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Non-coding RNAs help silence the mammalian transcription
May 15, 2006Dr. Shirley Tilghman and colleagues (Princeton University) lend new insight into the mechanism of genomic imprinting, demonstrating a necessary role for a non-coding RNA transcript in the silencing of an imprinted gene cluster in mice.
Imprinting, or the differential expression of a gene based upon which parent it has been inherited from, is integral to normal growth and development. Two human disorders, Prader-Willi and Angelman syndromes, result from the deletion of the identical portion of chromosome 15. Imprinting determines which disorder arises: When the deletion involves the chromosome 15 that came from the father, the child has Prader-Willi syndrome, but when the deletion involves the chromosome 15 that came from the mother, the child has Angelman syndrome.
In the mouse, a cluster of nine genes on the distal end of the number 7 chromosome is imprinted. Dr. Tilghman and colleagues made a series of targeted alterations to ascertain which sequences are responsible for their paternal-specific silencing. The researchers show that this imprinted gene silencing requires the elongation of a paternally-expressed non-coding RNA transcript, Kcnq1ot1.
"As we explore the mechanism of genomic imprinting in greater detail, it is becoming clear that there is not a single explanation for the silencing of all imprinted genes. Rather mammals have co-opted multiple transcriptional regulatory mechanisms that were already evolved. In the case of the Kcnqt1ot1, the mechanism utilizes some form of RNA silencing. The variation in silencing mechanisms lends further support to the argument that imprinting arose gradually over a long period in mammals, not all at once," explains Dr. Tilghman.
Cold Spring Harbor Laboratory
"As we explore the mechanism of genomic imprinting in greater detail, it is becoming clear that there is not a single explanation for the silencing of all imprinted genes. Rather mammals have co-opted multiple transcriptional regulatory mechanisms that were already evolved. In the case of the Kcnqt1ot1, the mechanism utilizes some form of RNA silencing. The variation in silencing mechanisms lends further support to the argument that imprinting arose gradually over a long period in mammals, not all at once," explains Dr. Tilghman.
Cold Spring Harbor Laboratory
Genomic Imprinting Current Events and Genomic Imprinting News RSSThe evolutionary foundation of genomic imprinting in lower vertebrates
A Chinese scientist group working in College of Life Science, Zhejiang University, has shown that, as mammalian Igf2 CpG island, goldfish Igf2 CpG island has a parental differentially methylated region (DMR).
Not just humans benefit from animal biotechnology
Laboratory animals are the source of major discoveries and breakthroughs in biology, not just in tackling disease but also unravelling fundamental molecular processes. Delegates at a recent research conference organised by the European Science Foundation (ESF) and Wellcome Trust heard how technology capable of analysing animal genes across the whole genome is yielding many benefits for agriculture and human society.
Evolution of genomic imprinting
How we come to express the genes of one parent over the other is now better understood through studying the platypus and marsupial wallaby - and it doesn't seem to have originated in association with sex chromosomes.
New hope for regenerative medicine
In the February 15th issue of G&D, Dr. K. John McLaughlin and colleagues report on their success in using uniparental embryonic stem cells to replace blood stem cells in mice.
How IVF could be causing genetic errors in embryos
The conditions in which embryos are cultured in the laboratory during in vitro fertilisation could be causing genetic errors that are associated with certain developmental syndromes and other abnormalities in growth and development, such as low birth weight.
Sex: Why bother? Evolutionary mysteries probed at UH
What advantage did sex offer when it first appeared and why does sex persist in modern organisms, stopping them from becoming asexual again?
