Current Genomics, Vol. 6, No. 4, 2005
Contents
Human Races: Classifying People vs Understanding
Diversity Pp. 215-226
Guido Barbujani
Chromatin Assembly from Yeast to Man: Conserved Factors
and Conserved Molecular Mechanisms Pp. 227-240
Troy A.A. Harkness
Parkinson Disease: From Cellular and Animal Models to
Genomics Pp. 241-250
Ignacio Marin and Jorge Vallejo
Drosophila Neoplasias: Clues Towards the
Understanding of Human Cancers Pp. 251-256
E.C. Woodhouse and L.A. Liotta
What Have Microarrays Told Us About the Neuronal Ceroid
Lipofuscinoses? Pp. 257-268
Chun-Hung Chan and David A. Pearce
Functional Analyses of the Human Genome Based on
Large-Scale Fulllength cDNA Resources Pp. 269-291
Yutaka Suzuki and Sumio Sugano
Abstracts
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Human Races: Classifying People vs Understanding Diversity
Guido Barbujani
The idea that all humans naturally belong to one of a few biological types or races that evolved in isolation was unchallenged for centuries, but large-scale modern studies failed to associate racial labels with recognizable genetic clusters. Recently, the conclusions of those studies have been questioned by authors who argue that racial classification has objective scientific bases and is indispensable in epidemiology and genetics. However, no classification is useful if the classification units are vague or controversial, and no consensus was ever reached on the number and definition of the human races. The available studies show that there is geographic structure in human genome diversity, and that it is possible to infer with reasonable accuracy the continent of origin from an individual’s multilocus genotype. However, clear-cut genetic boundaries between human groups, which would be necessary to recognise these groups as relatively isolated mating units which zoologists would call races, have not been identified so far. On the contrary, allele frequencies and synthetic descriptors of genetic variation appear distributed in gradients over much of the planet, which points to gene flow, rather than to isolation, as the main evolutionary force shaping human genome diversity. A better understanding of patterns of human diversity and of the underlying evolutionary processes is important for its own sake, but is also indispensable for the development of diagnostic and therapeutic tools designed for the individual genotype, rather than for ill-defined race-specific genotypes.
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Chromatin Assembly from Yeast to Man: Conserved Factors and Conserved
Molecular Mechanisms
Troy A.A. Harkness
[Back to top] Parkinson
Disease: From Cellular and Animal Models to Genomics
Ignacio Marin and Jorge Vallejo
Parkinson disease is one of the most common human neurodegenerative diseases. Its importance has led to a large number of studies focused on the development of cellular and animal models for the disease. We first discuss the potentials and limitations of the available mammalian models for PD. The results obtained so far in some alternative models, such as yeasts or invertebrates (Drosophila, Caenorhabditis), that may be used to develop rapid genetic or pharmacological screenings, are also summarized. Finally, we briefly discuss the results derived from novel approaches, such as the analysis of expression profiles using microarrays and proteomic analyses of cellular and animal models of Parkinson disease. Integration of the data derived from all those approaches emerges as a significant problem to be solved in the next few years.
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to top] Drosophila Neoplasias: Clues Towards
the Understanding of Human Cancers
E.C. Woodhouse and L.A. Liotta
A large number of tumor suppressor genes have been identified in Drosophila. Mutations in these genes cause effects in a wide range of tissues resulting in, hyperplastic and, in the case of a few specific genes, neoplastic growth. The study of these tumors can provide molecular and cellular information that may shed some light on the possible mechanisms of tumorigenesis and invasiveness of human tumor cells. Recently, several studies have shown links between homologs of Drosophila tumor suppressor genes and human cancer. These recent advances are reviewed.
[Back
to top] What Have Microarrays Told Us About the Neuronal Ceroid
Lipofuscinoses?
Chun-Hung Chan and David A. Pearce
The neuronal ceroid lipofuscinoses (NCL) are the most common childhood neurodegenerative disorders with a worldwide incidence of up to 1 in 12, 500 live births. Various subtypes have been described on a clinical and genetic level, with mutations in one of at least eight genes, termed CLN1-8, forming the molecular basis of the disease. Since mutations in distinct genes result in similar pathologies, suggesting a common biological pathway, it is important to not only elucidate the function of the proteins they encode but also to examine the possible consequences of protein dysfunction in cellular processes. Development of animal models of NCL disease and advancements in genomic and proteomic technologies provide valuable tools in the search for the underlying basis of disease. Application of DNA microarray analysis has revealed alterations in the expression of genes involved in a number of cellular processes including inflammation, neuronal function, oxidative stress, energy metabolism and proteolytic processing. Comparison of DNA microarray data from various NCL animal models has revealed not only alterations in a number of common pathological pathways characteristic of neurodegenerative disorders, but also some unique changes that may provide an insight into the function of the mutated proteins that underlie these diseases. Here, we review and discuss how such studies have furthered our current understanding of protein function and related pathological processes.
[Back
to top] Functional Analyses of the Human Genome Based on Large-Scale
Fulllength cDNA Resources
Yutaka Suzuki and Sumio Sugano
Newly developed full-length cDNA library technologies have enabled us to generate an unprecedented scale of cDNA resources with respect to both the forms of the physical cDNA clones and cDNA sequence information. Detailed annotations were attached to each of the cDNAs both computationally and manually and several integrated databases on the cDNA information were launched in a publicly accessible manner. Now, taking advantage of the physical cDNA clone resources, which are thought to cover most of the entire protein-coding genes in humans and mice non-redundantly, efficient high-throughput approaches, collectively called functional genomics approaches, are underway for characterizing biological functions of the encoded proteins from various points of view. In addition, it has become clear that the full-length cDNA resources are also useful for determining the precise genomic positions of the transcriptional start sites. The positional information of the TSSs allowed us to identify and analyze the adjacent promoter regions as putative transcriptional regulatory regions. Moreover, several very recently developed methods, combining full-length cDNA technologies with SAGE technologies, have enabled further high-throughput identification of the TSSs. Based on further expansion of the full-length cDNA data, attempts have been started towards a comprehensive understanding of what genomic elements, including genic regions and non-genic regions such as promoters, would bring about what biological consequences in what cellular contexts. Rapid compilation of genomic sequence data as well as multifaceted use of the full-length cDNA resources will shortly lay a firm foundation for a global understanding of the complex molecular biological systems which convert the information in the genomic DNA into a living cell.