A Genome-Wide Study of Allele-Specific Expression in Colorectal Cancer

Utilization of heterosis has greatly increased the productivity of many crops worldwide. Although tremendous progress has been made in characterizing the genetic basis of heterosis using genomic technologies, molecular mechanisms underlying the genetic components are much less understood. Allele-specific expression (ASE), or imbalance between the expression levels of two parental alleles in the hybrid, has been suggested as a mechanism of heterosis. Here, we performed a genome-wide analysis of ASE by comparing the read ratios of the parental alleles in RNA-sequencing data of an elite rice hybrid and its parents using three tissues from plants grown under four conditions. The analysis identified a total of 3,270 genes showing ASE (ASEGs) in various ways, which can be classified into two patterns: consistent ASEGs such that the ASE was biased toward one parental allele in all tissues/conditions, and inconsistent ASEGs such that ASE was found in some but not all tissues/conditions, including direction-shifting ASEGs in which the ASE was biased toward one parental allele in some tissues/conditions while toward the other parental allele in other tissues/conditions. The results suggested that these patterns may have distinct implications in the genetic basis of heterosis: The consistent ASEGs may cause partial to full dominance effects on the traits that they regulate, and direction-shifting ASEGs may cause overdominance. We also showed that ASEGs were significantly enriched in genomic regions that were differentially selected during rice breeding. These ASEGs provide an index of the genes for future pursuit of the genetic and molecular mechanism of heterosis.

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Genome-wide analysis of expression QTL (eQTL) and allele-specific expression (ASE) in pig muscle identifies candidate genes for meat quality traits

Genetics Selection Evolution ◽

10.1186/s12711-020-00579-x ◽

2020 ◽

Vol 52 (1) ◽

Author(s):

Yan Liu ◽

Xiaolei Liu ◽

Zhiwei Zheng ◽

Tingting Ma ◽

Ying Liu ◽

...

Keyword(s):

Candidate Genes ◽

Meat Quality ◽

Quality Traits ◽

Q Value ◽

Specific Expression ◽

Allele Specific Expression ◽

Meat Quality Traits ◽

Genome Wide ◽

A Genome ◽

Allele Specific

Abstract Background Genetic analysis of gene expression level is a promising approach for characterizing candidate genes that are involved in complex economic traits such as meat quality. In the present study, we conducted expression quantitative trait loci (eQTL) and allele-specific expression (ASE) analyses based on RNA-sequencing (RNAseq) data from the longissimus muscle of 189 Duroc × Luchuan crossed pigs in order to identify some candidate genes for meat quality traits. Results Using a genome-wide association study based on a mixed linear model, we identified 7192 cis-eQTL corresponding to 2098 cis-genes (p ≤ 1.33e-3, FDR ≤ 0.05) and 6400 trans-eQTL corresponding to 863 trans-genes (p ≤ 1.13e-6, FDR ≤ 0.05). ASE analysis using RNAseq SNPs identified 9815 significant ASE-SNPs in 2253 unique genes. Integrative analysis between the cis-eQTL and ASE target genes identified 540 common genes, including 33 genes with expression levels that were correlated with at least one meat quality trait. Among these 540 common genes, 63 have been reported previously as candidate genes for meat quality traits, such as PHKG1 (q-value = 1.67e-6 for the leading SNP in the cis-eQTL analysis), NUDT7 (q-value = 5.67e-13), FADS2 (q-value = 8.44e-5), and DGAT2 (q-value = 1.24e-3). Conclusions The present study confirmed several previously published candidate genes and identified some novel candidate genes for meat quality traits via eQTL and ASE analyses, which will be useful to prioritize candidate genes in further studies.

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A Genome-Wide Study of Cytogenetic Changes in Colorectal Cancer Using SNP Microarrays: Opportunities for Future Personalized Treatment

PLoS ONE ◽

10.1371/journal.pone.0031968 ◽

2012 ◽

Vol 7 (2) ◽

pp. e31968 ◽

Cited By ~ 39

Author(s):

Farzana Jasmine ◽

Ronald Rahaman ◽

Charlotte Dodsworth ◽

Shantanu Roy ◽

Rupash Paul ◽

...

