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The IPW Gene is Imprinted and is not Expressed in the Prader-Willi Syndrome

Published online by Cambridge University Press:  01 August 2014

R. Wevrick ,
J.A. Kerns  and
U. Francke
R. Wevrick
Affiliation:
Department of Genetics, Stanford University School of Medicine
J.A. Kerns
Affiliation:
Howard Hughes Medical Institute, Stanford, California, USA
U. Francke*
Affiliation:
Department of Genetics, Stanford University School of Medicine Department of Pediatrics, Stanford University School of Medicine Howard Hughes Medical Institute, Stanford, California, USA
*
Howard Hughes Medical Institute, Beckman Center for Molecular and Genetic Medicine, Stanford University Medical Center, Stanford, CA 94305-5428 (USA).

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Since the original description of the Prader-Willi syndrome (PWS) in 1956 [1], and the recognition of the involvement of the proximal region of chromosome 15 in this disorder [2], understanding of the molecular basis of the genetic defect in PWS has progressed rapidly. A set of clinical criteria has been defined [3], although the diagnosis on clinical grounds alone remains difficult in the first year of life. Research has focussed both on improving the diagnostic molecular and cytogenetic tests for PWS and on identifying and defining the functions of genes whose expression is altered in this neurobehavioral disorder. Furthermore, this region is known to be subject to genomic imprinting effects, so that expression of genes involved in PWS is expected to be exclusively from the paternal allele.

A critical step in the definition of the region containing such genes was the identification of a subset of unusual patients affected with either PWS or the Angelman syndrome, which also involves a gene or genes in the proximal region of chromosome 15. These unique patients, who have chromosome 15 translocations or deletions, helped to narrow the critical region to an interval containing less than 500 kb of DNA [4-6] (Fig. 1). As will be discussed, below, regulatory elements exist in this 500 kb region which alter the expression of genes located outside this interval [7, 8].

Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 45 , Issue 1-2 , April 1996 , pp. 191 - 197
Copyright
Copyright © The International Society for Twin Studies 1996

