Occurrence Of Nondisjunction Research Articles

Mathematical modeling of human oocyte aneuploidy

Aneuploidy is the leading contributor to pregnancy loss, congenital anomalies, and in vitro fertilization (IVF) failure in humans. Although most aneuploid conceptions are thought to originate from meiotic division errors in the female germline, quantitative studies that link the observed phenotypes to underlying error mechanisms are lacking. In this study, we developed a mathematical modeling framework to quantify the contribution of different mechanisms of erroneous chromosome segregation to the production of aneuploid eggs. Our model considers the probabilities of all possible chromosome gain/loss outcomes that arise from meiotic errors, such as nondisjunction (NDJ) in meiosis I and meiosis II, and premature separation of sister chromatids (PSSC) and reverse segregation (RS) in meiosis I. To understand the contributions of different meiotic errors, we fit our model to aneuploidy data from 11,157 blastocyst-stage embryos. Our best-fitting model captures several known features of female meiosis, for instance, the maternal age effect on PSSC. More importantly, our model reveals previously undescribed patterns, including an increased frequency of meiosis II errors among eggs affected by errors in meiosis I. This observation suggests that the occurrence of NDJ in meiosis II is associated with the ploidy status of an egg. We further demonstrate that the model can be used to identify IVF patients who produce an extreme number of aneuploid embryos. The dynamic nature of our mathematical model makes it a powerful tool both for understanding the relative contributions of mechanisms of chromosome missegregation in human female meiosis and for predicting the outcomes of assisted reproduction.

Influence of DNA methylation on rye B-chromosome nondisjunction

Regulation of nondisjunction of the rye B chromosome was investigated using the cytidine analog 5-azacytidine, which affects DNA methylation. The B chromosome of rye normally undergoes nondisjunction at first pollen grain mitosis and is stable at all other mitotic nuclear divisions. Observations on mitosis in the control root cells showed normal chromosome behaviour, whereas the treated roots were characterized by a high frequency of anaphases with lagging chromosomes showing evidence of failure of chromatid separation. The occurrence of nondisjunction was confirmed by the presence of variable numbers of B chromosomes between cells within roots, whereas the A-chromosome number remained constant. These results suggest that the epigenetic process by which somatic cells maintain the inactivity of the gene(s) responsible for B chromosome nondisjunction, between fertilization and meiosis, is mediated through DNA methylation.Key words: B chromosome, DNA methylation, meiotic reprogramming, 5-azacytidine, rye.

Correlation of the Down Syndrome Protein with Down Syndrome

Abstract The sera of two hundred and fifty-nine individuals have been investigated for the presence of the Down syndrome protein (DSP) by a modified immunoelectrophoretic procedure. The results showed that 66.25 percent of the eighty couples with Down syndrome (DS) affected children were DSP positive which was well in accordance with the reported occurrence of nondisjunction at meiosis I from various research groups (53.8% to 90.3%). Furthermore, from the study of 56 pure meiotic nondisjunction trisomy 21 cases, 40 cases (71.4%) showed that the DSP was present in the sera of the parents who were responsible for the extra chromosome in the DS affected children. This evidence strongly supported the original hypothesis by Miles that the presence of the DSP was associated with non disjunction occurring during the first meiotic divsion.

Detection of the time of occurrence of nondisjunction induced by the r-X1 deficiency in Zea mays L.

The r-X1 deficiency in maize produces high frequencies of aneuploid progeny by inducing nondisjunction during embryo sac development. The purpose of this investigation was to determine the embryo sac division at which the nondisjunctive event takes place. Monosomic-6 individuals were generated by crossing r-X1 containing plants by those carrying the y-pastel-8549 allele of the Y locus on chromosome 6. A strict dosage relationship exists between the number of dominant alleles of the Y locus and the level of β-carotene in the endosperm. We found that the level of β-carotene in the endosperm of kernels containing monosomic-6 embryos was comparable with that found in endosperms with one Y allele. This indicated that they contained only one maternally contributed chromosome 6. Only nondisjunction at the second postmeiotic division could have produced such an endosperm; thus, the nondisjunctive event occurs at this division. Another endosperm type expected from nondisjunction at this same division, with three dominant Y alleles, was not found. The absence of this endosperm type suggests that the egg nucleus and the polar nucleus originating at the micropylar pole are sister nuclei that arose from the same cell at the third embryo sac mitotic division. Key words: aneuploidy, embryo sac, nondisjunction, r-X1 deficiency, Zea.

1, 9, and 16 C-band heteromorphisms in parents of Down's syndrome patients: Distribution and etiological significance

The C-band areas of chromosomes 1, 9, and 16 were studied in 50 Japanese individuals, parents of Down's syndrome patients. In order to measure these areas, a modular system for semiautomatic quantitative evaluation of images (VIP-11, Olympus) was used. Each area was distributed according to a system of classfication proposed by Patil and Lubs (1977). The distribution of the C-band areas for each chromosome appeared to be significantly different from the distribution of these areas in a normal population chosen at random. The role that large constitutive heterochromatin variants may have in the occurrence of nondisjunction is considered.

EFFECTS OF TEMPERATURE AND SOIL MOISTURE ON FREQUENCY OF ACCESSORY CHROMOSOMES IN RYE, SECALE CEREALE L.

In order to find the correlation between the environmental factors and frequency of accessory chromosomes in different populations of rye, clonal plants divided from a plant to get the uniformly genotypical constitution were grown under the different temperature or soil moisture conditions. The frequency of acc. chromosomes was lower in the progeny populations derived from the plants grown under the high temperature or dry soil conditions. Such a low frequency may be due to the highly meiotic elimination of acc. chromosomes, the less occurrence of nondisjunction at pollen mitosis and the decrease of seed fertility of the parental plants under such unfavourable conditions.

Origin of Attached-X Chromosomes in Drosophila melanogaster and the Occurrence of Non-Disjunction of X's in the Male

Two X-chromosomes of Drosophila melanogaster may become attached to each other by replacement of the two arms of a Y by X's. The first step, crossing-over between one arm of Y and X, is known to take place in $$\underline{XX}$$Y females and in males (XY) (Kaufmann, Neuhaus), and may take place in XXY females, forming an $$\underline{XY}^{S or L}$$ -chromosome. The second step, crossing-over between an arm of Y attached to X and another X, has been observed in males (Stern, Philip, Neuhaus). An $$\underline{XY}^{S or L}$$-chromosome may be transmitted in the same way as an X, back and forth from males to females or directly through females in stocks with separate X's, or directly through males in attached-X stocks. The second step is known to take place in males in the 4-strand stage of spermatogenesis, two like X's becoming attached to each other. The chances of recovering the attached X's will depend upon the frequency of egg nuclei with which the $$\underline{XX}$$ sperm may produce a viable zygote. If ...

The Effect of Carbon Dioxide On the Occurrence of Non-Disjunction In Drosophila

ABSTRACT The fact that X-rays and radium produce permanent changes in the mechanism of heredity (originally observed by Mavor (1) for non-disjunction and by Muller(2) for mutations) has been widely confirmed by many workers(3). Apart from these radiations no other agent has been found to effect heredity similarly, except for the claim made by Harrison and Garrett (4) that feeding the larval of several species of Lepidoptera on metallic salts results in melanotic mutations.