Meiotic Errors Research Articles

Advanced grandmaternal age on the mother's side--a risk of giving rise to trisomy 21.

The age distribution of maternal grandmothers of children with Down syndrome was compared with paternal grandparents of the same group and with grandparents of healthy children (controls). The significant advanced maternal grandmaternal age was found in cases of Down syndrome caused by first meiotic error in the maternal oogenesis. The advanced maternal grandmaternal age was found independent of maternal age. No differences were found between the ages of grandfathers of Down syndrome and of controls.

Excess paternal meiotic errors in Turner syndrome: natural result of ascertainment bias.

Excess paternal meiotic errors in Turner syndrome: natural result of ascertainment bias.

Trisomy 21: origin of non-disjunction.

The Q-band heteromorphisms of chromosome 21 were used in a sample of 48 families with a Down's syndrome child to evaluate the origin of non-disjunction. The parental origin and the meiotic error were determined in 27 families, and in eight families only partial information was obtained. Paternal and maternal origin of non-disjunction was in a 1:3 ratio. Failures were five times more frequent in first than in second meiotic division in both sexes. The mean parental age and environmental factors in relation to the origin of the anomaly are discussed. Our results are compared with those obtained previously in similar studies by other authors.

Parental origin of the extra chromosome in Down's Syndrome.

In 11 studies of patients with Down's syndrome and their parents non-disjunction was maternal in 306 cases and paternal in 77 cases. In 258 families, parental origin could not be conclusively determined. The percentage of paternal failures varied between 4.3 and 35.3% in different studies. When the type of non-disjunction was compared to the type of meiotic error, more males were born when the error was maternal (sex ratio 0.55) and more females when the error was paternal (sex ratio 0.43). An overall sex ratio of 0.52 was found. De novo translocation trisomy of type (21;21) originated paternally in one third of the cases. In (14;21) de novo translocation trisomy only one of eight cases was of paternal origin.

13S+. Giant satellites or de novo rearrangement?

A seven-year-old Japanese girl with mental retardation, epileptic seizures controllable by anticonvulsants, short stature, and multiple minor malformations was found to have apparent giant satellites on chromosome No.13. The karyotypes of her parents and elder brother were normal. Banding studies revealed that the apparent giant satellites consist of four G-bands, and are thus a de novo rearrangement product. The origin of the aberrant No. 13 was traced to a paternal meiotic error, using Q-banding and silver staining heteromorphisms as markers. Thus, the patient represents an unbalanced, de novo chromosomal rearrangement masquerading as giant satellites, with the origin of the extra chromosomal material unknown, a hitherto undescribed situation.

Etiology of mongolism

Beside the rare cares of translocation mongolism, Down syndrome is caused by meiotic malsegregation of chromosomes, No. 21. The meiotic error can take place in both sexes and was found twice as frequently in the female as in the male. The same 2:1 ratio was found concerning nondisjunction in the first and in the second meiotic division. The rate of meiotic errors, which occur at random, is largely dependent on age; this tendency is more pronounced in oogenesis than in spermatogenesis. The results of prenatal chromosomal diagnosis indicate that the recurrence risk of trisomy 21 is not above the age-dependent average.

Experiments on chiasmata and nondisjunction in mice.

Meiosis in the female mammal has both an intrinsic interest and a practical one. Intrinsically, it is interesting because of the complexity of its control and because the whole of its prophase, including recombination of linked genes by crossing over, occurs in utero and is followed by a long dormant stage before final maturation of the ova, in readiness for fertilization. Its practical interest lies in the frequency with which errors at meiotic divisions are the source of numerical chromosome aberrations in man and other mammals. Though meiotic errors are documented also in the male, probably more commonly errors occur at first meiotic division in the female by chromosomal nondisjunction and are incremental with her age. There are two alternative explanatory sets of hypotheses for the maternal age relationship; the first, of postnatal aging (for example, the terminalization hypothesis), and the second, which is one of prenatal aging, and is in essence a production line hypothesis. Whichever of these two hypotheses proves in the end to be correct, the important mechanism for the origin of numerical chromosome anomalies through nondisjunction at first meiotic division is failure of formation, or of persistence, of chiasmata: the mechanical properties of chiasmata are essential for normal disjunction. These general points, including older ideas concerning the nature of chiasmata, will be discussed briefly.Because of the largely cryptic nature of the meiotic prophase in female mammals, a technique had to be developed for its experimental study, which would allow a more direct approach to the developing oogonia and oocytes than is possible in vivo during fetal life. More direct control was achieved by tackling oogenesis and meiosis in vitro during embryonic gonadogenesis, well before the final maturation of the ova in vivo. The technique consists in removing the fetal ovaries during early development (often at day 14, taking as day 1 the day of plug detection), and allowing these to mature in vitro, in an organ culture system, for 8 days at 37° C. Subsequently the fetal ovaries, which have by now grown considerably in size, are transplanted under the renal capsule of a previously spayed young adult female. After 19 days, to allow for maturation of the ovaries in vivo, the gonads are removed, the maturing oocytes are harvested and chromosome preparations are made for analysis at 1st or at 2nd meiotic metaphase, at will. The technique we have developed for the experimental study of mammalian female meiosis is versatile in many ways, and one of its applications is exemplified in Polani et al. (1979)KeywordsMeiotic DivisionMeiotic ProphaseRenal CapsuleOrgan Culture SystemFinal MaturationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Non-disjunction in trisomy 21: study of chromosomal heteromorphisms in 110 families.

