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J Med Genet. 2003 August; 40(8): 568–574.
PMCID: PMC1735542

Microarray analysis of gene/transcript expression in Prader-Willi syndrome: deletion versus UPD


Background: Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity, is caused by genomic imprinting and loss of expression of paternal genes in the 15q11–q13 region. There is a paucity of data examining simultaneous gene expression in this syndrome.

Methods: We generated cDNA microarrays representing 73 non-redundant genes/transcripts from the 15q11–q13 region, the majority within the PWS critical region and others distally on chromosome 15. We used our custom microarrays to compare gene expression from actively growing lymphoblastoid cell lines established from nine young adult males (six with PWS (three with deletion and three with UPD) and three controls).

Results: There was no evidence of expression of genes previously identified as paternally expressed in the PWS cell lines with either deletion or UPD. We detected no difference in expression of genes with known biallelic expression located outside the 15q11–q13 region in all cell lines studied. There was no difference in expression levels of biallelically expressed genes (for example, OCA2) from within 15q11–q13 when comparing UPD cell lines with controls. However, two genes previously identified as maternally expressed (UBE3A and ATP10C) showed a significant increase in expression in UPD cell lines compared with control and PWS deletion subjects. Several genes/transcripts (for example, GABRA5, GABRB3) had increased expression in UPD cell lines compared with deletion, but less than controls indicating paternal bias.

Conclusions: Our results suggest that differences in expression of candidate genes may contribute to phenotypic differences between PWS subjects with deletion or UPD and warrant further investigations.

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Selected References

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  • Cassidy SB, Forsythe M, Heeger S, Nicholls RD, Schork N, Benn P, Schwartz S. Comparison of phenotype between patients with Prader-Willi syndrome due to deletion 15q and uniparental disomy 15. Am J Med Genet. 1997 Feb 11;68(4):433–440. [PubMed]
  • Nicholls RD, Knepper JL. Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet. 2001;2:153–175. [PubMed]
  • Brannan CI, Bartolomei MS. Mechanisms of genomic imprinting. Curr Opin Genet Dev. 1999 Apr;9(2):164–170. [PubMed]
  • Meguro M, Kashiwagi A, Mitsuya K, Nakao M, Kondo I, Saitoh S, Oshimura M. A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome. Nat Genet. 2001 May;28(1):19–20. [PubMed]
  • Nicholls RD. Incriminating gene suspects, Prader-Willi style. Nat Genet. 1999 Oct;23(2):132–134. [PubMed]
  • Meguro M, Mitsuya K, Nomura N, Kohda M, Kashiwagi A, Nishigaki R, Yoshioka H, Nakao M, Oishi M, Oshimura M. Large-scale evaluation of imprinting status in the Prader-Willi syndrome region: an imprinted direct repeat cluster resembling small nucleolar RNA genes. Hum Mol Genet. 2001 Feb 15;10(4):383–394. [PubMed]
  • Lee S, Wevrick R. Identification of novel imprinted transcripts in the Prader-Willi syndrome and Angelman syndrome deletion region: further evidence for regional imprinting control. Am J Hum Genet. 2000 Mar;66(3):848–858. [PubMed]
  • Runte M, Hüttenhofer A, Gross S, Kiefmann M, Horsthemke B, Buiting K. The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Hum Mol Genet. 2001 Nov 1;10(23):2687–2700. [PubMed]
  • Gallagher Renata C, Pils Birgit, Albalwi Mohammed, Francke Uta. Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome. Am J Hum Genet. 2002 Sep;71(3):669–678. [PubMed]
  • Roof E, Stone W, MacLean W, Feurer ID, Thompson T, Butler MG. Intellectual characteristics of Prader-Willi syndrome: comparison of genetic subtypes. J Intellect Disabil Res. 2000 Feb;44(Pt 1):25–30. [PubMed]
  • Dykens Elisabeth M. Are jigsaw puzzle skills 'spared' in persons with Prader-Willi syndrome? J Child Psychol Psychiatry. 2002 Mar;43(3):343–352. [PubMed]
  • Dykens EM, Cassidy SB, King BH. Maladaptive behavior differences in Prader-Willi syndrome due to paternal deletion versus maternal uniparental disomy. Am J Ment Retard. 1999 Jan;104(1):67–77. [PubMed]
  • Churchill Gary A. Fundamentals of experimental design for cDNA microarrays. Nat Genet. 2002 Dec;32 (Suppl):490–495. [PubMed]
  • Horvath TL, Bechmann I, Naftolin F, Kalra SP, Leranth C. Heterogeneity in the neuropeptide Y-containing neurons of the rat arcuate nucleus: GABAergic and non-GABAergic subpopulations. Brain Res. 1997 May 9;756(1-2):283–286. [PubMed]
  • Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev. 1999 Feb;20(1):68–100. [PubMed]
  • Baxter LR, Jr, Saxena S, Brody AL, Ackermann RF, Colgan M, Schwartz JM, Allen-Martinez Z, Fuster JM, Phelps ME. Brain Mediation of Obsessive-Compulsive Disorder Symptoms: Evidence From Functional Brain Imaging Studies in the Human and Nonhuman Primate. Semin Clin Neuropsychiatry. 1996 Jan;1(1):32–47. [PubMed]
  • Rosenberg DR, Keshavan MS. A.E. Bennett Research Award. Toward a neurodevelopmental model of of obsessive--compulsive disorder. Biol Psychiatry. 1998 May 1;43(9):623–640. [PubMed]
  • Lee HS, Chong W, Han SK, Lee MH, Ryu PD. Activation of metabotropic glutamate receptors inhibits GABAergic transmission in the rat subfornical organ. Neuroscience. 2001;102(2):401–411. [PubMed]
  • Huang B, Mitchell CK, Redburn-Johnson DA. GABA and GABA(A) receptor antagonists alter developing cone photoreceptor development in neonatal rabbit retina. Vis Neurosci. 2000 Nov-Dec;17(6):925–935. [PubMed]
  • Berninger B, Marty S, Zafra F, da Penha Berzaghi M, Thoenen H, Lindholm D. GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro. Development. 1995 Aug;121(8):2327–2335. [PubMed]
  • Rudolph U, Crestani F, Möhler H. GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol Sci. 2001 Apr;22(4):188–194. [PubMed]
  • Behar T, Schaffner A, Laing P, Hudson L, Komoly S, Barker J. Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development. Brain Res Dev Brain Res. 1993 Apr 16;72(2):203–218. [PubMed]
  • Fritschy JM, Paysan J, Enna A, Mohler H. Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study. J Neurosci. 1994 Sep;14(9):5302–5324. [PubMed]
  • Laurie DJ, Wisden W, Seeburg PH. The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J Neurosci. 1992 Nov;12(11):4151–4172. [PubMed]
  • Clarren SK, Smith DW. Prader-Willi syndrome. Variable severity and recurrence risk. Am J Dis Child. 1977 Jul;131(7):798–800. [PubMed]
  • Tobet SA, Henderson RG, Whiting PJ, Sieghart W. Special relationship of gamma-aminobutyric acid to the ventromedial nucleus of the hypothalamus during embryonic development. J Comp Neurol. 1999 Mar 1;405(1):88–98. [PubMed]
  • Wisden W, Laurie DJ, Monyer H, Seeburg PH. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci. 1992 Mar;12(3):1040–1062. [PubMed]
  • Herzing Laura B K, Cook Edwin H, Jr, Ledbetter David H. Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications. Hum Mol Genet. 2002 Jul 15;11(15):1707–1718. [PubMed]

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