang, Sandy; Legerski, Randy J

2010-12-01

Conserved metallo β-Lactamase and β-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice. © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Transcriptomic Profiling of Fruit Development in Black Raspberry Rubus coreanus

PubMed Central

Hu, Yaodong

2018-01-01

The wild Rubus species R. coreanus, which is widely distributed in southwest China, shows great promise as a genetic resource for breeding. One of its outstanding properties is adaptation to high temperature and humidity. To facilitate its use in selection and breeding programs, we assembled de novo 179,738,287 R. coreanus reads (125 bp in length) generated by RNA sequencing from fruits at three representative developmental stages. We also used the recently released draft genome of R. occidentalis to perform reference-guided assembly. We inferred a final 95,845-transcript reference for R. coreanus. Of these genetic resources, 66,597 (69.5%) were annotated. Based on these results, we carried out a comprehensive analysis of differentially expressed genes. Flavonoid biosynthesis, phenylpropanoid biosynthesis, plant hormone signal transduction, and cutin, suberin, and wax biosynthesis pathways were significantly enriched throughout the ripening process. We identified 23 transcripts involved in the flavonoid biosynthesis pathway whose expression perfectly paralleled changes in the metabolites. Additionally, we identified 119 nucleotide-binding site leucine-rich repeat (NBS-LRR) protein-coding genes, involved in pathogen resistance, of which 74 were in the completely conserved domain. These results provide, for the first time, genome-wide genetic information for understanding developmental regulation of R. coreanus fruits. They have the potential for use in breeding through functional genetic approaches in the near future. PMID:29805970

48 CFR 519.7012 - Developmental assistance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7012 Developmental assistance. The forms of developmental assistance a mentor can provide to a protégé include: (a) Management... Mentor-Protégé Program Manager. ...

Developmental Specificity in Targeting and Teaching Play Activities to Children with Pervasive Developmental Disorders

ERIC Educational Resources Information Center

Lifter, Karin; Ellis, James; Cannon, Barbara; Anderson, Stephen R.

2005-01-01

Developmentally specific play programs were designed for three children with pervasive developmental disorders being served in a home-based program. Using the Developmental Play Assessment, six activities for each of three adjacent developmentally sequenced play categories were targeted for direct instruction using different toy sets. A modified…

45 CFR 1388.5 - Program criteria-preparation of personnel.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., integration and inclusion of individuals with developmental disabilities and their families. (f) The UAP must... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM THE UNIVERSITY AFFILIATED PROGRAMS § 1388.5 Program criteria—preparation of...

45 CFR 1388.6 - Program criteria-services and supports.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., integration and inclusion of individuals with developmental disabilities and their families. (b) UAP community... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM THE UNIVERSITY AFFILIATED PROGRAMS § 1388.6 Program criteria—services and...

The Genome of the Sea Urchin Strongylocentrotus purpuratus

PubMed Central

2011-01-01

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes. PMID:17095691

Array comparative genome hybridization in patients with developmental delay: two example cases.

PubMed

Hancarova, Miroslava; Drabova, Jana; Zmitkova, Zuzana; Vlckova, Marketa; Hedvicakova, Petra; Novotna, Drahuse; Vlckova, Zdenka; Vejvalkova, Sarka; Marikova, Tatana; Sedlacek, Zdenek

2012-02-15

Developmental delay is often a predictor of mental retardation (MR) or autism, two relatively frequent developmental disorders severely affecting intellectual and social functioning. The causes of these conditions remain unknown in most patients. They have a strong genetic component, but the specific genetic defects can only be identified in a fraction of patients. Recent developments in genomics supported the establishment of the causal link between copy number variants in the genomes of some patients and their affection. One of the techniques suitable for this analysis is array comparative genome hybridization, which can be used both for detailed mapping of chromosome rearrangements identified by classical cytogenetics and for the identification of novel submicroscopic gains or losses of genetic material. We illustrate the power of this approach in two patients. Patient 1 had a cytogenetically visible deletion of chromosome X and the molecular analysis was used to specify the gene content of the deletion and the prognosis of the child. Patient 2 had a seemingly normal karyotype and the analysis revealed a small recurrent deletion of chromosome 1 likely to be responsible for his phenotype. However, the genetic dissection of MR and autism is complicated by high heterogeneity of the genetic aberrations among patients and by broad variability of phenotypic effects of individual genetic defects. Copyright © 2010 Elsevier B.V. All rights reserved.

RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans

PubMed Central

Hall, Sarah E.; Chirn, Gung-Wei; Lau, Nelson C.; Sengupta, Piali

2013-01-01

Early environmental experiences profoundly influence adult phenotypes through complex mechanisms that are poorly understood. We previously showed that adult Caenorhabditis elegans that transiently passed through the stress-induced dauer larval stage (post-dauer adults) exhibit significant changes in gene expression profiles, chromatin states, and life history traits when compared with adults that bypassed the dauer stage (control adults). These wild-type, isogenic animals of equivalent developmental stages exhibit different signatures of molecular marks that reflect their distinct developmental trajectories. To gain insight into the mechanisms that contribute to these developmental history-dependent phenotypes, we profiled small RNAs from post-dauer and control adults by deep sequencing. RNA interference (RNAi) pathways are known to regulate genome-wide gene expression both at the chromatin and post-transcriptional level. By quantifying changes in endogenous small interfering RNA (endo-siRNA) levels in post-dauer as compared with control animals, our analyses identified a subset of genes that are likely targets of developmental history-dependent reprogramming through a complex RNAi-mediated mechanism. Mutations in specific endo-siRNA pathways affect expected gene expression and chromatin state changes for a subset of genes in post-dauer animals, as well as disrupt their increased brood size phenotype. We also find that both chromatin state and endo-siRNA distribution in dauers are unique, and suggest that remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Our results indicate a role for endo-siRNA pathways as a contributing mechanism to early experience-dependent phenotypic plasticity in adults, and describe how developmental history can program adult physiology and behavior via epigenetic mechanisms. PMID:23329696

Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways | Office of Cancer Genomics

Cancer.gov

Malignant rhabdoid tumors (MRTs) are rare lethal tumors of childhood that most commonly occur in the kidney and brain. MRTs are driven by SMARCB1 loss, but the molecular consequences of SMARCB1 loss in extra-cranial tumors have not been comprehensively described and genomic resources for analyses of extra-cranial MRT are limited.

Differences in the genetic control of early egg development and reproduction between C. elegans and its parthenogenetic relative D. coronatus.

PubMed

Kraus, Christopher; Schiffer, Philipp H; Kagoshima, Hiroshi; Hiraki, Hideaki; Vogt, Theresa; Kroiher, Michael; Kohara, Yuji; Schierenberg, Einhard

2017-01-01

The free-living nematode Diploscapter coronatus is the closest known relative of Caenorhabditis elegans with parthenogenetic reproduction. It shows several developmental idiosyncracies, for example concerning the mode of reproduction, embryonic axis formation and early cleavage pattern (Lahl et al. in Int J Dev Biol 50:393-397, 2006). Our recent genome analysis (Hiraki et al. in BMC Genomics 18:478, 2017) provides a solid foundation to better understand the molecular basis of developmental idiosyncrasies in this species in an evolutionary context by comparison with selected other nematodes. Our genomic data also yielded indications for the view that D. coronatus is a product of interspecies hybridization. In a genomic comparison between D. coronatus , C. elegans , other representatives of the genus Caenorhabditis and the more distantly related Pristionchus pacificus and Panagrellus redivivus , certain genes required for central developmental processes in C. elegans like control of meiosis and establishment of embryonic polarity were found to be restricted to the genus Caenorhabditis . The mRNA content of early D. coronatus embryos was sequenced and compared with similar stages in C. elegans and Ascaris suum . We identified 350 gene families transcribed in the early embryo of D. coronatus but not in the other two nematodes. Looking at individual genes transcribed early in D. coronatus but not in C. elegans and A. suum , we found that orthologs of most of these are present in the genomes of the latter species as well, suggesting heterochronic shifts with respect to expression behavior. Considerable genomic heterozygosity and allelic divergence lend further support to the view that D. coronatus may be the result of an interspecies hybridization. Expression analysis of early acting single-copy genes yields no indication for silencing of one parental genome. Our comparative cellular and molecular studies support the view that the genus Caenorhabditis differs considerably from the other studied nematodes in its control of development and reproduction. The easy-to-culture parthenogenetic D. coronatus , with its high-quality draft genome and only a single chromosome when haploid, offers many new starting points on the cellular, molecular and genomic level to explore alternative routes of nematode development and reproduction.

Organogenesis in deep time: A problem in genomics, development, and paleontology.

PubMed

Pieretti, Joyce; Gehrke, Andrew R; Schneider, Igor; Adachi, Noritaka; Nakamura, Tetsuya; Shubin, Neil H

2015-04-21

The fossil record is a unique repository of information on major morphological transitions. Increasingly, developmental, embryological, and functional genomic approaches have also conspired to reveal evolutionary trajectory of phenotypic shifts. Here, we use the vertebrate appendage to demonstrate how these disciplines can mutually reinforce each other to facilitate the generation and testing of hypotheses of morphological evolution. We discuss classical theories on the origins of paired fins, recent data on regulatory modulations of fish fins and tetrapod limbs, and case studies exploring the mechanisms of digit loss in tetrapods. We envision an era of research in which the deep history of morphological evolution can be revealed by integrating fossils of transitional forms with direct experimentation in the laboratory via genome manipulation, thereby shedding light on the relationship between genes, developmental processes, and the evolving phenotype.

Identifying genomic and developmental causes of adverse drug reactions in children

PubMed Central

Becker, Mara L; Leeder, J Steven

2011-01-01

Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed. PMID:21121777

Evolutionarily diverse determinants of meiotic DNA break and recombination landscapes across the genome

PubMed Central

Fowler, Kyle R.; Sasaki, Mariko; Milman, Neta

2014-01-01

Fission yeast Rec12 (Spo11 homolog) initiates meiotic recombination by forming developmentally programmed DNA double-strand breaks (DSBs). DSB distributions influence patterns of heredity and genome evolution, but the basis of the highly nonrandom choice of Rec12 cleavage sites is poorly understood, largely because available maps are of relatively low resolution and sensitivity. Here, we determined DSBs genome-wide at near-nucleotide resolution by sequencing the oligonucleotides attached to Rec12 following DNA cleavage. The single oligonucleotide size class allowed us to deeply sample all break events. We find strong evidence across the genome for differential DSB repair accounting for crossover invariance (constant cM/kb in spite of DSB hotspots). Surprisingly, about half of all crossovers occur in regions where DSBs occur at low frequency and are widely dispersed in location from cell to cell. These previously undetected, low-level DSBs thus play an outsized and crucial role in meiosis. We further find that the influence of underlying nucleotide sequence and chromosomal architecture differs in multiple ways from that in budding yeast. DSBs are not strongly restricted to nucleosome-depleted regions, as they are in budding yeast, but are nevertheless spatially influenced by chromatin structure. Our analyses demonstrate that evolutionarily fluid factors contribute to crossover initiation and regulation. PMID:25024163

Genomic identification of direct target genes of LEAFY

PubMed Central

William, Dilusha A.; Su, Yanhui; Smith, Michael R.; Lu, Meina; Baldwin, Don A.; Wagner, Doris

2004-01-01

The switch from vegetative to reproductive development in plants necessitates a switch in the developmental program of the descendents of the stem cells in the shoot apical meristem. Genetic and molecular investigations have demonstrated that the plant-specific transcription factor and meristem identity regulator LEAFY (LFY) controls this developmental transition by inducing expression of a second transcription factor, APETALA1, and by regulating the expression of additional, as yet unknown, genes. Here we show that the additional LFY targets include the APETALA1-related factor, CAULI-FLOWER, as well as three transcription factors and two putative signal transduction pathway components. These genes are up-regulated by LFY even when protein synthesis is inhibited and, hence, appear to be direct targets of LFY. Supporting this conclusion, cis-regulatory regions upstream of these genes are bound by LFY in vivo. The newly identified LFY targets likely initiate the transcriptional changes that are required for the switch from vegetative to reproductive development in Arabidopsis. PMID:14736918

A Framework for Assessing Developmental Education Programs

ERIC Educational Resources Information Center

Goldwasser, Molly; Martin, Kimberly; Harris, Eugenia

2017-01-01

This paper presents a framework for educators, administrators, and researchers to assess distinct facets of developmental education programs. The researchers review the literature on best practices in developmental education with regards to program cost, program structure, and student placement procedures. This paper also identifies seven model…

A unique combination of 17pter trisomy and 21qter monosomy in a boy with developmental delay, severe intellectual disability, growth retardation and dysmorphisms.

PubMed

Zheng, Zhaojing; Yao, Ru-En; Geng, Juan; Jin, Xingming; Shen, Yongnian; Ying, Daming; Fu, Qihua; Yu, Yongguo

2013-03-10

Microduplication at 17p13.3 and microdeletion at 21q22 are both rare chromosomal aberrations. The presence of both genomic imbalances in one patient has not been previously reported in literature. In this study, we performed a molecular diagnostic testing with a whole genome microarray on a 3-year-old boy with developmental delay, mental retardation and multiple malformations. A routine G-banding karyotype analysis was performed using peripheral lymphocytes. Chromosome microarray analysis (CMA) was done using Affymetrix CytoScan™ HD array. Genomic imbalances were further confirmed by multiple ligation-dependent probe amplification (MLPA). The result of karyotyping was normal but CMA detected a 9.8 Mb microduplication at 17p13.3-13.1 (chr17: 1-9,875,545) and a 2.8 Mb microdeletion involving 21q22.3-qter (chr21: 45,239,077-48,097,372). The imbalances were due to a balanced translocation present in patient's mother. The patient was characterized with short stature, profound developmental delay, non-verbal, intellectual disability as well as craniofacial dysmorphism, subtle brain structural anomaly and sparse scalp hair. This is the first patient reported with a combination of a microduplication at 17p13.3-13.1 and a microdeletion at 21q22.3-qter. Both genomic imbalances were undetected by conventional karyotyping but were delineated with CMA test. Synergistic effect from the two rare genomic imbalances is likely responsible for the severe clinical phenotypes observed in this patient. Copyright © 2012 Elsevier B.V. All rights reserved.

Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci.

PubMed

Amaral, Paulo P; Leonardi, Tommaso; Han, Namshik; Viré, Emmanuelle; Gascoigne, Dennis K; Arias-Carrasco, Raúl; Büscher, Magdalena; Pandolfini, Luca; Zhang, Anda; Pluchino, Stefano; Maracaja-Coutinho, Vinicius; Nakaya, Helder I; Hemberg, Martin; Shiekhattar, Ramin; Enright, Anton J; Kouzarides, Tony

2018-03-15

The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes. These positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are coexpressed in a tissue-specific manner. Over half of positionally conserved RNAs in this set are linked to chromatin organization structures, overlapping binding sites for the CTCF chromatin organiser and located at chromatin loop anchor points and borders of topologically associating domains (TADs). We define these RNAs as topological anchor point RNAs (tapRNAs). Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other's expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Furthermore, we find that tapRNAs contain conserved sequence domains that are enriched in motifs for zinc finger domain-containing RNA-binding proteins and transcription factors, whose binding sites are found mutated in cancers. This work leverages positional conservation to identify lncRNAs with potential importance in genome organization, development and disease. The evidence that many developmental transcription factors are physically and functionally connected to lncRNAs represents an exciting stepping-stone to further our understanding of genome regulation.

Evolving Ideas on the Origin and Evolution of Flowers: New Perspectives in the Genomic Era

PubMed Central

Chanderbali, Andre S.; Berger, Brent A.; Howarth, Dianella G.; Soltis, Pamela S.; Soltis, Douglas E.

2016-01-01

The origin of the flower was a key innovation in the history of complex organisms, dramatically altering Earth’s biota. Advances in phylogenetics, developmental genetics, and genomics during the past 25 years have substantially advanced our understanding of the evolution of flowers, yet crucial aspects of floral evolution remain, such as the series of genetic and morphological changes that gave rise to the first flowers; the factors enabling the origin of the pentamerous eudicot flower, which characterizes ∼70% of all extant angiosperm species; and the role of gene and genome duplications in facilitating floral innovations. A key early concept was the ABC model of floral organ specification, developed by Elliott Meyerowitz and Enrico Coen and based on two model systems, Arabidopsis thaliana and Antirrhinum majus. Yet it is now clear that these model systems are highly derived species, whose molecular genetic-developmental organization must be very different from that of ancestral, as well as early, angiosperms. In this article, we will discuss how new research approaches are illuminating the early events in floral evolution and the prospects for further progress. In particular, advancing the next generation of research in floral evolution will require the development of one or more functional model systems from among the basal angiosperms and basal eudicots. More broadly, we urge the development of “model clades” for genomic and evolutionary-developmental analyses, instead of the primary use of single “model organisms.” We predict that new evolutionary models will soon emerge as genetic/genomic models, providing unprecedented new insights into floral evolution. PMID:27053123

Fish from Head to Tail: The 9th European Zebrafish Meeting in Oslo.

PubMed

Griffiths, Gareth; Müller, Ferenc; Ledin, Johan; Patton, E Elizabeth; Gjøen, Tor; Lobert, Viola Hélène; Winther-Larsen, Hanne Cecilie; Mullins, Mary; Joly, Jean-Stephane; Weltzien, Finn-Arne; Press, Charles McLean; Aleström, Peter

2016-04-01

The 9th European Zebrafish Meeting took place recently in Oslo (June 28-July 2, 2015). A total of 650 participants came to hear the latest research news focused on the zebrafish, Danio rerio, and to its distant evolutionary relative medaka, Oryzias latipes. The packed program included keynote and plenary talks, short oral presentations and poster sessions, workshops, and strategic discussions. The meeting was a great success and revealed dramatically how important the zebrafish in particular has become as a model system for topics, such as developmental biology, functional genomics, biomedicine, toxicology, and drug development. A new emphasis was given to its potential as a model for aquaculture, a topic of great economic interest to the host country Norway and for the future global food supply in general. Zebrafish husbandry as well as its use in teaching were also covered in separate workshops. As has become a tradition in these meetings, there was a well-attended Wellcome Trust Sanger Institute and ZFIN workshop focused on Zebrafish Genome Resources on the first day. The full EZM 2015 program with abstracts can be read and downloaded from the EZM 2015 Web site zebrafish2015.org .

45 CFR 1386.30 - State plan requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and inclusion into the community of individuals with developmental disabilities. Direct service..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS Federal Assistance to State Developmental Disabilities Councils...

Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

PubMed Central

Arenas-Mena, Cesar; Coffman, James A.

2016-01-01

Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

48 CFR 819.7110 - Developmental assistance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7110 Developmental assistance. The forms of developmental assistance a mentor can provide to a protégé include, but are not limited...

Sequencing and comparative genomic analysis of 1227 Felis catus cDNA sequences enriched for developmental, clinical and nutritional phenotypes

PubMed Central

2012-01-01

Background The feline genome is valuable to the veterinary and model organism genomics communities because the cat is an obligate carnivore and a model for endangered felids. The initial public release of the Felis catus genome assembly provided a framework for investigating the genomic basis of feline biology. However, the entire set of protein coding genes has not been elucidated. Results We identified and characterized 1227 protein coding feline sequences, of which 913 map to public sequences and 314 are novel. These sequences have been deposited into NCBI's genbank database and complement public genomic resources by providing additional protein coding sequences that fill in some of the gaps in the feline genome assembly. Through functional and comparative genomic analyses, we gained an understanding of the role of these sequences in feline development, nutrition and health. Specifically, we identified 104 orthologs of human genes associated with Mendelian disorders. We detected negative selection within sequences with gene ontology annotations associated with intracellular trafficking, cytoskeleton and muscle functions. We detected relatively less negative selection on protein sequences encoding extracellular networks, apoptotic pathways and mitochondrial gene ontology annotations. Additionally, we characterized feline cDNA sequences that have mouse orthologs associated with clinical, nutritional and developmental phenotypes. Together, this analysis provides an overview of the value of our cDNA sequences and enhances our understanding of how the feline genome is similar to, and different from other mammalian genomes. Conclusions The cDNA sequences reported here expand existing feline genomic resources by providing high-quality sequences annotated with comparative genomic information providing functional, clinical, nutritional and orthologous gene information. PMID:22257742

A developmental transcriptome map for allotetraploid arachis hypogaea

USDA-ARS?s Scientific Manuscript database

The advent of the genome sequences of Arachis duranensis and Arachis ipaensis has ushered in a new era for peanut genomics. With the goal of producing a gene atlas for cultivated peanut (Arachis hypogaea), 22 different tissue types and ontogenies that represent the full development of peanut were s...

Interview: Professor Andrew Feinberg speaks to Epigenomics.

PubMed

Feinberg, Andrew

2009-10-01

Andrew Feinberg studied mathematics and humanities at Yale University (CT, USA) in the Directed Studies honors program, and he received his BA (1973) and MD (1976) from the accelerated medical program at Johns Hopkins University (MD, USA), as well as an MPH from Johns Hopkins (1981). He performed a postdoctoral fellowship in developmental biology at the University of California, San Diego (UCSD, CA, USA), clinical training in medicine and medical genetics at the University of Pennsylvania (PA, USA) and genetics research with Bert Vogelstein at Johns Hopkins, discovering altered DNA methylation in human cancer. Dr Feinberg continued to perform seminal work in cancer epigenetics as a Howard Hughes investigator at the University of Michigan (MI, USA), discovering human imprinted genes and loss of imprinting in cancer, and the molecular basis of Beckwith-Wiedemann syndrome. He returned to John Hopkins in 1994 as King Fahd Professor of Medicine, Molecular Biology & Genetics and Oncology, and he holds an Adjunct Professorship at the Karolinska Institute in Sweden. Dr Feinberg is Director of the Center for Epigenetics, a National Human Genome Research Institute-designated Center of Excellence in Genome Sciences. The Center is pioneering genome-scale tools in molecular, statistical and epidemiological epigenetics, and is applying them to the study of cancer, neuropsychiatric disease and aging. As part of the center, Dr Feinberg has organized a highly innovative program to bring gifted minority high-school students into genetics and genomics. Dr Feinberg has also invented a number of widely used molecular tools, including random priming. His honors include election to the American Society for Clinical Investigation, the Association of American Physicians, the Institute of Medicine of the National Academy of Sciences, and the American Academy of Arts and Sciences, as well as membership on the ISI most-cited authors list, a MERIT Award of the National Cancer Institute, a Doctor of Philosophy (Hon. Caus.) from Uppsala University (Sweden), and the President's Diversity Recognition Award of Johns Hopkins University.

Network Analysis of a Demonstration Program for the Developmentally Disabled

ERIC Educational Resources Information Center

Fredericks, Kimberly A.

2005-01-01

This chapter presents the findings from a network analysis of a demonstration program for the developmentally disabled to show the application of graphical network analysis in program evaluation. The developmentally disabled demonstration (DDD) program was a five-year pilot project to provide person-centered service environments to people with …

The zebrafish genome: a review and msx gene case study.

PubMed

Postlethwait, J H

2006-01-01

Zebrafish is one of several important teleost models for understanding principles of vertebrate developmental, molecular, organismal, genetic, evolutionary, and genomic biology. Efficient investigation of the molecular genetic basis of induced mutations depends on knowledge of the zebrafish genome. Principles of zebrafish genomic analysis, including gene mapping, ortholog identification, conservation of syntenies, genome duplication, and evolution of duplicate gene function are discussed here using as a case study the zebrafish msxa, msxb, msxc, msxd, and msxe genes, which together constitute zebrafish orthologs of tetrapod Msx1, Msx2, and Msx3. Genomic analysis suggests orthologs for this difficult to understand group of paralogs.

Caste development and reproduction: a genome-wide analysis of hallmarks of insect eusociality

PubMed Central

Cristino, A S; Nunes, F M F; Lobo, C H; Bitondi, M M G; Simões, Z L P; Da Fontoura Costa, L; Lattorff, H M G; Moritz, R F A; Evans, J D; Hartfelder, K

2006-01-01

The honey bee queen and worker castes are a model system for developmental plasticity. We used established expressed sequence tag information for a Gene Ontology based annotation of genes that are differentially expressed during caste development. Metabolic regulation emerged as a major theme, with a caste-specific difference in the expression of oxidoreductases vs. hydrolases. Motif searches in upstream regions revealed group-specific motifs, providing an entry point to cis-regulatory network studies on caste genes. For genes putatively involved in reproduction, meiosis-associated factors came out as highly conserved, whereas some determinants of embryonic axes either do not have clear orthologs (bag of marbles, gurken, torso), or appear to be lacking (trunk) in the bee genome. Our results are the outcome of a first genome-based initiative to provide an annotated framework for trends in gene regulation during female caste differentiation (representing developmental plasticity) and reproduction. PMID:17069641

The grapevine expression atlas reveals a deep transcriptome shift driving the entire plant into a maturation program.

PubMed

Fasoli, Marianna; Dal Santo, Silvia; Zenoni, Sara; Tornielli, Giovanni Battista; Farina, Lorenzo; Zamboni, Anita; Porceddu, Andrea; Venturini, Luca; Bicego, Manuele; Murino, Vittorio; Ferrarini, Alberto; Delledonne, Massimo; Pezzotti, Mario

2012-09-01

We developed a genome-wide transcriptomic atlas of grapevine (Vitis vinifera) based on 54 samples representing green and woody tissues and organs at different developmental stages as well as specialized tissues such as pollen and senescent leaves. Together, these samples expressed ∼91% of the predicted grapevine genes. Pollen and senescent leaves had unique transcriptomes reflecting their specialized functions and physiological status. However, microarray and RNA-seq analysis grouped all the other samples into two major classes based on maturity rather than organ identity, namely, the vegetative/green and mature/woody categories. This division represents a fundamental transcriptomic reprogramming during the maturation process and was highlighted by three statistical approaches identifying the transcriptional relationships among samples (correlation analysis), putative biomarkers (O2PLS-DA approach), and sets of strongly and consistently expressed genes that define groups (topics) of similar samples (biclustering analysis). Gene coexpression analysis indicated that the mature/woody developmental program results from the reiterative coactivation of pathways that are largely inactive in vegetative/green tissues, often involving the coregulation of clusters of neighboring genes and global regulation based on codon preference. This global transcriptomic reprogramming during maturation has not been observed in herbaceous annual species and may be a defining characteristic of perennial woody plants.

Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells

PubMed Central

MacLennan, Marie; García-Cañadas, Marta; Reichmann, Judith; Khazina, Elena; Wagner, Gabriele; Playfoot, Christopher J; Salvador-Palomeque, Carmen; Mann, Abigail R; Peressini, Paula; Sanchez, Laura; Dobie, Karen; Read, David; Hung, Chao-Chun; Eskeland, Ragnhild; Meehan, Richard R; Weichenrieder, Oliver; García-Pérez, Jose Luis; Adams, Ian R

2017-01-01

Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals. DOI: http://dx.doi.org/10.7554/eLife.26152.001 PMID:28806172

Developmental Kindergarten Program Evaluation Report.

ERIC Educational Resources Information Center

Blois, George T.; Cushing, Katherine S.

The evaluation of the Developmental Kindergarten (DK) Program at the Harrison School District #2, Colorado Springs, Colorado, involved pre- and post-testing of student academic gains and interviewing of principals and teachers. The program aimed to provide developmentally appropriate activities for students believed to be "at risk" of…

The Effects of a Developmentally Appropriate Music and Movement Program on Motor Performance

ERIC Educational Resources Information Center

Zachopoulou, E.; Tsapakidou, A.; Derri, V.

2004-01-01

Basic motor skills development is achieved through the implementation of different types of physical education programs. The purpose of this study was to investigate and to compare the effect of a developmentally appropriate music and movement program and of a developmentally appropriate physical education program on the development of jumping and…

Identification and resolution of artifacts in the interpretation of imprinted gene expression.

PubMed

Proudhon, Charlotte; Bourc'his, Déborah

2010-12-01

Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has failed to uncover a significant number of new imprinted genes, probably because of the high tissue- and developmental-stage specificity of imprinted gene expression. A very large number of technical and biological artifacts can also lead to the erroneous evidence of imprinted gene expression. In this article, we focus on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoallelic expression and (iii) contamination or infiltration of embryonic tissues with maternal material. This last situation specifically applies to genes that occur as maternally expressed in the placenta. Beside the use of reciprocal crosses that are instrumental to confirm the parental specificity of expression, we provide additional methods for the detection and elimination of these situations that can be misinterpreted as cases of imprinted expression.

Transcriptome Analysis and Discovery of Genes Relevant to Development in Bradysia odoriphaga at Three Developmental Stages.

PubMed

Gao, Huanhuan; Zhai, Yifan; Wang, Wenbo; Chen, Hao; Zhou, Xianhong; Zhuang, Qianying; Yu, Yi; Li, Rumei

2016-01-01

Bradysia odoriphaga (Diptera: Sciaridae) is the most important pest of Chinese chive (Allium tuberosum) in Asia; however, the molecular genetics are poorly understood. To explore the molecular biological mechanism of development, Illumina sequencing and de novo assembly were performed in the third-instar, fourth-instar, and pupal B. odoriphaga. The study resulted in 16.2 Gb of clean data and 47,578 unigenes (≥125 bp) contained in 7,632,430 contigs, 46.21% of which were annotated from non-redundant protein (NR), Gene Ontology (GO), Clusters of Orthologous Groups (COG), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. It was found that 19.67% of unigenes matched the homologous species mainly, including Aedes aegypti, Culex quinquefasciatus, Ceratitis capitata, and Anopheles gambiae. According to differentially expressed gene (DEG) analysis, 143, 490, and 309 DEGs were annotated as involved in the developmental process in the GO database respectively, in the comparisons of third-instar and fourth-instar larvae, third-instar larvae and pupae, and fourth-instar larvae and pupae. Twenty-five genes were closely related to these processes, including developmental process, reproduction process, and reproductive organs development and programmed cell death (PCD). The information of unigenes assembled in B. odoriphaga through transcriptome and DEG analyses could provide a detailed genetic basis and regulated information for elaborating the developmental mechanism from the larval, pre-pupal to pupal stages of B. odoriphaga.

Use of Genomic Data in Risk Assessment Caes Study: II. Evaluation of the Dibutyl Phthalate Toxicogenomic Dataset

EPA Science Inventory

An evaluation of the toxicogenomic data set for dibutyl phthalate (DBP) and male reproductive developmental effects was performed as part of a larger case study to test an approach for incorporating genomic data in risk assessment. The DBP toxicogenomic data set is composed of ni...

Chromosomal Mapping and Candidate Gene Discovery of Chicken Developmental Mutants and Genome-wide Variation Analysis of MHC-congenics

USDA-ARS?s Scientific Manuscript database

The chicken has been widely used in experimental research given its importance to agriculture and its utility as a model for vertebrate biology and biomedical pursuits for over 100 years. Herein we used recently developed advanced technologies to investigate the genomic characteristics of specialize...

A genome-wide association study for the incidence of persistent bovine viral diarrhea virus infection in cattle

USDA-ARS?s Scientific Manuscript database

Bovine Viral Diarrhea Viruses (BVDV) comprises a diverse group of viruses that causes disease in cattle. BVDV may establish both, transient and persistent infections depending on the developmental stage of the animal at exposure. The objective was to determine if genomic regions harboring single nuc...

A genome-wide association study for the incidence of persistent bovine viral diarrhea virus infection in cattle

USDA-ARS?s Scientific Manuscript database

Bovine Viral Diarrhea Viruses (BVDV) comprise a diverse group of viruses that cause disease in cattle. BVDV may establish both, transient and persistent infections depending on the developmental stage of the animal at exposure. The objective was to determine if genomic regions harboring single nucle...

Genomic Sciences for Developmentalists: A Merge of Science and Practice

ERIC Educational Resources Information Center

Grigorenko, Elena L.

2015-01-01

The etiological forces of development have been a central question for the developmental sciences (however defined) since their crystallization as a distinct branch of scientific inquiry. Although the history of these sciences contains examples of extreme positions capitalizing on either the predominance of the genome (i.e., the accumulation of…

DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.

PubMed

White, Eric J; Emanuelsson, Olof; Scalzo, David; Royce, Thomas; Kosak, Steven; Oakeley, Edward J; Weissman, Sherman; Gerstein, Mark; Groudine, Mark; Snyder, Michael; Schübeler, Dirk

2004-12-21

Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insights into the contribution of developmental state, genomic sequence, and transcriptional activity to replication timing, we investigated the timing of DNA replication at high resolution along an entire human chromosome (chromosome 22) in two different cell types. The pattern of replication timing was correlated with respect to annotated genes, gene expression, novel transcribed regions of unknown function, sequence composition, and cytological features. We observed that chromosome 22 contains regions of early- and late-replicating domains of 100 kb to 2 Mb, many (but not all) of which are associated with previously described chromosomal bands. In both cell types, expressed sequences are replicated earlier than nontranscribed regions. However, several highly transcribed regions replicate late. Overall, the DNA replication-timing profiles of the two different cell types are remarkably similar, with only nine regions of difference observed. In one case, this difference reflects the differential expression of an annotated gene that resides in this region. Novel transcribed regions with low coding potential exhibit a strong propensity for early DNA replication. Although the cellular function of such transcripts is poorly understood, our results suggest that their activity is linked to the replication-timing program.

Regulatory gene networks and the properties of the developmental process

NASA Technical Reports Server (NTRS)

Davidson, Eric H.; McClay, David R.; Hood, Leroy

2003-01-01

Genomic instructions for development are encoded in arrays of regulatory DNA. These specify large networks of interactions among genes producing transcription factors and signaling components. The architecture of such networks both explains and predicts developmental phenomenology. Although network analysis is yet in its early stages, some fundamental commonalities are already emerging. Two such are the use of multigenic feedback loops to ensure the progressivity of developmental regulatory states and the prevalence of repressive regulatory interactions in spatial control processes. Gene regulatory networks make it possible to explain the process of development in causal terms and eventually will enable the redesign of developmental regulatory circuitry to achieve different outcomes.

Developmental Screening in Community Health Care Centers and Pediatric Practices: An Evaluation of the Baby Steps Program

ERIC Educational Resources Information Center

Shannon, Patrick; Anderson, Patti Rawding

2008-01-01

The Baby Steps Program (Easter Seals of New Hampshire, 2003) is a child-find program that introduces developmental specialists into health care settings to conduct developmental screenings with children during well-child visits. This article presents the Baby Steps Program model, summaries of screening and referral data, and the results of 3 focus…

Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs. NCPR Brief

ERIC Educational Resources Information Center

Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

2011-01-01

In 2009, the National Center for Postsecondary Research (NCPR) launched an evaluation of eight developmental summer bridge programs in Texas to assess whether these programs reduce the need for developmental coursework and improve student outcomes in college. The evaluation uses an experimental design to measure the effects of these programs on…

Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

PubMed

Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

2010-04-01

Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

A Lifespan Developmental-Stage Approach to Tobacco and Other Drug Abuse Prevention

PubMed Central

2013-01-01

At least by informal design, tobacco and other drug abuse prevention programs are tailored to human developmental stage. However, few papers have been written to examine how programming has been formulated as a function of developmental stage throughout the lifespan. In this paper, I briefly define lifespan development, how it pertains to etiology of tobacco and other drug use, and how prevention programming might be constructed by five developmental stages: (a) young child, (b) older child, (c) young teen, (d) older teen, and (e) adult (emerging, young-to-middle and older adult substages). A search of the literature on tobacco and other drug abuse prevention by developmental stage was conducted, and multiple examples of programs are provided for each stage. A total of 34 programs are described as examples of each stage (five-young children, 12-older children, eight-young teens, four-older teens, and five-adults). Implications for future program development research are stated. In particular, I suggest that programming continue to be developed for all stages in the lifespan, as opposed to focusing on a single stage and that developmentally appropriate features continues to be pursued to maximize program impact. PMID:25298961

A Predoctoral Program in Dental Care for the Developmentally Disabled.

ERIC Educational Resources Information Center

Ferguson, Fred S.; And Others

1990-01-01

In 1980, the State University of New York at Stony Brook began a program, integrated into the program of children's dentistry, to train students in care for the developmentally disabled. Management of developmentally disabled patients is provided over three years, and represents an extension of pediatric behavior management. (MSE)

Distal Limb Patterning Requires Modulation of cis-Regulatory Activities by HOX13

DOE PAGES

Sheth, Rushikesh; Barozzi, Iros; Langlais, David; ...

2016-12-13

The combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in Hoxa13–/–; Hoxd13–/– limbs. Ourmore » results show that proper termination of the early limb transcriptional program and activation of the late-distal limb program are coordinated by the dual action of HOX13 on cis-regulatory modules.« less

Parenting from before conception.

PubMed

Lane, Michelle; Robker, Rebecca L; Robertson, Sarah A

2014-08-15

At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte cytosine methylation and chromatin patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic effects interact with conditions at conception to program the developmental trajectory of the embryo and fetus, ultimately affecting the lifetime health of the child. These insights compel us to revise generally held notions to accommodate the prospect that biological parenting commences well before birth, even prior to conception. Copyright © 2014, American Association for the Advancement of Science.

Regulatory states in the developmental control of gene expression.

