Further understanding human disease genes by comparing with housekeeping genes and other genes

Tu, Zhidong; Wang, Li; Xu, Min; Zhou, Xianghong Jasmine; Chen, Ting; Sun, Fengzhu

doi:10.1186/1471-2164-7-31

Cited by 130 publications

(113 citation statements)

References 41 publications

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“…We also observed a greater proportion of essential genes in large proteins than nonessential genes. This may be because those essential proteins often play the role of hub proteins (highly connected) in the proteinprotein physical interaction (Jeong et al 2001) and have higher average interaction degrees (Tu et al 2006), such that essential genes may contain relatively more proteins with higher physical interaction degrees than nonessential genes. Furthermore, the degree of protein-protein interaction is positively correlated with protein length (Tan et al 2005), and large proteins undergo more frequent proteinprotein interactions than small proteins (Warringer and Blomberg 2006).…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of essential genes and nonessential genes in Escherichia coli K12

et al. 2007

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Genes can be classified as essential or nonessential based on their indispensability for a living organism. Previous researches have suggested that essential genes evolve more slowly than nonessential genes and the impact of gene dispensability on a gene's evolutionary rate is not as strong as expected. However, findings have not been consistent and evidence is controversial regarding the relationship between the gene indispensability and the rate of gene evolution. Understanding how different classes of genes evolve is essential for a full understanding of evolutionary biology, and may have medical relevance in the design of new antibacterial agents. We therefore performed an investigation into the properties of essential and nonessential genes. Analysis of evolutionary conservation, protein length distribution and amino acid usage between essential and nonessential genes in Escherichia coli K12 demonstrated that essential genes are relatively preserved throughout the bacterial kingdom when compared to nonessential genes. Furthermore, results show that essential genes, compared to nonessential genes, have a significantly higher proportion of large (>534 amino acids) and small proteins (<139 amino acids) relative to medium-sized proteins. The pattern of amino acids usage shows a similar trend for essential and nonessential genes, although some notable exceptions are observed. These findings help to clarify our understanding of the evolutionary mechanisms of essential and nonessential genes, relevant to the study of mutagenesis and possibly allowing prediction of gene properties in other poorly understood organisms.

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Section: Discussionmentioning

confidence: 99%

Comparative analysis of essential genes and nonessential genes in Escherichia coli K12

et al. 2007

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“…Biochemically, beta-cells have vanishingly low expression levels of both the lactate/pyruvate transporter MCT1 (Zhao et al 2001) and lactate dehydrogenases (Sekine et al 1994;Schuit et al 1997). Despite this tissue-specific repression, lactate dehydrogenase A (Ldha), for example, appears in many published lists of housekeeping genes (Warrington et al 2000;Hsiao et al 2001;Eisenberg and Levanon 2003;Tu et al 2006). Inappropriate activation of a tissue-specifically repressed gene was previously demonstrated to be associated with human disease (Otonkoski et al 2007).…”

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confidence: 99%

Tissue-specific disallowance of housekeeping genes: The other face of cell differentiation

Thorrez¹,

Laudadio²,

Deun³

et al. 2010

Genome Res.

175

204

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We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of “disallowed genes.” In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease.

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“…DRPs that were drug targets, drug-related enzymes, or drug-related transporters were collected from DrugBank15 (Version Jan/14/2011). Essential genes, which are indispensable for cellular life, were taken from the literature published by Tu et al16. Protein-tissue distribution data were obtained from the EST databases of the NCBI17.…”

Section: Methodsmentioning

confidence: 99%

Network Characteristic Analysis of ADR-related Proteins and Identification of ADR-ADR Associations

Chen

Liu

Jia

et al. 2013

Sci Rep

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Adverse drug reactions (ADRs) are caused by interactions between drugs or their metabolites and specific proteins. Knowledge of these proteins is important for facilitating mechanistic research of ADRs and new drug discovery. Here, we identified 41 network modules from an ADR-protein network; analysed the function of each module; revealed the potential accompanying actions of the ADRs and the new ADR-related proteins (ADRPs) to a unique ADR and studied the characteristics of composition, subcellular location and tissue distribution of these ADRPs by comparing them with drug-related proteins (DRPs). The results indicated that ADRs are mainly caused by risk drug-related proteins (RDRPs) and that drug off-target effects are a secondary cause. Biological processes that enzymes involve are the main reason for the occurrence of ADRs. However, drug-related transporters have a higher risk of inducing ADRs than drug-related enzymes do, and ADRPs locating in the cell membrane tend to induce multiple ADRs.

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Further understanding human disease genes by comparing with housekeeping genes and other genes

Cited by 130 publications

References 41 publications

Comparative analysis of essential genes and nonessential genes in Escherichia coli K12

Comparative analysis of essential genes and nonessential genes in Escherichia coli K12

Tissue-specific disallowance of housekeeping genes: The other face of cell differentiation

Network Characteristic Analysis of ADR-related Proteins and Identification of ADR-ADR Associations

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