Allele-Biased Expression in Differentiating Human Neurons: Implications for Neuropsychiatric Disorders

Mingyan Lin, Anastasia Hrabovsky, Erika Pedrosa, Tao Wang, Deyou Zheng, Herbert M. Lachman

Research output: Contribution to journalArticle

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Abstract

Stochastic processes and imprinting, along with genetic factors, lead to monoallelic or allele-biased gene expression. Stochastic monoallelic expression fine-tunes information processing in immune cells and the olfactory system, and imprinting plays an important role in development. Recent studies suggest that both stochastic events and imprinting may be more widespread than previously considered. We are interested in allele-biased gene expression occurring in the brain because parent-of-origin effects suggestive of imprinting appear to play a role in the transmission of schizophrenia (SZ) and autism spectrum disorders (ASD) in some families. In addition, allele-biased expression could help explain monozygotic (MZ) twin discordance and reduced penetrance. The ability to study allele-biased expression in human neurons has been transformed with the advent of induced pluripotent stem cell (iPSC) technology and next generation sequencing. Using transcriptome sequencing (RNA-Seq) we identified 801 genes in differentiating neurons that were expressed in an allele-biased manner. These included a number of putative SZ and ASD candidates, such as A2BP1 (RBFOX1), ERBB4, NLGN4X, NRG1, NRG3, NRXN1, and NLGN1. Overall, there was a modest enrichment for SZ and ASD candidate genes among those that showed evidence for allele-biased expression (chi-square, p = 0.02). In addition to helping explain MZ twin discordance and reduced penetrance, the capacity to group many candidate genes affecting a variety of molecular and cellular pathways under a common regulatory process - allele-biased expression - could have therapeutic implications.

Original languageEnglish (US)
Article numbere44017
JournalPLoS One
Volume7
Issue number8
DOIs
StatePublished - Aug 30 2012

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Neurons
Genes
neurons
Alleles
genomic imprinting
alleles
Gene expression
penetrance
Schizophrenia
Stem cells
Monozygotic Twins
Random processes
Penetrance
Brain
RNA
Stochastic Processes
RNA Sequence Analysis
Gene Expression
Induced Pluripotent Stem Cells
gene expression

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Allele-Biased Expression in Differentiating Human Neurons : Implications for Neuropsychiatric Disorders. / Lin, Mingyan; Hrabovsky, Anastasia; Pedrosa, Erika; Wang, Tao; Zheng, Deyou; Lachman, Herbert M.

In: PLoS One, Vol. 7, No. 8, e44017, 30.08.2012.

Research output: Contribution to journalArticle

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