Sequence-based bioinformatic prediction and QUASEP identify genomic imprinting of the KCNK9 potassium channel gene in mouse and human

Item Type:	Article
Title:	Sequence-based bioinformatic prediction and QUASEP identify genomic imprinting of the KCNK9 potassium channel gene in mouse and human
Creators Name:	Ruf, N. and Bähring, S. and Galetzka, D. and Pliushch, G. and Luft, F.C. and Nuernberg, P. and Haaf, T. and Kelsey, G. and Zechner, U.
Abstract:	Genomic imprinting is the epigenetic marking of gene subsets resulting in monoallelic or predominant expression of one of the two parental alleles according to their parental origin. We describe the systematic experimental verification of a prioritized 16 candidate imprinted gene set predicted by sequence-based bioinformatic analyses. We used Quantification of Allele-Specific Expression by Pyrosequencing (QUASEP) and discovered maternal-specific imprinted expression of the Kcnk9 gene as well as strain-dependent preferential expression of the Rarres1 gene in E11.5 (C57BL/6 x Cast/Ei)F1 and informative (C57BL/6 x Cast/Ei) x C57BL/6 backcross mouse embryos. For the remaining 14 candidate imprinted genes, we observed biallelic expression. In adult mouse tissues, we found that Kcnk9 expression was restricted to the brain and also was maternal-specific. QUASEP analysis of informative human fetal brain samples further demonstrated maternal-specific imprinted expression of the human KCNK9 orthologue. The CpG islands associated with the mouse and human Kcnk9/KCNK9 genes were not differentially methylated but strongly hypomethylated. Thus, we speculate that mouse Kcnk9 imprinting may be regulated by the maternal germline differentially methylated region (DMR) in Peg13, an imprinted non-coding RNA gene in close proximity to Kcnk9 on distal mouse chromosome 15. Our data have major implications for the proposed role of Kcnk9 in neurodevelopment, apoptosis, and tumorigenesis, as well as for the efficiency of sequence-based bioinformatic predictions of novel imprinted genes.
Keywords:	Base Sequence, Brain, Computational Biology, CpG Islands, DNA Methylation, DNA Sequence Analysis, Genomic Imprinting, Potassium Channels, Single Nucleotide Polymorphism, Tandem Pore Domain Potassium Channels, Animals, Mice
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	16
Number:	21
Page Range:	2591-2599
Date:	1 November 2007
Official Publication:	https://doi.org/10.1093/hmg/ddm216
PubMed:	View item in PubMed

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