Genomic imprinting effects on brain development and function

In a small fraction of mammalian genes — at present estimated at less than 1% of the total — one of the two alleles that is inherited by the offspring is partially or completely switched off. The decision as to which one is silenced depends on which allele was inherited from the mother and which from the father. These idiosyncratic loci are known as imprinted genes, and their existence is an evolutionary enigma, as they effectively nullify the advantages of diploidy. Although they are small in number, these genes have important effects on physiology and behaviour, and many are expressed in the brain. There is increasing evidence that imprinted genes influence brain function and behaviour by affecting neurodevelopmental processes.

[1]  C. Francks,et al.  Parent-of-origin effects on handedness and schizophrenia susceptibility on chromosome 2p12-q11. , 2003, Human molecular genetics.

[2]  J. Frade Nuclear Translocation of the p75 Neurotrophin Receptor Cytoplasmic Domain in Response to Neurotrophin Binding , 2005, The Journal of Neuroscience.

[3]  E. Weeber,et al.  Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of αCaMKII inhibitory phosphorylation , 2007, Nature Neuroscience.

[4]  E. M. Cooper,et al.  Biochemical Analysis of Angelman Syndrome-associated Mutations in the E3 Ubiquitin Ligase E6-associated Protein* , 2004, Journal of Biological Chemistry.

[5]  H. Zoghbi Postnatal Neurodevelopmental Disorders: Meeting at the Synapse? , 2003, Science.

[6]  A. Beaudet,et al.  A rheostat model for a rapid and reversible form of imprinting-dependent evolution. , 2002, American journal of human genetics.

[7]  Wolf Reik,et al.  Resourceful imprinting , 2004, Nature.

[8]  K. Yoshikawa,et al.  Expression of necdin, an embryonal carcinoma-derived nuclear protein, in developing mouse brain. , 1992, Brain research. Developmental brain research.

[9]  L. Wilkinson,et al.  Imprinted genes and mental dysfunction , 2001, Annals of medicine.

[10]  D. Barlow,et al.  The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus , 1991, Nature.

[11]  G. Cheron,et al.  Fast cerebellar oscillation associated with ataxia in a mouse model of angelman syndrome , 2005, Neuroscience.

[12]  L. Stubbs,et al.  Zim1, a maternally expressed mouse Kruppel-type zinc-finger gene located in proximal chromosome 7. , 1999, Human molecular genetics.

[13]  Jeong-Sun Seo,et al.  Birth of parthenogenetic mice that can develop to adulthood , 2004, Nature.

[14]  Takaaki Kuwajima,et al.  Necdin Interacts with the Msx2 Homeodomain Protein via MAGE-D1 to Promote Myogenic Differentiation of C2C12 Cells* , 2004, Journal of Biological Chemistry.

[15]  Takaaki Kuwajima,et al.  Necdin Downregulates Cdc2 Expression to Attenuate Neuronal Apoptosis , 2006, The Journal of Neuroscience.

[16]  Atul J. Butte,et al.  Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin , 2005, Nature Cell Biology.

[17]  E B Keverne,et al.  Primate brain evolution : genetic and functional considerations , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[18]  U. Ikeda,et al.  Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase , 1998, Genes to cells : devoted to molecular & cellular mechanisms.

[19]  E. Keverne,et al.  Coadaptation in mother and infant regulated by a paternally expressed imprinted gene , 2004, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[20]  K. Srivenugopal,et al.  The DNA repair protein, O6-Methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein , 2002, Oncogene.

[21]  S. Cichon,et al.  Polymorphic imprinting of the serotonin-2A (5-HT2A) receptor gene in human adult brain. , 1998, Brain research. Molecular brain research.

[22]  N. Blom,et al.  Midbrain expression of Delta-like 1 homologue is regulated by GDNF and is associated with dopaminergic differentiation , 2007, Experimental Neurology.

[23]  T. Moore,et al.  Genomic imprinting in mammalian development: a parental tug-of-war. , 1991, Trends in genetics : TIG.

[24]  A M Owen,et al.  Neural representations of hunger and satiety in Prader–Willi syndrome , 2006, International Journal of Obesity.

[25]  A. Petronis,et al.  Human morbid genetics revisited: relevance of epigenetics. , 2001, Trends in genetics : TIG.

[26]  W. Reik,et al.  Genomic imprinting: parental influence on the genome , 2001, Nature Reviews Genetics.

[27]  L. Wilkinson,et al.  Imprinted Nesp55 Influences Behavioral Reactivity to Novel Environments , 2005, Molecular and Cellular Biology.

[28]  Mark D. Johnson,et al.  Peg3/Pw1 Is a Mediator between p53 and Bax in DNA Damage-induced Neuronal Death* , 2002, The Journal of Biological Chemistry.

