Defense Response To Other Organism Process Attribute
Background
The "defense response to other organism process attribute" refers to the intricate collection of biological mechanisms an organism employs to detect, resist, and eliminate threats posed by other living entities. These threats can range from microscopic pathogens like bacteria and viruses to larger parasites or even predators. This fundamental biological imperative is crucial for an organism's survival, ensuring its integrity and health against constant challenges from its environment. The defense response encompasses a wide array of strategies, from physical barriers to complex molecular and cellular cascades, all aimed at protecting the host from foreign invaders and maintaining physiological balance.
Biological Basis
At its core, the defense response is genetically encoded and highly regulated. It involves sophisticated recognition systems that distinguish self from non-self, initiating a cascade of events designed to neutralize threats. These systems include both innate immunity, which provides immediate, non-specific protection, and adaptive immunity, which offers specific, memory-based responses. Genetic variations within genes involved in these pathways can significantly impact an individual's ability to mount an effective defense. For instance, functional variations in genes like _LGALS2_ have been studied for their role in immune responses, influencing processes such as lymphotoxin-alpha secretion, which is a key signaling molecule in inflammation and immune cell communication. [1] Such genetic differences can alter the strength, speed, or specificity of an organism's defense mechanisms.
Clinical Relevance
Understanding the defense response is of paramount importance in clinical medicine. Variations in these responses can determine an individual's susceptibility to infectious diseases, the severity of autoimmune conditions, and even the efficacy of cancer treatments. For example, genetic variations in germline DNA have been interrogated to understand their association with treatment response in childhood acute lymphoblastic leukemia, highlighting how an individual's inherent genetic makeup influences their interaction with disease and therapy. [2] Furthermore, defense responses, including low-grade inflammation, are implicated in the development of chronic conditions such as atherosclerosis and metabolic disorders. [3] Modulating these responses through therapeutic interventions, vaccinations, or lifestyle changes is a cornerstone of modern healthcare.
Social Importance
The societal impact of defense responses is profound, directly influencing public health, global disease patterns, and economic stability. Effective defense mechanisms are essential for containing epidemics, developing successful vaccines, and managing the spread of infectious diseases across populations. Research into genetic variations affecting these responses contributes to personalized medicine approaches, allowing for tailored prevention and treatment strategies based on an individual's genetic profile. Furthermore, understanding the intricate interplay between host defense and environmental pathogens is critical for addressing emerging infectious threats and ensuring global health security.
Methodological and Statistical Considerations
Research into complex biological attributes, such as defense responses, is often constrained by study design and statistical power. Many genome-wide association studies (GWAS) require extensive sample sizes to reliably detect genetic variants with small effect sizes, and studies conducted with more modest cohorts, such as those focusing on specific founder populations, may have limited statistical power to identify all relevant associations. [3] This can lead to an inflation of reported effect sizes in initial findings, underscoring the critical need for independent replication in larger, well-powered cohorts to validate preliminary associations and ensure their robustness. [4]
Furthermore, the replication of genetic findings across independent studies remains a significant challenge, creating replication gaps that can hinder the accumulation of consistent evidence. Differences in study populations, phenotyping methods, or environmental exposures can contribute to inconsistent findings, making it difficult to definitively establish the role of specific genetic variants in influencing complex traits. Robust validation efforts are essential to distinguish true biological signals from chance associations and to build a comprehensive understanding of genetic contributions to defense mechanisms. [4]
Population Specificity and Phenotypic Complexity
The generalizability of genetic findings is a critical limitation, as associations identified in specific populations may not translate universally across diverse ancestral groups. Studies conducted in genetically homogeneous or founder populations, such as the Framingham Heart Study or specific birth cohorts, provide valuable insights but may not fully capture the genetic architecture present in more diverse populations. [1] Variations in allele frequencies, linkage disequilibrium patterns, and historical population structures can influence the portability of genetic risk factors, necessitating broad validation across multiple ancestries to ensure the relevance of findings to the wider human population. [5]
Defining and measuring complex phenotypes, including various aspects of defense responses or related health outcomes, can also pose significant challenges. Subtle differences in how a trait is characterized, the diagnostic criteria employed, or the methodologies used for measurement across different studies can introduce substantial heterogeneity. [1] For instance, the timing and precision of measuring early life growth trajectories and their impact on later-life health, such as coronary events or serum lipids, demonstrate how phenotypic nuances can profoundly affect the detection and interpretation of genetic associations, potentially obscuring true biological relationships. [6]
Environmental and Genetic Interactions
Complex biological attributes, including defense responses, are rarely determined by genetics alone but are instead shaped by intricate interactions between an individual's genetic makeup and their environment. The challenge of comprehensively accounting for environmental or gene–environment confounders, such as lifestyle factors, diet, or specific exposures, can limit the ability of current research to fully elucidate the etiology of these traits. [6] Unmeasured or poorly characterized environmental variables can mask genuine genetic effects or create spurious associations, leading to an incomplete understanding of the complex interplay that drives variation in defense responses.
