Genomic Imprinting in Mammals

Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 18)


This is a good time to write a general article on imprinting. In the last 5 years or so imprinting has progressed from an intriguing embryological observation to a firmly established biological principle with far-reaching consequences for mammalian development, genetics, and human disease. We now know why parthenogenesis in some mammals is not possible. We know of some imprinted genes and we even know what they do. We know that disomy can cause disease in humans. We know of genetic phenomena that extend classical Mendelian concepts. And we are gaining knowledge of the molecular mechanism of imprinting, knowledge that makes us believe that imprinting-like epigenetic controls guide differentiation in all multicellular organisms.


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  1. Allen ND, Norris ML, Surani MAH (1990) Epigenetic control of transgene expression and imprinting by genotype-specific modifiers. Cell 61: 853–861PubMedCrossRefGoogle Scholar
  2. Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N (1991) The mouse Igf-II receptor maps to the maternal-effect locus on chromosome 17 and is expressed only from the maternally inherited chromosome. Nature 349: 84–87PubMedCrossRefGoogle Scholar
  3. Bartolomei MS, Zemel S, Tilghman SM (1991) Parental imprinting of the mouse H19 gene. Nature 351: 153–155PubMedCrossRefGoogle Scholar
  4. Barton SC, Surani MA, Norris ML (1984) Role of paternal and maternal genomes in mouse development. Nature 311: 374–376PubMedCrossRefGoogle Scholar
  5. Barton SC, Adams CA, Norris ML, Surani MAH (1985) Development of gynogenetic and parthenogenetic inner cell mass and trophectoderm tissues in reconstituted blastocysts in the mouse. J Embryol Exp Morphol 90: 267–285PubMedGoogle Scholar
  6. Barton SC, Ferguson-Smith AC, Fundele R, Surani MA (1991) Influence of paternally imprinted genes on development. Development 113: 679–688PubMedGoogle Scholar
  7. Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321: 209–213PubMedCrossRefGoogle Scholar
  8. Brown KW, Williams JC, Maitland NJ, Mott MG (1990) Genomic imprinting and the Beckwith-Wiedemann syndrome. Am J Hum Genet 46: 1000–1001PubMedGoogle Scholar
  9. Brunkow ME, Tilghman SM (1991) Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes Dev 5: 1092–1101PubMedCrossRefGoogle Scholar
  10. Cattanach BM (1986) Parental origin effects in mice. J Embryol Exp Morphol (Suppl): 137–150Google Scholar
  11. Cattanach BM, Beechey CV (1990) Autosomal and X-chromosome imprinting. Development (Suppl): 63–72Google Scholar
  12. Cattanach BM, Kirk M (1985) Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315: 496–498PubMedCrossRefGoogle Scholar
  13. Chaillet JR (1992) DNA methylation and genomic imprinting in the mouse. Sem Dev Biol 3: 99–105CrossRefGoogle Scholar
  14. Chaillet JR, Vogt.TF, Beier DR, Leder P (1991) Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis. Cell 66: 77–84PubMedCrossRefGoogle Scholar
  15. DeChiara TM, Robertson EJ, Efstratiadis A (1991) Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64: 849–859PubMedCrossRefGoogle Scholar
  16. DeLoia JA, Solter D (1990) A transgene insertional mutation at an imprinted locus in the mouse genome. Development (Suppl): 73–80Google Scholar
  17. Engel E (1980) A new genetic concept: uniparental disomy and its potential effect. Am J Med Genet 6: 137–143PubMedCrossRefGoogle Scholar
  18. Engler P, Haasch D, Pinkert CA, Doglio L, Glymour M, Brinster R, Storb U (1991) A strain-specific modifier on mouse chromosome 4 controls the methylation of independent transgene loci. Cell 65: 939–948PubMedCrossRefGoogle Scholar
