Ribosomal protein genes are highly enriched among genes with allele-specific expression in the interspecific F1 hybrid catfish

Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth syndrome Beckwith–Wiedemann (BWS). We have recently shown LOI at the KCNQ1 locus in LOS, the most common epimutation in BWS. Although the first case of ART-induced LOS was reported in 1995, studies have not yet determined the extent of LOI in this condition. Here, we determined allele-specific expression of imprinted genes previously identified in human and/or mouse in day ∼105 Bos taurus indicus × Bos taurus taurus F1 hybrid control and LOS fetuses using RNAseq. Our analysis allowed us to determine the monoallelic expression of 20 genes in tissues of control fetuses. LOS fetuses displayed variable LOI compared with controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. In addition, a positive correlation was observed between body weight and the number of biallelically expressed imprinted genes in LOS fetuses. Furthermore, not only was there loss of allele-specific expression of imprinted genes in LOS, but also differential transcript amounts of these genes between control and overgrown fetuses. In summary, we characterized previously unidentified imprinted genes in bovines and identified misregulation of imprinting at multiple loci in LOS. We concluded that LOS is a multilocus LOI syndrome, as is BWS.

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Hierarchical Analysis of Multi-mapping RNA-Seq Reads Improves the Accuracy of Allele-specific Expression

10.1101/166900 ◽

2017 ◽

Author(s):

Narayanan Raghupathy ◽

Kwangbom Choi ◽

Matthew J. Vincent ◽

Glen L. Beane ◽

Keith Sheppard ◽

...

Keyword(s):

Integrated Approach ◽

Estimation Methods ◽

Rna Seq ◽

Specific Expression ◽

Allele Specific Expression ◽

F1 Hybrid ◽

Cis Acting ◽

Allele Specific ◽

Total Gene Expression ◽

Hybrid Mice

AbstractAllele-specific expression (ASE) refers to the differential abundance of the allelic copies of a transcript. Direct RNA sequencing (RNA-Seq) can provide quantitative estimates of ASE for genes with transcribed polymorphisms. However, estimating ASE is challenging due to ambiguities in read alignment. Current approaches do not account for the hierarchy of multiple read alignments to genes, isoforms, and alleles. We have developed EMASE (Expectation-Maximization for Allele Specific Expression), an integrated approach to estimate total gene expression, ASE, and isoform usage based on hierarchical allocation of multi-mapping reads. In simulations, EMASE outperforms standard ASE estimation methods. We apply EMASE to RNA-Seq data from F1 hybrid mice where we observe widespread ASE associated with cis-acting polymorphisms and a small number of parent-of-origin effects at known imprinted genes. The EMASE software is freely available under GNU license at https://github.com/churchill-lab/emase and it can be adapted to other sequencing applications.

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Genomic analysis of allele-specific expression in the mouse liver

10.1101/024588 ◽

2015 ◽

Cited By ~ 1

Author(s):

Ashutosh K Pandey ◽

Robert W Williams

Keyword(s):

Gene Expression ◽

Phenotypic Diversity ◽

Direct Method ◽

Eqtl Analysis ◽

Specific Expression ◽

Allele Specific Expression ◽

F1 Hybrid ◽

Cis Acting ◽

Functional Variants ◽

Allele Specific

Genetic differences in gene expression contribute significantly to phenotypic diversity and differences in disease susceptibility. In fact, the great majority of causal variants highlighted by genome-wide association are in non-coding regions that modulate expression. In order to quantify the extent of allelic differences in expression, we analyzed liver transcriptomes of isogenic F1 hybrid mice. Allele-specific expression (ASE) effects are pervasive and are detected in over 50% of assayed genes. Genes with strong ASE do not differ from those with no ASE with respect to their length or promoter complexity. However, they have a higher density of sequence variants, higher functional redundancy, and lower evolutionary conservation compared to genes with no ASE. Fifty percent of genes with no ASE are categorized as house-keeping genes. In contrast, the high ASE set may be critical in phenotype canalization. There is significant overlap between genes that exhibit ASE and those that exhibit strong cis expression quantitative trait loci (cis eQTLs) identified using large genetic expression data sets. Eighty percent of genes with cis eQTLs also have strong ASE effects. Conversely, 40% of genes with ASE effects are associated with strong cis eQTLs. Cis-acting variation detected at the protein level is also detected at the transcript level, but the converse is not true. ASE is a highly sensitive and direct method to quantify cis-acting variation in gene expression and complements and extends classic cis eQTL analysis. ASE differences can be combined with coding variants to produce a key resource of functional variants for precision medicine and genome-to-phenome mapping.

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Investigation of allele specific expression in various tissues of broiler chickens using the detection tool VADT

Scientific Reports ◽

10.1038/s41598-021-83459-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

M. Joseph Tomlinson ◽

Shawn W. Polson ◽

Jing Qiu ◽

Juniper A. Lake ◽

William Lee ◽

...

Keyword(s):

Broiler Chickens ◽

Nucleotide Polymorphisms ◽

Rna Seq ◽

Specific Expression ◽

Single Nucleotide ◽

Allele Specific Expression ◽

Detection Tool ◽

Commercial Broiler ◽

Significant Phenomenon ◽

Allele Specific

AbstractDifferential abundance of allelic transcripts in a diploid organism, commonly referred to as allele specific expression (ASE), is a biologically significant phenomenon and can be examined using single nucleotide polymorphisms (SNPs) from RNA-seq. Quantifying ASE aids in our ability to identify and understand cis-regulatory mechanisms that influence gene expression, and thereby assist in identifying causal mutations. This study examines ASE in breast muscle, abdominal fat, and liver of commercial broiler chickens using variants called from a large sub-set of the samples (n = 68). ASE analysis was performed using a custom software called VCF ASE Detection Tool (VADT), which detects ASE of biallelic SNPs using a binomial test. On average ~ 174,000 SNPs in each tissue passed our filtering criteria and were considered informative, of which ~ 24,000 (~ 14%) showed ASE. Of all ASE SNPs, only 3.7% exhibited ASE in all three tissues, with ~ 83% showing ASE specific to a single tissue. When ASE genes (genes containing ASE SNPs) were compared between tissues, the overlap among all three tissues increased to 20.1%. Our results indicate that ASE genes show tissue-specific enrichment patterns, but all three tissues showed enrichment for pathways involved in translation.

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