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PubMed2006

Molecular phylogenetics and evolutionary diversification of labyrinth fishes (Perciformes: Anabantoidei).

Labyrinth fishes (Perciformes: Anabantoidei) are primary freshwater fishes with a disjunct African-Asian distribution that exhibit a wide variety of morphological and behavioral traits. These intrinsic features make them particularly well suited for studying patterns and processes of evolutionary diversification. We reconstructed the first molecular-based phylogenetic hypothesis of anabantoid intrarelationships using both mitochondrial and nuclear nucleotide sequence data to address anabantoid evolution. The mitochondrial data set included the complete cytochrome b, partial 12S rRNA, complete tRNA Val, and partial 16S rRNA genes (3332 bp) of 57 species representing all 19 anabantoid genera. The nuclear data set included the partial RAG1 gene (1494 bp) of 21 representative species. The phylogenetic analyses of a combined (mitochondrial+nuclear) data set recovered almost fully resolved trees at the intrafamily level with different methods of phylogenetic inference. Phylogenetic relationships at this taxonomic level were compared with previous morphology-based hypotheses. In particular, the enigmatic pike-head (Luciocephalus) was confidently placed within the "spiral egg" clade, thus resolving the long-standing controversy on its relative phylogenetic position. The molecular phylogeny was used to study the evolution of the different forms of parental care within the suborder. Our results suggest that the evolution of breeding behavior in anabantoids is highly correlated with phylogeny, and that brood care evolved three times independently from an ancestral free spawning condition without parental care. Ancestral character state reconstructions under maximum parsimony and maximum likelihood further indicated that both bubble nesting and mouthbrooding have evolved recurrently during anabantoid evolution. The new phylogenetic framework was also used to test alternative biogeographic hypotheses that account for the disjunct African-Asian distribution. Molecular divergence time estimates support either a drift vicariance linked to the breakup of Gondwana or Late Mesozoic Early Tertiary dispersal from Africa to Asia or vice versa.

Animals↗

PubMed1991

The diagnostic accuracy of rapid dipstick tests to predict urinary tract infection.

This study summarizes the diagnostic accuracy data for dipstick nitrite and/or leukocyte esterase tests (the index tests) as predictors of bacterial urinary tract infection as defined by quantitative culture (the reference test). On-line search of the literature using the MEDLARS database identified 1,017 citations, 51 of which were relevant and contained sufficient data for further analysis. From each citation, 2 x 2 tables of true-positive, true-negative, false-positive, and false-negative results were extracted. Four categories of index test were assessed: nitrite only, leukocyte esterase only, disjunctive pairing (dipstick positive if nitrite, leukocyte esterase, or both were positive), and conjunctive pairing (dipstick positive only if both nitrite and leukocyte esterase were positive). The true- and false-positive rates were calculated from each 2 x 2 table. Plots of true-positive rates versus false-positive rates demonstrated widely scattered points, indicating heterogeneity. A receiver-operating characteristic curve was fitted to the data using logistic transforms and weighted linear regression. This analysis revealed that the disjunctive pair is the most accurate index test. However, in many clinical settings, the posterior probability of urinary tract infection given a negative dipstick is too high to exclude it. Within most clinically relevant ranges of true- and false-positive rates, a negative urine dipstick test cannot exclude the diagnosis of urinary tract infection in patients with high prior probabilities of contracting this infection. For lower prior probabilities, the clinical efficacy of these rapid tests would best be determined by decision analysis, for which these receiver-operating characteristic functions would serve as valuable analytical tools.

Diagnostic Tests, Routine↗

PubMed2006

Aneuploidy-inducing capacity of two widely used pesticides.

The aneuploidy-inducing activity of alachlor and dichlorvos, two pesticides representing an important source of human exposure to potential carcinogens, has been evaluated in a cytokinesis block micronucleus assay combined with anti-kinetochore (CREST) staining to detect chromosome loss and in situ hybridization with chromosome-specific centromeric probes for the analysis of non-disjunction. Cytofluorimetric analysis to assess potential interference of the chemicals with cell cycle progression and TUNEL assay to detect apoptosis were also performed. The results obtained show that both environmental compounds induced significant and dose-related increases of total micronuclei (MN) and CREST-positive MN as compared with the concurrent solvent control. The chemicals were also capable of promoting chromosome non-disjunction. However, the two pesticides differed in their mode of action: alachlor induced both chromosomal aberrations and aneuploidy, while the genotoxic activity of dichlorvos was only related to aneuploidy induction. Cytofluorimetric analyses showed that dichlorvos caused a marked accumulation of cells in the G2/M phase of cell cycle and indicate a potential for this chemical to interfere with mitosis. Furthermore, dichlorvos induced CREST-positive MN at a concentration lower than the one producing apoptosis, suggesting that dichlorvos-induced aneuploid cells may persist in the growing cell population.