[29]  D. Haig Parental antagonism, relatedness asymmetries, and genomic imprinting , 1997, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[30]  N. C. Schanen,et al.  Epigenetics of autism spectrum disorders. , 2006, Human molecular genetics.

[31]  J. Zimmer,et al.  Neurons in the monoaminergic nuclei of the rat and human central nervous system express FA1/dlk , 2001, Neuroreport.

[32]  C. Williams Neurological aspects of the Angelman syndrome , 2005, Brain and Development.

[33]  T. Mukai,et al.  Comparative analyses of genomic imprinting and CpG island-methylation in mouse Murr1 and human MURR1 loci revealed a putative imprinting control region in mice. , 2006, Gene.

[34]  S. Srinivasan,et al.  Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. , 2006, Molecular endocrinology.

[35]  D. Solter,et al.  Completion of mouse embryogenesis requires both the maternal and paternal genomes , 1984, Cell.

[36]  M. Surani,et al.  The Imprinted Gene Peg3 Is Not Essential for Tumor Necrosis Factor α Signaling , 2000, Laboratory Investigation.

[37]  Gregor Eichele,et al.  Mutation of the Angelman Ubiquitin Ligase in Mice Causes Increased Cytoplasmic p53 and Deficits of Contextual Learning and Long-Term Potentiation , 1998, Neuron.

[38]  R. Elston,et al.  A Novel Approach to Detect Parent‐of‐Origin Effects from Pedigree Data with Application to Beckwith‐Wiedemann Syndrome , 2007, Annals of human genetics.

[39]  P. Howley,et al.  Identification of HHR23A as a Substrate for E6-associated Protein-mediated Ubiquitination* , 1999, The Journal of Biological Chemistry.

[40]  J. Sutcliffe,et al.  Dense linkage disequilibrium mapping in the 15q11–q13 maternal expression domain yields evidence for association in autism , 2003, Molecular Psychiatry.

[41]  N. Niikawa,et al.  Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. , 2003, Human molecular genetics.

[42]  M. Butler,et al.  Appetitive behavior, compulsivity, and neurochemistry in Prader-Willi syndrome. , 2000, Mental retardation and developmental disabilities research reviews.

[43]  A. Beaudet,et al.  Cognitive and adaptive behavior profiles of children with Angelman syndrome , 2004, American journal of medical genetics. Part A.

[44]  P. Howley,et al.  E6AP and Calmodulin Reciprocally Regulate Estrogen Receptor Stability* , 2006, Journal of Biological Chemistry.

[45]  Suzanne B. Cassidy,et al.  Prader-Willi Syndrome , 2005 .

[46]  F. McMahon,et al.  Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees , 2004, Biological Psychiatry.

[47]  M. Mann,et al.  Genomic imprinting--defusing the ovarian time bomb. , 1994, Trends in genetics : TIG.

[48]  R. Feil,et al.  Epigenetic regulation of mammalian genomic imprinting. , 2004, Current opinion in genetics & development.

[49]  Alcino J. Silva,et al.  Derangements of Hippocampal Calcium/Calmodulin-Dependent Protein Kinase II in a Mouse Model for Angelman Mental Retardation Syndrome , 2003, The Journal of Neuroscience.

[50]  Giovanni Lucignani,et al.  GABAA receptor abnormalities in Prader–Willi syndrome assessed with positron emission tomography and [11C]flumazenil , 2004, NeuroImage.

[51]  David Y. Thomas,et al.  Localization of Endogenous Grb10 to the Mitochondria and Its Interaction with the Mitochondrial-associated Raf-1 Pool* , 1999, The Journal of Biological Chemistry.

[52]  L. Hurst,et al.  Peg3 and the Conflict Hypothesis , 2000, Science.

[53]  Michael J Meaney,et al.  Epigenetic programming by maternal behavior , 2004, Nature Neuroscience.

[54]  E. Bier,et al.  Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase. , 2006, Human molecular genetics.

[55]  J. Summers,et al.  Distinctive pattern of behavioral functioning in Angelman syndrome. , 1999, American journal of mental retardation : AJMR.

[56]  C. Oliver,et al.  Environmental influences on the behavioral phenotype of Angelman syndrome. , 2006, American journal of mental retardation : AJMR.

[57]  C. Rougeulle,et al.  The Angelman syndrome candidate gene, UBE3AIE6-AP, is imprinted in brain , 1997, Nature Genetics.

[58]  R. Hager,et al.  A Maternal–Offspring Coadaptation Theory for the Evolution of Genomic Imprinting , 2006, PLoS biology.

[59]  K. Devriendt,et al.  Chromosome 15 maternal uniparental disomy and psychosis in Prader-Willi syndrome , 2003, Journal of medical genetics.