Despite advances in identifying numerous genetic loci associated with various traits, a significant portion of the heritability for many complex attributes remains unexplained, a phenomenon referred to as "missing heritability." This suggests that current research methodologies may not fully capture the contributions of rare genetic variants, structural genomic variations, epigenetic modifications, or more complex gene–gene and gene–environment interactions. [7] Consequently, substantial knowledge gaps persist in fully delineating the complete genetic architecture and the multifaceted regulatory mechanisms underlying defense responses, indicating that further research employing diverse approaches is necessary.
Variants
Toll-like receptors (TLRs) are fundamental components of the innate immune system, serving as crucial sentinels that detect molecular patterns characteristic of invading microorganisms. Among these, TLR1 and TLR10 are important members, often functioning in concert with TLR2 to form heterodimers that recognize specific microbial ligands, such as bacterial lipopeptides. This recognition is a critical first step in triggering intracellular signaling pathways that orchestrate a robust immune defense, leading to the production of cytokines and chemokines vital for combating infections . [8], [9] The intricate signaling cascades initiated by TLR activation are essential for coordinating the body's rapid and effective response against a wide array of foreign organisms.
The single nucleotide polymorphism *rs10004195* within the TLR1 gene can introduce subtle yet significant changes to the receptor's structure and function. Such a variant might alter the binding affinity of TLR1 for its microbial ligands, or affect its ability to properly partner with TLR2 to form a functional signaling complex. [10] Consequently, individuals carrying this variant may exhibit altered sensitivity to pathogen detection, potentially leading to variations in the strength or duration of their innate immune response. These subtle genetic differences in TLR1 activity are relevant to the body's defense response, influencing susceptibility to various infections and the overall effectiveness of the immune system in neutralizing threats posed by other organisms. [11]
The FCGR2A gene encodes the Fc gamma receptor FcγRIIa, an activating receptor prominently expressed on immune cells like macrophages and neutrophils, playing a pivotal role in the adaptive immune response. This receptor's primary function involves binding to the Fc domain of immunoglobulin G (IgG) antibodies that are already bound to pathogens or infected cells, thereby bridging innate and adaptive immunity. [12] Upon antibody binding, FcγRIIa initiates crucial effector functions such as phagocytosis and antibody-dependent cellular cytotoxicity, which are essential for the efficient clearance of foreign invaders. The *rs368433* variant in FCGR2A is particularly notable as it can lead to a functional change in the receptor, specifically impacting its binding affinity for different IgG subclasses, especially IgG2. [13] This polymorphism can influence an individual's capacity to mount effective antibody-mediated responses, affecting their defense against specific bacterial pathogens that primarily elicit IgG2 responses.