Acetamides↗

PubMed1989

Genetic analysis of the claret locus of Drosophila melanogaster.

The claret (ca) locus of Drosophila melanogaster comprises two separately mutable domains, one responsible for eye color and one responsible for proper disjunction of chromosomes in meiosis and early cleavage divisions. Previously isolated alleles are of three types: (1) alleles of the claret (ca) type that affect eye color only, (2) alleles of the claret-nondisjunctional (cand) type that affect eye color and chromosome behavior, and (3) a meiotic mutation, non-claret disjunctional (ncd), that affects chromosome behavior only. In order to investigate the genetic structure of the claret locus, we have isolated 19 radiation-induced alleles of claret on the basis of the eye color phenotype. Two of these 19 new alleles are of the cand type, while 17 are of the ca type, demonstrating that the two domains do not often act as a single target for mutagenesis. This suggests that the two separately mutable functions are likely to be encoded by separate or overlapping genes rather than by a single gene. One of the new alleles of the cand type is a chromosome rearrangement with a breakpoint at the position of the claret locus. If this breakpoint is the cause of the mutant phenotype and there are no other mutations associated with the rearrangement, the two functions must be encoded by overlapping genes.

Alleles↗

PubMed1990

The genetic analysis of distributive segregation in Drosophila melanogaster. II. Further genetic analysis of the nod locus.

In Drosophila melanogster females the segregation of nonexchange chromosomes is ensured by the distributive segregation system. The mutation noda specifically impairs distributive disjunction and induces nonexchange chromosomes to undergo nondisjunction, as well as both meiotic and mitotic chromosome loss. We report here the isolation of seven recessive X-linked mutations that are allelic to noda. As homozygotes, all of these mutations exhibit a phenotype that is similar to that exhibited by noda homozygotes. We have also used these mutations to demonstrate that nod mutations induce nonexchange chromosomes to nondisjoin at meiosis II. Our data demonstrate that the effects of noda on meiotic chromosome behavior are a general property of mutations at the nod locus. Several of these mutations exhibit identical phenotypes as homozygotes and as heterozygotes with a deficiency for the nod locus; these likely correspond to complete loss-of-function or null alleles. None of these mutations causes lethality, decreases the frequency of exchange, or impairs the disjunction of exchange chromosomes in females. Thus, either the nod locus defines a function that is specific to distributive segregation or exchange can fully compensate for the absence of the nod+ function.

Alleles↗

PubMed1995

Cis-acting determinants affecting centromere function, sister-chromatid cohesion and reciprocal recombination during meiosis in Saccharomyces cerevisiae.

We have employed a system that utilizes homologous pairs of human DNA-derived yeast artificial chromosomes (YACs) as marker chromosomes to assess the specific role(s) of conserved centromere DNA elements (CDEI, CDEII and CDEIII) in meiotic chromosome disjunction fidelity. Thirteen different centromere (CEN) mutations were tested for their effects on meiotic centromere function. YACs containing a wild-type CEN DNA sequence segregate with high fidelity in meiosis I (99% normal segregation) and in meiosis II (96% normal segregation). YACs containing a 31-bp deletion mutation in centromere DNA element II (CDEII delta 31) in either a heterocentric (mutant/wild type), homocentric (mutant/mutant) or monosomic (mutant/--) YAC pair configuration exhibited high levels (16-28%) of precocious sister-chromatid segregation (PSS) and increased levels (1-6%) of nondisjunction meiosis I (NDI). YACs containing this mutation also exhibit high levels (21%) of meiosis II nondisjunction. Interestingly, significant alterations in homolog recombination frequency were observed in the exceptional PSS class of tetrads, suggesting unusual interactions between prematurely separated sister chromatids and their homologous nonsister chromatids. We also have assessed the meiotic segregation effects of rare gene conversion events occurring at sites located immediately adjacent to or distantly from the centromere region. Proximal gene conversion events were associated with extremely high levels (60%) of meiosis I segregation errors (including both PSS and NDI), whereas distal events had no apparent effect. Taken together, our results indicate a critical role for CDEII in meiosis and underscore the importance of maintaining sister-chromatid cohesion for proper recombination in meiotic prophase and for proper disjunction in meiosis I.

