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Santure, Anna Wensley, and n/a. "Quantitative genetic models for genomic imprinting." University of Otago. Department of Zoology, 2006. http://adt.otago.ac.nz./public/adt-NZDU20060811.134008.
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A gene is imprinted when its expression is dependent on the sex of the parent from which it was inherited. An increasing number of studies are suggesting that imprinted genes have a major influence on medically, agriculturally and evolutionarily important traits, such as disease severity and livestock production traits. While some genes have a large effect on the traits of an individual, quantitative characters such as height are influenced by many genes and by the environment, including maternal effects. The interaction between these genes and the environment produces variation in the characteristics of individuals. Many quantitative characters are likely to be influenced by a small number of imprinted genes, but at present there is no general theoretical model of the quantitative genetics of imprinting incorporating multiple loci, environmental effects and maternal effects. This research develops models for the quantitative genetics of imprinting incorporating these effects, including deriving expressions for genetic variation and resemblances between relatives. Imprinting introduces both parent-of-origin and generation dependent differences in the derivation of standard quantitative genetic models that are generally equivalent under Mendelian expression. Further, factors such as epistasis, maternal effects and interactions between genotype and environment may mask the effect of imprinting in a quantitative trait. Maternal effects may also mimic a number of signatures in variance and covariance components that are expected in a population with genomic imprinting. This research allows a more comprehensive understanding of the processes influencing an individual�s characteristics.
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Whitehead, Joanne. "Genomic Imprinting in Development and Evolution." Doctoral thesis, Uppsala universitet, Zoologisk utvecklingsbiologi, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4491.
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Genetic information is encoded by the linear sequence of the DNA double helix, while epigenetic information is overlayed as the packaging of DNA and associated proteins into the chromatin structure. Variations in chromatin structure play a vital role in establishing and maintaining patterns of gene expression during differentiation and development of higher eukaryotes, and disruption of this epigenetic gene regulation can lead to cancer. Mammals display an epigenetic phenomenon known as genomic imprinting, which provides an ideal model system for the study of epigenetics. Genes subject to genomic imprinting are differentially expressed within a single cell depending on the parental origin of the chromosome. Imprinting of the maternally expressed H19 gene and the adjacent paternally expressed Igf2 gene is regulated by the chromatin insulator protein CTCF. The studies presented in this thesis aim to investigate the functional mechanisms of CTCF-dependent gene regulation at the H19/Igf2 locus and at numerous other target sites throughout the genome. We have investigated the role of CTCF and a related protein BORIS in establishing the maternal to paternal imprint transition in chromatin structure at the H19/Igf2 locus in the male germline. We have developed novel microarray based methods to identify and characterize numerous new CTCF target sites throughout the mouse genome. We have shown that CTCF acts as part of the RNA polymerase II complex. We have identified the post-translational modification by addition of ADP-ribose polymers to CTCF, and demonstrated that this modification regulates its insulating ability. The results of these studies of CTCF-dependent epigenetic gene regulation are discussed in light of the evolution of genomic imprinting and chromatin insulators, and a novel role for poly ADP-ribosylation of CTCF in the progression of cancer is proposed.
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McCann, Jennifer. "Variability of genomic imprinting in human disease." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84294.
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Genomic imprinting is the differential expression of genetic material depending on the parent from which it is transmitted. It is involved in the pathogenesis of many diseases, especially those involved in development, growth abnormalities and cancer. We examined the extent of and the variability of genomic imprinting amongst individuals in three human diseases, Wilms' tumour, Type 1 diabetes and Silver-Russell syndrome.Wilms' tumour (WT) is a renal embryonal cancer associated with overexpression of the insulin-like growth factor 2 (IGF2). IGF2 is directed to the lysosomes for degradation by the mannose-6-phosphate/insulin-like growth factor two receptor (M6P/IGF2R) encoded by the IGF2R gene, a known tumour suppressor gene on 6826. IGF2R is imprinted in the mouse, with exclusive maternal expression. In humans, however, IGF2R imprinting is a polymorphic phenomenon only being found in a small subset of people. We present results suggesting that IGF2R imprinting provides the first "hit" in IGF2R inactivation in WT, and show the presence of a second "hit" in the form of deletions detectable as loss of heterozygosity.
Another disease investigated in this report is Type 1 diabetes (TID), an autoimmune, polygenic disease. Of the several T1D loci, IDDM8 on 6q, has been found to be subject to parent-of-origin effects and encompasses IGF2R. M6P/IGF2R is involved in immune system regulation. In this study we show an association between TID and IGF2R that is confined to maternally inherited alleles. Our results strongly suggest that IGF2R is a TID susceptibility gene and may be universally imprinted at some tissue or developmental stage not yet studied.
A third disease displaying both tissue-specific and isoform-specific imprinting is Silver-Russell syndrome (SRS), a growth disorder associated with double dose of a maternally expressed gene within 7p11.2--p13, a region in which the imprinted GRB10 gene was a prime candidate. We studied the complex tissue and isoform-dependence of GRB10 imprinting and demonstrated absence of imprinting in growth plate cartilage, the tissue most directly involved in linear growth thus eliminating GRB10 as the gene responsible for SRS.
It is evident that genomic imprinting plays a prominent role in various diseases. Imprinted genes can be expressed in a tissue-specific, isoform-specific or a temporally regulated manner. In addition, there is a wide variability of imprinting between individuals.
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Sun, Bowen. "Genomic imprinting in mouse pluripotent stem cells." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609478.
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Zhou, Jiyuan. "Single-marker and haplotype analyses for detecting parent-of-origin effects using family and pedigree data." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B4308543X.
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Lucifero, Diana. "Developmental regulation of genomic imprinting by DNA methylation." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85573.
