Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Mar;144(3):431–443.

Genomic imprinting: mechanism and role in human pathology.

B Tycko 1
PMCID: PMC1887089  PMID: 8129028

Abstract

Most genes are expressed from two alleles, one maternal and the other paternal. The term "genomic imprinting" refers to a genetic phenomenon which produces some interesting exceptions to this rule. Genes which are subject to imprinting are molecularly marked before fertilization such that they are transcriptionally silenced at one of the parental alleles in the offspring. A growing body of evidence implicates genomic imprinting in the pathogenesis of certain human genetic diseases, inherited tumor syndromes, and sporadic tumors. This review discusses examples of imprinting, theories as to why the phenomenon exists, possible molecular mechanisms of imprinting, and our current understanding of the role of imprinting in human pathology.

Full text

PDF
431

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen N. D., Norris M. L., Surani M. A. Epigenetic control of transgene expression and imprinting by genotype-specific modifiers. Cell. 1990 Jun 1;61(5):853–861. doi: 10.1016/0092-8674(90)90195-k. [DOI] [PubMed] [Google Scholar]
  2. Baccarini P., Fiorentino M., D'Errico A., Mancini A. M., Grigioni W. F. Detection of anti-sense transcripts of the insulin-like growth factor-2 gene in Wilms' tumor. Am J Pathol. 1993 Dec;143(6):1535–1542. [PMC free article] [PubMed] [Google Scholar]
  3. Barlow D. P. Methylation and imprinting: from host defense to gene regulation? Science. 1993 Apr 16;260(5106):309–310. doi: 10.1126/science.8469984. [DOI] [PubMed] [Google Scholar]
  4. Barlow D. P., Stöger R., Herrmann B. G., Saito K., Schweifer N. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature. 1991 Jan 3;349(6304):84–87. doi: 10.1038/349084a0. [DOI] [PubMed] [Google Scholar]
  5. Bartolomei M. S., Webber A. L., Brunkow M. E., Tilghman S. M. Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev. 1993 Sep;7(9):1663–1673. doi: 10.1101/gad.7.9.1663. [DOI] [PubMed] [Google Scholar]
  6. Bartolomei M. S., Zemel S., Tilghman S. M. Parental imprinting of the mouse H19 gene. Nature. 1991 May 9;351(6322):153–155. doi: 10.1038/351153a0. [DOI] [PubMed] [Google Scholar]
  7. Barton S. C., Surani M. A., Norris M. L. Role of paternal and maternal genomes in mouse development. 1984 Sep 27-Oct 3Nature. 311(5984):374–376. doi: 10.1038/311374a0. [DOI] [PubMed] [Google Scholar]
  8. Bell M. V., Hirst M. C., Nakahori Y., MacKinnon R. N., Roche A., Flint T. J., Jacobs P. A., Tommerup N., Tranebjaerg L., Froster-Iskenius U. Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome. Cell. 1991 Feb 22;64(4):861–866. doi: 10.1016/0092-8674(91)90514-y. [DOI] [PubMed] [Google Scholar]
  9. Bird A. The essentials of DNA methylation. Cell. 1992 Jul 10;70(1):5–8. doi: 10.1016/0092-8674(92)90526-i. [DOI] [PubMed] [Google Scholar]
  10. Blanquet V., Turleau C., de Grouchy J., Creau-Goldberg N. Physical map around the retinoblastoma gene: possible genomic imprinting suggested by NruI digestion. Genomics. 1991 Jun;10(2):350–355. doi: 10.1016/0888-7543(91)90319-a. [DOI] [PubMed] [Google Scholar]
  11. Brandeis M., Kafri T., Ariel M., Chaillet J. R., McCarrey J., Razin A., Cedar H. The ontogeny of allele-specific methylation associated with imprinted genes in the mouse. EMBO J. 1993 Sep;12(9):3669–3677. doi: 10.1002/j.1460-2075.1993.tb06041.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brannan C. I., Dees E. C., Ingram R. S., Tilghman S. M. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990 Jan;10(1):28–36. doi: 10.1128/mcb.10.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Brodeur G. M., Seeger R. C., Schwab M., Varmus H. E., Bishop J. M. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984 Jun 8;224(4653):1121–1124. doi: 10.1126/science.6719137. [DOI] [PubMed] [Google Scholar]
