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The New England Journal of Medicine Dec 2012Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis.
METHODS
Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray.
RESULTS
We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results.
CONCLUSIONS
In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.).
Topics: Adult; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human; Down Syndrome; Female; Fetal Diseases; Genetic Testing; Humans; Karyotype; Karyotyping; Maternal Age; Oligonucleotide Array Sequence Analysis; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 23215555
DOI: 10.1056/NEJMoa1203382 -
Prenatal Diagnosis Jan 2020The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality... (Review)
Review
The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal testing (NIPT) results. Clinicians need to understand the biological influences on FF to be able to provide optimal post-test counseling and clinical management. There are many different technologies available for the measurement of FF. Clinicians do not need to know the details behind the bioinformatics algorithms of FF measurements, but they do need to appreciate the significant variations between the different sequencing technologies used by different laboratories. There is no universal FF threshold that is applicable across all platforms and there have not been any differences demonstrated in NIPT performance by sequencing platform or method of FF calculation. Importantly, while FF should be routinely measured, there is not yet a consensus as to whether it should be routinely reported to the clinician. The clinician should know what to expect from a standard test report and whether reasons for failed NIPT results are revealed. Emerging solutions to the challenges of samples with low FF should reduce rates of failed NIPT in the future. In the meantime, having a "plan B" prepared for those patients for whom NIPT is unsuccessful is essential in today's clinical practice.
Topics: Algorithms; Aneuploidy; Anticoagulants; Autoimmune Diseases; Body Weight; Cell-Free Nucleic Acids; Chorionic Gonadotropin, beta Subunit, Human; Computational Biology; Crown-Rump Length; DNA Copy Number Variations; Female; Gestational Age; Heparin, Low-Molecular-Weight; High-Throughput Nucleotide Sequencing; Humans; Maternal Age; Mosaicism; Noninvasive Prenatal Testing; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Pregnancy-Associated Plasma Protein-A; Reproductive Techniques, Assisted; Triploidy
PubMed: 31821597
DOI: 10.1002/pd.5620 -
Facts, Views & Vision in ObGyn 2011First trimester spontaneous abortions occur in 15 to 20% of all clinically recognized pregnancies. Chromosomal -anomalies are responsible for more than 50% of... (Review)
Review
First trimester spontaneous abortions occur in 15 to 20% of all clinically recognized pregnancies. Chromosomal -anomalies are responsible for more than 50% of spontaneous abortions. The majority (90%) of these chromosomal anomalies are numerical, particularly autosomal trisomies (involving chromosomes 13,16, 18, 21, 22), polyploidy and monosomy X. At birth chromosomal anomalies are still an important cause of congenital malformations occurring in 0,55% of newborns (autosomal: 0,40%, sex chromosomal: 0,15%). Autosomal trisomies result from maternal -meiotic nondisjunction of gametogenesis and the risk increases with maternal age. Polyploidy (triploidy (3n = 69) or tetraploidy (4n = 92)), results from a contribution of one or more extra haploid chromosome sets at fertilization. Unlike the risk for autosomal trisomies, the risk for polyploidies and for monosomy X (Turner syndrome) does not increase with maternal age. In the prenatal period the ultrasonographic diagnosis of some autosomal trisomies such as trisomy 13 and 18 is feasible based on the frequently seen major malformations while the diagnosis of trisomy 21 often remains challenging due to the absence of major malformations in > 50% of cases. For Turner syndrome (monosomy X), the lethal form will present with cystic hygroma colli and hydrops but the non lethal form is difficult to recognize by -ultrasound in the second trimester. The 5 frequently encountered chromosomal anomalies (Trisomy 13, 18, 21, Turner syndrome and Triploidy) referred here as the 5T's have specific hand features which will be discussed.
PubMed: 24753843
DOI: No ID Found -
Journal de Gynecologie, Obstetrique Et... Jan 1998Triploidies are pregnancies that show a 69 chromosome karyotype. This chromosomal abnormality gives rise to early abortion in most cases. Triploid pregnancies, after the... (Review)
Review
Triploidies are pregnancies that show a 69 chromosome karyotype. This chromosomal abnormality gives rise to early abortion in most cases. Triploid pregnancies, after the first three months, become molar pregnancies (molar changes inside the placenta with identifiable embryonic structures and a preeclampsia) or non molar pregnancies (isolated intauterin growth retardation). Several possibilities concerning the origin of the additional set of chromosomes exist: dispermy (the most common), diandry and digyny. The maternal and fetal clinical manifestations of this chromosomal abnormality are very diverse, which explains the difficulty of finding and recognizing this pathology. Mac Fadden's classification does not explain all the phenotypic triploid physiopathology. Formal diagnosis of triploidy depends on the fetal karyotype. The better the maternal prognosis is, the worst the fetal prognosis is. Postnatal life expectancy is not more than a few weeks. In most cases, maternal associated complications disappear with the molar evacuation. The risk of post molar tumor is discussed. However, good management of triploidy is based on an early diagnosis, before birth if that is possible.