  19. Ferguson-Smith AC, Cattanach BM, Barton SC, Beechey CV, Surani MA (1991) Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351: 667–670PubMedCrossRefGoogle Scholar
  20. Fundele R, Norris ML, Barton SC, Reik W, Surani MA (1989) Systematic elimina- tion of parthenogenetic cells in mouse chimeras. Development 106: 29–35PubMedGoogle Scholar
  21. Fundele R, Norris ML, Barton SC, Fehlau M, Howlett SK, Mills SK, Surani MA (1990) Temporal and spatial selection against parthenogenetic cells during development of fetal chimeras. Development 108: 203–211PubMedGoogle Scholar
  22. Fundele R, Howlett SK, Kothary R, Norris ML, Mills WE, Surani MA (1991) Developmental potential of parthenogenetic cells: role of genotype-specific modifiers. Development 113: 941–946PubMedGoogle Scholar
  23. Gardner, RL, Barton SC, Surani MA (1990) Use of triple tissue blatocyst reconstitution to study the development of diploid parthenogenetic primitive ectoderm in combination with fertilization-derived trophectoderm and primitive endoderm. Genet Res 56: 209–222PubMedCrossRefGoogle Scholar
  24. Haack H, Hodgkin J (1991) Test for parental imprinting in the nematode C. elegans. Mol Gen Genet 228: 482–485PubMedCrossRefGoogle Scholar
  25. Hadchouel M, Farza H, Simon D, Tiollais P, Pourcel C (1987) Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation. Nature 329: 454–456PubMedCrossRefGoogle Scholar
  26. Haig D (1992) Genomic imprinting and the theory of parent-offspring conflict. Sem Dev Biol 3: 153–160Google Scholar
  27. Haig D, Graham C (1991) Genomic imprinting and the strange case of the insulin-like growth factor-II receptor. Cell 64: 1045–1046PubMedCrossRefGoogle Scholar
  28. Hall JG (1990) Genomic imprinting: review and relevance to human diseases. Am J Hum Genet 46: 857–873PubMedGoogle Scholar
  29. Henry I, Bonaiti-Pellie C, Chehensse V, Beldjord C, Schwartz C, Utermann G, Junien C (1991) Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 351: 665–666PubMedCrossRefGoogle Scholar
  30. Howlett SK (1991) Genomic imprinting and nuclear totipotency during embryonic development. Int Rev Cytol 127: 175–192PubMedCrossRefGoogle Scholar
  31. Howlett SK, Reik W (1991) Methylation levels of maternal and paternal genomes during preimplantation development. Development 113: 119–127PubMedGoogle Scholar
  32. Kajii T, Ohama K (1977) Androgenetic origin of hydatidiform mole. Nature 268: 633–634PubMedCrossRefGoogle Scholar
  33. Kaufman MH, Lee KKH, Spiers S (1989) Postimplantation development and cytogenetic analysis of diandric heterozygous diploid mouse embryos. Cytogenet Cell Genet 52: 15–18PubMedCrossRefGoogle Scholar
  34. Kirkels VGHJ, Hustinx TWJ, Scheres JMJC (1980) Habitual abortion and translocation (22q; 22q): unexpected transmission from a mother to her phenotypically normal daughter. Clin Genet 18: 456–461PubMedCrossRefGoogle Scholar
  35. Klose J, Reik W (1992) Expression of maternal and paternal phenotypes at the protein level. Sem Dev Biol 3: 119–126Google Scholar
  36. Laird CD (1990) Proposed genetic basis of Huntington’s disease. Trends Genet 6: 242–247PubMedCrossRefGoogle Scholar
  37. Latham KE, Solter D (1991) Effect of egg composition on the developmental capacity of androgenetic mouse embryos. Development 113: 561–568PubMedGoogle Scholar
  38. Lyon MF, Glenister P (1977) Factors affecting the observed number of young resulting from adjacent-2 disjunction in mice carrying a translocation. Genet Res 29: 83–92PubMedCrossRefGoogle Scholar
  39. Malcolm S, Clayton-Smith J, Nicholas M, Robb S, Webb T, Armour JAL, Jeffreys AJ, Pembrey ME (1991) Uniparental disomy in Angelman’s syndrome. Lancet 337: 694–697PubMedCrossRefGoogle Scholar