PubMed

Peter, Isabelle S

2017-09-01

A growing body of evidence shows that gene expression in multicellular organisms is controlled by the combinatorial function of multiple transcription factors. This indicates that not the individual transcription factors or signaling molecules, but the combination of expressed regulatory molecules, the regulatory state, should be viewed as the functional unit in gene regulation. Here, I discuss the concept of the regulatory state and its proposed role in the genome-wide control of gene expression. Recent analyses of regulatory gene expression in sea urchin embryos have been instrumental for solving the genomic control of cell fate specification in this system. Some of the approaches that were used to determine the expression of regulatory states during sea urchin embryogenesis are reviewed. Significant developmental changes in regulatory state expression leading to the distinct specification of cell fates are regulated by gene regulatory network circuits. How these regulatory state transitions are encoded in the genome is illuminated using the sea urchin endoderm-mesoderms cell fate decision circuit as an example. These observations highlight the importance of considering developmental gene regulation, and the function of individual transcription factors, in the context of regulatory states. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Complete Mitochondrial Genome of the Medicinal Mushroom Ganoderma lucidum

PubMed Central

Chen, Haimei; Chen, Xiangdong; Lan, Jin; Liu, Chang

2013-01-01

Ganoderma lucidum is one of the well-known medicinal basidiomycetes worldwide. The mitochondrion, referred to as the second genome, is an organelle found in most eukaryotic cells and participates in critical cellular functions. Elucidating the structure and function of this genome is important to understand completely the genetic contents of G. lucidum. In this study, we assembled the mitochondrial genome of G. lucidum and analyzed the differential expressions of its encoded genes across three developmental stages. The mitochondrial genome is a typical circular DNA molecule of 60,630 bp with a GC content of 26.67%. Genome annotation identified genes that encode 15 conserved proteins, 27 tRNAs, small and large rRNAs, four homing endonucleases, and two hypothetical proteins. Except for genes encoding trnW and two hypothetical proteins, all genes were located on the positive strand. For the repeat structure analysis, eight forward, two inverted, and three tandem repeats were detected. A pair of fragments with a total length around 5.5 kb was found in both the nuclear and mitochondrial genomes, which suggests the possible transfer of DNA sequences between two genomes. RNA-Seq data for samples derived from three stages, namely, mycelia, primordia, and fruiting bodies, were mapped to the mitochondrial genome and qualified. The protein-coding genes were expressed higher in mycelia or primordial stages compared with those in the fruiting bodies. The rRNA abundances were significantly higher in all three stages. Two regions were transcribed but did not contain any identified protein or tRNA genes. Furthermore, three RNA-editing sites were detected. Genome synteny analysis showed that significant genome rearrangements occurred in the mitochondrial genomes. This study provides valuable information on the gene contents of the mitochondrial genome and their differential expressions at various developmental stages of G. lucidum. The results contribute to the understanding of the functions and evolution of fungal mitochondrial DNA. PMID:23991034

Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs

ERIC Educational Resources Information Center

Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

2011-01-01

In 2007, the Texas Higher Education Coordinating Board (THECB) funded 22 colleges to establish developmental summer bridge programs. Aimed at providing an alternative to traditional developmental education, these programs involve intensive remedial instruction in math, reading, and/or writing and college preparation content for students entering…

A resource for characterizing genome-wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus

Treesearch

Lijun Liu; Trevor Ramsay; Matthew S. Zinkgraf; David Sundell; Nathaniel Robert Street; Vladimir Filkov; Andrew Groover

2015-01-01

Identifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP-seq) resource consisting of genome-wide binding regions and associated putative target genes for four Populus homeodomain transcription factors...

A rare example of germ-line chromothripsis resulting in large genomic imbalance.

PubMed

Anderson, Sarah E; Kamath, Arveen; Pilz, Daniela T; Morgan, Sian M

2016-04-01

Chromothripsis is a recently described 'chromosome catastrophe' phenomenon in which multiple genomic rearrangements are generated in a single catastrophic event. Chromothripsis has most frequently been associated with cancer, but there have also been rare reports of chromothripsis in patients with developmental disorders and congenital anomalies. In contrast to the massive DNA loss that often accompanies chromothripsis in cancer, only minimal DNA loss has been reported in the majority of cases of chromothripsis that have occurred in the germ line. Presumably, this is because in most instances, large genomic losses would be lethal in utero. We report on a female patient with developmental delay and dysmorphism. G-banded chromosome analysis detected a subtle, interstitial deletion of chromosome 13 and a complex rearrangement of one X chromosome. Subsequent array comparative genomic hybridisation studies indicated nine deletions on the X chromosome ranging from 327 kb to 8 Mb in size. A 4.4 Mb deletion on chromosome 13 was also confirmed, compatible with the patient's clinical phenotype. We propose that this is a rare example of constitutional chromothripsis in association with relatively large genomic imbalances and that these have been tolerated in this case as they have occurred in a female on the X chromosome, which has undergone preferential X inactivation.

DNA Remodeling by Strict Partial Endoreplication in Orchids, an Original Process in the Plant Kingdom

PubMed Central

Brown, Spencer C.; Bourge, Mickaël; Maunoury, Nicolas; Wong, Maurice; Wolfe Bianchi, Michele; Lepers-Andrzejewski, Sandra; Besse, Pascale; Siljak-Yakovlev, Sonja

2017-01-01

DNA remodeling during endoreplication appears to be a strong developmental characteristic in orchids. In this study, we analyzed DNA content and nuclei in 41 species of orchids to further map the genome evolution in this plant family. We demonstrate that the DNA remodeling observed in 36 out of 41 orchids studied corresponds to strict partial endoreplication. Such process is developmentally regulated in each wild species studied. Cytometry data analyses allowed us to propose a model where nuclear states 2C, 4E, 8E, etc. form a series comprising a fixed proportion, the euploid genome 2C, plus 2–32 additional copies of a complementary part of the genome. The fixed proportion ranged from 89% of the genome in Vanilla mexicana down to 19% in V. pompona, the lowest value for all 148 orchids reported. Insterspecific hybridization did not suppress this phenomenon. Interestingly, this process was not observed in mass-produced epiphytes. Nucleolar volumes grow with the number of endocopies present, coherent with high transcription activity in endoreplicated nuclei. Our analyses suggest species-specific chromatin rearrangement. Towards understanding endoreplication, V. planifolia constitutes a tractable system for isolating the genomic sequences that confer an advantage via endoreplication from those that apparently suffice at diploid level. PMID:28419219

Genomic Sequence around Butterfly Wing Development Genes: Annotation and Comparative Analysis

PubMed Central

Conceição, Inês C.; Long, Anthony D.; Gruber, Jonathan D.; Beldade, Patrícia

2011-01-01

Background Analysis of genomic sequence allows characterization of genome content and organization, and access beyond gene-coding regions for identification of functional elements. BAC libraries, where relatively large genomic regions are made readily available, are especially useful for species without a fully sequenced genome and can increase genomic coverage of phylogenetic and biological diversity. For example, no butterfly genome is yet available despite the unique genetic and biological properties of this group, such as diversified wing color patterns. The evolution and development of these patterns is being studied in a few target species, including Bicyclus anynana, where a whole-genome BAC library allows targeted access to large genomic regions. Methodology/Principal Findings We characterize ∼1.3 Mb of genomic sequence around 11 selected genes expressed in B. anynana developing wings. Extensive manual curation of in silico predictions, also making use of a large dataset of expressed genes for this species, identified repetitive elements and protein coding sequence, and highlighted an expansion of Alcohol dehydrogenase genes. Comparative analysis with orthologous regions of the lepidopteran reference genome allowed assessment of conservation of fine-scale synteny (with detection of new inversions and translocations) and of DNA sequence (with detection of high levels of conservation of non-coding regions around some, but not all, developmental genes). Conclusions The general properties and organization of the available B. anynana genomic sequence are similar to the lepidopteran reference, despite the more than 140 MY divergence. Our results lay the groundwork for further studies of new interesting findings in relation to both coding and non-coding sequence: 1) the Alcohol dehydrogenase expansion with higher similarity between the five tandemly-repeated B. anynana paralogs than with the corresponding B. mori orthologs, and 2) the high conservation of non-coding sequence around the genes wingless and Ecdysone receptor, both involved in multiple developmental processes including wing pattern formation. PMID:21909358

[Comparative genomic hybridisation as a first option in genetic diagnosis: 1,000 cases and a cost-benefit analysis].

PubMed

Castells-Sarret, Neus; Cueto-González, Anna M; Borregan, Mar; López-Grondona, Fermina; Miró, Rosa; Tizzano, Eduardo; Plaja, Alberto

2017-09-25

Conventional cytogenetics diagnoses 3-5% of patients with unexplained developmental delay/intellectual disability and/or multiple congenital anomalies. The Multiplex Ligation-dependent Probe Amplification increases diagnostic rates from between 2.4 to 5.8%. Currently the comparative genomic hybridisation array or aCGH is the highest performing diagnostic tool in patients with developmental delay/intellectual disability, congenital anomalies and autism spectrum disorders. Our aim is to evaluate the efficiency of the use of aCGH as first-line test in these and other indications (epilepsy, short stature). A total of 1000 patients referred due to one or more of the abovementioned disorders were analysed by aCGH. Pathogenic genomic imbalances were detected in 14% of the cases, with a variable distribution of diagnosis according to the phenotypes: 18.9% of patients with developmental delay/intellectual disability; 13.7% of multiple congenital anomalies, 9.76% of psychiatric pathologies, 7.02% of patients with epilepsy, and 13.3% of patients with short stature. Within the multiple congenital anomalies, central nervous system abnormalities and congenital heart diseases accounted for 14.9% and 10.6% of diagnoses, respectively. Among the psychiatric disorders, patients with autism spectrum disorders accounted for 8.9% of the diagnoses. Our results demonstrate the effectiveness and efficiency of the use of aCGH as the first line test in genetic diagnosis of patients suspected of genomic imbalances, supporting its inclusion within the National Health System. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Whole-Genome Sequencing of Sordaria macrospora Mutants Identifies Developmental Genes.

PubMed

Nowrousian, Minou; Teichert, Ines; Masloff, Sandra; Kück, Ulrich

2012-02-01

The study of mutants to elucidate gene functions has a long and successful history; however, to discover causative mutations in mutants that were generated by random mutagenesis often takes years of laboratory work and requires previously generated genetic and/or physical markers, or resources like DNA libraries for complementation. Here, we present an alternative method to identify defective genes in developmental mutants of the filamentous fungus Sordaria macrospora through Illumina/Solexa whole-genome sequencing. We sequenced pooled DNA from progeny of crosses of three mutants and the wild type and were able to pinpoint the causative mutations in the mutant strains through bioinformatics analysis. One mutant is a spore color mutant, and the mutated gene encodes a melanin biosynthesis enzyme. The causative mutation is a G to A change in the first base of an intron, leading to a splice defect. The second mutant carries an allelic mutation in the pro41 gene encoding a protein essential for sexual development. In the mutant, we detected a complex pattern of deletion/rearrangements at the pro41 locus. In the third mutant, a point mutation in the stop codon of a transcription factor-encoding gene leads to the production of immature fruiting bodies. For all mutants, transformation with a wild type-copy of the affected gene restored the wild-type phenotype. Our data demonstrate that whole-genome sequencing of mutant strains is a rapid method to identify developmental genes in an organism that can be genetically crossed and where a reference genome sequence is available, even without prior mapping information.

Whole-Genome Sequencing of Sordaria macrospora Mutants Identifies Developmental Genes

PubMed Central

Nowrousian, Minou; Teichert, Ines; Masloff, Sandra; Kück, Ulrich

2012-01-01

The study of mutants to elucidate gene functions has a long and successful history; however, to discover causative mutations in mutants that were generated by random mutagenesis often takes years of laboratory work and requires previously generated genetic and/or physical markers, or resources like DNA libraries for complementation. Here, we present an alternative method to identify defective genes in developmental mutants of the filamentous fungus Sordaria macrospora through Illumina/Solexa whole-genome sequencing. We sequenced pooled DNA from progeny of crosses of three mutants and the wild type and were able to pinpoint the causative mutations in the mutant strains through bioinformatics analysis. One mutant is a spore color mutant, and the mutated gene encodes a melanin biosynthesis enzyme. The causative mutation is a G to A change in the first base of an intron, leading to a splice defect. The second mutant carries an allelic mutation in the pro41 gene encoding a protein essential for sexual development. In the mutant, we detected a complex pattern of deletion/rearrangements at the pro41 locus. In the third mutant, a point mutation in the stop codon of a transcription factor-encoding gene leads to the production of immature fruiting bodies. For all mutants, transformation with a wild type-copy of the affected gene restored the wild-type phenotype. Our data demonstrate that whole-genome sequencing of mutant strains is a rapid method to identify developmental genes in an organism that can be genetically crossed and where a reference genome sequence is available, even without prior mapping information. PMID:22384404

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks

PubMed Central

Liu, Kun-hsiang; Niu, Yajie; Konishi, Mineko; Wu, Yue; Du, Hao; Sun Chung, Hoo; Li, Lei; Boudsocq, Marie; McCormack, Matthew; Maekawa, Shugo; Ishida, Tetsuya; Zhang, Chao; Shokat, Kevan; Yanagisawa, Shuichi; Sheen, Jen

2018-01-01

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report novel Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca2+-sensor protein kinases (CPKs) as master regulators orchestrating primary nitrate responses. A chemical switch with the engineered CPK10(M141G) kinase enables conditional analyses of cpk10,30,32 to define comprehensive nitrate-associated regulatory and developmental programs, circumventing embryo lethality. Nitrate-CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors (TFs) to specify reprogramming of gene sets for downstream TFs, transporters, N-assimilation, C/N-metabolism, redox, signalling, hormones, and proliferation. Conditional cpk10,30,32 and nlp7 similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture. PMID:28489820

Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly

PubMed Central

Peacock, Lori; Ferris, Vanessa; Sharma, Reuben; Sunter, Jack; Bailey, Mick; Carrington, Mark; Gibson, Wendy

2011-01-01

Elucidating the mechanism of genetic exchange is fundamental for understanding how genes for such traits as virulence, disease phenotype, and drug resistance are transferred between pathogen strains. Genetic exchange occurs in the parasitic protists Trypanosoma brucei, T. cruzi, and Leishmania major, but the precise cellular mechanisms are unknown, because the process has not been observed directly. Here we exploit the identification of homologs of meiotic genes in the T. brucei genome and demonstrate that three functionally distinct, meiosis-specific proteins are expressed in the nucleus of a single specific cell type, defining a previously undescribed developmental stage occurring within the tsetse fly salivary gland. Expression occurs in clonal and mixed infections, indicating that the meiotic program is an intrinsic but hitherto cryptic part of the developmental cycle of trypanosomes. In experimental crosses, expression of meiosis-specific proteins usually occurred before cell fusion. This is evidence of conventional meiotic division in an excavate protist, and the functional conservation of the meiotic machinery in these divergent organisms underlines the ubiquity and basal evolution of meiosis in eukaryotes. PMID:21321215

LMO2 is required for TAL1 DNA binding activity and initiation of definitive haematopoiesis at the haemangioblast stage.

PubMed

Stanulovic, Vesna S; Cauchy, Pierre; Assi, Salam A; Hoogenkamp, Maarten

2017-09-29

LMO2 is a bridging factor within a DNA binding complex and is required for definitive haematopoiesis to occur. The developmental stage of the block in haematopoietic specification is not known. We show that Lmo2-/- mouse embryonic stem cells differentiated to Flk-1+ haemangioblasts, but less efficiently to haemogenic endothelium, which only produced primitive haematopoietic progenitors. Genome-wide approaches indicated that LMO2 is required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are important for the establishment of the haematopoietic developmental program. In the absence of LMO2, the target site recognition of TAL1 is impaired. The lack of LMO2 resulted in altered gene expression levels already at the haemangioblast stage, with transcription factor genes accounting for ∼15% of affected genes. Comparison of Lmo2-/- with Tal1-/- Flk-1+ cells further showed that TAL1 was required to initiate or sustain Lmo2 expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Intranuclear DNA density affects chromosome condensation in metazoans

PubMed Central

Hara, Yuki; Iwabuchi, Mari; Ohsumi, Keita; Kimura, Akatsuki

2013-01-01

Chromosome condensation is critical for accurate inheritance of genetic information. The degree of condensation, which is reflected in the size of the condensed chromosomes during mitosis, is not constant. It is differentially regulated in embryonic and somatic cells. In addition to the developmentally programmed regulation of chromosome condensation, there may be adaptive regulation based on spatial parameters such as genomic length or cell size. We propose that chromosome condensation is affected by a spatial parameter called the chromosome amount per nuclear space, or “intranuclear DNA density.” Using Caenorhabditis elegans embryos, we show that condensed chromosome sizes vary during early embryogenesis. Of importance, changing DNA content to haploid or polyploid changes the condensed chromosome size, even at the same developmental stage. Condensed chromosome size correlates with interphase nuclear size. Finally, a reduction in nuclear size in a cell-free system from Xenopus laevis eggs resulted in reduced condensed chromosome sizes. These data support the hypothesis that intranuclear DNA density regulates chromosome condensation. This suggests an adaptive mode of chromosome condensation regulation in metazoans. PMID:23783035

Polycomb-like 2 Associates with PRC2 and Regulates Transcriptional Networks during Mouse Embryonic Stem Cell Self-Renewal and Differentiation

PubMed Central

Walker, Emily; Chang, Wing Y.; Hunkapiller, Julie; Cagney, Gerard; Garcha, Kamal; Torchia, Joseph; Krogan, Nevan J.; Reiter, Jeremy F.; Stanford, William L.

2010-01-01

Summary Polycomb group (PcG) proteins are conserved epigenetic transcriptional repressors that control numerous developmental gene expression programs and have recently been implicated in modulating embryonic stem cell (ESC) fate. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for regulators of self-renewal and pluripotency and predicted that it would play an important role in mouse ESC fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation and altered patterns of histone methylation. Integration of global gene expression and promoter occupancy analyses allowed us to identify PCL2 and PRC2 transcriptional targets and draft regulatory networks. We describe the role of PCL2 in both modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation. PMID:20144788

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks.

PubMed

Liu, Kun-Hsiang; Niu, Yajie; Konishi, Mineko; Wu, Yue; Du, Hao; Sun Chung, Hoo; Li, Lei; Boudsocq, Marie; McCormack, Matthew; Maekawa, Shugo; Ishida, Tetsuya; Zhang, Chao; Shokat, Kevan; Yanagisawa, Shuichi; Sheen, Jen

2017-05-18

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca 2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca 2+ -sensor protein kinases (CPKs) as master regulators that orchestrate primary nitrate responses. A chemical switch with the engineered mutant CPK10(M141G) circumvents embryo lethality and enables conditional analyses of cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated regulatory and developmental programs. Nitrate-coupled CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify the reprogramming of gene sets for downstream transcription factors, transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox, signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7 mutants similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca 2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture.

Genes Contributing to Genetic Variation of Muscling in Sheep

PubMed Central

Tellam, Ross L.; Cockett, Noelle E.; Vuocolo, Tony; Bidwell, Christopher A.

2012-01-01

Selective breeding programs aiming to increase the productivity and profitability of the sheep meat industry use elite, progeny tested sires. The broad genetic traits of primary interest in the progeny of these sires include skeletal muscle yield, fat content, eating quality, and reproductive efficiency. Natural mutations in sheep that enhance muscling have been identified, while a number of genome scans have identified and confirmed quantitative trait loci (QTL) for skeletal muscle traits. The detailed phenotypic characteristics of sheep carrying these mutations or QTL affecting skeletal muscle show a number of common biological themes, particularly changes in developmental growth trajectories, alterations of whole animal morphology, and a shift toward fast twitch glycolytic fibers. The genetic, developmental, and biochemical mechanisms underpinning the actions of some of these genetic variants are described. This review critically assesses this research area, identifies gaps in knowledge, and highlights mechanistic linkages between genetic polymorphisms and skeletal muscle phenotypic changes. This knowledge may aid the discovery of new causal genetic variants and in some cases lead to the development of biochemical and immunological strategies aimed at enhancing skeletal muscle. PMID:22952470

Getting Ready for College: An Implementation and Early Impacts Study of Eight Texas Developmental Summer Bridge Programs. Executive Summary

ERIC Educational Resources Information Center

Wathington, Heather D.; Barnett, Elisabeth A.; Weissman, Evan; Teres, Jedediah; Pretlow, Joshua; Nakanishi, Aki

2011-01-01

In 2007, the Texas Higher Education Coordinating Board (THECB) funded 22 colleges to establish developmental summer bridge programs. Aimed at providing an alternative to traditional developmental education, these programs involve intensive remedial instruction in math, reading, and/or writing and college preparation content for students entering…

The Impact of the Developmental Training Model on Staff Development in Air Force Child Development Programs

ERIC Educational Resources Information Center

Bird, Candace Maria Edmonds

2010-01-01

In an effort to standardize training delivery and to individualize staff development based on observation and reflective practice, the Air Force implemented the Developmental Training Model (DTM) in its Child Development Programs. The goal of the Developmental Training Model is to enhance high quality programs through improvements in the training…

[Introduction to Genetic/Rare Disease and the Application of Genetic Counseling].

PubMed

Chu, Shao-Yin; Weng, Chun-Ying

2017-10-01

Genetic disease or hereditary disease is a group of disorders that is caused by mutations in an individual's genome. The mutated genome or gene may be transmitted through the germ line during reproduction, causing certain recurrence risk in offspring and other family members. The heritability of these disorders is thus an important issue to deal with clinically. In Taiwan, a rare disease is defined as a disease that is prevalent in fewer than 1 in 10,000 individuals. As up to 80% of rare disease cases in Taiwan are genetic disease disorders, genetic disease may not rare. The pathophysiology of genetic/ rare disease is very complicated. Individual disorders may have their own unique mechanisms (such as Fragile X syndrome), with most of these mechanisms still unclear or unknown. The symptoms and signs of genetic/rare disease thus present the greatest variabilities and cause difficulties in making diagnoses. Most related patients may present multiple congenital anomalies, metabolic disorders, growth and developmental delays, defects in cognition, neuromuscular abnormalities, and defects in vision, hearing or other organ functions. Symptomatic and supportive treatment still comprise a major component of treatment of genetic/rare disease (with the exception of special formulae for several inborn errors of metabolic disease and enzyme replacement therapy in some lysosomal storage disease). Poor self-care ability is common and the burden on caregivers is huge. Most rare disease patients are treated using a comprehensive rehabilitation program that begins during very early childhood, receive individual educational programs, and are continuously monitored with regard to their growth, developmental, and nutritional status. Inter-professional patient care, genetic counseling, and the creation of family support networks play an important role in family management. Public awareness and the creation of appropriate social systems and resources allocation are mandatory for proper care. The incidence of each genetic/rare disease is rare, but collectively they are important public health issue and a challenge to medical care.

45 CFR 1386.33 - Protection of employee's interests.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 1386.33 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS Federal Assistance to State Developmental Disabilities...

Ovule identity mediated by pre-mRNA processing in Arabidopsis

PubMed Central

Rodríguez-Cazorla, Encarnación; Candela, Héctor; Bailey-Steinitz, Lindsay J.; Yanofsky, Martin F.; Martínez-Laborda, Antonio

2018-01-01

Ovules are fundamental for plant reproduction and crop yield as they are the precursors of seeds. Therefore, ovule specification is a critical developmental program. In Arabidopsis thaliana, ovule identity is redundantly conferred by the homeotic D-class genes SHATTERPROOF1 (SHP1), SHP2 and SEEDSTICK (STK), phylogenetically related to the MADS-domain regulatory gene AGAMOUS (AG), essential in floral organ specification. Previous studies have shown that the HUA-PEP activity, comprised of a suite of RNA-binding protein (RBP) encoding genes, regulates AG pre-mRNA processing and thus flower patterning and organ identity. Here, we report that the HUA-PEP activity additionally governs ovule morphogenesis. Accordingly, in severe hua-pep backgrounds ovules transform into flower organ-like structures. These homeotic transformations are most likely due to the dramatic reduction in SHP1, SHP2 and STK activity. Our molecular and genome-wide profiling strategies revealed the accumulation of prematurely terminated transcripts of D-class genes in hua-pep mutants and reduced amounts of their respective functional messengers, which points to pre-mRNA processing misregulation as the origin of the ovule developmental defects in such backgrounds. RNA processing and transcription are coordinated by the RNA polymerase II (RNAPII) carboxyl-terminal domain (CTD). Our results show that HUA-PEP activity members can interact with the CTD regulator C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 (CPL1), supporting a co-transcriptional mode of action for the HUA-PEP activity. Our findings expand the portfolio of reproductive developmental programs in which HUA-PEP activity participates, and further substantiates the importance of RNA regulatory mechanisms (pre-mRNA co-transcriptional regulation) for correct gene expression during plant morphogenesis. PMID:29329291

Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster.

PubMed

Tolhuis, Bas; de Wit, Elzo; Muijrers, Inhua; Teunissen, Hans; Talhout, Wendy; van Steensel, Bas; van Lohuizen, Maarten

2006-06-01

Polycomb group (PcG) proteins maintain transcriptional repression of developmentally important genes and have been implicated in cell proliferation and stem cell self-renewal. We used a genome-wide approach to map binding patterns of PcG proteins (Pc, esc and Sce) in Drosophila melanogaster Kc cells. We found that Pc associates with large genomic regions of up to approximately 150 kb in size, hereafter referred to as 'Pc domains'. Sce and esc accompany Pc in most of these domains. PcG-bound chromatin is trimethylated at histone H3 Lys27 and is generally transcriptionally silent. Furthermore, PcG proteins preferentially bind to developmental genes. Many of these encode transcriptional regulators and key components of signal transduction pathways, including Wingless, Hedgehog, Notch and Delta. We also identify several new putative functions of PcG proteins, such as in steroid hormone biosynthesis. These results highlight the extensive involvement of PcG proteins in the coordination of development through the formation of large repressive chromatin domains.

Cell identity regulators link development and stress responses in the Arabidopsis root.

PubMed

Iyer-Pascuzzi, Anjali S; Jackson, Terry; Cui, Hongchang; Petricka, Jalean J; Busch, Wolfgang; Tsukagoshi, Hironaka; Benfey, Philip N

2011-10-18

Stress responses in plants are tightly coordinated with developmental processes, but interaction of these pathways is poorly understood. We used genome-wide assays at high spatiotemporal resolution to understand the processes that link development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. However, common stress responses appear to exist with many showing cell type specificity. Common stress responses may be mediated by cell identity regulators because mutations in these genes resulted in altered responses to stress. Evidence for a direct role for cell identity regulators came from genome-wide binding profiling of the key regulator SCARECROW, which showed binding to regulatory regions of stress-responsive genes. Coexpression in response to stress was used to identify genes involved in specific developmental processes. These results reveal surprising linkages between stress and development at cellular resolution, and show the power of multiple genome-wide data sets to elucidate biological processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Prokaryotic Caspase Homologs: Phylogenetic Patterns and Functional Characteristics Reveal Considerable Diversity

PubMed Central

Asplund-Samuelsson, Johannes; Bergman, Birgitta; Larsson, John

2012-01-01

Caspases accomplish initiation and execution of apoptosis, a programmed cell death process specific to metazoans. The existence of prokaryotic caspase homologs, termed metacaspases, has been known for slightly more than a decade. Despite their potential connection to the evolution of programmed cell death in eukaryotes, the phylogenetic distribution and functions of these prokaryotic metacaspase sequences are largely uncharted, while a few experiments imply involvement in programmed cell death. Aiming at providing a more detailed picture of prokaryotic caspase homologs, we applied a computational approach based on Hidden Markov Model search profiles to identify and functionally characterize putative metacaspases in bacterial and archaeal genomes. Out of the total of 1463 analyzed genomes, merely 267 (18%) were identified to contain putative metacaspases, but their taxonomic distribution included most prokaryotic phyla and a few archaea (Euryarchaeota). Metacaspases were particularly abundant in Alphaproteobacteria, Deltaproteobacteria and Cyanobacteria, which harbor many morphologically and developmentally complex organisms, and a distinct correlation was found between abundance and phenotypic complexity in Cyanobacteria. Notably, Bacillus subtilis and Escherichia coli, known to undergo genetically regulated autolysis, lacked metacaspases. Pfam domain architecture analysis combined with operon identification revealed rich and varied configurations among the metacaspase sequences. These imply roles in programmed cell death, but also e.g. in signaling, various enzymatic activities and protein modification. Together our data show a wide and scattered distribution of caspase homologs in prokaryotes with structurally and functionally diverse sub-groups, and with a potentially intriguing evolutionary role. These features will help delineate future characterizations of death pathways in prokaryotes. PMID:23185476

45 CFR 1386.23 - Periodic reports: Protection and Advocacy System.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.23 Periodic reports...

Transcriptional profiling reveals elevated Sox2 in DNA polymerase ß null mouse embryonic fibroblasts

PubMed Central

Li, Jianfeng; Luthra, Soumya; Wang, Xiao-Hong; Chandran, Uma R; Sobol, Robert W

2012-01-01

There are over 150 human proteins that have been categorized as bona fide DNA repair proteins. These DNA repair proteins maintain the integrity of the genome, reducing the onset of cancer, disease and aging phenotypes. Variations in expression and/or function would therefore impact genome integrity as well as the cellular response to genotoxins. Global gene expression analysis is an effective approach to uncover defects in DNA repair gene expression and to discover cellular and/or organismal effects brought about by external stimuli such as environmental genotoxicants, chemotherapeutic regimens, viral infections as well as developmental and age-related stimuli. Given the significance of genome stability in cell survival and response to stimuli, we have hypothesized that cells may undergo transcriptional re-programming to accommodate defects in basal DNA repair capacity to promote survival. As a test of this hypothesis, we have compared the transcriptome in three DNA polymerase ß knockout (Polß-KO) mouse embryonic fibroblasts (MEFs) and the corresponding wild-type (WT) littermate control cell lines. Each Polß-KO cell line was found to have a range of genes up-regulated, when compared to its WT littermate control cell line. Interestingly, six (6) genes were commonly up regulated in all three Polß-KO cell lines, including Sox2, one of several genes associated with the induction of pluripotent stem cells. Herein, we present these findings and suggest that loss of DNA repair and the induction of cellular transcriptional re-programming may, in part, contribute to tumor formation and the cellular response to external stimuli. PMID:23226616

Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side

USDA-ARS?s Scientific Manuscript database

Background: Number of functional teats is an important trait in commercial swine production. As litter size increases, the number of teats must also increase to supply nutrition to all piglets. Therefore, a genome-wide association analysis was conducted to identify genomic regions that affect this ...

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

PubMed

Di Gregorio, E; Riberi, E; Belligni, E F; Biamino, E; Spielmann, M; Ala, U; Calcia, A; Bagnasco, I; Carli, D; Gai, G; Giordano, M; Guala, A; Keller, R; Mandrile, G; Arduino, C; Maffè, A; Naretto, V G; Sirchia, F; Sorasio, L; Ungari, S; Zonta, A; Zacchetti, G; Talarico, F; Pappi, P; Cavalieri, S; Giorgio, E; Mancini, C; Ferrero, M; Brussino, A; Savin, E; Gandione, M; Pelle, A; Giachino, D F; De Marchi, M; Restagno, G; Provero, P; Cirillo Silengo, M; Grosso, E; Buxbaum, J D; Pasini, B; De Rubeis, S; Brusco, A; Ferrero, G B

2017-10-01

Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). Identification of genomic disorders in DD/ID. We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Embryonic development of the grass pufferfish (Takifugu niphobles): From egg to larvae.

PubMed

Gallego, V; Yoshida, M; Kurokawa, D; Asturiano, J F; Fraser, G J

2017-03-01

Tetraodontidae (pufferfish) family members carry the smallest genomes among vertebrates, and these pocket-sized genomes have directly contributed to our understanding of the structure and evolution of higher animals. The grass pufferfish (Takifugu niphobles) could be considered a potential new model organism for comparative genomics and development due to the potential access to embryos, and availability of sequence data for two similar genomes: that of spotted green pufferfish (Tetraodon nigroviridis) and Fugu (Takifugu rubripes). In this study, we provide the first description of the normal embryonic development of T. niphobles, by drawing comparisons with the closely related species cited above. Embryos were obtained by in vitro fertilization of eggs, and subsequent development was monitored at a constant temperature consistent with natural conditions. T. niphobles development was divided into seven periods of embryogenesis: the zygote, cleavage, blastula, gastrula, segmentation, pharyngula, and hatching periods; and stages subdividing these periods are defined based on morphological characteristics. The developmental stage series described in this study aims to provide the utilization of T. niphobles as an experimental model organism for comparative developmental studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictors of Developmental Outcomes of High-Risk and Developmentally Delayed Infants and Children Enrolled in a State Early Childhood Intervention Program

ERIC Educational Resources Information Center

Giannoni, Peggy P.; Kass, Philip H.

2012-01-01

A retrospective cohort study was conducted to identify child, maternal, family, and community factors associated with rate of developmental disability among children enrolled in the California Early Start Program. The cohort included 8,987 children considered at high risk for developmental disability due to medical risks and/or developmental…

funRNA: a fungi-centered genomics platform for genes encoding key components of RNAi.

PubMed

Choi, Jaeyoung; Kim, Ki-Tae; Jeon, Jongbum; Wu, Jiayao; Song, Hyeunjeong; Asiegbu, Fred O; Lee, Yong-Hwan

2014-01-01

RNA interference (RNAi) is involved in genome defense as well as diverse cellular, developmental, and physiological processes. Key components of RNAi are Argonaute, Dicer, and RNA-dependent RNA polymerase (RdRP), which have been functionally characterized mainly in model organisms. The key components are believed to exist throughout eukaryotes; however, there is no systematic platform for archiving and dissecting these important gene families. In addition, few fungi have been studied to date, limiting our understanding of RNAi in fungi. Here we present funRNA http://funrna.riceblast.snu.ac.kr/, a fungal kingdom-wide comparative genomics platform for putative genes encoding Argonaute, Dicer, and RdRP. To identify and archive genes encoding the abovementioned key components, protein domain profiles were determined from reference sequences obtained from UniProtKB/SwissProt. The domain profiles were searched using fungal, metazoan, and plant genomes, as well as bacterial and archaeal genomes. 1,163, 442, and 678 genes encoding Argonaute, Dicer, and RdRP, respectively, were predicted. Based on the identification results, active site variation of Argonaute, diversification of Dicer, and sequence analysis of RdRP were discussed in a fungus-oriented manner. funRNA provides results from diverse bioinformatics programs and job submission forms for BLAST, BLASTMatrix, and ClustalW. Furthermore, sequence collections created in funRNA are synced with several gene family analysis portals and databases, offering further analysis opportunities. funRNA provides identification results from a broad taxonomic range and diverse analysis functions, and could be used in diverse comparative and evolutionary studies. It could serve as a versatile genomics workbench for key components of RNAi.

From Mice to Men: research models of developmental programming

PubMed Central

Rabadán-Diehl, C.; Nathanielsz, P.

2012-01-01

Developmental programming can be defined as a response to a specific challenge to the mammalian organism during a critical developmental time window that alters the trajectory of development with persistent effects on offspring phenotype and predisposition to future illness. We focus on the need for studies in relevant, well-characterized animal models in the context of recent research discoveries on the challenges, mechanisms and outcomes of developmental programming. We discuss commonalities and differences in general principles of developmental programming as they apply to several species, including humans. The consequences of these differences are discussed. Obesity, metabolic disorders and cardiovascular diseases are associated with the highest percentage of morbidity and mortality worldwide. Although many of the causes are associated with lifestyle, high-energy diets and lack of physical activity, recent evidence has linked developmental programming to the epidemic of metabolic diseases. A better understanding of comparative systems physiology of mother, fetus and neonate using information provided by rapid advances in molecular biology has the potential to improve the lifetime health of future generations by providing better women’s health, diagnostic tools and preventative and therapeutic interventions in individuals exposed during their development to programming influences. PMID:23525085

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

PubMed

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

Genetics Home Reference: McKusick-Kaufman syndrome

MedlinePlus

... Kaufman syndrome Additional NIH Resources (1 link) National Human Genome Research Institute: Gene Linked to Developmental Syndrome in Old Order Amish Identified by NIH Scientists Educational Resources ( ...

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure

PubMed Central

Jorgensen, Elisa M.; Alderman, Myles H.; Taylor, Hugh S.

2016-01-01

Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)–binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERα. Gene–environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.—Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure. PMID:27312807

Multifaceted biological insights from a draft genome sequence of the tobacco hornworm moth, Manduca sexta

PubMed Central

Kanost, Michael R.; Arrese, Estela L.; Cao, Xiaolong; Chen, Yun-Ru; Chellapilla, Sanjay; Goldsmith, Marian R; Grosse-Wilde, Ewald; Heckel, David G.; Herndon, Nicolae; Jiang, Haobo; Papanicolaou, Alexie; Qu, Jiaxin; Soulages, Jose L.; Vogel, Heiko; Walters, James; Waterhouse, Robert M.; Ahn, Seung-Joon; Almeida, Francisca C.; An, Chunju; Aqrawi, Peshtewani; Bretschneider, Anne; Bryant, William B.; Bucks, Sascha; Chao, Hsu; Chevignon, Germain; Christen, Jayne M.; Clarke, David F.; Dittmer, Neal T.; Ferguson, Laura C.F.; Garavelou, Spyridoula; Gordon, Karl H.J.; Gunaratna, Ramesh T.; Han, Yi; Hauser, Frank; He, Yan; Heidel-Fischer, Hanna; Hirsh, Ariana; Hu, Yingxia; Jiang, Hongbo; Kalra, Divya; Klinner, Christian; König, Christopher; Kovar, Christie; Kroll, Ashley R.; Kuwar, Suyog S.; Lee, Sandy L.; Lehman, Rüdiger; Li, Kai; Li, Zhaofei; Liang, Hanquan; Lovelace, Shanna; Lu, Zhiqiang; Mansfield, Jennifer H.; McCulloch, Kyle J.; Mathew, Tittu; Morton, Brian; Muzny, Donna M.; Neunemann, David; Ongeri, Fiona; Pauchet, Yannick; Pu, Ling-Ling; Pyrousis, Ioannis; Rao, Xiang-Jun; Redding, Amanda; Roesel, Charles; Sanchez-Gracia, Alejandro; Schaack, Sarah; Shukla, Aditi; Tetreau, Guillaume; Wang, Yang; Xiong, Guang-Hua; Traut, Walther; Walsh, Tom K.; Worley, Kim C.; Wu, Di; Wu, Wenbi; Wu, Yuan-Qing; Zhang, Xiufeng; Zou, Zhen; Zucker, Hannah; Briscoe, Adriana D.; Burmester, Thorsten; Clem, Rollie J.; Feyereisen, René; Grimmelikhuijzen, Cornelis J.P; Hamodrakas, Stavros J.; Hansson, Bill S.; Huguet, Elisabeth; Jermiin, Lars S.; Lan, Que; Lehman, Herman K.; Lorenzen, Marce; Merzendorfer, Hans; Michalopoulos, Ioannis; Morton, David B.; Muthukrishnan, Subbaratnam; Oakeshott, John G.; Palmer, Will; Park, Yoonseong; Passarelli, A. Lorena; Rozas, Julio; Schwartz, Lawrence M.; Smith, Wendy; Southgate, Agnes; Vilcinskas, Andreas; Vogt, Richard; Wang, Ping; Werren, John; Yu, Xiao-Qiang; Zhou, Jing-Jiang; Brown, Susan J.; Scherer, Steven E.; Richards, Stephen; Blissard, Gary W.

