Methylation screening of reciprocal genome-wide UPDs identifies novel human-specific imprinted genes†
| Autor: | David Monk, Cristina Camprubí, Chiharu Tayama, Hidenobu Soejima, Hiroyuki Aburatani, Alex Martin Trujillo, Pablo Lapunzina, Kenichiro Hata, Genta Nagae, Kazuhiko Nakabayashi, Tsutomu Ogata, Wataru Yoshida, Aurora Sánchez |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Molecular Sequence Data Bisulfite sequencing Biology Genome Genomic Imprinting Mice Young Adult Databases Genetic Genetics medicine Animals Humans Molecular Biology Alleles Genetics (clinical) Base Sequence Genome Human Chromosome Mapping Proteins General Medicine DNA Methylation Middle Aged Uniparental Disomy medicine.disease Uniparental disomy Differentially methylated regions CpG site Genetic Loci DNA methylation Illumina Methylation Assay CpG Islands Genomic imprinting Chromosomes Human Pair 16 Transcription Factors |
| Zdroj: | Human Molecular Genetics. 20:3188-3197 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Nuclear transfer experiments undertaken in the mid-80's revealed that both maternal and paternal genomes are necessary for normal development. This is due to genomic imprinting, an epigenetic mechanism that results in parent-of-origin monoallelic expression of genes regulated by germline-derived allelic methylation. To date, ∼100 imprinted transcripts have been identified in mouse, with approximately two-thirds showing conservation in humans. It is currently unknown how many imprinted genes are present in humans, and to what extent these transcripts exhibit human-specific imprinted expression. This is mainly due to the fact that the majority of screens for imprinted genes have been undertaken in mouse, with subsequent analysis of the human orthologues. Utilizing extremely rare reciprocal genome-wide uniparental disomy samples presenting with Beckwith-Wiedemann and Silver-Russell syndrome-like phenotypes, we analyzed ∼0.1% of CpG dinculeotides present in the human genome for imprinted differentially methylated regions (DMRs) using the Illumina Infinium methylation27 BeadChip microarray. This approach identified 15 imprinted DMRs associated with characterized imprinted domains, and confirmed the maternal methylation of the RB1 DMR. In addition, we discovered two novel DMRs, first, one maternally methylated region overlapping the FAM50B promoter CpG island, which results in paternal expression of this retrotransposon. Secondly, we found a paternally methylated, bidirectional repressor located between maternally expressed ZNF597 and NAT15 genes. These three genes are biallelically expressed in mice due to lack of differential methylation, suggesting that these genes have become imprinted after the divergence of mouse and humans. |
| Databáze: | OpenAIRE |
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