Double trisomy in spontaneous miscarriages: cytogenetic and molecular approach (original) (raw)
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Preimplantation genetic diagnosis of aneuploidy: Were we looking at the wrong chromosomes?
1999
stage embryos. These frequencies were compared to spontaneous abortion data to determine differences in survival rate of their aneuploidies. Methods: One hundred ninety-four embryos were analyzed with multicolor fluorescence in situ hybridization. Embryos were divided into three maternal age groups: 20 to 34.9 years, (2) 35 to 39.9 years, and (3) 40 years and older. Embryos were also divided into two developmental and morphological groups: arrested and nonarrested embryos. Results: The rate of aneuploidy was 14.51%, 14.10%, and 31.48% for age groups 1, 2, and 3, respectively (P < 0.005). The chromosomes most frequently involved in aneuploidy events were 22, 15, 1, and 17. Conclusions: The chromosomes most involved in spontaneous abortions are not necessarily the ones causing a decrease in implantation rates with maternal age. Other aneuploidies, such as for chromosomes 1 and 17, may seldom implant or die shortly after implantation.
TroX: a new method to learn about the genesis of aneuploidy from trisomic products of conception
Bioinformatics, 2014
Motivation : An estimated 10–30% of clinically recognized conceptions are aneuploid, leading to spontaneous miscarriages, in vitro fertilization failures and, when viable, severe developmental disabilities. With the ongoing reduction in the cost of genotyping and DNA sequencing, the use of high-density single nucleotide polymorphism (SNP) markers for clinical diagnosis of aneuploidy and biomedical research into its causes is becoming common practice. A reliable, flexible and computationally feasible method for inferring the sources of aneuploidy is thus crucial. Results : We propose a new method, TroX, for analyzing human trisomy data using high density SNP markers from a trisomic individual or product of conception and one parent. Using a hidden Markov model, we infer the stage of the meiotic error (I or II) and the individual in which non-disjunction event occurred, as well as the crossover locations on the trisomic chromosome. A novel and important feature of the method is its re...
2021
Chromosomal aneuploidies are the most chromosomal abnormalities at birth due to maternal meiosis I errors. Pregnancies with autosomal chromosomal aneuploidies that survive are namely trisomies 13 (Patau syndrome), 18 (Edward syndrome), and 21 (Down syndrome), account for 89% of chromosome abnormalities. Quantitative fluorescent polymerase chain reaction (QF-PCR) which amplifies specific DNA sequences called short tandem repeats (STRs), by using fluorescently labeled primers is a rapid technique for prenatal diagnosis of common aneuploidies. In this study, DNA extraction was performed from 100 samples isolated from muscle tissue of aborted fetuses. The analysis was performed by multiplex QF-PCR using a panel of 25 STRs markers for chromosomes X, Y, 13, 18, and 21. Our results showed that 20% of abortions were due to aneuploidy. 53% of mothers who had abortions were aged 26-35 years old and 32% of them were aged 36-45 years old. The analysis of muscle samples of aborted fetuses indica...
Avicenna Journal of Medical Biotechnology
Background: Around 70% of all pregnancies (Including 15% of clinically-recognized ones) are lost due to various fetal or maternal disorders. Chromosomal aneuploidies are among the most common causes of pregnancy loss. Standard chromosome analysis using G-banding technique (Karyotype) is the technique of choice in studying such abnormalities; however, this technique is time-consuming and sensitive, and limited by vulnerabilities such as cell culture failure. The use of molecular cytogenetic techniques, including array-based techniques and Multiplex Ligation-Dependent Probe Amplification (MLPA), has been proposed to overcome the limitations of this method to study the products of conception. This study has been designed to investigate the feasibility of using MLPA technique as a standalone genetic testing, with histopathologic examinations and genetic counseling to detect aneuploidies in products of conception and neonatal deaths. Methods: Forty-two verified fetal and neonatal samp...