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Maintaining appropriate patterns of gene expression in the gametes and during early embryogenesis is essential for normal development. DNA methylation is an epigenetic means of regulating gene expression and is an important molecular mark regulating the sex-specific expression of genes subject to genomic imprinting. Imprinted genes are expressed from only one of two inherited chromosomes and are differentially marked during gametogenesis to allow for their parental allele specific expression. These genes affect embryo growth, placental function, behavior after birth and are implicated in the etiology of a number of human diseases. The primary objective of this thesis was to gain a better understanding of the developmental dynamics and origins of DNA methylation profiles regulating maternally methylated imprinted genes during mouse oocyte development. Studies revealed that maternally methylated imprinted genes acquire methylation within their DMRs during postnatal oocyte growth and that this acquisition occurs in a gene and allele specific manner. It was also observed that maternal methylation imprint acquisition is related to oocyte diameter and that a repetitive parasitic element also acquires methylation during this period. DNA methylation is catalyzed by DNMTs and investigations into the developmental expression profiles of Dnmt3a, Dnmt3b and Dnmt3L indicated that transcript accumulation of these enzymes during oocyte development coincided with the timing of maternal methylation imprint establishment. Moreover, expression analysis in DNMT-depleted oocytes suggested these enzymes to be coordinately regulated. Additional studies aimed at developing another model of oocyte imprinting lead to the identification and characterization of a putative bovine Snrpn DMR. Its DNA methylation profile was found to be conserved with that of mouse and human. Snrpn DNA methylation analysis in bovine IVF and SCNT embryos revealed slight loss of methylatio
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Rancourt, Rebecca Catherine. "Functional genomic analysis of an imprinting control region." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608514.
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Adams, Sally. "Genomic imprinting in the endosperm of Arabidopsis thaliana." Thesis, University of Bath, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.760803.
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Coan, Philip Michael. "Placental development and genomic imprinting in the mouse." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613928.
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Hore, Timothy Alexander, and timothy hore@anu edu au. "THE EVOLUTION OF GENOMIC IMPRINTING AND X CHROMOSOME INACTIVATION IN MAMMALS." The Australian National University. Research School of Biological Sciences, 2008. http://thesis.anu.edu.au./public/adt-ANU20081216.152553.
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Genomic imprinting is responsible for monoallelic gene expression that depends on the sex of the parent from which the alleles (one active, one silent) were inherited. X-chromosome inactivation is also a form of monoallelic gene expression. One of the two X chromosomes is transcriptionally silenced in the somatic cells of females, effectively equalising gene dosage with males who have only one X chromosome that is not complemented by a gene poor Y chromosome. X chromosome inactivation is random in eutherian mammals, but imprinted in marsupials, and in the extraembryonic membranes of some placentals. Imprinting and X inactivation have been studied in great detail in placental mammals (particularly humans and mice), and appear to occur also in marsupial mammals. However, both phenomena appear to have evolved specifically in mammals, since there is no evidence of imprinting or X inactivation in non-mammalian vertebrates, which do not show parent of origin effects and possess different sex chromosomes and dosage compensation mechanisms to mammals.¶
In order to understand how imprinting and X inactivation evolved, I have focused on the mammals most distantly related to human and mouse. I compared the sequence, location and expression of genes from major imprinted domains, and genes that regulate genomic imprinting and X-chromosome inactivation in the three extant mammalian groups and other vertebrates. Specifically, I studied the evolution of an autosomal region that is imprinted in humans and mouse, the evolution of the X-linked region thought to control X inactivation, and the evolution of the genes thought to establish and control differential expression of various imprinted loci. This thesis is presented as a collection of research papers that examines each of these topics, and a review and discussion that synthesizes my findings.¶
The first paper reports a study of the imprinted locus responsible for the human Prader-Willi and Angelman syndromes (PWS and AS). A search for kangaroo and platypus orthologues of PWS-AS genes identified only the putative AS gene UBE3A, and showed it was in a completely different genomic context to that of humans and mice. The only PWS gene found in marsupials (SNRPN) was located in tandem with its ancient paralogue SNRPB, on a different chromosome to UBE3A. Monotremes apparently have no orthologue of SNRPN. The several intronless genes of the PWS-AS domain also have no orthologues in marsupials or monotremes or non-mammal vertebrates, but all have close paralogues scattered about the genome from which they evidently retrotransposed. UBE3A in marsupials and monotremes, and SNRPN in marsupials were found to be expressed from both alleles, so are not imprinted. Thus, the PWA-AS imprinted domain was assembled from many non-imprinted components relatively recently, demonstrating that the evolution of imprinting has been an ongoing process during mammalian radiation.¶
In the second paper, I examine the evolution of the X-inactivation centre, the key regulatory region responsible for X-chromosome inactivation in humans and mice, which is imprinted in mouse extraembryonic membranes. By sequencing and aligning flanking regions across the three mammal groups and non-mammal vertebrates, I discovered that the region homologous to the X-inactivation centre, though intact in birds and frogs, was disrupted independently in marsupial and monotreme mammals. I showed that the key regulatory RNA of this locus (X-inactive specific transcript or XIST) is absent, explaining why a decade-long search for marsupial XIST was unsuccessful. Thus, XIST is eutherian-specific and is therefore not a basic requirement for X-chromosome inactivation in all mammals.¶
The broader significance of the findings reported in these two papers is explored with respect to other current work regarding the evolution and construction of imprinted loci in mammals in the form of a review. This comparison enabled me to conclude that like the PWS-AS domain and the X-inactivation centre, many domains show unexpected construction from disparate genomic elements that correlate with their acquisition of imprinting.¶
The fourth and last paper examines the evolution of CCCTC-binding Factor (CTCF) and its parologue Brother Of Regulator of Imprinted Sites (BORIS) which contribute to the establishment and interpretation of genomic imprinting at the Insulin-Like Growth Factor 2/H19 locus. In this paper I show that the duplication of CTCF giving rise to BORIS occurred much earlier than previously recognised, and demonstrate that a major change in BORIS expression (restriction to the germline) occurred in concert with the evolution of genomic imprinting. The papers that form the bulk of this thesis show that the evolution of epigenetic traits such as genomic imprinting and X-chromosome inactivation is labile and has apparently responded rapidly to different selective pressures during the independent evolution of the three mammal groups. I have introduced these papers, and discussed them generally in terms of current theories of how and why these forms of monoallelic expression have evolved in mammals.
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Mungall, Andrew James. "Evolution and gene regulation of the genomic imprinting mechanism." Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487154.