2016-01-01

Manduca sexta, known as the tobacco hornworm or Carolina sphinx moth, is a lepidopteran insect that is used extensively as a model system for research in insect biochemistry, physiology, neurobiology, development, and immunity. One important benefit of this species as an experimental model is its extremely large size, reaching more than 10 g in the larval stage. M. sexta larvae feed on solanaceous plants and thus must tolerate a substantial challenge from plant allelochemicals, including nicotine. We report the sequence and annotation of the M. sexta genome, and a survey of gene expression in various tissues and developmental stages. The Msex_1.0 genome assembly resulted in a total genome size of 419.4 Mbp. Repetitive sequences accounted for 25.8% of the assembled genome. The official gene set is comprised of 15,451 protein-coding genes, of which 2498 were manually curated. Extensive RNA-seq data from many tissues and developmental stages were used to improve gene models and for insights into gene expression patterns. Genome wide synteny analysis indicated a high level of macrosynteny in the Lepidoptera. Annotation and analyses were carried out for gene families involved in a wide spectrum of biological processes, including apoptosis, vacuole sorting, growth and development, structures of exoskeleton, egg shells, and muscle, vision, chemosensation, ion channels, signal transduction, neuropeptide signaling, neurotransmitter synthesis and transport, nicotine tolerance, lipid metabolism, and immunity. This genome sequence, annotation, and analysis provide an important new resource from a well-studied model insect species and will facilitate further biochemical and mechanistic experimental studies of many biological systems in insects. PMID:27522922

PREFACE Physical Aspects of Developmental Biology: 21st Century Perspectives 'On Growth and Form' Physical Aspects of Developmental Biology: 21st Century Perspectives 'On Growth and Form'

NASA Astrophysics Data System (ADS)

Hutson, M. Shane

2008-04-01

There is a long and circuitous route from an organism_s genome to its steady-state adult form—all of which falls under the wide umbrella of developmental biology. Given this breadth, how does one answer the question: what is the mechanism by which developmental event X takes place? The answer depends strongly on what one considers an acceptable explanation. In some scientific circles, the answer would focus on the regulatory genes involved. In others, the focus would be on the signaling pathways activated, or on the associated cellular movements, or maybe even on the intra- and intercellular forces. In the long term, the goal must be to provide an explanation that connects all of these perspectives. During the last several decades, molecular biology has made enormous progress towards understanding development from the genome-side. Unfortunately, progress has been much slower on the relevant physical biology—which had a huge head start in the late 19th century age of developmental mechanics. It is just a slight exaggeration to claim that we_ve made little progress on the physical side since D_Arcy Thompson_s On Growth and Form in 1917. Hopefully, such statements will be recognized as large exaggerations in years to come as developmental mechanics is now in resurgence. This special issue of Physical Biology brings together current work in developmental mechanics from an international cadre of scientists—including physicists, biologists and engineers. The works include both models and experiments. They span scales from subcellular microrheology to finite element models of entire embryos. I hope that students looking for one of these articles will dive into the rest. The field of developmental mechanics is in the process of training a new generation of students who are comfortable with both the necessary biology and physics. Enormous opportunities are available for those who can work across those traditional disciplinary boundaries.

48 CFR 1019.202-70-13 - Developmental assistance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 1019.202-70-13 Developmental assistance. The forms of developmental assistance a mentor can provide to a protégé include: (a) Management guidance relating to financial management, organizational management, overall business management/planning, business development...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection...

Functional Study of Genes Essential for Autogamy and Nuclear Reorganization in Paramecium▿§

PubMed Central

Nowak, Jacek K.; Gromadka, Robert; Juszczuk, Marek; Jerka-Dziadosz, Maria; Maliszewska, Kamila; Mucchielli, Marie-Hélène; Gout, Jean-François; Arnaiz, Olivier; Agier, Nicolas; Tang, Thomas; Aggerbeck, Lawrence P.; Cohen, Jean; Delacroix, Hervé; Sperling, Linda; Herbert, Christopher J.; Zagulski, Marek; Bétermier, Mireille

2011-01-01

Like all ciliates, Paramecium tetraurelia is a unicellular eukaryote that harbors two kinds of nuclei within its cytoplasm. At each sexual cycle, a new somatic macronucleus (MAC) develops from the germ line micronucleus (MIC) through a sequence of complex events, which includes meiosis, karyogamy, and assembly of the MAC genome from MIC sequences. The latter process involves developmentally programmed genome rearrangements controlled by noncoding RNAs and a specialized RNA interference machinery. We describe our first attempts to identify genes and biological processes that contribute to the progression of the sexual cycle. Given the high percentage of unknown genes annotated in the P. tetraurelia genome, we applied a global strategy to monitor gene expression profiles during autogamy, a self-fertilization process. We focused this pilot study on the genes carried by the largest somatic chromosome and designed dedicated DNA arrays covering 484 genes from this chromosome (1.2% of all genes annotated in the genome). Transcriptome analysis revealed four major patterns of gene expression, including two successive waves of gene induction. Functional analysis of 15 upregulated genes revealed four that are essential for vegetative growth, one of which is involved in the maintenance of MAC integrity and another in cell division or membrane trafficking. Two additional genes, encoding a MIC-specific protein and a putative RNA helicase localizing to the old and then to the new MAC, are specifically required during sexual processes. Our work provides a proof of principle that genes essential for meiosis and nuclear reorganization can be uncovered following genome-wide transcriptome analysis. PMID:21257794

Genome-wide expression analysis of soybean NF-Y genes reveals potential function in development and drought response.

PubMed

Quach, Truyen N; Nguyen, Hanh T M; Valliyodan, Babu; Joshi, Trupti; Xu, Dong; Nguyen, Henry T

2015-06-01

Nuclear factor-Y (NF-Y), a heterotrimeric transcription factor, is composed of NF-YA, NF-YB and NF-YC proteins. In plants, there are usually more than 10 genes for each family and their members have been identified to be key regulators in many developmental and physiological processes controlling gametogenesis, embryogenesis, nodule development, seed development, abscisic acid (ABA) signaling, flowering time, primary root elongation, blue light responses, endoplasmic reticulum (ER) stress response and drought tolerance. Taking the advantages of the recent soybean genome draft and information on functional characterizations of nuclear factor Y (NF-Y) transcription factor family in plants, we identified 21 GmNF-YA, 32 GmNF-YB, and 15 GmNF-YC genes in the soybean (Glycine max) genome. Phylogenetic analyses show that soybean's proteins share strong homology to Arabidopsis and many of them are closely related to functionally characterized NF-Y in plants. Expression analysis in various tissues of flower, leaf, root, seeds of different developmental stages, root hairs under rhizobium inoculation, and drought-treated roots and leaves revealed that certain groups of soybean NF-Y are likely involved in specific developmental and stress responses. This study provides extensive evaluation of the soybean NF-Y family and is particularly useful for further functional characterization of GmNF-Y proteins in seed development, nodulation and drought adaptation of soybean.

Identification of pathways directly regulated by SHORT VEGETATIVE PHASE during vegetative and reproductive development in Arabidopsis

PubMed Central

2013-01-01

Background MADS-domain transcription factors play important roles during plant development. The Arabidopsis MADS-box gene SHORT VEGETATIVE PHASE (SVP) is a key regulator of two developmental phases. It functions as a repressor of the floral transition during the vegetative phase and later it contributes to the specification of floral meristems. How these distinct activities are conferred by a single transcription factor is unclear, but interactions with other MADS domain proteins which specify binding to different genomic regions is likely one mechanism. Results To compare the genome-wide DNA binding profile of SVP during vegetative and reproductive development we performed ChIP-seq analyses. These ChIP-seq data were combined with tiling array expression analysis, induction experiments and qRT-PCR to identify biologically relevant binding sites. In addition, we compared genome-wide target genes of SVP with those published for the MADS domain transcription factors FLC and AP1, which interact with SVP during the vegetative and reproductive phases, respectively. Conclusions Our analyses resulted in the identification of pathways that are regulated by SVP including those controlling meristem development during vegetative growth and flower development whereas floral transition pathways and hormonal signaling were regulated predominantly during the vegetative phase. Thus, SVP regulates many developmental pathways, some of which are common to both of its developmental roles whereas others are specific to only one of them. PMID:23759218

Genome-Wide Characterization and Expression Profiling of the AUXIN RESPONSE FACTOR (ARF) Gene Family in Eucalyptus grandis

PubMed Central

Yu, Hong; Soler, Marçal; Mila, Isabelle; San Clemente, Hélène; Savelli, Bruno; Dunand, Christophe; Paiva, Jorge A. P.; Myburg, Alexander A.; Bouzayen, Mondher; Grima-Pettenati, Jacqueline; Cassan-Wang, Hua

2014-01-01

Auxin is a central hormone involved in a wide range of developmental processes including the specification of vascular stem cells. Auxin Response Factors (ARF) are important actors of the auxin signalling pathway, regulating the transcription of auxin-responsive genes through direct binding to their promoters. The recent availability of the Eucalyptus grandis genome sequence allowed us to examine the characteristics and evolutionary history of this gene family in a woody plant of high economic importance. With 17 members, the E. grandis ARF gene family is slightly contracted, as compared to those of most angiosperms studied hitherto, lacking traces of duplication events. In silico analysis of alternative transcripts and gene truncation suggested that these two mechanisms were preeminent in shaping the functional diversity of the ARF family in Eucalyptus. Comparative phylogenetic analyses with genomes of other taxonomic lineages revealed the presence of a new ARF clade found preferentially in woody and/or perennial plants. High-throughput expression profiling among different organs and tissues and in response to environmental cues highlighted genes expressed in vascular cambium and/or developing xylem, responding dynamically to various environmental stimuli. Finally, this study allowed identification of three ARF candidates potentially involved in the auxin-regulated transcriptional program underlying wood formation. PMID:25269088

Environmental Estrogens Differentially Engage the Histone Methyltransferase EZH2 to Increase Risk of Uterine Tumorigenesis

PubMed Central

Greathouse, K. Leigh; Bredfeldt, Tiffany; Everitt, Jeffrey I.; Lin, Kevin; Berry, Tia; Kannan, Kurunthachalam; Mittelstadt, Megan L.; Ho, Shuk-mei; Walker, Cheryl L.

2013-01-01

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylstilbestrol (DES) during reproductive tract development can reprogram estrogen-responsive gene expression in the myometrium, resulting in hyper-responsiveness to hormone in the adult uterus and promotion of hormone-dependent uterine leiomyoma. We show here that the environmental estrogens genistein (GEN), a soy phytoestrogen, and the plasticizer bisphenol A (BPA), differ in their pattern of developmental reprogramming and promotion of tumorigenesis (leiomyomas) in the uterus. While both GEN and BPA induce genomic estrogen receptor (ER) signaling in the developing uterus, only GEN induced PI3K/AKT non-genomic ER signaling to the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2). As a result, this “pre-genomic” signaling phosphorylates and represses EZH2, and reduces levels of H3K27 repressive mark in chromatin. Furthermore, only GEN caused estrogen-responsive genes in the adult myometrium to become hyper-responsive to hormone; estrogen-responsive genes were repressed in BPA exposed uteri. Importantly, this pattern of EZH2 engagement to decrease versus increase H3K27 methylation correlated with the effect of these xenoestrogens on tumorigenesis. Developmental reprogramming by GEN promoted development of uterine leiomyomas, increasing tumor incidence and multiplicity, while BPA did not. These data demonstrate that environmental estrogens have distinct non-genomic effects in the developing uterus that determines their ability to engage the epigenetic regulator EZH2, decrease levels of the repressive epigenetic histone H3K27 methyl mark in chromatin during developmental reprogramming, and promote uterine tumorigenesis. PMID:22504913

A Model of Evolution of Development Based on Germline Penetration of New “No-Junk” DNA

PubMed Central

Fontana, Alessandro; Wróbel, Borys

2012-01-01

There is a mounting body of evidence that somatic transposition may be involved in normal development of multicellular organisms and in pathology, especially cancer. Epigenetic Tracking (ET) is an abstract model of multicellular development, able to generate complex 3-dimensional structures. Its aim is not to model the development of a particular organism nor to merely summarise mainstream knowledge on genetic regulation of development. Rather, the goal of ET is to provide a theoretical framework to test new postulated genetic mechanisms, not fully established yet in mainstream biology. The first proposal is that development is orchestrated through a subset of cells which we call driver cells. In these cells, the cellular state determines a specific pattern of gene activation which leads to the occurrence of developmental events. The second proposal is that evolution of development is affected by somatic transposition events. We postulate that when the genome of a driver cell does not specify what developmental event should be undertaken when the cell is in a particular cellular state, somatic transposition events can reshape the genome, build new regulatory regions, and lead to a new pattern of gene activation in the cell. Our third hypothesis, not supported yet by direct evidence, but consistent with some experimental observations, is that these new “no-junk” sequences—regulatory regions created by transposable elements at new positions in the genome—can exit the cell and enter the germline, to be incorporated in the genome of the progeny. We call this mechanism germline penetration. This process allows heritable incorporation of novel developmental events in the developmental trajectory. In this paper we will present the model and link these three postulated mechanisms to biological observations. PMID:24704981

The RNA-Seq-based high resolution gene expression atlas of chickpea (Cicer arietinum L.) reveals dynamic spatio-temporal changes associated with growth and development.

PubMed

Kudapa, Himabindu; Garg, Vanika; Chitikineni, Annapurna; Varshney, Rajeev K

2018-04-10

Chickpea is one of the world's largest cultivated food legumes and is an excellent source of high-quality protein to the human diet. Plant growth and development are controlled by programmed expression of a suite of genes at the given time, stage, and tissue. Understanding how the underlying genome sequence translates into specific plant phenotypes at key developmental stages, information on gene expression patterns is crucial. Here, we present a comprehensive Cicer arietinum Gene Expression Atlas (CaGEA) across different plant developmental stages and organs covering the entire life cycle of chickpea. One of the widely used drought tolerant cultivars, ICC 4958 has been used to generate RNA-Seq data from 27 samples at 5 major developmental stages of the plant. A total of 816 million raw reads were generated and of these, 794 million filtered reads after quality control (QC) were subjected to downstream analysis. A total of 15,947 unique number of differentially expressed genes across different pairwise tissue combinations were identified. Significant differences in gene expression patterns contributing in the process of flowering, nodulation, and seed and root development were inferred in this study. Furthermore, differentially expressed candidate genes from "QTL-hotspot" region associated with drought stress response in chickpea were validated. © 2018 The Authors. Plant, Cell & Environment Published by John Wiley & Sons Ltd.

Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells

PubMed Central

Choi, Jiho; Huebner, Aaron J; Clement, Kendell; Walsh, Ryan M; Savol, Andrej; Lin, Kaixuan; Gu, Hongcang; Di Stefano, Bruno; Brumbaugh, Justin; Kim, Sang-Yong; Sharif, Jafar; Rose, Christopher M.; Mohammad, Arman; Odajima, Junko; Charron, Jean; Shioda, Toshi; Gnirke, Andreas; Gygi, Steven; Koseki, Haruhiko; Sadreyev, Ruslan I.; Xiao, Andrew; Meissner, Alexander; Hochedlinger, Konrad

2018-01-01

Concomitant activation of the Wnt pathway and suppression of Mapk signaling by two small molecules in the presence of LIF (2i/L) induces a naïve state in mouse embryonic stem cells (ESCs) that resembles the inner cell mass (ICM) of the pre-implantation embryo1. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naïve ESCs in vitro affects their stability and functionality. Here we show that prolonged culture of male ESCs in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential. Additionally, we find that female ESCs cultured in conventional serum/LIF (S/L) media phenocopy male ESCs cultured in 2i/L. Mechanistically, we demonstrate that Mek1/2 inhibition is predominantly responsible for these effects, in part through downregulation of DNA methyltransferases and their associated cofactors. Finally, we show that replacement of the Mek1/2 inhibitor with a Src inhibitor preserves the epigenetic and genomic integrity as well as developmental potential of ESCs. Taken together, our data suggest that, while short-term suppression of Mek1/2 in ESCs helps maintain an ICM-like epigenetic state, prolonged suppression results in irreversible changes that compromise their developmental potential. PMID:28746311

Genome-Wide Association Mapping of Fertility Reduction upon Heat Stress Reveals Developmental Stage-Specific QTLs in Arabidopsis thaliana.

PubMed

Bac-Molenaar, Johanna A; Fradin, Emilie F; Becker, Frank F M; Rienstra, Juriaan A; van der Schoot, J; Vreugdenhil, Dick; Keurentjes, Joost J B

2015-07-01

For crops that are grown for their fruits or seeds, elevated temperatures that occur during flowering and seed or fruit set have a stronger effect on yield than high temperatures during the vegetative stage. Even short-term exposure to heat can have a large impact on yield. In this study, we used Arabidopsis thaliana to study the effect of short-term heat exposure on flower and seed development. The impact of a single hot day (35°C) was determined in more than 250 natural accessions by measuring the lengths of the siliques along the main inflorescence. Two sensitive developmental stages were identified, one before anthesis, during male and female meiosis, and one after anthesis, during fertilization and early embryo development. In addition, we observed a correlation between flowering time and heat tolerance. Genome-wide association mapping revealed four quantitative trait loci (QTLs) strongly associated with the heat response. These QTLs were developmental stage specific, as different QTLs were detected before and after anthesis. For a number of QTLs, T-DNA insertion knockout lines could validate assigned candidate genes. Our findings show that the regulation of complex traits can be highly dependent on the developmental timing. © 2015 American Society of Plant Biologists. All rights reserved.

Genome-Wide Association Mapping of Fertility Reduction upon Heat Stress Reveals Developmental Stage-Specific QTLs in Arabidopsis thaliana

PubMed Central

Bac-Molenaar, Johanna A.; Fradin, Emilie F.; Becker, Frank F.M.; Rienstra, Juriaan A.; van der Schoot, J.; Vreugdenhil, Dick; Keurentjes, Joost J.B.

2015-01-01

For crops that are grown for their fruits or seeds, elevated temperatures that occur during flowering and seed or fruit set have a stronger effect on yield than high temperatures during the vegetative stage. Even short-term exposure to heat can have a large impact on yield. In this study, we used Arabidopsis thaliana to study the effect of short-term heat exposure on flower and seed development. The impact of a single hot day (35°C) was determined in more than 250 natural accessions by measuring the lengths of the siliques along the main inflorescence. Two sensitive developmental stages were identified, one before anthesis, during male and female meiosis, and one after anthesis, during fertilization and early embryo development. In addition, we observed a correlation between flowering time and heat tolerance. Genome-wide association mapping revealed four quantitative trait loci (QTLs) strongly associated with the heat response. These QTLs were developmental stage specific, as different QTLs were detected before and after anthesis. For a number of QTLs, T-DNA insertion knockout lines could validate assigned candidate genes. Our findings show that the regulation of complex traits can be highly dependent on the developmental timing. PMID:26163573

Growth, morphology, and developmental instability of rainbow trout, Yellowstone cutthroat trout, and four hybrid generations

USGS Publications Warehouse

Ostberg, C.O.; Duda, J.J.; Graham, J.H.; Zhang, S.; Haywood, K. P.; Miller, B.; Lerud, T.L.

2011-01-01

Hybridization of cutthroat trout Oncorhynchus clarkii with nonindigenous rainbow trout O. mykiss contributes to the decline of cutthroat trout subspecies throughout their native range. Introgression by rainbow trout can swamp the gene pools of cutthroat trout populations, especially if there is little selection against hybrids. We used rainbow trout, Yellowstone cutthroat trout O. clarkii bouvieri, and rainbow trout × Yellowstone cutthroat trout F1 hybrids as parents to construct seven different line crosses: F1 hybrids (both reciprocal crosses), F2 hybrids, first-generation backcrosses (both rainbow trout and Yellowstone cutthroat trout), and both parental taxa. We compared growth, morphology, and developmental instability among these seven crosses reared at two different temperatures. Growth was related to the proportion of rainbow trout genome present within the crosses. Meristic traits were influenced by maternal, additive, dominant, overdominant, and (probably) epistatic genetic effects. Developmental stability, however, was not disturbed in F1 hybrids, F2 hybrids, or backcrosses. Backcrosses were morphologically similar to their recurrent parent. The lack of developmental instability in hybrids suggests that there are few genetic incompatibilities preventing introgression. Our findings suggest that hybrids are not equal: that is, growth, development, character traits, and morphology differ depending on the genomic contribution from each parental species as well as the hybrid generation.

A Path to Pattern.

PubMed

Kornberg, Thomas B

2016-01-01

The field of developmental biology is not the same one that I entered in 1975. At that time, it seemed that most of its practitioners used various kinds of microscopes to watch animals as they matured, described morphological details with impressive temporal and spatial resolution, and recorded responses to physical and genetic insults. The number of genes whose mutant phenotypes offered insights into developmental mechanisms was small, the expression and functionalities of these genes were unknown, and because the extent of evolutionary conservation between different animals or even different organs in the same animal was also unknown, the vocabularies that were used to describe development were unique to each system. The distance between the descriptors and inferred molecular mechanisms was vast; it was a descriptive discipline. Today genome sequences are available for the animals that developmental biologists study, saturation genetic screens are possible, transgenesis offers powerful ways to modify genomes, and the proteins that direct and implement developmental processes can be imaged in real time. These advances have transformed the field into one that merges with cell biology, physiology, neurobiology, and immunology, and they have transformed our understanding of development. In this essay, I offer my perspectives and my sense of some principles that have emerged. © 2016 Elsevier Inc. All rights reserved.

Selection of reliable reference genes for normalization of quantitative RT-PCR from different developmental stages and tissues in amphioxus

PubMed Central

Zhang, Qi-Lin; Zhu, Qian-Hua; Liao, Xin; Wang, Xiu-Qiang; Chen, Tao; Xu, Han-Ting; Wang, Juan; Yuan, Ming-Long; Chen, Jun-Yuan

2016-01-01

Amphioxus is a closest living proxy to the ancestor of cephalochordates with vertebrates, and key animal for novel understanding in the evolutionary origin of vertebrate body plan, genome, tissues and immune system. Reliable analyses using quantitative real-time PCR (qRT-PCR) for answering these scientific questions is heavily dependent on reliable reference genes (RGs). In this study, we evaluated stability of thirteen candidate RGs in qRT-PCR for different developmental stages and tissues of amphioxus by four independent (geNorm, NormFinder, BestKeeper and deltaCt) and one comparative algorithms (RefFinder). The results showed that the top two stable RGs were the following: (1) S20 and 18 S in thirteen developmental stages, (2) EF1A and ACT in seven normal tissues, (3) S20 and L13 in both intestine and hepatic caecum challenged with lipopolysaccharide (LPS), and (4) S20 and EF1A in gill challenged with LPS. The expression profiles of two target genes (EYA and HHEX) in thirteen developmental stages were used to confirm the reliability of chosen RGs. This study identified optimal RGs that can be used to accurately measure gene expression under these conditions, which will benefit evolutionary and functional genomics studies in amphioxus. PMID:27869224

45 CFR 1386.36 - Final disapproval of the State plan or plan amendments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS Federal Assistance to State Developmental Disabilities Councils § 1386.36 Final disapproval of the State plan or plan...

Wood formation in Angiosperms.

PubMed

Déjardin, Annabelle; Laurans, Françoise; Arnaud, Dominique; Breton, Christian; Pilate, Gilles; Leplé, Jean-Charles

2010-04-01

Wood formation is a complex biological process, involving five major developmental steps, including (1) cell division from a secondary meristem called the vascular cambium, (2) cell expansion (cell elongation and radial enlargement), (3) secondary cell wall deposition, (4) programmed cell death, and (5) heartwood formation. Thanks to the development of genomic studies in woody species, as well as genetic engineering, recent progress has been made in the understanding of the molecular mechanisms underlying wood formation. In this review, we will focus on two different aspects, the lignification process and the control of microfibril angle in the cell wall of wood fibres, as they are both key features of wood material properties. Copyright (c) 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

PubMed

Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako

2014-02-28

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.

Genome wide analysis reveals Zic3 interaction with distal regulatory elements of stage specific developmental genes in zebrafish.

PubMed

Winata, Cecilia L; Kondrychyn, Igor; Kumar, Vibhor; Srinivasan, Kandhadayar G; Orlov, Yuriy; Ravishankar, Ashwini; Prabhakar, Shyam; Stanton, Lawrence W; Korzh, Vladimir; Mathavan, Sinnakaruppan

2013-10-01

Zic3 regulates early embryonic patterning in vertebrates. Loss of Zic3 function is known to disrupt gastrulation, left-right patterning, and neurogenesis. However, molecular events downstream of this transcription factor are poorly characterized. Here we use the zebrafish as a model to study the developmental role of Zic3 in vivo, by applying a combination of two powerful genomics approaches--ChIP-seq and microarray. Besides confirming direct regulation of previously implicated Zic3 targets of the Nodal and canonical Wnt pathways, analysis of gastrula stage embryos uncovered a number of novel candidate target genes, among which were members of the non-canonical Wnt pathway and the neural pre-pattern genes. A similar analysis in zic3-expressing cells obtained by FACS at segmentation stage revealed a dramatic shift in Zic3 binding site locations and identified an entirely distinct set of target genes associated with later developmental functions such as neural development. We demonstrate cis-regulation of several of these target genes by Zic3 using in vivo enhancer assay. Analysis of Zic3 binding sites revealed a distribution biased towards distal intergenic regions, indicative of a long distance regulatory mechanism; some of these binding sites are highly conserved during evolution and act as functional enhancers. This demonstrated that Zic3 regulation of developmental genes is achieved predominantly through long distance regulatory mechanism and revealed that developmental transitions could be accompanied by dramatic changes in regulatory landscape.

Genome-Wide Analysis Reveals Novel Regulators of Growth in Drosophila melanogaster

PubMed Central

Vonesch, Sibylle Chantal; Lamparter, David; Mackay, Trudy F. C.; Bergmann, Sven; Hafen, Ernst

2016-01-01

Organismal size depends on the interplay between genetic and environmental factors. Genome-wide association (GWA) analyses in humans have implied many genes in the control of height but suffer from the inability to control the environment. Genetic analyses in Drosophila have identified conserved signaling pathways controlling size; however, how these pathways control phenotypic diversity is unclear. We performed GWA of size traits using the Drosophila Genetic Reference Panel of inbred, sequenced lines. We find that the top associated variants differ between traits and sexes; do not map to canonical growth pathway genes, but can be linked to these by epistasis analysis; and are enriched for genes and putative enhancers. Performing GWA on well-studied developmental traits under controlled conditions expands our understanding of developmental processes underlying phenotypic diversity. PMID:26751788

DNA remodelling by Strict Partial Endoreplication in orchids, an original process in the plant kingdom.

PubMed

Brown, Spencer C; Bourge, Mickaël; Maunoury, Nicolas; Wong, Maurice; Bianchi, Michele Wolfe; Lepers-Andrzejewski, Sandra; Besse, Pascale; Siljak-Yakovlev, Sonja; Dron, Michel; Satiat-Jeunemaître, Béatrice

2017-04-13

DNA remodelling during endoreplication appears to be a strong developmental characteristic in orchids. In this study, we analysed DNA content and nuclei in 41 species of orchids to further map the genome evolution in this plant family. We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied corresponds to strict partial endoreplication. Such process is developmentally regulated in each wild species studied. Cytometry data analyses allowed us to propose a model where nuclear states 2C, 4E, 8E, etc. form a series comprising a fixed proportion, the euploid genome 2C, plus 2 to 32 additional copies of a complementary part of the genome. The fixed proportion ranged from 89% of the genome in Vanilla mexicana down to 19% in V. pompona, the lowest value for all 148 orchids reported. Insterspecific hybridisation did not suppress this phenomenon. Interestingly, this process was not observed in mass-produced epiphytes. Nucleolar volumes grow with the number of endocopies present, coherent with high transcription activity in endoreplicated nuclei. Our analyses suggest species-specific chromatin rearrangement. Towards understanding endoreplication, V. planifolia constitutes a tractable system for isolating the genomic sequences that confer an advantage via endoreplication from those that apparently suffice at diploid level. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.

PubMed

Adkins, Daniel E; Clark, Shaunna L; Copeland, William E; Kennedy, Martin; Conway, Kevin; Angold, Adrian; Maes, Hermine; Liu, Youfang; Kumar, Gaurav; Erkanli, Alaattin; Patkar, Ashwin A; Silberg, Judy; Brown, Tyson H; Fergusson, David M; Horwood, L John; Eaves, Lindon; van den Oord, Edwin J C G; Sullivan, Patrick F; Costello, E J

2015-08-01

The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N=2,126, obs=12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR<0.1) and six others met our 'suggestive' criterion (FDR<0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.

School-Based Peer Mediation Programs: A Natural Extension of Developmental Guidance Programs.

ERIC Educational Resources Information Center

Robertson, Gwendolyn

School-based peer mediation programs are natural extensions of the kindergarten-grade 12 developmental guidance programs. Peer mediation programs not only provide schools with alternatives to traditional discipline practices, but also teach students important life skills. Existing research on peer mediation is very limited, yet promising. This…

Project PLANTWORK: A Horticulture Employment Initiative for Workers with Developmental Disabilities.

ERIC Educational Resources Information Center

National Council for Therapy and Rehabilitation through Horticulture, Inc., Gaithersburg, MD.

Intended for persons establishing job development programs for developmentally disabled individuals, this training manual details the structure and procedures of Project PLANTWORK, a 21-month demonstration program which placed approximately 70 workers with developmental disabilities into employment in horticulture industry firms or into…

77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy; Request for Comments; Peer Review Panel Meeting AGENCY: Division of the... Monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy Use during...

45 CFR 1386.24 - Non-allowable costs for the Protection and Advocacy System.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.24 Non-allowable...

45 CFR 1388.4 - Program criteria-governance and administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM THE UNIVERSITY AFFILIATED PROGRAMS § 1388.4 Program criteria—governance and... integral part of, a university and promote the independence, productivity, integration, and inclusion of...

A genomic view of 500 million years of cnidarian evolution

PubMed Central

Steele, Robert E.; David, Charles N.; Technau, Ulrich

2010-01-01

Cnidarians (corals, anemones, jellyfish, and hydras) are a diverse group of animals of interest to evolutionary biologists, ecologists, and developmental biologists. With the publication of the genome sequences of Hydra and Nematostella, whose last common ancestor was the stem cnidarian, we are beginning to see the genomic underpinnings of cnidarian biology. Cnidarians are known for the remarkable plasticity of their morphology and life cycles. This plasticity is reflected in the Hydra and Nematostella genomes, which differ to an exceptional degree in size, base composition, transposable element content, and gene conservation. We now know what cnidarian genomes are capable of doing given 500 million years; the next challenge is to understand how this genomic history has led to the striking diversity we see in cnidarians. PMID:21047698

Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).

PubMed

Narla, S T; Lee, Y-W; Benson, C A; Sarder, P; Brennand, K J; Stachowiak, E K; Stachowiak, M K

2017-07-01

The watershed-hypothesis of schizophrenia asserts that over 200 different mutations dysregulate distinct pathways that converge on an unspecified common mechanism(s) that controls disease ontogeny. Consistent with this hypothesis, our RNA-sequencing of neuron committed cells (NCCs) differentiated from established iPSCs of 4 schizophrenia patients and 4 control subjects uncovered a dysregulated transcriptome of 1349 mRNAs common to all patients. Data reveals a global dysregulation of developmental genome, deconstruction of coordinated mRNA networks, and the formation of aberrant, new coordinated mRNA networks indicating a concerted action of the responsible factor(s). Sequencing of miRNA transcriptomes demonstrated an overexpression of 16 miRNAs and deconstruction of interactive miRNA-mRNA networks in schizophrenia NCCs. ChiPseq revealed that the nuclear (n) form of FGFR1, a pan-ontogenic regulator, is overexpressed in schizophrenia NCCs and overtargets dysregulated mRNA and miRNA genes. The nFGFR1 targeted 54% of all human gene promoters and 84.4% of schizophrenia dysregulated genes. The upregulated genes reside within major developmental pathways that control neurogenesis and neuron formation, whereas downregulated genes are involved in oligodendrogenesis. Our results indicate (i) an early (preneuronal) genomic etiology of schizophrenia, (ii) dysregulated genes and new coordinated gene networks are common to unrelated cases of schizophrenia, (iii) gene dysregulations are accompanied by increased nFGFR1-genome interactions, and (iv) modeling of increased nFGFR1 by an overexpression of a nFGFR1 lead to up or downregulation of selected genes as observed in schizophrenia NCCs. Together our results designate nFGFR1 signaling as a potential common dysregulated mechanism in investigated patients and potential therapeutic target in schizophrenia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Wanted: A Developmentally Oriented Alcohol Prevention Program.

ERIC Educational Resources Information Center

Spoth, Richard; Rosenthal, David

1980-01-01

Describes an alcohol prevention program with a comprehensive developmental skills orientation. The program includes values clarification, decision making, career planning and communication skills, assertiveness and relaxation training, and relationship with parents and peers. (Author/JAC)

Characterization of a complex chromosomal rearrangement using chromosome, FISH, and microarray assays in a girl with multiple congenital abnormalities and developmental delay.

PubMed

Hemmat, Morteza; Yang, Xiaojing; Chan, Patricia; McGough, Robert A; Ross, Leslie; Mahon, Loretta W; Anguiano, Arturo L; Boris, Wang T; Elnaggar, Mohamed M; Wang, Jia-Chi J; Strom, Charles M; Boyar, Fatih Z

2014-01-01

Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving three or more cytogenetic breakpoints on two or more chromosomal pairs. The phenotypic anomalies in such cases are attributed to gene disruption, superimposed cryptic imbalances in the genome, and/or position effects. We report a 14-year-old girl who presented with multiple congenital anomalies and developmental delay. Chromosome and FISH analysis indicated a highly complex chromosomal rearrangement involving three chromosomes (3, 7 and 12), seven breakpoints as a result of one inversion, two insertions, and two translocations forming three derivative chromosomes. Additionally, chromosomal microarray study (CMA) revealed two submicroscopic deletions at 3p12.3 (467 kb) and 12q13.12 (442 kb). We postulate that microdeletion within the ROBO1 gene at 3p12.3 may have played a role in the patient's developmental delay, since it has potential activity-dependent role in neurons. Additionally, factors other than genomic deletions such as loss of function or position effects may also contribute to the abnormal phenotype in our patient.

Tracing the evolutionary origin of vertebrate skeletal tissues: insights from cephalochordate amphioxus.

PubMed

Yong, Luok Wen; Yu, Jr-Kai

2016-08-01

Vertebrate mineralized skeletal tissues are widely considered as an evolutionary novelty. Despite the importance of these tissues to the adaptation and radiation of vertebrate animals, the evolutionary origin of vertebrate skeletal tissues remains largely unclear. Cephalochordates (Amphioxus) occupy a key phylogenetic position and can serve as a valuable model for studying the evolution of vertebrate skeletal tissues. Here we summarize recent advances in amphioxus developmental biology and comparative genomics that can help to elucidate the evolutionary origins of the vertebrate skeletal tissues and their underlying developmental gene regulatory networks (GRN). By making comparisons to the developmental studies in vertebrate models and recent discoveries in paleontology and genomics, it becomes evident that the collagen matrix-based connective tissues secreted by the somite-derived cells in amphioxus likely represent the rudimentary skeletal tissues in chordates. We propose that upon the foundation of this collagenous precursor, novel tissue mineralization genes that arose from gene duplications were incorporated into an ancestral mesodermal GRN that makes connective and supporting tissues, leading to the emergence of highly-mineralized skeletal tissues in early vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Germline mutations affecting the histone H4 core cause a developmental syndrome by altering DNA damage response and cell cycle control.

PubMed

Tessadori, Federico; Giltay, Jacques C; Hurst, Jane A; Massink, Maarten P; Duran, Karen; Vos, Harmjan R; van Es, Robert M; Scott, Richard H; van Gassen, Koen L I; Bakkers, Jeroen; van Haaften, Gijs

2017-11-01

Covalent modifications of histones have an established role as chromatin effectors, as they control processes such as DNA replication and transcription, and repair or regulate nucleosomal structure. Loss of modifications on histone N tails, whether due to mutations in genes belonging to histone-modifying complexes or mutations directly affecting the histone tails, causes developmental disorders or has a role in tumorigenesis. More recently, modifications affecting the globular histone core have been uncovered as being crucial for DNA repair, pluripotency and oncogenesis. Here we report monoallelic missense mutations affecting lysine 91 in the histone H4 core (H4K91) in three individuals with a syndrome of growth delay, microcephaly and intellectual disability. Expression of the histone H4 mutants in zebrafish embryos recapitulates the developmental anomalies seen in the patients. We show that the histone H4 alterations cause genomic instability, resulting in increased apoptosis and cell cycle progression anomalies during early development. Mechanistically, our findings indicate an important role for the ubiquitination of H4K91 in genomic stability during embryonic development.

Reprogramming: A Preventive Strategy in Hypertension Focusing on the Kidney

PubMed Central

Tain, You-Lin; Joles, Jaap A.

2015-01-01

Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies. PMID:26712746

The Draft Genome and Transcriptome of Panagrellus redivivus Are Shaped by the Harsh Demands of a Free-Living Lifestyle

PubMed Central

Srinivasan, Jagan; Dillman, Adler R.; Macchietto, Marissa G.; Heikkinen, Liisa; Lakso, Merja; Fracchia, Kelley M.; Antoshechkin, Igor; Mortazavi, Ali; Wong, Garry; Sternberg, Paul W.

2013-01-01

Nematodes compose an abundant and diverse invertebrate phylum with members inhabiting nearly every ecological niche. Panagrellus redivivus (the “microworm”) is a free-living nematode frequently used to understand the evolution of developmental and behavioral processes given its phylogenetic distance to Caenorhabditis elegans. Here we report the de novo sequencing of the genome, transcriptome, and small RNAs of P. redivivus. Using a combination of automated gene finders and RNA-seq data, we predict 24,249 genes and 32,676 transcripts. Small RNA analysis revealed 248 microRNA (miRNA) hairpins, of which 63 had orthologs in other species. Fourteen miRNA clusters containing 42 miRNA precursors were found. The RNA interference, dauer development, and programmed cell death pathways are largely conserved. Analysis of protein family domain abundance revealed that P. redivivus has experienced a striking expansion of BTB domain-containing proteins and an unprecedented expansion of the cullin scaffold family of proteins involved in multi-subunit ubiquitin ligases, suggesting proteolytic plasticity and/or tighter regulation of protein turnover. The eukaryotic release factor protein family has also been dramatically expanded and suggests an ongoing evolutionary arms race with viruses and transposons. The P. redivivus genome provides a resource to advance our understanding of nematode evolution and biology and to further elucidate the genomic architecture leading to free-living lineages, taking advantage of the many fascinating features of this worm revealed by comparative studies. PMID:23410827

Differential gene transcription across the life cycle in Daphnia magna using a new all genome custom-made microarray.