References

REFERENCES

1. Prader, A, Labhart, A, Willi, H: Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach myatonieartigem Zustand im Neugeborenenalter. Schweiz Med Wochenschr 1956; 86 1260–1261.Google Scholar
2. Ledbetter, D, Riccardi, V, Airhart, S, Strobel, R, Keenan, B, Crawford, J: Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med 1981; 304 235–329.Google Scholar
3. Holm, VA, Cassidy, SB, Butler, MG, Hanchen, JM, Greenswag, LR, Whitman, BY, Greenberg, F: Prader-Willi syndrome: Consensus diagnostic criteria. Pediatrics 1993; 91 398–402.CrossRefGoogle ScholarPubMed
4. Saitoh, S, Kubota, T, Ohta, T, Jinno, Y, Mikawa, N, Sugimoto, T, Wagstaff, J, Lalande, M: Familial Angelman syndrome caused by imprinted submicroscopic deletion encompassing GABAA receptor ß3-subunit gene. Lancet 1992; 339: 366–367.Google Scholar
5. Robinson, WP, Bottani, A, Xie, YG, Balakrishman, J, Binkert, F, Machler, M, Prader, A, Schinzel, A: Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients. Am J Hum Genet 1991; 49 1219–1234.Google Scholar
6. Buiting, K, Dittrich, B, Gross, S, Greger, V, Lalande, M, Robinson, W, Mutirangura, A, Ledbetter, D, Horsthemke, B: Molecular definition of the Prader-Willi syndrome chromosome region and orientation of the SNRPN gene. Hum Mol Genet 1993; 2: 1991–1994.Google Scholar
7. Reis, A, Dittrich, B, Greger, V, Buiting, K, Lalande, M, Gillessen-Kaesbach, G, Anvret, M, Horsthemke, K: Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes. Am J Hum Genet 1994; 54: 741–747.Google ScholarPubMed
8. Sutcliffe, JS, Nakao, M, Christian, S, Orstavik, KH, Tommerup, N, Ledbetter, DH, Beaudet, AL: Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. Nat Genet 1994; 8: 52–58.Google Scholar
9. Özçelik, 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; 2: 265–269.CrossRefGoogle ScholarPubMed
10. Glenn, CC, Porter, KA, Jong, MT, Nicholls, RD, Driscoll, DJ: Functional imprinting and epigenetic modification of the human SNRPN gene. Hum Mol Genet 1993; 2: 2001–2005.CrossRefGoogle ScholarPubMed
11. Reed, M, Leff, S: Maternal imprinting of human SNRPN, a gene deleted in Prader-Willi syndrome. Nat Genet 1994; 6: 163–167.Google Scholar
12. McAllister, G, Amara, SG, Lerner, MR: Tissue specific expression and cDNA cloning of small ribonucleoprotein-associated polypeptide N. Procy Natlx Acad, Sci USA 1988; 85: 5296–5300.CrossRefGoogle ScholarPubMed
13. Schmauss, C, Brines, M, Lerner, M: The gene encoding the small nuclear ribonuclear protein-associated protein N is expressed at high levels in neurons. J Biol Chem 1992; 267: 8521–8529.CrossRefGoogle Scholar
14. Grimaldi, K, Horn, D, Hudson, L, Therenghi, G, Barton, P, Polak, J, Latchman, D: Expression of the SmN splicing protein is developmentally regulated in the rodent brain but not in the rodent heart. Dev Biol 1993; 156: 319–323.CrossRefGoogle Scholar
15. Wevrick, R, Kerns, J, Francke, U: Identification of a novel paternally expressed gene in the Prader-Willi syndrome region. Hum Mol Genet 1994; 3: 1877–1882.Google Scholar
16. Glenn, CC, Nicholls, RD, Robinson, WP, Saitoh, S, Niikawa, N, Schinzel, A, Horsthemke, B, Driscoll, DJ: Modification of 15q11-q13 DNA methylation imprints in unique Angelman and Prader-Willi patients. Humx Mol Genet 1993; 2: 1377–1382.Google Scholar
17. Genetics Computer Group: Program Manual for the GCG Package. Madison, 1991.Google Scholar
18. Lovett, M, Kere, J, Hinton, L: Direct selection: A method for the isolation of cDNAs encoded by large genomic regions. Proc Natl Acad Sci USA 1991; 88: 9628–9632.CrossRefGoogle ScholarPubMed
19. Morgan, J, Dolganov, G, Robbins, S, Hinton, L, Lovett, M: The selective isolation of novel cDNAs encoded by the regions surrounding the human interleukin 4 and 5 genes. Nucleic Acids Res 1992; 20: 5173–5179.Google Scholar
20. Greger, V, Woolf, E, Lalande, M: Cloning of the breakpoints of a submicroscopic deletion in an Angelman syndrome patient. Hum Mol Genet 1993; 2: 921–924.Google Scholar
21. Brannan, C, Claire, E, Ingram, R, Tilghman, S: The product of the HI9 gene may function as a RNA. Mol Cell Biol 1990; 10: 28–36.Google Scholar
22. Brown, C, Ballabio, A, Rupert, J, Lafreniere, R, Grompe, M, Tonlorenzi, R, Willard, H: A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 1991; 349: 38–44.Google Scholar
23. Barlow, DP: Imprinting: A gamete's point of view. Trends Genet 1994; 10: 194–199.Google Scholar
24. Steenman, MJC, Rainier, S, Dobry, CJ, Grundy, P, Horon, IL, Feinberg, AP: Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour. Nat Genet 1994; 7: 433–439.Google Scholar
25. Moulton, T, Crenshaw, T, Hao, Y, Moosikasuwan, J, Lin, N, Dembitzer, F, Hensle, T, Weiss, L, McMorrow, L, Loew, T, Kraus, W, Gerald, W, Tycko, B: Epigenetic lesions at the H19 locus in Wilms' tumour patients. Nat Genet 1994; 7: 440–447.Google Scholar
26. Hao, Y, Crenshaw, T, Moulton, T, Newcomb, E, Tycko, B: Tumour-suppressor activity of H19 RNA. Nature 1993; 365: 764–767.Google Scholar
27. Bartolomei, MS, Webber, AL, Brunkow, ME, Tilghman, SM: Epigenetic mechanisms underlying the imprinting of the mouse H 19 gene. Genes Dev 1993; 7: 1663–1673.CrossRefGoogle Scholar
28. Heard, E, Avner, P: Role play in X-inactivation. Hum Mol Genet 1994; 3: 1481–1485.Google Scholar