Skip to main content
Journal cover image

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism.

Publication ,  Journal Article
Gregory, SG; Connelly, JJ; Towers, AJ; Johnson, J; Biscocho, D; Markunas, CA; Lintas, C; Abramson, RK; Wright, HH; Ellis, P; Langford, CF ...
Published in: BMC Med
October 22, 2009

BACKGROUND: Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders. METHODS: We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR). RESULTS: Our analysis revealed a genomic deletion containing the oxytocin receptor gene, OXTR (MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate OXTR expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that OXTR mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls. CONCLUSION: Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of OXTR in the development of the disorder.See the related commentary by Gurrieri and Neri: http://www.biomedcentral.com/1741-7015/7/63.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

BMC Med

DOI

EISSN

1741-7015

Publication Date

October 22, 2009

Volume

7

Start / End Page

62

Location

England

Related Subject Headings

  • Young Adult
  • Sequence Deletion
  • Receptors, Oxytocin
  • Microarray Analysis
  • Male
  • Humans
  • General & Internal Medicine
  • Female
  • DNA Methylation
  • DNA
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., … Pericak-Vance, M. A. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med, 7, 62. https://doi.org/10.1186/1741-7015-7-62
Gregory, Simon G., Jessica J. Connelly, Aaron J. Towers, Jessica Johnson, Dhani Biscocho, Christina A. Markunas, Carla Lintas, et al. “Genomic and epigenetic evidence for oxytocin receptor deficiency in autism.BMC Med 7 (October 22, 2009): 62. https://doi.org/10.1186/1741-7015-7-62.
Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, et al. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009 Oct 22;7:62.
Gregory, Simon G., et al. “Genomic and epigenetic evidence for oxytocin receptor deficiency in autism.BMC Med, vol. 7, Oct. 2009, p. 62. Pubmed, doi:10.1186/1741-7015-7-62.
Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009 Oct 22;7:62.
Journal cover image

Published In

BMC Med

DOI

EISSN

1741-7015

Publication Date

October 22, 2009

Volume

7

Start / End Page

62

Location

England

Related Subject Headings

  • Young Adult
  • Sequence Deletion
  • Receptors, Oxytocin
  • Microarray Analysis
  • Male
  • Humans
  • General & Internal Medicine
  • Female
  • DNA Methylation
  • DNA