Epigenome analyses using BAG microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3

Tsui Ting Ching, Alika K. Maunakea, Peter Jun, Chibo Hong, Giuseppe Zardo, Daniel Pinkel, Donna G. Albertson, Jane Fridlyand, Jian Hua Mao, Ksenya Shchors, William A. Weiss, Joseph F. Costello

Research output: Contribution to journalArticle

Abstract

CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme Notl. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all Notl sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.

Original languageEnglish (US)
Pages (from-to)645-651
Number of pages7
JournalNature Genetics
Volume37
Issue number6
DOIs
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Genetics

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    Ching, T. T., Maunakea, A. K., Jun, P., Hong, C., Zardo, G., Pinkel, D., Albertson, D. G., Fridlyand, J., Mao, J. H., Shchors, K., Weiss, W. A., & Costello, J. F. (2005). Epigenome analyses using BAG microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3. Nature Genetics, 37(6), 645-651. https://doi.org/10.1038/ng1563