Base Sequence↗

PubMed2000

Recombination can partially substitute for SPO13 in regulating meiosis I in budding yeast.

Recombination and chromosome synapsis bring homologous chromosomes together, creating chiasmata that ensure accurate disjunction during reductional division. SPO13 is a key gene required for meiosis I (MI) reductional segregation, but dispensable for recombination, in Saccharomyces cerevisiae. Absence of SPO13 leads to single-division meiosis where reductional segregation is largely eliminated, but other meiotic events occur relatively normally. This phenotype allows haploids to produce viable meiotic products. Spo13p is thought to act by delaying nuclear division until sister centromeres/chromatids undergo proper cohesion for segregation to the same pole at MI. In the present study, a search for new spo13-like mutations that allow haploid meiosis recovered only new spo13 alleles. Unexpectedly, an unusual reduced-expression allele (spo13-23) was recovered that behaves similarly to a null mutant in haploids but to a wild-type allele in diploids, dependent on the presence of recombining homologs rather than on a diploid genome. This finding demonstrates that in addition to promoting accurate homolog disjunction, recombination can also function to partially substitute for SPO13 in promoting sister cohesion. Analysis of various recombination-defective mutants indicates that this contribution of recombination to reductional segregation requires full levels of crossing over. The implications of these results regarding SPO13 function are discussed.

Alleles↗

PubMed2005

Evaluation of movement speed and reaction time as predictors of all-cause mortality in men.

Muscle power is associated with mortality independent of strength, suggesting that movement speed and coordination convey health-related information. We hypothesized that movement speed is a marker of longevity. Our participants included 1196 men who performed a tapping and/or auditory simple (respond to a sound) and disjunctive (respond to a higher pitched sound) reaction-time tasks while participating in the Baltimore Longitudinal Study of Aging. Mortality was assessed over 40 years. Tapping time was associated with mortality (relative risk [RR] = 1.34 per minute, 95% confidence interval [CI], 1.05-1.70) adjusted for age, and persisted with adjustments for arm strength and power. Simple (RR = 1.17 per 100 ms, 95% CI, 1.03-1.32) and disjunctive (RR = 1.14 per 100 ms, 95% CI, 1.03-1.27) reaction times but not their difference (RR = 1.04 per 100 ms, 95% CI, 0.92-1.19) were associated with mortality after adjustments for age, neurological/psychiatric and neck/arm pain histories. Age-associated impairments in motor control systems but not the decision to move affects longevity.

Baltimore↗

PubMed1998

The meiotic competence of in-vitro matured human oocytes is influenced by donor age: evidence that folliculogenesis is compromised in the reproductively aged ovary.

The human oocyte appears to be particularly prone to meiotic errors, and the incidence of these errors is strongly influenced by maternal age. We have initiated studies of human oocytes from unstimulated ovaries and have observed age-related effects on the meiotic process in oocytes from unselected antral follicles. Specifically, in oocytes obtained from donors over the age of 35 years, the majority of oocytes that extruded a first polar body in culture and arrested at second meiotic metaphase had aberrations in spindle formation and chromosome alignment. Similarly, observations of a limited number of oocytes at first meiotic metaphase suggest disturbances at this stage of meiosis as well. Finally, preliminary results of non-disjunction studies suggest that the frequency of errors in chromosome segregation at the first meiotic division is influenced by donor age in in-vitro matured oocytes as it is in oocytes undergoing meiotic maturation in vivo. These data provide direct evidence that the meiotic competence of oocytes from unstimulated ovaries declines with donor age. Similarly, studies of in-vitro fertilization (IVF) pregnancies in older women indicate that the developmental competence of the human oocyte declines with age. Since both meiotic and developmental competence are acquired during the late stages of oocyte growth, we postulate that an age-related decline in the process of folliculogenesis results in reduced oocyte quality and that the well characterized age-related increase in meiotic non-disjunction is one symptom of compromised oocyte growth.

Adolescent↗

PubMed2001

Study of the occurrence of interchromosomal effect in spermatozoa of chromosomal rearrangement carriers by fluorescence in-situ hybridization and primed in-situ labelling techniques.

