Genome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620805
Title:
Genome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion.
Authors:
Clissold, Rhian L. ( 0000-0002-3090-3492 ) ; Ashfield, B.; Burrage, J.; Hannon, E.; Bingham, Coralie; Mill, Jonathan; Hattersley, Andrew T.; Dempster, E. L.
Abstract:
Heterozygous mutation of the transcription factor HNF1B is the most common cause of monogenetic developmental renal disease. Disease-associated mutations fall into two categories: HNF1B intragenic mutations and a 1.3 Mb deletion at chromosome 17q12. An increase in neurodevelopmental disorders has been observed in individuals harbouring the 17q12 deletion but not in patients with HNF1B coding mutations.Previous investigations have concentrated on identifying a genetic cause for the increase in behavioural problems seen in 17q12 deletion carriers. We have taken the alternative approach of investigating the DNA methylation profile of these two HNF1B genotype groups along with controls matched for age, gender and diabetes status using the Illumina 450K DNA methylation array (total sample n = 60).We identified a number of differentially methylated probes (DMPs) that were associated with HNF1B-associated disease and passed our stringent experiment-wide significance threshold. These associations were largely driven by the deletion patients and the majority of the significant probes mapped to the 17q12 deletion locus. The observed changes in DNA methylation at this locus were not randomly dispersed and occurred in clusters, suggesting a regulatory mechanism reacting to haploinsufficiency across the entire deleted region.Along with these deletion-specific changes in DNA methylation, we also identified a shared DNA methylation signature in both mutation and deletion patient groups indicating that haploinsufficiency of HNF1B impacts on the methylome of a number of genes, giving further insight to the role of HNF1B.
Citation:
Genome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion. 2018, 10 (1):97 Clin Epigenetics
Publisher:
BioMed Central
Journal:
Clinical epigenetics
Issue Date:
18-Jul-2018
URI:
http://hdl.handle.net/11287/620805
DOI:
10.1186/s13148-018-0530-z
PubMed ID:
30021660
Additional Links:
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0530-z
Note:
This article is freely available under Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
1868-7083
Appears in Collections:
Exeter Kidney Unit (Renal); Diabetes/Endocrine Services; Honorary contracts publications; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorClissold, Rhian L.en
dc.contributor.authorAshfield, B.en
dc.contributor.authorBurrage, J.en
dc.contributor.authorHannon, E.en
dc.contributor.authorBingham, Coralieen
dc.contributor.authorMill, Jonathanen
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorDempster, E. L.en
dc.date.accessioned2018-07-30T11:11:42Z-
dc.date.available2018-07-30T11:11:42Z-
dc.date.issued2018-07-18-
dc.identifier.citationGenome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion. 2018, 10 (1):97 Clin Epigeneticsen
dc.identifier.issn1868-7083-
dc.identifier.pmid30021660-
dc.identifier.doi10.1186/s13148-018-0530-z-
dc.identifier.urihttp://hdl.handle.net/11287/620805-
dc.description.abstractHeterozygous mutation of the transcription factor HNF1B is the most common cause of monogenetic developmental renal disease. Disease-associated mutations fall into two categories: HNF1B intragenic mutations and a 1.3 Mb deletion at chromosome 17q12. An increase in neurodevelopmental disorders has been observed in individuals harbouring the 17q12 deletion but not in patients with HNF1B coding mutations.Previous investigations have concentrated on identifying a genetic cause for the increase in behavioural problems seen in 17q12 deletion carriers. We have taken the alternative approach of investigating the DNA methylation profile of these two HNF1B genotype groups along with controls matched for age, gender and diabetes status using the Illumina 450K DNA methylation array (total sample n = 60).We identified a number of differentially methylated probes (DMPs) that were associated with HNF1B-associated disease and passed our stringent experiment-wide significance threshold. These associations were largely driven by the deletion patients and the majority of the significant probes mapped to the 17q12 deletion locus. The observed changes in DNA methylation at this locus were not randomly dispersed and occurred in clusters, suggesting a regulatory mechanism reacting to haploinsufficiency across the entire deleted region.Along with these deletion-specific changes in DNA methylation, we also identified a shared DNA methylation signature in both mutation and deletion patient groups indicating that haploinsufficiency of HNF1B impacts on the methylome of a number of genes, giving further insight to the role of HNF1B.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttps://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0530-zen
dc.rightsArchived with thanks to Clinical epigenetics. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleGenome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion.en
dc.typeJournal Articleen
dc.identifier.journalClinical epigeneticsen
dc.description.noteThis article is freely available under Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.