QM variants on chromosome 21 and silver staining of NOR regions were applied in the study of non-disjunction in 110 families from different parts of Denmark. In 76% of the families the study was informative. Paternal failures were observed in 11% on Funen as compared 23.5% on Zealand. In one family, crossing-over on the short arms of chromosome 21 in the mother and mitotic non-disjunction of chromosome 21 was observed. Maternal first meiotic error predominates in both high maternal and low maternal age. Also in paternal non-disjunction failures of first meiotic division predominate. Two maternally and one paternally originated cases of de novo translocations were observed.

Parental origin of de novo chromosome rearrangements.

Nineteen patients with de novo chromosome rearrangements and their parents were studied for parental origin using fluorescent heteromorphisms as heritable markers. Conclusions were possible in all 19. Eighteen of these rearrangements involved at least one acrocentric chromosome, and one involved a chromosome number three. A strong bias toward paternal meiotic errors was evident with those rearrangements which were not Robertsonian in type or which did not involve segregation errors. Of nine such cases eight were paternal in origin. Of the remaining ten rearrangements nine were Robertsonian translocations; four of the nine were paternal in origin. The supernumerary bisatellited 15, which was the result of a non-disjunctive event, was maternal in origin.

A new genetic concept: uniparental disomy and its potential effect, isodisomy.

AbstractIn recent years, cytogenetic studies of spontaneous abortion products have disclosed a relatively high frequency of aneuploid embryos. These karyotypic anomalies chiefly stem from meiotic errors affecting the distribution of the chromosomes in one of the two gametes. This information not only implies the remarkable frequency of gonocyte aneuploidy but also reveals the prevalence of certain types of errors. It follows that gametal haploidy is often altered by the loss (nullisomy) or the addition (disomy) of certain members, in particular the X, the Y, and chromosomes 15, 16, 21, and 22.Therefore, it is to be expected that, in some exceptional zygotes, euploidy could result from the random union of a disomic gamete with a gamete nullisomic for the homologue. To this hypothetical phenomenon ‐ which is, however, statistically likely and foreseeable ‐ we have ascribed the name of uniparental disomy, owing to the fact that both members of such a pair arise from only one parent. Furthermore, such a mechanism implies the probability of introducing into the genome pairs of chromosomes with whole sequences of identical alleles, a consequence which we describe by the neologism of isodisomy. Such homozygosity for a series of colinear alleles implies, from the genetic stand‐point, risks and advantages akin to those of parental consanguinity.An analogous mechanism could also modulate and modify the consequences of trisomies in which entire segments of two of the three implicated chromosomes, including the supernumerary one, could as well be isoallelic (isodisomic trisomy or di‐isotrisomy). This article briefly states some other predictions stemming from the concept of uniparental disomy, whose confirmation should serve as a test of the proposed hypothesis.

Chromosomal imbalance in ovulated oocytes from Syrian hamsters (Mesocricetus auratus) and Chinese hamsters (Cricetulus griseus).

Chromosomes were studied in ovulated oocytes from Syrian hamsters (Mesocricetus auratus) and Chinese hamster (Cricetulus griseus) to assess the degree of chromosomal imbalance after first meiotic division of oogenesis. Only one hyperploid oocyte among 307 studied was detected in the former, and none in oocytes from the latter species. Structural chromosome alterations, single chromatids due to presegregation, and diploid chromosome sets resulting from meiotic blockage were not observed. The hormones which were used to stimulate ovulation apparently did not enhance first meiotic cleavage errors in these hamster oocytes. The low figures of chromosomal anomalies in hamster oocytes are compared to those from a large sample of mouse oocytes obtained from three different strains and prepared under identical conditions. The relevance of these findings to the obviously higher impact of chromosomal aneuploidy in man is discussed.

Partial monosomy of the long arm of chromosome 16: A distinct clinical entity?

A 7-month-old male child with a de novo, seemingly balanced reciprocal 5p/16q translocation and karyotype 46,XY,t(5;16) (p14;q21), resulting from a maternal meiotic error, is described. The clinical findings in this patient are strikingly similar to those in the only patient with partial deletion 16q hitherto described, [del(16)(q21)], indicating that during the 5p/16q rearrangement, 16q material was lost and suggesting that partial or total deletion of the long arm of chromosome 16 distal to band q21 is accompanied by a distinct clinical phenotype.

On the origin of the supernumerary chromosome in autosomal trisomies--with special reference to Down's syndrome. A bias in tracing nondisjunction by chromosomal and biochemical polymorphisms.

