Abstract
As evidence for the existence of brain-expressed imprinted genes accumulates, we need to address exactly what they are doing in this tissue, especially in terms of organisational themes and the major challenges posed by reconciling imprinted gene action in brain with current evolutionary theories attempting to explain the origin and maintenance of geneomic imprinting. We are at the beginning of this endeavor and much work remains to be done but already it is clear that imprinted genes have the potential to influence diverse behavioral processes via multiple brain mechanisms. There are also grounds to believe that imprinting may contribute to risk of mental and neurological disease. As well as being a source of basic information about imprinted genes in the brain (e.g., via the newly established website, www.bgg.cardiff.ac.uk/imprinted_tables/index. html), we have used this chapter to identify and focus on a number of key questions. How are brain-expressed imprinted genes organised at the molecular and cellular levels? To what extent does imprinted action depend on neurodevelopmental mechanisms? Do imprinted gene effects interact with other epigenetic influences, especially early on in life? Are imprinted effects on adult behaviors adaptive or just epiphenomena? If they are adaptive, what areas of brain function and behavior might be sensitive to imprinted effects? These are big questions and, as shall become apparent, we need much more data, arising from interactions between behavioral neuroscientists, molecular biologists and evolutionary theorists, if we are to begin to answer them.
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References
Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001; 2(1):21–32.
Tycko B. Imprinted genes in placental growth and obstetric disorders. Cytogenet Genome Res 2006; 113(1–4):271–278.
Davies W, Isles AR, Wilkinson LS. Imprinted gene expression in the brain. Neurosci Biobehav Rev 2005; 29(3):421–430.
Bassett SS, Avramopoulos D, Fallin D. Evidence for parent of origin effect in late-onset Alzheimer disease. Am J Med Genet 2002; 114(6):679–686.
Davies W, Isles AR, Wilkinson LS. Imprinted genes and mental dysfunction. Ann Med 2001; 33(6):428–436.
Ebers GC, Sadovnick AD, Dyment DA et al. Parent-of-origin effect in multiple sclerosis: observations in half-siblings. Lancet 2004; 363(9423):1773–1774.
Isles AR, Wilkinson LS. Imprinted genes, cognition and behaviour. Trends Cogn Sci 2000; 4(8):309–318.
Keverne EB, Fundele R, Narasimha M et al. Genomic imprinting and the differential roles of parental genomes in brain development. Brain Res Dev Brain Res 1996; 92(1):91–100.
Hager R, Johnstone RA. The genetic basis of family conflict resolution in mice. Nature 2003; 421(6922):533–535.
Isles AR, Baum MJ, Ma D et al. Urinary odour preferences in mice. Nature 2001; 409(6822):783–784.
Cassidy SB, Dykens E, Williams CA. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet Summer 2000; 97(2):136–146.
Francks C, DeLisi LE, Shaw SH et al. Parent-of-origin effects on handedness and schizophrenia susceptibility on chromosome 2p12-q11. Hum Mol Genet 2003; 12(24):3225–3230.
Lamb JA, Barnby G, Bonora E et al. Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects. J Med Genet 2005; 42(2):132–137.
Yamasaki K, Joh K, Ohta T et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum Mol Genet 2003; 12(8):837–847.
Yamasaki Y, Kayashima T, Soejima H et al. Neuron-specific relaxation of Igf2r imprinting is associated with neuron-specific histone modifications and lack of its antisense transcript Air. Hum Mol Genet 2005; 14(17):2511–2520.
Joseph R, Dou D, Tsang W. Neuronation mRNA: alternatively spliced forms of a novel brain-specific mammalian developmental gene. Brain Res 1995; 690(1):92–98.
Kim J, Lu X, Stubbs L. Zim 1, a maternally expressed mouse Kruppel-type zinc-finger gene located in proximal chromosome 7. Hum Mol Genet 1999; 8(5):847–854.
Rougeulle C, Glatt H, Lalande M. The Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain. Nat Genet 1997; 17(1):14–15.
Albrecht U, Sutcliffe JS, Cattanach BM et al. Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat Genet 1997; 17(1):75–78.
Hetts SW, Rosen KM, Dikkes P et al. Expression and imprinting of the insulin-like growth factor II gene in neonatal mouse cerebellum. J Neurosci Res 1997; 50(6):958–966.
Davies W, Isles A, Smith R et al. Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice. Nat Genet 2005; 37(6):625–629.
Wang Y, Joh K, Masuko S et al. The mouse Murrl gene is imprinted in the adult brain, presumably due to transcriptional interference by the antisense-oriented U2af1-rs1 gene. Mol Cell Biol 2004; 24(1):270–279.
Lee S, Walker CL, Karten B et al. Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum Mol Genet 2005; 14(5):627–637.
Muscatelli F, Abrous DN, Massacrier A et al. Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 2000; 9(20):3101–3110.
Kuwako K, Hosokawa A, Nishimura I et al. Disruption of the paternal necdin gene diminishes TrkA signaling for sensory neuron survival. J Neurosci 2005; 25(30):7090–7099.
Li L, Keverne EB, Aparicio SA et al. Regulation of maternal behavior and offspring growth by paternally expressed Peg3. Science 1999; 284(5412):330–333.
Jiang YH, Armstrong D, Albrecht U et al. Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron 1998; 21(4):799–811.
Miura K, Kishino T, Li E et al. Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice. Neurobiol Dis 2002; 9(2):149–159.
Kikyo N, Williamson CM, John RM et al. Genetic and functional analysis of neuronatin in mice with maternal or paternal duplication of distal Chr 2. Dev Biol 1997; 190(1):66–77.
Yang H, Mattingly RR. The Ras-GRF1 exchange factor coordinates activation of H-Ras and Rac1 to control neuronal morphology. Mol Biol Cell 2006; 17(5):2177–2189.
