IVF Whole genome prediction
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001005619 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF), its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis, a high number of embryos containing abnormal cells can pass this strong selection barrier. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF- and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF- and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.
2018-12-31 | GSE93353 | GEO
Project description:Pigs are important animals for agricultural and biomedical research, and its assisted reproductive technologies are urgently needed to be improved. Determining the underlying mechanism of epigenetic reprogramming in the early stage of preimplantation embryos derived from in vitro fertilization (IVF), parthenogenesis (PA) and androgenesis (AG), will not only contribute to assisted reproduction technologies of pigs but also will shed light into early human development. We generated 3D chromatin profiles for pig somatic cells, IVF, PA and AG preimplantation embryos. We found that the chromosomes in the pig preimplantation embryos are enriched for superdomains, i.e., the larger than 10M compartment domains, which are much rarer in mice. Wheras, p(s) curves, compartments and TADs, are largely conserved in somatic cells, and are gradually establishing during preimplantation embryogenesis. In the uniparental pig embryos, the establishment of chromatin architecture was highly asynchronized at all levels from IVF embryos, and a remarkably strong decompartmentalization was observed during zygotic genome activation (ZGA). Finally, chromosomes originating from oocytes always establish TADs faster than chromosomes originating from sperm, both before and during ZGA.
2020-07-02 | GSE153451 | GEO
Project description:Pigs are important animals for agricultural and biomedical research, and its assisted reproductive technologies are urgently needed to be improved. Determining the underlying mechanism of epigenetic reprogramming in the early stage of preimplantation embryos derived from in vitro fertilization (IVF), parthenogenesis (PA) and androgenesis (AG), will not only contribute to assisted reproduction technologies of pigs but also will shed light into early human development. We generated 3D chromatin profiles for pig somatic cells, IVF, PA and AG preimplantation embryos. We found that the chromosomes in the pig preimplantation embryos are enriched for superdomains, i.e., the larger than 10M compartment domains, which are much rarer in mice. Wheras, p(s) curves, compartments and TADs, are largely conserved in somatic cells, and are gradually establishing during preimplantation embryogenesis. In the uniparental pig embryos, the establishment of chromatin architecture was highly asynchronized at all levels from IVF embryos, and a remarkably strong decompartmentalization was observed during zygotic genome activation (ZGA). Finally, chromosomes originating from oocytes always establish TADs faster than chromosomes originating from sperm, both before and during ZGA.
2020-07-02 | GSE153450 | GEO
Project description:Atrial fibrillation (AF) is the most common abnormality of heart rhythm and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies (GWAS) increased the power to detect single-nucleotide variant (SNV) associations, and we report more than 350 AF-associated genetic loci. At 139 loci we identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication. We next assayed chromatin accessibility by ATAC-seq and histone H3 Lysine 4 trimethylation in stem cell derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility of our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, we found that a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known AF risk loci will facilitate a greater understanding of the pathways underlying this heart rhythm disorder.
2024-02-08 | GSE225293 | GEO
Project description:BACKGROUND:
Preimplantation genetic diagnosis (PGD) enables profiling of embryos for genetic disorders prior to implantation. The majority of PGD testing is restricted in the scope of variants assayed or by the availability of extended family members. While recent advances in single cell sequencing show promise, they remain limited by bias in DNA amplification and the rapid turnaround time (<36 h) required for fresh embryo transfer. Here, we describe and validate a method for inferring the inherited whole genome sequence of an embryo for preimplantation genetic diagnosis (PGD).
METHODS:
We combine haplotype-resolved, parental genome sequencing with rapid embryo genotyping to predict the whole genome sequence of a day-5 human embryo in a couple at risk of transmitting alpha-thalassemia.
RESULTS:
Inheritance was predicted at approximately 3 million paternally and/or maternally heterozygous sites with greater than 99% accuracy. Furthermore, we successfully phase and predict the transmission of an HBA1/HBA2 deletion from each parent.
CONCLUSIONS:
Our results suggest that preimplantation whole genome prediction may facilitate the comprehensive diagnosis of diseases with a known genetic basis in embryos.
| EGAS00001001020 | EGA
Project description:Currently, in vitro fertilization (IVF) is one of the most common approaches towards treating infertility. However, the success of this approach is still relatively low an the outcome of the IVF procedure is challenging to predict. At present, there is no highly successful marker that could reliably predict the pregnancy outcome in the process of assisted reproduction (AR). Currently, multiple embryo transfers are performed to warrant a successful pregnancy outcome, but this commonly results in multiple pregnancies, narrowing the feasibility of this method for a subset of couples affected by infertility. Recently IVF cycles with single-embryo transfers have become an option of interest in AR approaches. Such cycles, however, are significantly less successful and for this reason, there is an incentive to improve the pregnancy chance per IVF cycle by incorporating more criteria for selection of the embryo with the highest implantation potential. Gene expression in follicular cells, including granulosa cells (GC) and cumulus cells (CC) has previously been considered as a tool to predict the quality of the oocytes in several studies in addition to assessing the morphologic criteria of the embryos. Gene expression estimation in these cells, especially of the CC population, carries along several benefits as their harvesting is non-invasive, they are in direct contact with the oocyte and are usually discarded during the process of intracytoplasmatic sperm injection procedure (ICSI), making them any easily accessible surrogate tissue for gene expression analyses. Considering that several studies reporting various rates of success in prediction of AR cycle outcome with expression as a biomarker have been published, we attempted to perform the largest study of global gene expression alterations in finding novel biomarkers to outcome of in- vitro fertilization, which would encompass discovery of new biomarker genes and subsequent confirmational study of the selected biomarker set on an independent validation group. In this experiments 4 samples were hybridized twice, to allow for inspection of technical validity of microarray experiments.