The differential staining methods for chromosomes have led to the demonstration of more chromosomal polymorphisms. Not rarely, these polymorphisms allow in autosomal trisomies the detection of parental origin of the supernumerary chromosome. In addition, the malsegregation may be ascribed to 1st or 2nd meiotic division in informative families. This approach of analyzing possible causes of trisomies is subject to a considerable bias. Trisomic phenotypes are twice as frequent for 2nd meiotic errors than for 1st meiotic errors. Also, rare chromosome variants seldom occur in matings where malsegregation in 1st meiotic division can be detected. In the present paper this bias is analyzed mathematically on the family as well as on the population level. From this mathematical analysis and from the data in the literature we conclude that Down's syndrome as a whole is caused about 5-10 times more often by a malsegregation in 1st meiotic than by an error in 2nd meiotic division. Mainly from experimental studies in rodents, causes for errors in 1st and 2nd meiotic division are becoming apparent. They are summarized in the context of the results of the present paper.

Chiasmata, meiotic univalents, and age in relation to aneuploid imbalance in mice.

Chiamata were counted and paired and unpaired configurations at first meiotic division and chromosome errors at second meiotic division were assessed at different ages in males and females of two strains of laboratory mice. In the females a decrease of chiasma frequency and an increase of univalents at first meiotic metaphase (MI) were confirmed. In the males, diakineses had higher chiasma frequencies (in the range of the female MIs) and fewer univalents than the MIs had. In these male cells there was no decrease of chiasmata or increase of autosomal univalents with age, and there were some interstrain differences. In the older females there was no parallelism between the frequencies of univalents at MI and the chromosome errors that could be identified at second meiotic division; these were fewer than might be expected on the assumption that all the univalents were true univalents. The relevance of this finding to the question of the nature of most of the univalents observed at first meiotic division in aged female mice is discussed.

Chromosome abnormalities in chicken (Gallus domesticus) embryos: types, frequencies and phenotypic effects.

Cytological screening of 4182 chick embryos from 10 strains and 5 strain crosses was performed to determine the types and frequencies of chromosome abnormalities. Gross phenotypic effects, such as growth retardation and malformation, were noted. Clues to the etiology of such chromosome aberrations were also sought. The following euploid series was observed: Haploid mosaics (A-Z/2A-ZZ, A-Z/2A-ZZ/3A-ZZZ, A-Z/A-W/2A-ZW/2A-ZZ, A-Z/A-W/2A-ZW/ 3A-Z?), diploid (2A-ZZ and 2A-ZW), triploid (3A-ZWW, 3A-ZZW, 3A-ZZZ, 3A-ZZZW) and tetraploid (4A-ZZWW and 4A-ZZZZ). Aneuploidy was observed as follows: Trisomy for chromosome numbers 1, 2, 3, 4 and double trisomy 2/5. Trisomy-4 with deletion of 50% of the long arm of one member of the trisomic triplet was observed. A 3A-ZWW embryo was found with two cell populations: one, disomic for chromosome 2 and 6; the other, tetrasomic for 2 and 6. Of the 4182 embryos sampled 1.4% were haploids, 97.5% diploids, 0.8% triploids, 0.1% tetraploids and 0.2% trisomics. On the average 10.8% of the early dead embryos were euploid (excluding diploid) or aneuploid. However, the range for euploidy and aneuploidy among strains was 2.3–23.7% of early deads. Haploid embryos were consistently underdeveloped at 4 days of incubation (D.I.), and died by 5–7 D.I. About 90% of (36) triploid embryos died at or before 4 D.I. The remaining 10% (normal embryos) died prior to hatching. Trisomic embryos were dead or underdeveloped at 4 D.I. Tetraploidy appeared to be lethal at a very early stage. The various strains examined had different overall rates of chromosome aberrations (0.4–8.9%), and also showed different varieties of such aberrations. The modes and possible causes of meiotic, mitotic and fertilization errors are considered. Genetic control of chromosome abnormalities, particularly haploidy, is postulated.

Meiotic errors in rye related to chiasma formation

Bridges and fragments at meiotic anaphase stages resulting from the spontaneous breakage and reunion of chromatids are common in genotypes of rye which are genetically unbalanced as a result of inbreeding or hybridisation. Similar configurations have been described in a variety of other plant and animal species, and ascribed to the same cause. Attention is drawn to the many similarities of the postulated breakage-reunion event to the exchange process involved in meiotic crossing-over, and the question is asked whether this anomalous behaviour could result from errors in crossing-over. Previous work employing different species having characteristically different and localised patterns of chiasma distribution has suggested the presence of a correlation between the distribution of chiasmata and the distribution of breakage-reunion events within bivalents. In the present investigation this approach has been followed, and extended, by comparing the distributions of breakage-reunion events in rye genotypes which have very different patterns of chiasma distribution. The results obtained indicate a marked similarity in the distribution patterns of these two events, suggesting that they are causally related and that they may therefore represent different manifestations of the same basic process.

Klinefelter's syndrome, Down's syndrome (Mongolism), and twinning in the same sibship: Chromosomal studies in 2 families

Two sibships are reported upon in which Klinefelter's syndrome, Mongolism, and twinning were present. Each family was initially identified by the presence of the individual with Klinefelter's syndrome. The frequency with which multiple chromosome aberrations within families has been reported suggests a common factor producing repeated meiotic errors.