PubMed

Campos, Bruno; Fletcher, Danielle; Piña, Benjamín; Tauler, Romà; Barata, Carlos

2018-05-18

Unravelling the link between genes and environment across the life cycle is a challenging goal that requires model organisms with well-characterized life-cycles, ecological interactions in nature, tractability in the laboratory, and available genomic tools. Very few well-studied invertebrate model species meet these requirements, being the waterflea Daphnia magna one of them. Here we report a full genome transcription profiling of D. magna during its life-cycle. The study was performed using a new microarray platform designed from the complete set of gene models representing the whole transcribed genome of D. magna. Up to 93% of the existing 41,317 D. magna gene models showed differential transcription patterns across the developmental stages of D. magna, 59% of which were functionally annotated. Embryos showed the highest number of unique transcribed genes, mainly related to DNA, RNA, and ribosome biogenesis, likely related to cellular proliferation and morphogenesis of the several body organs. Adult females showed an enrichment of transcripts for genes involved in reproductive processes. These female-specific transcripts were essentially absent in males, whose transcriptome was enriched in specific genes of male sexual differentiation genes, like doublesex. Our results define major characteristics of transcriptional programs involved in the life-cycle, differentiate males and females, and show that large scale gene-transcription data collected in whole animals can be used to identify genes involved in specific biological and biochemical processes.

Identification and resolution of artifacts in the interpretation of imprinted gene expression

PubMed Central

Proudhon, Charlotte

2010-01-01

Genomic imprinting refers to genes that are epigenetically programmed in the germline to express exclusively or preferentially one allele in a parent-of-origin manner. Expression-based genome-wide screening for the identification of imprinted genes has failed to uncover a significant number of new imprinted genes, probably because of the high tissue- and developmental-stage specificity of imprinted gene expression. A very large number of technical and biological artifacts can also lead to the erroneous evidence of imprinted gene expression. In this article, we focus on three common sources of potential confounding effects: (i) random monoallelic expression in monoclonal cell populations, (ii) genetically determined monoallelic expression and (iii) contamination or infiltration of embryonic tissues with maternal material. This last situation specifically applies to genes that occur as maternally expressed in the placenta. Beside the use of reciprocal crosses that are instrumental to confirm the parental specificity of expression, we provide additional methods for the detection and elimination of these situations that can be misinterpreted as cases of imprinted expression. PMID:20829207

Three Accelerated Developmental Education Programs: Features, Student Outcomes, and Implications

ERIC Educational Resources Information Center

Jaggars, Shanna Smith; Hodara, Michelle; Cho, Sung-Woo; Xu, Di

2015-01-01

To support the long-term success of underprepared students, many community colleges are experimenting with accelerated developmental education models, which allow students to complete remediation and enroll in college-level math and English within a shorter time frame. This study examines three developmental acceleration programs, including two in…

Developmental Reading at Livingston College, 1974-1976. A Final Report.

ERIC Educational Resources Information Center

Kussat, Reinhart; Farrow, Earl V.

A developmental reading program with a unified approach to the teaching of developmental reading to nontraditional freshmen was designed and initiated at Livingston College, Rutgers University. The two-level program, consisting of curriculum modules based on behavioral objectives and performance criteria, was required for all freshmen who ranked…

45 CFR 1385.4 - Rights of individuals with developmental disabilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROGRAM § 1385.4 Rights of individuals with developmental disabilities. (a) Section 110 of the Act, Rights... that the human rights of individuals assisted by these programs will be protected consistent with... 45 Public Welfare 4 2010-10-01 2010-10-01 false Rights of individuals with developmental...

Codon bias and gene ontology in holometabolous and hemimetabolous insects.

PubMed

Carlini, David B; Makowski, Matthew

2015-12-01

The relationship between preferred codon use (PCU), developmental mode, and gene ontology (GO) was investigated in a sample of nine insect species with sequenced genomes. These species were selected to represent two distinct modes of insect development, holometabolism and hemimetabolism, with an aim toward determining whether the differences in developmental timing concomitant with developmental mode would be mirrored by differences in PCU in their developmental genes. We hypothesized that the developmental genes of holometabolous insects should be under greater selective pressure for efficient translation, manifest as increased PCU, than those of hemimetabolous insects because holometabolism requires abundant protein expression over shorter time intervals than hemimetabolism, where proteins are required more uniformly in time. Preferred codon sets were defined for each species, from which the frequency of PCU for each gene was obtained. Although there were substantial differences in the genomic base composition of holometabolous and hemimetabolous insects, both groups exhibited a general preference for GC-ending codons, with the former group having higher PCU averaged across all genes. For each species, the biological process GO term for each gene was assigned that of its Drosophila homolog(s), and PCU was calculated for each GO term category. The top two GO term categories for PCU enrichment in the holometabolous insects were anatomical structure development and cell differentiation. The increased PCU in the developmental genes of holometabolous insects may reflect a general strategy to maximize the protein production of genes expressed in bursts over short time periods, e.g., heat shock proteins. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 686-698, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Developmental programming of energy balance regulation: is physical activity more 'programmable' than food intake?

PubMed

Zhu, Shaoyu; Eclarinal, Jesse; Baker, Maria S; Li, Ge; Waterland, Robert A

2016-02-01

Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mechanisms underlying such developmental programming of energy balance are poorly understood, limiting our ability to intervene. Most studies of developmental programming of energy balance have focused on persistent alterations in the regulation of energy intake; energy expenditure has been relatively underemphasised. In particular, very few studies have evaluated developmental programming of physical activity. The aim of this review is to summarise recent evidence that early environment may have a profound impact on establishment of individual propensity for physical activity. Recently, we characterised two different mouse models of developmental programming of obesity; one models fetal growth restriction followed by catch-up growth, and the other models early postnatal overnutrition. In both studies, we observed alterations in body-weight regulation that persisted to adulthood, but no group differences in food intake. Rather, in both cases, programming of energy balance appeared to be due to persistent alterations in energy expenditure and spontaneous physical activity (SPA). These effects were stronger in female offspring. We are currently exploring the hypothesis that developmental programming of SPA occurs via induced sex-specific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system. We will summarise the current progress towards testing this hypothesis. Early environmental influences on establishment of physical activity are likely an important factor in developmental programming of energy balance. Understanding the fundamental underlying mechanisms in appropriate animal models will help determine whether early life interventions may be a practical approach to promote physical activity in man.

Developmental Programming of Adult Disease: Reprogramming by Melatonin?

PubMed

Tain, You-Lin; Huang, Li-Tung; Hsu, Chien-Ning

2017-02-16

Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the "developmental origins of health and disease" (DOHaD) or "developmental programming". The DOHaD concept offers the "reprogramming" strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs.

Genome-wide analysis of coordinated transcript abundance during seed development in different Brassica rapa morphotypes.

PubMed

Basnet, Ram Kumar; Moreno-Pachon, Natalia; Lin, Ke; Bucher, Johan; Visser, Richard G F; Maliepaard, Chris; Bonnema, Guusje

2013-12-01

Brassica seeds are important as basic units of plant growth and sources of vegetable oil. Seed development is regulated by many dynamic metabolic processes controlled by complex networks of spatially and temporally expressed genes. We conducted a global microarray gene co-expression analysis by measuring transcript abundance of developing seeds from two diverse B. rapa morphotypes: a pak choi (leafy-type) and a yellow sarson (oil-type), and two of their doubled haploid (DH) progenies, (1) to study the timing of metabolic processes in developing seeds, (2) to explore the major transcriptional differences in developing seeds of the two morphotypes, and (3) to identify the optimum stage for a genetical genomics study in B. rapa seed. Seed developmental stages were similar in developing seeds of pak choi and yellow sarson of B. rapa; however, the colour of embryo and seed coat differed among these two morphotypes. In this study, most transcriptional changes occurred between 25 and 35 DAP, which shows that the timing of seed developmental processes in B. rapa is at later developmental stages than in the related species B. napus. Using a Weighted Gene Co-expression Network Analysis (WGCNA), we identified 47 "gene modules", of which 27 showed a significant association with temporal and/or genotypic variation. An additional hierarchical cluster analysis identified broad spectra of gene expression patterns during seed development. The predominant variation in gene expression was according to developmental stages rather than morphotype differences. Since lipids are the major storage compounds of Brassica seeds, we investigated in more detail the regulation of lipid metabolism. Four co-regulated gene clusters were identified with 17 putative cis-regulatory elements predicted in their 1000 bp upstream region, either specific or common to different lipid metabolic pathways. This is the first study of genome-wide profiling of transcript abundance during seed development in B. rapa. The identification of key physiological events, major expression patterns, and putative cis-regulatory elements provides useful information to construct gene regulatory networks in B. rapa developing seeds and provides a starting point for a genetical genomics study of seed quality traits.

Developmental programming of the metabolic syndrome - critical windows for intervention

PubMed Central

Vickers, Mark H

2011-01-01

Metabolic disease results from a complex interaction of many factors, including genetic, physiological, behavioral and environmental influences. The recent rate at which these diseases have increased suggests that environmental and behavioral influences, rather than genetic causes, are fuelling the present epidemic. In this context, the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome. Although the mechanisms are yet to be fully elucidated, this programming was generally considered an irreversible change in developmental trajectory. Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity. This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment. PMID:21954418

A Systematic Genetic Screen to Dissect the MicroRNA Pathway in Drosophila.

PubMed

Pressman, Sigal; Reinke, Catherine A; Wang, Xiaohong; Carthew, Richard W

2012-04-01

A central goal of microRNA biology is to elucidate the genetic program of miRNA function and regulation. However, relatively few of the effectors that execute miRNA repression have been identified. Because such genes may function in many developmental processes, mutations in them are expected to be pleiotropic and thus are discarded in most standard genetic screens. Here, we describe a systematic screen designed to identify all Drosophila genes in ∼40% of the genome that function in the miRNA pathway. To identify potentially pleiotropic genes, the screen analyzed clones of homozygous mutant cells in heterozygous animals. We identified 45 mutations representing 24 genes, and we molecularly characterized 9 genes. These include 4 previously known genes that encode core components of the miRNA pathway, including Drosha, Pasha, Dicer-1, and Ago1. The rest are new genes that function through chromatin remodeling, signaling, and mRNA decapping. The results suggest genetic screens that use clonal analysis can elucidate the miRNA program and that ∼100 genes are required to execute the miRNA program.

Contribution of Large Animals to Translational Research on Prenatal Programming of Obesity and Associated Diseases.

PubMed

Gonzalez-Bulnes, Antonio; Chavatte-Palmer, Pascale

2017-01-01

The awareness of factors causing obesity and associated disorders has grown up in the last years from genome to a more complicated concept (developmental programming) in which prenatal and early-postnatal conditions markedly modify the phenotype and homeostasis of the individuals and determine juvenile growth, life-time fitness/obesity and disease risks. Experimentation in human beings is impeded by ethical issues plus inherent high variability and confounding factors (genetics, lifestyle and socioeconomic heterogeneity) and preclinical studies in adequate translational animal models are therefore decisive. Most of the studies have been performed in rodents, whilst the use of large animals is scarce. Having in mind body-size, handlingeasiness and cost-efficiency, the main large animal species for use in biomedical research are rabbits, sheep and swine. The choice of the model depends on the research objectives. To outline the main features of the use of rabbits, sheep and swine and their contributions as translational models in prenatal programming of obesity and associated disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multifaceted biological insights from a draft genome sequence of the tobacco hornworm moth, Manduca sexta.

PubMed

Kanost, Michael R; Arrese, Estela L; Cao, Xiaolong; Chen, Yun-Ru; Chellapilla, Sanjay; Goldsmith, Marian R; Grosse-Wilde, Ewald; Heckel, David G; Herndon, Nicolae; Jiang, Haobo; Papanicolaou, Alexie; Qu, Jiaxin; Soulages, Jose L; Vogel, Heiko; Walters, James; Waterhouse, Robert M; Ahn, Seung-Joon; Almeida, Francisca C; An, Chunju; Aqrawi, Peshtewani; Bretschneider, Anne; Bryant, William B; Bucks, Sascha; Chao, Hsu; Chevignon, Germain; Christen, Jayne M; Clarke, David F; Dittmer, Neal T; Ferguson, Laura C F; Garavelou, Spyridoula; Gordon, Karl H J; Gunaratna, Ramesh T; Han, Yi; Hauser, Frank; He, Yan; Heidel-Fischer, Hanna; Hirsh, Ariana; Hu, Yingxia; Jiang, Hongbo; Kalra, Divya; Klinner, Christian; König, Christopher; Kovar, Christie; Kroll, Ashley R; Kuwar, Suyog S; Lee, Sandy L; Lehman, Rüdiger; Li, Kai; Li, Zhaofei; Liang, Hanquan; Lovelace, Shanna; Lu, Zhiqiang; Mansfield, Jennifer H; McCulloch, Kyle J; Mathew, Tittu; Morton, Brian; Muzny, Donna M; Neunemann, David; Ongeri, Fiona; Pauchet, Yannick; Pu, Ling-Ling; Pyrousis, Ioannis; Rao, Xiang-Jun; Redding, Amanda; Roesel, Charles; Sanchez-Gracia, Alejandro; Schaack, Sarah; Shukla, Aditi; Tetreau, Guillaume; Wang, Yang; Xiong, Guang-Hua; Traut, Walther; Walsh, Tom K; Worley, Kim C; Wu, Di; Wu, Wenbi; Wu, Yuan-Qing; Zhang, Xiufeng; Zou, Zhen; Zucker, Hannah; Briscoe, Adriana D; Burmester, Thorsten; Clem, Rollie J; Feyereisen, René; Grimmelikhuijzen, Cornelis J P; Hamodrakas, Stavros J; Hansson, Bill S; Huguet, Elisabeth; Jermiin, Lars S; Lan, Que; Lehman, Herman K; Lorenzen, Marce; Merzendorfer, Hans; Michalopoulos, Ioannis; Morton, David B; Muthukrishnan, Subbaratnam; Oakeshott, John G; Palmer, Will; Park, Yoonseong; Passarelli, A Lorena; Rozas, Julio; Schwartz, Lawrence M; Smith, Wendy; Southgate, Agnes; Vilcinskas, Andreas; Vogt, Richard; Wang, Ping; Werren, John; Yu, Xiao-Qiang; Zhou, Jing-Jiang; Brown, Susan J; Scherer, Steven E; Richards, Stephen; Blissard, Gary W

2016-09-01

Manduca sexta, known as the tobacco hornworm or Carolina sphinx moth, is a lepidopteran insect that is used extensively as a model system for research in insect biochemistry, physiology, neurobiology, development, and immunity. One important benefit of this species as an experimental model is its extremely large size, reaching more than 10 g in the larval stage. M. sexta larvae feed on solanaceous plants and thus must tolerate a substantial challenge from plant allelochemicals, including nicotine. We report the sequence and annotation of the M. sexta genome, and a survey of gene expression in various tissues and developmental stages. The Msex_1.0 genome assembly resulted in a total genome size of 419.4 Mbp. Repetitive sequences accounted for 25.8% of the assembled genome. The official gene set is comprised of 15,451 protein-coding genes, of which 2498 were manually curated. Extensive RNA-seq data from many tissues and developmental stages were used to improve gene models and for insights into gene expression patterns. Genome wide synteny analysis indicated a high level of macrosynteny in the Lepidoptera. Annotation and analyses were carried out for gene families involved in a wide spectrum of biological processes, including apoptosis, vacuole sorting, growth and development, structures of exoskeleton, egg shells, and muscle, vision, chemosensation, ion channels, signal transduction, neuropeptide signaling, neurotransmitter synthesis and transport, nicotine tolerance, lipid metabolism, and immunity. This genome sequence, annotation, and analysis provide an important new resource from a well-studied model insect species and will facilitate further biochemical and mechanistic experimental studies of many biological systems in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

PubMed Central

Chambers, Emily V.; Bickmore, Wendy A.; Semple, Colin A.

2013-01-01

Several recent studies have examined different aspects of mammalian higher order chromatin structure – replication timing, lamina association and Hi-C inter-locus interactions — and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution. PMID:23592965

Genome editing in sea urchin embryos by using a CRISPR/Cas9 system.

PubMed

Lin, Che-Yi; Su, Yi-Hsien

2016-01-15

Sea urchin embryos are a useful model system for investigating early developmental processes and the underlying gene regulatory networks. Most functional studies using sea urchin embryos rely on antisense morpholino oligonucleotides to knockdown gene functions. However, major concerns related to this technique include off-target effects, variations in morpholino efficiency, and potential morpholino toxicity; furthermore, such problems are difficult to discern. Recent advances in genome editing technologies have introduced the prospect of not only generating sequence-specific knockouts, but also providing genome-engineering applications. Two genome editing tools, zinc-finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs), have been utilized in sea urchin embryos, but the resulting efficiencies are far from satisfactory. The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system serves as an easy and efficient method with which to edit the genomes of several established and emerging model organisms in the field of developmental biology. Here, we apply the CRISPR/Cas9 system to the sea urchin embryo. We designed six guide RNAs (gRNAs) against the well-studied nodal gene and discovered that five of the gRNAs induced the expected phenotype in 60-80% of the injected embryos. In addition, we developed a simple method for isolating genomic DNA from individual embryos, enabling phenotype to be precisely linked to genotype, and revealed that the mutation rates were 67-100% among the sequenced clones. Of the two potential off-target sites we examined, no off-target effects were observed. The detailed procedures described herein promise to accelerate the usage of CRISPR/Cas9 system for genome editing in sea urchin embryos. Copyright © 2015 Elsevier Inc. All rights reserved.

48 CFR 919.7011 - Developmental assistance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... limited to: (1) Management guidance relating to: (i) Financial management, (ii) Organizational management, (iii) Overall business management planning, (iv) Business development, and (v) Marketing assistance; (2... PROGRAMS SMALL BUSINESS PROGRAMS The Department of Energy Mentor-Protege Program 919.7011 Developmental...

TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements

PubMed Central

Maliszewska-Olejniczak, Kamila; Gruchota, Julita; Gromadka, Robert; Denby Wilkes, Cyril; Arnaiz, Olivier; Mathy, Nathalie; Duharcourt, Sandra; Bétermier, Mireille; Nowak, Jacek K.

2015-01-01

Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for the first time a specific role of TFIIS in non-coding transcription in eukaryotes. PMID:26177014

Improving Developmentally Appropriate Practices in the Kindergarten Program by Introducing Therapeutic Sensory Motor and Play Activities.

ERIC Educational Resources Information Center

Blakes-Greenway, Doris

This practicum was designed to increase teacher knowledge base in developmentally appropriate practices and increase understanding of the need for play and sensory motor activities in the kindergarten program. The primary goal was that the kindergarten teachers would use more developmentally appropriate practices in achieving curriculum…

Project Developmental Continuity Evaluation: Final Report. Volume II: The Process of Program Implementation in PDC.

ERIC Educational Resources Information Center

Wacker, Sally; And Others

The second of two volumes, this document continues the final evaluation report of Project Developmental Continuity (PDC), a Head Start demonstration project initiated in 1974 to develop program models which enhance children's social competence by fostering developmental continuity from preschool through the early elementary grades. In particular,…

Transmitting Success: Comprehensive Peer Mentoring for At-Risk Students in Developmental Math

ERIC Educational Resources Information Center

Morales, Erik E.; Ambrose-Roman, Sarah; Perez-Maldonado, Rosa

2016-01-01

This study presents and assesses a developmental math focused peer mentoring program at a public urban university. Over three semesters 45 mentees participated in the program. Results include substantive increases in developmental pass rates as well as increases in self-efficacy and social integration. Other noteworthy findings include the…

A POSITION PAPER ON THE TEACHING OF READING, DEVELOPMENTAL AND CORRECTIVE.

ERIC Educational Resources Information Center

HODDER, VELMA; AND OTHERS

THE BASIC DEVELOPMENTAL READING PROGRAM IS REVIEWED AS A FOUNDATION FOR SOUND REMEDIAL OR CORRECTIVE PROGRAMS IN A GUIDE FOR THE IMPROVEMENT OF ELEMENTARY AND SECONDARY READING IN NEBRASKA SCHOOLS. THE PRESENTATION IS DEVELOPED AROUND FOUR TOPICS--(1) DEVELOPMENTAL READING (CHILDREN'S GROWTH CHARACTERISTICS AND NEEDS, INSTRUCTIONAL READING LEVEL,…

Fetal programming of reproduction, what we know and how we manage it

USDA-ARS?s Scientific Manuscript database

For the purposes of this paper, fetal programming will cover developmental and nutritional programming both before and after birth. Developmental programming is defined as changes in anatomical structure and/or physiology that result from differences in gene function instead of variation in DNA seq...

Benefits of the NADE Certification Process: Self-Knowledge, Informed Choices & Programmatic Strength

ERIC Educational Resources Information Center

Greci, Dana

2016-01-01

Research shows that systematic, ongoing program evaluation is needed to adequately assess the effectiveness of developmental programs. Ongoing evaluation provides both (1) validation of programs to educational institutions and legislators; and (2) impetus for program improvement. The author of this article works in the Developmental Education…

Word Reading Fluency: Role of Genome-Wide Single-Nucleotide Polymorphisms in Developmental Stability and Correlations with Print Exposure

ERIC Educational Resources Information Center

Harlaar, Nicole; Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

2014-01-01

The genetic effects on individual differences in reading development were examined using genome-wide complex trait analysis (GCTA) in a twin sample. In unrelated individuals (one twin per pair, n = 2,942), the GCTA-based heritability of reading fluency was ~20%-29% at ages 7 and 12. GCTA bivariate results showed that the phenotypic stability of…

Evo-Devo-EpiR: a genome-wide search platform for epistatic control on the evolution of development.

PubMed

Jiang, Libo; Zhang, Miaomiao; Sang, Mengmeng; Ye, Meixia; Wu, Rongling

2017-09-01

Evo-devo is a theory proposed to study how phenotypes evolve by comparing the developmental processes of different organisms or the same organism experiencing changing environments. It has been recognized that nonallelic interactions at different genes or quantitative trait loci, known as epistasis, may play a pivotal role in the evolution of development, but it has proven difficult to quantify and elucidate this role into a coherent picture. We implement a high-dimensional genome-wide association study model into the evo-devo paradigm and pack it into the R-based Evo-Devo-EpiR, aimed at facilitating the genome-wide landscaping of epistasis for the diversification of phenotypic development. By analyzing a high-throughput assay of DNA markers and their pairs simultaneously, Evo-Devo-EpiR is equipped with a capacity to systematically characterize various epistatic interactions that impact on the pattern and timing of development and its evolution. Enabling a global search for all possible genetic interactions for developmental processes throughout the whole genome, Evo-Devo-EpiR provides a computational tool to illustrate a precise genotype-phenotype map at interface between epistasis, development and evolution. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans

PubMed Central

Ow, Maria C.; Nichitean, Alexandra M.; Dorus, Steve; Hall, Sarah E.

2018-01-01

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite (“seesaw”) transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome. PMID:29447162

Nutritional programming of reproductive development in heifers

USDA-ARS?s Scientific Manuscript database

Developmental programming is the biological process by which environmental factors influence the development of the organs and tissues in the body. There are two areas of developmental programming being investigated with applicability to beef production systems to improve performance of replacement...

The Trichoplax Genome and the Nature of Placozoans

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

Srivastava, Mansi; Begovic, Emina; Chapman, Jarrod

2008-08-01

Placozoans are arguably the simplest free-living animals, possibly evoking an early stage in metazoan evolution, yet their biology is poorly understood. Here we report the sequencing and analysis of the {approx}98 million base pair nuclear genome of the placozoan Trichoplax adhaerens. Whole genome phylogenetic analysis suggests that placozoans belong to a 'eumetazoan' clade that includes cnidarians and bilaterians, with sponges as the earliest diverging animals. The compact genome exhibits conserved gene content, gene structure, and synteny relative to the human and other complex eumetazoan genomes. Despite the apparent cellular and organismal simplicity of Trichoplax, its genome encodes a rich arraymore » of transcription factor and signaling pathway genes that are typically associated with diverse cell types and developmental processes in eumetazoans, motivating further searches for cryptic cellular complexity and/or as yet unobserved life history stages.« less

Chironomid midges (Diptera, chironomidae) show extremely small genome sizes.

PubMed

Cornette, Richard; Gusev, Oleg; Nakahara, Yuichi; Shimura, Sachiko; Kikawada, Takahiro; Okuda, Takashi

2015-06-01

Chironomid midges (Diptera; Chironomidae) are found in various environments from the high Arctic to the Antarctic, including temperate and tropical regions. In many freshwater habitats, members of this family are among the most abundant invertebrates. In the present study, the genome sizes of 25 chironomid species were determined by flow cytometry and the resulting C-values ranged from 0.07 to 0.20 pg DNA (i.e. from about 68 to 195 Mbp). These genome sizes were uniformly very small and included, to our knowledge, the smallest genome sizes recorded to date among insects. Small proportion of transposable elements and short intron sizes were suggested to contribute to the reduction of genome sizes in chironomids. We discuss about the possible developmental and physiological advantages of having a small genome size and about putative implications for the ecological success of the family Chironomidae.

A genomic view of 500 million years of cnidarian evolution.

PubMed

Steele, Robert E; David, Charles N; Technau, Ulrich

2011-01-01

Cnidarians (corals, anemones, jellyfish and hydras) are a diverse group of animals of interest to evolutionary biologists, ecologists and developmental biologists. With the publication of the genome sequences of Hydra and Nematostella, whose last common ancestor was the stem cnidarian, researchers are beginning to see the genomic underpinnings of cnidarian biology. Cnidarians are known for the remarkable plasticity of their morphology and life cycles. This plasticity is reflected in the Hydra and Nematostella genomes, which differ to an exceptional degree in size, base composition, transposable element content and gene conservation. It is now known what cnidarian genomes, given 500 million years, are capable of; as we discuss here, the next challenge is to understand how this genomic history has led to the striking diversity seen in this group. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

The effect of adding a home program to weekly institutional-based therapy for children with undefined developmental delay: a pilot randomized clinical trial.

PubMed

Tang, Mei-Hua; Lin, Chin-Kai; Lin, Wen-Hsien; Chen, Chao-Huei; Tsai, Sen-Wei; Chang, Yin-Yi

2011-06-01

Early rehabilitation for children with developmental delay without a defined etiology have included home and clinic programs, but no comparisons have been made and efficacy is uncertain. We compared a weekly visit for institutional-based therapy (IT) to IT plus a structured home activity program (HAP). Seventy children who were diagnosed with motor or global developmental delay (ages 6-48 months and mean developmental age 12.5 months) without defined etiology were recruited (including 45 males and 23 females). The outcomes included the comprehensive developmental inventory for infants and toddlers test and the pediatric evaluation of disability inventory. Children who received only IT improved in developmental level by 2.11 months compared with 3.11 months for those who received a combination of IT and HAP (p = 0.000). On all domains of the comprehensive developmental inventory for infants and toddlers test, except for self-help, children who participated in HAP showed greater improvements, including in cognition (p = 0.015), language (p = 0.010), motor (p = 0.000), and social (p = 0.038) domains. Except on the subdomain of self-care with caregiver assistance, the HAP group showed greater improvement in all the pediatric evaluation of disability inventory subdomains (p < 0.05). Early intervention programs are helpful for these children, and the addition of structured home activity programs may augment the effects on developmental progression. Copyright © 2011. Published by Elsevier B.V.

Genetic variation of growth dynamics in maize (Zea mays L.) revealed through automated non-invasive phenotyping.

PubMed

Muraya, Moses M; Chu, Jianting; Zhao, Yusheng; Junker, Astrid; Klukas, Christian; Reif, Jochen C; Altmann, Thomas

2017-01-01

Hitherto, most quantitative trait loci of maize growth and biomass yield have been identified for a single time point, usually the final harvest stage. Through this approach cumulative effects are detected, without considering genetic factors causing phase-specific differences in growth rates. To assess the genetics of growth dynamics, we employed automated non-invasive phenotyping to monitor the plant sizes of 252 diverse maize inbred lines at 11 different developmental time points; 50 k SNP array genotype data were used for genome-wide association mapping and genomic selection. The heritability of biomass was estimated to be over 71%, and the average prediction accuracy amounted to 0.39. Using the individual time point data, 12 main effect marker-trait associations (MTAs) and six pairs of epistatic interactions were detected that displayed different patterns of expression at various developmental time points. A subset of them also showed significant effects on relative growth rates in different intervals. The detected MTAs jointly explained up to 12% of the total phenotypic variation, decreasing with developmental progression. Using non-parametric functional mapping and multivariate mapping approaches, four additional marker loci affecting growth dynamics were detected. Our results demonstrate that plant biomass accumulation is a complex trait governed by many small effect loci, most of which act at certain restricted developmental phases. This highlights the need for investigation of stage-specific growth affecting genes to elucidate important processes operating at different developmental phases. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells.

PubMed

Choi, Jiho; Huebner, Aaron J; Clement, Kendell; Walsh, Ryan M; Savol, Andrej; Lin, Kaixuan; Gu, Hongcang; Di Stefano, Bruno; Brumbaugh, Justin; Kim, Sang-Yong; Sharif, Jafar; Rose, Christopher M; Mohammad, Arman; Odajima, Junko; Charron, Jean; Shioda, Toshi; Gnirke, Andreas; Gygi, Steven; Koseki, Haruhiko; Sadreyev, Ruslan I; Xiao, Andrew; Meissner, Alexander; Hochedlinger, Konrad

2017-08-10

Concomitant activation of the Wnt pathway and suppression of Mapk signalling by two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES) cells that resembles the inner cell mass (ICM) of the pre-implantation embryo. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naive ES cells in vitro affects their stability and functionality. Here we show that prolonged culture of male mouse ES cells in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential. Furthermore, we find that female ES cells cultured in conventional serum plus LIF medium phenocopy male ES cells cultured in 2i/L. Mechanistically, we demonstrate that the inhibition of Mek1/2 is predominantly responsible for these effects, in part through the downregulation of DNA methyltransferases and their cofactors. Finally, we show that replacement of the Mek1/2 inhibitor with a Src inhibitor preserves the epigenetic and genomic integrity as well as the developmental potential of ES cells. Taken together, our data suggest that, although short-term suppression of Mek1/2 in ES cells helps to maintain an ICM-like epigenetic state, prolonged suppression results in irreversible changes that compromise their developmental potential.

Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability.

PubMed

Reggiani, Claudio; Coppens, Sandra; Sekhara, Tayeb; Dimov, Ivan; Pichon, Bruno; Lufin, Nicolas; Addor, Marie-Claude; Belligni, Elga Fabia; Digilio, Maria Cristina; Faletra, Flavio; Ferrero, Giovanni Battista; Gerard, Marion; Isidor, Bertrand; Joss, Shelagh; Niel-Bütschi, Florence; Perrone, Maria Dolores; Petit, Florence; Renieri, Alessandra; Romana, Serge; Topa, Alexandra; Vermeesch, Joris Robert; Lenaerts, Tom; Casimir, Georges; Abramowicz, Marc; Bontempi, Gianluca; Vilain, Catheline; Deconinck, Nicolas; Smits, Guillaume

2017-07-19

Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders. Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play. Integrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients' clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories. While protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases.

Predictive computation of genomic logic processing functions in embryonic development

PubMed Central

Peter, Isabelle S.; Faure, Emmanuel; Davidson, Eric H.

2012-01-01

Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model. This Boolean model computes spatial and temporal gene expression according to the regulatory logic and gene interactions specified in a GRN model for embryonic development in the sea urchin. Additional information input into the model included the progressive embryonic geometry and gene expression kinetics. The resulting model predicted gene expression patterns for a large number of individual regulatory genes each hour up to gastrulation (30 h) in four different spatial domains of the embryo. Direct comparison with experimental observations showed that the model predictively computed these patterns with remarkable spatial and temporal accuracy. In addition, we used this model to carry out in silico perturbations of regulatory functions and of embryonic spatial organization. The model computationally reproduced the altered developmental functions observed experimentally. Two major conclusions are that the starting GRN model contains sufficiently complete regulatory information to permit explanation of a complex developmental process of gene expression solely in terms of genomic regulatory code, and that the Boolean model provides a tool with which to test in silico regulatory circuitry and developmental perturbations. PMID:22927416

Demographic history, selection and functional diversity of the canine genome.

PubMed

Ostrander, Elaine A; Wayne, Robert K; Freedman, Adam H; Davis, Brian W

2017-12-01

The domestic dog represents one of the most dramatic long-term evolutionary experiments undertaken by humans. From a large wolf-like progenitor, unparalleled diversity in phenotype and behaviour has developed in dogs, providing a model for understanding the developmental and genomic mechanisms of diversification. We discuss pattern and process in domestication, beginning with general findings about early domestication and problems in documenting selection at the genomic level. Furthermore, we summarize genotype-phenotype studies based first on single nucleotide polymorphism (SNP) genotyping and then with whole-genome data and show how an understanding of evolution informs topics as different as human history, adaptive and deleterious variation, morphological development, ageing, cancer and behaviour.

78 FR 18680 - Genomic Medicine Program Advisory Committee, Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... DEPARTMENT OF VETERANS AFFAIRS Genomic Medicine Program Advisory Committee, Notice of Meeting The..., that the Genomic Medicine Program Advisory Committee will meet on April 11, 2013, in Suite 1000 at the... ongoing Million Veteran Program, as well as the clinical Genomic Medicine Service. The emerging...

The Silkworm (Bombyx mori) microRNAs and Their Expressions in Multiple Developmental Stages

PubMed Central

Luo, Qibin; Cai, Yimei; Lin, Wen-chang; Chen, Huan; Yang, Yue; Hu, Songnian; Yu, Jun

2008-01-01

Background MicroRNAs (miRNAs) play crucial roles in various physiological processes through post-transcriptional regulation of gene expressions and are involved in development, metabolism, and many other important molecular mechanisms and cellular processes. The Bombyx mori genome sequence provides opportunities for a thorough survey for miRNAs as well as comparative analyses with other sequenced insect species. Methodology/Principal Findings We identified 114 non-redundant conserved miRNAs and 148 novel putative miRNAs from the B. mori genome with an elaborate computational protocol. We also sequenced 6,720 clones from 14 developmental stage-specific small RNA libraries in which we identified 35 unique miRNAs containing 21 conserved miRNAs (including 17 predicted miRNAs) and 14 novel miRNAs (including 11 predicted novel miRNAs). Among the 114 conserved miRNAs, we found six pairs of clusters evolutionarily conserved cross insect lineages. Our observations on length heterogeneity at 5′ and/or 3′ ends of nine miRNAs between cloned and predicted sequences, and three mature forms deriving from the same arm of putative pre-miRNAs suggest a mechanism by which miRNAs gain new functions. Analyzing development-related miRNAs expression at 14 developmental stages based on clone-sampling and stem-loop RT PCR, we discovered an unusual abundance of 33 sequences representing 12 different miRNAs and sharply fluctuated expression of miRNAs at larva-molting stage. The potential functions of several stage-biased miRNAs were also analyzed in combination with predicted target genes and silkworm's phenotypic traits; our results indicated that miRNAs may play key regulatory roles in specific developmental stages in the silkworm, such as ecdysis. Conclusions/Significance Taking a combined approach, we identified 118 conserved miRNAs and 151 novel miRNA candidates from the B. mori genome sequence. Our expression analyses by sampling miRNAs and real-time PCR over multiple developmental stages allowed us to pinpoint molting stages as hotspots of miRNA expression both in sorts and quantities. Based on the analysis of target genes, we hypothesized that miRNAs regulate development through a particular emphasis on complex stages rather than general regulatory mechanisms. PMID:18714353

NCI: DCTD: Biometric Research Program

Cancer.gov

The Biometric Research Program (BRP) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

NCI: DCTD: Biometric Research Program

Cancer.gov

The Biometric Research Program (BRB) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

A Process Evaluation of Project Developmental Continuity. Interim Report IV, Volume 2: Development of the Implementation and Cost Studies.

ERIC Educational Resources Information Center

Smith, Allen G.; And Others

This interim report describes the development of program implementation and cost studies for Year II of the process evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. Specific areas focused…

"It's All about the 'Ganas'": Incorporating a Multicultural Curriculum in Developmental Education

ERIC Educational Resources Information Center

Doran, Erin E.; Singh, Anupma

2018-01-01

Despite the overrepresentation of students of color in developmental education, there is a lack of research on programs that promote the success and transfer of these students beginning in developmental education, especially Latinx students. Since 2012, the Dream Catchers program in Texas has targeted the recruitment, retention, and completion of…

The Political History of Developmental Studies in the University System of Georgia

ERIC Educational Resources Information Center

Presley, John W.; Dodd, William M.

2008-01-01

The political history of developmental education in post-secondary education is as revealing as its intellectual history. With a University system-wide Developmental Studies program initiated in 1974, the State of Georgia was a pioneer in remedial education and open access. Unfortunately, the program became linked in Georgia media, and in Georgia…

The Transition to School of Children with Developmental Disabilities: Views of Parents and Teachers

ERIC Educational Resources Information Center

Walker, Sue; Dunbar, Stephanie; Meldrum, Katrina; Whiteford, Chrystal; Carrington, Suzanne; Berthelsen, Donna; Hand, Kirstine; Nicholson, Jan

2012-01-01

The transition from early intervention programs to inclusive school settings presents a range of social challenges for children with developmental disabilities. In Queensland, in the year of transition to school, many children with developmental disabilities attend an Early Childhood Development Program for two to three days each week and also…

Developmental Relationship Programs: An Empirical Study of the Impact of Peer-Mentoring Programs

ERIC Educational Resources Information Center

Shojai, Siamack; Davis, William J.; Root, Patricia S.

2014-01-01

This paper provides an empirical analysis of the impact and effectiveness of developmental relationships provided through academic intervention programs at a medium-size master's level public university in the Northeastern United States. The programs' curriculum follows the Model of Strategic Learning's four pillars of learning and is administered…

The Chief Executive Officer's Leadership Role in Remedial and Developmental Programs.

