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Allele-specific gene expression is widespread across the genome and biological processes.

ABSTRACT: Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sample and expressed in peripheral blood mononuclear cells), 2,934 (57%) SNPs had differential allelic expression. Such SNPs were equally distributed along human chromosomes and biological processes. We validated the presence or absence of ASGE in 18 out 20 SNPs (90%) randomly selected by real time PCR in 48 human subjects. In addition, we observed that SNPs close to -but not included in- segmental duplications had increased levels of ASGE. Finally, we found that transcripts of unknown function or non-coding RNAs, also display ASGE: from a total of 2,308 intronic SNPs, 1510 (65%) SNPs underwent differential allelic expression. In summary, ASGE is a widespread mechanism in the human genome whose regulation seems to be far more complex than expected.

SUBMITTER: Palacios R

PROVIDER: S-EPMC2613524 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Allele-specific gene expression is widespread across the genome and biological processes.

Palacios Ricardo R Gazave Elodie E Goñi Joaquín J Piedrafita Gabriel G Fernando Olga O Navarro Arcadi A Villoslada Pablo P

PloS one 20090107 1

Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sam ...[more]

PMID: 19127300

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Project description:We investigated the role of tumor copy number (CN)-altered genome (CN-AG) in the carcinogenesis of cervical cancer (CC), especially its effect on gene expression, biological processes, and patient survival. Fifty-nine human papillomavirus 16 (HPV16)-positive CCs were investigated with microarrays-31 for mapping CN-AG and 55 for global gene expression, with 27 CCs in common. Five-year survival was investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as CN alterations. The %CN-AG varied from 0 to 32.2% (mean = 8.1±8.9). Tumors were classified as low (mean = 0.5±0.6, n = 11), medium (mean = 5.4±2.4, n = 10), or high (mean = 19.2±6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated directly by gene dosage. In contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of deregulated genes in whole tumors (r2 = 0.232, p = 0.006; analysis of variance), including genes located in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This suggests that the remaining genes are not deregulated directly by gene dosage, but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profile of APC/C-dependent proteasome proteolysis were associated with poor patient survival (p<0.05, log-rank test). Along with glycolysis, they were linearly associated with FIGO stage (r>0.38, p<0.01, Spearman test). Therefore, inhibition of APC/C-dependent proteasome proteolysis and glycolysis could be useful for CC treatment. However, whether they are indispensable for tumor growth remains to be demonstrated.

Dataset Information

Allele-specific gene expression is widespread across the genome and biological processes.

Publications

Allele-specific gene expression is widespread across the genome and biological processes.

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