[60]  N. Risch,et al.  Parent-of-origin effect in multiple sclerosis: observations in half-siblings , 2004, The Lancet.

[61]  D. Haig,et al.  What good is genomic imprinting: the function of parent-specific gene expression , 2003, Nature Reviews Genetics.

[62]  A. Holland,et al.  Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy , 2002, The Lancet.

[63]  J. LaSalle,et al.  15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. , 2007, Human molecular genetics.

[64]  A. Kashiwagi,et al.  Dlx5, the mouse homologue of the human-imprinted DLX5 gene, is biallelically expressed in the mouse brain , 2004, Journal of Human Genetics.

[65]  Jodi R Parrish,et al.  Yeast two-hybrid contributions to interactome mapping. , 2006, Current opinion in biotechnology.

[66]  Gavin Kelsey,et al.  Resourceful imprinting : Fertility , 2004 .

[67]  E. Keverne,et al.  Regulation of maternal behavior and offspring growth by paternally expressed Peg3. , 1999, Science.

[68]  K. Yoshikawa,et al.  Physical and Functional Interactions of Neuronal Growth Suppressor Necdin with p53* , 1999, The Journal of Biological Chemistry.

[69]  Philip Stanier,et al.  Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark. , 2003, Human molecular genetics.

[70]  B. O’Malley,et al.  The Ubiquitin-Conjugating Enzyme UBCH7 Acts as a Coactivator for Steroid Hormone Receptors , 2004, Molecular and Cellular Biology.

[71]  L. Wilkinson,et al.  Imprinted gene expression in the brain , 2005, Neuroscience & Biobehavioral Reviews.

[72]  S. Nada,et al.  Disruption of the Paternal Necdin Gene Diminishes TrkA Signaling for Sensory Neuron Survival , 2005, The Journal of Neuroscience.

[73]  M. Scheffner,et al.  The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53 , 1993, Cell.

[74]  E. Keverne,et al.  Genomic imprinting and the differential roles of parental genomes in brain development. , 1996, Brain research. Developmental brain research.

[75]  D. Sassoon,et al.  Peg3/Pw1 is an imprinted gene involved in the TNF-NFκB signal transduction pathway , 1998, Nature Genetics.

[76]  D. Abrous,et al.  Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. , 2000, Human molecular genetics.

[77]  K. Någren,et al.  Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABAA receptor β3 subunit deletions , 2001, Annals of neurology.

[78]  J. Sutcliffe,et al.  Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons , 1997, Nature Genetics.

[79]  Takaaki Kuwajima,et al.  Necdin Promotes GABAergic Neuron Differentiation in Cooperation with Dlx Homeodomain Proteins , 2006, The Journal of Neuroscience.

[80]  William M. Brown,et al.  Just how happy is the happy puppet? An emotion signaling and kinship theory perspective on the behavioral phenotype of children with Angelman syndrome. , 2004, Medical hypotheses.

[81]  J. Olefsky,et al.  Grb10 Interacts Differentially with the Insulin Receptor, Insulin-like Growth Factor I Receptor, and Epidermal Growth Factor Receptor via the Grb10 Src Homology 2 (SH2) Domain and a Second Novel Domain Located between the Pleckstrin Homology and SH2 Domains* , 1998, The Journal of Biological Chemistry.

[82]  J. Clayton-Smith,et al.  Angelman syndrome: a review of the clinical and genetic aspects , 2003, Journal of medical genetics.

[83]  D. Horn,et al.  SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome , 2004, Human Genetics.

[84]  A. Hoffman,et al.  Dissociation of IGF2 and H19 imprinting in human brain , 1998, Brain Research.

[85]  A. Holland,et al.  The course and outcome of psychiatric illness in people with Prader-Willi syndrome: implications for management and treatment. , 2007, Journal of intellectual disability research : JIDR.

[86]  P. A. Jacobs,et al.  Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function , 1997, Nature.

[87]  L. Wilkinson,et al.  Genomic imprinting and the social brain , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[88]  T. Yamashita,et al.  Peg3/Pw1 Is Involved in p53-mediated Cell Death Pathway in Brain Ischemia/Hypoxia* , 2002, The Journal of Biological Chemistry.

[89]  W. Reik,et al.  Imprinted Genes, Placental Development and Fetal Growth , 2006, Hormone Research in Paediatrics.

[90]  K. Yoshikawa,et al.  Necdin, a postmitotic growth suppressor , 2001 .

[91]  Rodney C Samaco,et al.  Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. , 2005, Human molecular genetics.

[92]  C. Oliver,et al.  Genomic imprinting and the expression of affect in Angelman syndrome: what's in the smile? , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[93]  M. Surani,et al.  Role of paternal and maternal genomes in mouse development , 1984, Nature.

