Assessment of imprinting- and genetic variation-dependent monoallelic expression using reciprocal allele descendants between human family trios

Sci Rep. 2017 Aug 1;7(1):7038. doi: 10.1038/s41598-017-07514-z.

Abstract

Genomic imprinting is an important epigenetic process that silences one of the parentally-inherited alleles of a gene and thereby exhibits allelic-specific expression (ASE). Detection of human imprinting events is hampered by the infeasibility of the reciprocal mating system in humans and the removal of ASE events arising from non-imprinting factors. Here, we describe a pipeline with the pattern of reciprocal allele descendants (RADs) through genotyping and transcriptome sequencing data across independent parent-offspring trios to discriminate between varied types of ASE (e.g., imprinting, genetic variation-dependent ASE, and random monoallelic expression (RME)). We show that the vast majority of ASE events are due to sequence-dependent genetic variant, which are evolutionarily conserved and may themselves play a cis-regulatory role. Particularly, 74% of non-RAD ASE events, even though they exhibit ASE biases toward the same parentally-inherited allele across different individuals, are derived from genetic variation but not imprinting. We further show that the RME effect may affect the effectiveness of the population-based method for detecting imprinting events and our pipeline can help to distinguish between these two ASE types. Taken together, this study provides a good indicator for categorization of different types of ASE, opening up this widespread and complex mechanism for comprehensive characterization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Family Health*
  • Gene Expression Profiling / methods*
  • Genetic Variation*
  • Genomic Imprinting*
  • Genotype*
  • Genotyping Techniques / methods*
  • Humans