The possibility that a chromosomal rearrangement might disturb the meiotic behaviour of chromosomes not involved in the rearrangement and favour non-disjunction is a controversial issue in human cytogenetics. Using two-colour fluorescence in-situ hybridization and primed in-situ labelling techniques, we have investigated the segregation pattern of 10 chromosomes (chromosomes 1, 4, 9, 13, 15, 16, 20, 21, X and Y) in spermatozoa from nine carriers of balanced structural rearrangements and three normal men. The patients were divided into two groups according to their semen parameters. In rearrangement carriers and normal subjects, sex chromosomes and chromosome 21 displayed a higher rate of disomy than the other chromosomes. No evidence for the occurrence of interchromosomal effect was found in the spermatozoa of fertile rearrangement carriers, but significant variations were observed for all chromosomes tested in the group of infertile translocation carriers, suggesting a direct correlation between poor quality spermatozoa and increased aneuploidy rate in this group. In fertile carriers of chromosomal rearrangements, the occurrence of non-disjunction of chromosomes not involved in the rearrangement might therefore be considered as fortuitous, whereas in infertile carriers, the risk for interchromosomal effect appears to be real and should be taken into consideration in the genetic counselling of infertile couples with a male partner carrying a chromosomal rearrangement.

Adult↗

PubMedDate not supplied

Chromosome studies in human sperm nuclei using fluorescence in-situ hybridization (FISH).

The use of chromosome specific DNA probes labelled with fluorochromes and especially the combination of several probes has been used to indirectly study the chromosome constitution of decondensed sperm nuclei by fluorescence in-situ hybridization (FISH), and has allowed to include this test in the protocol of study of infertile males. Still, if the test is to be valid, several strict conditions must be met, and some specific characteristics have to be taken into account. This becomes evident when comparing earlier results with more recent ones. The basic technical factors to be taken into account are the methods of chromatin decondensation, the number of spermatozoa and of individuals to study, the use of internal controls, the scoring criteria, the specificity of the probes and the possible existence of polymorphisms that may interfere with the detection of fluorescent signals. In the last 7 or 8 years, a large number of papers has been published, describing the incidence of aneuploidies in controls, in individuals in whom a tendency to non-disjunction was suspected and in infertile males. Studies in controls have shown a considerable intra- and inter-individual variability in the frequency of aneuploidies, the tendency of some chromosomes to undergo non-disjunction (chromosome 21 and the sex chromosomes) and the importance of alpha-satellite polymorphisms when using centromere probes. In the control population, the frequency of aneuploidy per haploid set has been estimated at approximately 6%. The incidence of aneuploidies in sperm nuclei for some of the chromosomes more frequently involved in trisomies is considerably higher than the incidence of these trisomies established through epidemiological data using the global incidence of chromosome abnormalities during the peri-implantation stage. In infertile males and in males with sex-chromosome abnormalities (usually with very low numbers of spermatozoa) the results show an increased incidence of sex chromosome aneuploidies and diploid (multi-aneuploid?) sperm nuclei. The results could be related to the higher incidence of chromosome abnormalities (especially sex-chromosome aneuploidies) observed in children conceived by intracytoplasmic sperm injection (ICSI).

Cell Nucleus↗

PubMedDate not supplied

Aberrant recombination and the origin of Klinefelter syndrome.

Trisomy is the most commonly identified chromosome abnormality in humans, occurring in at least 4% of all clinically recognized pregnancies; it is the leading known cause of pregnancy loss and of mental retardation. Over the past decade, molecular studies have demonstrated that most human trisomies originate from errors at maternal meiosis I. However, Klinefelter syndrome is a notable exception, as nearly one-half of all cases derive from paternal non-disjunction. In this review, the data on the origin of sex chromosome trisomies are summarized, focusing on the 47,XXY condition. Additionally, the results of recent genetic mapping studies are reviewed that have led to the identification of the first molecular correlate of autosomal and sex chromosome non-disjunction; i.e. altered levels and positioning of meiotic recombinational events.

Chromosome Aberrations↗

PubMed2004

The chromosomal analysis of human oocytes. An overview of established procedures.

