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

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

1088-9051
1271-1278
Sharp, Andrew J.
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Migliavacca, Eugenia
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Dupre, Yann
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Stathaki, Elisavet
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Sailani, Mohammad Reza
232be586-8cb5-4a2a-973b-bcaeb71e8698
Baumer, Alessandra
bac4f0ba-a48a-4f3e-82bc-5c7bd3c8e36e
Schinzel, Albert
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Mackay, Deborah J.
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Robinson, David O.
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Cobellis, Gilda
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Cobellis, Luigi
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Brunner, Han G.
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Steiner, Bernhard
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Antonarakis, Stylianos E.
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Sharp, Andrew J.
4f814cb9-0069-4850-ad81-5ad57435f414
Migliavacca, Eugenia
eda5ed6b-ec9d-4f00-9308-6fa2cfbad9d2
Dupre, Yann
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Stathaki, Elisavet
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Sailani, Mohammad Reza
232be586-8cb5-4a2a-973b-bcaeb71e8698
Baumer, Alessandra
bac4f0ba-a48a-4f3e-82bc-5c7bd3c8e36e
Schinzel, Albert
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Mackay, Deborah J.
588a653e-9785-4a00-be71-4e547850ee4a
Robinson, David O.
9db1b26b-6c2b-4ac5-879e-20f8a2dc30ec
Cobellis, Gilda
df5d226d-a270-4c45-afb6-432ec07f457d
Cobellis, Luigi
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Brunner, Han G.
05804df4-c21b-4b65-b87c-e1cefe53713e
Steiner, Bernhard
96a4b74a-13a4-4d2f-a7e8-2eddc9c119f0
Antonarakis, Stylianos E.
0590e0a2-82a2-4672-816b-0c9396c62c4c

Sharp, Andrew J., Migliavacca, Eugenia, Dupre, Yann, Stathaki, Elisavet, Sailani, Mohammad Reza, Baumer, Alessandra, Schinzel, Albert, Mackay, Deborah J., Robinson, David O., Cobellis, Gilda, Cobellis, Luigi, Brunner, Han G., Steiner, Bernhard and Antonarakis, Stylianos E. (2010) Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15. Genome Research, 20 (9), 1271-1278. (doi:10.1101/gr.108597.110).

Record type: Article

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.

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Accepted/In Press date: 14 July 2010
Published date: September 2010

Identifiers

Local EPrints ID: 161295
URI: http://eprints.soton.ac.uk/id/eprint/161295
ISSN: 1088-9051
PURE UUID: 945b8694-969b-42e0-afb9-41ce9d6bb89d
ORCID for Deborah J. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

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Date deposited: 27 Jul 2010 15:21
Last modified: 17 Dec 2019 01:54

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Contributors

Author: Andrew J. Sharp
Author: Eugenia Migliavacca
Author: Yann Dupre
Author: Elisavet Stathaki
Author: Mohammad Reza Sailani
Author: Alessandra Baumer
Author: Albert Schinzel
Author: David O. Robinson
Author: Gilda Cobellis
Author: Luigi Cobellis
Author: Han G. Brunner
Author: Bernhard Steiner
Author: Stylianos E. Antonarakis

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