Exploring genome-wide DNA methylation patterns in Aicardi syndrome

Ignazio S Piras; Gabrielle Mills; Lorida Llaci; Marcus Naymik; Keri Ramsey; Newell Belnap; Chris D Balak; Wayne M Jepsen; Szabolcs Szelinger; Ashley L Siniard; Candace R Lewis; Madison LaFleur; Ryan F Richholt; Matt D De Both; Kristiina Avela; Sampathkumar Rangasamy; David W Craig; Vinodh Narayanan; Irma Järvelä; Matthew J Huentelman; Isabelle Schrauwen

doi:10.2217/epi-2017-0060

Exploring genome-wide DNA methylation patterns in Aicardi syndrome

Epigenomics. 2017 Nov;9(11):1373-1386. doi: 10.2217/epi-2017-0060. Epub 2017 Oct 2.

Authors

Ignazio S Piras^{1

2}, Gabrielle Mills^{1

2}, Lorida Llaci^{1

2}, Marcus Naymik^{1

2}, Keri Ramsey^{1

2}, Newell Belnap^{1

2}, Chris D Balak^{1

2}, Wayne M Jepsen^{1

2}, Szabolcs Szelinger^{1

2

3}, Ashley L Siniard^{1

2}, Candace R Lewis^{1

2}, Madison LaFleur^{1

2}, Ryan F Richholt^{1

2}, Matt D De Both^{1

2}, Kristiina Avela⁴, Sampathkumar Rangasamy^{1

2}, David W Craig^{1

2

5}, Vinodh Narayanan^{1

2}, Irma Järvelä⁶, Matthew J Huentelman^{1

2}, Isabelle Schrauwen^{1

2

7}

Affiliations

¹ Center for Rare Childhood Disorders, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, USA.
² Neurogenomics Division, Translational Genomics Research Institute, 445 N 5th Street, Phoenix, AZ, USA.
³ Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, Los Angeles, CA 90095, USA.
⁴ Department of Clinical Genetics, Helsinki University Hospital, Meilahdentie 2, FI-00029 Helsinki, Finland.
⁵ University of Southern California, Keck School of Medicine, Department of Translational Genomics, Los Angeles, NRT 1450 Biggy Street, CA 90033, USA.
⁶ Department of Medical Genetics, University of Helsinki, Haartmaninkatu 8, 00251 Helsinki, Finland.
⁷ Center for Statistical Genetics, Department of Molecular & Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

PMID: 28967789
DOI: 10.2217/epi-2017-0060

Abstract

Aim: To explore differential DNA methylation (DNAm) in Aicardi syndrome (AIC), a severe neurodevelopmental disorder with largely unknown etiology.

Patients & methods: We characterized DNAm in AIC female patients and parents using the Illumina 450 K array. Differential DNAm was assessed using the local outlier factor algorithm, and results were validated via qPCR in a larger set of AIC female patients, parents and unrelated young female controls. Functional epigenetic modules analysis was used to detect pathways integrating both genome-wide DNAm and RNA-seq data.

Results & conclusion: We detected differential methylation patterns in AIC patients in several neurodevelopmental and/or neuroimmunological networks. These networks may be part of the underlying pathogenic mechanisms involved in the disease.

Keywords: Aicardi syndrome; DNA methylation; KCNAB3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aicardi Syndrome / genetics*
Algorithms
DNA Methylation*
Epigenesis, Genetic*
Female
Gene Regulatory Networks
Humans
Infant
Infant, Newborn
Male
Molecular Diagnostic Techniques / methods
Pedigree
Whole Genome Sequencing / methods