Genomic imprinting in disruptive spermatogenesis (p 1700)
Low sperm counts could be associated with genomic imprinting disease and could carry a raised risk of transmitting imprinting defects following assisted reproductive technologies, claim researchers in this week's issue of THE LANCET. Genomic imprinting is a gene regulatory mechanism based on differential methylation, whereby only one of two parental alleles is expressed. Imprinting disorders can lead to abnormal fetal development and malignant disease, and have been previously noted in oocytes (Lancet 2003; 361: 1975-77), but this is the first report showing imprinting defects in sperm. To investigate whether abnormal genomic imprinting could be associated with disturbed spermatogenesis, Pro
Media Invitation: British Neuroscience Association National Meeting
The British Neuroscience Association (BNA) is about to host its 17th National Meeting in Harrogate (13-16 April) and is attracting more delegates than ever before. With seven plenary lectures, 20 symposia and over 40 poster sessions, this will be quite a neuroscience festival for the UK. It will be supported by a full scale exhibition and numerous peripheral events, including a workshop on the 'Public Understanding of Science' that will be addressed by Lord Robert Winston, and a presentation of 'The Foresight Cognitive Systems Project', a new government initiative to foster interaction between neuroscientists and the computer industry. 'The quality of science on display this year is particu
Link between assisted reproduction techniques and genetic disruption
Evidence that assisted reproduction techniques may carry a risk of genetic 'imprinting disorders' in the resulting babies, emerges in a study published in the Journal of Medical Genetics. To assess the likely risk of genetic disruption, geneticists from the University of Birmingham and the West Midlands Genetics Service assessed the birth histories of 149 babies with Beckwith-Wiedemann syndrome. Features of Beckwith-Wiedemann syndrome include overgrowth, abdominal wall defects, low blood sugar, kidney abnormalities, and an increased risk of tumours - up to 10% of children with the syndrome develop childhood tumours, usually in the kidney. Beckwith-Wiedemann syndrome results from errors in ge
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Genomic Imprinting and Kinship (The Rutgers Series in Human Evolution, edited by Robert Trivers, Lee Cronk, Helen Fisher, and Lionel Tiger) by David Haig (Author) Until twenty years ago we had no idea which of our genes came from our father and which came from our mother. We took it for granted that our genes expressed themselves identically and that there was a 50/50 chance that they came from either parent. We also assumed that they worked in cooperation with each other. The biggest breakthrough in genetics in the past two decades has been the discovery of genomic imprinting, which allows us to trace genes to the parent of origin. David Haig has been at the forefront of theorizing these developments arguing that these "paternally and maternally active genes" comprising less than one percent of our total gene count are far from being cooperative, and have in fact been shown to be in competition with one another. If Haig's theory is correct,... |
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Genomic Imprinting (Advances in Experimental Medicine and Biology) by Jon F. Wilkins (Editor) Genomic imprinting refers to a recently discovered phenomenon in which the expression pattern of an allele depends on whether that allele was inherited from the mother or the father. This difference in expression strategy correlates with differences in the epigenetic state of the two alleles. These epigenetic differences include DNA methylation at CpG dinucleotides, as well as modifications on the histones associated with the locus. In the simplest possible cases, the promoter region of the imprinted gene is methylated during oogenesis, but not spermatogenesis (or vice versa). This methylation (and its accompanying histone modifications) results in inactivation of the modified allele. Of course, most imprinted genes do not fall into this simplest case. The goal of this book is neither... |
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Cellular Echoes, Environmental Influences in the Journey From the Womb to the World Directed By: DeAnna Elliott Also With: DeAnna Elliott (Producer), DeAnna Elliott (Writer), Bill Sitkin (Producer) Cellular Echoes, Environmental Influences in the Journey From the Womb to the World is an exploration of imprinting as it occurs in animals and humans in the first 6 stages of physical development - preconception, conception, gestation, birth and the early years. The first form of intelligence in a newly forming human being is in the cellular stage. Cells have 30,000 functions and are actually as highly sophisticated as a computer chip. The most important functions of the cell, for the purpose of this film are the gathering and storage of date from the environment in which they reside. In the human infant these functions are active from the moment of conception.This film is designed to show ordinary people how the function of cell memory works. In addition, great attention is given to... |