The cytogenetic survey of mature human oocytes has been and remains a subject of great interest because of the prevalence of aneuploidy of maternal origin in abnormal human conceptuses, and the lack of understanding about the non-disjunction processes in human meiosis. The first attempts to analyse the chromosomal content of human female gametes were made in the early 1970s, and led to limited data because of the paucity of materials and the inadequacy of the procedure used. The years to follow brought a resurgence of interest in this field, because of the development of human IVF techniques which made oocytes unfertilized in vitro available for cytogenetic analysis. Numerous studies have since been performed. However, the difficulties in obtaining good chromosome preparations and of performing accurate chromosome identification have reduced the viability of these studies, resulting in large variations in the reported incidences of chromosomal abnormalities. The further introduction of new procedures for oocyte fixation and the screening of large oocyte samples have allowed more reliable data to be obtained and to identify premature chromatid separation as a major mechanism in aneuploidy occurrence. The last decade has been privileged to witness the adaptation of molecular cytogenetic techniques to human oocytes, and thus various powerful procedures have been tried not only on female gametes, but also on polar bodies, involving sequential and multicolour fluorescent in situ hybridization (FISH) labelling, comparative genomic hybridization (CGH), spectral karyotyping and alternative methods such as primed in situ labelling (PRINS) and peptide nucleic acid (PNA) techniques. A large body of data has been obtained, but these studies also display a great variability in the frequency of abnormalities, which may be essentially attributable to the technical limitations of these in situ methods when applied to human oocytes. However, molecular cytogenetic approaches have also evidenced the co-existence of both whole chromosome non-disjunction and chromatid separation in maternal aneuploidy. In addition, the extension of these techniques to oocyte polar body materials has provided additional data on the mechanism of meiotic malsegregation. Improvements of some of these techniques have already been reported. The further development of new approaches for the in situ analysis of human meiosis will increase the impact of cytogenetic investigation of human oocytes in the understanding of aneuploidy processes in humans.

Aneuploidy↗

PubMed2006

Multilocus analysis of nucleotide variation and speciation in Oryza officinalis and its close relatives.

Nucleotide variation in 10 unlinked nuclear genes was investigated in species-wide samples of Oryza officinalis and its close relatives (Oryza eichingeri and Oryza rhizomatis). Average estimates of nucleotide diversity were the lowest in O. rhizomatis ((sil) = 0.0038) and the highest in O. eichingeri ((sil) = 0.0057) that is disjunctly distributed in Africa and Sri Lanka. These wild rice species appeared to harbor relatively low levels of nucleotide variation relative to other plant species because the diversity level of O. eichingeri is only 23-46% of those in Zea species and 35% of that in Arabidopsis thaliana. The lower nucleotide diversity in these Oryza species could be best explained by their smaller historic effective population sizes. The speciation model test indicated that O. officinalis and its close relatives might have undergone a process of population contraction since divergence from their ancestor. Incongruent topologies among 10 gene trees, particularly regarding the positions of O. eichingeri and O. rhizomatis accessions might be attributed to lineage sorting arising from ancient polymorphism and hybridization/introgression between the Sri Lankan O. eichingeri and O. rhizomatis. However, the null hypothesis of the isolation model was not rejected for any contrast between taxa, which suggested that no subsequent gene flow shaped the present patterns of nucleotide variation since their divergence and that introgression was not pervasive in this group of species. Our molecular dating provides an approximate divergence time of 0.37 Myr between 2 geographical races of O. eichingeri, much more recent compared with the times of other speciation events in this group (0.63-0.68 Myr). A long-distance dispersal from West Africa to Sri Lanka was more likely to play a role in the disjunct distribution of O. eichingeri.

Africa↗

PubMed1998

Concurrent use of flow cytometry and fluorescence in-situ hybridization techniques for detecting faulty meiosis in a human sperm sample.

Routine semen analysis in an infertile patient revealed severe teratospermia associated with malformation of head and tail in 100% of the sperm cells. Flow cytometry and fluorescence in-situ hybridization (FISH) were shown to supplement routine semen analysis by providing information on the sperm chromatin. Using flow cytometry, propidium iodide-stained spermatozoa from the same sperm sample were compared with a normal reference pool, and with human lymphocytes. The results point to a population of diploid sperm cells rather than to mature haploid spermatozoa. Numerical chromosomal abnormalities of the spermatozoa were subsequently evaluated using FISH. A total of 1000 sperm cells were scored for X and Y chromosomes, and an additional 1128 sperm cells for chromosome 18. Aneuploidy of chromosomes X and Y was revealed in 96.9% of the cells and of chromosome 18 in 90.3% of the cells. Non-disjunction of chromosome X and Y in meiosis I and II occurred in 54.8 and 2.7% of the sperm cells respectively. Non-disjunction in both meiosis I and II occurred in 39.4% of the sperm cells. A normal haploid pattern for chromosomes X and Y was observed in only 3.1%, and for chromosome 18 in 9.7%, of the cells. Using three colour FISH for the sex chromosomes and for chromosome 18, diploidy was demonstrated in 19.4% of 500 sperm cells and aneuploidy in virtually all sperm cells (99.2%). The use of flow cytometry and FISH in cases where genetic and developmental chromatin abnormalities are suspected is a valuable adjunct to other available techniques, and can guide the clinicians to decide which samples are unsuitable for intracytoplasmic injection.