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Genomic imprinting describes an epigenetic mechanism by which genes are active or silent depending on their parental origin. Imprinting exists in plants and mammals, but how this monoallelic expression mechanism has evolved is not understood at the molecular leveL Here I describe the mapping, sequencing and analysis of vertebrate orthologous imprinted regions spanning 11.5 Mb of genomic sequence from species with and without genomic imprinting. In eutherian (placental) mammals, imprinting can be regulated by differential DNA methylation, non-coding RNAs, enhancers and insulator elements. The systematic sequence comparison of the IGF2-HI9 imprinting cluster, in eutherians and marsupials (tammar wallaby and opossum), has revealed the presence of the enigmatic noncoding Ri'JA H19 in marsupials. Furthermore, we have characterised the marsupial / H19 expression status and identified key regulatory elements required for the germline imprinting of the neighbouring IGF2 gene. All the major hallmarks of the imprinting mechanism of the IGF2-HI9 locus were found to be conserved in therian mammals. In mammals, this imprinting system is therefore the most conserved germline derived epigenetic mechanism discovered so far. The high-quality genomic sequences have provided early glimpses of the genomic landscapes for species such as the monotreme platypus and marsupial tammar wallaby for which little was previously known. Comparative sequence analysis was used to identify candidate regulatory elements in the neighbouring imprinting centre 1 and 2 regions of human chromosome llp1S.5. Nine novel enhancer elements were identified following in zitro gene-reporter assays and correlation of conserved sequences with recent ENCODE data revealed probable functions for a further 24 elements.
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James, Rowena Sarah. "Genomic imprinting and the aetiology of human chromosome abnormalities." Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295874.
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Mathers, Lucille Sarah. "The role of DNA methyltransferases in plant genomic imprinting." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512263.
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Genomic imprinting is the epigenetic modification of loci, primarily by DNA methylation, which results in parent-of-origin-specific monoallelic expression of a small subset of genes. In plants, imprinting occurs during endosperm development and a balance of maternally- and paternally-expressed imprinted genes is essential for normal seed development. Dependence on DNA methylation for imprinting highlights the potential to manipulate seed development, and consequently seed size, by altering DNA methyltransferase activity. DNA METHYLTRANSFERASE 1 (MET1) is the primary plant maintenance DNA methyltransferase and plays a significant role in imprinting. However, no evaluation of the potential role for other MET1 family members in genomic imprinting has been reported. The current model for the control of imprinting in plants suggests that maintenance DNA methyltransferases are required throughout development, yet the tissue-specific requirement of these enzymes is unconfirmed as analysis has relied solely on constitutive DNA methyltransferase mutants. To address these problems and to evaluate the potential to alter seed size, the work reported in this thesis investigated the potential involvement of putative maintenance DNA methyltransferases MET2a, MET2b and MET3 and the tissue-specific role of MET1 in imprinting. Imprinting was not significantly altered in met2a-1, met2b-1 and met3-1 mutants, indicating that MET1 is the sole DNA methyltransferase required for imprinting. Transcriptional analysis suggested MET1 is expressed throughout floral organ development and in the male and female gametophyte generation indicating that MET1 is potentially available to maintain imprinting-dependent methylation in these tissues. Tools to suppress MET1 tissuespecifically were developed to investigate the tissue-specific requirement of MET1 for imprinting. Analysis indicates that such tools could also be used to alter seed size by manipulating imprinting in commercially important species. Further work is needed to validate this approach.
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Tucker, Kerry Lee. "A genetic investigation of the establishment of genomic imprinting." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/46070.
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Clayton, Crisenthiya Indunil. "Methylation and genomic imprinting in the bumblebee, Bombus terrestris." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/27798.
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Genomic imprinting, the parent-of-origin specific silencing of alleles, plays an important role in phenotypic plasticity and consequently evolution. The leading explanation for genomic imprinting is Haig's conflict theory, which suggests that alleles from each parent have evolved under different selectional pressures, resulting in the differential expression of patrigenes and matrigenes. Previous studies have mainly used mammals and flowering plants to test Haig’s theory. However, there is a lack of independent evidence to support the theory. My PhD thesis attempts to conduct an independent test of Haig’s conflict theory using buff tailed bumblebee Bombus terrestris. A methylation system to facilitate genomic imprinting has not been found in this species. Therefore the first aim of the study was to establish the presence of a functional methylation system in B. terrestris before testing Haig's conflict theory using worker reproduction in queen-less colonies. The initial finding is that a methylation system exists in B. terrestris. The next study, investigating the presence of methylated genes, revealed differential methylation patterns in caste and life stages. Finally, genes involved with worker reproduction in a range of social insects were identified, but distinguishing the matrigene and the patrigene for each gene was unsuccessful. Therefore the final study investigating the presence of imprinted genes in B. terrestris and whether they conform to the expression patterns hypothesised by Haig’s conflict theory could not be analysed. Although this study did not provide conclusive evidence to support Haig’s conflict theory, the presence of methylation in genes involved with worker reproduction in reproducing and non-reproducing B. terrestris workers suggests that further analysis is needed. With adequate evidence, proving Haig’s conflict theory will not only expand our knowledge of invertebrate methylation, but also our understanding of conflict within social insect societies and our knowledge of how genomic imprinting affects phenotypic plasticity.
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Picard, Colette Lafontaine. "Dynamics of DNA methylation and genomic imprinting in arabidopsis." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122539.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2019Cataloged from PDF version of thesis.
Includes bibliographical references (pages 210-226).
DNA methylation is an epigenetic mark that is highly conserved and important in diverse cellular processes, ranging from transposon silencing to genomic imprinting. In plants, DNA methylation is both mitotically and meiotically heritable, and changes in DNA methylation can be generationally stable and have long-lasting consequences. This thesis aims to improve understanding of DNA methylation dynamics in plants, particularly across generations and during reproduction. In the first project, I present an analysis of the generational dynamics of gene body methylation using recombinant inbred lines derived from differentially methylated parents. I show that while gene body methylation is highly generationally stable, changes in methylation state occur nonrandomly and are enriched in regions of intermediate methylation.