  40. Mann JR, Lovell-Badge RH (1984) Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm. Nature 310: 66–67PubMedCrossRefGoogle Scholar
  41. Mann JR, Gadi I, Harbison ML, Abbondanzo SJ, Stewart CL (1990) Androgenetic mouse embryonic stem cells are pluripotent and cause skeletal defects in chimeras: implications for genetic imprinting. Cell 62: 251–260PubMedCrossRefGoogle Scholar
  42. McGowan R, Campbell R, Peterson A, Sapienza C (1989) Cellular mosaicism in the methylation and expression of hemizygous loci in the mouse. Genes Dev 3: 1669–1676PubMedCrossRefGoogle Scholar
  43. McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37: 179–183PubMedCrossRefGoogle Scholar
  44. McGrath J, Solter D (1986) Nucleocytoplasmic interactions in the mouse embryo. J Embryol Exp Morphol (Suppl): 277–290Google Scholar
  45. Monk M, Surani MA (1990) Genomic imprinting. Development (Suppl )Google Scholar
  46. Monk M, Adams RLP, Rinaldi A (1991) Decrease in methylase activity during preimplantation development in the mouse. Development 112: 189–192PubMedGoogle Scholar
  47. Moore T, Haig D (1991) Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 7: 45–49PubMedGoogle Scholar
  48. Nagy A, Sass M, Markkula M (1989) Systematic non-uniform distribution of parthenogenetic cells in adult mouse chimeras. Development 106: 321–324PubMedGoogle Scholar
  49. Nagy A, Gócza E, Diaz EM, Prideaux VR, Ivànyi E, Markkula M, Rossant J (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110: 815–821PubMedGoogle Scholar
  50. Nicholls RD, Knoll JHM, Butler MG, Karam S, Lalande M (1989) Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader Willi syndrome. Nature 342: 281–285PubMedCrossRefGoogle Scholar
  51. Nicholls RD, Rinchik EM, Driscoll DJ (1992) Genomic imprinting in mammalian development: Prader-Willi and Angelman syndromes as disease models. Sem Dev Biol 3: 139–152Google Scholar
  52. Palmer CG, Schwartz S, Hodes ME (1980) Transmission of a balanced homologous t (22q; 22q) translocation from mother to normal daughter. Clin Genet 17: 418–422PubMedCrossRefGoogle Scholar
  53. Paro R (1990) Imprinting a determined state into the chromation of Drosophila. Trends Genet 6: 416–421PubMedCrossRefGoogle Scholar
  54. Reik W (1988) Genomic imprinting: a possible mechanism for the parental origin effect in Huntington’s chorea. J Med Genet 25: 805–808PubMedCrossRefGoogle Scholar
  55. Reik W (1989) Genomic imprinting and genetic disorders in man. Trends Genet 5: 331–336PubMedCrossRefGoogle Scholar
  56. Reik W (1992) Genome imprinting. In: Grosveld F, Kollias G (eds) Transgenic animals. Academic Press: 99–126Google Scholar
  57. Reik W, Collick A, Norris ML, Barton SC, Surani MAH (1987) Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature 328: 248–251PubMedCrossRefGoogle Scholar
  58. Reik W, Howlett SK, Surani MA (1990) Imprinting by DNA methylation: from transgenes to endogenous gene sequences. Development (Suppl): 99–106Google Scholar
  59. Sapienza C (1989) Genome imprinting and dominance modification. Ann NY Acad Sci 564: 24–38PubMedCrossRefGoogle Scholar
  60. Sapienza C (1990) Sex-linked dosage-sensitive modifiers as imprinting genes. Development (Suppl): 107–114Google Scholar
  61. Sapienza C, Tran TH, Paquette J, McGowan R, Peterson A (1987) Degree of methylation of transgene is dependent on gamete of origin. Nature 328: 251–254PubMedCrossRefGoogle Scholar
  62. Sapienza C, Paquette J, Tran TH, Peterson A (1989) Epigenetic and genetic factors affect transgene methylation imprinting. Development 107: 165–168PubMedGoogle Scholar
