title: Placental methylome analysis from a prospective autism study.
abstract: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo.
  
  
  
  In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three.
  
  
  
  We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer nearDLL1was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing.
  
  
  
  These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families.
authors.affiliation: Department of Medical Microbiology and Immunology, Genome Center, Davis, CA 95616 USA.
authors.forename: Diane I
authors.initials: DI
authors.lastname: Schroeder
authors.affiliation: Department of Public Health Sciences, University of California, Davis, CA 95616 USA ; MIND Institute, University of California, Davis, CA 95616 USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Schmidt
authors.affiliation: Department of Medical Microbiology and Immunology, Genome Center, Davis, CA 95616 USA.
authors.forename: Florence K
authors.initials: FK
authors.lastname: Crary-Dooley
authors.affiliation: Department of Obstetrics and Gynecology, University of California, Davis, CA 95616 USA ; MIND Institute, University of California, Davis, CA 95616 USA.
authors.forename: Cheryl K
authors.initials: CK
authors.lastname: Walker
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95616 USA ; MIND Institute, University of California, Davis, CA 95616 USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Ozonoff
authors.affiliation: Department of Pediatrics, University of California, Davis, CA 95616 USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tancredi
authors.affiliation: Department of Public Health Sciences, University of California, Davis, CA 95616 USA ; MIND Institute, University of California, Davis, CA 95616 USA.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
authors.affiliation: Department of Medical Microbiology and Immunology, Genome Center, Davis, CA 95616 USA ; MIND Institute, University of California, Davis, CA 95616 USA.
authors.forename: Janine M
authors.initials: JM
authors.lastname: LaSalle
mesh_terms: D000067877:Autism Spectrum Disorder / Q000175:diagnosis* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002675:Child, Preschool; D019175:DNA Methylation; D042241:Early Diagnosis; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: Biomarkers; DNA methylation; Epigenetics; Genomics; Methylome; Placenta