Important DNA methylation changes also occur during seed development in flowering plants, and these changes underlie genomic imprinting, the phenomenon of parent-of-origin specific gene expression. In plants, imprinting occurs in the endosperm, a seed tissue that functions analogously to the mammalian placenta. Imprinted expression is linked to DNA methylation patterns that serve to differentiate the maternally- and paternally-inherited alleles, but the mechanisms used to achieve imprinted expression are often unknown. I next explore imprinted expression and DNA methylation in Arabidopsis lyrata, a close relative of the model plant Arabidopsis thaliana. I find that the majority of imprinted genes in A. lyrata endosperm are also imprinted in A. thaliana, suggesting that imprinted expression is generally conserved. Surprisingly, a subset of A. lyrata imprinted genes are associated with a novel DNA methylation pattern and may be regulated by a different mechanism than their A.
thaliana counterparts. I then explore the genetics of paternal suppression of the seed abortion phenotype caused by mutation of a maternally expressed imprinted gene. Finally, I present the first large single-nuclei RNA-seq dataset generated in plants, reporting data from 1,093 individual nuclei obtained from developing seeds. I find evidence of previously uncharacterized cell states in endosperm, and examine imprinted expression at the single-cell level. Together, these projects contribute to our understanding of DNA methylation and imprinting dynamics during plant development, and highlight the strong generational stability of certain DNA methylation patterns.
by Colette Lafontaine Picard.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Computational and Systems Biology Program
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Leung, Tsin-wah. "Imprinting genes in gestational trophoblastic diseases /." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36434504.
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Leung, Tsin-wah, and 梁展華. "Imprinting genes in gestational trophoblastic diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B45010845.
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Bowden, Lucy M. "Analysis of parent-specific gene expression in the mouse using high resolution two-dimensional electrophoresis of proteins." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337986.
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Holmes, Rebecca Jane. "Analysis of a novel cluster of imprinted genes." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270370.
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Tavoosidana, Gholamreza. "Epigenetic Regulation of Genomic Imprinting and Higher Order Chromatin Conformation." Doctoral thesis, Uppsala universitet, Zoologisk utvecklingsbiologi, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7435.
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The genetic information encoded by the DNA sequence, can be expressed in different ways. Genomic imprinting is an epigenetic phenomenon that results in monoallelic expression of imprinted genes in a parent of origin-dependent manner. Imprinted genes are frequently found in clusters and can share common regulatory elements. Most of the imprinted genes are regulated by Imprinting Control Regions (ICRs). H19/Igf2 region is a well known imprinted cluster, which is regulated by insulator function of ICR located upstream of the H19 gene. It has been proposed that the epigenetic control of the insulator function of H19 ICR involves organization of higher order chromatin interactions. In this study we have investigated the role of post-translational modification in regulating insulator protein CTCF (CCCTC-binding factor). The results indicated novel links between poly(ADP-ribosyl)ation and CTCF, which are essential for regulating insulators function. We also studied the higher order chromatin conformation of Igf2/H19 region. The results indicated there are different chromatin structures on the parental alleles. We identified CTCF-dependent loop on the maternal allele which is different from the paternal chromatin and is essential for proper imprinting of Igf2 and H19 genes. The interaction of H19 ICR with Differentially Methylated Regions (DMRs) of Igf2 in a parent-specific manner maintains differential epigenetic marks on maternal and paternal alleles. The results indicate that CTCF occupies specific sites on highly condensed mitotic chromosomes. CTCF-dependent long-range key interaction on the maternal allele is maintained during mitosis, suggesting the possible epigenetic memory of dividing cells. In this study, we developed a new method called Circular Chromosome Conformation Capture (4C) to screen genome-wide interactions with H19 ICR. The results indicated there are wide intra- and inter-chromosomal interactions which are mostly dependent on CTCF-binding site at H19 ICR. These observations suggest new aspects of epigenetic regulation of the H19/Igf2 imprinted region and higher order chromatin structure.
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Tavoosidana, Gholamreza. "Epigenetics Regulation of Genomic Imprinting and Higher Order Chromatin Conformation /." Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7435.
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Gygax, Derek. "Comprehensive Review on the Existence of Genomic Imprinting in Aves." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3375.
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Genomic imprinting results in monoallelic parent-of-origin gene expression. Therian mammals show conclusive evidence for imprinting, while the evidence in Aves is conflicting. It’s unclear if Aves have the proteins necessary for establishment and maintenance of imprinting loci. Every examined avian orthologue to mammalian imprinted genes shows biallelic expression providing evidence for a lack of imprinting in Aves. While the known parent-of-origin quantitative trait loci in chicken do not overlap with differentiated methylated regions, further analysis with a larger sample size is required. No transcript in the chicken transcriptome at incubation day 4.5 shows parent-of-origin expression, providing strong evidence for a lack of imprinting at this stage of development. Investigating expression of the chicken transcriptome at additional developmental time points, and the transcriptome of other Aves would provide decisive evidence on the presence or lack of imprinting in Aves. Based on current knowledge, Aves lack imprinting as observed in mammals.
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Wroe, Stephanie Fay. "Identification of imprinted genes on mouse distal Chr 2 by suppression subtractive hybridisation and a candidate gene approach." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343038.
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Zhou, Jiyuan, and 周基元. "Single-marker and haplotype analyses for detecting parent-of-origin effects using family and pedigree data." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B4308543X.
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Norris, Dominic Paul. "X chromosome inactivation in the mouse." Thesis, Open University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282142.
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Hore, Timothy Alexander. "The evolution of genomic imprinting and X chromosome inactivation in mammals /." View thesis entry in Australian Digital Theses Program, 2008. http://thesis.anu.edu.au/public/adt-ANU20081216.152553/index.html.
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陳春玲 and Chunling Chen. "A study of genomic imprinting and DNA methylation in gynecological cancers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31241517.
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Wakeling, Emma Louise. "Genomic imprinting and Silver-Russell syndrome : candidate genes on chromosome 7." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325386.
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Ragsdale, Gillian. "Genomic imprinting and human cognition : parent-of-origin effects on behaviour." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611803.
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Amarasinghe, Kankanamge Harindra Eranthi. "DNA methylation, genomic imprinting and polyphenism in the bumblebee, Bombus terrestris." Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/32434.
