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A Novel Variant of Inpp5f Is Imprinted in Brain, and Its Expression Is Correlated with Differential Methylation of an Internal CpG Island

Jonathan D. Choi,^1, Lara A. Underkoffler,^2, Andrew J. Wood,¹ Joelle N. Collins,² Patrick T. Williams,² Jeffrey A. Golden,⁴ Eugene F. Schuster Jr.,¹ Kathleen M. Loomes,³ and Rebecca J. Oakey^1*

Department of Medical and Molecular Genetics, Guy's, King's and St. Thomas' School of Medicine, King's College London, 8th Floor, Guy's Tower, London SE1 9RT, United Kingdom,¹ Division of Human Genetics,² Division of Gastroenterology,³ Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104⁴

Received 20 January 2005/ Returned for modification 19 February 2005/ Accepted 23 March 2005

Using a tissue-specific microarray screen in combination with chromosome anomalies in the mouse, we identified a novel imprinted gene, Inpp5f_v2 on mouse chromosome 7. Characterization of this gene reveals a 3.2-kb transcript that is paternally expressed in the brain. Inpp5f_v2 is a variant of the related 4.7-kb transcript, Inpp5f, an inositol phosphatase gene that is biallelically expressed in the mouse. Inpp5f_v2 uses an alternative transcriptional start site within an intron of Inpp5f and thus has a unique alternative first exon. Whereas other imprinted transcripts have a unique first exon located within intron 1 of a longer transcript variant (such as at the Gnas and WT1 loci), Inpp5f_v2 is the first example of which we are aware in which the alternative first exon of an imprinted gene is embedded in a downstream intron (intron 15) of a transcript variant. The CpG island associated with the nonimprinted Inpp5f gene is hypomethylated on both alleles, a finding consistent with biallelic expression, whereas the CpG island present 5' of Inpp5f_v2 is differentially methylated on the maternal versus paternal alleles consistent with its imprinting status.

J.D.C. and L.A.U. contributed equally to this study.

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