Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Capture-based DNA methylation sequencing facilitates diagnosis and reveals potential pathogenic mechanisms in teratogenic diabetes exposure

Katharina V. Schulze, Amit Bhatt, Mahshid S. Azamian, Nathan C. Sundgren, Gladys Zapata, Patricia Hernandez, Karin Fox, Jeffrey R. Kaiser, John W. Belmont, Neil A. Hanchard
doi: https://doi.org/10.1101/172262
Katharina V. Schulze
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amit Bhatt
2Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mahshid S. Azamian
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan C. Sundgren
2Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gladys Zapata
2Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patricia Hernandez
2Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karin Fox
4Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeffrey R. Kaiser
2Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;
4Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John W. Belmont
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;
3USDA/ARS/Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA;
5Illumina, Inc., San Diego, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Neil A. Hanchard
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;
3USDA/ARS/Children’s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: hanchard@bcm.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Diabetic embryopathy (DE) describes a spectrum of birth defects associated with a teratogenic exposure to maternal diabetes in utero. These defects strongly overlap the phenotypes of known genetic syndromes; however, the pathogenic mechanisms underlying DE remain uncertain and there are no definitive tests that distinguish the diagnosis. Here, we explore the potential of DNA methylation as both a diagnostic biomarker and a means of informing disease pathogenesis in DE. Capture-based bisulfite sequencing was used to compare patterns of DNA methylation at 2,800,516 sites genome-wide in seven DE neonates and 11 healthy neonates, including five with in utero diabetes exposure. DE infants had significantly lower global DNA methylation (ANOVA, Tukey HSD p=0.045) than diabetes-unexposed, healthy controls (UH), with multiple sites showing large (mean methylation difference = 16.6%) and significant (p<0.001) differential methylation between the two groups. We found that a subset of 237 highly differentially methylated loci could accurately distinguish DE infants from both UH and diabetes-exposed healthy infants (sensitivity 80% -100%). Differentially methylated sites were enriched in intergenic (p<3.52×10-15) and intronic (p<0.001) regions found proximal to genes either associated with Mendelian syndromes that overlap the DE phenotype (e.g. TRIO, ANKRD11), or known to influence early organ development (e.g. BRAX1, RASA3). Further, by integrating information on cis-sequence variation, we found that 39.3% of loci with evidence for allele-specific methylation also showed differential methylation between DE and controls. Our study suggests a role for aberrant DNA methylation and cis-sequence variation in the pathogenesis of DE, and highlights the diagnostic potential of DNA methylation for teratogenic birth defects.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 04, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Capture-based DNA methylation sequencing facilitates diagnosis and reveals potential pathogenic mechanisms in teratogenic diabetes exposure
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Capture-based DNA methylation sequencing facilitates diagnosis and reveals potential pathogenic mechanisms in teratogenic diabetes exposure
Katharina V. Schulze, Amit Bhatt, Mahshid S. Azamian, Nathan C. Sundgren, Gladys Zapata, Patricia Hernandez, Karin Fox, Jeffrey R. Kaiser, John W. Belmont, Neil A. Hanchard
bioRxiv 172262; doi: https://doi.org/10.1101/172262
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Capture-based DNA methylation sequencing facilitates diagnosis and reveals potential pathogenic mechanisms in teratogenic diabetes exposure
Katharina V. Schulze, Amit Bhatt, Mahshid S. Azamian, Nathan C. Sundgren, Gladys Zapata, Patricia Hernandez, Karin Fox, Jeffrey R. Kaiser, John W. Belmont, Neil A. Hanchard
bioRxiv 172262; doi: https://doi.org/10.1101/172262

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4382)
  • Biochemistry (9591)
  • Bioengineering (7090)
  • Bioinformatics (24856)
  • Biophysics (12600)
  • Cancer Biology (9955)
  • Cell Biology (14349)
  • Clinical Trials (138)
  • Developmental Biology (7948)
  • Ecology (12105)
  • Epidemiology (2067)
  • Evolutionary Biology (15988)
  • Genetics (10925)
  • Genomics (14738)
  • Immunology (9869)
  • Microbiology (23659)
  • Molecular Biology (9484)
  • Neuroscience (50855)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2681)
  • Physiology (4013)
  • Plant Biology (8657)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2394)
  • Systems Biology (6433)
  • Zoology (1346)