Dosage effects for superoxide dismutase-1 in nucleated cells aneuploid for chromosome 21.

Assays of the activity of chromosome 21 determined superoxide dismutase-1 (SOD-1) in lymphocytes and polymorphonuclear granulocytes have demonstrated 38% and 40% increases, respectively, in cells from individuals with trisomy 21. Similarly, SOD-1 activity in trisomic fibroblasts is increased by 81%, while cells monosomic for chromosome 21 have only 60% of normal activity. Taken together with the data on SOD-1 activities in trisomic erythrocytes and platelets, the present results firmly confirm the existence of a true dosage effect for this enzyme in cells aneuploid for chromosome 21. However, the results of assays of the activity of glutathione peroxidase in trisomic fibroblasts did not confirm the possibility previously reported of a chromosome 21 related dosage effect for this enzyme.     

B chromosome in a rice aneuploid variation

An awned rice plant was discovered among the progeny of the triploid Zhongxian 3037. Cytological investigation showed that this awned plant was a variation with extra chromosomes. Based on the properties of the extra chromosomes during both meiosis and mitosis – e.g., short stature, darkly staining, instability in chromosome number, and lack of synapsis with A chromosomes – they could be considered to be B chromosomes in rice. The B chromosome(s) in both asexual and sexual progenies exhibited a unique segregation that is different from that of telotrisomics and other aneuploids. Moreover molecular marker analysis detected no dosage effects between the B-chromosome plant and the normal diploid of Zhongxian 3037, indicating that the B chromosomes might not be directly derived from any A-chromosome fragments in rice. Received: 8 June 1999 / Accepted: 30 December 1999     

Gene dosage effect for glycinamide ribonucleotide synthetase in human fibroblasts trisomic for chromosome 21

The mean activity of glycinamide ribonucleotide synthetase of fibroblasts from fetuses with trisomy 21 is 1.64 — times that of normal cells. This gene dosage effect is confirmatory of the assignment of the gene for this enzyme to human chromosome 21.     

Triple chromosome pairing in an aneuploid bull spermatocyte

A triple synaptonemal complex was observed between three midsized chromosomes in an aneuploid bull spermatocyte. Fifteen other spermatocytes examined from the same animal displayed normal chromosome complements and pairing. This is the second case reported of triple synapsis in a mammal and the first case in an apparently normal individual.     

Phosphofructokinase activity in the preimplantation mouse embryo

Summary Phosphofructokinase activity remains relatively constant during the preimplantation period in the mouse, with a low point at day 4 (approximately 3.0×1^–11 moles of substrate converted per embryo per hour).     

Karyotypic determinants of chromosome instability in aneuploid budding yeast

Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated chromosome instability (CIN), i.e. the propensity of gaining and losing chromosomes at a high frequency. Here we have investigated ploidy- and chromosome-specific determinants underlying aneuploidy-induced CIN by observing karyotype dynamics in fully isogenic aneuploid yeast strains with ploidies between 1N and 2N obtained through a random meiotic process. The aneuploid strains exhibited various levels of whole-chromosome instability (i.e. chromosome gains and losses). CIN correlates with cellular ploidy in an unexpected way: cells with a chromosomal content close to the haploid state are significantly more stable than cells displaying an apparent ploidy between 1.5 and 2N. We propose that the capacity for accurate chromosome segregation by the mitotic system does not scale continuously with an increasing number of chromosomes, but may occur via discrete steps each time a full set of chromosomes is added to the genome. On top of such general ploidy-related effect, CIN is also associated with the presence of specific aneuploid chromosomes as well as dosage imbalance between specific chromosome pairs. Our findings potentially help reconcile the divide between gene-centric versus genome-centric theories in cancer evolution.     

Cell selection in vivo in normal/aneuploid chromosome abnormalities

Summary Cytogenetic follow-up examination has been made of the 9 mixoploid children found among 11148 newborn children. In 4 of the 9 children there was a significant increase in the frequency of the cell line with normal chromosome constitution and a significant decrease in the normal cell line was found in 1 child. In 4 there was no significant difference from the first to the last examination.The frequency of the cell line with normal chromosomes increased from 32–68% to between 93–97% in 3 cases and to 86% in 1. The possibility that children with mixoploid chromosome abnormalities at birth will reveal no cell line with chromosome abnormality in lymphocyte cultures as adults in spite of having clinical signs of the chromosome aberration found in one cell line at birth is discussed.     

The distribution of spontaneous chromosome aberrations in BHK21/C13 fibroblasts.

Previous investigations of spontaneous aberrations in mammalian cells have been carried out on large heterogeneous samples of individuals, each of whom had had a different exposure to exogenous clastogens. In the present analysis using Syrian Hamster cells, a large number of metaphases were analysed from one sample of control cells. In this way all cells were exposed to the same doses of any unknown clastogens. The overall distribution of spontaneous breaks was found to be nonrandom. Breaks involved in different types of aberration had a nonrandom distribution, which was specific for each type. (e.g. terminal deletion and rearrangement).     