ERIC Educational Resources Information Center

Lawler, Muriel; Bowes, S. Gregory

1988-01-01

Eighty percent of New Mexico's 17 community college and vocational school CEOs responded to a survey revealing that they have different views on what constitutes remedial and developmental programs; and although these programs are considered compatible with the CEOs' educational philosophy, programs are not viewed on equal basis with other college…

Genome-wide association study (GWAS) for growth rate and age at sexual maturation in Atlantic salmon (Salmo salar).

PubMed

Gutierrez, Alejandro P; Yáñez, José M; Fukui, Steve; Swift, Bruce; Davidson, William S

2015-01-01

Early sexual maturation is considered a serious drawback for Atlantic salmon aquaculture as it retards growth, increases production times and affects flesh quality. Although both growth and sexual maturation are thought to be complex processes controlled by several genetic and environmental factors, selection for these traits has been continuously accomplished since the beginning of Atlantic salmon selective breeding programs. In this genome-wide association study (GWAS) we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ∼ 480 individuals from the Cermaq Canada broodstock program and search for SNPs associated with growth and age at sexual maturation. Using a mixed model approach we identified markers showing a significant association with growth, grilsing (early sexual maturation) and late sexual maturation. The most significant associations were found for grilsing, with markers located in Ssa10, Ssa02, Ssa13, Ssa25 and Ssa12, and for late maturation with markers located in Ssa28, Ssa01 and Ssa21. A lower level of association was detected with growth on Ssa13. Candidate genes, which were linked to these genetic markers, were identified and some of them show a direct relationship with developmental processes, especially for those in association with sexual maturation. However, the relatively low power to detect genetic markers associated with growth (days to 5 kg) in this GWAS indicates the need to use a higher density SNP array in order to overcome the low levels of linkage disequilibrium observed in Atlantic salmon before the information can be incorporated into a selective breeding program.

Programs | Office of Cancer Genomics

Cancer.gov

OCG facilitates cancer genomics research through a series of highly-focused programs. These programs generate and disseminate genomic data for use by the cancer research community. OCG programs also promote advances in technology-based infrastructure and create valuable experimental reagents and tools. OCG programs encourage collaboration by interconnecting with other genomics and cancer projects in order to accelerate translation of findings into the clinic. Below are OCG’s current, completed, and initiated programs:

A genetic screen for zygotic embryonic lethal mutations affecting cuticular morphology in the wasp Nasonia vitripennis.

PubMed Central

Pultz, M A; Zimmerman, K K; Alto, N M; Kaeberlein, M; Lange, S K; Pitt, J N; Reeves, N L; Zehrung, D L

2000-01-01

We have screened for zygotic embryonic lethal mutations affecting cuticular morphology in Nasonia vitripennis (Hymenoptera; Chalcidoidea). Our broad goal was to investigate the use of Nasonia for genetically surveying conservation and change in regulatory gene systems, as a means to understand the diversity of developmental strategies that have arisen during the course of evolution. Specifically, we aim to compare anteroposterior patterning gene functions in two long germ band insects, Nasonia and Drosophila. In Nasonia, unfertilized eggs develop as haploid males while fertilized eggs develop as diploid females, so the entire genome can be screened for recessive zygotic mutations by examining the progeny of F1 females. We describe 74 of >100 lines with embryonic cuticular mutant phenotypes, including representatives of coordinate, gap, pair-rule, segment polarity, homeotic, and Polycomb group functions, as well as mutants with novel phenotypes not directly comparable to those of known Drosophila genes. We conclude that Nasonia is a tractable experimental organism for comparative developmental genetic study. The mutants isolated here have begun to outline the extent of conservation and change in the genetic programs controlling embryonic patterning in Nasonia and Drosophila. PMID:10866651

Immune cell identity: perspective from a palimpsest

PubMed Central

Rothenberg, Ellen V.

2016-01-01

The immune system in mammals is composed of multiple different immune cell types that migrate through the body and are made continuously throughout life. Lymphocytes and myeloid cells interact with each other and depend upon each other, but are each highly diverse and specialized for different roles. Lymphocytes uniquely require developmentally programmed mutational changes in the genome itself for their maturation. Despite profound differences between their mechanisms of threat recognition and threat response, however, the developmental origins of lymphocytes and myeloid cells are interlinked, and important aspects of their response mechanisms remain shared. As the immune defense system has been elucidated in the past 50 years, it is notable that the chain of logic toward our current understanding was driven by strongly posited models that led to crucial discoveries even though these models ended up being partly wrong. It has been the predictive strength of these models and their success as guides to incisive experimental research that has also illuminated the limits of each model’s explanatory scope, beyond which another model needed to assume the lead. This brief review describes how a succession of distinct paradigms has helped to clarify a sophisticated picture of immune cell generation and control. PMID:26750603

The paternal hidden agenda: Epigenetic inheritance through sperm chromatin.

PubMed

Puri, Deepika; Dhawan, Jyotsna; Mishra, Rakesh K

2010-07-01

Epigenetic modifications play a crucial role in developmental gene regulation. These modifications, being reversible, provide a layer of information over and above the DNA sequence, that has plasticity and leads to the generation of cell type-specific epigenomes during cellular differentiation. In almost all higher eukaryotes, the oocyte provides not only its cytoplasm, mitochondria, maternally deposited RNA and proteins but also an epigenetic component in the form of DNA and histone-modifications. During spermeiogenesis however, most of the histones are replaced by protamines, leading to a loss of the epigenetic component. The sperm is, therefore, viewed as a passive carrier of the paternal genome with a disproportionate, lower epigenetic contribution except for DNA methylation, to the next generation. A recent study overturns this view by demonstrating a locus-specific retention of histones, with specific modifications in the sperm chromatin at the promoters of developmentally important genes. This programmed retention of epigenetic marks with a role in embryonic development is suggested to offset, in some measure, the dominant maternal effect. This new finding helps in addressing the question of epigenetic transmission of environmental and 'lifestyle' experiences across generations and raises the question of 'parental conflict' at the loci that may be differentially marked.

The genome and transcriptome of the enteric parasite Entamoeba invadens, a model for encystation

PubMed Central

2013-01-01

Background Several eukaryotic parasites form cysts that transmit infection. The process is found in diverse organisms such as Toxoplasma, Giardia, and nematodes. In Entamoeba histolytica this process cannot be induced in vitro, making it difficult to study. In Entamoeba invadens, stage conversion can be induced, but its utility as a model system to study developmental biology has been limited by a lack of genomic resources. We carried out genome and transcriptome sequencing of E. invadens to identify molecular processes involved in stage conversion. Results We report the sequencing and assembly of the E. invadens genome and use whole transcriptome sequencing to characterize changes in gene expression during encystation and excystation. The E. invadens genome is larger than that of E. histolytica, apparently largely due to expansion of intergenic regions; overall gene number and the machinery for gene regulation are conserved between the species. Over half the genes are regulated during the switch between morphological forms and a key signaling molecule, phospholipase D, appears to regulate encystation. We provide evidence for the occurrence of meiosis during encystation, suggesting that stage conversion may play a key role in recombination between strains. Conclusions Our analysis demonstrates that a number of core processes are common to encystation between distantly related parasites, including meiosis, lipid signaling and RNA modification. These data provide a foundation for understanding the developmental cascade in the important human pathogen E. histolytica and highlight conserved processes more widely relevant in enteric pathogens. PMID:23889909

Genomic resources for songbird research and their use in characterizing gene expression during brain development

PubMed Central

Li, XiaoChing; Wang, Xiu-Jie; Tannenhauser, Jonathan; Podell, Sheila; Mukherjee, Piali; Hertel, Moritz; Biane, Jeremy; Masuda, Shoko; Nottebohm, Fernando; Gaasterland, Terry

2007-01-01

Vocal learning and neuronal replacement have been studied extensively in songbirds, but until recently, few molecular and genomic tools for songbird research existed. Here we describe new molecular/genomic resources developed in our laboratory. We made cDNA libraries from zebra finch (Taeniopygia guttata) brains at different developmental stages. A total of 11,000 cDNA clones from these libraries, representing 5,866 unique gene transcripts, were randomly picked and sequenced from the 3′ ends. A web-based database was established for clone tracking, sequence analysis, and functional annotations. Our cDNA libraries were not normalized. Sequencing ESTs without normalization produced many developmental stage-specific sequences, yielding insights into patterns of gene expression at different stages of brain development. In particular, the cDNA library made from brains at posthatching day 30–50, corresponding to the period of rapid song system development and song learning, has the most diverse and richest set of genes expressed. We also identified five microRNAs whose sequences are highly conserved between zebra finch and other species. We printed cDNA microarrays and profiled gene expression in the high vocal center of both adult male zebra finches and canaries (Serinus canaria). Genes differentially expressed in the high vocal center were identified from the microarray hybridization results. Selected genes were validated by in situ hybridization. Networks among the regulated genes were also identified. These resources provide songbird biologists with tools for genome annotation, comparative genomics, and microarray gene expression analysis. PMID:17426146

Conserved Noncoding Elements in the Most Distant Genera of Cephalochordates: The Goldilocks Principle

PubMed Central

Yue, Jia-Xing; Kozmikova, Iryna; Ono, Hiroki; Nossa, Carlos W.; Kozmik, Zbynek; Putnam, Nicholas H.; Yu, Jr-Kai; Holland, Linda Z.

2016-01-01

Cephalochordates, the sister group of vertebrates + tunicates, are evolving particularly slowly. Therefore, genome comparisons between two congeners of Branchiostoma revealed so many conserved noncoding elements (CNEs), that it was not clear how many are functional regulatory elements. To more effectively identify CNEs with potential regulatory functions, we compared noncoding sequences of genomes of the most phylogenetically distant cephalochordate genera, Asymmetron and Branchiostoma, which diverged approximately 120–160 million years ago. We found 113,070 noncoding elements conserved between the two species, amounting to 3.3% of the genome. The genomic distribution, target gene ontology, and enriched motifs of these CNEs all suggest that many of them are probably cis-regulatory elements. More than 90% of previously verified amphioxus regulatory elements were re-captured in this study. A search of the cephalochordate CNEs around 50 developmental genes in several vertebrate genomes revealed eight CNEs conserved between cephalochordates and vertebrates, indicating sequence conservation over >500 million years of divergence. The function of five CNEs was tested in reporter assays in zebrafish, and one was also tested in amphioxus. All five CNEs proved to be tissue-specific enhancers. Taken together, these findings indicate that even though Branchiostoma and Asymmetron are distantly related, as they are evolving slowly, comparisons between them are likely optimal for identifying most of their tissue-specific cis-regulatory elements laying the foundation for functional characterizations and a better understanding of the evolution of developmental regulation in cephalochordates. PMID:27412606

Do Developmental Mathematics Programs Have a Causal Impact on Student Retention? An Application of Discrete-Time Survival and Regression-Discontinuity Analysis

ERIC Educational Resources Information Center

Lesik, Sally A.

2007-01-01

The impact of academic programs--such as developmental mathematics programs--on student retention, has been a controversial topic for administrators, policy makers, and faculty in higher education. Despite deep interest in the effectiveness of these programs in retaining students, scholars have been unable to determine whether such programs have a…

Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae

PubMed Central

Symington, Lorraine S.; Rothstein, Rodney; Lisby, Michael

2014-01-01

Homology-dependent exchange of genetic information between DNA molecules has a profound impact on the maintenance of genome integrity by facilitating error-free DNA repair, replication, and chromosome segregation during cell division as well as programmed cell developmental events. This chapter will focus on homologous mitotic recombination in budding yeast Saccharomyces cerevisiae. However, there is an important link between mitotic and meiotic recombination (covered in the forthcoming chapter by Hunter et al. 2015) and many of the functions are evolutionarily conserved. Here we will discuss several models that have been proposed to explain the mechanism of mitotic recombination, the genes and proteins involved in various pathways, the genetic and physical assays used to discover and study these genes, and the roles of many of these proteins inside the cell. PMID:25381364

Surviving an Identity Crisis: A Revised View of Chromatin Insulators in the Genomics Era

PubMed Central

Matzat, Leah H.; Lei, Elissa P.

2013-01-01

The control of complex, developmentally regulated loci and partitioning of the genome into active and silent domains is in part accomplished through the activity of DNA-protein complexes termed chromatin insulators. Together, the multiple, well-studied classes of insulators in Drosophila melanogaster appear to be generally functionally conserved. In this review, we discuss recent genomic-scale experiments and attempt to reconcile these newer findings in the context of previously defined insulator characteristics based on classical genetic analyses and transgenic approaches. Finally, we discuss the emerging understanding of mechanisms of chromatin insulator regulation. PMID:24189492

The dynamic evolutionary history of genome size in North American woodland salamanders.

PubMed

Newman, Catherine E; Gregory, T Ryan; Austin, Christopher C

2017-04-01

The genus Plethodon is the most species-rich salamander genus in North America, and nearly half of its species face an uncertain future. It is also one of the most diverse families in terms of genome sizes, which range from 1C = 18.2 to 69.3 pg, or 5-20 times larger than the human genome. Large genome size in salamanders results in part from accumulation of transposable elements and is associated with various developmental and physiological traits. However, genome sizes have been reported for only 25% of the species of Plethodon (14 of 55). We collected genome size data for Plethodon serratus to supplement an ongoing phylogeographic study, reconstructed the evolutionary history of genome size in Plethodontidae, and inferred probable genome sizes for the 41 species missing empirical data. Results revealed multiple genome size changes in Plethodon: genomes of western Plethodon increased, whereas genomes of eastern Plethodon decreased, followed by additional decreases or subsequent increases. The estimated genome size of P. serratus was 21 pg. New understanding of variation in genome size evolution, along with genome size inferences for previously unstudied taxa, provide a foundation for future studies on the biology of plethodontid salamanders.

Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives.

PubMed

Grandjean, Philippe; Barouki, Robert; Bellinger, David C; Casteleyn, Ludwine; Chadwick, Lisa H; Cordier, Sylvaine; Etzel, Ruth A; Gray, Kimberly A; Ha, Eun-Hee; Junien, Claudine; Karagas, Margaret; Kawamoto, Toshihiro; Paige Lawrence, B; Perera, Frederica P; Prins, Gail S; Puga, Alvaro; Rosenfeld, Cheryl S; Sherr, David H; Sly, Peter D; Suk, William; Sun, Qi; Toppari, Jorma; van den Hazel, Peter; Walker, Cheryl L; Heindel, Jerrold J

2015-10-01

The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.

Evolutionary Nephrology.

PubMed

Chevalier, Robert L

2017-05-01

Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as "maladaptive." In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic) adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or evolutionary tradeoffs. Evolutionary adaptation to a terrestrial environment resulted in a vulnerable energy-consuming renal tubule and a hypoxic, hyperosmolar microenvironment. Natural selection favors successful energy investment strategy: energy is allocated to maintenance of nephron integrity through reproductive years, but this declines with increasing senescence after ~40 years of age. Risk factors for chronic kidney disease include restricted fetal growth or preterm birth (life history tradeoff resulting in fewer nephrons), evolutionary selection for APOL1 mutations (that provide resistance to trypanosome infection, a tradeoff), and modern life experience (Western diet mismatch leading to diabetes and hypertension). Current advances in genomics, epigenetics, and developmental biology have revealed proximate causes of kidney disease, but attempts to slow kidney disease remain elusive. Evolutionary medicine provides a complementary approach by addressing ultimate causes of kidney disease. Marked variation in nephron number at birth, nephron heterogeneity, and changing susceptibility to kidney injury throughout life history are the result of evolutionary processes. Combined application of molecular genetics, evolutionary developmental biology (evo-devo), developmental programming and life history theory may yield new strategies for prevention and treatment of chronic kidney disease.

Is Transcriptomic Regulation of Berry Development More Important at Night than During the Day?

PubMed Central

Rienth, Markus; Torregrosa, Laurent; Kelly, Mary T.; Luchaire, Nathalie; Pellegrino, Anne; Grimplet, Jérôme; Romieu, Charles

2014-01-01

Diurnal changes in gene expression occur in all living organisms and have been studied on model plants such as Arabidopsis thaliana. To our knowledge the impact of the nycthemeral cycle on the genetic program of fleshly fruit development has been hitherto overlooked. In order to circumvent environmental changes throughout fruit development, young and ripening berries were sampled simultaneously on continuously flowering microvines acclimated to controlled circadian light and temperature changes. Gene expression profiles along fruit development were monitored during both day and night with whole genome microarrays (Nimblegen® vitis 12x), yielding a total number of 9273 developmentally modulated probesets. All day-detected transcripts were modulated at night, whereas 1843 genes were night-specific. Very similar developmental patterns of gene expression were observed using independent hierarchical clustering of day and night data, whereas functional categories of allocated transcripts varied according to time of day. Many transcripts within pathways, known to be up-regulated during ripening, in particular those linked to secondary metabolism exhibited a clearer developmental regulation at night than during the day. Functional enrichment analysis also indicated that diurnally modulated genes considerably varied during fruit development, with a shift from cellular organization and photosynthesis in green berries to secondary metabolism and stress-related genes in ripening berries. These results reveal critical changes in gene expression during night development that differ from daytime development, which have not been observed in other transcriptomic studies on fruit development thus far. PMID:24551177

Is transcriptomic regulation of berry development more important at night than during the day?

PubMed

Rienth, Markus; Torregrosa, Laurent; Kelly, Mary T; Luchaire, Nathalie; Pellegrino, Anne; Grimplet, Jérôme; Romieu, Charles

2014-01-01

Diurnal changes in gene expression occur in all living organisms and have been studied on model plants such as Arabidopsis thaliana. To our knowledge the impact of the nycthemeral cycle on the genetic program of fleshly fruit development has been hitherto overlooked. In order to circumvent environmental changes throughout fruit development, young and ripening berries were sampled simultaneously on continuously flowering microvines acclimated to controlled circadian light and temperature changes. Gene expression profiles along fruit development were monitored during both day and night with whole genome microarrays (Nimblegen® vitis 12x), yielding a total number of 9273 developmentally modulated probesets. All day-detected transcripts were modulated at night, whereas 1843 genes were night-specific. Very similar developmental patterns of gene expression were observed using independent hierarchical clustering of day and night data, whereas functional categories of allocated transcripts varied according to time of day. Many transcripts within pathways, known to be up-regulated during ripening, in particular those linked to secondary metabolism exhibited a clearer developmental regulation at night than during the day. Functional enrichment analysis also indicated that diurnally modulated genes considerably varied during fruit development, with a shift from cellular organization and photosynthesis in green berries to secondary metabolism and stress-related genes in ripening berries. These results reveal critical changes in gene expression during night development that differ from daytime development, which have not been observed in other transcriptomic studies on fruit development thus far.

Understanding the Broad Influence of Sex Hormones and Sex Differences in the Brain

PubMed Central

McEwen, Bruce S.; Milner, Teresa A.

2016-01-01

Sex hormones act throughout the entire brain of both males and females via both genomic and non-genomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes where they are associated with presynaptic terminals, mitochondria, spine apparatus, post-synaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects upon gene expression induce spine synapses, up- or down-regulate and alter the distribution of neurotransmitter receptors, regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not-yet-precisely-defined genetic factors including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, and upon functions not previously regarded as subject to such differences, indicates that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. PMID:27870427

No boundaries: genomes, organisms, and ecological interactions responsible for divergence and reproductive isolation.

PubMed

Etges, William J

2014-01-01

Revealing the genetic basis of traits that cause reproductive isolation, particularly premating or sexual isolation, usually involves the same challenges as most attempts at genotype-phenotype mapping and so requires knowledge of how these traits are expressed in different individuals, populations, and environments, particularly under natural conditions. Genetic dissection of speciation phenotypes thus requires understanding of the internal and external contexts in which underlying genetic elements are expressed. Gene expression is a product of complex interacting factors internal and external to the organism including developmental programs, the genetic background including nuclear-cytotype interactions, epistatic relationships, interactions among individuals or social effects, stochasticity, and prevailing variation in ecological conditions. Understanding of genomic divergence associated with reproductive isolation will be facilitated by functional expression analysis of annotated genomes in organisms with well-studied evolutionary histories, phylogenetic affinities, and known patterns of ecological variation throughout their life cycles. I review progress and prospects for understanding the pervasive role of host plant use on genetic and phenotypic expression of reproductive isolating mechanisms in cactophilic Drosophila mojavensis and suggest how this system can be used as a model for revealing the genetic basis for species formation in organisms where speciation phenotypes are under the joint influences of genetic and environmental factors. © The American Genetic Association. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Live imaging of muscles in Drosophila metamorphosis: Towards high-throughput gene identification and function analysis.

PubMed

Puah, Wee Choo; Wasser, Martin

2016-03-01

Time-lapse microscopy in developmental biology is an emerging tool for functional genomics. Phenotypic effects of gene perturbations can be studied non-invasively at multiple time points in chronological order. During metamorphosis of Drosophila melanogaster, time-lapse microscopy using fluorescent reporters allows visualization of alternative fates of larval muscles, which are a model for the study of genes related to muscle wasting. While doomed muscles enter hormone-induced programmed cell death, a smaller population of persistent muscles survives to adulthood and undergoes morphological remodeling that involves atrophy in early, and hypertrophy in late pupation. We developed a method that combines in vivo imaging, targeted gene perturbation and image analysis to identify and characterize genes involved in muscle development. Macrozoom microscopy helps to screen for interesting muscle phenotypes, while confocal microscopy in multiple locations over 4-5 days produces time-lapse images that are used to quantify changes in cell morphology. Performing a similar investigation using fixed pupal tissues would be too time-consuming and therefore impractical. We describe three applications of our pipeline. First, we show how quantitative microscopy can track and measure morphological changes of muscle throughout metamorphosis and analyze genes involved in atrophy. Second, our assay can help to identify genes that either promote or prevent histolysis of abdominal muscles. Third, we apply our approach to test new fluorescent proteins as live markers for muscle development. We describe mKO2 tagged Cysteine proteinase 1 (Cp1) and Troponin-I (TnI) as examples of proteins showing developmental changes in subcellular localization. Finally, we discuss strategies to improve throughput of our pipeline to permit genome-wide screens in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A Process Evaluation of Project Developmental Continuity. Interim Report II, Part A: Program Case Studies. Volume 2.

ERIC Educational Resources Information Center

Spencer, Lynn, Ed.

These 7 case studies are part of a series of documents on the evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. Each case study reviews the planning year at a PDC demonstration site in one…

A Process Evaluation of Project Developmental Continuity. Interim Report II, Part A: Program Case Studies. Volume I.

ERIC Educational Resources Information Center

Spencer, Lynn, Ed.

These 8 case studies are part of a series of documents on the evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. Each case study reviews the planning year at a PDC demonstration site in one…

The Biggest Mover: Empowering Students with Intellectual and Developmental Delays and Physical Challenges

ERIC Educational Resources Information Center

Brown, Michelle J.

2018-01-01

The Biggest Mover Program, an educational program to improve daily exercise and healthy eating was developed to address the learning needs of students with intellectual and developmental disabilities and physical challenges. The program was part of a three-part program to improve the knowledge of students, staff, and teachers through the use of…

After-School Youth Development Programs: A Developmental-Ecological Model of Current Research

ERIC Educational Resources Information Center

Riggs, Nathaniel R.; Greenberg, Mark T.

2004-01-01

Although there has been a rapid increase in funding and attention to after-school programs, there is little understanding of how after-school programs impact children's developmental trajectories. The heterogeneity of American children makes it very unlikely that all children need after-school programming or that there is but one brand of…

Experiences of Families with Relatives with Intellectual and Developmental Disabilities in a Consumer-Directed Support Program

ERIC Educational Resources Information Center

Caldwell, Joe

2007-01-01

The current study explores the experiences of families with relatives with intellectual and developmental disabilities participating in a consumer-directed support program in the USA. The Illinois Home Based Support Services Program provides a limited budget to purchase and manage services. However, within recent years the program has faced cuts…

Language Development Component, Secondary Developmental Reading Program. Final Evaluation Report.

ERIC Educational Resources Information Center

Beck, Donald; Chamberlain, Ed

This report evaluates the Secondary Developmental Reading Program, a component of the Ohio Disadvantaged Pupil Program Fund (DPPF), in terms of the 1982-83 program objectives. Twelve project reading teachers worked in eight Columbus senior high schools with 843 pupils scoring at or below the 36th percentile in reading achievement. A pilot project…

Characterization of a complex chromosomal rearrangement using chromosome, FISH, and microarray assays in a girl with multiple congenital abnormalities and developmental delay

PubMed Central

2014-01-01

Complex chromosomal rearrangements (CCRs) are balanced or unbalanced structural rearrangements involving three or more cytogenetic breakpoints on two or more chromosomal pairs. The phenotypic anomalies in such cases are attributed to gene disruption, superimposed cryptic imbalances in the genome, and/or position effects. We report a 14-year-old girl who presented with multiple congenital anomalies and developmental delay. Chromosome and FISH analysis indicated a highly complex chromosomal rearrangement involving three chromosomes (3, 7 and 12), seven breakpoints as a result of one inversion, two insertions, and two translocations forming three derivative chromosomes. Additionally, chromosomal microarray study (CMA) revealed two submicroscopic deletions at 3p12.3 (467 kb) and 12q13.12 (442 kb). We postulate that microdeletion within the ROBO1 gene at 3p12.3 may have played a role in the patient’s developmental delay, since it has potential activity-dependent role in neurons. Additionally, factors other than genomic deletions such as loss of function or position effects may also contribute to the abnormal phenotype in our patient. PMID:25478007

Sordaria macrospora, a model organism to study fungal cellular development.

PubMed

Engh, Ines; Nowrousian, Minou; Kück, Ulrich

2010-12-01

During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

Genes and networks regulating root anatomy and architecture.

PubMed

Wachsman, Guy; Sparks, Erin E; Benfey, Philip N

2015-10-01

The root is an excellent model for studying developmental processes that underlie plant anatomy and architecture. Its modular structure, the lack of cell movement and relative accessibility to microscopic visualization facilitate research in a number of areas of plant biology. In this review, we describe several examples that demonstrate how cell type-specific developmental mechanisms determine cell fate and the formation of defined tissues with unique characteristics. In the last 10 yr, advances in genome-wide technologies have led to the sequencing of thousands of plant genomes, transcriptomes and proteomes. In parallel with the development of these high-throughput technologies, biologists have had to establish computational, statistical and bioinformatic tools that can deal with the wealth of data generated by them. These resources provide a foundation for posing more complex questions about molecular interactions, and have led to the discovery of new mechanisms that control phenotypic differences. Here we review several recent studies that shed new light on developmental processes, which are involved in establishing root anatomy and architecture. We highlight the power of combining large-scale experiments with classical techniques to uncover new pathways in root development. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The Capsaspora genome reveals a complex unicellular prehistory of animals.

PubMed

Suga, Hiroshi; Chen, Zehua; de Mendoza, Alex; Sebé-Pedrós, Arnau; Brown, Matthew W; Kramer, Eric; Carr, Martin; Kerner, Pierre; Vervoort, Michel; Sánchez-Pons, Núria; Torruella, Guifré; Derelle, Romain; Manning, Gerard; Lang, B Franz; Russ, Carsten; Haas, Brian J; Roger, Andrew J; Nusbaum, Chad; Ruiz-Trillo, Iñaki

2013-01-01

To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filasterean Capsaspora owczarzaki, the closest known unicellular relative of metazoans besides choanoflagellates. Analyses of this genome alter our understanding of the molecular complexity of metazoans' unicellular ancestors showing that they had a richer repertoire of proteins involved in cell adhesion and transcriptional regulation than previously inferred only with the choanoflagellate genome. Some of these proteins were secondarily lost in choanoflagellates. In contrast, most intercellular signalling systems controlling development evolved later concomitant with the emergence of the first metazoans. We propose that the acquisition of these metazoan-specific developmental systems and the co-option of pre-existing genes drove the evolutionary transition from unicellular protists to metazoans.

Evolution and coevolution of developmental programs

NASA Astrophysics Data System (ADS)

Jacob, Christian

1999-09-01

The developmental processes of single organisms, such as growth and structure formation, can be described by parallel rewrite systems in the form of Lindenmayer systems, which also allow one to generate geometrical structures in 3D space using turtle interpretation. We present examples of L-systems for growth programs of plant-like structures. Evolution-based programming techniques are applied to design L-systems by Genetic L-system Programming (GLP), demonstrating how developmental programs for plants, exhibiting specific morphogenetic properties can be interactively bred or automatically evolved. Finally, we demonstrate coevolutionary effects among plant populations consisting of different species, interacting with each other, competing for resources like sunlight and nutrients, and evolving successful reproduction strategies in their specific environments.

Expanding Omics Resources for Improvement of Soybean Seed Composition Traits

PubMed Central

Chaudhary, Juhi; Patil, Gunvant B.; Sonah, Humira; Deshmukh, Rupesh K.; Vuong, Tri D.; Valliyodan, Babu; Nguyen, Henry T.

2015-01-01

Food resources of the modern world are strained due to the increasing population. There is an urgent need for innovative methods and approaches to augment food production. Legume seeds are major resources of human food and animal feed with their unique nutrient compositions including oil, protein, carbohydrates, and other beneficial nutrients. Recent advances in next-generation sequencing (NGS) together with “omics” technologies have considerably strengthened soybean research. The availability of well annotated soybean genome sequence along with hundreds of identified quantitative trait loci (QTL) associated with different seed traits can be used for gene discovery and molecular marker development for breeding applications. Despite the remarkable progress in these technologies, the analysis and mining of existing seed genomics data are still challenging due to the complexity of genetic inheritance, metabolic partitioning, and developmental regulations. Integration of “omics tools” is an effective strategy to discover key regulators of various seed traits. In this review, recent advances in “omics” approaches and their use in soybean seed trait investigations are presented along with the available databases and technological platforms and their applicability in the improvement of soybean. This article also highlights the use of modern breeding approaches, such as genome-wide association studies (GWAS), genomic selection (GS), and marker-assisted recurrent selection (MARS) for developing superior cultivars. A catalog of available important resources for major seed composition traits, such as seed oil, protein, carbohydrates, and yield traits are provided to improve the knowledge base and future utilization of this information in the soybean crop improvement programs. PMID:26635846

Function and Evolution of DNA Methylation in Nasonia vitripennis

PubMed Central

Wang, Xu; Wheeler, David; Avery, Amanda; Rago, Alfredo; Choi, Jeong-Hyeon; Colbourne, John K.; Clark, Andrew G.; Werren, John H.

2013-01-01

The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5′ regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5′ and 3′ UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression. PMID:24130511

Embryonic and larval development in the Midas cichlid fish species flock (Amphilophus spp.): a new evo-devo model for the investigation of adaptive novelties and species differences.

PubMed

Kratochwil, Claudius F; Sefton, Maggie M; Meyer, Axel

2015-02-26

Central American crater lake cichlid fish of the Midas species complex (Amphilophus spp.) are a model system for sympatric speciation and fast ecological diversification and specialization. Midas cichlids have been intensively analyzed from an ecological and morphological perspective. Genomic resources such as transcriptomic and genomic data sets, and a high-quality draft genome are available now. Many ecologically relevant species-specific traits and differences such as pigmentation and cranial morphology arise during development. Detailed descriptions of the early development of the Midas cichlid in particular, will help to investigate the ontogeny of species differences and adaptations. We describe the embryonic and larval development of the crater lake cichlid, Amphilophus xiloaensis, until seven days after fertilization. Similar to previous studies on teleost development, we describe six periods of embryogenesis - the zygote, cleavage, blastula, gastrula, segmentation, and post-hatching period. Furthermore, we define homologous stages to well-described teleost models such as medaka and zebrafish, as well as other cichlid species such as the Nile tilapia and the South American cichlid Cichlasoma dimerus. Key morphological differences between the embryos of Midas cichlids and other teleosts are highlighted and discussed, including the presence of adhesive glands and different early chromatophore patterns, as well as variation in developmental timing. The developmental staging of the Midas cichlid will aid researchers in the comparative investigation of teleost ontogenies. It will facilitate comparative developmental biological studies of Neotropical and African cichlid fish in particular. In the past, the species flocks of the African Great Lakes have received the most attention from researchers, but some lineages of the 300-400 species of Central American lakes are fascinating model systems for adaptive radiation and rapid phenotypic evolution. The availability of genetic resources, their status as a model system for evolutionary research, and the possibility to perform functional experiments including transgenesis makes the Midas cichlid complex a very attractive model for evolutionary-developmental research.

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.

Sequential Turnovers of Sex Chromosomes in African Clawed Frogs (Xenopus) Suggest Some Genomic Regions Are Good at Sex Determination

PubMed Central

Furman, Benjamin L. S.; Evans, Ben J.

2016-01-01

Sexual differentiation is fundamentally important for reproduction, yet the genetic triggers of this developmental process can vary, even between closely related species. Recent studies have uncovered, for example, variation in the genetic triggers for sexual differentiation within and between species of African clawed frogs (genus Xenopus). Here, we extend these discoveries by demonstrating that yet another sex determination system exists in Xenopus, specifically in the species Xenopus borealis. This system evolved recently in an ancestor of X. borealis that had the same sex determination system as X. laevis, a system which itself is newly evolved. Strikingly, the genomic region carrying the sex determination factor in X. borealis is homologous to that of therian mammals, including humans. Our results offer insights into how the genetic underpinnings of conserved phenotypes evolve, and suggest an important role for cooption of genetic building blocks with conserved developmental roles. PMID:27605520

Effects of Staff Implementation of a Choice Program on Challenging Behaviors in Persons with Developmental Disabilities.

ERIC Educational Resources Information Center

Ip, Sau M. V.; And Others

1994-01-01

Describes quasiexperimental investigation constructed to examine effects of staff implementation of choice program on reduction of challenging behaviors of people with developmental disabilities residing in supported community residences. Results suggest that choice program implementation produced significant decreases in frequency and severity of…

In-Home Respite Care Program Development. Background. Coordinator's Manual. Training Manual.

ERIC Educational Resources Information Center

Parham, J. D.; And Others

This volume consists of a background discussion, coordinator's manual, and training manual dealing with developing programs for the in-home respite care (IHRC) of the developmentally disabled. Addressed in the background information unit are the nature of developmental disabilities; program variables, planning, and funding; and practical…

75 FR 26846 - Genomic Medicine Program Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-12

... DEPARTMENT OF VETERANS AFFAIRS Genomic Medicine Program Advisory Committee; Notice of Meeting The...) that the Genomic Medicine Program Advisory Committee will meet on May 21, 2010, at the Westin... appropriate ethical oversight and protecting the privacy of Veterans; presentations on genomic medicine...

Transcriptome profiling of the demosponge Amphimedon queenslandica reveals genome-wide events that accompany major life cycle transitions

PubMed Central

2012-01-01

Background The biphasic life cycle with pelagic larva and benthic adult stages is widely observed in the animal kingdom, including the Porifera (sponges), which are the earliest branching metazoans. The demosponge, Amphimedon queenslandica, undergoes metamorphosis from a free-swimming larva into a sessile adult that bears no morphological resemblance to other animals. While the genome of A. queenslandica contains an extensive repertoire of genes very similar to that of complex bilaterians, it is as yet unclear how this is drawn upon to coordinate changing morphological features and ecological demands throughout the sponge life cycle. Results To identify genome-wide events that accompany the pelagobenthic transition in A. queenslandica, we compared global gene expression profiles at four key developmental stages by sequencing the poly(A) transcriptome using SOLiD technology. Large-scale changes in transcription were observed as sponge larvae settled on the benthos and began metamorphosis. Although previous systematics suggest that the only clear homology between Porifera and other animals is in the embryonic and larval stages, we observed extensive use of genes involved in metazoan-associated cellular processes throughout the sponge life cycle. Sponge-specific transcripts are not over-represented in the morphologically distinct adult; rather, many genes that encode typical metazoan features, such as cell adhesion and immunity, are upregulated. Our analysis further revealed gene families with candidate roles in competence, settlement, and metamorphosis in the sponge, including transcription factors, G-protein coupled receptors and other signaling molecules. Conclusions This first genome-wide study of the developmental transcriptome in an early branching metazoan highlights major transcriptional events that accompany the pelagobenthic transition and point to a network of regulatory mechanisms that coordinate changes in morphology with shifting environmental demands. Metazoan developmental and structural gene orthologs are well-integrated into the expression profiles at every stage of sponge development, including the adult. The utilization of genes involved in metazoan-associated processes throughout sponge development emphasizes the potential of the genome of the last common ancestor of animals to generate phenotypic complexity. PMID:22646746

History of the DOE Human Genome Program

Science.gov Websites

History of the DOE Human Genome Program The following history is taken from the U.S. Department of Energy 1991-91 Human Genome Program Report (June 1992). This is an archived item. A brief history of the U.S. Department of Energy (DOE) Human Genome Program will be useful in a discussion of the objectives

45 CFR 1386.103 - Discovery.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS Practice and Procedure for Hearings Pertaining to States...

Intrapopulation Genome Size Variation in D. melanogaster Reflects Life History Variation and Plasticity

PubMed Central

Ellis, Lisa L.; Huang, Wen; Quinn, Andrew M.; Ahuja, Astha; Alfrejd, Ben; Gomez, Francisco E.; Hjelmen, Carl E.; Moore, Kristi L.; Mackay, Trudy F. C.; Johnston, J. Spencer; Tarone, Aaron M.

