Chromosome materials

CHROMATIN IS THE CHROMOSOMAL MATERIAL EXTRACTED FROM NUCLEI OF CELLS OF EUKARYOTIC ORGANISMS... 

Chinese hamster ovary cells in which there has been an extensive rearrangement of chromosome material and the chromosome number may not be constant from cell to cell, are frequently used. Polyploidy, endoreduplication and high spontaneous chromosome aberration frequencies can sometimes be found in these established cell lines, but careful cell culture techniques should minimize such effects. Cells should be treated in exponential growth when cells are in all stages of the cell cycle. 

Large molecular weight compounds are unlikely to react with DNA or other chromosomal material and therefore a genotoxicity evaluation may be of little value. However, genotoxicity studies may provide useful information about the safety of products containing organic linkers. 

As its name implies, a translocation is reciprocal when genetic material is exchanged between two chromosomes. For example, parts of the short arms of chromosomes 2 and 8 could be exchanged (Fig II-3-4). The individual who carries the reciprocal translocation (46,XX,t[2p 8p]) will not usually be affected clinically because he or she has the normal complement of genetic material. However, his or her offspring can inherit unbalanced chromosome material (e.g., a copy of the normal 8 and a copy of chromosome 2 that contains the translocated piece of 8, resulting in a partial trisomy of the 8th chromosome and partial monosomy of the second chromosome [Fig II-3-4]). 

Related to this are recent attempts to produce unisex children, i.e., embryos that are from male-male and those from female-female as sources of the chromosomal material. In both cases the attempt failed. The two-mother-derived chromosomes could not make a placenta and the two-father-derived chromosomes could not make a discernible head so that chromosomes from both sexes are required to give a healthy successful embryo. 

The eukaryotic cell cycle (see Fig. 12-41) produces remarkable changes in the structure of chromosomes (Fig. 24-25). In nondividing eukaryotic cells (in GO) and those in interphase (Gl, S, and G2), the chromosomal material, chromatin, is amorphous and appears to be randomly dispersed in certain parts of the nucleus. In the S phase of interphase the DNA in this amorphous state replicates, each chromosome producing two sister chromosomes (called sister chromatids) that remain associated with each other after replication is complete. The chromosomes become much more condensed during prophase of mitosis, taking the form of a species-specific number of well-defined pairs of sister chromatids (Fig. 24-5). 

Translocation can also cause gains or losses of chromosomal material and generate new gene products. Simple translocations are characterized by distinctive rearrangements of chromosomal segments in specific neoplastic diseases, including leukemias and lymphomas. These specific translocations are necessary for the development and progression of the neoplasms in which they occur. 

The routine studies for potential mutagenic activity normally performed on chemical drugs do not apply to biopharmaceuticals, as the administration of large amounts of peptides or proteins makes the results difficult to analyze. There is no evidence that these substances interact with DNA or other chromosomal material. In some instances the tests verify the effect of new excipients added to the formulated product. 

Deoxyribonucleic acid (DNA) A linear polymer, made up of deoxyribo-nucleotide units, that is the carrier of genetic information, present in chromosomes and chromosomal material of cell orgenelles such as mitrochondria and chloroplasts, and also in some viruses. Every characteristic inherited trait has its origin in the code of each individual s DNA. 

Similar to protein-based biopharmaceuticals, the standard battery of genotox-icity studies is not considered to be relevant for cell-based therapies unless there is a specific cause for concern regarding the nature of any expressed products that would indicate a potential interaction directly with DNA or other chromosomal material [50,52], The conduct of genotoxicity studies for assessing the genotoxic potential of process related contaminants is also not considered to be appropriate [50],... 

The answer is e. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 57-84. Wilson, pp 123-148.) Children with chromosome abnormalities often exhibit poor growth (failure to thrive) and developmental delay with an abnormal facial appearance. This baby is too young for developmental assessment, but the catlike cry should provoke suspicion of cri-du-chat syndrome. Cri-du-chat syndrome is caused by deletion of the terminal short arm of chromosome 5 [46,XX,del(5p), also abbreviated as 5p—] as depicted in panel e. When a partial deletion or duplication like this one is found, the parents must be karyotyped to determine if one carries a balanced reciprocal translocation. The other karyotypes show (a) deletion of the short arm of chromosome 4 [46,XY,del(4p) or 4p—] (b) XYY syndrome (47,XYY) (c) deletion of the long arm of chromosome 13 [46,XX,del(13q) or 13q-] (d) Klinefelter s syndrome (47,XXY). Most disorders involving excess or deficient chromosome material produce a characteristic and recognizable phenotype (e.g., Down s, cri-du-chat, or Turner s syndrome). The deletion of 4p- (panel A) produces a pattern of abnormalities (syndrome) known as Wolf-Hirschhorn syndrome deletion of 13q- produces a 13q— syndrome (no eponym). The mechanism(s) by which imbalanced chromosome material produces a distinctive phenotype is completely unknown. 

No convincing case of autosomal monosomy has been reported in man, but several cases of partial deletions (effectively partial monosomy) involving several autosomes are known (see review by Pfeiffer, 1967). Furthermore, the chromosome complement of some translocation heterozygotes, such as D/D, D/G, or G/G translocations, may lose a part of the chromosomal material if the small centric chromosome element is lost. Somatic cells isolated from these individulls may conceivably contain genes in the hemizygous state. 

Fig. 18 (cont.). B, One of a complete series of twelve serial sections through the manipulated chromosome, this one at the level of the first half-bivalent s kinetochores. Two chromosomal microtubules are indicated by arrows they lie in the direction of bivalent motion, as does a third microtubule seen in an adjacent section. X80,000. C, A section at the level of the second half-bivalent s kinetochores, which had evinced no motion up to the time of fixation. Neither this nor the adjacent sections disclose any microtubules here, but kinetochore structure (the less electron opaque chromosome material indicated by the arrows) is Identical with that of unmanipulated bivalents. X80,000. (From unpublished studies of Brinkley and Nicklas.)... 

Hybrids of diploid and tetraploid Citrus species exhibited essential oil composition that varied widely from those of the parental stock. In many cases, the tetraploid and diploid parents contributed almost equally in terms of essential oil composition, despite the fact that two-thirds of the chromosomal material was from the tetraploid parent. The trends observed in leaf oil composition often did not coincide with those of the rind oil (Scora et al., 1970). 

The nucleic acids have been the subject of continuous investigation almost from the time they were first isolated as nuclein by Miescher from ceU nuclei, in the nineteenth century [17]. By 1900 Wilson had confirmed that nuclein was identical with chromatin , the classical chromosomal material. 

Chromatin the stainable material of the interphase nucleus, consisting of DNA, RNA and several specialized proteins, which is dispersed randomly in the nucleus. The chromosomal DNA is intact in this phase it is merely uncoiled or relaxed . Immediately prior to cell division, C. condenses into dense bodies (chromosomes), which can be intensely stained. Heterochromatin is tightly coiled and densely packed chromosomal material which is not being transcribed. Euchromatin has a looser structure and is the site of transcription. See Nucleosomes. See Chromosome. 

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