Chromosome human, structure

The recent explosion of information from the study of the human genome has impacted pharmacology in a big way. Genes are made up iong strings of DNA moiecuies (see below) that are highly coiled and compacted into structures called chromosomes. Humans have 23 pairs of chromosomes. 

Identification of chromosomes (human as well as mouse and hamster) Determination of ploidy Detection and characterization of aneuploidy Gene mapping localization of specific DNA sequences Gene mapping detection of heteromorphisms and determination of parental origin of heteromorphisms Detection of gene mutations Characterization of structural aberrations Identification of marker chromosomes Characterization of tumor cells Chromosome and karyotype evolution Spatial topography of chromosomes... 

Ikemura T. and Aota S. (1988). Alternative chromatic structure at CpG islands and quinacrine-brightness of human chromosomes. Global variation in G-tC content along vertebrate genome DNA. Possible correlation with chromosome band structures. J. Mol. Biol. 60 909-920. 

Telomeres are essential structures that cap the ends of linear chromosomes. Human telomeres are made of a simple DNA repeat, (TTAGGG)n [1,2]. These repeats serve as anchor for the recruitment of sequence-specific DNA-binding... 

Human male chromosomes, the structures in the cell that cany the genetic information encoded in their component DNA. 

FIGURE 12.31 A model for chromosome structure, human chromosome 4. The 2-um DNA helix is wound twice around histone octamers to form 10-um uucleosomes, each of which contains 160 bp (80 per turn). These uucleosomes are then wound in solenoid fashion with six uucleosomes per turn to form a 30-nm filament. In this model, the 30-nm filament forms long DNA loops, each containing about 60,000 bp, which are attached at their base to the nuclear matrix. Eighteen of these loops are then wound radially around the circumference of a single turn to form a miniband unit of a chromosome. Approximately 10 of these minibands occur in each chromatid of human chromosome 4 at mitosis. 

Genotoxicity studies are required to identify compounds that can induce genetic damage ranging from single point gene mutations to gross alterations of chromosomal structure. Such effects are taken as indicative of the potential to cause cancer or heritable defects in humans. A standard battery of three types of test is recommended ... 

There are 17 human type I IFN genes, all clustering on chromosome 9. They are intronless and encode secretory signal peptide sequences that are proteolytically cleaved prior to secretion from the cell. Type I IFNs are genetically and structurally closely related. They range in length from 161 to 208 amino acids and have apparent molecular weights of 15-24 kDa (Table 1) (Chen et al. 2004). The different subtypes of human IFN-a have approximately 50% amino acid sequence identity, whereas IFN-a shares approximately 22% amino acid identity with human IFN-p and 37% with human IFN-m (Chen et al. 2004). 

Lipkowitz MS et al Functional reconstitution, membrane targeting, genomic structure, and chromosomal localization of a human urate transporter. J Clin Invest 2001 107 1103. 

In 1990, work was started to characterize the human genome which had been shown to consist of about 3 billion base pairs. The final result was announced in the year 2000. All of the chromosomes have been characterized. The human genome has been shown to contain some 30,000 genes (which are sections of the chromosome which code for specific proteins). Each cell produces the t T)e of proteins needed for it to function. The function of mRNA is to transfer information from the DNA. so as is to fix the limits of the protein needed. The vast majority of the proteins found in living organisms are composed of only 20 different kinds of amino acids, repeated many times and strung together in a particular order. Each type of protein has its own unique sequence of amino acids. This sequence, known as its primary structure, actually... 

KULLING s E, ROSENBERG B, JACOBS E, METZLER M (1999) The phytoestrogens coumestrol and genistein induce structural and chromosomal aberrations in cultured human peripheral blood lympocytes. Arch Toxicol. Ti 50-54. 

In humans, the structural gene locus is on chromosome 19 (M17), and the gene spans over 40 kilobases (kb) including 18 exons and 17 introns (W2, X2). Neu-roleukin, a protein that acts as both a neurotrophic factor and a lymphokine, has been isolated from mouse salivary glands (G7), and subsequently the primary structure of neuroleukin was found to be identical to that of GPI by comparison of the cDNA sequences (C7, FI). The cDNA sequence encodes 558 amino acid residues. The enzyme consists of two identical subunits with a molecular weight of approximately 63,000 and neuroleukin is active as a monomer. 

The pall of fog that has shrouded the sister separation process for over a century is starting to lift and this long mysterious process has started to reveal its secrets. There is now convincing evidence that the sudden movement of chromosomes to the poles at the onset of anaphase is triggered by cleavage of specific sister chromatid cohesion proteins. Future research must address the structural basis of cohesion and how it is established only at replication forks. It must also address the generality of mechanisms that dismantle cohesion at the metaphase to anaphase transition and how mistakes in this process contribute to human disease. 

Genotoxic Effects. Evaluation of the genotoxicity of lead in humans has focused on evaluations of lymphocytes from occupationally or environmentally exposed persons (Table 2-10) and in vitro studies of structural chromosomal aberrations and sister chromatid exchange in cultures of lymphocytes taken from healthy individuals (Table 2-11). Results of studies with human lymphocyte cultures exposed in vitro to lead acetate were nearly equally divided between positive (Beek and Obe 1974 Niebuhr and Wulf 1984) and negative (Beek and Obe 1975 Deknudt and Deminatti 1978 Gasiorek and Bauchinger 1981 Schmid etal. 1972). 

Human lymphocyte cultures Structural chromosomal aberration NA + Beek and Obe 1974 Deknudtand Deminatti 1978... 

White, D. M., et al. (1992). Structure and chromosomal localization of the human gene for a brain form of prostaglandin D2 synthase. J. Biol. Chem. 267,... 

Chromosome A subnuclear structure comprising DNA and associated proteins. Apart from the sex cells, each human cell has 23 pairs of chromosomes comprising 22 autosomes and a pair of sex chromosomes (XX in females, XY in males). 

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