2014-12-31 | GSE55654 | GEO
Project description:Background and aims: As genome sequencing technologies rapidly expand in capacity and availability, understanding how genetic background in different populations modifies IBD risk will be an important factor in disease prediction, prevention, and treatment. However, most of the datasets that are used to generate polygenic risk scores (PRS) contain predominantly European ancestry patients. To address this, we tested different models for prediction of IBD cases using PRS built using association data from multiple races and also assessed the penetrance of rare very early onset IBD (VEOIBD) SNPs. Methods: PRS were calculated using association data from European, African American, and Ashkenazi Jewish (AJ) studies, as well as a meta-GWAS run using all three association datasets. PRS were then combined using regression modelling to assess which combination of scores was best able to predict IBD status in European, AJ, Hispanic, and African American BioMe Biobank populations. Additionally, rare variants were assessed in genes associated with very early onset IBD, taking into account genetic penetrance in each BioMe population, deleteriousness, and evolutionary conservation. Results: Combining risk scores based on IBD association results from multiple racial populations resulted in improved IBD prediction for every population in BioMe. We also identified highly penetrant rare variants in previously established VEOIBD genes which were predicted to be deleterious, including SNPs in established risk genes such as NOD2 as well as novel variants, including some in LRBA which appear to be particularly relevant for risk of IBD in African Americans.
2021-04-07 | GSE150516 | GEO
Project description:The efficiency of somatic cell nuclear transfer (scNT) for production of viable offspring is relatively low as compared to in vitro fertilization (IVF), presumably due to deficiencies in epigenetic reprogramming of the donor cell genome. Such defects may also involve the population of small non-coding RNAs (sncRNAs), which are important during early embryonic developmeNT.The objective of this study was to examine dynamic changes in relative abundance of sncRNAs during the maternal-to embryonic transition (MET) in bovine embryos produced by scNT as compared to IVF by using RNA sequencing. When comparing populations of miRNA in scNT versus IVF embryos, only miR-2340, miR-345, and miR34a were differentially expressed in morulae, though many more miRNAs were differentially expressed when comparing across developmental stages. Also of interest, distinct populations of piwi-interacting like RNAs (pilRNAs) were identified in bovine embryos prior to and during embryonic genome activation (EGA) as compared bovine embryos post EGA and differentiated cells. Overall, sncRNA sequencing analysis of preimplantation embryos revealed largely similar profiles of sncRNAs for IVF and scNT embryos at the 2-cell, 8-cell, morula and blastocyst stages of developmeNT.However, these sncRNA profiles, including miRNA, piRNA and tRNA fragments, were notably distinct prior to and after completion of the MET.
2021-06-18 | GSE178437 | GEO
Project description:We develop a non-invasive method for comprehensive characterization of the extracellular RNAs (exRNA) in a single droplet of spent media that was used to culture human in vitro fertilization (IVF) embryos. We generate and provide as a resource the temporal extracellular transcriptome atlas of human preimplantation development (TETA). TETA consists of 245 exRNA sequencing datasets, corresponding to 245 collections of spent media at five developmental stages.
2023-11-14 | GSE227442 | GEO
Project description:Transcriptome analysis of mouse embryonic stem cell lines derived from embryos cultured in optimal and suboptimal conditions compared to cell lines derived from control embryos. The use of assisted reproductive technologies (ART) such as in vitro fertilization (IVF) has resulted in the birth of more than 5 million children. While children conceived by these technologies are generally healthy, there is conflicting evidence suggesting an increase in adult-onset complications like glucose intolerance and high blood pressure in IVF children. Animal models indicate similar potential risks. It remains unclear what molecular mechanisms may be operating during in vitro culture to predispose the embryo to these diseases. One of the limitations faced by investigators is the paucity of the material in the preimplantation embryo to test for molecular analysis. To address this problem, we generated mouse embryonic stem cells (mESC) from blastocysts conceived after natural mating (mESCFB) or after IVF, using optimal (KSOM + 5% O2; mESCKAA) and suboptimal (Whitten’s Medium, + 20% O2, mESCWM) conditions.
2015-03-31 | GSE63821 | GEO