Adult↗

PubMed1998

Disomy rates for chromosomes 14 and 21 studied by fluorescent in-situ hybridization in spermatozoa from three men over 60 years of age.

In order to further investigate the paternal-age effect on meiotic non-disjunction rates for the chromosomes 14 and 21, we examined spermatozoa from three men aged > 60, using multicolour fluorescent in-situ hybridization (FISH). More than 10,000 sperm cells were analysed for each of the three subjects (A, B and C), by simultaneously hybridizing two YAC probes specific for chromosomes 14 and 21 respectively using two-colour FISH. The results show that the disomy 21 rates observed in the spermatozoa of two out of the three men aged > 60 years were higher (1.02 and 1.17% respectively) than the rates observed in eight control adults aged < 30 years (mean frequency 0.48%) analysed under similar conditions. These results suggest that there may be a small effect of age on male non-disjunction rates for chromosome 21. However, before any firm conclusions could be drawn, a much bigger sample of older men would have to be compared with a paired control population using the same FISH experimental approach.

Adult↗

PubMed2003

Sequential multiple probe fluorescence in-situ hybridization analysis of human oocytes and polar bodies by combining centromeric labelling and whole chromosome painting.

The incidence of chromosomal aneuploidy was analysed in 104 unfertilized human oocytes and 56 first polar bodies using a double-label fluorescence in-situ hybridization (FISH) procedure. Combinations of centromeric (or locus-specific) DNA probes and whole chromosome painting probes for chromosomes 9, 13, 16, 18, 21 and X were applied on oocyte preparations, in a sequential FISH protocol. This combined approach allowed a precise in-situ identification of both chromosomes and free chromatids, and consequently a reliable analysis of chromosomal segregation errors. Of the 104 analysed oocytes, 84 (80.7%) displayed a normal chromosome constitution. Three cases of chromosome non-disjunction (2.8%) were found, whereas seven oocytes (6.7%) presented extra single chromatids. In addition, 12 oocytes (11.5%) showed balanced pre-division of one pair of sister chromatids. Although this phenomenon was not classified as aneuploidy, it could lead to aneuploidy at anaphase II. Abnormalities were observed in all the targetted chromosomes. The present data confirm that both whole chromosome non-disjunction and premature chromatid separation constitute the two major mechanisms of aneuploidy in human female meiosis.

Centromere↗

PubMed2004

Mitotic errors in chromosome 21 of human preimplantation embryos are associated with non-viability.

Fluorescent in situ hybridization (FISH) studies of human preimplantation embryos have demonstrated a high proportion of chromosomal mosaicism. To investigate the different timings and nature of chromosomal mosaicism, we developed single cell multiplex fluorescent (FL)-PCR to distinguish meiotic and mitotic cell division errors. Chromosome 21 was investigated as the model chromosome as trisomy 21 (Down's syndrome) represents the most common chromosomal aneuploidy that reaches live birth. Sister blastomeres from a total of 25 chromosome 21 aneuploid embryos were analysed. Of these, 13 (52%) comprised cells with concordant DNA fingerprints indicative of meiotic non-disjunction errors. The remaining 12 (48%) aneuploid embryos comprised discordant sister blastomere allelic profiles and thus were mosaic. Errors at all stages including metaphase (MI) (12%) and first (38%), second (31%) and third (19%) mitotic cleavage divisions were identified from the types and proportion of different allelic profiles. In addition, three embryos showed combined meiotic and mitotic cell division errors including non-disjunction and anaphase lag, suggesting that diploid cells had resulted from an aneuploid zygote. However, the majority of the mosaic aneuploid embryos showed mitotic gains and losses from a diploid zygote occurring prior to the activation of the embryonic genome. Allelic profiling of amniocytes from 15 prenatal diagnosis samples displayed only meiotic errors. There appears to be a large difference between the proportion of mosaic mitotic-derived trisomy 21 embryos and fetuses. These findings indicate that mosaic mitotic error of chromosome 21 is associated with non-viability.

Adult↗