  14. Brown K. W., Gardner A., Williams J. C., Mott M. G., McDermott A., Maitland N. J. Paternal origin of 11p15 duplications in the Beckwith-Wiedemann syndrome. A new case and review of the literature. Cancer Genet Cytogenet. 1992 Jan;58(1):66–70. doi: 10.1016/0165-4608(92)90136-v. [DOI] [PubMed] [Google Scholar]
  15. Brown K. W., Williams J. C., Maitland N. J., Mott M. G. Genomic imprinting and the Beckwith-Wiedemann syndrome. Am J Hum Genet. 1990 May;46(5):1000–1001. [PMC free article] [PubMed] [Google Scholar]
  16. Brunkow M. E., Tilghman S. M. Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes Dev. 1991 Jun;5(6):1092–1101. doi: 10.1101/gad.5.6.1092. [DOI] [PubMed] [Google Scholar]
  17. Butler M. G., Palmer C. G. Parental origin of chromosome 15 deletion in Prader-Willi syndrome. Lancet. 1983 Jun 4;1(8336):1285–1286. doi: 10.1016/s0140-6736(83)92745-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Byrne J. A., Smith P. J. The 11p15.5 ribonucleotide reductase M1 subunit locus is not imprinted in Wilms' tumour and hepatoblastoma. Hum Genet. 1993 Apr;91(3):275–277. doi: 10.1007/BF00218271. [DOI] [PubMed] [Google Scholar]
  19. Carlson L. L., Page A. W., Bestor T. H. Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. Genes Dev. 1992 Dec;6(12B):2536–2541. doi: 10.1101/gad.6.12b.2536. [DOI] [PubMed] [Google Scholar]
  20. Caron H., van Sluis P., van Hoeve M., de Kraker J., Bras J., Slater R., Mannens M., Voûte P. A., Westerveld A., Versteeg R. Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N-myc amplification. Nat Genet. 1993 Jun;4(2):187–190. doi: 10.1038/ng0693-187. [DOI] [PubMed] [Google Scholar]
  21. Cattanach B. M., Barr J. A., Evans E. P., Burtenshaw M., Beechey C. V., Leff S. E., Brannan C. I., Copeland N. G., Jenkins N. A., Jones J. A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression. Nat Genet. 1992 Dec;2(4):270–274. doi: 10.1038/ng1292-270. [DOI] [PubMed] [Google Scholar]
  22. Cattanach B. M., Kirk M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature. 1985 Jun 6;315(6019):496–498. doi: 10.1038/315496a0. [DOI] [PubMed] [Google Scholar]
  23. Cedar H., Razin A. DNA methylation and development. Biochim Biophys Acta. 1990 May 24;1049(1):1–8. doi: 10.1016/0167-4781(90)90076-e. [DOI] [PubMed] [Google Scholar]
  24. Cheng J. M., Hiemstra J. L., Schneider S. S., Naumova A., Cheung N. K., Cohn S. L., Diller L., Sapienza C., Brodeur G. M. Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas. Nat Genet. 1993 Jun;4(2):191–194. doi: 10.1038/ng0693-191. [DOI] [PubMed] [Google Scholar]
  25. Comings D. E. A general theory of carcinogenesis. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3324–3328. doi: 10.1073/pnas.70.12.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  27. DeChiara T. M., Robertson E. J., Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991 Feb 22;64(4):849–859. doi: 10.1016/0092-8674(91)90513-x. [DOI] [PubMed] [Google Scholar]
  28. Donlon T. A. Similar molecular deletions on chromosome 15q11.2 are encountered in both the Prader-Willi and Angelman syndromes. Hum Genet. 1988 Dec;80(4):322–328. doi: 10.1007/BF00273644. [DOI] [PubMed] [Google Scholar]
  29. Driscoll D. J., Migeon B. R. Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations. Somat Cell Mol Genet. 1990 May;16(3):267–282. doi: 10.1007/BF01233363. [DOI] [PubMed] [Google Scholar]
