X-chromosomes

Color Vision Defects. Anomalous color vision is present, eg, if one of the three sets of cones is iaoperative (dichromacy) or defective (anomalous trichromacy). This affects 2—3% of the population with males mote prone because these defects reside on the X-chromosome, with one present ia males but two ia females. Eye specialists have standard tests for detecting these and other defects. Summaries of this whole field are available (6,9,22). 

The two major types of genotypic sex determination, the mammalian and the avian types, can be referred to as XX/XY or ZZ/ZW, respectively. In animals expressing the XX/XY system, the male is the heterogametic sex (XY) while the female is homogametic (XX). The avian equivalent to the Y-chromosome of mammals is designated by the letter W, and the X-chromosome denoted by the... 

Figure 1. Immunofluorescent labeling of dystrophin in the Xp21 muscular dystrophies. In normal muscle, clear uniform labeling is present at the membrane of each muscle fiber. In Becker muscular dystrophy (BMD), there is inter- and intrafiber variation in labeling intensity. In Duchenne muscular dystrophy (DMD), most fibers are devoid of labeling (note, however, that in most biopsies occasional fibers exhibit weak labeling). In the biopsy from a manifesting carrier, some fibers show normal labeling and others are negative. In the former, the normal X-chromosome is active while in the latter the abnormal X-chromosome is active.

Hyperammonemia Type 2. A deficiency of ornithine transcarbamoylase (reaction 2, Figure 29-9) produces this X chromosome-linked deficiency. The mothers also exhibit hyperammonemia and an aversion to high-protein foods. Levels of glutamine are elevated in blood, cerebrospinal fluid, and urine, probably due to enhanced glutamine synthesis in response to elevated levels of tissue ammonia. 

Duchenne-type muscular dystrophy is due to mutations in the gene, located on the X chromosome, encoding the protein dystrophin. 

Inherited deficiencies of the clotting system that result in bleeding are found in humans. The most common is deficiency of factor VIII, causing hemophilia A, an X chromosome-hnked disease that has played a major role in the history of the royal families of Europe. Hemophilia B is due to a deficiency of factor IX its clinical Feamres are almost identical to those of hemophilia A, but the conditions can be separated on the basis of specific assays that distinguish between the two factors. 

Figure 52-7. Simplified scheme of the sequence of events involved in the causation of chronic granulomatous disease (MIM 306400). Mutations in any of the genes for the four polypeptides involved (two are components of cytochrome b55gand two are derived from the cytoplasm) can cause the disease. The polypeptide of 91 kDa is encoded by a gene in the X chromosome approximately 60% of cases of chronic granulomatous disease are X-linked, with the remainder being inherited in an autosomal recessive fashion.

The discovery that MAO has two isoenzymes with different distributions, substrate specificity and inhibitor sensitivity has helped to rehabilitate the MAOIs to some extent. These isoenzymes are the products of different genes on the X-chromosome and share about 70% sequence homology. Whereas noradrenaline and 5-HT are metabolised preferentially by MAOa, tyramine and dopamine can be metabolised by either isoenzyme. Selective inhibitors of MAOa (e-g- moclobemide Da Prada et al. 1989) should therefore be safe and effective antidepressants whereas the selective MAOb inhibitor, selegiline, should not have any appreciable antidepressant activity (Table 20.5). 

Legouis R., Cohen-Salmon M., Delcastillo I. and Petit C. (1994). Isolation and characterization of the gene responsible for the X-chromosome linked Kallmann syndrome. Biomed Pharm 48, 241-246. 

M19. Michelson, A. M Markham, A. F and Orkin, S. H Isolation and DNA sequence of a full-length cDNA clone for human X-chromosome-encoded phosphoglycerate kinase. Proc. Natl. Acad. Sci. U.S.A. 80,472-476 (1983). 

The reaction differs from excision of the X chromosome because the Entry Clone contains two attL sites and the destination vector contains two attR sites (Hartley et al., 2000). The att sites are mutated to ensure recombination only occurs between attLl and attRl and between attL2 and att.R2. The recombination reaction proceeds through a cointegrate molecule that is resolved to create a destination vector containing the gene of interest with the desired promoter and tag sequences (Fig. 4.6). 

Fitzgerald PH, Pickering AF, Mercer JM, Miethke PM 1975 Premature centromere division a mechanism of non-disjunction causing X chromosome aneuploidy in somatic cells of man. Ann Hum Genet 38 417-428... 

Carbamyl phosphate condenses with ornithine to yield citrulline in the ornithine transcarbamylase (OTC) reaction. OTC is encoded on band p21.1 of the X chromosome, where the gene contains 8 exons and spans 85 kb of DNA. The activity of this enzyme is directly related to dietary protein. There may be tunneling of ornithine transported from the cytosol to OTC, with the availability of intramitochondrial ornithine serving to regulate the reaction. 

Ornithine transcarbamylase deficiency. This is the most common of the urea cycle defects. Presentation is variable, ranging from a fulminant, fatal disorder of neonates to a schizophrenic-like illness in an otherwise healthy adult. Males characteristically fare more poorly than do females with this X-linked disorder because of random inactivation (lyonization) of the X chromosome. If inactivation affects primarily the X chromosome bearing the mutant OTC gene, then a more favorable outcome can be anticipated. Conversely, the unfavorably lyonized female has a more active disease. 

Red-green color blindness is explained by unequal intragenic recombination between a pair of X chromosomes 814... 

The concordance rate of mood disorders is 60-80% for monozygotic twins and 14-20% for dizygotic twins. Linkage studies suggest that certain loci on genes and the X chromosome may contribute to genetic susceptibility of bipolar disorder,... 

The pathway of delivery seems to be an important determinant in the geno-toxicity of nickel compounds in vitro. Regarding X-chromosome fragmentation in CHO cells [306, 444], nickel chloride was reported to be ineffective by contrast to crystalline NiS. Delivery and uptake by phagocytosis of NiCl2, artificially encapsulated in liposomes, induced fragmentation. 

An 8.5-meter-high model of the human X chromosome is constructed out of stainless steel and synthetic rubber. Solar energy powers the object, engendering a pulsating motion in two of the form s extremities. The overdimensional representation of the central component of our human identity focuses attention on questions relating to its technological manipulability. 

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