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Genomic imprinting, the parent-of-origin specific expression of alleles is an important area of research in evolutionary biology and human health (cancers and developmental syndromes). Haig’s kinship theory suggests that the maternally and paternally derived alleles of offspring resource allocation genes have evolved under different selectional pressures. Thus within different kin related individuals they are expressed unequally, each allele favouring their own inclusive fitness. Social insects provide the best independent model system to study the evolution of imprinting. However, imprinting has not been discovered in any social insect. My PhD lays the groundwork for a social insect model of genomic imprinting. Methylation is a common epigenetic tag of genomic imprinting in mammals and flowering plants. I found that a functional methylation system which is involved in the reproductive caste formation, development and social behaviour is present in the bumblebee, Bombus terrestris. Under queenless conditions, reproducing and non-reproducing worker castes show different brain methylome patterns. Alteration of methylation can cause a sterile worker to turn into a reproductive worker with increased aggressive behaviour and ovary development. Next I found monoallelic methylation associated with monoallelic expression in genes predicted to be imprinted by Haig’s theory. Also, differential allele specific expression that are apparently due to parent-of-origin effects is present in reproduction loci of B. terrestris. Reciprocal crosses at these loci is recommended as further work, to check whether these expression patterns are due to genomic imprinting. I assess the effects of maternally and paternally contributed sociobiological factors on worker male production and found that the paternity or the queen mating frequency has a significant influence on worker male production in eusocial Hymenoptera. Finally, I also studied the polyphenism involved in phase dependent behavioural plasticity of locusts. I found that the transition of solitarious to fully gregarious behaviour in the desert locust, Schistocerca gregaria begins without significant changes in the DNA methylation landscape of the CNS but subjected to the pronounced differences at a later stage.
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Zhang, Fangyuan. "Detecting Genomic Imprinting and Maternal Effects in Family-Based Association Studies." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429820748.
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Frost, Jennfier May. "Genomic imprinting in human stem cells and human peripheral blood leukocytes." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/4661.
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Genomic imprinting in mammals is the monoallelic expression of genes in a parent-of origin dependent manner. Imprinting can be transient and tissue specific, indicative of its role in specific developmental regimes. Placental specific imprinting has been found to be non-conserved between humans and mice. A new model of human trophoblast, trophoblast stem cells (hTS), differentiated from human embryonic stem (hES) cells, allows analysis of placental specific imprinting during the earliest stages of placentation. The use of cell lines to characterise imprinting in vivo is limited by epigenetic alterations during cell line derivation and culture. hES cells may harbour exceptional dichotomy in epigenotype compared to their in vivo counterpart, the preimplantation embryo, due to their derivation from superovulated embryos during genome-wide epigenetic remodelling. There are very limited options for analysis of imprinting in vivo in human tissue, and the most practical and available resource is human peripheral blood. Imprinted gene expression and in normal healthy blood is currently uncharacterised. Analysis of the Kcnq1/KCNQ1 cluster, which contains six ubiquitous and eight murine placental specific imprinted transcripts, in hTS cells showed that imprinting was not conserved for the placental specific transcripts. In addition, one of the ubiquitously imprinted transcripts was not imprinted in hTS cells or undifferentiated hES cells. Subsequent genome-wide imprinting analysis in undifferentiated hES cells and human fetal mesenchymal stem cells (fMSC), not derived from superovulated conceptions or during genome remodelling, found abnormal biallelic expression of several imprinted genes, to an extent consistent between both types of stem cell. In fMSC, differentially methylated imprinting control regions (ICRs) were unexpectedly normal. In hES cells, however, both hypo- and hypermethylation was detected at several ICRs. Imprinted gene expression following differentiation and expression of pluripotentiality conferring transcription factors were measured to further assess the potential of fMSC. Imprinting did not change following differentiation, however, pluripotency transcription factor expression was almost negligible compared to that in hES cells. Imprinting in peripheral blood was characterised by virtually undetectable expression of most transcripts, biallelic expression of those which could be detected and only a minority of genes remaining imprinted. These findings provide an overview of imprinted gene expression in human stem cells, complimenting previous work on hES cells. Whilst imprinted gene expression is universally disrupted by cell culture, the results suggest that methylation at ICRs may be sensitive to derivation associated specifically with hES cells, as it was normal in the fMSC lines. This lack of correlation between methylation at ICRs and imprinted expression was also mirrored in the hES cells as aberrant methylation patterns were stochastic, and did not correlate with the abnormal imprinted expression. This indicates that the loss of imprinting in cultured cells is caused by an epigenetic mechanism other than aberrant methylation. In peripheral blood, the often biallelic nature of imprinted gene expression limits the use of this tissue as a control, and also of this feature as an indicator of disease. Six of the 36 transcripts analysed remained monoallelic in blood giving them potential as biomarkers, so their imprinting status in disease should be characterised further.
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Chen, Chunling. "A study of genomic imprinting and DNA methylation in gynecological cancers /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2344017X.
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Madon, Marta. "Characterisation of the imprinted genes in mouse, Grb10 and Dlk1." Thesis, University of Bath, 2012. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557801.
