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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01178

Pervasive Inter-individual Variation in Allele-Specific Expression in Monozygotic Twins

  • 1National Laboratory for Scientific Computing (LNCC), Brazil
  • 2Universidade Estadual do Norte Fluminense Darcy Ribeiro, Brazil
  • 3Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Brazil
  • 4Federal University of Minas Gerais, Brazil
  • 5Center for Biosciences and Biotechnology, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Brazil

Despite being developed from one zygote, heterokaryotypic monozygotic (MZ) co-twins exhibit discordant karyotypes. Epigenomic studies in biological samples from heterokaryotypic MZ co-twins are of the most significant value for assessing the effects on gene- and allele-specific expression of an extranumerary chromosomal copy or structural chromosomal disparities in otherwise nearly identical germline genetic contributions. Here, we use RNA-Seq data from existing repositories to establish within-pair correlations for the breadth and magnitude of allele-specific expression (ASE) in heterokaryotypic MZ co-twins discordant for trisomy 21 and maternal 21q inheritance, as well as homokaryotypic co-twins. We show that there is a genome-wide disparity at ASE sites between the heterokaryotypic MZ co-twins. Although most of the disparity corresponds to changes in the magnitude of biallelic imbalance, ASE sites switching from either strictly monoallelic to biallelic imbalance or the reverse occur in few genes that are known or predicted to be imprinted, subject to X-chromosome inactivation or A-to-I(G) RNA edited. We also uncovered comparable ASE differences between homokaryotypic MZ twins. The extent of ASE discordance in MZ twins (2.7%) was about 10-fold lower than the expected between pairs of unrelated, non-twin males or females. The results indicate that the observed within-pair dissimilarities in breadth and magnitude of ASE sites in the heterokaryotypic MZ co-twins could not solely be attributable to the aneuploidy and the missing allelic heritability at 21q.

Keywords: allele-specific expression, allelic bias, allele imbalance, biallelic expression, Down Syndrome, Genomic Imprinting, heterokaryotypic monozygotic co-twins, mitochondrial heteroplasmy, pathogenic expression-altering, random monoallelic expression, recombination, RNA-Seq, trisomy 21

Received: 11 Jul 2019; Accepted: 24 Oct 2019.

Copyright: © 2019 Junior, Ferreira, Santos e Silva, Machado, Martins Cortes, Ramos, Simões Carnivali, Garcia and Medina-Acosta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Enrique Medina-Acosta, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Center for Biosciences and Biotechnology, Campos dos Goytacazes, 28013602, Rio de Janeiro, Brazil,