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Genomic Imprinting: Methods and Protocols (Methods in Molecular Biology) by Andrew Ward (Editor) Univ. of Bath, UK. Brings together the essential molecular, genetic, and embryological methods used in today's laboratories for the identification and analysis of imprinted genes. Each technique is described in detail. Outline format. |
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Genomic Imprinting and Uniparental Disomy in Medicine: Clinical and Molecular Aspects by Eric Engel (Author), Stylianos E. Antonarakis (Author) Eric Engel and Stylianos Antonarakis have written the most authoritative and vital reference on molecular and clinical aspects of uniparental disomy (UPD) and genomic imprinting to date. Genomic Imprinting and Uniparental Disomy in Medicine features comprehensive overviews of a multitude of genetic disorders linked to UPD, with a strong emphasis on clinical consequences. This book will provide readers with the tools necessary to identify and treat diseases associated with nontraditional chromosomal inheritance. Genomic Imprinting and Uniparental Disomy in Medicine features handy tables summarizing clinical phenotypes and chromosomal involvement in UPD, as well as clear illustrations on imprinting mechanisms and diagnostic testing. This authoritative, completely up-to-date... |
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Genomic Imprinting (Cytogenetic and Genomic Research) by Hiroyuki Sasaki (Editor), Fumitoshi Ishino (Editor) Genomic imprinting, a parent-of-origin-specific epigenetic modification of the genome, is observed in placental mammals and some plants (angiosperms). Since its discovery in the early 1980s, this intriguing phenomenon has been intensively investigated and has spawned an exciting new research area. Imprinting is relevant to a variety of biological events such as embryogenesis, growth and behavior, and its disruption can lead to congenital malformation syndromes and cancers.Furthermore, imprinting has been serving as an excellent model system to study epigenetic mechanisms of gene regulation and helping us to understand how gene clusters and genome domains are regulated. This special issue provides an overview of the current knowledge of genomic imprinting. Including both excellent reviews... |
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Genomic Imprinting: An Interdisciplinary Approach (Results and Problems in Cell Differentiation) by Rolf Ohlsson (Editor) This book provides an unrivalled in-depth treatise of genomic imprinting, a phenomenon which plays a vital role in many biological processes in developmental biology, evolution and human diseases and genetics. The reason for this broad range of influence derives from the fact that genomic imprinting shields a number of important genes from the full effects of Mendelian inheritance. The importance of this surprising observation, which was discovered less than two decades ago, has been only slowly recognized. The reason for this may be that genomic imprinting is a difficult concept to understand. This book aims at providing interesting, entertaining and detailed information for any scientist, irrespective of their particular field of study. |
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Genomic Imprinting (Frontiers in Molecular Biology) by Wolf Reik (Editor), Azim Surani (Editor) Genomic imprinting has been recognized since the late 1970's and known to be involved in several inherited diseases, but only recently have the questions surrounding the mechanisms behind it been answered. This volume reviews the latest exciting developments, with full citations of the key bibliography, discussions of the major questions in the field and outlines of directions for future research. Chapters range from a discussion of the genetic analysis of DNA methylation to a comprehensive evaluation of evolutionary theories. In between lie discussions of sequence signals and their recognition during development, expositions of some of the best studied imprint genes, and a summary for methods of identification. |
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GNAS: A Gene with a Complex Pattern of Genomic Imprinting (Dissertation; Yale University) by Helen Choi Kam KWAN (Author) | |
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Genomic Imprinting: Causes and Consequences by R. Ohlsson (Editor), K. Hall (Editor), M. Ritzen (Editor) Genomic imprinting results in the preferential expression of one gene, depending on the parent of origin, and it is associated with several disease syndromes in humans. This book covers a wealth of research material on chromatin structure, epigenetics, clinical genetics, developmental biology, cancer, hypotheses of evolution, and the molecular basis of the imprinting process, which will help explain not only the mechanisms of genomic imprinting, but also its biological and medical consequences. |
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