2014-01-01

We determined female genome sizes using flow cytometry for 211 Drosophila melanogaster sequenced inbred strains from the Drosophila Genetic Reference Panel, and found significant conspecific and intrapopulation variation in genome size. We also compared several life history traits for 25 lines with large and 25 lines with small genomes in three thermal environments, and found that genome size as well as genome size by temperature interactions significantly correlated with survival to pupation and adulthood, time to pupation, female pupal mass, and female eclosion rates. Genome size accounted for up to 23% of the variation in developmental phenotypes, but the contribution of genome size to variation in life history traits was plastic and varied according to the thermal environment. Expression data implicate differences in metabolism that correspond to genome size variation. These results indicate that significant genome size variation exists within D. melanogaster and this variation may impact the evolutionary ecology of the species. Genome size variation accounts for a significant portion of life history variation in an environmentally dependent manner, suggesting that potential fitness effects associated with genome size variation also depend on environmental conditions. PMID:25057905

Stress and the Emerging Roles of Chromatin Remodeling in Signal Integration and Stable Transmission of Reversible Phenotypes

PubMed Central

Weaver, Ian C. G.; Korgan, Austin C.; Lee, Kristen; Wheeler, Ryan V.; Hundert, Amos S.; Goguen, Donna

2017-01-01

The influence of early life experience and degree of parental-infant attachment on emotional development in children and adolescents has been comprehensively studied. Structural and mechanistic insight into the biological foundation and maintenance of mammalian defensive systems (metabolic, immune, nervous and behavioral) is slowly advancing through the emerging field of developmental molecular (epi)genetics. Initial evidence revealed that differential nurture early in life generates stable differences in offspring hypothalamic-pituitary-adrenal (HPA) regulation, in part, through chromatin remodeling and changes in DNA methylation of specific genes expressed in the brain, revealing physical, biochemical and molecular paths for the epidemiological concept of gene-environment interactions. Herein, a primary molecular mechanism underpinning the early developmental programming and lifelong maintenance of defensive (emotional) responses in the offspring is the alteration of chromatin domains of specific genomic regions from a condensed state (heterochromatin) to a transcriptionally accessible state (euchromatin). Conversely, DNA methylation promotes the formation of heterochromatin, which is essential for gene silencing, genomic integrity and chromosome segregation. Therefore, inter-individual differences in chromatin modifications and DNA methylation marks hold great potential for assessing the impact of both early life experience and effectiveness of intervention programs—from guided psychosocial strategies focused on changing behavior to pharmacological treatments that target chromatin remodeling and DNA methylation enzymes to dietary approaches that alter cellular pools of metabolic intermediates and methyl donors to affect nutrient bioavailability and metabolism. In this review article, we discuss the potential molecular mechanism(s) of gene regulation associated with chromatin modeling and programming of endocrine (e.g., HPA and metabolic or cardiovascular) and behavioral (e.g., fearfulness, vigilance) responses to stress, including alterations in DNA methylation and the role of DNA repair machinery. From parental history (e.g., drugs, housing, illness, nutrition, socialization) to maternal-offspring exchanges of nutrition, microbiota, antibodies and stimulation, the nature of nurture provides not only mechanistic insight into how experiences propagate from external to internal variables, but also identifies a composite therapeutic target, chromatin modeling, for gestational/prenatal stress, adolescent anxiety/depression and adult-onset neuropsychiatric disease. PMID:28360846

A Comparative Study of a Kodaly-Based Developmental Music Program and a Traditional Public School Music Program at the Kindergarten Level.

ERIC Educational Resources Information Center

Beatty, Rodger James

A 9-month longitudinal study of two kindergarten classes compared two types of music instruction: a Kodaly-based developmental music program and a traditional public school music program. The class taught through the Kodaly method received instruction that emphasized the development of rhythmic and melodic perception through visual, aural, and…

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

PubMed Central

Tain, You-Lin; Hsu, Chien-Ning

2017-01-01

Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

Developmental Programming of Adult Disease: Reprogramming by Melatonin?

PubMed Central

Tain, You-Lin; Huang, Li-Tung; Hsu, Chien-Ning

2017-01-01

Adult-onset chronic non-communicable diseases (NCDs) can originate from early life through so-called the “developmental origins of health and disease” (DOHaD) or “developmental programming”. The DOHaD concept offers the “reprogramming” strategy to shift the treatment from adulthood to early life, before clinical disease is apparent. Melatonin, an endogenous indoleamine produced by the pineal gland, has pleiotropic bioactivities those are beneficial in a variety of human diseases. Emerging evidence support that melatonin is closely inter-related to other proposed mechanisms contributing to the developmental programming of a variety of chronic NCDs. Recent animal studies have begun to unravel the multifunctional roles of melatonin in many experimental models of developmental programming. Even though some progress has been made in research on melatonin as a reprogramming strategy to prevent DOHaD-related NCDs, future human studies should aim at filling the translational gap between animal models and clinical trials. Here, we review several key themes on the reprogramming effects of melatonin in DOHaD research. We have particularly focused on the following areas: mechanisms of developmental programming; the interrelationship between melatonin and mechanisms underlying developmental programming; pathophysiological roles of melatonin in pregnancy and fetal development; and insight provided by animal models to support melatonin as a reprogramming therapy. Rates of NCDs are increasing faster than anticipated all over the world. Hence, there is an urgent need to understand reprogramming mechanisms of melatonin and to translate experimental research into clinical practice for halting a growing list of DOHaD-related NCDs. PMID:28212315

Prevalence and architecture of de novo mutations in developmental disorders.

PubMed

2017-02-23

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year.

High fat programming of beta cell compensation, exhaustion, death and dysfunction.

PubMed

Cerf, Marlon E

2015-03-01

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish.

PubMed

Kawahara, Atsuo; Hisano, Yu; Ota, Satoshi; Taimatsu, Kiyohito

2016-05-13

The zebrafish (Danio rerio) is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs) at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

Australian black field crickets show changes in neural gene expression associated with socially-induced morphological, life-history, and behavioral plasticity.

PubMed

Kasumovic, Michael M; Chen, Zhiliang; Wilkins, Marc R

2016-10-24

Ecological and evolutionary model organisms have provided extensive insight into the ecological triggers, adaptive benefits, and evolution of life-history driven developmental plasticity. Despite this, we still have a poor understanding of the underlying genetic changes that occur during shifts towards different developmental trajectories. The goal of this study is to determine whether we can identify underlying gene expression patterns that can describe the different life-history trajectories individuals follow in response to social cues of competition. To do this, we use the Australian black field cricket (Teleogryllus commodus), a species with sex-specific developmental trajectories moderated by the density and quality of calls heard during immaturity. In this study, we manipulated the social information males and females could hear by rearing individuals in either calling or silent treatments. We next used RNA-Seq to develop a reference transcriptome to study changes in brain gene expression at two points prior to sexual maturation. We show accelerated development in both sexes when exposed to calling; changes were also seen in growth, lifespan, and reproductive effort. Functional relationships between genes and phenotypes were apparent from ontological enrichment analysis. We demonstrate that increased investment towards traits such as growth and reproductive effort were often associated with the expression of a greater number of genes with similar effect, thus providing a suite of candidate genes for future research in this and other invertebrate organisms. Our results provide interesting insight into the genomic underpinnings of developmental plasticity and highlight the potential of a genomic exploration of other evolutionary theories such as condition dependence and sex-specific developmental strategies.

Characterization of transcriptome in the Indian meal moth Plodia interpunctella (Lepidoptera: Pyralidae) and gene expression analysis during developmental stages.

PubMed

Tang, Pei-An; Wu, Hai-Jing; Xue, Hao; Ju, Xing-Rong; Song, Wei; Zhang, Qi-Lin; Yuan, Ming-Long

2017-07-30

The Indian meal moth Plodia interpunctella (Lepidoptera: Pyralidae) is a worldwide pest that causes serious damage to stored foods. Although many efforts have been conducted on this species due to its economic importance, the study of genetic basis of development, behavior and insecticide resistance has been greatly hampered due to lack of genomic information. In this study, we used high throughput sequencing platform to perform a de novo transcriptome assembly and tag-based digital gene expression profiling (DGE) analyses across four different developmental stages of P. interpunctella (egg, third-instar larvae, pupae and adult). We obtained approximate 9gigabyte (GB) of clean data and recovered 84,938 unigenes, including 37,602 clusters and 47,336 singletons. These unigenes were annotated using BLAST against the non-redundant protein databases and then functionally classified based on Gene Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes databases (KEGG). A large number of differentially expressed genes were identified by pairwise comparisons among different developmental stages. Gene expression profiles dramatically changed between developmental stage transitions. Some of these differentially expressed genes were related to digestion and cuticularization. Quantitative real-time PCR results of six randomly selected genes conformed the findings in the DGEs. Furthermore, we identified over 8000 microsatellite markers and 97,648 single nucleotide polymorphisms which will be useful for population genetics studies of P. interpunctella. This transcriptomic information provided insight into the developmental basis of P. interpunctella and will be helpful for establishing integrated management strategies and developing new targets of insecticides for this serious pest. Copyright © 2017 Elsevier B.V. All rights reserved.

Descriptive vs. mechanistic network models in plant development in the post-genomic era.

PubMed

Davila-Velderrain, J; Martinez-Garcia, J C; Alvarez-Buylla, E R

2015-01-01

Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.

Zebrafish models for the functional genomics of neurogenetic disorders.

PubMed

Kabashi, Edor; Brustein, Edna; Champagne, Nathalie; Drapeau, Pierre

2011-03-01

In this review, we consider recent work using zebrafish to validate and study the functional consequences of mutations of human genes implicated in a broad range of degenerative and developmental disorders of the brain and spinal cord. Also we present technical considerations for those wishing to study their own genes of interest by taking advantage of this easily manipulated and clinically relevant model organism. Zebrafish permit mutational analyses of genetic function (gain or loss of function) and the rapid validation of human variants as pathological mutations. In particular, neural degeneration can be characterized at genetic, cellular, functional, and behavioral levels. Zebrafish have been used to knock down or express mutations in zebrafish homologs of human genes and to directly express human genes bearing mutations related to neurodegenerative disorders such as spinal muscular atrophy, ataxia, hereditary spastic paraplegia, amyotrophic lateral sclerosis (ALS), epilepsy, Huntington's disease, Parkinson's disease, fronto-temporal dementia, and Alzheimer's disease. More recently, we have been using zebrafish to validate mutations of synaptic genes discovered by large-scale genomic approaches in developmental disorders such as autism, schizophrenia, and non-syndromic mental retardation. Advances in zebrafish genetics such as multigenic analyses and chemical genetics now offer a unique potential for disease research. Thus, zebrafish hold much promise for advancing the functional genomics of human diseases, the understanding of the genetics and cell biology of degenerative and developmental disorders, and the discovery of therapeutics. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of the Affymetrix CytoScan® Dx Assay for Developmental Delay

PubMed Central

Webb, Bryn D.; Scharf, Rebecca J.; Spear, Emily A.; Edelmann, Lisa J.; Stroustrup, Annemarie

2015-01-01

The goal of molecular cytogenetic testing for children presenting with developmental delay is to identify or exclude genetic abnormalities that are associated with cognitive, behavioral, and/or motor symptoms. Until 2010, chromosome analysis was the standard first-line genetic screening test for evaluation of patients with developmental delay when a specific syndrome was not suspected. In 2010, The American College of Medical Genetics and several other groups recommended chromosomal microarray (CMA) as the first-line test in children with developmental delays, multiple congenital anomalies, and/or autism. This test is able to detect regions of genomic imbalances at a much finer resolution than G-banded karyotyping. Until recently, no CMA testing had been approved by the United States Food and Drug Administration (FDA). This review will focus on the use of the Affymetrix CytoScan® Dx Assay, the first CMA to receive FDA approval for the genetic evaluation of individuals with developmental delay. PMID:25350348

The Ciona intestinalis genome: when the constraints are off

NASA Technical Reports Server (NTRS)

Holland, Linda Z.; Gibson-Brown, Jeremy J.

2003-01-01

The recent genome sequencing of a non-vertebrate deuterostome, the ascidian tunicate Ciona intestinalis, makes a substantial contribution to the fields of evolutionary and developmental biology.1 Tunicates have some of the smallest bilaterian genomes, embryos with relatively few cells, fixed lineages and early determination of cell fates. Initial analyses of the C. intestinalis genome indicate that it has been evolving rapidly. Comparisons with other bilaterians show that C. intestinalis has lost a number of genes, and that many genes linked together in most other bilaterians have become uncoupled. In addition, a number of independent, lineage-specific gene duplications have been detected. These new results, although interesting in themselves, will take on a deeper significance once the genomes of additional invertebrate deuterostomes (e.g. echinoderms, hemichordates and amphioxus) have been sequenced. With such a broadened database, comparative genomics can begin to ask pointed questions about the relationship between the evolution of genomes and the evolution of body plans. Copyright 2003 Wiley Periodicals, Inc.

The dynamic genome of Hydra.

PubMed

Chapman, Jarrod A; Kirkness, Ewen F; Simakov, Oleg; Hampson, Steven E; Mitros, Therese; Weinmaier, Thomas; Rattei, Thomas; Balasubramanian, Prakash G; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E; Putnam, Nicholas H; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E; Gee, Lydia; Kibler, Dennis F; Law, Lee; Lindgens, Dirk; Martinez, Daniel E; Peng, Jisong; Wigge, Philip A; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R H; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M; Wheeler, Benjamin M; Peterson, Kevin J; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C G; Holstein, Thomas W; Fujisawa, Toshitaka; Bode, Hans R; David, Charles N; Rokhsar, Daniel S; Steele, Robert E

2010-03-25

The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.

45 CFR 1386.19 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of...

Dynamics of DNA methylomes underlie oyster development

PubMed Central

Sourdaine, Pascal; Guo, Ximing; Favrel, Pascal

2017-01-01

DNA methylation is a critical epigenetic regulator of development in mammals and social insects, but its significance in development outside these groups is not understood. Here we investigated the genome-wide dynamics of DNA methylation in a mollusc model, the oyster Crassostrea gigas, from the egg to the completion of organogenesis. Large-scale methylation maps reveal that the oyster genome displays a succession of methylated and non methylated regions, which persist throughout development. Differentially methylated regions (DMRs) are strongly regulated during cleavage and metamorphosis. The distribution and levels of methylated DNA within genomic features (exons, introns, promoters, repeats and transposons) show different developmental lansdscapes marked by a strong increase in the methylation of exons against introns after metamorphosis. Kinetics of methylation in gene-bodies correlate to their transcription regulation and to distinct functional gene clusters, and DMRs at cleavage and metamorphosis bear the genes functionally related to these steps, respectively. This study shows that DNA methylome dynamics underlie development through transcription regulation in the oyster, a lophotrochozoan species. To our knowledge, this is the first demonstration of such epigenetic regulation outside vertebrates and ecdysozoan models, bringing new insights into the evolution and the epigenetic regulation of developmental processes. PMID:28594821

Dynamics of DNA methylomes underlie oyster development.

PubMed

Riviere, Guillaume; He, Yan; Tecchio, Samuele; Crowell, Elizabeth; Gras, Michaël; Sourdaine, Pascal; Guo, Ximing; Favrel, Pascal

2017-06-01

DNA methylation is a critical epigenetic regulator of development in mammals and social insects, but its significance in development outside these groups is not understood. Here we investigated the genome-wide dynamics of DNA methylation in a mollusc model, the oyster Crassostrea gigas, from the egg to the completion of organogenesis. Large-scale methylation maps reveal that the oyster genome displays a succession of methylated and non methylated regions, which persist throughout development. Differentially methylated regions (DMRs) are strongly regulated during cleavage and metamorphosis. The distribution and levels of methylated DNA within genomic features (exons, introns, promoters, repeats and transposons) show different developmental lansdscapes marked by a strong increase in the methylation of exons against introns after metamorphosis. Kinetics of methylation in gene-bodies correlate to their transcription regulation and to distinct functional gene clusters, and DMRs at cleavage and metamorphosis bear the genes functionally related to these steps, respectively. This study shows that DNA methylome dynamics underlie development through transcription regulation in the oyster, a lophotrochozoan species. To our knowledge, this is the first demonstration of such epigenetic regulation outside vertebrates and ecdysozoan models, bringing new insights into the evolution and the epigenetic regulation of developmental processes.

Formative Evaluation in a Cognitive Developmental Program for Young Children.

ERIC Educational Resources Information Center

Willis, Sherry L.; And Others

The Cognitive Developmental Early Childhood program at Pennsylvania State University has formulated a program, curriculum, and evaluation system guided by Piagetian theory. The evaluation system described in this paper is a result of an intensive examination of the purposes and types of evaluation systems for their compatibility with the Piagetian…

A Report on College-Level Remedial/Developmental Programs in SREB States.

ERIC Educational Resources Information Center

Abraham, Ansley A., Jr.

Remedial and developmental programs at two-year and four-year colleges in states belonging to the Southern Regional Education Board (SREB) were studied, along with placement standards for degree-credit, college-level work in SREB states and institutions. These programs, courses, and activities were designed specifically for first-time entering…

Initiating a Developmental Motor Skills Program for Identified Primary Students.

ERIC Educational Resources Information Center

Harville, Valerie Terrill

A physical education specialist at an elementary school in one of the fastest growing sections of the country developed and implemented a developmental motor skills program for primary school students. The program focused on: (1) developing a method of referring students for testing; (2) providing a specialized motor diagnostic test; (3) improving…

Plant Reactome: a resource for plant pathways and comparative analysis

PubMed Central

Naithani, Sushma; Preece, Justin; D'Eustachio, Peter; Gupta, Parul; Amarasinghe, Vindhya; Dharmawardhana, Palitha D.; Wu, Guanming; Fabregat, Antonio; Elser, Justin L.; Weiser, Joel; Keays, Maria; Fuentes, Alfonso Munoz-Pomer; Petryszak, Robert; Stein, Lincoln D.; Ware, Doreen; Jaiswal, Pankaj

2017-01-01

Plant Reactome (http://plantreactome.gramene.org/) is a free, open-source, curated plant pathway database portal, provided as part of the Gramene project. The database provides intuitive bioinformatics tools for the visualization, analysis and interpretation of pathway knowledge to support genome annotation, genome analysis, modeling, systems biology, basic research and education. Plant Reactome employs the structural framework of a plant cell to show metabolic, transport, genetic, developmental and signaling pathways. We manually curate molecular details of pathways in these domains for reference species Oryza sativa (rice) supported by published literature and annotation of well-characterized genes. Two hundred twenty-two rice pathways, 1025 reactions associated with 1173 proteins, 907 small molecules and 256 literature references have been curated to date. These reference annotations were used to project pathways for 62 model, crop and evolutionarily significant plant species based on gene homology. Database users can search and browse various components of the database, visualize curated baseline expression of pathway-associated genes provided by the Expression Atlas and upload and analyze their Omics datasets. The database also offers data access via Application Programming Interfaces (APIs) and in various standardized pathway formats, such as SBML and BioPAX. PMID:27799469

Metabolic pathways in tropical dicotyledonous albuminous seeds: Coffea arabica as a case study

PubMed Central

Joët, Thierry; Laffargue, Andréina; Salmona, Jordi; Doulbeau, Sylvie; Descroix, Frédéric; Bertrand, Benoît; de Kochko, Alexandre; Dussert, Stéphane

2009-01-01

The genomic era facilitates the understanding of how transcriptional networks are interconnected to program seed development and filling. However, to date, little information is available regarding dicot seeds with a transient perisperm and a persistent, copious endosperm. Coffea arabica is the subject of increasing genomic research and is a model for nonorthodox albuminous dicot seeds of tropical origin. The aim of this study was to reconstruct the metabolic pathways involved in the biosynthesis of the main coffee seed storage compounds, namely cell wall polysaccharides, triacylglycerols, sucrose, and chlorogenic acids. For this purpose, we integrated transcriptomic and metabolite analyses, combining real-time RT-PCR performed on 137 selected genes (of which 79 were uncharacterized in Coffea) and metabolite profiling. Our map-drawing approach derived from model plants enabled us to propose a rationale for the peculiar traits of the coffee endosperm, such as its unusual fatty acid composition, remarkable accumulation of chlorogenic acid and cell wall polysaccharides. Comparison with the developmental features of exalbuminous seeds described in the literature revealed that the two seed types share important regulatory mechanisms for reserve biosynthesis, independent of the origin and ploidy level of the storage tissue. PMID:19207685

Developmentally programmed DNA splicing in Paramecium reveals short-distance crosstalk between DNA cleavage sites

PubMed Central

Gratias, Ariane; Lepère, Gersende; Garnier, Olivier; Rosa, Sarah; Duharcourt, Sandra; Malinsky, Sophie; Meyer, Eric; Bétermier, Mireille

2008-01-01

Somatic genome assembly in the ciliate Paramecium involves the precise excision of thousands of short internal eliminated sequences (IESs) that are scattered throughout the germline genome and often interrupt open reading frames. Excision is initiated by double-strand breaks centered on the TA dinucleotides that are conserved at each IES boundary, but the factors that drive cleavage site recognition remain unknown. A degenerate consensus was identified previously at IES ends and genetic analyses confirmed the participation of their nucleotide sequence in efficient excision. Even for wild-type IESs, however, variant excision patterns (excised or nonexcised) may be inherited maternally through sexual events, in a homology-dependent manner. We show here that this maternal epigenetic control interferes with the targeting of DNA breaks at IES ends. Furthermore, we demonstrate that a mutation in the TA at one end of an IES impairs DNA cleavage not only at the mutant end but also at the wild-type end. We conclude that crosstalk between both ends takes place prior to their cleavage and propose that the ability of an IES to adopt an excision-prone conformation depends on the combination of its nucleotide sequence and of additional determinants. PMID:18420657

Exploitation of induced 2n-gametes for plant breeding.

PubMed

Younis, Adnan; Hwang, Yoon-Jung; Lim, Ki-Byung

2014-02-01

Unreduced gamete formation derived via abnormal meiotic cell division is an important approach to polyploidy breeding. This process is considered the main driving force in spontaneous polyploids formation in nature, but the potential application of these gametes to plant breeding has not been fully exploited. An effective mechanism for their artificial induction is needed to attain greater genetic variation and enable efficient use of unreduced gametes in breeding programs. Different approaches have been employed for 2n-pollen production including interspecific hybridization, manipulation of environmental factors and treatment with nitrous oxide, trifluralin, colchicine, oryzalin and other chemicals. These chemicals can act as a stimulus to produce viable 2n pollen; however, their exact mode of action, optimum concentration and developmental stages are still not known. Identification of efficient methods of inducing 2n-gamete formation will help increase pollen germination of sterile interspecific hybrids for inter-genomic recombination and introgression breeding to develop new polyploid cultivars and increase heterozygosity among plant populations. Additionally, the application of genomic tools and identification and isolation of genes and mechanisms involved in the induction of 2n-gamete will enable increased exploitation in different plant species, which will open new avenues for plant breeding.

Structure and expression of genes for a class of cysteine-rich proteins of the cuticle layers of differentiating wool and hair follicles

PubMed Central

1990-01-01

The major histological components of the hair follicle are the hair cortex and cuticle. The hair cuticle cells encase and protect the cortex and undergo a different developmental program to that of the cortex. We report the molecular characterization of a set of evolutionarily conserved hair genes which are transcribed in the hair cuticle late in follicle development. Two genes were isolated and characterized, one expressed in the human follicle and one in the sheep follicle. Each gene encodes a small protein of 16 kD, containing greater than 50 cysteine residues, ranging from 31 to 36 mol% cysteine. Their high cysteine content and in vitro expression data identify them as ultra-high-sulfur (UHS) keratin proteins. The predicted proteins are composed almost entirely of cysteine-rich and glycine-rich repeats. Genomic blots reveal that the UHS keratin proteins are encoded by related multigene families in both the human and sheep genomes. Tissue in situ hybridization demonstrates that the expression of both genes is localized to the hair fiber cuticle and occurs at a late stage in fiber morphogenesis. PMID:1703541

27nt-RNAs guide histone variant deposition via 'RNA-induced DNA replication interference' and thus transmit parental genome partitioning in Stylonychia.

PubMed

Postberg, Jan; Jönsson, Franziska; Weil, Patrick Philipp; Bulic, Aneta; Juranek, Stefan Andreas; Lipps, Hans-Joachim

2018-06-12

During sexual reproduction in the unicellular ciliate Stylonychia somatic macronuclei differentiate from germline micronuclei. Thereby, programmed sequence reduction takes place, leading to the elimination of > 95% of germline sequences, which priorly adopt heterochromatin structure via H3K27me3. Simultaneously, 27nt-ncRNAs become synthesized from parental transcripts and are bound by the Argonaute protein PIWI1. These 27nt-ncRNAs cover sequences destined to the developing macronucleus and are thought to protect them from degradation. We provide evidence and propose that RNA/DNA base-pairing guides PIWI1/27nt-RNA complexes to complementary macronucleus-destined DNA target sequences, hence transiently causing locally stalled replication during polytene chromosome formation. This spatiotemporal delay enables the selective deposition of temporarily available histone H3.4K27me3 nucleosomes at all other sequences being continuously replicated, thus dictating their prospective heterochromatin structure before becoming developmentally eliminated. Concomitantly, 27nt-RNA-covered sites remain protected. We introduce the concept of 'RNA-induced DNA replication interference' and explain how the parental functional genome partition could become transmitted to the progeny.

Deep analysis of wild Vitis flower transcriptome reveals unexplored genome regions associated with sex specification.

PubMed

Ramos, Miguel Jesus Nunes; Coito, João Lucas; Fino, Joana; Cunha, Jorge; Silva, Helena; de Almeida, Patrícia Gomes; Costa, Maria Manuela Ribeiro; Amâncio, Sara; Paulo, Octávio S; Rocheta, Margarida

2017-01-01

RNA-seq of Vitis during early stages of bud development, in male, female and hermaphrodite flowers, identified new loci outside of annotated gene models, suggesting their involvement in sex establishment. The molecular mechanisms responsible for flower sex specification remain unclear for most plant species. In the case of V. vinifera ssp. vinifera, it is not fully understood what determines hermaphroditism in the domesticated subspecies and male or female flowers in wild dioecious relatives (Vitis vinifera ssp. sylvestris). Here, we describe a de novo assembly of the transcriptome of three flower developmental stages from the three Vitis vinifera flower types. The validation of de novo assembly showed a correlation of 0.825. The main goals of this work were the identification of V. v. sylvestris exclusive transcripts and the characterization of differential gene expression during flower development. RNA from several flower developmental stages was used previously to generate Illumina sequence reads. Through a sequential de novo assembly strategy one comprehensive transcriptome comprising 95,516 non-redundant transcripts was assembled. From this dataset 81,064 transcripts were annotated to V. v. vinifera reference transcriptome and 11,084 were annotated against V. v. vinifera reference genome. Moreover, we found 3368 transcripts that could not be mapped to Vitis reference genome. From all the non-redundant transcripts that were assembled, bioinformatics analysis identified 133 specific of V. v. sylvestris and 516 transcripts differentially expressed among the three flower types. The detection of transcription from areas of the genome not currently annotated suggests active transcription of previously unannotated genomic loci during early stages of bud development.

Correlation of LNCR rasiRNAs Expression with Heterochromatin Formation during Development of the Holocentric Insect Spodoptera frugiperda

PubMed Central

Stanojcic, Slavica; Gimenez, Sylvie; Permal, Emmanuelle; Cousserans, François; Quesneville, Hadi; Fournier, Philippe; d'Alençon, Emmanuelle

2011-01-01

Repeat-associated small interfering RNAs (rasiRNAs) are derived from various genomic repetitive elements and ensure genomic stability by silencing endogenous transposable elements. Here we describe a novel subset of 46 rasiRNAs named LNCR rasiRNAs due to their homology with one long non-coding RNA (LNCR) of Spodoptera frugiperda. LNCR operates as the intermediate of an unclassified transposable element (TE-LNCR). TE-LNCR is a very invasive transposable element, present in high copy numbers in the S. frugiperda genome. LNCR rasiRNAs are single-stranded RNAs without a prominent nucleotide motif, which are organized in two distinct, strand-specific clusters. The expression of LNCR and LNCR rasiRNAs is developmentally regulated. Formation of heterochromatin in the genomic region where three copies of the TE-LNCR are embedded was followed by chromatin immunoprecipitation (ChIP) and we observed this chromatin undergo dynamic changes during development. In summary, increased LNCR expression in certain developmental stages is followed by the appearance of a variety of LNCR rasiRNAs which appears to correlate with subsequent accumulation of a heterochromatic histone mark and silencing of the genomic region with TE-LNCR. These results support the notion that a repeat-associated small interfering RNA pathway is linked to heterochromatin formation and/or maintenance during development to establish repression of the TE-LNCR transposable element. This study provides insights into the rasiRNA silencing pathway and its role in the formation of fluctuating heterochromatin during the development of one holocentric organism. PMID:21980354

Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions

PubMed Central

Wu, Hao; Zhang, Yi

2014-01-01

Methylation of cytosines in the mammalian genome represents a key epigenetic modification and is dynamically regulated during development. Compelling evidence now suggests that dynamic regulation of DNA methylation is mainly achieved through a cyclic enzymatic cascade comprised of cytosine methylation, iterative oxidation of methyl group by TET dioxygenases, and restoration of unmodified cytosines by either replication-dependent dilution or DNA glycosylase-initiated base excision repair. In this review, we discuss the mechanism and function of DNA demethylation in mammalian genomes, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes. PMID:24439369

A CRISPR view of development

PubMed Central

Harrison, Melissa M.; Jenkins, Brian V.; O’Connor-Giles, Kate M.

2014-01-01

The CRISPR (clustered regularly interspaced short palindromic repeat)–Cas9 (CRISPR-associated nuclease 9) system is poised to transform developmental biology by providing a simple, efficient method to precisely manipulate the genome of virtually any developing organism. This RNA-guided nuclease (RGN)-based approach already has been effectively used to induce targeted mutations in multiple genes simultaneously, create conditional alleles, and generate endogenously tagged proteins. Illustrating the adaptability of RGNs, the genomes of >20 different plant and animal species as well as multiple cell lines and primary cells have been successfully modified. Here we review the current and potential uses of RGNs to investigate genome function during development. PMID:25184674

Annual Statistical Report, 1988. Client Assistance Program, Protection & Advocacy System for Persons with Mental Illness, Protection & Advocacy System for Persons with Developmental Disabilities.

ERIC Educational Resources Information Center

National Association of Protection and Advocacy Systems, Washington, DC.

The report summarizes: (1) 1988 program data for state Protection and Advocacy Systems for persons with developmental disabilities and persons with mental illness, and (2) 1988 program data for Client Assistance Programs. The data are derived from reports from 56 states and territories. In addition to nationwide data totals, each state's…

45 CFR 1386.25 - Allowable litigation costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

....25 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON DEVELOPMENTAL DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights...

Community Based Competitive Employment Preparation of Developmentally Disabled Persons: A Program Description and Evaluation.

ERIC Educational Resources Information Center

Stodden, Robert A.; Browder, Phyllis Meighen

1986-01-01

Success in competitive employment placement of a demonstration project serving 53 persons with developmental disabilities is associated with three factors: (1) training approach and methodology; (2) program management; and (3) trainee characteristics. (CL)

A Protocol for Epigenetic Imprinting Analysis with RNA-Seq Data.

PubMed

Zou, Jinfeng; Xiang, Daoquan; Datla, Raju; Wang, Edwin

2018-01-01

Genomic imprinting is an epigenetic regulatory mechanism that operates through expression of certain genes from maternal or paternal in a parent-of-origin-specific manner. Imprinted genes have been identified in diverse biological systems that are implicated in some human diseases and in embryonic and seed developmental programs in plants. The molecular underpinning programs and mechanisms involved in imprinting are yet to be explored in depth in plants. The recent advances in RNA-Seq-based methods and technologies offer an opportunity to systematically analyze epigenetic imprinting that operates at the whole genome level in the model and crop plants. We are interested using Arabidopsis model system, to investigate gene expression patterns associated with parent of origin and their implications to imprinting during embryo and seed development. Toward this, we have generated early embryo development RNA-Seq-based transcriptome datasets in F1s from a genetic cross between two diverse Arabidopsis thaliana ecotypes Col-0 and Tsu-1. With the data, we developed a protocol for evaluating the maternal and paternal contributions of genes during the early stages of embryo development after fertilization. This protocol is also designed to consider the contamination from other potential seed tissues, sequencing quality, proper processing of sequenced reads and variant calling, and appropriate inference of the parental contributions based on the parent-of-origin-specific single-nucleotide polymorphisms within the expressed genes. The approach, methods and the protocol developed in this study can be used for evaluating the effects of epigenetic imprinting in plants.

Mouse Models for Down Syndrome-Associated Developmental Cognitive Disabilities

PubMed Central

Liu, Chunhong; Belichenko, Pavel V.; Zhang, Li; Fu, Dawei; Kleschevnikov, Alexander M.; Baldini, Antonio; Antonarakis, Stylianos E.; Mobley, William C.; Yu, Y. Eugene

2011-01-01

Down syndrome (DS) is mainly caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is a leading genetic cause for developmental cognitive disabilities in humans. The mouse is a premier model organism for DS because the regions on Hsa21 are syntenically conserved with three regions in the mouse genome, which are located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. With the advance of chromosomal manipulation technologies, new mouse mutants have been generated to mimic DS at both the genotypic and phenotypic levels. Further mouse-based molecular genetic studies in the future may lead to the unraveling of the mechanisms underlying DS-associated developmental cognitive disabilities, which would lay the groundwork for developing effective treatments for this phenotypic manifestation. In this review, we will discuss recent progress and future challenges in modeling DS-associated developmental cognitive disability in mice with an emphasis on hippocampus-related phenotypes. PMID:21865664

Genomic organization, evolution, and expression of photoprotein and opsin genes in Mnemiopsis leidyi: a new view of ctenophore photocytes.

PubMed

Schnitzler, Christine E; Pang, Kevin; Powers, Meghan L; Reitzel, Adam M; Ryan, Joseph F; Simmons, David; Tada, Takashi; Park, Morgan; Gupta, Jyoti; Brooks, Shelise Y; Blakesley, Robert W; Yokoyama, Shozo; Haddock, Steven Hd; Martindale, Mark Q; Baxevanis, Andreas D

2012-12-21

Calcium-activated photoproteins are luciferase variants found in photocyte cells of bioluminescent jellyfish (Phylum Cnidaria) and comb jellies (Phylum Ctenophora). The complete genomic sequence from the ctenophore Mnemiopsis leidyi, a representative of the earliest branch of animals that emit light, provided an opportunity to examine the genome of an organism that uses this class of luciferase for bioluminescence and to look for genes involved in light reception. To determine when photoprotein genes first arose, we examined the genomic sequence from other early-branching taxa. We combined our genomic survey with gene trees, developmental expression patterns, and functional protein assays of photoproteins and opsins to provide a comprehensive view of light production and light reception in Mnemiopsis. The Mnemiopsis genome has 10 full-length photoprotein genes situated within two genomic clusters with high sequence conservation that are maintained due to strong purifying selection and concerted evolution. Photoprotein-like genes were also identified in the genomes of the non-luminescent sponge Amphimedon queenslandica and the non-luminescent cnidarian Nematostella vectensis, and phylogenomic analysis demonstrated that photoprotein genes arose at the base of all animals. Photoprotein gene expression in Mnemiopsis embryos begins during gastrulation in migrating precursors to photocytes and persists throughout development in the canals where photocytes reside. We identified three putative opsin genes in the Mnemiopsis genome and show that they do not group with well-known bilaterian opsin subfamilies. Interestingly, photoprotein transcripts are co-expressed with two of the putative opsins in developing photocytes. Opsin expression is also seen in the apical sensory organ. We present evidence that one opsin functions as a photopigment in vitro, absorbing light at wavelengths that overlap with peak photoprotein light emission, raising the hypothesis that light production and light reception may be functionally connected in ctenophore photocytes. We also present genomic evidence of a complete ciliary phototransduction cascade in Mnemiopsis. This study elucidates the genomic organization, evolutionary history, and developmental expression of photoprotein and opsin genes in the ctenophore Mnemiopsis leidyi, introduces a novel dual role for ctenophore photocytes in both bioluminescence and phototransduction, and raises the possibility that light production and light reception are linked in this early-branching non-bilaterian animal.

Genomic organization, evolution, and expression of photoprotein and opsin genes in Mnemiopsis leidyi: a new view of ctenophore photocytes

PubMed Central

2012-01-01

Background Calcium-activated photoproteins are luciferase variants found in photocyte cells of bioluminescent jellyfish (Phylum Cnidaria) and comb jellies (Phylum Ctenophora). The complete genomic sequence from the ctenophore Mnemiopsis leidyi, a representative of the earliest branch of animals that emit light, provided an opportunity to examine the genome of an organism that uses this class of luciferase for bioluminescence and to look for genes involved in light reception. To determine when photoprotein genes first arose, we examined the genomic sequence from other early-branching taxa. We combined our genomic survey with gene trees, developmental expression patterns, and functional protein assays of photoproteins and opsins to provide a comprehensive view of light production and light reception in Mnemiopsis. Results The Mnemiopsis genome has 10 full-length photoprotein genes situated within two genomic clusters with high sequence conservation that are maintained due to strong purifying selection and concerted evolution. Photoprotein-like genes were also identified in the genomes of the non-luminescent sponge Amphimedon queenslandica and the non-luminescent cnidarian Nematostella vectensis, and phylogenomic analysis demonstrated that photoprotein genes arose at the base of all animals. Photoprotein gene expression in Mnemiopsis embryos begins during gastrulation in migrating precursors to photocytes and persists throughout development in the canals where photocytes reside. We identified three putative opsin genes in the Mnemiopsis genome and show that they do not group with well-known bilaterian opsin subfamilies. Interestingly, photoprotein transcripts are co-expressed with two of the putative opsins in developing photocytes. Opsin expression is also seen in the apical sensory organ. We present evidence that one opsin functions as a photopigment in vitro, absorbing light at wavelengths that overlap with peak photoprotein light emission, raising the hypothesis that light production and light reception may be functionally connected in ctenophore photocytes. We also present genomic evidence of a complete ciliary phototransduction cascade in Mnemiopsis. Conclusions This study elucidates the genomic organization, evolutionary history, and developmental expression of photoprotein and opsin genes in the ctenophore Mnemiopsis leidyi, introduces a novel dual role for ctenophore photocytes in both bioluminescence and phototransduction, and raises the possibility that light production and light reception are linked in this early-branching non-bilaterian animal. PMID:23259493

Genetic interactions underlying tree branch orientation

USDA-ARS?s Scientific Manuscript database

Expanding our understanding of the molecular and genetic mechanisms behind branch orientation in trees both addresses a fundamental developmental phenomenon and can lead to significant impacts on tree crop agriculture and forestry. Using the p-nome (pooled genome) sequencing-based mapping approac...

Avian models in teratology and developmental toxicology.

PubMed

Smith, Susan M; Flentke, George R; Garic, Ana

2012-01-01

The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function.

A Part, Not Apart: A Systematic Approach to Integrated Recreation and Leisure for Developmentally Disabled Adults.