Topics: Abortion, Spontaneous; Chromosome Aberrations; Chromosome Disorders; Female; Fetal Growth Retardation; Humans; Hydatidiform Mole; Karyotyping; Polyploidy; Pregnancy; Prenatal Diagnosis; Prognosis
PubMed: 9583043
DOI: No ID Found -
Proceedings of the National Academy of... Nov 2021Extra or missing chromosomes-a phenomenon termed aneuploidy-frequently arise during human meiosis and embryonic mitosis and are the leading cause of pregnancy loss,...
Extra or missing chromosomes-a phenomenon termed aneuploidy-frequently arise during human meiosis and embryonic mitosis and are the leading cause of pregnancy loss, including in the context of in vitro fertilization (IVF). While meiotic aneuploidies affect all cells and are deleterious, mitotic errors generate mosaicism, which may be compatible with healthy live birth. Large-scale abnormalities such as triploidy and haploidy also contribute to adverse pregnancy outcomes, but remain hidden from standard sequencing-based approaches to preimplantation genetic testing for aneuploidy (PGT-A). The ability to reliably distinguish meiotic and mitotic aneuploidies, as well as abnormalities in genome-wide ploidy, may thus prove valuable for enhancing IVF outcomes. Here, we describe a statistical method for distinguishing these forms of aneuploidy based on analysis of low-coverage whole-genome sequencing data, which is the current standard in the field. Our approach overcomes the sparse nature of the data by leveraging allele frequencies and linkage disequilibrium (LD) measured in a population reference panel. The method, which we term LD-informed PGT-A (LD-PGTA), retains high accuracy down to coverage as low as 0.05 × and at higher coverage can also distinguish between meiosis I and meiosis II errors based on signatures spanning the centromeres. LD-PGTA provides fundamental insight into the origins of human chromosome abnormalities, as well as a practical tool with the potential to improve genetic testing during IVF.
Topics: Abortion, Spontaneous; Aneuploidy; Blastocyst; Chromosome Aberrations; Chromosomes, Human; Female; Fertilization in Vitro; Genetic Testing; Haplotypes; Humans; Live Birth; Meiosis; Mosaicism; Pregnancy; Preimplantation Diagnosis
PubMed: 34772814
DOI: 10.1073/pnas.2109307118 -
Journal of Assisted Reproduction and... Sep 2021To establish the distribution of diandric and digynic triploidy depending on gestational age. (Clinical Trial)
Clinical Trial
PURPOSE
To establish the distribution of diandric and digynic triploidy depending on gestational age.
METHODS
107 triploid samples tested prospectively in a single genetic department during a four-year period were analyzed for parental origin of triploidy by Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) (n=95) with the use of matching parental samples or by MS-MLPA (n=12), when parental samples were unavailable. Tested pregnancies were divided into three subgroups with regard to the gestational age at spontaneous pregnancy loss: <11 gestational weeks, 11-14 gestational weeks, and >14 gestational weeks.
RESULTS
Diandric triploidy constituted overall 44.9% (46.5% in samples miscarried <11 gestational weeks, 64.3% in samples miscarried between 11 and 14 gestational weeks, and 27.8% in pregnancies which survived >14 gestational weeks).
CONCLUSIONS
The distribution of diandric and digynic triploidy depends on gestational age. The majority of diandric triploid pregnancies is lost in the first trimester of pregnancy. In the second trimester, diandric cases are at least twice less frequent than digynic ones.
Topics: Abortion, Spontaneous; Female; Gestational Age; Humans; Male; Poland; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prospective Studies; Triploidy
PubMed: 33982170
DOI: 10.1007/s10815-021-02202-4 -
Biology Feb 2022Reciprocal (cross-overs = COs) and non-reciprocal (gene conversion) DNA exchanges between the parental chromosomes (the homologs) during meiotic recombination are,... (Review)
Review
Reciprocal (cross-overs = COs) and non-reciprocal (gene conversion) DNA exchanges between the parental chromosomes (the homologs) during meiotic recombination are, together with mutation, the drivers for the evolution and adaptation of species. In plant breeding, recombination combines alleles from genetically diverse accessions to generate new haplotypes on which selection can act. In recent years, a spectacular progress has been accomplished in the understanding of the mechanisms underlying meiotic recombination in both model and crop plants as well as in the modulation of meiotic recombination using different strategies. The latter includes the stimulation and redistribution of COs by either modifying environmental conditions (e.g., T°), harnessing particular genomic situations (e.g., triploidy in Brassicaceae), or inactivating/over-expressing meiotic genes, notably some involved in the DNA double-strand break (DSB) repair pathways. These tools could be particularly useful for shuffling diversity in pre-breeding generations. Furthermore, thanks to the site-specific properties of genome editing technologies the targeting of meiotic recombination at specific chromosomal regions nowadays appears an attainable goal. Directing COs at desired chromosomal positions would allow breaking linkage situations existing between favorable and unfavorable alleles, the so-called linkage drag, and accelerate genetic gain. This review surveys the recent achievements in the manipulation of meiotic recombination in plants that could be integrated into breeding schemes to meet the challenges of deploying crops that are more resilient to climate instability, resistant to pathogens and pests, and sparing in their input requirements.
