Frequent monoallelic or skewed expression for developmental genes in CNS-derived cells and evidence for balancing selection

Branciamore, Sergio; Valo, Zuzana; Li, Min; Wang, Jinhui; Riggs, Arthur D.; Singer-Sam, Judith

doi:10.1073/pnas.1808652115

Cited by 15 publications

(16 citation statements)

References 37 publications

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“…aASE has been reported extensively in mammalian tissues 6 – 12 but also in Drosophila 13 , Arabidopsis thaliana 14 and Candida albicans 15 . aASE effects are known in certain gene families.…”

Section: Introductionmentioning

confidence: 99%

“…Besides X-chromosome linked genes and imprinted genes, widespread allele-specific expression can also be found on autosomal non sex-linked or imprinted genes ('autosomal' ASE-aASE) 4,5 . aASE has been reported extensively in mammalian tissues [6][7][8][9][10][11][12] but also in Drosophila 13 , Arabidopsis thaliana 14 and Candida albicans 15 . aASE effects are known in certain gene families.…”

mentioning

confidence: 99%

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Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum

Hoguin

Rastogi

Bowler

et al. 2021

Sci Rep

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Recent advances in next generation sequencing technologies have allowed the discovery of widespread autosomal allele-specific expression (aASE) in mammals and plants with potential phenotypic effects. Extensive numbers of genes with allele-specific expression have been described in the diatom Fragilariopsis cylindrus in association with adaptation to external cues, as well as in Fistulifera solaris in the context of natural hybridization. However, the role of aASE and its extent in diatoms remain elusive. In this study, we investigate allele-specific expression in the model diatom Phaeodactylum tricornutum by the re-analysis of previously published whole genome RNA sequencing data and polymorphism calling. We found that 22% of P. tricornutum genes show moderate bias in allelic expression while 1% show nearly complete monoallelic expression. Biallelic expression associates with genes encoding components of protein metabolism while moderately biased genes associate with functions in catabolism and protein transport. We validated candidate genes by pyrosequencing and found that moderate biases in allelic expression were less stable than monoallelically expressed genes that showed consistent bias upon experimental validations at the population level and in subcloning experiments. Our approach provides the basis for the analysis of aASE in P. tricornutum and could be routinely implemented to test for variations in allele expression under different environmental conditions.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum

Hoguin

Rastogi

Bowler

et al. 2021

Sci Rep

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“…The investigation of RME and RAExI faces technical challenges, as their observation can be confounded with poor detection, genetic aberrations, or transcriptional bursting 14, 17 . In this study, we managed to overcome these limitations.…”

Section: Discussionmentioning

confidence: 99%

“…We established 249 independent NPC clonal cell lines from single cells, from six independent differentiation experiments (Supplementary Table 1). The analysis of such a large number of clones confers better statistical power and robustness compared to all previous studies [6][7][8][9][10][11][12][13][14] .…”

Section: The Study Of Rme Reveals the Existence Of Raeximentioning

confidence: 99%

“…A less well-understood category concerns autosomal, clonally heritable "random monoallelically expressed" (RME) genes (estimated to comprise 1 to 10% of genes) 5 . RME genes were identified through numerous genome-wide allele-specific analyses of gene expression in single-cell derived clones from hybrid cell lines [6][7][8][9][10][11][12][13][14] . These studies showed that some genes can be expressed monoallelically from the maternal or paternal allele, or biallelically, and that these expression patterns are inherited during cell division.…”

Section: Introductionmentioning

confidence: 99%

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Locus specific epigenetic modalities of random allelic expression imbalance

Marion‐Poll

Forêt

Zielinski

et al. 2021

Preprint

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Most autosomal genes are thought to be expressed from both alleles, with some notable exceptions, including imprinted genes and genes showing random monoallelic expression (RME). The extent and nature of RME has been the subject of debate. Here we investigate the expression of several candidate RME genes in F1 hybrid mouse cells before and after differentiation, to define how they become persistently, monoallelically expressed. Clonal monoallelic expression was not observed in ESCs, but when we assessed expression status in more than 200 clones of neuronal progenitor cells, we observed high frequencies of monoallelism. We uncovered unforeseen modes of allelic expression that appear to be gene-specific and epigenetically regulated. This non-canonical allelic regulation has important implications for development and disease, including autosomal dominant disorders and opens up novel therapeutic perspectives.

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Biologic characterization of ABCA3 variants in lung tissue from infants and children with ABCA3 deficiency

Wegner

Geurts

et al. 2022

Pediatric Pulmonology

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ABCA3 is a phospholipid transporter protein required for surfactant assembly in lamellar bodies of alveolar type II cells. Biallelic pathogenic ABCA3 variants cause severe neonatal respiratory distress syndrome or childhood interstitial lung disease.However, ABCA3 genotype alone does not explain the diversity in disease presentation, severity, and progression. Additionally, monoallelic ABCA3 variants have been reported in infants and children with ABCA3-deficient phenotypes. The effects of most ABCA3 variants identified in patients have not been characterized at the RNA level. ABCA3 allele-specific expression occurs in some cell types due to epigenetic regulation. We obtained lung tissue at transplant or autopsy from 16 infants and children with ABCA3 deficiency due to compound heterozygous ABCA3 variants for biologic characterization of the predicted effects of ABCA3 variants at the RNA level and determination of ABCA3 allele expression. We extracted DNA and RNA from frozen lung tissue and reverse-transcribed cDNA from mRNA. We performed Sanger sequencing to assess allele-specific expression by comparing the heights of variant nucleotide peaks in amplicons from genomic DNA and cDNA. We found similar genomic and cDNA variant nucleotide peak heights and no evidence of allelespecific expression among explant or autopsy samples with biallelic missense ABCA3 variants (n = 6). We observed allele-specific expression of missense alleles in trans with frameshift (n = 4) or nonsense (n = 1) variants, attributable to nonsensemediated decay. The missense variant c.53 A > G;p.Gln18Arg, located near an exonintron junction, encoded abnormal splicing with skipping of exon 4. Biologic characterization of ABCA3 variants can inform discovery of variant-specific disease mechanisms.

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Frequent monoallelic or skewed expression for developmental genes in CNS-derived cells and evidence for balancing selection

Cited by 15 publications

References 37 publications

Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum

Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum

Locus specific epigenetic modalities of random allelic expression imbalance

Biologic characterization of ABCA3 variants in lung tissue from infants and children with ABCA3 deficiency

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