  63. Sasaki H, Hamada T, Ueda T, Seki R, Higashinakagawa T, Sakaki Y (1991) Inherited type of allelic methylation variations in a mouse chromosome region where an integrated transgene shows methylation imprinting. Development 111: 573–581PubMedGoogle Scholar
  64. Searle AG, Beechey CV (1978) Complementation studies with mouse translocations. Cytogenet Cell Genet 20: 282–303PubMedCrossRefGoogle Scholar
  65. Searle AG, Beechey CV (1990) Genetic imprinting phenomena on mouse chromosome 7. Genet Res 56: 237–244PubMedCrossRefGoogle Scholar
  66. Singh PB, Miller JR, Pearce J, Kothary R, Burton RD, Paro R, James TC, Gaunt SJ (1991) A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants. Nucleic Acids Res 19: 789–794PubMedCrossRefGoogle Scholar
  67. Solter D (1988) Differential imprinting and expression of maternal and paternal genomes. Annu Rev Genet 22: 127–146PubMedCrossRefGoogle Scholar
  68. Spence JE, Perciaccante RG, Greig GM, Willard HF, Ledbetter DH, Heijtmancik JF, Pollack MS, O’Brien WE, Beaudet AL (1988) Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet 42: 217–226PubMedGoogle Scholar
  69. Surani MA (1991) Genomic imprinting: developmental significance and molecular mechanism. Curr Op Genet Dev 1: 241–246PubMedCrossRefGoogle Scholar
  70. Surani MAH, Barton SC, Norris ML (1984) Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308: 548–550PubMedCrossRefGoogle Scholar
  71. Surani MA, Barton SC, Norris ML (1986a) Nuclear transplantation in the mouse: heritable differences between parental genomes after activation of the embryonic genome. Cell 45: 127–136PubMedCrossRefGoogle Scholar
  72. Surani MAH, Reik W, Norris ML, Barton SC (1986b) Influence of germline modifications of homologous chromosomes on mouse development. J Embryol Exp Morphol (Suppl): 123–136Google Scholar
  73. Surani MA, Barton SC, Howlett SK, Norris M (1988a) Influence of chromosomal determinants on development of androgenetic and parthenogenetic cells. Development 103: 171–178PubMedGoogle Scholar
  74. Surani MA, Reik W, Allen ND (1988b) Transgenes as molecular probes for genomic imprinting. Trends Genet 4: 59–62PubMedCrossRefGoogle Scholar
  75. Surani MA, Allen ND, Barton SC, Fundele R, Howlett SK, Norris ML, Reik W (1990a) Developmental consequences of imprinting of parental chromosomes by DNA methylation. Philos Trans R Soc Lond B326: 313–327CrossRefGoogle Scholar
  76. Surani MA, Kothary R, Allen ND, Singh PB, Fundele R, Ferguson-Smith AC, Barton SC (1990b) Genome imprinting and development in the mouse. Development (Suppl): 89–98Google Scholar
  77. Swain JL, Stewart TA, Leder P (1987) Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell 50: 719–727PubMedCrossRefGoogle Scholar
  78. Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P (1991) Maternal uniparental disomy for chromosome 14. J Med Genet 28: 511–514PubMedCrossRefGoogle Scholar
  79. Thomson JA, Solter D (1987) The developmental fate of androgenetic, parthenogenetic, and gynogenetic cells in chimeric gastrulating mouse embryos. Genes Dev 2: 1344–1351CrossRefGoogle Scholar
  80. Thomson JA, Solter D (1988) Chimeras between parthenogenetic or androgenetic blastomeres and normal embryos: allocation to the inner cell mass and trophectoderm. Dev Biol 131: 580–583CrossRefGoogle Scholar
  81. Voss R, Ben-Simon E, Avital A, Zlotogora Y, Dagan J, Godfrey S, Tikochinski Y, Hillel J (1989) Isodisomy of chromosome 7 in a patient with cystic fibrosis: could uniparental disomy be common in humans? Am J Hum Genet 45: 373–380PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  1. 1.Department of Molecular EmbryologyInstitute of Animal Physiology and Genetics ResearchBabraham, CambridgeUK

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