Non-disjunction of chromosome 18 (original) (raw)
Related papers
Non-disjunction of chromosome 13
Human Molecular Genetics, 2007
We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89 % the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter finding is unique among human autosomal trisomies, where maternal MI (trisomies 15, 16, 21, 22) or MII (trisomy 18) errors dominate. Of the 9 paternally derived cases 5 were of MII origin but none arose from MI errors. There was some evidence for elevated maternal age in cases with maternal meiotic origin for liveborn infants. Maternal and paternal ages were elevated in cases with paternal meiotic origin. This is in contrast to results from a similar study of nondisjunction of trisomy 21 where paternal but not maternal age was elevated. We find clear evidence for reduced recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms that determine non-disjunction of human chromosomes, consistent with the diversity of findings for other trisomies.
Cytogenetic and molecular studies of trisomy 13
Journal of Medical Genetics, 1987
Chromosome heteromorphisms, restriction fragment length polymorphisms, or both were used to study the parental origin of 33 cases of simple trisomy 13 and eight cases of translocation trisomy 13. The most common origin for the simple trisomies was non-disjunction at maternal meiosis I, while for the translocations an equal number of paternally and maternally derived cases was observed. In seven of the simple trisomies, information was obtained from both the cytogenetic and molecular markers, making it possible to study recombination between the two non-disjoined chromosomes. Five of the seven cases involved errors at meiosis I, with crossing over being detected in two of three cases of maternal origin and in one of two cases of paternal origin. This indicates that absence of recombination because of pairing failure is unlikely to be of major importance in the genesis of trisomy 13.
Recombination and maternal age-dependent nondisjunction: molecular studies of trisomy 16
American journal of human genetics, 1995
Trisomy 16 is the most common human trisomy, occurring in > or = 1% of all clinically recognized pregnancies. It is thought to be completely dependent on maternal age and thus provides a useful model for studying the association of increasing maternal age and nondisjunction. We have been conducting a study to determine the parent and meiotic stage of origin of trisomy 16 and the possible association of nondisjunction and aberrant recombination. In the present report, we summarize our observations on 62 spontaneous abortions with trisomy 16. All trisomies were maternally derived, and in virtually all the error occurred at meiosis I. In studies of genetic recombination, we observed a highly significant reduction in recombination in the trisomy-generating meioses by comparison with normal female meioses. However, most cases of trisomy 16 had at least one detectable crossover between the nondisjoined chromosomes, indicating that it is reduced--and not absent--recombination that is th...
Human Molecular Genetics, 1998
Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t-test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome-specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by ma-ternal age in a different way and varying in importance for each chromosome.
Molecular studies of non-disjunction in trisomy 16
Journal of Medical Genetics, 1991
The origin of the additional chromosome in 26 trisomy 16 spontaneous abortions was studied using DNA probes for chromosome 16, including a probe for centromeric a satellite sequences. We were able to determine the parent and meiotic stage of origin of trisomy in 22 cases, with all being attributable to maternal meiosis I non-disjunction. Furthermore, in each of the remaining four cases the results were compatible with this origin. Thus, it is likely that
Nondisjunction in trisomy 21: Origin and mechanisms
Cytogenetic and Genome Research, 2000
Chromosomal aneuploidy is a fundamental characteristic of the human species. In this review we summarize the knowledge about the origin and mechanisms of nondisjunction in human trisomy 21 that has accumulated during the last decade by using DNA polymorphism analysis. The first molecular correlate of nondisjunction in humans is altered recombination, meiosis I errors being associated with reduced recombination and maternal meiosis II errors with increased recombination between the nondisjoined chromosomes. Thus, virtually all maternal meiotic errors of chromosome 21 seem to be initiated in meiosis I. Advanced maternal age remains the only well documented risk factor for maternal meiotic nondisjunction, but there is, however, still a surprising lack of understanding of the basic mechanisms behind the maternal age effect.
Altered patterns of multiple recombinant events are associated with nondisjunction of chromosome 21
Human Genetics, 2011
We have previously examined characteristics of maternal chromosomes 21 that exhibited a single recombination on 21q and proposed that certain recombination con-Wgurations are risk factors for either meiosis I (MI) or meiosis II (MII) nondisjunction. The primary goal of this analysis was to examine characteristics of maternal chromosomes 21 that exhibited multiple recombinant events on 21q to determine whether additional risk factors or mechanisms are suggested. In order to identify the origin (maternal or paternal) and stage (MI or MII) of the meiotic errors, as well as placement of recombination, we genotyped over 1,500 SNPs on 21q. Our analyses included 785 maternal MI errors, 87 of which exhibited two recombinations on 21q, and 283 maternal MII errors, 81 of which exhibited two recombinations on 21q. Among MI cases, the average location of the distal recombination was proximal to that of normally segregating chromosomes 21 (35.28 vs. 38.86 Mb), a diVerent pattern than that seen for single events and one that suggests an association with genomic features. For MII errors, the most proximal recombination was closer to the centromere than that on normally segregating chromosomes 21 and this proximity was associated with increasing maternal age. This pattern is same as that seen among MII errors that exhibit only one recombination. These Wndings are important as they help us better understand mechanisms that may underlie both age-related and nonage-related meiotic chromosome mal-segregation.
Relationship of recombination patterns and maternal age among non-disjoined chromosomes 21
Biochemical Society Transactions, 2006
Advancing maternal age has long been identified as the primary risk factor for human chromosome trisomy. More recently, altered patterns of meiotic recombination have been found to be associated with non-disjunction. We have used trisomy 21 as a model for human non-disjunction that occurs during the formation of oocytes to understand the role of maternal age and recombination. Patterns of recombination that increase the risk for non-disjunction of chromosome 21 include absence of any exchange, an exchange near the centromere or a single, telomeric exchange. Our recent work has shown that different susceptibility patterns are associated with the origin of the meiotic error and maternal age. For MI (meiosis I) errors, the proportion of oocytes with susceptible recombination patterns is highest among young mothers and decreases significantly in the oldest age group. In fact, the pattern of exchanges among the oldest age group mimics the pattern observed among normally disjoining chromo...
The meiotic stage of nondisjunction in trisomy 21: Determination by using DNA polymorphisms
The American Journal of Human Genetics, 1992
We have studied DNA polymorphisms at loci in the pericentromeric region on the long arm of chromosome 21 in 200 families with trisomy 21, in order to determine the meiotic origin of nondisjunction. Maintenance of heterozygosity for parental markers in the individual with trisomy 21 was interpreted as resulting from a meiosis I error, while reduction to homozygosity was attributed to a meiosis II error. Nondisjunction was paternal in 9 cases and was maternal in 188 cases, as reported earlier. Among the 188 maternal cases, nondisjunction occurred in meiosis I in 128 cases and in meiosis II in 38 cases; in 22 cases the DNA markers used were uninformative. Therefore meiosis I was responsible for 77.1% and meiosis II for 22.9% of maternal nondisjunction. Among the 9 paternal nondisjunction cases the error occurred in meiosis I in 2 cases (22.2%) and in meiosis II in 7 (77.8%) cases. Since there was no significant difference in the distribution of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular meiotic stage contributes significantly to the increasing incidence of Down syndrome with advancing maternal age. Although the DNA polymorphisms used were at loci which map close to the centromere, it is likely that rare errors in meiotic-origin assignments may have occurred because of a small number of crossovers between the markers and the centromere. Analysis of these polymorphisms may provide a more accurate understanding of the meiotic stage of nondisjunction in trisomy 21 than that previously provided by chromosomal heteromorphisms.