PubMed: 35336743
DOI: 10.3390/biology11030369 -
Scientific Reports Feb 2022Animal behaviour is increasingly recognised as critical to the prediction of non-native species success and impacts. Rainbow trout and brown trout have been introduced...
Animal behaviour is increasingly recognised as critical to the prediction of non-native species success and impacts. Rainbow trout and brown trout have been introduced globally, but there appear to be differences in their patterns of invasiveness and ecological impact. Here, we investigated whether diploid rainbow trout and diploid and triploid brown trout differ among several key behavioural measures linked to invasiveness and impact. We assessed activity, boldness, aggression, and feeding, using open field, novel object, shelter, mirror, feeding, and functional response experiments. We also tested within each fish type for behavioural syndromes comprising correlations among activity, boldness and aggression. Rainbow trout were more active and aggressive but less bold than diploid and triploid brown trout. In small groups, however, rainbow trout were bolder than both types of brown trout. Diploid brown trout were more active and bolder than triploids when tested individually, and had a higher functional response than both rainbow trout and triploid brown trout. In terms of behavioural syndromes, there was no association between activity and boldness in rainbow trout, however, there was in both brown trout types. The increased activity and aggression of rainbow trout may reflect an increased stress response to novel situations, with this response reduced in a group. These results suggest that rainbow trout do not manage their energy budgets effectively, and may explain why they have limited survival as invaders. In addition, the lower functional response of rainbow trout may explain why they are implicated in fewer ecological impacts, and the triploidy treatment also appears to lower the potential impact of brown trout. Comparative analyses of multiple behaviours of invasive species and genetic variants may thus be key to understanding and predicting invader success and ecological impacts.
Topics: Animal Distribution; Animals; Behavior, Animal; Diploidy; Introduced Species; Oncorhynchus mykiss; Phenotype; Triploidy; Trout
PubMed: 35110590
DOI: 10.1038/s41598-022-05484-5 -
American Journal of Medical Genetics.... Feb 2010Holoprosencephaly (HPE) is the most common malformation of the human forebrain. When a clinician identifies a patient with HPE, a routine chromosome analysis is often... (Review)
Review
Holoprosencephaly (HPE) is the most common malformation of the human forebrain. When a clinician identifies a patient with HPE, a routine chromosome analysis is often the first genetic test sent for laboratory analysis in order to assess for a structural or numerical chromosome anomaly. An abnormality of chromosome number is overall the most frequently identified etiology in a patient with HPE. These abnormalities include trisomy 13, trisomy 18, and triploidy, though several others have been reported. Such chromosome number abnormalities are almost universally fatal early in gestation or in infancy. Clinical features of specific chromosome number abnormalities may be recognized by phenotypic manifestations in addition to the HPE.
Topics: Chromosome Aberrations; Chromosomes, Human, Pair 13; Female; Genetic Counseling; Holoprosencephaly; Humans; Infant, Newborn; Mutation; Polyploidy; Pregnancy; Prenatal Diagnosis
PubMed: 20104610
DOI: 10.1002/ajmg.c.30232 -
The International Journal of... 2008The advent of assisted reproductive technology (ART) has taught us a great deal about human fertilization patterns. Thirty years of experience with IVF and cultivation... (Review)
Review
The advent of assisted reproductive technology (ART) has taught us a great deal about human fertilization patterns. Thirty years of experience with IVF and cultivation of early embryos has provided a unique view into the mechanisms of normal and aberrant human fertilization. Here we review the different types of triploidy following conventional in vitro fertilization and intracytoplasmic sperm injection, as well as the mechanisms giving rise to digynic and dispermic fertilization. Additionally, the role of the centrosome in triploidy, the genetic analysis of triploid embryos and the potential for therapeutic enucleation are explored. Lastly, we review our own clinical experience with human fertilization patterns following > 20,000 treatment cycles of assisted reproduction.
Topics: Centrosome; Female; Fertilization; Fertilization in Vitro; Humans; In Situ Hybridization, Fluorescence; Male; Models, Genetic; Ovum; Polyploidy; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 18649257
DOI: 10.1387/ijdb.082602hk