Molecular studies of non-disjunction in trisomy 16 (original) (raw)
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Origin of the extra chromosome in trisomy 16
Clinical Genetics, 2008
Chromosome analysis was carried out on 22 spontaneous abortuses with trisomy 16 and their parents by means of sequential Q- and C-banding techniques. In seven cases, the extra chromosome No. 16 originated from a non-disjunctional error in the first meiotic division in the mother, and in two cases from an error in the first meiotic division in the father. In two cases, non-disjunction had occurred during the second meiotic division (one in the mother and one in the father). It seems that trisomy 16, although independent of maternal age, most frequently results from a first meiotic non-disjunction in the mother.
Double trisomy in spontaneous miscarriages: cytogenetic and molecular approach
Human Reproduction, 2005
BACKGROUND: Although single trisomy is the most common chromosomal abnormality observed within first trimester spontaneous abortions (SA) (>50%), double trisomy (DT) ranges from 0.21 to 2.8% in the literature. Since little is known about mechanisms underlying DT, we report the results of our experience with 517 SA, establishing parental origin and cell stage of non-disjunction when possible in DT cases, and making a revision of those previously reported. METHODS: Cytogenetic analysis was performed in all aborted specimens. Quantitative fluorescent PCR (QF-PCR) and multiplex ligation-dependent probe amplification (MLPA) were performed in DT cases in order to assess parental origin and stage of error of aneuploidy in addition to its reliability in detecting aneuploidies. RESULTS: Karyotyping was successful in 321 miscarriages; the rate of DT was 2.18%. Among the seven DT cases reported, three new combinations were found. Maternal origin was established for all DT SA analysed. Meiotic stage of error was presumed meiosis I (MI) for 48,XX+15+22 and 48,XX+8+21, meiosis II (MII) for 48,XXX+18, and MII and MI respectively for 48,XY+18+22. Molecular results agreed with cytogenetic results. CONCLUSIONS: Similar maternal age-related mechanisms could be implicated in both single and double trisomy. Molecular techniques could be useful in diagnosing not only single but multiple aneuploidy and determining its origin. This will improve our knowledge about mechanisms underlying human aneuploidy, and enable appropiate genetic counselling.
Journal of Human Genetics, 2005
To investigate the involvement of uniparental disomies (UPDs) in spontaneous abortion, the polymorphic patterns of microsatellites on each chromosome were analyzed in 164 cases of abortion. Eighty-three of the 164 cases had chromosomal abnormalities. In 79 of the remaining 81 cases with normal karyotypes, the microsatellite analysis revealed that biparental patterns were present in the informative microsatellites in all chromosomes. In one of the remaining two cases, however, the polymorphic patterns of chromosome 14 appeared to be both of paternal origin. The patterns of the distal of the long arm were homozygous, and those of the remaining region were heterozygous. That is, this fetus had paternal UPD 14, originating from meiosis I nondisjunction. In the other case, the polymorphic patterns of the distal one third of the long arm of chromosome 7 were uniparental (maternal) in origin whereas those of the remaining region of this chromosome were biparental. These findings thus suggested that this chromosome might have originated from chromatid exchange between the long arms of paternal and maternal chromosome 7 at the first mitotic division. Microsatellite analysis, however, produced no evidence of duplication or deletion of any segments. The findings also suggest the possibility that some UPDs may cause spontaneous abortion.
Uniparental disomy for chromosome 16 in humans
American journal of human genetics, 1993
The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally...
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...
Objective: About 15% of clinically recognized pregnancies result in spontaneous abortion in the first trimester and the vast majority of these are the result of chromosome abnormalities. Studies of chromosomal constitutions of first trimester spontaneous abortions have revealed that at least 50% of the abortions have an abnormal karyotype. In this study we aimed to report the single centre experience of anomalies detected in spontaneous abortions.
Double non-disjunction in maternal meiosis II giving rise to a fetus with 48,XXX,+21
Journal of Medical Genetics, 1995
We describe a prenatally detected case of double trisomy involving chromosome 21 and the X chromosome (48,XXX, + 21) along with determination of the segregation errors responsible for the double aneuploidy. The patient was ascertained as a result of an abnormal maternal serum analyte screen showing an increased risk for fetal Down's syndrome. Following determination of the abnormal karyotype, pregnancy termination was elected. Microsatellite polymorphisms and cytogenetic heteromorphisms were used to determine that both aneuploidies arose as a result of non-disjunction in maternal meiosis II. These results support hypotheses that a segregation defect at a cellular level may cause non-disjunction involving more than one chromosome.
Journal of Medical Genetics, 1998
Recently, there have been several molecular studies of trisomic fetuses and liveborns which have examined the parent and meiotic stage of origin of nondisjunction. However, little is known about the possible phenotypic effects of the origin of trisomy. For trisomic spontaneous abortions, no distinct phenotype has been described, although some have been reported to have features, such as trophoblastic hyperplasia, similar to hydatidiform moles. In the present report, we describe molecular and histological studies of spontaneous abortions with trisomies 2, 7, 15, or 22, conditions occasionally linked to trophoblastic hyperplasia. Our results provide strong evidence for chromosome specific mechanisms of nondisjunction, with trisomy 2 having a high frequency of paternally derived cases and trisomy 7 typically originating postzygotically. In studies correlating parental origin of trisomy with phenotype, we found no difference in the proportion of cases with trophoblastic hyperplasia, fetal tissue, nucleated red blood cells, or hydropic villi among paternally or maternally derived trisomies 2, 7, 15, or 22. However, paternally derived trisomies tended to abort earlier than maternally derived trisomies. This suggests that parental origin might affect the developmental stage at which abortion occurs but not other features of placental phenotype.
Mosaic autosomal trisomy in cultures from spontaneous abortions
American journal of human genetics, 1978
In a consecutive series of 592 karyotyped spontaneous abortions, ten of 103 autosomal trisomies were mosaic, with a normal cell line also present. The frequency of mosaicism (10%) is much higher than that reported in Down syndrome, but similar to that reported in amniotic fluid cultures and in induced abortions. The most likely explanations for this discrepancy are (1) previous underestimation of mosaicism in live births or (2) mosaicism which is often restricted to extraembryonic fetal tissue.