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Genomic imprinting provides an exception to the Mendelian rule of inheritance, as imprinted genes are preferentially expressed in a parent-of-origin specific manner. They play important roles in the development of embryonic and extra-embryonic lineages and postnatally in the maintenance of correct metabolic homeostasis as well as regulation of adult behaviour. The parental conflict theory predicts that maternally expressed genes act as growth suppressors, limiting the usage of maternal resources, and that paternally expressed genes function in an opposite manner to promote growth at the expense of maternal resources. Growth factor bound protein 10 (Grb10) is an imprinted gene encoding an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules. Recently, our lab has identified Grb10 as a unique imprinted gene capable of influencing fetal growth, postnatal energy metabolism and adult behaviour depending on functions of each of the parental alleles in distinct tissues. Grb10 predominantly expressed from the maternal allele during embryogenesis affects fetal and placental growth along with postnatal glucose homeostasis, whereas paternal Grb10 expression within the CNS influences social behaviour. Delta-like homologue 1 is (Dlk1) a paternally expressed imprinted gene coding for a protein belonging to the Notch/Delta family that acts as a membrane-associated or a soluble protein known to regulate differentiation of various cell types, notably adipocytes. In vivo Dlk1 has been associated with perinatal survival, regulation of normal growth and development and maintenance of the correct course of adipogenesis. Here a hypothesis is proposed that Grb10, as a predominantly maternally expressed growth inhibitor and Dlk1, a paternally expressed growth promoter, act antagonistically in a common genetic pathway. To test this hypothesis, we have generated Grb10m/+/Dlk1+/p double knockout mice and performed a phenotypic characterisation in comparison with wild type as well as the respective single knockout animals. Results obtained from allometric and metabolic analyses, together with histological studies, reveal strong similarities between the phenotypes of Grb10m/+and Grb10m/+/Dlk1+/p knockout mice. We found that overgrowth of Grb10m/+/Dlk1+/p embryos and placentae resemble the phenotype seen in Grb10m/+ mutants and that tissue overgrowth most likely results from higher proliferation rates of Grb10m/+and Grb10m/+/Dlk1+/p cells. Furthermore, Grb10m/+and Grb10m/+/Dlk1+/p knockout mice each exhibit improved glucose clearance and share an unusual characteristic accumulation of lipid in neonatal liver. These results are consistent with the proposed hypothesis and indicate that the Dlk1 and Grb10 genes might be involved in the same genetic pathway. Moreover, the data suggest Dlk1 is an inhibitor of Grb10 which is in turn acting as a growth suppressor.
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Jones, Meaghan Jessica. "Characterization of a novel fluorescent reporter of genomic imprinting in the mouse." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/23320.
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Regulation of inserted transcriptional units by epigenetic means has been reported for many years, and has been used to study characteristics of epigenetic regulation. Some of these transgenes have become regulated by genomic imprinting, and thus are expressed from only one of the two parental chromosomes and, occasionally, acquire parent-of-origin-specific epigenetic markings such as DNA methylation. These transgenes in particular have been useful in elucidating mechanisms of imprinted regulation. Here is described the first imprinted fluorescent transgene, a green fluorescent protein (GFP) gene inserted in the distal MMU7 imprinted domain between the imprinting centers 1 and 2 (IC1 and IC2) regulated regions. This transgene, called Tel7KI, exhibits imprinted expression only from the maternal allele, and is silenced and DNA methylated on the paternal allele in post-implantation embryos. In the embryo this allele-specificity is consistent throughout all tissues and developmental stages analyzed except the developing germ line, making Tel7KI a potential reporter of epigenetic reprogramming in that lineage. In the placenta, imprinted expression and DNA methylation of Tel7KI is lost, and both alleles are expressed and methylated at moderate levels. Finally, an analysis of the effect of IC2 on silencing of Tel7KI in an embryonic stem cell differentiation assay revealed a possible extension of the region of influence for that imprinting centre a further 300kb proximal. Thus, Tel7KI has the potential to be an extremely useful tool in the study of genomic imprinting.
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Oh-McGinnis, Rosemary. "Placental phenotypes associated with abnormal genomic imprinting on distal mouse chromosome 7." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/36801.
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Imprinted genes are expressed either from the maternal or paternal allele during development and tend to be found in clusters throughout the mammalian genome, suggesting they may be regulated by long-range mechanisms. Many of them have important roles in placental development. The Beckwith-Wiedemann Syndrome (BWS) region on human chromosome 11p15.5 contains two imprinted subdomains each regulated by their own differentially methylated regions, known as imprinting centres (IC1 and IC2). These two imprinted subdomains are separated by an evolutionarily conserved region of about 300 kilobases. Distal mouse chromosome 7 (MMU7) shares syntenic homology with the human BWS region. Since the mechanisms by which imprinting occurs are unclear, we sought to characterize this region further using two mouse lines carrying deletions within the BWS imprinted region. The first mouse line, called DelTel7/IC2KO, allows us to dissect out the role of imprinting centre 2 in the silencing of imprinted genes. We demonstrate that all of the distal MMU7 imprinted genes implicated in placental function are silenced by IC2 and the noncoding RNA Kcnq1ot1. The second mouse line, called Del⁷AI, allows us to determine whether placental imprinting is perturbed when the region between IC1 and IC2 is deleted. We found that maternal inheritance of Del⁷AI leads to partial loss of the gene Ascl2, and we show that this affects all three layers of the mature mouse placenta. We found that paternal inheritance of Del⁷AI leads to partial loss of Ascl2 imprinting. Detailed investigation of the underlying mechanisms of imprinting and phenotypes in these mouse lines provides us with new fundamental insights into placental biology and the regulation of gene expression by imprinting centres on distal mouse chromosome 7.
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Szeto, Yuk Yee. "Studies on genomic imprinting and gene expression of the mouse Peg3 locus." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620959.
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Perez, Julio David. "Genomic Imprinting in the Brain: the persistent influences from Mom and Dad." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467497.
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Most mammalian genes are equally expressed from the two inherited parental alleles. However, a puzzling subgroup known as imprinted genes are preferentially expressed from either the maternally- or paternally-inherited copy. Interestingly, many imprinted genes identified so far are expressed in the brain and mutations cause striking defects in brain development and function, in some cases leading to mental disorders such as autism-spectrum disorders. To better understand the extent of genomic imprinting in the brain and gain insights into its potential roles, I have investigated genomic imprinting in the Cerebellum. The Cerebellum provides several experimental advantages and has interesting functions, some of them recently associated with autism. Using RNA-Seq I have profiled the maternal and paternal transcriptomes in the developing and adult mouse Cerebellum, and uncovered 124 genes under imprinting regulation, 40 of which had not been described as imprinted before. Interestingly, the parental bias of 50% of detected genes are regulated according to age. Furthermore, parental biases appear to substantially vary across adult brain regions and are often not observed in non-brain tissues. Finally, I observed an overrepresentation of genes involved in programed cell death among imprinted genes, suggesting that the phenomenon of imprinting may target this pathway with interesting functional implications.Biology, Molecular and Cellular
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Kinser, Taliesin. "Misregulation of Genomic Imprinting Drives Abnormal Seed Development in Hybrid Monkeyflowers (Mimulus)." W&M ScholarWorks, 2017. https://scholarworks.wm.edu/etd/1516639867.