Seasonal variation in the birth of children with aneuploid chromosome abnormalities

Summary The seasonal variation in frequency of birth of 297 patients with karyotypes 47,XXY, 47,XYY, 47,XXX and 45,X registered in the Danish Cytogenetic Central Register until January 1st, 1971, was significantly different from the variation expected. The frequency of conception was higher than expected in June, July and August and lower in September, October and December. The variation in frequency of birth of the 791 patients with trisomy 21 was not significantly different from the expected value.There was no coincidence between the peak frequency of conception of children with aneuploid sex chromosome abnormalities and the peak frequency of a number of infectious diseases.It is concluded that the cause of the seasonal variation in frequency of conception and birth of children with aneuploid sex chromosome abnormalities is unknown. A number of possible factors are mentioned.

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Zusammenfassung Bei den 297 Patienten mit Karyotypen 47,XXY, 47,XYY, 47,XXX und 45,X, die bis zum 1. Januar 1971 im Dänischen Cytogenetischen Centralergister registriert worden sind, unterschied sich die jahreszeitliche Variation in der Geburtenhäufigkeit signifikant von der erwarteten Variation. Die Konzeptionshäufigkeit war in den Monaten Juni, Juli und August erhöht und im September, Oktober und Dezember erniedrigt, wohingegen die Variation in der Geburtenhäufigkeit von 791 Patienten mit Karyotypen 47,XX order XY,+21 Abnormitäten nicht signifikant unterschiedlich von der erwarteten Variation war.Es fand sich kein Zusammentreffen zwischen dem Häufigkeitsgipfel der Konzeption von Kindern mit aneuploiden Geschlechtschromosomenabnormitäten und dem Gipfel einer Reihe von Infektionskrankheiten.Daraus wird geschlossen, daß die Ätiologie der jahreszeitlichen Variation der Konzeptions-häufigkeit und Geburten von Kindern mit aneuploiden Geschlechtschromosomenabnormitäten unbekannt ist. Eine Reihe möglicher Faktoren wird erwähnt.

     

Low level chromosome instability in embryonic cells of primary aneuploid mice

Karyotypic analyses of Down syndrome patients have identified a low level of chromosome mosaicism, suggesting that the primary aneuploid status of the cells promotes further chromosomal segregation errors. Sycp3-null female mice produce aneuploid oocytes, which after fusion with normal haploid sperm, result in offspring with systemic whole chromosome, aneuploid embryo cells. Using the Sycp3-null female as a model, we observe an increase in the number of embryonic cells at E7.0 that exhibit abnormal chromosomal bridges at the anaphas estage of mitosis. This result suggests that global changes in gene expression patterns resulting from primary aneuploidy can affect mitotic chromosome segregation, resulting in a low level of chromosomal instability. The increased level of chromosomal instability could in the absence of mitotic checkpoints, lead to chromosomal mosaicism within the adult organism, as seen in Down syndrome patients.     

Diabetes mellitus in patients with aneuploid chromosome aberrations and in their parents

Summary The frequency of chemical diabetes is increased in patients with aneuploid sex chromosome aberrations such as Klinefelter's syndrome and Turner's syndrome, and a high frequency of chemical diabetes has been found in parents of patients with Down's syndrome. Abnormal pattern in plasma insulin and growth hormone during a glucose load has been found in patients with Klinefelter's syndrome and Turner's syndrome.These findings might, if they are confirmed on large and well selected groups of patients with different chromosome abnormalities, shed some new light on the genetic background of diabetes mellitus, i.e. on the role of the sex chromosomes in the aetiology of diabetes mellitus or alternatively on the possibility that the frequency of non-disjunction in increased in patients with diabetes mellitus.     

Immunological aberrations in patients with aneuploid chromosome abnormalities and in their parents

Summary Studies of autoantibody reactions towards different organs in patients with aneuploid sex chromosome aberrations have been controversial, and no conclusions can be drawn at present. If the findings by certain authors of increased thyroid autoantibody titers in patients with Down's syndrome as well as in the mothers are confirmed by further studies, this might indicate that the increased thyroid autoantibody titers found in mothers of patients with Down's syndrome in some way might be aetiologically connected with the risk of non-disjunction resulting in trisomy 21.     

Evidence for a striking increase in acetylcholinesterase activity in cultured human fibroblasts which are trisomic for chromosome two

Acetylcholinesterase (AchE) is reported to have a narrowly restricted distribution among human tissues. Three strains of human fibroblasts which are trisomic for chromosome 2 had an average level of AchE activity over 28 times higher than the average level in 19 control strains of human fibroblasts. In contrast, the mean pseudocholinesterase activity of the trisomy-2 strains did not differ appreciably, or significantly, from the mean for the control strains. The 19 control strains included 10 strains trisomic for autosomes other than 2, and 9 euploid strains. Our estimate of the mean AchE activity in the control strains did not differ significantly from zero and might, in any case, have originated from a minute amount of activity contributed to the cells by an esterase in our culture medium. Despite the striking elevation of AchE activity in fibroblasts trisomic for chromosome 2, extracts of these cells had only about 1.5% of the specific AchE activity (per microgram DNA) present in extracts of human cerebral cortex. None of the 22 strains studied had detectable activity for two other enzymes which, like AchE, have a restricted distribution among human tissues: xanthine oxidase and choline acetyltransferase.