  30. Driscoll D. J., Waters M. F., Williams C. A., Zori R. T., Glenn C. C., Avidano K. M., Nicholls R. D. A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. Genomics. 1992 Aug;13(4):917–924. doi: 10.1016/0888-7543(92)90001-9. [DOI] [PubMed] [Google Scholar]
  31. Eversole-Cire P., Ferguson-Smith A. C., Sasaki H., Brown K. D., Cattanach B. M., Gonzales F. A., Surani M. A., Jones P. A. Activation of an imprinted Igf 2 gene in mouse somatic cell cultures. Mol Cell Biol. 1993 Aug;13(8):4928–4938. doi: 10.1128/mcb.13.8.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Feinberg A. P. Genomic imprinting and gene activation in cancer. Nat Genet. 1993 Jun;4(2):110–113. doi: 10.1038/ng0693-110. [DOI] [PubMed] [Google Scholar]
  33. Ferguson-Smith A. C., Cattanach B. M., Barton S. C., Beechey C. V., Surani M. A. Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature. 1991 Jun 20;351(6328):667–670. doi: 10.1038/351667a0. [DOI] [PubMed] [Google Scholar]
  34. Ferguson-Smith A. C., Sasaki H., Cattanach B. M., Surani M. A. Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature. 1993 Apr 22;362(6422):751–755. doi: 10.1038/362751a0. [DOI] [PubMed] [Google Scholar]
  35. Forejt J., Gregorová S. Genetic analysis of genomic imprinting: an Imprintor-1 gene controls inactivation of the paternal copy of the mouse Tme locus. Cell. 1992 Aug 7;70(3):443–450. doi: 10.1016/0092-8674(92)90168-c. [DOI] [PubMed] [Google Scholar]
  36. Frank D., Keshet I., Shani M., Levine A., Razin A., Cedar H. Demethylation of CpG islands in embryonic cells. Nature. 1991 May 16;351(6323):239–241. doi: 10.1038/351239a0. [DOI] [PubMed] [Google Scholar]
  37. Fu Y. H., Kuhl D. P., Pizzuti A., Pieretti M., Sutcliffe J. S., Richards S., Verkerk A. J., Holden J. J., Fenwick R. G., Jr, Warren S. T. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 1991 Dec 20;67(6):1047–1058. doi: 10.1016/0092-8674(91)90283-5. [DOI] [PubMed] [Google Scholar]
  38. Garvin A. J., Re G. G., Tarnowski B. I., Hazen-Martin D. J., Sens D. A. The G401 cell line, utilized for studies of chromosomal changes in Wilms' tumor, is derived from a rhabdoid tumor of the kidney. Am J Pathol. 1993 Feb;142(2):375–380. [PMC free article] [PubMed] [Google Scholar]
  39. Giannoukakis N., Deal C., Paquette J., Goodyer C. G., Polychronakos C. Parental genomic imprinting of the human IGF2 gene. Nat Genet. 1993 May;4(1):98–101. doi: 10.1038/ng0593-98. [DOI] [PubMed] [Google Scholar]
  40. Goldberg Y. P., Kremer B., Andrew S. E., Theilmann J., Graham R. K., Squitieri F., Telenius H., Adam S., Sajoo A., Starr E. Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects. Nat Genet. 1993 Oct;5(2):174–179. doi: 10.1038/ng1093-174. [DOI] [PubMed] [Google Scholar]
  41. Greger V., Passarge E., Höpping W., Messmer E., Horsthemke B. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet. 1989 Sep;83(2):155–158. doi: 10.1007/BF00286709. [DOI] [PubMed] [Google Scholar]
  42. Grundy P., Telzerow P., Paterson M. C., Haber D., Berman B., Li F., Garber J. Chromosome 11 uniparental isodisomy predisposing to embryonal neoplasms. Lancet. 1991 Oct 26;338(8774):1079–1080. doi: 10.1016/0140-6736(91)91937-p. [DOI] [PubMed] [Google Scholar]
  43. Hadchouel M., Farza H., Simon D., Tiollais P., Pourcel C. Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation. Nature. 1987 Oct 1;329(6138):454–456. doi: 10.1038/329454a0. [DOI] [PubMed] [Google Scholar]
  44. Haig D., Graham C. Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell. 1991 Mar 22;64(6):1045–1046. doi: 10.1016/0092-8674(91)90256-x. [DOI] [PubMed] [Google Scholar]
  45. Hall J. G. Genomic imprinting: review and relevance to human diseases. Am J Hum Genet. 1990 May;46(5):857–873. [PMC free article] [PubMed] [Google Scholar]