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs10004195 | TLR10 - TLR1 | defense response to other organism process attribute |
| rs368433 | FCGR2A | defense response to other organism process attribute |
Conceptualization and Core Terminology
The concept of 'defense response to other organism process attribute' encompasses the intricate biological reactions an organism mounts in response to stimuli originating from another organism's biological processes. This broadly includes immune responses, inflammatory pathways, and various resistance mechanisms activated to maintain homeostasis or combat external threats. [9] Operationally, these responses can be characterized by specific physiological changes, biomarker levels, or clinical outcomes that reflect the organism's protective actions. For instance, C-reactive protein (CRP) concentrations serve as a measurable attribute of systemic inflammation, a fundamental defense response. [3] Understanding these attributes involves defining the specific traits, such as therapeutic responsiveness in inflammatory conditions, and establishing conceptual frameworks that delineate the interplay between host factors and external biological influences. [9] Key terminology in this domain includes "phenotype associations," which link observable traits to underlying genetic or environmental factors, and "therapeutic outcomes," which assess the efficacy of interventions aimed at modulating these defense mechanisms. [9]
Classification of Defense Response Attributes
Defense response attributes are categorized through various classification systems, often reflecting the specific nature of the interacting organisms or the host's physiological reaction. In the context of human health, these classifications can range from broad disease categories to specific subtypes and severity gradations. For example, inflammatory bowel disease (IBD) can be classified into distinct forms such as Ulcerative Colitis (UC) and Crohn's Disease (CD), each representing a specific pattern of chronic inflammatory defense response. [9] Similarly, nonalcoholic fatty liver disease (NAFLD) involves histological classifications like steatosis, lobular inflammation, ballooning, and fibrosis, which indicate different facets and severity levels of the liver's response to metabolic stressors, potentially influenced by gut microbiome interactions or other organismal processes. [13] These classifications often employ both categorical distinctions, such as "NON-RESPONSE" to a therapeutic agent like anti-TNFα, and dimensional approaches, which grade severity (e.g., lobular inflammation quantified by the number of foci per microscopic field). [9]
Measurement and Diagnostic Criteria
Measuring defense response attributes involves a diverse array of methodologies, from biochemical assays to histological examinations and clinical assessments. Precise diagnostic and measurement criteria are crucial for characterizing these responses in both clinical and research settings. For instance, metabolic traits related to inflammatory responses, such as serum CRP, insulin (INS), and glucose (GLU) concentrations, are determined using methods like radioimmunoassay, glucose dehydrogenase methods, or immunoenzymometric assays from fasting blood samples. [3] Histological criteria, including the presence and severity of steatosis, lobular inflammation, ballooning, and fibrosis, are critical for diagnosing and grading conditions like NAFLD. [13] In genetic association studies, specific thresholds for statistical significance, such as p-values less than 5 × 10−8 or 5 × 10−7, are established to identify genetic variants associated with these traits, often adjusted for multiple comparisons using methods like the Benjamini-Hochberg procedure to control the false discovery rate (FDR). [14] The predictive performance of models assessing therapeutic responsiveness can be evaluated using measures like the area under the Receiver Operating Characteristic (ROC) curve (AUC), sensitivity, and specificity. [9]
Cellular Stress Responses and Regulatory Pathways
Organisms possess intricate cellular defense mechanisms to maintain homeostasis and respond to external threats, ranging from pathogens to toxic substances and radiation. A central aspect of this defense involves the activation of specific signaling pathways that orchestrate cellular responses. For instance, the NFKB, PI3K/Akt, and MAPK/ERK pathways are critical "network hubs" that regulate cell death and survival in response to various stressors, including radiation exposure. [12] The NFKB pathway, in particular, has been implicated in responses to high-dose radiation in cells with compromised TP53 function, highlighting its role in alternative survival strategies when primary tumor suppressor mechanisms are deficient. [15] Beyond survival, these pathways modulate cellular functions like proliferation, senescence, and apoptosis, ensuring appropriate cellular outcomes in the face of damage. [16]
Another crucial component of cellular defense involves stress proteins, such as Heat Shock Protein 70 kDa (HSP70), which play a vital role in the mammalian stress response by maintaining cell physiology and protein integrity. [17] These molecular chaperones help cells cope with various forms of stress, including heat, toxins, and inflammation, by refolding damaged proteins or targeting them for degradation. Furthermore, cell cycle progression is tightly regulated by positive-feedback loops and specific kinases like Polo-like kinase-1 (PLK1), which is activated by Aurora A to facilitate checkpoint recovery and ensure genetic stability after cellular insult. [18] These interconnected molecular and cellular pathways form a robust regulatory network essential for an effective defense response.
