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Am J Hum Genet. 2015 Jan 8;96(1):70-80. doi: 10.1016/j.ajhg.2014.12.001. Epub 2014 Dec 31.

Biased allelic expression in human primary fibroblast single cells.

Author information

1
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
2
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
3
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan.
4
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Service of Genetic Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
5
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland; Center of Excellence for Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Biomedical Research Foundation Academy of Athens, Athens 11527, Greece. Electronic address: emmanouil.dermitzakis@unige.ch.
6
Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Service of Genetic Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland. Electronic address: stylianos.antonarakis@unige.ch.

Abstract

The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.

PMID:
25557783
PMCID:
PMC4289680
DOI:
10.1016/j.ajhg.2014.12.001
[Indexed for MEDLINE]
Free PMC Article

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