Abstract
Traditionally eukaryotic genes are considered independently expressed under the control of their promoters and cis-regulatory domains. However, recent studies in worms, flies, mice and humans have shown that genes co-habiting a chromatin domain or “genomic neighborhood” are frequently co-expressed. Often these co-expressed genes neither constitute part of an operon nor function within the same biological pathway. The mechanisms underlying the partitioning of the genome into transcriptional genomic neighborhoods are poorly defined. However, cross-species analyses find that the linkage among the co-expressed genes of these clusters is significantly conserved and that the expression patterns of genes within clusters have coevolved with the clusters. Such selection could be mediated by chromatin interactions with the nuclear matrix and long-range remodeling of chromatin structure. In the context of human disease, we propose that dysregulation of gene expression across genomic neighborhoods will cause highly pleiotropic diseases. Candidate genomic neighborhood diseases include the nuclear laminopathies, chromosomal translocations and genomic instability disorders, imprinting disorders of errant insulator function, syndromes from impaired cohesin complex assembly, as well as diseases of global covalent histone modifications and DNA methylation. The alteration of transcriptional genomic neighborhoods provides an exciting and novel model for studying epigenetic alterations as quantitative traits in complex common human diseases.
Keywords: Gene Clusters, Molecular Evolution, eukaryotic genes, DNA methylation, genomic neighborhoods
Current Genomics
Title: Gene Clusters, Molecular Evolution and Disease: A Speculation
Volume: 10 Issue: 1
Author(s): Leah I. Elizondo, Paymaan Jafar-Nejad, J. Marietta Clewing and Cornelius F. Boerkoel
Affiliation:
Keywords: Gene Clusters, Molecular Evolution, eukaryotic genes, DNA methylation, genomic neighborhoods
Abstract: Traditionally eukaryotic genes are considered independently expressed under the control of their promoters and cis-regulatory domains. However, recent studies in worms, flies, mice and humans have shown that genes co-habiting a chromatin domain or “genomic neighborhood” are frequently co-expressed. Often these co-expressed genes neither constitute part of an operon nor function within the same biological pathway. The mechanisms underlying the partitioning of the genome into transcriptional genomic neighborhoods are poorly defined. However, cross-species analyses find that the linkage among the co-expressed genes of these clusters is significantly conserved and that the expression patterns of genes within clusters have coevolved with the clusters. Such selection could be mediated by chromatin interactions with the nuclear matrix and long-range remodeling of chromatin structure. In the context of human disease, we propose that dysregulation of gene expression across genomic neighborhoods will cause highly pleiotropic diseases. Candidate genomic neighborhood diseases include the nuclear laminopathies, chromosomal translocations and genomic instability disorders, imprinting disorders of errant insulator function, syndromes from impaired cohesin complex assembly, as well as diseases of global covalent histone modifications and DNA methylation. The alteration of transcriptional genomic neighborhoods provides an exciting and novel model for studying epigenetic alterations as quantitative traits in complex common human diseases.
Export Options
About this article
Cite this article as:
Elizondo I. Leah, Jafar-Nejad Paymaan, Clewing Marietta J. and Boerkoel F. Cornelius, Gene Clusters, Molecular Evolution and Disease: A Speculation, Current Genomics 2009; 10 (1) . https://dx.doi.org/10.2174/138920209787581271
DOI https://dx.doi.org/10.2174/138920209787581271 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
G Protein-Coupled Receptor Kinase 2 - a Feedback Regulator of Gq Pathway Signalling
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Sarcoidosis in Pregnancy and Postpartum Period
Current Respiratory Medicine Reviews Inotropic and Vasoactive Drugs in Pediatric ICU
Current Drug Targets Meet Our Editorial Board Member:
Current Drug Targets Immune Checkpoint Inhibitor Therapy and Risk of Myocarditis: A Review of the Literature
Current Immunology Reviews (Discontinued) Editorial (Thematic Issue: The Life Cycle of the Heart Failure Patient)
Current Cardiology Reviews Pediatric Immune Dysfunction and Health Risks Following Early-Life Immune Insult
Current Pediatric Reviews Mechanisms of Intimal Hyperplasia Learned from a Murine Carotid Artery Ligation Model
Current Vascular Pharmacology Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets Metformin and Anti-Cancer Therapeutics: Hopes for a More Enhanced Armamentarium Against Human Neoplasias?
Current Medicinal Chemistry New Approach to Immunotherapy Against Organ-specific Autoimmune Diseases with T Cell Receptor and Chemokine Receptor DNA Vaccines
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Patent Selections
Recent Patents on Cardiovascular Drug Discovery Artificial Neural Networks in Cardiovascular Diseases and its Potential for Clinical Application in Molecular Imaging
Current Radiopharmaceuticals Hydrogen Peroxide Produced by Mitochondrial Monoamine Oxidase Catalysis: Biological Implications
Current Pharmaceutical Design Role of Oxidative-Nitrosative Stress and Downstream Pathways in Various Forms of Cardiomyopathy and Heart Failure
Current Vascular Pharmacology T Lymphocytes as Targets of Statins: Molecular Mechanisms and Therapeutic Perspectives
Inflammation & Allergy - Drug Targets (Discontinued) Curcumin: A Natural Product for Diabetes and its Complications
Current Topics in Medicinal Chemistry Twenty Years of Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy
Current Cardiology Reviews Pathophysiology of Diabetic Secondary Complication and their Management
Current Diabetes Reviews Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction
Current Drug Targets