Keyword(s):

Colorectal Cancer ◽

Personalized Treatment ◽

Genome Wide ◽

A Genome ◽

Snp Microarrays ◽

Cytogenetic Changes ◽

Genome Wide Study

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Genome-Wide Regulatory Interactions in the Early Stages of Drosophila Speciation

10.36939/ir.202012151547 ◽

2020 ◽

Author(s):

◽

Alwyn Clark Go

Keyword(s):

Reproductive Isolation ◽

Expression Analysis ◽

Regulatory Elements ◽

Specific Expression ◽

Allele Specific Expression ◽

Regulatory Interactions ◽

Early Stages ◽

Genome Wide ◽

Allele Specific ◽

Incomplete Reproductive Isolation

Speciation occurs when reproductive barriers prevent the exchange of genetic information between individuals. A common form of reproductive barrier between species capable of interbreeding is hybrid sterility. Genomic incompatibilities between the divergent genomes of different species contribute to a reduction in hybrid fitness. These incompatibilities continue to accumulate after speciation, therefore, young divergent taxa with incomplete reproductive isolation are important in understating the genetics leading to speciation. Here, I use two Drosophila subspecies pairs. The first is D. willistoni consisting of D. w. willistoni and D. w. winge. The second subspecies pair is D. pseudoobscura, which is composed of D. p. pseudoobscura and D. p. bogotana. Both subspecies pairs are at the early stages of speciation and show incomplete reproductive isolation through unidirectional hybrid male sterility. In this thesis, I performed an exploratory survey of genome-wide expression analysis using RNA-sequencing on D. willistoni and determined the extent of regulatory divergence between the subspecies using allele-specific expression analysis. I found that misexpressed genes showed a degree of tissue specificity and that the sterile male hybrids had a higher proportion of misexpressed genes in the testes relative to the fertile hybrids. The analysis of regulatory divergence between this subspecies pair found a large (66-70%) proportion of genes with conserved regulatory elements. Of the genes showing evidence or regulatory divergence between subspecies, cis-regulatory divergence was more common than other types. In the D. pseudoobscura subspecies pair, I compared sequence and expression divergence and found no support for directional selection driving gene misexpression in their hybrids. Allele-specific expression analysis revealed that compensatory cis-trans mutations partly explained gene misexpression in the hybrids. The remaining hybrid misexpression occurs due to interacting gene networks or possible co-option of cis-regulatory elements by divergent transacting factors. Overall, the results of this thesis highlight the role of regulatory interactions in a hybrid genome and how these interactions could lead to hybrid breakdown by disrupting gene interaction networks.

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Genome-wide identification of allele-specific expression (ASE) in response to Marek’s disease virus infection using next generation sequencing

BMC Proceedings ◽

10.1186/1753-6561-5-s4-s14 ◽

2011 ◽

Vol 5 (Suppl 4) ◽

pp. S14 ◽

Cited By ~ 13

Author(s):

Sean MacEachern ◽

William M Muir ◽

Seth Crosby ◽

Hans H Cheng

Keyword(s):

Next Generation Sequencing ◽

Virus Infection ◽

Disease Virus ◽

Marek's Disease Virus ◽

Next Generation ◽

Specific Expression ◽

Allele Specific Expression ◽

Genome Wide ◽

Allele Specific ◽

Generation Sequencing

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Genetic and transcriptional analysis of human host response to healthy gut microbiome

10.1101/058784 ◽

2016 ◽

Author(s):

Allison L. Richards ◽

Michael B. Burns ◽

Adnan Alazizi ◽

Luis B. Barreiro ◽

Roger Pique-Regi ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiome ◽

Molecular Mechanisms ◽

Transcriptional Response ◽

Experimental System ◽

Transcriptional Analysis ◽

Specific Expression ◽

Allele Specific Expression ◽

Disease States ◽

Allele Specific

AbstractMany studies have demonstrated the importance of the gut microbiome in healthy and disease states. However, establishing the causality of host-microbiome interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiome in human cells and to shed light on the molecular mechanisms underlying host-gut microbiome interactions. In primary human colonic epithelial cells, we identified over 6,000 genes that change expression at various time points following co-culturing with the gut microbiome of a healthy individual. The differentially expressed genes are enriched for genes associated with several microbiome-related diseases, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host SNPs that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiome. Of these 12 genes, eight have been associated with diseases linked to the gut microbiome, specifically colorectal cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiome interactions and can be used to identify putative mechanisms for the interplay between host genetics and microbiome in health and disease.

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