  46. Han D. K., Liau G. Identification and characterization of developmentally regulated genes in vascular smooth muscle cells. Circ Res. 1992 Sep;71(3):711–719. doi: 10.1161/01.res.71.3.711. [DOI] [PubMed] [Google Scholar]
  47. Hansen R. S., Gartler S. M., Scott C. R., Chen S. H., Laird C. D. Methylation analysis of CGG sites in the CpG island of the human FMR1 gene. Hum Mol Genet. 1992 Nov;1(8):571–578. doi: 10.1093/hmg/1.8.571. [DOI] [PubMed] [Google Scholar]
  48. Hao Y., Crenshaw T., Moulton T., Newcomb E., Tycko B. Tumour-suppressor activity of H19 RNA. Nature. 1993 Oct 21;365(6448):764–767. doi: 10.1038/365764a0. [DOI] [PubMed] [Google Scholar]
  49. Harper P. S. Congenital myotonic dystrophy in Britain. II. Genetic basis. Arch Dis Child. 1975 Jul;50(7):514–521. doi: 10.1136/adc.50.7.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Haselbacher G. K., Irminger J. C., Zapf J., Ziegler W. H., Humbel R. E. Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms tumors: expression at the mRNA and protein level. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1104–1106. doi: 10.1073/pnas.84.4.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Henry I., Bonaiti-Pellié C., Chehensse V., Beldjord C., Schwartz C., Utermann G., Junien C. Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature. 1991 Jun 20;351(6328):665–667. doi: 10.1038/351665a0. [DOI] [PubMed] [Google Scholar]
  52. Heutink P., van der Mey A. G., Sandkuijl L. A., van Gils A. P., Bardoel A., Breedveld G. J., van Vliet M., van Ommen G. J., Cornelisse C. J., Oostra B. A. A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. Hum Mol Genet. 1992 Apr;1(1):7–10. doi: 10.1093/hmg/1.1.7. [DOI] [PubMed] [Google Scholar]
  53. Howlett S. K., Reik W. Methylation levels of maternal and paternal genomes during preimplantation development. Development. 1991 Sep;113(1):119–127. doi: 10.1242/dev.113.1.119. [DOI] [PubMed] [Google Scholar]
  54. Hultén M., Armstrong S., Challinor P., Gould C., Hardy G., Leedham P., Lee T., McKeown C. Genomic imprinting in an Angelman and Prader-Willi translocation family. Lancet. 1991 Sep 7;338(8767):638–639. doi: 10.1016/0140-6736(91)90652-6. [DOI] [PubMed] [Google Scholar]
  55. Jost J. P. Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4684–4688. doi: 10.1073/pnas.90.10.4684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Junien C. Beckwith-Wiedemann syndrome, tumourigenesis and imprinting. Curr Opin Genet Dev. 1992 Jun;2(3):431–438. doi: 10.1016/s0959-437x(05)80154-6. [DOI] [PubMed] [Google Scholar]
  57. Jähner D., Jaenisch R. Chromosomal position and specific demethylation in enhancer sequences of germ line-transmitted retroviral genomes during mouse development. Mol Cell Biol. 1985 Sep;5(9):2212–2220. doi: 10.1128/mcb.5.9.2212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Kafri T., Ariel M., Brandeis M., Shemer R., Urven L., McCarrey J., Cedar H., Razin A. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 1992 May;6(5):705–714. doi: 10.1101/gad.6.5.705. [DOI] [PubMed] [Google Scholar]
  59. Knoll J. H., Nicholls R. D., Magenis R. E., Graham J. M., Jr, Lalande M., Latt S. A. Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet. 1989 Feb;32(2):285–290. doi: 10.1002/ajmg.1320320235. [DOI] [PubMed] [Google Scholar]
  60. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Koufos A., Grundy P., Morgan K., Aleck K. A., Hadro T., Lampkin B. C., Kalbakji A., Cavenee W. K. Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am J Hum Genet. 1989 May;44(5):711–719. [PMC free article] [PubMed] [Google Scholar]
  62. Laird C. D. Possible erasure of the imprint on a fragile X chromosome when transmitted by a male. Am J Med Genet. 1991 Feb-Mar;38(2-3):391–395. doi: 10.1002/ajmg.1320380247. [DOI] [PubMed] [Google Scholar]