ERIC Educational Resources Information Center

Congdon, David M.; And Others

This program manual was developed by the Grant-Blackford Development Center in order to help other professionals and organizations working with developmentally disabled persons to improve their recreation and leisure programs. The manual's philosophy is to structure recreation programs for fun, not just for skill teaching: stressing abilities, not…

Serving the Needs of Struggling Developmental Education Students: The Development of a Program Planning Guidebook for Community College Administrators

ERIC Educational Resources Information Center

Bohnet, Kimberly Jean

2016-01-01

This dissertation describes the process of creating a guidebook that developmental education administrators can use to build their capacity as leaders, learners, and program planners. The guidebook is the product of a qualitative study designed to better understand how community college administrators who have program planning responsibilities for…

A Guide To Setting Up a Creative Art Experiences Program for Older Adults with Developmental Disabilities.

ERIC Educational Resources Information Center

Harlan, Jane E.

This guide is intended to help agencies serving older adults with mental retardation and other developmental disabilities in setting up a relatively inexpensive creative art program. The first section presents a rationale for creative art experiences for this population and then provides specific information on program development, including…

Understanding the Diversity: A Taxonomy for Postsecondary Education Programs and Services for Students with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

McEathron, Mary A.; Beuhring, Trisha; Maynard, Amelia; Mavis, Ann

2013-01-01

The number of postsecondary education (PSE) programs for individuals with intellectual and developmental disabilities (IDD) has been steadily growing over the last few decades. There has been little public information regarding these programs and schools. Consequently, students, families, and researchers alike lack details about the various…

Child health developmental plasticity, and epigenetic programming

USDA-ARS?s Scientific Manuscript database

Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to the organism under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology and long-term health. Developm...

Developmental programming: the role of growth hormone.

PubMed

Oberbauer, Anita M

2015-01-01

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

PubMed Central

KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

PubMed

Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

Genome health nutrigenomics and nutrigenetics--diagnosis and nutritional treatment of genome damage on an individual basis.

PubMed

Fenech, Michael

2008-04-01

The term nutrigenomics refers to the effect of diet on gene expression. The term nutrigenetics refers to the impact of inherited traits on the response to a specific dietary pattern, functional food or supplement on a specific health outcome. The specific fields of genome health nutrigenomics and genome health nutrigenetics are emerging as important new research areas because it is becoming increasingly evident that (a) risk for developmental and degenerative disease increases with DNA damage which in turn is dependent on nutritional status and (b) optimal concentration of micronutrients for prevention of genome damage is also dependent on genetic polymorphisms that alter function of genes involved directly or indirectly in uptake and metabolism of micronutrients required for DNA repair and DNA replication. Development of dietary patterns, functional foods and supplements that are designed to improve genome health maintenance in humans with specific genetic backgrounds may provide an important contribution to a new optimum health strategy based on the diagnosis and individualised nutritional treatment of genome instability i.e. Genome Health Clinics.

Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass

PubMed Central

Portha, Bernard; Chavey, Audrey; Movassat, Jamileh

2011-01-01

A substantial body of evidence suggests that an abnormal intrauterine milieu elicited by maternal metabolic disturbances as diverse as undernutrition, placental insufficiency, diabetes or obesity, may program susceptibility in the fetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. This paper examines the developmental programming of glucose intolerance/diabetes by disturbed intrauterine metabolic condition experimentally obtained in various rodent models of maternal protein restriction, caloric restriction, overnutrition or diabetes, with a focus on the alteration of the developing beta-cell mass. In most of the cases, whatever the type of initial maternal metabolic stress, the beta-cell adaptive growth which normally occurs during gestation, does not take place in the pregnant offspring and this results in the development of gestational diabetes. Therefore gestational diabetes turns to be the ultimate insult targeting the offspring beta-cell mass and propagates diabetes risk to the next generation again. The aetiology and the transmission of spontaneous diabetes as encountered in the GK/Par rat model of type 2 diabetes, are discussed in such a perspective. This review also discusses the non-genomic mechanisms involved in the installation of the programmed effect as well as in its intergenerational transmission. PMID:22110471

Multimedia presentations on the human genome: Implementation and assessment of a teaching program for the introduction to genome science using a poster and animations.

PubMed

Kano, Kei; Yahata, Saiko; Muroi, Kaori; Kawakami, Masahiro; Tomoda, Mari; Miyaki, Koichi; Nakayama, Takeo; Kosugi, Shinji; Kato, Kazuto

2008-11-01

Genome science, including topics such as gene recombination, cloning, genetic tests, and gene therapy, is now an established part of our daily lives; thus we need to learn genome science to better equip ourselves for the present day. Learning from topics directly related to the human has been suggested to be more effective than learning from Mendel's peas not only because many students do not understand that plants are organisms, but also because human biology contains important social and health issues. Therefore, we have developed a teaching program for the introduction to genome science, whose subjects are focused on the human genome. This program comprises mixed multimedia presentations: a large poster with illustrations and text on the human genome (a human genome map for every home), and animations on the basics of genome science. We implemented and assessed this program at four high schools. Our results indicate that students felt that they learned about the human genome from the program and some increases in students' understanding were observed with longer exposure to the mixed multimedia presentations. Copyright © 2008 International Union of Biochemistry and Molecular Biology, Inc.

CnidBase: The Cnidarian Evolutionary Genomics Database

PubMed Central

Ryan, Joseph F.; Finnerty, John R.

2003-01-01

CnidBase, the Cnidarian Evolutionary Genomics Database, is a tool for investigating the evolutionary, developmental and ecological factors that affect gene expression and gene function in cnidarians. In turn, CnidBase will help to illuminate the role of specific genes in shaping cnidarian biodiversity in the present day and in the distant past. CnidBase highlights evolutionary changes between species within the phylum Cnidaria and structures genomic and expression data to facilitate comparisons to non-cnidarian metazoans. CnidBase aims to further the progress that has already been made in the realm of cnidarian evolutionary genomics by creating a central community resource which will help drive future research and facilitate more accurate classification and comparison of new experimental data with existing data. CnidBase is available at http://cnidbase.bu.edu/. PMID:12519972

A Review of Intervention Programs to Prevent and Treat Behavioral Problems in Young Children with Developmental Disabilities

PubMed Central

Petrenko, Christie L. M.

2013-01-01

Children with developmental disabilities are at higher risk for internalizing and externalizing behavioral problems than children in the general population. Effective prevention and treatment programs are necessary to reduce the burden of behavioral problems in this population. The current review identified 17 controlled trials of nine intervention programs for young children with developmental disabilities, with parent training the most common type of intervention in this population. Nearly all studies demonstrated medium to large intervention effects on child behavior post-intervention. Preliminary evidence suggests interventions developed for the general population can be effective for children with developmental disabilities and their families. A greater emphasis on the prevention of behavior problems in young children with developmental disabilities prior to the onset of significant symptoms or clinical disorders is needed. Multi-component interventions may be more efficacious for child behavior problems and yield greater benefits for parent and family adjustment. Recommendations for future research directions are provided. PMID:24222982

45 CFR 1388.4 - Program criteria-governance and administration.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and programs. (k) The UAP must maintain collaborative relationships with the State Developmental.... (l) The UAP must maintain collaborative relationships and be an active participant with the UAP... must demonstrate commitment to the field of developmental disabilities and leadership and vision in...

The Impact of Developmental Education at Triton College.

ERIC Educational Resources Information Center

Chand, Sunil

1985-01-01

Describes the following aspects of the Developmental Education Program at Triton College: student placement, courses, faculty selection, reading and writing instruction, mathematics instruction, the Learning Assistance Center (LAC), LAC tutoring, LAC special projects, LAC management, special needs assistance program for disabled students, and…

2012 U.S. Department of Energy: Joint Genome Institute: Progress Report

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

Gilbert, David

2013-01-01

The mission of the U.S. Department of Energy Joint Genome Institute (DOE JGI) is to serve the diverse scientific community as a user facility, enabling the application of large-scale genomics and analysis of plants, microbes, and communities of microbes to address the DOE mission goals in bioenergy and the environment. The DOE JGI's sequencing efforts fall under the Eukaryote Super Program, which includes the Plant and Fungal Genomics Programs; and the Prokaryote Super Program, which includes the Microbial Genomics and Metagenomics Programs. In 2012, several projects made news for their contributions to energy and environment research.

The ABC Model and its Applicability to Basal Angiosperms

PubMed Central

Soltis, Douglas E.; Chanderbali, André S.; Kim, Sangtae; Buzgo, Matyas; Soltis, Pamela S.

2007-01-01

Background Although the flower is the central feature of the angiosperms, little is known of its origin and subsequent diversification. The ABC model has long been the unifying paradigm for floral developmental genetics, but it is based on phylogenetically derived eudicot models. Synergistic research involving phylogenetics, classical developmental studies, genomics and developmental genetics has afforded valuable new insights into floral evolution in general, and the early flower in particular. Scope and Conclusions Genomic studies indicate that basal angiosperms, and by inference the earliest angiosperms, had a rich tool kit of floral genes. Homologues of the ABCE floral organ identity genes are also present in basal angiosperm lineages; however, C-, E- and particularly B-function genes are more broadly expressed in basal lineages. There is no single model of floral organ identity that applies to all angiosperms; there are multiple models that apply depending on the phylogenetic position and floral structure of the group in question. The classic ABC (or ABCE) model may work well for most eudicots. However, modifications are needed for basal eudicots and, the focus of this paper, basal angiosperms. We offer ‘fading borders’ as a testable hypothesis for the basal-most angiosperms and, by inference, perhaps some of the earliest (now extinct) angiosperms. PMID:17616563

Molecular dissection of transcriptional reprogramming of steviol glycosides synthesis in leaf tissue during developmental phase transitions in Stevia rebaudiana Bert.

PubMed

Singh, Gopal; Singh, Gagandeep; Singh, Pradeep; Parmar, Rajni; Paul, Navgeet; Vashist, Radhika; Swarnkar, Mohit Kumar; Kumar, Ashok; Singh, Sanatsujat; Singh, Anil Kumar; Kumar, Sanjay; Sharma, Ram Kumar

2017-09-19

Stevia is a natural source of commercially important steviol glycosides (SGs), which share biosynthesis route with gibberellic acids (GAs) through plastidal MEP and cytosolic MVA pathways. Ontogeny-dependent deviation in SGs biosynthesis is one of the key factor for global cultivation of Stevia, has not been studied at transcriptional level. To dissect underlying molecular mechanism, we followed a global transcriptome sequencing approach and generated more than 100 million reads. Annotation of 41,262 de novo assembled transcripts identified all the genes required for SGs and GAs biosynthesis. Differential gene expression and quantitative analysis of important pathway genes (DXS, HMGR, KA13H) and gene regulators (WRKY, MYB, NAC TFs) indicated developmental phase dependent utilization of metabolic flux between SGs and GAs synthesis. Further, identification of 124 CYPs and 45 UGTs enrich the genomic resources, and their PPI network analysis with SGs/GAs biosynthesis proteins identifies putative candidates involved in metabolic changes, as supported by their developmental phase-dependent expression. These putative targets can expedite molecular breeding and genetic engineering efforts to enhance SGs content, biomass and yield. Futuristically, the generated dataset will be a useful resource for development of functional molecular markers for diversity characterization, genome mapping and evolutionary studies in Stevia.

Using the Developmental Gene Bicoid to Identify Species of Forensically Important Blowflies (Diptera: Calliphoridae)

PubMed Central

Park, Seong Hwan; Park, Chung Hyun; Zhang, Yong; Piao, Huguo; Chung, Ukhee; Kim, Seong Yoon; Ko, Kwang Soo; Yi, Cheong-Ho; Jo, Tae-Ho; Hwang, Juck-Joon

2013-01-01

Identifying species of insects used to estimate postmortem interval (PMI) is a major subject in forensic entomology. Because forensic insect specimens are morphologically uniform and are obtained at various developmental stages, DNA markers are greatly needed. To develop new autosomal DNA markers to identify species, partial genomic sequences of the bicoid (bcd) genes, containing the homeobox and its flanking sequences, from 12 blowfly species (Aldrichina grahami, Calliphora vicina, Calliphora lata, Triceratopyga calliphoroides, Chrysomya megacephala, Chrysomya pinguis, Phormia regina, Lucilia ampullacea, Lucilia caesar, Lucilia illustris, Hemipyrellia ligurriens and Lucilia sericata; Calliphoridae: Diptera) were determined and analyzed. This study first sequenced the ten blowfly species other than C. vicina and L. sericata. Based on the bcd sequences of these 12 blowfly species, a phylogenetic tree was constructed that discriminates the subfamilies of Calliphoridae (Luciliinae, Chrysomyinae, and Calliphorinae) and most blowfly species. Even partial genomic sequences of about 500 bp can distinguish most blowfly species. The short intron 2 and coding sequences downstream of the bcd homeobox in exon 3 could be utilized to develop DNA markers for forensic applications. These gene sequences are important in the evolution of insect developmental biology and are potentially useful for identifying insect species in forensic science. PMID:23586044

Human genome. 1993 Program report

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

Not Available

1994-03-01

The purpose of this report is to update the Human Genome 1991-92 Program Report and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes.

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

PubMed Central

Stel, Jente

2015-01-01

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans. PMID:26241072

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals.

PubMed

Stel, Jente; Legler, Juliette

2015-10-01

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

A CROSS-SPECIES APPROACH TO USING GENOMICS TOOLS IN AQUATIC TOXICOLOGY

EPA Science Inventory

Microarray technology has proven to be a useful tool for analyzing the transcriptome of various organisms representing conditions such as disease states, developmental stages, and responses to chemical exposure. Most commercially available arrays are limited to organisms that ha...

20180312 - Mechanistic Modeling of Developmental Defects through Computational Embryology (SOT)

EPA Science Inventory

Significant advances in the genome sciences, in automated high-throughput screening (HTS), and in alternative methods for testing enable rapid profiling of chemical libraries for quantitative effects on diverse cellular activities. While a surfeit of HTS data and information is n...

Gender differences in developmental programming of cardiovascular diseases

PubMed Central

Dasinger, John Henry; Alexander, Barbara T.

2016-01-01

Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr. David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increases blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood in addition to exposure to adverse influences during fetal life contribute to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life with later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex impacts the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low birth weight men and women. Fewer still assess how aging impacts sex differences in programmed cardiovascular risk. Thus, the aim of this review is to highlight current data regarding sex differences in the developmental programming of blood pressure and cardiovascular disease. PMID:26814204

Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications

PubMed Central

Lucas-Herald, Angela K.; Alves-Lopes, Rheure; Montezano, Augusto C.; Ahmed, S. Faisal

2017-01-01

The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca2+ mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function. PMID:28645930

A Digest and Comparative Analysis of Major Federal Programs Affecting Infants and Toddlers with Handicaps and Their Families.

ERIC Educational Resources Information Center

O'Reilly, Fran E.; And Others

This study analyzes major federal programs designed to provide services to children, from birth through age 2, who have developmental delays or a high probability of developmental delays, and their families. Programs were selected based on their provision of education or health-related services to infants and toddlers with handicaps and their…

Applied Developmental Science: An Advanced Textbook. The SAGE Program on Applied Developmental Science

ERIC Educational Resources Information Center

Lerner, Richard M., Ed.; Jacobs, Fraincine, Ed.; Wertlieb, Donald, Ed.

2005-01-01

This course textbook has been adapted from the four-volume "Handbook of Applied Developmental Science" (SAGE 2003), a work that offers a detailed roadmap for action and research in ensuring positive child, youth, and family development. In 20 chapters, "Applied Developmental Science: An Advanced Textbook" brings together theory and application…

Wheat EST resources for functional genomics of abiotic stress

PubMed Central

Houde, Mario; Belcaid, Mahdi; Ouellet, François; Danyluk, Jean; Monroy, Antonio F; Dryanova, Ani; Gulick, Patrick; Bergeron, Anne; Laroche, André; Links, Matthew G; MacCarthy, Luke; Crosby, William L; Sarhan, Fathey

2006-01-01

Background Wheat is an excellent species to study freezing tolerance and other abiotic stresses. However, the sequence of the wheat genome has not been completely characterized due to its complexity and large size. To circumvent this obstacle and identify genes involved in cold acclimation and associated stresses, a large scale EST sequencing approach was undertaken by the Functional Genomics of Abiotic Stress (FGAS) project. Results We generated 73,521 quality-filtered ESTs from eleven cDNA libraries constructed from wheat plants exposed to various abiotic stresses and at different developmental stages. In addition, 196,041 ESTs for which tracefiles were available from the National Science Foundation wheat EST sequencing program and DuPont were also quality-filtered and used in the analysis. Clustering of the combined ESTs with d2_cluster and TGICL yielded a few large clusters containing several thousand ESTs that were refractory to routine clustering techniques. To resolve this problem, the sequence proximity and "bridges" were identified by an e-value distance graph to manually break clusters into smaller groups. Assembly of the resolved ESTs generated a 75,488 unique sequence set (31,580 contigs and 43,908 singletons/singlets). Digital expression analyses indicated that the FGAS dataset is enriched in stress-regulated genes compared to the other public datasets. Over 43% of the unique sequence set was annotated and classified into functional categories according to Gene Ontology. Conclusion We have annotated 29,556 different sequences, an almost 5-fold increase in annotated sequences compared to the available wheat public databases. Digital expression analysis combined with gene annotation helped in the identification of several pathways associated with abiotic stress. The genomic resources and knowledge developed by this project will contribute to a better understanding of the different mechanisms that govern stress tolerance in wheat and other cereals. PMID:16772040

76 FR 77836 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... of the Developmental Disabilities Assistance and Bill of Rights Act. The SF-425, ordinarily mandated... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Proposed... Developmental Disabilities Program. OMB No. 0980-0212. Description For the program of the State Councils on...

The Developmental Program--Is It Working?

ERIC Educational Resources Information Center

Cosby, Jon P.

At the North Campus of Florida Junior College at Jacksonville, a Developmental Education Program has been initiated to serve the needs of students entering college with deficient skills. Individualized instruction, open-ended courses, counseling to improve student self-concept, performance objectives, and objective evaluations are ingredients…

The effect of parent education program for preschool children with developmental disabilities: A randomized controlled trial.

PubMed

Leung, Cynthia; Chan, Stanley; Lam, Tiney; Yau, Sharon; Tsang, Sandra

2016-09-01

This study aimed to evaluate the efficacy of a parent education program, the Happy Parenting program, for Chinese preschool children with developmental disabilities. This study adopted randomized controlled trial design without blinding. Participants were randomized into intervention group (n=62) who were offered the Happy Parenting program delivered by educational psychologists and trainee educational psychologists, and a control group (n=57) who were offered a parent talk after the intervention group had completed treatment. Parent participants were requested to complete questionnaires on their children's behavior, their parenting stress, and discipline strategies. Analysis was by intention-to-treat. The results indicated significant decrease in child problem behaviors, parenting stress and dysfunctional discipline strategies in the intervention group at post-intervention. This study provided promising evidence on the effectiveness of a parent education program, the Happy Parenting program, for Chinese preschool children with developmental disabilities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inclusive intervention to enhance the fundamental movement skills of children without hearing: a preliminary study.

PubMed

Gursel, Ferda

2014-02-01

The purpose of this study was to assess an intervention program on the fundamental movement skill of students with and without hearing impairment, using the Test of Gross Motor Development-2 (TGMD-2) standardized Turkish norm. Preschool children with and without hearing impairment participated in this study. At the beginning of the study, most of the children with hearing impairment demonstrated developmental delay on the Locomotor subscale (6/7), as did about one-third (4/11) of the children without hearing impairment. For the Object control subscale, 4/7 of children with hearing impairment and none without hearing impairment showed developmental delay prior to the intervention program. After the intervention program, 3/7 children with hearing impairment had developmental delay on the Locomotor subscale. On the Object control subscale, 2/7 children with hearing impairment and none without hearing impairment showed developmental delay. The six-week intervention program improved TGMD-2 scores of children with hearing impairment, yet did not yield statistically significant improvement of fundamental movement skills.

Genome-wide identification and analysis of the MADS-box gene family in apple.

PubMed

Tian, Yi; Dong, Qinglong; Ji, Zhirui; Chi, Fumei; Cong, Peihua; Zhou, Zongshan

2015-01-25

The MADS-box gene family is one of the most widely studied families in plants and has diverse developmental roles in flower pattern formation, gametophyte cell division and fruit differentiation. Although the genome-wide analysis of this family has been performed in some species, little is known regarding MADS-box genes in apple (Malus domestica). In this study, 146 MADS-box genes were identified in the apple genome and were phylogenetically clustered into six subgroups (MIKC(c), MIKC*, Mα, Mβ, Mγ and Mδ) with the MADS-box genes from Arabidopsis and rice. The predicted apple MADS-box genes were distributed across all 17 chromosomes at different densities. Additionally, the MADS-box domain, exon length, gene structure and motif compositions of the apple MADS-box genes were analysed. Moreover, the expression of all of the apple MADS-box genes was analysed in the root, stem, leaf, flower tissues and five stages of fruit development. All of the apple MADS-box genes, with the exception of some genes in each group, were expressed in at least one of the tissues tested, which indicates that the MADS-box genes are involved in various aspects of the physiological and developmental processes of the apple. To the best of our knowledge, this report describes the first genome-wide analysis of the apple MADS-box gene family, and the results should provide valuable information for understanding the classification, cloning and putative functions of this family. Copyright © 2014 Elsevier B.V. All rights reserved.

Emergence, development and diversification of the TGF-beta signalling pathway within the animal kingdom.

PubMed

Huminiecki, Lukasz; Goldovsky, Leon; Freilich, Shiri; Moustakas, Aristidis; Ouzounis, Christos; Heldin, Carl-Henrik

2009-02-03

The question of how genomic processes, such as gene duplication, give rise to co-ordinated organismal properties, such as emergence of new body plans, organs and lifestyles, is of importance in developmental and evolutionary biology. Herein, we focus on the diversification of the transforming growth factor-beta (TGF-beta) pathway -- one of the fundamental and versatile metazoan signal transduction engines. After an investigation of 33 genomes, we show that the emergence of the TGF-beta pathway coincided with appearance of the first known animal species. The primordial pathway repertoire consisted of four Smads and four receptors, similar to those observed in the extant genome of the early diverging tablet animal (Trichoplax adhaerens). We subsequently retrace duplications in ancestral genomes on the lineage leading to humans, as well as lineage-specific duplications, such as those which gave rise to novel Smads and receptors in teleost fishes. We conclude that the diversification of the TGF-beta pathway can be parsimoniously explained according to the 2R model, with additional rounds of duplications in teleost fishes. Finally, we investigate duplications followed by accelerated evolution which gave rise to an atypical TGF-beta pathway in free-living bacterial feeding nematodes of the genus Rhabditis. Our results challenge the view of well-conserved developmental pathways. The TGF-beta signal transduction engine has expanded through gene duplication, continually adopting new functions, as animals grew in anatomical complexity, colonized new environments, and developed an active immune system.

Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence

PubMed Central

Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

2015-01-01

The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445

Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence.

PubMed

Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

2015-05-06

The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.

Draft genome sequence of the silver pomfret fish, Pampus argenteus.

PubMed

AlMomin, Sabah; Kumar, Vinod; Al-Amad, Sami; Al-Hussaini, Mohsen; Dashti, Talal; Al-Enezi, Khaznah; Akbar, Abrar

2016-01-01

Silver pomfret, Pampus argenteus, is a fish species from coastal waters. Despite its high commercial value, this edible fish has not been sequenced. Hence, its genetic and genomic studies have been limited. We report the first draft genome sequence of the silver pomfret obtained using a Next Generation Sequencing (NGS) technology. We assembled 38.7 Gb of nucleotides into scaffolds of 350 Mb with N50 of about 1.5 kb, using high quality paired end reads. These scaffolds represent 63.7% of the estimated silver pomfret genome length. The newly sequenced and assembled genome has 11.06% repetitive DNA regions, and this percentage is comparable to that of the tilapia genome. The genome analysis predicted 16 322 genes. About 91% of these genes showed homology with known proteins. Many gene clusters were annotated to protein and fatty-acid metabolism pathways that may be important in the context of the meat texture and immune system developmental processes. The reference genome can pave the way for the identification of many other genomic features that could improve breeding and population-management strategies, and it can also help characterize the genetic diversity of P. argenteus.

Post-Genome Era Pedagogy: How a BS Biotechnology Program Benefits the Liberal Arts Institution

ERIC Educational Resources Information Center

Eden, Peter

2005-01-01

Genomics profoundly affects society, because genome sequence information is widely used in such areas as genetic testing, genomic medicine/vaccine development, and so forth. Therefore, a responsibility to modernize science curricula exists for "post-genome era" educators. At my university, we developed a BS biotechnology program within a…

[Prenatal sex-specific programming and chronic diseases or Finis Ab Orígine Pendet].

PubMed

Arck, P C; Hecher, K

2014-09-01

An increasing incidence of chronic immune diseases such as allergies, multiple sclerosis, and type 2 diabetes, as well as obesity and cardiovascular and psychiatric disorders has been reported over the last five decades. Since the human genome has not altered significantly over this period of time, gene-environment interactions are suspected to be responsible for these increased disease incidences. In this context, the prenatal period is believed to significantly contribute to altered disease susceptibilities, which could be associated with environmental factors to which pregnant women were exposed to. This observation has led to a concept entitled 'developmental origin of health and disease', a topic that is enjoying much attention in clinical and basic science research. The aim of these research endeavors is to postulate guidelines for primary disease prevention. Whilst the emerging insights from this field of research provide significant pieces of the puzzle, one area is still largely neglected: the clear identification of a sex-specific programming effect. Thus it is essential that such an approach becomes fully integrated in future research goals.

Perinatal Origins of Adult Disease.

PubMed

Simeoni, Umberto; Armengaud, Jean-Baptiste; Siddeek, Benazir; Tolsa, Jean-François

2018-01-01

Epidemiological and experimental studies have shown that the peri-conception period, pregnancy, and infancy are windows of particular sensibility to environmental clues which influence lifelong trajectories across health and disease. Nutrition, stress, and toxins induce epigenetic marks that control long-term gene expression patterns and can be transmitted transgenerationally. Chronic diseases of adulthood such as hypertension, diabetes, and obesity thus have early, developmental origins in the perinatal period. The early epigenome, in interaction with other actors such as the microbiome, add powerful layers of diversity to the biological predisposition generated by the genome. Such "programming" is a normal, adaptive component of development, including in normal pregnancies and births. However, perinatal disease, either maternal (such as pre-eclampsia, ges-tational diabetes, or inflammatory disease) or fetal, and neonatal diseases (such as intrauterine growth restriction and preterm birth) are major conditions of altered programming, translated into an increased risk for chronic disease in these patients when they reach adulthood. Early prevention, optimal perinatal nutrition, and specific follow-up measures are key factors in the early preservation of long-term health. © 2018 S. Karger AG, Basel.

Expression analysis of fertilization/early embryogenesis-associated genes in Phalaenopsis orchids.

PubMed

Chen, Jhun-Chen; Wei, Miao-Ju; Fang, Su-Chiung

2016-10-02

One of the distinct reproductive programs in orchid species is pollination-triggered ovule development and megasporogenesis. During sexual reproduction, fertilization occurs days to months after pollination. The molecular mechanisms evolved to carry out this strategic reproductive program remain unclear. In the August issue of Plant Physiology 1 , we report comprehensive studies of comparative genome-wide gene expression in various reproductive tissues and the molecular events associated with developmental transitions unique to sexual reproduction of Phalaenopsis aphrodite. Transcriptional factors and signaling components whose expression is specifically enriched in interior ovary tissues when fertilization occurs and embryos start to develop have been identified. Here, we report verification of additional fertilization-associated genes, DOMAINS REARRANGED METHYLTRANSFERASE 1 (PaDRM1), CHROMOMETHYLTRANSFERASE 1 (PaCMT1), SU(VAR)3-9 RELATED PROTEIN 1 (PaSUVR1), INDOLE-3-ACETIC ACID inducible 30-like 1 (PaIAA30L1), and ETHYLENE INSENSITIVE 3-like 1 (PaEIN3L1), and discuss their potential roles in gametophyte development, epigenetic reprogramming, and hormone regulation during fertilization and establishment of embryo development in Phalaenopsis orchids.

Mating programs including genomic relationships and dominance effects

USDA-ARS?s Scientific Manuscript database

Breed associations, artificial-insemination organizations, and on-farm software providers need new computerized mating programs for genomic selection so that genomic inbreeding could be minimized by comparing genotypes of potential mates. Efficient methods for transferring elements of the genomic re...

Regulation of Sex Determination in Mice by a Non-coding Genomic Region

PubMed Central

Arboleda, Valerie A.; Fleming, Alice; Barseghyan, Hayk; Délot, Emmanuèle; Sinsheimer, Janet S.; Vilain, Eric

2014-01-01

To identify novel genomic regions that regulate sex determination, we utilized the powerful C57BL/6J-YPOS (B6-YPOS) model of XY sex reversal where mice with autosomes from the B6 strain and a Y chromosome from a wild-derived strain, Mus domesticus poschiavinus (YPOS), show complete sex reversal. In B6-YPOS, the presence of a 55-Mb congenic region on chromosome 11 protects from sex reversal in a dose-dependent manner. Using mouse genetic backcross designs and high-density SNP arrays, we narrowed the congenic region to a 1.62-Mb genomic region on chromosome 11 that confers 80% protection from B6-YPOS sex reversal when one copy is present and complete protection when two copies are present. It was previously believed that the protective congenic region originated from the 129S1/SviMJ (129) strain. However, genomic analysis revealed that this region is not derived from 129 and most likely is derived from the semi-inbred strain POSA. We show that the small 1.62-Mb congenic region that protects against B6-YPOS sex reversal is located within the Sox9 promoter and promotes the expression of Sox9, thereby driving testis development within the B6-YPOS background. Through 30 years of backcrossing, this congenic region was maintained, as it promoted male sex determination and fertility despite the female-promoting B6-YPOS genetic background. Our findings demonstrate that long-range enhancer regions are critical to developmental processes and can be used to identify the complex interplay between genome variants, epigenetics, and developmental gene regulation. PMID:24793290

48 CFR 719.273-8 - Developmental assistance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (USAID) Mentor-Protégé Program 719.273-8 Developmental assistance. The forms of developmental assistance a Mentor can provide to a Protégé include and are not limited to the following: (a) Guidance...

METROPOLITAN ATLANTA DEVELOPMENTAL DISABILITIES PROGRAM (MADDSP)

EPA Science Inventory

To address the problem of developmental disabilities among children, CDC, the former Division of Birth Defects and Developmental Disabilities, which was funded by the Agency for Toxic Substances and Disease Registry (ATSDR), and the Georgia Department of Human Resources, initiate...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2012 CFR

2012-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2012-10-01 2012-10-01 false Designated State Protection and Advocacy agency...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2013-10-01 2013-10-01 false Designated State Protection and Advocacy agency...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2011-10-01 2011-10-01 false Designated State Protection and Advocacy agency...

45 CFR 1386.20 - Designated State Protection and Advocacy agency.

Code of Federal Regulations, 2014 CFR

2014-10-01

... DISABILITIES, DEVELOPMENTAL DISABILITIES PROGRAM FORMULA GRANT PROGRAMS State System for Protection and Advocacy of the Rights of Individuals with Developmental Disabilities § 1386.20 Designated State Protection... 45 Public Welfare 4 2014-10-01 2014-10-01 false Designated State Protection and Advocacy agency...

Developmental Trends in the Dance Performance of Children Age Six to Nine

ERIC Educational Resources Information Center

Little, Stephanie Lane

2011-01-01

Quality elementary physical education programs recognize the changing development and movement abilities of children (NASPE, 2007). Educational dance within these programs provides opportunities to engage in developmentally appropriate rhythmic activities. Research to date provides modest information for physical educators regarding what rhythmic…

Active for Life: Developmentally Appropriate Movement Programs for Young Children.

ERIC Educational Resources Information Center

Sanders, Stephen W.

This book provides guidance on what high-quality movement programs for young children should include, offering a curricular foundation, strategies for teaching, and assessment ideas. It defines and illustrates specific interrelated components of developmentally appropriate practice in providing movement education for young children. There are…

A DEMETER-like DNA demethylase governs tomato fruit ripening

USDA-ARS?s Scientific Manuscript database

This work shows that active DNA demethylation governs ripening, an important plant developmental process. Our work defines a molecular mechanism, which has until now been missing, to explain the correlation between genomic DNA demethylation and fruit ripening. It demonstrates a direct cause-and-effe...

75 FR 1397 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... personal privacy. Name of Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group; Molecular Neuropharmacology and Signaling Study Section. Date: February 4-5, 2010. Time: 8 a.m....gov . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group; Prokaryotic Cell and...

Genetic control of rhizomes and genomic localization of a major-effect growth habit QTL in perennial wildrye

USDA-ARS?s Scientific Manuscript database

Subterranean rhizome branches facilitate vegetative dispersal, survival, and regrowth of perennial grasses. Developmental differences between upright, prostrate, and subterranean stem branching patterns may involve auxin-mediated responses to gravity or light, but genetic mechanisms controlling the...

The dynamic genome of Hydra

PubMed Central

Chapman, Jarrod A.; Kirkness, Ewen F.; Simakov, Oleg; Hampson, Steven E.; Mitros, Therese; Weinmaier, Therese; Rattei, Thomas; Balasubramanian, Prakash G.; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G.; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M.; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E.; Putnam, Nicholas H.; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E.; Gee, Lydia; Kibler, Dennis F.; Law, Lee; Lindgens, Dirk; Martinez, Daniel E.; Peng, Jisong; Wigge, Philip A.; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R. H.; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M.; Wheeler, Benjamin M.; Peterson, Kevin J.; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A.; Strausberg, Robert L.; Venter, J. Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C. G.; Holstein, Thomas W.; Fujisawa, Toshitaka; Bode, Hans R.; David, Charles N.; Rokhsar, Daniel S.; Steele, Robert E.

2015-01-01

The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction. PMID:20228792

The evolution of the plant genome-to-morphology auxin circuit.

PubMed

Kutschera, Ulrich; Niklas, Karl J

2016-09-01

In his Generelle Morphologie der Organismen (1866), 150 years ago, Ernst Haeckel (1834-1919) combined developmental patterns in animals with the concept of organismic evolution, and 50 years ago, a new era of plant research started when focus shifted from crop species (sunflower, maize etc.) to thale cress (Arabidopsis thaliana) as a model organism. In this contribution, we outline the general principles of developmental evolutionary biology sensu Haeckel and describe the evolutionary genome-to-morphology-plant hormone auxin (IAA, indole-3-acetic acid)-circuit with reference to other phytohormones and a focus on land plants (embryophytes) plus associated epiphytic microbes. Our primary conclusion is that a system-wide approach is required to truly understand the ontogeny of any organism, because development proceeds according to signal pathways that integrate and respond to external as well as internal stimuli. We also discuss IAA-regulated embryology in A. thaliana and epigenetic phenomena in the gametophyte development, and outline how these processes are connected to the seminal work of Ernst Haeckel.

Parallelism and Epistasis in Skeletal Evolution Identified through Use of Phylogenomic Mapping Strategies

PubMed Central

Daane, Jacob M.; Rohner, Nicolas; Konstantinidis, Peter; Djuranovic, Sergej; Harris, Matthew P.

2016-01-01

The identification of genetic mechanisms underlying evolutionary change is critical to our understanding of natural diversity, but is presently limited by the lack of genetic and genomic resources for most species. Here, we present a new comparative genomic approach that can be applied to a broad taxonomic sampling of nonmodel species to investigate the genetic basis of evolutionary change. Using our analysis pipeline, we show that duplication and divergence of fgfr1a is correlated with the reduction of scales within fishes of the genus Phoxinellus. As a parallel genetic mechanism is observed in scale-reduction within independent lineages of cypriniforms, our finding exposes significant developmental constraint guiding morphological evolution. In addition, we identified fixed variation in fgf20a within Phoxinellus and demonstrated that combinatorial loss-of-function of fgfr1a and fgf20a within zebrafish phenocopies the evolved scalation pattern. Together, these findings reveal epistatic interactions between fgfr1a and fgf20a as a developmental mechanism regulating skeletal variation among fishes. PMID:26452532

Whole transcriptome analysis using next-generation sequencing of model species Setaria viridis to support C4 photosynthesis research.

PubMed

Xu, Jiajia; Li, Yuanyuan; Ma, Xiuling; Ding, Jianfeng; Wang, Kai; Wang, Sisi; Tian, Ye; Zhang, Hui; Zhu, Xin-Guang

2013-09-01

Setaria viridis is an emerging model species for genetic studies of C4 photosynthesis. Many basic molecular resources need to be developed to support for this species. In this paper, we performed a comprehensive transcriptome analysis from multiple developmental stages and tissues of S. viridis using next-generation sequencing technologies. Sequencing of the transcriptome from multiple tissues across three developmental stages (seed germination, vegetative growth, and reproduction) yielded a total of 71 million single end 100 bp long reads. Reference-based assembly using Setaria italica genome as a reference generated 42,754 transcripts. De novo assembly generated 60,751 transcripts. In addition, 9,576 and 7,056 potential simple sequence repeats (SSRs) covering S. viridis genome were identified when using the reference based assembled transcripts and the de novo assembled transcripts, respectively. This identified transcripts and SSR provided by this study can be used for both reverse and forward genetic studies based on S. viridis.

Epigenomic Landscape of Human Fetal Brain, Heart, and Liver.

PubMed

Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

2016-02-26

The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Ethical, Legal, and Social Implications Program of the National Human Genome Research Institute: reflections on an ongoing experiment.

PubMed

McEwen, Jean E; Boyer, Joy T; Sun, Kathie Y; Rothenberg, Karen H; Lockhart, Nicole C; Guyer, Mark S

2014-01-01

For more than 20 years, the Ethical, Legal, and Social Implications (ELSI) Program of the National Human Genome Research Institute has supported empirical and conceptual research to anticipate and address the ethical, legal, and social implications of genomics. As a component of the agency that funds much of the underlying science, the program has always been an experiment. The ever-expanding number of issues the program addresses and the relatively low level of commitment on the part of other funding agencies to support such research make setting priorities especially challenging. Program-supported studies have had a significant impact on the conduct of genomics research, the implementation of genomic medicine, and broader public policies. The program's influence is likely to grow as ELSI research, genomics research, and policy development activities become increasingly integrated. Achieving the benefits of increased integration while preserving the autonomy, objectivity, and intellectual independence of ELSI investigators presents ongoing challenges and new opportunities.

