Human trisomies

Heavy irradiation has been shown to induce nondisjunction in some experimental animals, but there is no good evidence for a detectable effect on human trisomy (choice E). 

CITE, Chromosomal aberrations, human trisomy 21-lymphoeytes in vitro + NT 80 Sehulz et al. (1982)... 

Fiedler JL, Epstein CJ, Rapoport SI, Caviedes R, Caviedes P (1994) Regional alteration of cholinergic function in central neurons of trisomy 16 mouse fetuses, an animal model of human trisomy 21 (Down syndrome). Brain Res 658 27-32 Flores CM, Rogers SW, Pabreza LA, Wolfe BB, Kellar KJ (1992) A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol Pharmacol 41 31-37 Freedman R, Hall M, Adler LE, Leonard S (1995) Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 38 22-33... 

Aneuploidy in somatic cells is involved in the formation of human tumors. Up to ten percent of tumors are monosomic and trisomic for a specific chromosome as the single observable cytogenetic change. Most common among such tumors are trisomy 8, 9, 12, and 21 and monosomy for chromosomes 7, 22, and Y. 

Pinkel, D., Landegent, J., Collins, C., Fuscoe, J., Segraves, R., Lucas, J., and Gray, J. W. (1988) Fluorescence in situ hybridization with human chromosome specific libraries detection of trisomy 21 and translocations of chromosome 4. Proc. Natl. Acad. Sci. USA 85, 9138-9142. 

The gene for human (Cu,Zn)-SOD is located on chromosome 21 (two alleles have actually been described) In trisomy 21 (Down syndrome) an increase of about 50 % in SOD activity was observed in erythrocytes and in blood platelets... 

This is a controversial area with regard to humans where there is currently little hard data. Theoretically it is possible for a foreign compound to cause mutations in male germ cells, which result in malformations or the development of abnormal offspring. This is similar to the situation in which inherited mutations or chromosomal aberrations lead to the birth of abnormal offspring, such as occur in Down syndrome, for example, where an extra chromosome occurs (Trisomy 21). 

The unequal partition of chromosomes or nondisjunction is a serious effect if the affected daughter cells survive. Down syndrome or Trisomy 21 is the result of chromosome nondisjunction in humans, those affected having 47 chromosomes instead of 46. This unequal partitioning of chromosomes can occur at mitosis in germ cells or during meiosis in the production of sperm or ova. 

There has been much discussion about the potential utility of flow cytometry of chromosomes for clinical diagnosis. As regards its sensitivity, this technique appears to stand somewhere between the technique of flow analysis of whole cells for DNA content and that of microscope analysis of banded chromosomes. It may be a useful intellectual exercise for readers to ask themselves which technique or techniques would be most appropriate for detecting the following types of chromosome abnormalities (1) tetraploidy, where the normal chromosome content of cells is exactly doubled because of failure of cytokinesis after mitosis (2) an inversion in an arm of one particular chromosome and (3) trisomy (the existence of cells with three instead of two) of one of the small chromosomes. In addition to these limitations, the use of flow cytometry to look for abnormal chromosomes has been confounded by the fact that several human chromosomes are highly polymorphic, and flow karyotypes, therefore, vary considerably among normal individuals. 

Aberrations in newborn persons consist of both numerical changes (due primarily to nondisjunction) and structural deletions and rearrangements (due to chromosomal breakage). There has been no unambiguous demonstration in human beings that mutagens can cause nondisjunction. An additional problem, insofar as monitoring is concerned, is that the trisomies and monosomies seen in newborn persons also cause increased risk of abortion, Therefore, only an unknown fraction survive to birth. 

Manolova Y, Manolov G, Parvanova L, Petkova-Bocharova T, Castegnaro M, Chernozemsky IN. Induction of characteristic chromosomal aberrations, particularly X-trisomy, in cultured human lymphocytes treated by ochratoxin A, a mycotoxin implicated in Balkan endemic nephropathy. Mutat. Res. 1990 231 (2) 143-9. 

The answer is d. (Murray, pp 812—828. Scriver, pp 3-45. Sack, pp 57-84. Wilson, pp 123—148.) The case described represents one of the more common chromosomal causes of reproductive failure. Turner mosaicism. Turner s syndrome represents a pattern of anomalies including short stature, heart defects, and infertility. Turner s syndrome is often associated with a 45,X karyotype (monosomy X) in females, but mosaicism (i.e., two or more cell lines with different karyotypes in the same individual) is common. However, chimerism (i.e., two cell lines in an individual arising from different zygotes, such as fraternal twins who do not separate) is extremely rare. Trisomy refers to three copies of one chromosome, euploidy to a normal chromosome number, and monoploidy to one set of chromosomes (haploidy in humans). 

The human CuZnSOD (SODl) gene has been localized to chromosome 21 (region 21q22) [ 10]. Patients with Down syndrome (trisomy 21) show a 50% increase in SODl activity due to elevation of the level of CuZnSOD protein but the role of SODl in the pathology associated with this disease remains questionable [70]. 

Spencer, K., Souter, V., Tul, N., Snijders, R., and Nicolaides, K.H., 1999, A screening program for trisomy 21 at 10-14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet. Gynecol. 13 231-237. 

Malassine A, Frendo J-L, Blaise S, Handschuh P, Tsatsaris V, Heidmann T. Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta. Retrovirology. 2008 5 6. doi 10.1186/1742 690-5-6. 

Some very interesting information on localization of hemoglobin loci in human somatic chromosomes has recently been obtained in two studies of the hemoglobin pattern in certain chromosomal anomalies in man (trisomy) (Huehns et al., 1964 Powars et al., 1964). 

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