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Title

Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15

Authors
Migliavacca, Eugenia
Stathaki, Elisavet
Baumer, Alessandra
Schinzel, Albert
Mackay, Deborah J.
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Published in Genome Research. 2010, vol. 20, no. 9, p. 1271-1278
Abstract The maternal and paternal genomes possess distinct epigenetic marks that distinguish them at imprinted loci. In order to identify imprinted loci, we used a novel method, taking advantage of the fact that uniparental disomy (UPD) provides a system that allows the two parental chromosomes to be studied independently. We profiled the paternal and maternal methylation on chromosome 15 using immunoprecipitation of methylated DNA and hybridization to tiling oligonucleotide arrays. Comparison of six individuals with maternal versus paternal UPD15 revealed 12 differentially methylated regions (DMRs). Putative DMRs were validated by bisulfite sequencing, confirming the presence of parent-of-origin-specific methylation marks. We detected DMRs associated with known imprinted genes within the Prader-Willi/Angelman syndrome region, such as SNRPN and MAGEL2, validating this as a method of detecting imprinted loci. Of the 12 DMRs identified, eight were novel, some of which are associated with genes not previously thought to be imprinted. These include a site within intron 2 of IGF1R at 15q26.3, a gene that plays a fundamental role in growth, and an intergenic site upstream of GABRG3 that lies within a previously defined candidate region conferring an increased maternal risk of psychosis. These data provide a map of parent-of-origin-specific epigenetic modifications on chromosome 15, identifying DNA elements that may play a functional role in the imprinting process. Application of this methodology to other chromosomes for which UPD has been reported will allow the systematic identification of imprinted sites throughout the genome.
Keywords Angelman Syndrome/geneticsChromosomes, Human, Pair 15/*geneticsDNA/metabolism*DNA MethylationGene Expression ProfilingHumansPrader-Willi Syndrome/geneticsProteins/geneticsUniparental Disomy/*geneticsSnRNP Core Proteins/genetics
Identifiers
PMID: 20631049
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Research group Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
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SHARP, Andrew James et al. Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15. In: Genome Research, 2010, vol. 20, n° 9, p. 1271-1278. https://archive-ouverte.unige.ch/unige:21311

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Deposited on : 2012-05-23

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