Genetic and Epigenetic Modulation of Defense Responses
Genetic variation significantly influences an individual's defense response, determining susceptibility to diseases and efficacy of treatments. Genome-wide association studies (GWAS) are instrumental in identifying single nucleotide polymorphisms (SNPs) associated with differential responses to therapeutic agents, such as anti-TNFalpha treatments in inflammatory bowel disease and rheumatoid arthritis. [9] These genetic markers can affect the expression of genes involved in disease pathogenesis or drug mechanisms of action, providing insights into personalized medicine. [9] For example, variations in the basal expression of GSH pathway genes, involved in the detoxification of substances like NAPQI, can explain a portion of the variability in cellular toxicity responses. [19]
Regulatory elements and epigenetic modifications also play a role in shaping defense responses by controlling gene expression patterns. The regulation of gene expression is highly tissue-specific, meaning that the same genetic variation can have different effects depending on the cell type or tissue context. [20] This cell type-dependent regulation is critical for fine-tuning defense mechanisms in specific organs. Beyond SNPs, studies have identified expression quantitative trait loci (eQTLs) where genetic variants influence gene expression, thereby impacting traits like radiation response. [21] Genes involved in DNA repair, cell cycle control, cell survival, and apoptosis are frequently implicated in radiation sensitivity, demonstrating how genetic predispositions can dictate the cellular outcome of exposure to genotoxic agents. [12]
Pathophysiological Manifestations and Biomolecules in Defense
The effectiveness of defense responses is evident in various pathophysiological processes, where dysregulation can lead to disease or alter therapeutic outcomes. In inflammatory bowel disease (IBD) and rheumatoid arthritis, the immune system's defense against perceived threats can become overactive, leading to chronic inflammation. [9] Therapeutic interventions, such as anti-TNFalpha therapy, aim to modulate these immune responses, and individual variability in treatment success often stems from underlying genetic differences in defense pathways. [9] Biomarkers like anti-saccharomyces cereviciae antibodies (ASCA) and perinuclear anti-nuclear cytoplasmic antibody (pANCA) are indicative of the immune status in IBD, reflecting the organism's ongoing defense against microbial components. [9]
Defense against toxic compounds involves specific metabolic processes, as seen in acetaminophen-NAPQI hepatotoxicity, where the GSH conjugation pathway is crucial for detoxifying the reactive NAPQI metabolite. [19] Disruptions in this pathway can lead to liver damage, highlighting the importance of homeostatic mechanisms in preventing organ-specific pathology. [19] Key biomolecules like the _ATP-binding cassette transporter gene, ABCC4, are implicated in these detoxification processes. [19] Moreover, the expression of proteins such as CLIC1 and TPD52 can serve as potential biomarkers for diseases like colorectal cancer, reflecting cellular changes and compensatory responses during disease progression. [22] The interplay of these molecular players within tissues and organs dictates the overall defense capacity and susceptibility to disease.
Cellular Sensing and Signal Transduction
The defense response to other organism processes is initiated by intricate cellular sensing mechanisms that activate specific signaling pathways. For instance, exposure to radiation triggers distinct signaling pathways within human lymphoblast cell lines, with the specific cascades varying depending on the radiation dose, indicating a nuanced cellular response to external insults. [15] These pathways often involve precise regulatory proteins, such as Polo-like kinase-1 (PLK1), which becomes activated by Aurora A kinase to facilitate recovery from cell cycle checkpoints, ensuring proper cellular progression and integrity during stress. [18] Furthermore, positive-feedback loops are crucial for committing cells to specific outcomes in processes like cell cycle progression, providing robust and irreversible decisions necessary for an effective defense or repair. [23] Receptor tyrosine kinases also play a significant role, with genes like EB-1 (also known as TYK2B) showing transcriptional activation in particular cellular contexts, highlighting their importance in initiating downstream signaling cascades that mediate defense responses. [24]
Metabolic Adaptations for Detoxification and Repair
Effective defense against external organism processes often necessitates significant metabolic adaptations, particularly for detoxification and cellular repair. A prime example is the glutathione (GSH) pathway, which represents the primary mechanism for the biotransformation and subsequent detoxification of harmful compounds, such as N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite. [19] Variations in the baseline expression of genes within the GSH pathway can substantially influence the efficiency of this detoxification, underscoring the critical role of metabolic regulation in modulating a cell's capacity to defend itself against chemical stressors. [19] Beyond direct detoxification, metabolic processes also support the broader cellular defense by enabling repair and maintaining cellular homeostasis, with pathways like the farnesol pathway contributing to lipid biosynthesis, which can be modulated in response to various cellular needs or external influences. [25]
Coordinated Gene Expression and Protein Regulation