[94]  Philippe P Roux,et al.  NRAGE, A Novel MAGE Protein, Interacts with the p75 Neurotrophin Receptor and Facilitates Nerve Growth Factor–Dependent Apoptosis , 2000, Neuron.

[95]  J. Greer,et al.  Developmental abnormalities of neuronal structure and function in prenatal mice lacking the prader-willi syndrome gene necdin. , 2005, The American journal of pathology.

[96]  M. Tsai,et al.  The Angelman Syndrome-Associated Protein, E6-AP, Is a Coactivator for the Nuclear Hormone Receptor Superfamily , 1999, Molecular and Cellular Biology.

[97]  K. Yoshikawa,et al.  Necdin, A Postmitotic Neuron-specific Growth Suppressor, Interacts with Viral Transforming Proteins and Cellular Transcription Factor E2F1* , 1998, The Journal of Biological Chemistry.

[98]  E. Keverne,et al.  Distribution of parthenogenetic cells in the mouse brain and their influence on brain development and behavior. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[99]  S. Hall,et al.  Effects of environmental events on smiling and laughing behavior in Angelman syndrome. , 2002, American journal of mental retardation : AJMR.

[100]  A. Efstratiadis,et al.  Parental imprinting of the mouse insulin-like growth factor II gene , 1991, Cell.

[101]  R. Wevrick,et al.  Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. , 2005, Human molecular genetics.

[102]  D. Karagogeos,et al.  Expression pattern of the maternally imprinted gene Gtl2 in the forebrain during embryonic development and adulthood. , 2006, Gene expression patterns : GEP.

[103]  G. Holmes,et al.  Neurobehavioral and Electroencephalographic Abnormalities in Ube3a Maternal-Deficient Mice , 2002, Neurobiology of Disease.

[104]  E. Arenas,et al.  The p75 Neurotrophin Receptor Interacts with Multiple MAGE Proteins* , 2002, The Journal of Biological Chemistry.

[105]  C. Williams,et al.  Prader-Willi and Angelman syndromes: sister imprinted disorders. , 2000, American journal of medical genetics.

[106]  D. Bowtell,et al.  Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[107]  J. P. Jensen,et al.  Subcellular Localization and Ubiquitin-conjugating Enzyme (E2) Interactions of Mammalian HECT Family Ubiquitin Protein Ligases* , 1997, The Journal of Biological Chemistry.

[108]  D. Xie,et al.  DLK1: increased expression in gliomas and associated with oncogenic activities , 2006, Oncogene.

[109]  P H Harvey,et al.  Comparing brains. , 1990, Science.

[110]  Eric J. Nestler,et al.  Epigenetic regulation in psychiatric disorders , 2007, Nature Reviews Neuroscience.

[111]  G. Homanics,et al.  Mouse models of Angelman syndrome, a neurodevelopmental disorder, display different brain regional GABAA receptor alterations , 2003, Neuroscience Letters.

[112]  J. Bressler,et al.  A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A , 2004, American journal of medical genetics. Part A.

[113]  M. Surani,et al.  Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein , 1996, Nature Genetics.

[114]  V. Baladrón,et al.  dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats. , 2005, Experimental cell research.

[115]  Mitsuo Oshimura,et al.  A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids. , 2003, Genomics.

[116]  B. Leventhal,et al.  Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. , 1997, American journal of human genetics.

[117]  T. Nakada,et al.  Brain Developmental Abnormalities in Prader-Willi Syndrome Detected by Diffusion Tensor Imaging , 2006, Pediatrics.

[118]  William Davies,et al.  Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice , 2005, Nature Genetics.

[119]  J. Volpe,et al.  Angelman's Syndrome in Infancy , 1990, Developmental medicine and child neurology.

[120]  M. Meguro,et al.  A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome , 2001, Nature Genetics.

[121]  J. Sutcliffe,et al.  Dense linkage disequilibrium mapping in the 15q11–q13 maternal expression domain yields evidence for association in autism , 2003, Molecular Psychiatry.

[122]  T. Mukai,et al.  The Mouse Murr1 Gene Is Imprinted in the Adult Brain, Presumably Due to Transcriptional Interference by the Antisense-Oriented U2af1-rs1 Gene , 2004, Molecular and Cellular Biology.

[123]  W. Fung,et al.  An Extension of the Transmission Disequilibrium Test Incorporating Imprinting , 2007, Genetics.

[124]  G. Kelsey,et al.  The imprinted signaling protein XLαs is required for postnatal adaptation to feeding , 2004, Nature Genetics.

[125]  Seamus J. Martin,et al.  Suppression of TNF-α-Induced Apoptosis by NF-κB , 1996, Science.