Fischer-Colbrie R, Eder S, Lovisetti-Scamihorn P et al. Neuroendocrine secretory protein 55: a novel marker for the constitutive secretory pathway. Ann N Y Acad Sci 2002; 971:317–322.
Hinton EC, Holland AJ, Gellatly MS et al. Neural representations of hunger and satiety in Prader-Willi syndrome. Int J Obes (Lond) 2006; 30(2):313–321.
Boer H, Holland A, Whittington J et al. Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet 2002; 359(9301):135–136.
Cassidy SB. Prader-Willi syndrome. J Med Genet 1997; 34(11):917–923.
Summers JA, Feldman MA. Distinctive pattern of behavioral functioning in Angelman syndrome. Am J Ment Retard 1999; 104(4):376–384.
Skuse DH, James RS, Bishop DV et al. Evidence from Turner’s syndrome of an imprinted X-linked locus affecting cognitive function. Nature 1997; 387(6634):705–708.
Bishop DV, Canning E, Elgar K et al. Distinctive patterns of memory function in subgroups of females with Turner syndrome: evidence for imprinted loci on the X-chromosome affecting neurodevelopment. Neuropsychologia 2000; 38(5):712–721.
Davies W, Isles AR, Burgoyne PS et al. X-linked imprinting: effects on brain and behaviour. Bioessays 2006; 28(1):35–44.
Skuse DH. Imprinting, the X-chromosome and the male brain: explaining sex differences in the liability to autism. Pediatr Res 2000; 47(1):9–16.
Raefski AS, O’Neill MJ. Identification of a cluster of X-linked imprinted genes in mice. Nat Genet 2005; 37(6):620–624.
Cattanach BM, Kirk M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 1985; 315(6019):496–498.
Plagge A, Gordon E, Dean W et al. The imprinted signaling protein XL alphas is required for postnatal adaptation to feeding. Nat Genet 2004; 36(8):818–826.
Lefebvre L, Viville S, Barton SC et al. Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest. Nat Genet 1998; 20(2):163–169.
Brambilla R, Gnesutta N, Minichiello L et al. A role for the Ras signalling pathway in synaptic transmission and long-term memory. Nature 1997; 390(6657):281–286.
Li S, Tian X, Hartley DM et al. Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression. J Neurosci 2006; 26(6):1721–1729.
Plagge A, Isles AR, Gordon E et al. Imprinted Nesp55 influences behavioral reactivity to novel environments. Mol Cell Biol 2005; 25(8):3019–3026.
Luedi PP, Hartemink AJ, Jirtle RL. Genome-wide prediction of imprinted murine genes. Genome Res 2005; 15(6):875–884.
Angiolini E, Fowden A, Coan P et al. Regulation of placental efficiency for nutrient transport by imprinted genes. Placenta 2006; 27 Suppl A:S98–102.
Barker DJ. The developmental origins of chronic adult disease. Acta Paediatr Suppl 2004; 93(446):26–33.
Geva R, Eshel R, Leitner Y et al. Neuropsychological outcome of children with intrauterine growth restriction: a 9-year prospective study. Pediatrics 2006; 118(1):91–100.
Ozanne SE, Fernandez-Twinn D, Hales CN. Fetal growth and adult diseases Semin Perinatol 2004; 28(1):81–87.
Clapcott SJ, Peters J, Orban PC et al. Two ENU-induced mutations in Rasgrf1 and early mouse growth retardation. Mamm Genome 2003; 14(8):495–505.
Matthews K, Robbins TW. Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat. Neurosci Biobehav Rev 2003; 27(1–2):45–55.
Bredy TW, Grant RJ, Champagne DL et al. Maternal care influences neuronal survival in the hippocampus of the rat. Eur J Neurosci 2003; 18(10):2903–2909.
Champagne FA, Weaver IC, Diorio J et al. Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology 2006; 147(6):2909–2915.
Weaver IC, Cervoni N, Champagne FA et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004; 7(8):847–854.
Haig D. Genomic imprinting, sex-biased dispersal and social behavior. Ann N Y Acad Sci 2000; 907:149–163.
Isles AR, Davies W, Wilkinson LS. Genomic imprinting and the social brain. Phil Trans Roy Soc Series B, 2006; (in press).
Trivers R, Burt A. Kinship and genomic imprinting. Results Probl Cell Differ 1999; 25:1–21.
Wilkins JF, Haig D. What good is genomic imprinting: the function of parent-specific gene expression. Nat Rev Genet 2003; 4(5):359–368.
Orr HA. Somatic mutation favors the evolution of diploidy. Genetics 1995; 139(3):1441–1447.
Chepko-Sade DB, Halpin M, Zuleyman T. Mammalian Dispersal Patterns: The Effects of Social Structure on Population Genetics: University of Chicago Press; 1987.
Roulin A, Hager R. Indiscriminate nursing in communal breeders: a role for genomic imprinting. Ecology 2003; 6(3):165–166.
Poindron P. Mechanisms of activation of maternal behaviour in mammals. Reprod Nutr Dev 2005; 45(3):341–351.
Curley JP, Keverne EB. Genes, brains and mammalian social bonds. Trends Ecol Evol 2005; 20(10):561–567.
Stein CM, Millard C, Kluge A et al. Speech Sound Disorder Influenced by a Locus in 15q14 Region. Behav Genet 2006.
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Davies, W., Isles, A.R., Humby, T., Wilkinson, L.S. (2008). What Are Imprinted Genes Doing in the Brain?. In: Wilkins, J.F. (eds) Genomic Imprinting. Advances in Experimental Medicine and Biology, vol 626. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77576-0_5
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DOI: https://doi.org/10.1007/978-0-387-77576-0_5
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