Allelic expression analysis in the brain suggests a role for heterogeneous insults affecting epigenetic processes in autism spectrum disorders

Hum Mol Genet. 2014 Aug 1;23(15):4111-24. doi: 10.1093/hmg/ddu128. Epub 2014 Mar 21.


Monoallelic expression, including genomic imprinting, X-chromosome inactivation and random monoallelic expression of autosomal genes are epigenetic phenomena. Genes that are expressed in a monoallelic way may be more vulnerable to genetic or epigenetic mutations. Thus, comprehensive exploration of monoallelic expression in human brains may shed light on complex brain disorders. Autism-related disorders are known to be associated with imprinted genes on chromosome 15. However, it is not clear whether other imprinted regions or other types of monoallelic expression are associated with autism spectrum disorder (ASD). Here, we performed a genome-wide survey of allele expression imbalance (AEI) in the human brain using single-nucleotide polymorphisms (SNPs), in 18 individuals with ASD and 15 controls. Individuals with ASD had the most extreme number of monoallelic expressed SNPs in both the autosomes and the X chromosome. In two cases that were studied in detail, the monoallelic expression was confined to specific brain region or cell type. Using these data, we were also able to define the allelic expression status of known imprinted genes in the human brain and to identify abnormal imprinting in an individual with ASD. Lastly, we developed an analysis of individual-level expression, focusing on the difference of each individual from the mean. We found that individuals with ASD had more genes that were up- or down-regulated in an individual-specific manner. We also identified pathways perturbed in specific individuals. These results underline the heterogeneity in gene regulation in ASD, at the level of both allelic and total expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Brain / metabolism*
  • Brain / physiopathology
  • Case-Control Studies
  • Child
  • Child Development Disorders, Pervasive / genetics*
  • Child Development Disorders, Pervasive / physiopathology
  • Chromosomes, Human, Pair 15
  • Female
  • Genetic Heterogeneity
  • Genomic Imprinting*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • X Chromosome Inactivation*