  63. Laird C. D. Proposed mechanism of inheritance and expression of the human fragile-X syndrome of mental retardation. Genetics. 1987 Nov;117(3):587–599. doi: 10.1093/genetics/117.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Lawler S. D., Povey S., Fisher R. A., Pickthall V. J. Genetic studies on hydatidiform moles. II. The origin of complete moles. Ann Hum Genet. 1982 Jul;46(Pt 3):209–222. doi: 10.1111/j.1469-1809.1982.tb00713.x. [DOI] [PubMed] [Google Scholar]
  65. Lee J. E., Tantravahi U., Boyle A. L., Efstratiadis A. Parental imprinting of an Igf-2 transgene. Mol Reprod Dev. 1993 Aug;35(4):382–390. doi: 10.1002/mrd.1080350411. [DOI] [PubMed] [Google Scholar]
  66. Leff S. E., Brannan C. I., Reed M. L., Ozçelik T., Francke U., Copeland N. G., Jenkins N. A. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nat Genet. 1992 Dec;2(4):259–264. doi: 10.1038/ng1292-259. [DOI] [PubMed] [Google Scholar]
  67. Li E., Beard C., Jaenisch R. Role for DNA methylation in genomic imprinting. Nature. 1993 Nov 25;366(6453):362–365. doi: 10.1038/366362a0. [DOI] [PubMed] [Google Scholar]
  68. Linder D., McCaw B. K., Hecht F. Parthenogenic origin of benign ovarian teratomas. N Engl J Med. 1975 Jan 9;292(2):63–66. doi: 10.1056/NEJM197501092920202. [DOI] [PubMed] [Google Scholar]
  69. Lubinsky M., Herrmann J., Kosseff A. L., Opitz J. M. Letter: Autosomal-dominant sex-dependent transmission of the Wiedemann-Beckwith syndrome. Lancet. 1974 May 11;1(7863):932–932. doi: 10.1016/s0140-6736(74)90383-3. [DOI] [PubMed] [Google Scholar]
  70. Lyon M. F. Some milestones in the history of X-chromosome inactivation. Annu Rev Genet. 1992;26:16–28. doi: 10.1146/annurev.ge.26.120192.000313. [DOI] [PubMed] [Google Scholar]
  71. Magenis R. E., Toth-Fejel S., Allen L. J., Black M., Brown M. G., Budden S., Cohen R., Friedman J. M., Kalousek D., Zonana J. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. Am J Med Genet. 1990 Mar;35(3):333–349. doi: 10.1002/ajmg.1320350307. [DOI] [PubMed] [Google Scholar]
  72. Malcolm S., Clayton-Smith J., Nichols M., Robb S., Webb T., Armour J. A., Jeffreys A. J., Pembrey M. E. Uniparental paternal disomy in Angelman's syndrome. Lancet. 1991 Mar 23;337(8743):694–697. doi: 10.1016/0140-6736(91)90278-w. [DOI] [PubMed] [Google Scholar]
  73. Mandel J. L. Questions of expansion. Nat Genet. 1993 May;4(1):8–9. doi: 10.1038/ng0593-8. [DOI] [PubMed] [Google Scholar]
  74. McGrath J., Solter D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell. 1984 May;37(1):179–183. doi: 10.1016/0092-8674(84)90313-1. [DOI] [PubMed] [Google Scholar]
  75. Monk M., Boubelik M., Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987 Mar;99(3):371–382. doi: 10.1242/dev.99.3.371. [DOI] [PubMed] [Google Scholar]
  76. Moore T., Haig D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 1991 Feb;7(2):45–49. doi: 10.1016/0168-9525(91)90230-N. [DOI] [PubMed] [Google Scholar]
  77. Mutter G. L., Stewart C. L., Chaponot M. L., Pomponio R. J. Oppositely imprinted genes H19 and insulin-like growth factor 2 are coexpressed in human androgenetic trophoblast. Am J Hum Genet. 1993 Nov;53(5):1096–1102. [PMC free article] [PubMed] [Google Scholar]
  78. Nicholls R. D., Knoll J. H., Butler M. G., Karam S., Lalande M. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature. 1989 Nov 16;342(6247):281–285. doi: 10.1038/342281a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Oberlé I., Rousseau F., Heitz D., Kretz C., Devys D., Hanauer A., Boué J., Bertheas M. F., Mandel J. L. Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science. 1991 May 24;252(5009):1097–1102. doi: 10.1126/science.252.5009.1097. [DOI] [PubMed] [Google Scholar]