DNA methylation at differentially methylated regions of imprinted genes is resistant to developmental programming by maternal nutrition

PubMed Central

Ivanova, Elena; Chen, Jian-Hua; Segonds-Pichon, Anne; Ozanne, Susan E.; Kelsey, Gavin

2012-01-01

The nutritional environment in which the mammalian fetus or infant develop is recognized as influencing the risk of chronic diseases, such as type 2 diabetes and hypertension, in a phenomenon that has become known as developmental programming. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, because epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. One class of genes that has been considered a potential target or mediator of programming events is imprinted genes, because these genes critically depend upon epigenetic modifications for correct expression and because many imprinted genes have roles in controlling fetal growth as well as neonatal and adult metabolism. In this study, we have used an established model of developmental programming—isocaloric protein restriction to female mice during gestation or lactation—to examine whether there are effects on expression and DNA methylation of imprinted genes in the offspring. We find that although expression of some imprinted genes in liver of offspring is robustly and sustainably changed, methylation of the differentially methylated regions (DMRs) that control their monoallelic expression remains largely unaltered. We conclude that deregulation of imprinting through a general effect on DMR methylation is unlikely to be a common factor in developmental programming. PMID:22968513

gmos: Rapid Detection of Genome Mosaicism over Short Evolutionary Distances.

PubMed

Domazet-Lošo, Mirjana; Domazet-Lošo, Tomislav

2016-01-01

Prokaryotic and viral genomes are often altered by recombination and horizontal gene transfer. The existing methods for detecting recombination are primarily aimed at viral genomes or sets of loci, since the expensive computation of underlying statistical models often hinders the comparison of complete prokaryotic genomes. As an alternative, alignment-free solutions are more efficient, but cannot map (align) a query to subject genomes. To address this problem, we have developed gmos (Genome MOsaic Structure), a new program that determines the mosaic structure of query genomes when compared to a set of closely related subject genomes. The program first computes local alignments between query and subject genomes and then reconstructs the query mosaic structure by choosing the best local alignment for each query region. To accomplish the analysis quickly, the program mostly relies on pairwise alignments and constructs multiple sequence alignments over short overlapping subject regions only when necessary. This fine-tuned implementation achieves an efficiency comparable to an alignment-free tool. The program performs well for simulated and real data sets of closely related genomes and can be used for fast recombination detection; for instance, when a new prokaryotic pathogen is discovered. As an example, gmos was used to detect genome mosaicism in a pathogenic Enterococcus faecium strain compared to seven closely related genomes. The analysis took less than two minutes on a single 2.1 GHz processor. The output is available in fasta format and can be visualized using an accessory program, gmosDraw (freely available with gmos).

gmos: Rapid Detection of Genome Mosaicism over Short Evolutionary Distances

PubMed Central

Domazet-Lošo, Mirjana; Domazet-Lošo, Tomislav

2016-01-01

Prokaryotic and viral genomes are often altered by recombination and horizontal gene transfer. The existing methods for detecting recombination are primarily aimed at viral genomes or sets of loci, since the expensive computation of underlying statistical models often hinders the comparison of complete prokaryotic genomes. As an alternative, alignment-free solutions are more efficient, but cannot map (align) a query to subject genomes. To address this problem, we have developed gmos (Genome MOsaic Structure), a new program that determines the mosaic structure of query genomes when compared to a set of closely related subject genomes. The program first computes local alignments between query and subject genomes and then reconstructs the query mosaic structure by choosing the best local alignment for each query region. To accomplish the analysis quickly, the program mostly relies on pairwise alignments and constructs multiple sequence alignments over short overlapping subject regions only when necessary. This fine-tuned implementation achieves an efficiency comparable to an alignment-free tool. The program performs well for simulated and real data sets of closely related genomes and can be used for fast recombination detection; for instance, when a new prokaryotic pathogen is discovered. As an example, gmos was used to detect genome mosaicism in a pathogenic Enterococcus faecium strain compared to seven closely related genomes. The analysis took less than two minutes on a single 2.1 GHz processor. The output is available in fasta format and can be visualized using an accessory program, gmosDraw (freely available with gmos). PMID:27846272

Improving Physical Fitness of Individuals with Intellectual and Developmental Disability through a Virtual Reality Intervention Program

ERIC Educational Resources Information Center

Lotan, Meir; Yalon-Chamovitz, Shira; Weiss, Patrice L.

2009-01-01

Individuals with intellectual and developmental disabilities (IDD) are in need of effective physical fitness training programs. The aim was to test the effectiveness of a Virtual Reality (VR)-based exercise program in improving the physical fitness of adults with IDD. A research group (N = 30; mean age = 52.3 plus or minus 5.8 years; moderate IDD…

An Automatic Drag-and-Drop Assistive Program Developed to Assistive People with Developmental Disabilities to Improve Drag-and-Drop Efficiency

ERIC Educational Resources Information Center

Shih, Ching-Hsiang; Huang, Hsun-Chin; Liao, Yung-Kun; Shih, Ching-Tien; Chiang, Ming-Shan

2010-01-01

The latest researches adopted software technology to improve pointing performance; however, Drag-and-Drop (DnD) operation is also commonly used in modern GUI programming. This study evaluated whether two children with developmental disabilities would be able to improve their DnD performance, through an Automatic DnD Assistive Program (ADnDAP). At…

Effects of a Developmental Guidance Program on the Affective-Social Development of Third and Fourth Graders.

ERIC Educational Resources Information Center

Stilwell, William E.

This study compared the effects of the Stuttgart School District's developmental guidance program with the effects of one of its traditional school programs on children's affective-social development. Affective education data were collected at the end of third grade (May, 1975) and again at the end of fourth grade (May, 1976) for 58 boys and 47…

DNA methylation and genome rearrangement characteristics of phase change in cultured shoots of Sequoia sempervirens.

PubMed

Huang, Li-Chun; Hsiao, Lin-June; Pu, Szu-Yuan; Kuo, Ching-I; Huang, Bau-Lian; Tseng, Tsung-Che; Huang, Hao-Jen; Chen, Yu-Ting

2012-06-01

Epigenetic machinery regulates the expression of individual genes and plays a crucial role in globally shaping and maintaining developmental patterning. We studied the extent of DNA methylation in the nucleus, mitochondrion and chloroplast in cultured Sequoia sempervirens (coast redwood) adult, juvenile and rejuvenated shoots by measuring the ratio of methylcytosine to total cytosine using high-performance liquid chromatography (HPLC). We also analyzed nuclear DNA (nuDNA) polymorphisms of different shoot types by methylation-sensitive amplified fragment length polymorphism (MSAP) and Southern blot analysis. The extent of nuDNA methylation was greater in the adult vegetative than juvenile and rejuvenated shoots (8% vs 6.5-7.5%). In contrast, the proportion of methylcytosine was higher in mitochondrial DNA (mDNA) of juvenile and rejuvenated shoots than adult shoots (6.6% vs 7.8-8.2%). MSAP and Southern blot analyses identified three MSAP fragments which could be applied as phase-specific molecular markers. We also found nuclear genome and mtDNA rearrangement may be as important as DNA methylation status during the phase change. Our findings strongly suggest that DNA methylation and genome rearrangement may affect the dynamic tissue- and cell type-specific changes that determine the developmental phase of S. sempervirens shoots. Copyright © Physiologia Plantarum 2012.

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer

PubMed Central

An, Ning; Yang, Xue; Cheng, Shujun; Wang, Guiqi; Zhang, Kaitai

2015-01-01

Carcinogenesis is an exceedingly complicated process, which involves multi-level dysregulations, including genomics (majorly caused by somatic mutation and copy number variation), DNA methylomics, and transcriptomics. Therefore, only looking into one molecular level of cancer is not sufficient to uncover the intricate underlying mechanisms. With the abundant resources of public available data in the Cancer Genome Atlas (TCGA) database, an integrative strategy was conducted to systematically analyze the aberrant patterns of colorectal cancer on the basis of DNA copy number, promoter methylation, somatic mutation and gene expression. In this study, paired samples in each genomic level were retrieved to identify differentially expressed genes with corresponding genetic or epigenetic dysregulations. Notably, the result of gene ontology enrichment analysis indicated that the differentially expressed genes with corresponding aberrant promoter methylation or somatic mutation were both functionally concentrated upon developmental process, suggesting the intimate association between development and carcinogenesis. Thus, by means of random walk with restart, 37 significant development-related genes were retrieved from a priori-knowledge based biological network. In five independent microarray datasets, Kaplan–Meier survival and Cox regression analyses both confirmed that the expression of these genes was significantly associated with overall survival of Stage III/IV colorectal cancer patients. PMID:26691761

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer.

PubMed

An, Ning; Yang, Xue; Cheng, Shujun; Wang, Guiqi; Zhang, Kaitai

2015-12-22

Carcinogenesis is an exceedingly complicated process, which involves multi-level dysregulations, including genomics (majorly caused by somatic mutation and copy number variation), DNA methylomics, and transcriptomics. Therefore, only looking into one molecular level of cancer is not sufficient to uncover the intricate underlying mechanisms. With the abundant resources of public available data in the Cancer Genome Atlas (TCGA) database, an integrative strategy was conducted to systematically analyze the aberrant patterns of colorectal cancer on the basis of DNA copy number, promoter methylation, somatic mutation and gene expression. In this study, paired samples in each genomic level were retrieved to identify differentially expressed genes with corresponding genetic or epigenetic dysregulations. Notably, the result of gene ontology enrichment analysis indicated that the differentially expressed genes with corresponding aberrant promoter methylation or somatic mutation were both functionally concentrated upon developmental process, suggesting the intimate association between development and carcinogenesis. Thus, by means of random walk with restart, 37 significant development-related genes were retrieved from a priori-knowledge based biological network. In five independent microarray datasets, Kaplan-Meier survival and Cox regression analyses both confirmed that the expression of these genes was significantly associated with overall survival of Stage III/IV colorectal cancer patients.

The dynamic DNA methylation cycle from egg to sperm in the honey bee Apis mellifera

PubMed Central

Drewell, Robert A.; Bush, Eliot C.; Remnant, Emily J.; Wong, Garrett T.; Beeler, Suzannah M.; Stringham, Jessica L.; Lim, Julianne; Oldroyd, Benjamin P.

2014-01-01

In honey bees (Apis mellifera), the epigenetic mark of DNA methylation is central to the developmental regulation of caste differentiation, but may also be involved in additional biological functions. In this study, we examine the whole genome methylation profiles of three stages of the haploid honey bee genome: unfertilised eggs, the adult drones that develop from these eggs and the sperm produced by these drones. These methylomes reveal distinct patterns of methylation. Eggs and sperm show 381 genes with significantly different CpG methylation patterns, with the vast majority being more methylated in eggs. Adult drones show greatly reduced levels of methylation across the genome when compared with both gamete samples. This suggests a dynamic cycle of methylation loss and gain through the development of the drone and during spermatogenesis. Although fluxes in methylation during embryogenesis may account for some of the differentially methylated sites, the distinct methylation patterns at some genes suggest parent-specific epigenetic marking in the gametes. Extensive germ line methylation of some genes possibly explains the lower-than-expected frequency of CpG sites in these genes. We discuss the potential developmental and evolutionary implications of methylation in eggs and sperm in this eusocial insect species. PMID:24924193

Developmental delay and connective tissue disorder in four patients sharing a common microdeletion at 6q13-14.

PubMed

Van Esch, Hilde; Rosser, Elisabeth M; Janssens, Sandra; Van Ingelghem, Ingrid; Loeys, Bart; Menten, Bjorn

2010-10-01

Interstitial deletions of the long arm of chromosome 6 are rare, and most reported cases represent large, cytogenetically detectable deletions. The implementation of array comparative genome hybridisation in the diagnostic work-up of patients presenting with congenital disorders, including developmental delay, has enabled identification of many patients with smaller chromosomal imbalances. In this report, the cases are presented of four patients with a de novo interstitial deletion of chromosome 6q13-14, resulting in a common microdeletion of 3.7 Mb. All presented with developmental delay, mild dysmorphism and signs of lax connective tissue. Interestingly, the common deleted region harbours 16 genes, of which COL12A1 is a good candidate for the connective tissue pathology.

Epigenetics and the Developmental Origins of Health and Disease

EPA Science Inventory

Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). DNA methylation, posttranslational histone protein modif...

Epigenetics and the Developmental Origins of Health and Disease#

EPA Science Inventory

Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the reproductive and developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). Environmental exposures including paren...

Epigenetics and the Developmental Origins of Health and Disease#

EPA Science Inventory

Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). DNA methylation, posttranslational histone protei n modi...

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

PubMed

Gerstein, Mark B; Lu, Zhi John; Van Nostrand, Eric L; Cheng, Chao; Arshinoff, Bradley I; Liu, Tao; Yip, Kevin Y; Robilotto, Rebecca; Rechtsteiner, Andreas; Ikegami, Kohta; Alves, Pedro; Chateigner, Aurelien; Perry, Marc; Morris, Mitzi; Auerbach, Raymond K; Feng, Xin; Leng, Jing; Vielle, Anne; Niu, Wei; Rhrissorrakrai, Kahn; Agarwal, Ashish; Alexander, Roger P; Barber, Galt; Brdlik, Cathleen M; Brennan, Jennifer; Brouillet, Jeremy Jean; Carr, Adrian; Cheung, Ming-Sin; Clawson, Hiram; Contrino, Sergio; Dannenberg, Luke O; Dernburg, Abby F; Desai, Arshad; Dick, Lindsay; Dosé, Andréa C; Du, Jiang; Egelhofer, Thea; Ercan, Sevinc; Euskirchen, Ghia; Ewing, Brent; Feingold, Elise A; Gassmann, Reto; Good, Peter J; Green, Phil; Gullier, Francois; Gutwein, Michelle; Guyer, Mark S; Habegger, Lukas; Han, Ting; Henikoff, Jorja G; Henz, Stefan R; Hinrichs, Angie; Holster, Heather; Hyman, Tony; Iniguez, A Leo; Janette, Judith; Jensen, Morten; Kato, Masaomi; Kent, W James; Kephart, Ellen; Khivansara, Vishal; Khurana, Ekta; Kim, John K; Kolasinska-Zwierz, Paulina; Lai, Eric C; Latorre, Isabel; Leahey, Amber; Lewis, Suzanna; Lloyd, Paul; Lochovsky, Lucas; Lowdon, Rebecca F; Lubling, Yaniv; Lyne, Rachel; MacCoss, Michael; Mackowiak, Sebastian D; Mangone, Marco; McKay, Sheldon; Mecenas, Desirea; Merrihew, Gennifer; Miller, David M; Muroyama, Andrew; Murray, John I; Ooi, Siew-Loon; Pham, Hoang; Phippen, Taryn; Preston, Elicia A; Rajewsky, Nikolaus; Rätsch, Gunnar; Rosenbaum, Heidi; Rozowsky, Joel; Rutherford, Kim; Ruzanov, Peter; Sarov, Mihail; Sasidharan, Rajkumar; Sboner, Andrea; Scheid, Paul; Segal, Eran; Shin, Hyunjin; Shou, Chong; Slack, Frank J; Slightam, Cindie; Smith, Richard; Spencer, William C; Stinson, E O; Taing, Scott; Takasaki, Teruaki; Vafeados, Dionne; Voronina, Ksenia; Wang, Guilin; Washington, Nicole L; Whittle, Christina M; Wu, Beijing; Yan, Koon-Kiu; Zeller, Georg; Zha, Zheng; Zhong, Mei; Zhou, Xingliang; Ahringer, Julie; Strome, Susan; Gunsalus, Kristin C; Micklem, Gos; Liu, X Shirley; Reinke, Valerie; Kim, Stuart K; Hillier, LaDeana W; Henikoff, Steven; Piano, Fabio; Snyder, Michael; Stein, Lincoln; Lieb, Jason D; Waterston, Robert H

2010-12-24

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

Deciphering the transcriptional cis-regulatory code.

PubMed

Yáñez-Cuna, J Omar; Kvon, Evgeny Z; Stark, Alexander

2013-01-01

Information about developmental gene expression resides in defined regulatory elements, called enhancers, in the non-coding part of the genome. Although cells reliably utilize enhancers to orchestrate gene expression, a cis-regulatory code that would allow their interpretation has remained one of the greatest challenges of modern biology. In this review, we summarize studies from the past three decades that describe progress towards revealing the properties of enhancers and discuss how recent approaches are providing unprecedented insights into regulatory elements in animal genomes. Over the next years, we believe that the functional characterization of regulatory sequences in entire genomes, combined with recent computational methods, will provide a comprehensive view of genomic regulatory elements and their building blocks and will enable researchers to begin to understand the sequence basis of the cis-regulatory code. Copyright © 2012 Elsevier Ltd. All rights reserved.

MSW Programs: Gatekeepers to the Field of Developmental Disabilities

ERIC Educational Resources Information Center

Russo-Gleicher, Rosalie J.

2008-01-01

This article presents qualitative insights into the roles of master of social work programs in developing student practice interests in working with people with developmental disabilities (DD). Semistructured in-depth interviews were conducted with 24 MSW social workers practicing in the field of DD in the northeastern United States. Participants…

Employment Support Services for Students with Intellectual and Developmental Disabilities Attending Postsecondary Education Programs

ERIC Educational Resources Information Center

Petcu, Stefania D.; Chezan, Laura C.; Van Horn, M. Lee

2015-01-01

Our purpose in this study is to offer a more comprehensive understanding of how students with intellectual and developmental disabilities attending postsecondary education programs are prepared for competitive employment. Data collected through a national survey indicate that the vocational-related support services offered frequently by…

E-Sponsor Mentoring: Support for Students in Developmental Education

ERIC Educational Resources Information Center

Hodges, Russ; Payne, Emily Miller; Dietz, Albert; Hajovsky, Michelle

2014-01-01

Researchers investigated the use of two mentoring programs for students who were part of a support component of Fundamentals of Conceptual Understanding and Success (FOCUS), a comprehensive intervention grant for students enrolled in developmental mathematics coursework at a large public Texas university. The technology-based mentoring program,…

Bloomfield-Barnhart Developmental Reading Mastery Test: Evaluator's Handbook [and] Individual Pupil Packet.

ERIC Educational Resources Information Center

Barnhart, Cynthia A.; And Others

The Developmental Reading Mastery Test of oral reading, comprehension, spelling, and language skills is based on curriculum materials by the Bloomfield-Barnhart reading program, Let's Read. The non-graded program teaches reading in eleven steps (skill sequences), with corresponding subtests, as follows: (1) shape discrimination, directionality;…

Planning for School Transition: An Ecological-Developmental Approach.

ERIC Educational Resources Information Center

Diamond, Karen E.; And Others

1988-01-01

The paper describes an ecological-developmental model for planning a child's transition from a preschool special education program to a public school classroom. The model stresses interactions between the various environments in which the child functions. A description of a preschool transition program based on the model is also included.…

College Student Development: Theory and Practice for the ACPA Media Publication No. 49.

ERIC Educational Resources Information Center

Creamer, Don G., Ed.

This book contains articles on the most recent thinking about developmental programming in student affairs. "Progress Toward Intentional Student Development" (Don Creamer) introduces a concept orientation in developmental programming. "The Professional Practice of Student Development" (C. Carney Strange and Patricia King) presents a rationale for…

A Psychiatric Primer for Programs Serving People with Developmental Disabilities. Monograph #101.

ERIC Educational Resources Information Center

Dal Pozzo, Earlene; Bernstein, Gail S.

Intended for personnel in programs serving persons with developmental disabilities, the booklet provides basic information about the major psychiatric disorders and their treatment. Five sections cover: the major disorders; medications--uses and problems; assessment; cooordination of services; and psychiatric emergencies. Major disorders such as…

KEGG orthology-based annotation of the predicted proteome of Acropora digitifera: ZoophyteBase - an open access and searchable database of a coral genome

PubMed Central

2013-01-01

Background Contemporary coral reef research has firmly established that a genomic approach is urgently needed to better understand the effects of anthropogenic environmental stress and global climate change on coral holobiont interactions. Here we present KEGG orthology-based annotation of the complete genome sequence of the scleractinian coral Acropora digitifera and provide the first comprehensive view of the genome of a reef-building coral by applying advanced bioinformatics. Description Sequences from the KEGG database of protein function were used to construct hidden Markov models. These models were used to search the predicted proteome of A. digitifera to establish complete genomic annotation. The annotated dataset is published in ZoophyteBase, an open access format with different options for searching the data. A particularly useful feature is the ability to use a Google-like search engine that links query words to protein attributes. We present features of the annotation that underpin the molecular structure of key processes of coral physiology that include (1) regulatory proteins of symbiosis, (2) planula and early developmental proteins, (3) neural messengers, receptors and sensory proteins, (4) calcification and Ca2+-signalling proteins, (5) plant-derived proteins, (6) proteins of nitrogen metabolism, (7) DNA repair proteins, (8) stress response proteins, (9) antioxidant and redox-protective proteins, (10) proteins of cellular apoptosis, (11) microbial symbioses and pathogenicity proteins, (12) proteins of viral pathogenicity, (13) toxins and venom, (14) proteins of the chemical defensome and (15) coral epigenetics. Conclusions We advocate that providing annotation in an open-access searchable database available to the public domain will give an unprecedented foundation to interrogate the fundamental molecular structure and interactions of coral symbiosis and allow critical questions to be addressed at the genomic level based on combined aspects of evolutionary, developmental, metabolic, and environmental perspectives. PMID:23889801

The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum.

PubMed

Bozdech, Zbynek; Llinás, Manuel; Pulliam, Brian Lee; Wong, Edith D; Zhu, Jingchun; DeRisi, Joseph L

2003-10-01

Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200-300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a "just-in-time" manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates.

At-TAX: a whole genome tiling array resource for developmental expression analysis and transcript identification in Arabidopsis thaliana

PubMed Central

Laubinger, Sascha; Zeller, Georg; Henz, Stefan R; Sachsenberg, Timo; Widmer, Christian K; Naouar, Naïra; Vuylsteke, Marnik; Schölkopf, Bernhard; Rätsch, Gunnar; Weigel, Detlef

2008-01-01

Gene expression maps for model organisms, including Arabidopsis thaliana, have typically been created using gene-centric expression arrays. Here, we describe a comprehensive expression atlas, Arabidopsis thaliana Tiling Array Express (At-TAX), which is based on whole-genome tiling arrays. We demonstrate that tiling arrays are accurate tools for gene expression analysis and identified more than 1,000 unannotated transcribed regions. Visualizations of gene expression estimates, transcribed regions, and tiling probe measurements are accessible online at the At-TAX homepage. PMID:18613972

77 FR 58913 - Genomic Medicine Program Advisory Committee, Notice of Meeting

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Genetics and Epigenetics of Mating Type Determination in Paramecium and Tetrahymena.

PubMed

Orias, Eduardo; Singh, Deepankar Pratap; Meyer, Eric

2017-09-08

While sex is an ancient and highly conserved eukaryotic invention, self-incompatibility systems such as mating types or sexes appear to be derived limitations that show considerable evolutionary plasticity. Within a single class of ciliates, Paramecium and Tetrahymena species have long been known to present a wide variety of mating type numbers and modes of inheritance, but only recently have the genes involved been identified. Although similar transmembrane proteins mediate self/nonself recognition in both ciliates, the mechanisms of mating type determination differ widely, ranging from Mendelian systems to developmental nuclear differentiation, either stochastic or maternally inherited. The non-Mendelian systems rely on programmed editing of the germline genome that occurs during differentiation of the somatic nucleus, and they have co-opted different DNA recombination mechanisms-some previously unknown. Here we review the recent molecular advances and some remaining unsolved questions and discuss the possible implications of these diverse mechanisms for inbreeding/outbreeding balance regulation.

Chromatin programming by developmentally regulated transcription factors: lessons from the study of haematopoietic stem cell specification and differentiation.

PubMed

Obier, Nadine; Bonifer, Constanze

2016-11-01

Although the body plan of individuals is encoded in their genomes, each cell type expresses a different gene expression programme and therefore has access to only a subset of this information. Alterations to gene expression programmes are the underlying basis for the differentiation of multiple cell types and are driven by tissue-specific transcription factors (TFs) that interact with the epigenetic regulatory machinery to programme the chromatin landscape into transcriptionally active and inactive states. The haematopoietic system has long served as a paradigm for studying the molecular principles that regulate gene expression in development. In this review article, we summarize the current knowledge on the mechanism of action of TFs regulating haematopoietic stem cell specification and differentiation, and place this information into the context of general principles governing development. © 2016 Federation of European Biochemical Societies.

Pharmacogenomics in early-phase clinical development

PubMed Central

Burt, Tal; Dhillon, Savita

2015-01-01

Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

Nuclear Proximity of Mtr4 with RNA exosome restricts DNA mutational asymmetry

PubMed Central

Lim, Junghyun; Giri, Pankaj Kumar; Kazadi, David; Laffleur, Brice; Zhang, Wanwei; Grinstein, Veronika; Pefanis, Evangelos; Brown, Lewis M.; Ladewig, Erik; Martin, Ophélie; Chen, Yuling; Rabadan, Raul; Boyer, François; Rothschild, Gerson; Cogné, Michel; Pinaud, Eric; Deng, Haiteng; Basu, Uttiya

2017-01-01

SUMMARY The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus. Both the physical proximity and coupled activities of RNA helicase Mtr4 (and Senataxin) with the noncoding RNA processing function of RNA exosome determine the strand specific distribution of DNA mutations. Our study suggests that strand-specific DNA mutagenesis-associated mechanisms will play major roles in other undiscovered aspects of organismic development. PMID:28431250

Epigenetics and the Developmental Origins of Health and Disease 3rd ed

EPA Science Inventory

Epigenetic programming is likely to be an important mechanism underlying the lasting influence of the developmental environment on lifelong health, a concept known as the Developmental Origins of Health and Disease (DOHaD). DNA methylation, posttranslational histone protein modif...

Building a Database of Developmental Neurotoxitants: Evidence from Human and Animal Studies

EPA Science Inventory

EPA’s program for the screening and prioritization of chemicals for developmental neurotoxicity (DNT) necessitates the generation of a list of chemicals that are known mammalian developmental neurotoxicants. This chemical list will be used to evaluate the sensitivity, reliability...

47 CFR 87.37 - Developmental license.

Code of Federal Regulations, 2012 CFR

2012-10-01

... understanding. The showing must be signed by the applicant. (c) Assignable frequencies. Developmental stations may be authorized to use frequencies available for the service and class of station proposed. The number of frequencies assigned will depend upon the specific requirements of the developmental program...

The i5k Workspace@NAL—enabling genomic data access, visualization and curation of arthropod genomes

PubMed Central

Poelchau, Monica; Childers, Christopher; Moore, Gary; Tsavatapalli, Vijaya; Evans, Jay; Lee, Chien-Yueh; Lin, Han; Lin, Jun-Wei; Hackett, Kevin

2015-01-01

The 5000 arthropod genomes initiative (i5k) has tasked itself with coordinating the sequencing of 5000 insect or related arthropod genomes. The resulting influx of data, mostly from small research groups or communities with little bioinformatics experience, will require visualization, dissemination and curation, preferably from a centralized platform. The National Agricultural Library (NAL) has implemented the i5k Workspace@NAL (http://i5k.nal.usda.gov/) to help meet the i5k initiative's genome hosting needs. Any i5k member is encouraged to contact the i5k Workspace with their genome project details. Once submitted, new content will be accessible via organism pages, genome browsers and BLAST search engines, which are implemented via the open-source Tripal framework, a web interface for the underlying Chado database schema. We also implement the Web Apollo software for groups that choose to curate gene models. New content will add to the existing body of 35 arthropod species, which include species relevant for many aspects of arthropod genomic research, including agriculture, invasion biology, systematics, ecology and evolution, and developmental research. PMID:25332403

Behavior Problems in Toddlers with and without Developmental Delays: Comparison of Treatment Outcomes

ERIC Educational Resources Information Center

Holtz, Casey A.; Carrasco, Jennifer M.; Mattek, Ryan J.; Fox, Robert A.

2009-01-01

The purpose of this study is to examine the effectiveness of an in-home parent management program for toddlers with behavior problems and developmental delays by comparing outcomes for a group of toddlers with developmental delays (n = 27) and a group of toddlers without developmental delays (n = 27). The majority of children lived in single…

Inference of developmental gene regulatory networks beyond classical model systems: new approaches in the post-genomic era.

PubMed

Fernandez-Valverde, Selene L; Aguilera, Felipe; Ramos-Díaz, René Alexander

2018-06-18

The advent of high-throughput sequencing technologies has revolutionized the way we understand the transformation of genetic information into morphological traits. Elucidating the network of interactions between genes that govern cell differentiation through development is one of the core challenges in genome research. These networks are known as developmental gene regulatory networks (dGRNs) and consist largely of the functional linkage between developmental control genes, cis-regulatory modules and differentiation genes, which generate spatially and temporally refined patterns of gene expression. Over the last 20 years, great advances have been made in determining these gene interactions mainly in classical model systems, including human, mouse, sea urchin, fruit fly, and worm. This has brought about a radical transformation in the fields of developmental biology and evolutionary biology, allowing the generation of high-resolution gene regulatory maps to analyse cell differentiation during animal development. Such maps have enabled the identification of gene regulatory circuits and have led to the development of network inference methods that can recapitulate the differentiation of specific cell-types or developmental stages. In contrast, dGRN research in non-classical model systems has been limited to the identification of developmental control genes via the candidate gene approach and the characterization of their spatiotemporal expression patterns, as well as to the discovery of cis-regulatory modules via patterns of sequence conservation and/or predicted transcription-factor binding sites. However, thanks to the continuous advances in high-throughput sequencing technologies, this scenario is rapidly changing. Here, we give a historical overview on the architecture and elucidation of the dGRNs. Subsequently, we summarize the approaches available to unravel these regulatory networks, highlighting the vast range of possibilities of integrating multiple technical advances and theoretical approaches to expand our understanding on the global of gene regulation during animal development in non-classical model systems. Such new knowledge will not only lead to greater insights into the evolution of molecular mechanisms underlying cell identity and animal body plans, but also into the evolution of morphological key innovations in animals.

Early childhood development in deprived urban settlements.

PubMed

Nair, M K C; Radhakrishnan, S Rekha

2004-03-01

Poverty, the root cause of the existence of slums or settlement colonies in urban areas has a great impact on almost all aspects of life of the urban poor, especially the all-round development of children. Examples from countries, across the globe provide evidence of improved early child development, made possible through integrated slum improvement programs, are few in numbers. The observed 2.5% prevalence of developmental delay in the less than 2 year olds of deprived urban settlements, the presence of risk factors for developmental delay like low birth weight, birth asphyxia, coupled with poor environment of home and alternate child care services, highlights the need for simple cost effective community model for promoting early child development. This review on early child development focuses on the developmental status of children in the deprived urban settlements, who are yet to be on the priority list of Governments and international agencies working for the welfare of children, the contributory nature-nurture factors and replicable working models like infant stimulation, early detection of developmental delay in infancy itself, developmental screening of toddlers, skill assessment for preschool children, school readiness programs, identification of mental sub-normality and primary education enhancement program for primary school children. Further, the review probes feasible intervention strategies through community owned early child care and development facilities, utilizing existing programs like ICDS, Urban Basic Services and by initiating services like Development Friendly Well Baby Clinics, Community Extension services, Child Development Referral Units at district hospitals and involving trained manpower like anganwadi/creche workers, public health nurses and developmental therapists. With the decentralization process the local self-government at municipalities and city corporations are financially equipped to be the prime movers to initiate, monitor and promote early child development programs, to emerge as a part and parcel of community owned sustainable development process.

Exonic deletions of AUTS2 in Chinese patients with developmental delay and intellectual disability.

PubMed

Fan, Yanjie; Qiu, Wenjuan; Wang, Lili; Gu, Xuefan; Yu, Yongguo

2016-02-01

Genomic rearrangements involving dosage change of genes have been implicated in a range of developmental disorders. Increasing evidences suggest copy number variations (CNVs) of autism susceptibility candidate gene 2 (AUTS2) are associated with a syndromic form of developmental delay and intellectual disability. However, the genetic and clinical profiles involving AUTS2 variations have not been fully characterized in Asian patients yet, and the outcome of treatments has not been reported. Here we report de novo exonic deletions of AUTS2 detected by chromosomal microarray analysis (CMA) in three Chinese children referred to the clinic for developmental delay, including two deletions involving only exon 6 (98.4 and 262 kb, respectively) and one deletion involving the C-terminal of AUTS2 (2147 kb). The phenotypic presentations of these three patients were described and compared with previous cases in literature. In addition, we presented the outcome of hormonal treatment for short stature in one patient. © 2015 Wiley Periodicals, Inc.

Myxococcus xanthus Developmental Cell Fate Production: Heterogeneous Accumulation of Developmental Regulatory Proteins and Reexamination of the Role of MazF in Developmental Lysis

PubMed Central

Lee, Bongsoo; Holkenbrink, Carina; Treuner-Lange, Anke

2012-01-01

Myxococcus xanthus undergoes a starvation-induced multicellular developmental program during which cells partition into three known fates: (i) aggregation into fruiting bodies followed by differentiation into spores, (ii) lysis, or (iii) differentiation into nonaggregating persister-like cells, termed peripheral rods. As a first step to characterize cell fate segregation, we enumerated total, aggregating, and nonaggregating cells throughout the developmental program. We demonstrate that both cell lysis and cell aggregation begin with similar timing at approximately 24 h after induction of development. Examination of several known regulatory proteins in the separated aggregated and nonaggregated cell fractions revealed previously unknown heterogeneity in the accumulation patterns of proteins involved in type IV pilus (T4P)-mediated motility (PilC and PilA) and regulation of development (MrpC, FruA, and C-signal). As part of our characterization of the cell lysis fate, we set out to investigate the unorthodox MazF-MrpC toxin-antitoxin system which was previously proposed to induce programmed cell death (PCD). We demonstrate that deletion of mazF in two different wild-type M. xanthus laboratory strains does not significantly reduce developmental cell lysis, suggesting that MazF's role in promoting PCD is an adaption to the mutant background strain used previously. PMID:22493014

Translational Genomics in Low and Middle Income Countries: Opportunities and Challenges

PubMed Central

Tekola-Ayele, Fasil; Rotimi, Charles N.

2015-01-01

Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low and middle income countries (LMIC) have participated minimally in genomic research for several reasons including lack of coherent national policies, limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genome Project and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomics research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and socio-cultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomics research, we advocate that large-scale genomics research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and socio-cultural uniqueness. These policies should encourage international collaboration and promote link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC. PMID:26138992

Communication Deficits in Infants and Toddlers with Developmental Disabilities

ERIC Educational Resources Information Center

Hattier, Megan A.; Matson, Johnny L.; Sipes, Megan; Turygin, Nicole

2011-01-01

Research that focuses on detecting and assessing the presence of communication impairments in children with developmental disabilities exists. However, more research is needed which compares these deficits across individuals with various developmental disabilities. This information could inform the assessment process and treatment programs.…

Developmental biology, the stem cell of biological disciplines.

PubMed

Gilbert, Scott F

2017-12-01

Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

The Teacher Advisor Program: An Innovative Approach to School Guidance.

ERIC Educational Resources Information Center

Myrick, Robert D.; And Others

The Teacher Advisor Program (TAP) is an innovative developmental approach to counseling that directly involves teachers as advisors to 18 to 20 students, with whom they meet both individually and in group sessions. An introductory chapter that cites the need for a developmental approach to counseling in contemporary schools and the potential role…

Quality of Life of Adults with Pervasive Developmental Disorders and Intellectual Disabilities

ERIC Educational Resources Information Center

Gerber, F.; Baud, M. A.; Giroud, M.; Carminati, G. Galli

2008-01-01

The purpose of this study was to observe quality of life (QoL) and global evolution of persons with Pervasive Developmental Disorders (PDD) in three different groups. Individualized programs for PDD were compared to traditional programs for intellectual disabilities. Behavioural disorders were repeatedly evaluated using the Aberrant Behaviour…

Insights on Using Developmental Evaluation for Innovating: A Case Study on the Cocreation of an Innovative Program

ERIC Educational Resources Information Center

Lam, Chi Yan; Shulha, Lyn M.

2015-01-01

This article contributes to research on evaluation by examining the capacity and contribution of developmental evaluation for innovating. This case study describes the "preformative development" of an educational program (from conceptualization to pilot implementation) and analyzes the processes of innovation within a developmental…

Interdisciplinary Early Intervention for Developmentally Delayed Infants and Young Children: A Family-Oriented Approach.

ERIC Educational Resources Information Center

Russell, Fay F.; And Others

Intended to help developers of early intervention programs for children with developmental disabilities, the book provides philosophy, methods, and procedures based on experiences of the Child Development Center of the University of Tennessee Center for Health Sciences. The first section presents a program description including information on…

Integration Experiences Casebook: Program Ideas in Aging and Developmental Disabilities.

ERIC Educational Resources Information Center

Janicki, Matthew P.; Keefe, Robert M.

An assortment of 38 case studies illustrates efforts to integrate elderly individuals with developmental disabilities into generic aging services and into community life. The case studies include models and practice experiences that aided seniors to retire, participate in programs and services, and become part of their community's aging network.…

The Mistakes We Make and How We Correct Them: What I've Learned as a Consultant

ERIC Educational Resources Information Center

Boylan, Hunter R.

2009-01-01

This manuscript describes five of the most common mistakes made in developmental education programs based on the author's experiences, which include consulting at over 200 community colleges. These mistakes include failing to create a seamless transition, failing to train adjunct instructors, failing to coordinate developmental programs, failing…

Evolving Definitions of Autism and Impact on Eligibility for Developmental Disability Services: California Case Example

ERIC Educational Resources Information Center

Williams, Marian E.; Wheeler, Barbara Y.; Linder, Lisa; Jacobs, Robert A.

2017-01-01

When establishing eligibility for developmental disability (DD) services, definitions of specific diagnostic conditions, such as autism, impact policy. Under the Medicaid home and community-based waiver program, states have discretion in determining specific program or service eligibility criteria, the nature of supports to be provided, and the…

The Carolina Abecedarian Project: A Longitudinal and Multidisciplinary Approach to the Prevention of Developmental Retardation.

ERIC Educational Resources Information Center

Ramey, Craig T.; And Others

This progress report describes the subjects, program and curriculum development, and collected psychological and medical data of the Carolina Abecedarian Project, an intervention program, begun in 1972. The purpose of this project is to bring together a multidisciplinary team of researchers to demonstrate that the developmental retardation of…