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

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.

scholarly journals Patterns of genome-wide allele-specific expression in hybrid rice and the implications on the genetic basis of heterosis

2019 ◽  
Vol 116 (12) ◽  
pp. 5653-5658 ◽  
Author(s):  
Lin Shao ◽  
Feng Xing ◽  
Conghao Xu ◽  
Qinghua Zhang ◽  
Jian Che ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Sequencing Data ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Parental Allele ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Allele Specific

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.

scholarly journals Germline Allele-Specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer

Science ◽  
2008 ◽  
Vol 321 (5894) ◽  
pp. 1361-1365 ◽  
Author(s):  
L. Valle ◽  
T. Serena-Acedo ◽  
S. Liyanarachchi ◽  
H. Hampel ◽  
I. Comeras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Increased Risk ◽  
Allele Specific

scholarly journals Allelic Switching of DLX5, GRB10, and SVOPL during Colorectal Cancer Tumorigenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Arnoud Boot ◽  
Jan Oosting ◽  
Saskia Doorn ◽  
Sarah Ouahoud ◽  
Marina Ventayol Garcia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Normal Mucosa ◽  
Chromosome 7 ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Human Genes ◽  
Allele Specific ◽  
Somatic Alterations ◽  
Low Passage

Allele-specific expression (ASE) is found in approximately 20-30% of human genes. During tumorigenesis, ASE changes due to somatic alterations that change the regulatory landscape. In colorectal cancer (CRC), many chromosomes show frequent gains or losses while homozygosity of chromosome 7 is rare. We hypothesized that genes essential to survival show allele-specific expression (ASE) on both alleles of chromosome 7. Using a panel of 21 recently established low-passage CRC cell lines, we performed ASE analysis by hybridizing DNA and cDNA to Infinium HumanExome-12 v1 BeadChips containing cSNPs in 392 chromosome 7 genes. The results of this initial analysis were extended and validated in a set of 89 paired normal mucosa and CRC samples. We found that 14% of genes showed ASE in one or more cell lines and identified allelic switching of the potential cell survival genes DLX5, GRB10, and SVOPL on chromosome 7, whereby the most abundantly expressed allele in the normal tissue is the lowest expressed allele in the tumor and vice versa. We established that this allelic switch does not result from loss of imprinting. The allelic switching of SVOPL may be a result of transcriptional downregulation, while the exact mechanisms resulting in the allelic switching of DLX5 and GRB10 remain to be elucidated. In conclusion, our results show that profound changes take place in allelic transcriptional regulation during the tumorigenesis of CRC.

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