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Genomic imprinting is the preferential expression of one allele over the other. It is an epigenetic phenomenon that occurs in the placentas of mammals and the endosperm of angiosperms. Endosperm, like placentas, is a nutrient rich tissue that supports the growing embryo within the seed. All grains are predominantly composed of this tissue. It is the product of a second fertilization event, resulting in both maternal and paternal alleles. Some alleles are regulated differentially, resulting in imprinted genes. There are both paternally expressed imprinted genes (PEGs) and maternally expressed imprinted genes (MEGs) in the endosperm. In general PEGs tend to have functions that induce the proliferation of endosperm (and the placenta in mammals) and MEGs tend to regulate or limit proliferation. There are many theories on the evolution of imprinting and parent-specific functions in such diverged taxa. Interploidy hybridization systems are often used to study these parent-specific effects. Such systems occur when a diploid is crossed with a polyploid, typically a tetraploid. By switching the parentage, parent specific genome dosage can be altered: if the tetraploid is the mother, then the offspring, or endosperm, has maternal genomic excess, and if the tetraploid is the father, then the endosperm has paternal excess. Maternal excess is typically characterized by endosperm underproliferation and paternal excess is characterized by endosperm overproliferation, as predicted by MEG and PEG functions. While significant progress has been made in genomic imprinting, there is still much unknown. For example, in plants, maternal excess is predicted to be more stable for evolutionary and functional reasons, yet there are many cases where the opposite occurs. By using a system in Mimulus that is both interploidy and interspecies (M. guttatus is diploid and M. luteus is tetraploid) and where paternal excess is favored in offspring viability, we aim to uncover further clues behind the mechanisms and evolutionary drivers of genomic imprinting. Here we show that the paternal excess hybrid suffers from endosperm underproliferation, opposite of what is predicted, and the maternal excess hybrid suffers from complete endosperm and embryo failure. We show that smaller endosperm results in failed or delayed germination. Furthermore, using genomic techniques, we show that M. luteus is genomically dominant in the hybrids regardless of crossing direction, likely interfering with imprinting patterns. We identify new PEGs involved in cellular proliferation. We show an overall paternal bias in M. luteus, which is unexpected and uncommon – potentially suggesting other adaptive drivers in imprinting. We suggest that abnormalities in the hybrids may be due to this genomic dominance and potentially other genetic and developmental differences between the two species that interferes with MEG and PEG roles.
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Magalhães, Hélida Regina. "Análise do padrão de metilação do gene Peg3 em diferentes regiões de cérebro de bovinos da raça Nelore." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-02032010-145407/.
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O comportamento materno é essencial para a sobrevivência e desenvolvimento do filhote mamífero. Durante a prenhez, as fêmeas recebem estímulos sensoriais e hormonais capazes de modificar e preparar o cérebro da mãe para o início dos padrões de comportamento materno (por exemplo, aumentando o número neurônios produtores de oxitocina no hipotálamo). Estudos têm identificado o hipotálamo como o principal responsável por estas mudanças, porém outras áreas do cérebro também estão envolvidas no processo do comportamento materno. Peg3, um gene marcado paternalmente expresso, é conhecido por controlar o comportamento materno em camundongos. Fêmeas nocautes para o gene Peg3 falham em aumentar a ingestão de alimentos, na ejeção de leite e em algumas atividades maternais, como placentofagia e construção do ninho. Este estudo teve como objetivo determinar os padrões de metilação da região diferencialmente metilada de Peg3 (Peg3DMR) de animais da raça Nelore de bovinos em diversas áreas do cérebro. Amostras foram coletadas das seguintes áreas: córtex frontal, occipital, temporal e parietal, hipocampo e hipotálamo, num total de 8 animais (4 machos e 4 fêmeas). O padrão de metilação destas amostras foi analisado pelo protocolo COBRA (do inglês, Combined Bisulfite-Restriction Analysis), que combina a modificação do DNA por bissulfito de sódio, amplificação por PCR e digestão por enzima de restrição. Foram encontrados diferentes padrões de metilação entre as amostras, ocorrendo uma predominância de hipometilação entre as amostras do sexo masculino, e padrões mais variados nas amostras do sexo feminino. As variações nos padrões de metilação ocorreram de maneira mais marcante entre as amostras de uma mesma região cerebral de diferentes animais, do que entre as amostras de várias regiões de um mesmo animal. Os resultados indicam que pode haver uma variação no status de imprinting em nível populacional, porém estudos com um número maior de amostras são necessários para a verificação da significância estatística destas variações.The maternal behavior is essential to survival and development of mammalian offspring. Throughout pregnancy, females receive sensory and hormonal stimuli which promote modifications and prepare the mothers brain to the onset of maternal behavior patterns (for example, by increasing numbers of neurons producing oxytocin in the hypothalamus). Studies have identified the hypothalamus as the main responsible for these changes, but other areas of the brain are also involved in the maternal behavior process. Peg3, an imprinted paternally expressed gene, is known to control maternal behavior in mice. Peg3 knockout females failed in increasing food intake, milk ejection and some maternal activities as placentofagia and nest building. This study aimed to determine the methylation patterns of the differently methylated region of Peg3 (DMR-Peg3) of animals from Nellore cattle breed in several areas of the brain. Samples were collected from the following areas of cattle brain: the frontal, occipital, temporal and parietal cortices, hippocampus and hypothalamus, in a total of 8 animals (4 males and 4 females). The methylation pattern of these samples was analyzed by the protocol COBRA (Combined Bisulfite-Restriction Analysis), which combines DNA modification by sodium bisulfite, PCR amplification and digestion by restriction enzymes. It was found different methylation patterns among the samples. There was a predominance of hypomethylation among male samples, while different patterns were found among the female samples. Variation in the methylation patterns was more markedly observed among samples of the same cerebral region among different animals, then among samples of several regions within an animal. The results suggest that there may be a variation in the imprinting status at a population level, but further assays, with an increased number of samples are needed to verify the statistical significance of this variation.