Molecular methods for rapid detection of aneuploidy
Journal of applied genetics, 2005
Rapid molecular biological methods for prenatal diagnosis of the most common aneuploidies, collectively known as rapid aneuploidy testing, are compared in this review. We discuss methodological problems and limitations of these various methods. All these techniques are believed to be accurate and carry a low risk of misdiagnosis, but they differ in terms of labour-intensity and amenability to automation and high throughput testing. The question how to apply them safely and economically in a clinical setting has not been answered yet. The discussed techniques are so far not used as stand-alone tests, but some of them are routinely applied as a preliminary test that shortens the waiting time for classic cytogenetic karyotyping. In the future, mainly because of economical reasons, these methods may replace cytogenetics in the category of patients who make up the majority of those currently offered prenatal karyotyping: patients with moderately increased risk and no abnormalities detect...
The origin of human aneuploidy: where we have been, where we are going
Human Molecular Genetics, 2007
Aneuploidy is the most common chromosome abnormality in humans, and is the leading genetic cause of miscarriage and congenital birth defects. Since the identification of the first human aneuploid conditions nearly a half-century ago, a great deal of information has accrued on its origin and etiology. We know that most aneuploidy derives from errors in maternal meiosis I, that maternal age is a risk factor for most, if not all, human trisomies, and that alterations in recombination are an important contributor to meiotic non-disjunction. In this review, we summarize some of the data that have led to these conclusions, and discuss some of the approaches now being used to address the underlying causes of meiotic non-disjunction in humans.
Chromosomal abnormalities in embryos from couples with a previous aneuploid miscarriage
Fertility and Sterility, 2012
Objective: To compare the incidence of chromosomal abnormalities in preimplantation embryos from couples undergoing preimplantation genetic screening (PGS) after previous aneuploid miscarriage after either natural conception (NC) or assisted reproductive technology (ART) versus fertile couples who underwent PGS for sex-linked diseases as a control group. Design: Retrospective study. Setting: IVF clinic. Patient(s): Patients with previous aneuploid conception undergoing PGS. Intervention(s): Embryo biopsy, fluorescence in situ hybridization. Main Outcome Measure(s): Embryo aneuploidy rates and pregnancy and implantation rates in couples with a previous aneuploidy for autosomes or sex chromosomes. Result(s): The overall rates of chromosomal abnormalities in groups with previous autosomal aneuploidy were significantly higher compared with the control group (67.8% for those whose previous aneuploidy arose after NC and 65.8% for those previously arising after ART, vs. 34.0%). No significant differences were observed in those with previous sex chromosome abnormalities compared with control subjects. Within couples with previous aneuploidies after NC, no difference existed in the incidence of chromosomal abnormalities compared with the ART groups. Clinical outcomes were better (trend) in patients with previous autosomal aneuploidy after NC. Conclusion(s): In preimplantation embryos, the incidence of chromosomal abnormalities due to a previous aneuploid miscarriage after either NC or ART is significantly higher than in the control group. Furthermore, this incidence is higher when the previous aneuploidy was for autosomes; PGS is recommended in these couples. (Fertil Steril Ò 2012;-:---.
The Application of Clinical Genetics
Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of "truly unexplained RPL" would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.
Acta Obstetricia et Gynecologica Scandinavica, 2006
The cause of aneuploidy in fetuses of young women is not fully understood. As such women are considered to be at risk of repeating the ''error'', it is customary to recommend chromosomal evaluation (karyotyping) in subsequent pregnancies. Individuals predisposed to meiotic nondisjunction exhibit aneuploidy in their mitotic cells (mosaicism). The aim of this study was to assess the actual risk for repeated aneuploidy in patients who had a previous pregnancy with aneuploidy by estimating the rate of somatic random aneuploidy in their normal pregnancy and to assess whether this risk is heritable. With utilization of FISH, we assessed the number of chromosomes 9 and 18 in amniocytes from the following pregnancies: 1. Fourteen of the women had a history of chromosomal aneuploidy in a previous pregnancy (study group). 2. Ten women had previous normal pregnancies (control). 3. Nine samples were assessed in amniocytes taken from aneuploid pregnancies (positive controls). A mean of 4589/65.66 amniocytes were evaluated (range 97 Á500 nuclei). There was no significant difference in the rate of aneuploidy of both chromosomes between the study and control groups. However, this rate was significantly higher in the aneuploid pregnancies (p B/0.05).Conclusion. The known tendency for repeated nondisjunction shown in women with previous aneuploid babies could not be demonstrated in their offsprings.