  80. Ogawa O., Eccles M. R., Szeto J., McNoe L. A., Yun K., Maw M. A., Smith P. J., Reeve A. E. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature. 1993 Apr 22;362(6422):749–751. doi: 10.1038/362749a0. [DOI] [PubMed] [Google Scholar]
  81. Ohlsson R., Nyström A., Pfeifer-Ohlsson S., Töhönen V., Hedborg F., Schofield P., Flam F., Ekström T. J. IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome. Nat Genet. 1993 May;4(1):94–97. doi: 10.1038/ng0593-94. [DOI] [PubMed] [Google Scholar]
  82. Ozçelik T., Leff S., Robinson W., Donlon T., Lalande M., Sanjines E., Schinzel A., Francke U. Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nat Genet. 1992 Dec;2(4):265–269. doi: 10.1038/ng1292-265. [DOI] [PubMed] [Google Scholar]
  83. Pachnis V., Brannan C. I., Tilghman S. M. The structure and expression of a novel gene activated in early mouse embryogenesis. EMBO J. 1988 Mar;7(3):673–681. doi: 10.1002/j.1460-2075.1988.tb02862.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Ping A. J., Reeve A. E., Law D. J., Young M. R., Boehnke M., Feinberg A. P. Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet. 1989 May;44(5):720–723. [PMC free article] [PubMed] [Google Scholar]
  85. Poirier F., Chan C. T., Timmons P. M., Robertson E. J., Evans M. J., Rigby P. W. The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development. 1991 Dec;113(4):1105–1114. doi: 10.1242/dev.113.4.1105. [DOI] [PubMed] [Google Scholar]
  86. Rachmilewitz J., Gileadi O., Eldar-Geva T., Schneider T., de-Groot N., Hochberg A. Transcription of the H19 gene in differentiating cytotrophoblasts from human placenta. Mol Reprod Dev. 1992 Jul;32(3):196–202. doi: 10.1002/mrd.1080320303. [DOI] [PubMed] [Google Scholar]
  87. Rachmilewitz J., Goshen R., Ariel I., Schneider T., de Groot N., Hochberg A. Parental imprinting of the human H19 gene. FEBS Lett. 1992 Aug 31;309(1):25–28. doi: 10.1016/0014-5793(92)80731-u. [DOI] [PubMed] [Google Scholar]
  88. Rainier S., Johnson L. A., Dobry C. J., Ping A. J., Grundy P. E., Feinberg A. P. Relaxation of imprinted genes in human cancer. Nature. 1993 Apr 22;362(6422):747–749. doi: 10.1038/362747a0. [DOI] [PubMed] [Google Scholar]
  89. Read A. P. Huntington's disease: testing the test. Nat Genet. 1993 Aug;4(4):329–330. doi: 10.1038/ng0893-329. [DOI] [PubMed] [Google Scholar]
  90. Reeve A. E., Eccles M. R., Wilkins R. J., Bell G. I., Millow L. J. Expression of insulin-like growth factor-II transcripts in Wilms' tumour. Nature. 1985 Sep 19;317(6034):258–260. doi: 10.1038/317258a0. [DOI] [PubMed] [Google Scholar]
  91. Reik W., Collick A., Norris M. L., Barton S. C., Surani M. A. Genomic imprinting determines methylation of parental alleles in transgenic mice. Nature. 1987 Jul 16;328(6127):248–251. doi: 10.1038/328248a0. [DOI] [PubMed] [Google Scholar]
  92. Reik W., Surani M. A. Cancer genetics. Genomic imprinting and embryonal tumours. Nature. 1989 Mar 9;338(6211):112–113. doi: 10.1038/338112a0. [DOI] [PubMed] [Google Scholar]
  93. Reyniers E., Vits L., De Boulle K., Van Roy B., Van Velzen D., de Graaff E., Verkerk A. J., Jorens H. Z., Darby J. K., Oostra B. The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. Nat Genet. 1993 Jun;4(2):143–146. doi: 10.1038/ng0693-143. [DOI] [PubMed] [Google Scholar]
  94. Ridley R. M., Frith C. D., Crow T. J., Conneally P. M. Anticipation in Huntington's disease is inherited through the male line but may originate in the female. J Med Genet. 1988 Sep;25(9):589–595. doi: 10.1136/jmg.25.9.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Riggs A. D., Pfeifer G. P. X-chromosome inactivation and cell memory. Trends Genet. 1992 May;8(5):169–174. doi: 10.1016/0168-9525(92)90219-t. [DOI] [PubMed] [Google Scholar]