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Tevendale, Maxine Christine Lesley. "An embryological and mechanistic analysis of genomic imprinting of mouse distal chromosome 12." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619900.
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Jiang, Shan. "Establishing genomic imprinting by cell differentiation a model system using embryonic germ cells /." Available to US Hopkins community, 2000. http://wwwlib.umi.com/dissertations/dlnow/3099377.
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Kiefer, Christine Mione. "The identification, establishment, and maintenance of genomic imprints." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0010118.
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Thesis (Ph.D.)--University of Florida, 2005.Typescript. Title from title page of source document. Document formatted into pages; contains 137 pages. Includes Vita. Includes bibliographical references.
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Hu, Yueqing. "Some topics in the statistical analysis of forensic DNA and genetic family data." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38831491.
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Pandey, Gaurav Kumar. "Regulatory Roles of Noncoding RNA in Development and Disease." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-209596.
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Long noncoding RNAs (lncRNAs) are being realized as important players in gene regulation and their misregulation has been considered as one of the underlying causes for tumor initiation and progression in many human pathologies. In the current thesis, I have addressed the functional role of lncRNAs in development and disease model systems. Genomic imprinting is an epigenetic phenomenon by which subset of genes are expressed in a parent of origin-specific manner. The Kcnq1 imprinted locus is epigenetically regulated by Kcnq1ot1 lncRNA. Deletion of an 890bp region at the 5’ end of Kcnq1ot1 in mouse resulted in the loss of silencing of neighboring ubiqui-tously imprinted genes (UIGs). In addition, we observed loss of DNA methylation at the UIG promoters. We have shown that Kcnq1ot1 RNA establishes CpG methylation by interacting with DNMT1. To explore the stability of lncRNA mediated silencing pathways, we have conditionally deleted Kcnq1ot1 in the mouse in a stage and tissue-specific manner. We have shown that Kcnq1ot1 is continuously required for maintaining the silencing of UIGs, whereas the silencing of the placental im-printed genes is maintained in an RNA independent manner. To identify chromatin-associated lncRNA (CARs) on a genome-wide scale, we purified RNA from the sucrose gradient fractionated chromatin and subjected it to RNA sequencing. Our study has identified 141 intronic and 74 long intergenic CARs. Characterization of one of the CARs revealed that it regulates the expression of neighboring genes in cis by modulating the chromatin structure. We have explored the functional role of lncRNA in tumor progression and initiation by using pediatric neuroblastoma. By transcriptional profiling of low- and high-risk tumors, we have identified several lncRNAs differentially expressed between these subtypes. We report an uncharacterized RNA NBAT-1, expressed at lower levels in high-risk tumors relative to low-risk tumors. Using neuroblastoma cell culture system, we demonstrated that NBAT-1 has anti-cell proliferative and anti-invasive properties. In addition, it promotes differentiation of neurons from undifferentiated neuroblastoma cell lines. In summary, by employing mouse genetics, cell culture based model system and expression profiling in tumors, we have uncovered new roles of lncRNA in gene regulation.
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Jeffries, Sean Joseph. "Imprint erasure and DNA demethylation in mouse development." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608949.
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Robinett, Sheldon J. (Sheldon Jay). "Genomic imprinting: support for the concept from a study of Prader-Willi Syndrome patients." Thesis, University of North Texas, 1994. https://digital.library.unt.edu/ark:/67531/metadc332745/.
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In this study, nineteen cases of suspected or clinically diagnosed Prader-Willi Syndrome (PWS) were tested for molecular deletions by in situ hybridization with two DNA probes, IR4-3R and GABRB3. Both probes are specific for sequences within the chromosome region 15q11-13, with IR4-3R located within the putative PWS region and GABRB3 in the distal area associated with Angelman Syndrome.
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Neugebauer, Nadine [Verfasser]. "Investigations on the importance of genomic imprinting for genetic variation in livestock / Nadine Neugebauer." Kiel : Universitätsbibliothek Kiel, 2010. http://d-nb.info/1019904429/34.
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Elves, Rachel Leigh. "Consequences of mitotic loss of heterozygosity on genomic imprinting in mouse embryonic stem cells." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/1564.
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Epigenetic differences between maternally inherited and paternally inherited chromosomes, such as CpG methylation, render the maternal and paternal genome functionally inequivalent, a phenomenon called genomic imprinting. This functional inequivalence is exemplified with imprinted genes, whose expression is parent-of-origin specific. The dosage of imprinted gene expression is disrupted in cells with uniparental disomy (UPD), which is an unequal parental contribution to the genome. I have derived mouse embryonic stem (ES) cell sub-lines with maternal UPD (mUPD) for mouse chromosome 6 (MMU6) to characterize regulation and maintenance of imprinted gene expression.
The main finding from this study is that maintenance of imprinting in mitotic UPD is extremely variable. Imprint maintenance was shown to vary from gene to gene, and to vary between ES cell lines depending on the mechanism of loss of heterozygosity (LOH) in that cell line. Certain genes analyzed, such as Peg10, Sgce, Peg1, and Mit1 showed abnormal expression in ES cell lines for which they were mUPD. These abnormal expression levels are similar to that observed in ES cells with meiotically-derived full genome mUPD (parthenogenetic ES cells).
Imprinted CpG methylation at the Peg1 promoter was found to be abnormal in all sub-lines with mUPD for Peg1. Two cell sub-lines which incurred LOH through mitotic recombination showed hypermethylation of Peg1, consistent with the presence of two maternal alleles. Surprisingly, a cell sub-line which incurred LOH through full chromosome duplication/loss showed hypomethylation of Peg1. The levels of methylation observed in these sub-lines correlates with expression, as the first two sub-lines showed a near-consistent reduction of Peg1, while the latter showed Peg1 levels close to wild-type.
Altogether these results suggest that certain imprinted genes, like Peg1 and Peg10, have stricter imprinting maintenance, and as a result show abnormal expression in UPD. This strict imprint maintenance is disrupted, however, in UPD incurred through full chromosome duplication/loss, possibly because of the trisomic intermediate stage which occurs in this mechanism.