Cellular defense mechanisms are meticulously controlled through coordinated gene expression and sophisticated protein regulation, ensuring an appropriate and timely response to diverse threats. Comprehensive gene expression signatures can be developed to serve as practical biomarkers for assessing cellular stress responses, such as those induced by radiation exposure, reflecting the cell's underlying defense status. [26] Key transcription factors, including p53, are instrumental in orchestrating these responses by identifying and activating novel target genes in the context of ionizing radiation, which can lead to critical outcomes like cell cycle arrest or programmed cell death to prevent the propagation of damaged cells. [27] Moreover, the mammalian stress response involves the induction of specific protective proteins, such as heat shock protein 70 kDa (HSP70), which are vital for maintaining protein folding homeostasis and assisting in the recovery from various cellular insults, thereby bolstering the cell's resilience . [17], [28]
Systems-Level Integration and Disease Pathogenesis
The defense response to other organism processes is characterized by complex systems-level integration, involving intricate network interactions and pathway crosstalk, where dysregulation can significantly contribute to disease pathogenesis. For instance, a mutant form of COL13A1, a collagen gene, can profoundly alter the intestinal expression of immune response genes, which in turn predisposes transgenic mice to develop B-cell lymphomas, illustrating how genetic variations can compromise systemic defense mechanisms. [29] Similarly, the altered expression of proteins like chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) can serve as potential biomarkers for conditions such as colorectal cancer, reflecting underlying perturbations in cellular defense and growth regulatory networks. [22] Understanding these highly integrated networks and their emergent properties is paramount for identifying vulnerable points in the defense system and developing therapeutic targets for diseases where these protective mechanisms are either overwhelmed or misdirected.
Frequently Asked Questions About Defense Response To Other Organism Process Attribute
These questions address the most important and specific aspects of defense response to other organism process attribute based on current genetic research.
1. Why do I always catch every cold going around?
It's possible your personal genetic makeup makes you more susceptible. Variations in genes involved in your immune pathways can affect how quickly or strongly your body responds to viruses, making you more prone to catching infections. While lifestyle helps, your inherent genetic differences play a significant role in your defense against common bugs.
2. My sibling rarely gets sick, but I do. Why are we so different?
Even within families, genetic variations can create differences in immune responses. You and your sibling inherit different combinations of genetic variants, which can lead to one of you having a naturally stronger or faster defense system against pathogens. These subtle genetic differences contribute to varying susceptibility to illness.
3. Can eating healthy really boost my body's defenses against sickness?
Yes, eating healthy is a crucial part of a strong defense, but it's not the only factor. While diet provides essential nutrients for your immune system, your genetic blueprint also significantly influences your body's baseline ability to fight off invaders. It's a complex interplay where lifestyle supports your inherent genetic defenses, but can't entirely override them.
4. Does stress actually make me more likely to get sick?
Yes, stress can indeed influence your body's ability to defend itself. Environmental factors like stress interact with your genetic predisposition, potentially weakening your immune response and making you more vulnerable to infections. While your genes set a baseline, chronic stress can impact how effectively your defense mechanisms function.
5. If my family has a history of autoimmune issues, am I doomed to get them too?
Not necessarily "doomed," but a family history of autoimmune issues does suggest a genetic predisposition. Your inherited genetic variations can increase your susceptibility, but environmental factors also play a big role. Understanding your risk can help you focus on lifestyle choices that might mitigate or delay the onset of such conditions.
6. Could a DNA test tell me why I react so strongly to certain things?
Yes, a DNA test could potentially offer insights into why you react strongly to certain exposures. By analyzing your genetic variations, especially in genes involved in immune responses, it might reveal predispositions that influence your specific defense mechanisms. This information can contribute to a more personalized understanding of your body's unique reactions.
7. Why do some people recover from illnesses much faster than others?
The speed of recovery often comes down to individual differences in your defense mechanisms. Genetic variations can influence how quickly your immune system recognizes and neutralizes a threat, and how efficiently it repairs damage. This means some people naturally mount a faster and more effective response, leading to quicker recovery times.
8. Does my ethnic background change how my body fights off germs?
Yes, your ethnic background can play a role in how your body fights off germs. Different ancestral groups can have variations in allele frequencies and genetic structures that influence immune responses. This means genetic findings from one population might not fully apply to another, highlighting the importance of diverse research for personalized health insights.