  96. Sakai T., Toguchida J., Ohtani N., Yandell D. W., Rapaport J. M., Dryja T. P. Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet. 1991 May;48(5):880–888. [PMC free article] [PubMed] [Google Scholar]
  97. Sanford J. P., Clark H. J., Chapman V. M., Rossant J. Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. Genes Dev. 1987 Dec;1(10):1039–1046. doi: 10.1101/gad.1.10.1039. [DOI] [PubMed] [Google Scholar]
  98. Sapienza C., Paquette J., Tran T. H., Peterson A. Epigenetic and genetic factors affect transgene methylation imprinting. Development. 1989 Sep;107(1):165–168. doi: 10.1242/dev.107.1.165. [DOI] [PubMed] [Google Scholar]
  99. Sapienza C., Peterson A. C., Rossant J., Balling R. Degree of methylation of transgenes is dependent on gamete of origin. Nature. 1987 Jul 16;328(6127):251–254. doi: 10.1038/328251a0. [DOI] [PubMed] [Google Scholar]
  100. Schalling M., Hudson T. J., Buetow K. H., Housman D. E. Direct detection of novel expanded trinucleotide repeats in the human genome. Nat Genet. 1993 Jun;4(2):135–139. doi: 10.1038/ng0693-135. [DOI] [PubMed] [Google Scholar]
  101. Schroeder W. T., Chao L. Y., Dao D. D., Strong L. C., Pathak S., Riccardi V., Lewis W. H., Saunders G. F. Nonrandom loss of maternal chromosome 11 alleles in Wilms tumors. Am J Hum Genet. 1987 May;40(5):413–420. [PMC free article] [PubMed] [Google Scholar]
  102. Scott J., Cowell J., Robertson M. E., Priestley L. M., Wadey R., Hopkins B., Pritchard J., Bell G. I., Rall L. B., Graham C. F. Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues. Nature. 1985 Sep 19;317(6034):260–262. doi: 10.1038/317260a0. [DOI] [PubMed] [Google Scholar]
  103. Scrable H., Cavenee W., Ghavimi F., Lovell M., Morgan K., Sapienza C. A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7480–7484. doi: 10.1073/pnas.86.19.7480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Searle A. G., Beechey C. V. Complementation studies with mouse translocations. Cytogenet Cell Genet. 1978;20(1-6):282–303. doi: 10.1159/000130859. [DOI] [PubMed] [Google Scholar]
  105. Searle A. G., Beechey C. V. Genome imprinting phenomena on mouse chromosome 7. Genet Res. 1990 Oct-Dec;56(2-3):237–244. doi: 10.1017/s0016672300035333. [DOI] [PubMed] [Google Scholar]
  106. Searle A. G., Peters J., Lyon M. F., Hall J. G., Evans E. P., Edwards J. H., Buckle V. J. Chromosome maps of man and mouse. IV. Ann Hum Genet. 1989 May;53(Pt 2):89–140. doi: 10.1111/j.1469-1809.1989.tb01777.x. [DOI] [PubMed] [Google Scholar]
  107. Seeger R. C., Brodeur G. M., Sather H., Dalton A., Siegel S. E., Wong K. Y., Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985 Oct 31;313(18):1111–1116. doi: 10.1056/NEJM198510313131802. [DOI] [PubMed] [Google Scholar]
  108. Sotelo-Avila C., Gooch W. M., 3rd Neoplasms associated with the Beckwith-Wiedemann syndrome. Perspect Pediatr Pathol. 1976;3:255–272. [PubMed] [Google Scholar]
  109. Stevens L. C., Varnum D. S. The development of teratomas from parthenogenetically activated ovarian mouse eggs. Dev Biol. 1974 Apr;37(2):369–380. doi: 10.1016/0012-1606(74)90155-9. [DOI] [PubMed] [Google Scholar]
  110. Stöger R., Kubicka P., Liu C. G., Kafri T., Razin A., Cedar H., Barlow D. P. Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell. 1993 Apr 9;73(1):61–71. doi: 10.1016/0092-8674(93)90160-r. [DOI] [PubMed] [Google Scholar]
  111. Surani M. A., Barton S. C., Norris M. L. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature. 1984 Apr 5;308(5959):548–550. doi: 10.1038/308548a0. [DOI] [PubMed] [Google Scholar]
