Current Genomics - Volume 5, Issue 6, 2004

Comparative studies of the molecular control of development in diverse animal groups have revealed a surprising conservation in the genetic control of animal development. A dramatic demonstration of this conservation is seen in the expression and function of Hox genes deployed along the animal anterior-posterior (A-P) body axis, where similar expression and function of Hox genes are seen in animals as diverse as nematodes, insects and vertebrates. With the genome sequences of several metazoans now in hand and the availability of BAC genomic libraries from additional species, researchers have begun to characterize the genomic changes underlying divergent developmental programs. This review summarizes the role of Hox genes in evolution of the vertebrates. General patterns of Hox cluster evolution among the major lineages of vertebrates are described including lineage-specific instances of cluster duplication and gene loss. Following this are brief descriptions of the evolving role of Hox genes in evolution of primitive vertebrates, and their subsequent roles in evolution of vertebrate axial and appendicular diversity. A conceptual theme uniting all these studies is the remarkable plasticity of Hox genes in the evolution of vertebrate diversity. Finally, the increasingly important roles of experimental advances in genomics and bioinformatics are discussed along with suggestions for future directions in vertebrate Hox research.

Corticotropin-releasing factor (CRF) and its related peptides play a central role in the co-ordination of autonomic, behavioural, cardiovascular, immune and endocrine responses to stressful stimuli. Their actions are mediated through activation of two G-protein-coupled receptors encoded by separate genes, termed CRF-R1 and -R2. In this review we focus on the structure, phylogeny, and expression of CRF peptide family. We present up-to-date literature on divergent actions of the CRF peptide family, including stress and behaviour, cardiovascular physiology, energy balance and re pr oduction. We also pr ese nt a br ief over view of CRF rec eptor s inc luding pha rmacologic al aspe cts a nd potential therapeutic interventions for CRF receptors.

All creatures living in the earth have an indispensable instinct to anticipate and respond to time. Actually this is not due to the environment outside. The main pacemaker is supposed to be located in the suprachiasmatic nuclei (SCN), which can generate a free-running rhythm independent of environmental cues. Besides, most peripheral tissues also possess their own oscillators. The SCN coordinates peripheral clocks to synchronize with the real time. Since the investigation of circadian rhythm entered the “gene” era, many substantial findings have been made in each aspect of this subject, to name a few, the relationship between the SCN and peripheral oscillators, new insight in peripheral clocks. Here our goal is to describe and illustrate the general concept about mammalian circadian clocks from the discovery of clock genes to the latest findings of them. We are endeavoring to make a recapitulation of the crucial findings in this field including the definition of clock genesoregulation of clock genes in central and peripheral pacemakers and the relationship between them. True understanding of the mechanism of circadian rhythms will absolutely usher us into a new field in applying it in the treatment of some diseases related to the circadian rhythm.

Head and Neck Squamous Cell Carcinomas (HNSCC) are a collection of tumors located in the upper aerodigestive tract that account for ∼500, 000 new cases annually. Onset of the disease in the population has been attributed to multiple environmental factors. Pathways leading to the development and progression of head and neck squamous cell carcinomas remain largely unknown. Common genetic alterations have been identified, but many of the important genes of activation (oncogenes) or inactivation (tumor suppressor genes) have not yet been identified or characterized. Epigenetic mechanisms, such as histone modifications and DNA methylation, have also become accepted modes of transcriptional inactivation in human malignancies, but are still in their initial stages of evaluation in HNSCC. The majority of DNA methylation studies in HNSCC have focused on genes previously identified as being inactivated in other cancer types. Efforts using genome-wide methylation scanning techniques, such as Restriction Landmark Genomic Scanning (RLGS), have identified novel methylation targets in HNSCC. Due to the involvement of DNA methylation, clinical trials involving demethylating agents, such as Decitabine, alone or in combination with chromatin modifying agents, remain attractive therapeutic options in cancer currently under investigation. Better understanding of the role of DNA methylation in squamous cell carcinomas of the head and neck, as well as the targets of this epigenetic inactivation, may allow for more efficient and earlier detection screenings. In this review, we will discuss our current understanding of epigenetic alterations in HNSCC and their potential use as targets for therapeutic intervention.

Recently, microarray technology is reshaping the molecular biology, given the high number of fields of application like, gene expression analysis, rapid sequencing of DNA, mapping of allelic variation, identification polymorphisms. It is a recently developed technique, which allows analysing thousands of genes in a very short time. Due to the powerful nature of this genetic approach, the number of researches using microarray technology boosted in the last years (less than ten papers from 1995 to 1997, up to approximately one thousand in the following 5 years -PubMed). Nevertheless, in spite of the promising fields of application, many drawbacks need to be carefully considered before generalizing the results obtained with this new technology. In fact, up to now a number of drawbacks have been described in the use of DNA microarray: many errors of incorporation during the manufacturing of the chips, loss of splicing variants, variable reliability of differential expression data, low specificity of cDNA microarray probes, discrepancy in fold change calculation for a given gene and so on. In spite of all those troubles, there is no doubt that this new promising technology could give an overall idea of gene organization and expression and might contribute to understanding the molecular mechanisms involved in processes as disease diagnosis or drug discovery (Pharmacogenetics and Pharmacogenomics). The goal of the present review is to suggest a targeted use of DNA chip technology in the field of pharmacogenetics (with the example of antidepressants), suggesting the inclusion of only those genes, possibly candidates, through a step by step analysis of the pathways involved in the pharmacological action of antidepressants.

Gene overlap, consisting of two or more adjacent genes with partially or totally overlapping expressible units, has very recently emerged as a common feature, rather than an exception to the rule, in a significant portion of eukaryotic genomes. Considering the lack of strong evolutionary pressure on genome size in eukaryotes, the frequent recurrence of such a gene disposition is unexpected. However, these findings, along with the recent estimate that fewer genes than expected are encoded in the human genome, strengthen the hypothesis that organism complexity may reside in the interaction within and among genome, transcriptome and proteome. In this context, overlapping genes could represent a hidden source of complexity to modulate gene expression. In fact, overlapping genes, when transcribed in the opposite directions, give rise to sense-antisense transcript pairs, which often exhibit reciprocal expression patterns. These natural antisense transcripts (NATs) have been demonstrated to play a role in a variety of processes, including mRNA splicing and stability, RNA editing, genomic imprinting and control of translation. Here we present the first review on eukaryotic overlapping genes, an attempt of shedding light on this dark side of the genome. We also report the most interesting and well-studied cases and depict a general frame of this phenomenon.