9. I've heard chronic low-grade inflammation is bad. Does my body cause that?
Yes, your body can indeed contribute to chronic low-grade inflammation, which is linked to conditions like heart disease and metabolic disorders. This type of inflammation is part of your defense response, and genetic variations can influence how your body regulates it. Modulating these responses is a key focus in modern healthcare to maintain physiological balance.
10. Can I really "train" my immune system to be stronger?
You can certainly support and optimize your immune system through lifestyle choices, even if your genetic blueprint sets a baseline. Things like vaccinations, a healthy diet, and managing stress are key "lifestyle changes" that help modulate your defense responses. While you can't fundamentally change your genes, you can empower your body to respond more effectively.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
[1] O'Donnell, C. J. "Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study." BMC Med Genet, 2007.
[2] Yang, J. J., et al. "Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia." JAMA, 2009.
[3] Sabatti, C. et al. "Genome-wide association analysis of metabolic traits in a birth cohort from a founder population." Nat Genet, vol. 41, no. 1, 2009, pp. 35-42.
[4] Skol, A. D., et al. "Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies." Nat Genet, 2006, 38:209-213.
[5] Helgason, A., et al. "An Icelandic example of the impact of population structure on association studies." Nat. Genet., 2005, 37:90–95.
[6] Barker, D. J., et al. "Trajectories of growth among children who have coronary events as adults." N. Engl. J. Med., 2005, 353:1802–1809.
[7] Kaiser, J. "Genomic databases. NIH goes after whole genome in search of disease genes." Science, 2006, 311:933.
[8] Ingle JN, et al. "Genome-wide associations and functional genomic studies of musculoskeletal adverse events in women receiving aromatase inhibitors." J Clin Oncol. 2010.
[9] Dubinsky MC, et al. "Genome wide association (GWA) predictors of anti-TNFalpha therapeutic responsiveness in pediatric inflammatory bowel disease." Inflamm Bowel Dis. 2010.
[10] McClay JL, et al. "Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics." Mol Psychiatry. 2009.
[11] Stein JL, et al. "Voxelwise genome-wide association study (vGWAS)." Neuroimage. 2010.
[12] Niu N, et al. "Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines." Genome Res. 2010.
[13] Chalasani N, et al. "Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease." Gastroenterology. 2010.
[14] Ganesh, SK. et al. "Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium." Nat Genet, vol. 42, no. 3, 2010, pp. 232-237.
[15] Lu, T. P., et al. "Distinct signaling pathways after higher or lower doses of radiation in three closely related human lymphoblast cell lines." Int J Radiat Oncol Biol Phys, 2010.
[16] DeFilippis, R. A., et al. "Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells." J Virol, vol. 77, 2003, pp. 1551–1563.
[17] Welch, W. J. "Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease." Physiol. Rev., 1992.
[18] Macurek, L., et al. "Aurora-A and hBora join the game of Polo." Cancer Res, vol. 69, 2009, pp. 4555–4558.
[19] Moyer, A. M., et al. "Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study." Toxicol Sci, vol. 120, no. 1, 2011, pp. 182-192.
[20] Dimas, A. S., et al. "Common regulatory variation impacts gene expression in a cell type-dependent manner." Science, vol. 325, 2009, pp. 1246–1250.
[21] Correa, C. R., and V. G. Cheung. "Genetic variation in radiation-induced expression phenotypes." Am J Hum Genet, vol. 75, 2004, pp. 885–890.
[22] Petrova, D. T., et al. "Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer." Clin Biochem, 2008.
[23] Pomerening, J. R. "Positive-feedback loops in cell cycle progression." FEBS Lett, 2009.
[24] Fu, Xiaoping, et al. "EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1." Oncogene, 1999.
[25] Hiyoshi, Hitoshi, et al. "Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes." J Lipid Res, 2003.
[26] Paul, S., and S. A. Amundson. "Development of gene expression signatures for practical radiation biodosimetry." Int J Radiat Oncol Biol Phys, 2008.
[27] Jen, K. Y., and V. G. Cheung. "Identification of novel p53 target genes in ionizing radiation response." Cancer Res, vol. 65, 2005, pp. 7666–7673.
[28] Kiang, J. G., and G. C. Tsokos. "Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology." Pharmacol. Ther., vol. 80, 1998, pp. 183–201.
[29] Tuomisto, A., et al. "A mutant collagen XIII alters intestinal expression of immune response genes and predisp-oses transgenic mice to develop B-cell lymphomas." Cancer Res, 2008.