  112. Swain J. L., Stewart T. A., Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell. 1987 Aug 28;50(5):719–727. doi: 10.1016/0092-8674(87)90330-8. [DOI] [PubMed] [Google Scholar]
  113. Toguchida J., Ishizaki K., Sasaki M. S., Nakamura Y., Ikenaga M., Kato M., Sugimot M., Kotoura Y., Yamamuro T. Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma. Nature. 1989 Mar 9;338(6211):156–158. doi: 10.1038/338156a0. [DOI] [PubMed] [Google Scholar]
  114. Toth M., Lichtenberg U., Doerfler W. Genomic sequencing reveals a 5-methylcytosine-free domain in active promoters and the spreading of preimposed methylation patterns. Proc Natl Acad Sci U S A. 1989 May;86(10):3728–3732. doi: 10.1073/pnas.86.10.3728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Turleau C., de Grouchy J., Chavin-Colin F., Martelli H., Voyer M., Charlas R. Trisomy 11p15 and Beckwith-Wiedemann syndrome. A report of two cases. Hum Genet. 1984;67(2):219–221. doi: 10.1007/BF00273006. [DOI] [PubMed] [Google Scholar]
  116. Wagstaff J., Knoll J. H., Glatt K. A., Shugart Y. Y., Sommer A., Lalande M. Maternal but not paternal transmission of 15q11-13-linked nondeletion Angelman syndrome leads to phenotypic expression. Nat Genet. 1992 Jul;1(4):291–294. doi: 10.1038/ng0792-291. [DOI] [PubMed] [Google Scholar]
  117. Weksberg R., Shen D. R., Fei Y. L., Song Q. L., Squire J. Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nat Genet. 1993 Oct;5(2):143–150. doi: 10.1038/ng1093-143. [DOI] [PubMed] [Google Scholar]
  118. Weksberg R., Teshima I., Williams B. R., Greenberg C. R., Pueschel S. M., Chernos J. E., Fowlow S. B., Hoyme E., Anderson I. J., Whiteman D. A. Molecular characterization of cytogenetic alterations associated with the Beckwith-Wiedemann syndrome (BWS) phenotype refines the localization and suggests the gene for BWS is imprinted. Hum Mol Genet. 1993 May;2(5):549–556. doi: 10.1093/hmg/2.5.549. [DOI] [PubMed] [Google Scholar]
  119. Wiles M. V. Isolation of differentially expressed human cDNA clones: similarities between mouse and human embryonal carcinoma cell differentiation. Development. 1988 Nov;104(3):403–413. doi: 10.1242/dev.104.3.403. [DOI] [PubMed] [Google Scholar]
  120. Wilkins R. J. Genomic imprinting and carcinogenesis. Lancet. 1988 Feb 13;1(8581):329–331. doi: 10.1016/s0140-6736(88)91121-x. [DOI] [PubMed] [Google Scholar]
  121. Williams C. A., Zori R. T., Stone J. W., Gray B. A., Cantu E. S., Ostrer H. Maternal origin of 15q11-13 deletions in Angelman syndrome suggests a role for genomic imprinting. Am J Med Genet. 1990 Mar;35(3):350–353. doi: 10.1002/ajmg.1320350308. [DOI] [PubMed] [Google Scholar]
  122. Williams J. C., Brown K. W., Mott M. G., Maitland N. J. Maternal allele loss in Wilms' tumour. Lancet. 1989 Feb 4;1(8632):283–284. doi: 10.1016/s0140-6736(89)91300-7. [DOI] [PubMed] [Google Scholar]
  123. Zemel S., Bartolomei M. S., Tilghman S. M. Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2. Nat Genet. 1992 Sep;2(1):61–65. doi: 10.1038/ng0992-61. [DOI] [PubMed] [Google Scholar]
  124. Zhang Y., Shields T., Crenshaw T., Hao Y., Moulton T., Tycko B. Imprinting of human H19: allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching. Am J Hum Genet. 1993 Jul;53(1):113–124. [PMC free article] [PubMed] [Google Scholar]
  125. Zhang Y., Tycko B. Monoallelic expression of the human H19 gene. Nat Genet. 1992 Apr;1(1):40–44. doi: 10.1038/ng0492-40. [DOI] [PubMed] [Google Scholar]
  126. van der Mey A. G., Maaswinkel-Mooy P. D., Cornelisse C. J., Schmidt P. H., van de Kamp J. J. Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory. Lancet. 1989 Dec 2;2(8675):1291–1294. doi: 10.1016/s0140-6736(89)91908-9. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES