Homo sapiens
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PROVIDER: PRJNA124475 | ENA |
REPOSITORIES: ENA
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Project description:Many studies estimate that chromosomal mosaicism within the cleavage stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism is overestimated due to technical inconsistency rather than biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques.Thirteen arrested cleavage stage embryos were studied. Each was biopsied into individual cells (n=160). The cells from each embryo were randomized into two groups. Those destined for FISH based aneuploidy screening (n=75) were fixed, 1 cell per slide. Cells for SNP microarray based aneuploidy screening (n=85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P=0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (4 of 13 embryos; 31%) than by FISH (13 of 13 embryos; 100%)(P=0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2+0.2) than microarray (1.3+0.2)(P<0.0001). This is the first prospective, randomized, blinded, and paired comparison between microarray and FISH based aneuploidy screening. Aneuploidy and mosaicism were less common with microarray. While evaluating a smaller number of chromosomes with a proportionally smaller opportunity for finding mosaicism, FISH still had a dramatically higher level of inter-cell variation in diagnosis. SNP microarray based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH.
2010-05-19 | GSE20975 | GEO
Project description:Many studies estimate that chromosomal mosaicism within the cleavage stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism is overestimated due to technical inconsistency rather than biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques.Thirteen arrested cleavage stage embryos were studied. Each was biopsied into individual cells (n=160). The cells from each embryo were randomized into two groups. Those destined for FISH based aneuploidy screening (n=75) were fixed, 1 cell per slide. Cells for SNP microarray based aneuploidy screening (n=85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P=0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (4 of 13 embryos; 31%) than by FISH (13 of 13 embryos; 100%)(P=0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2+0.2) than microarray (1.3+0.2)(P<0.0001). This is the first prospective, randomized, blinded, and paired comparison between microarray and FISH based aneuploidy screening. Aneuploidy and mosaicism were less common with microarray. While evaluating a smaller number of chromosomes with a proportionally smaller opportunity for finding mosaicism, FISH still had a dramatically higher level of inter-cell variation in diagnosis. SNP microarray based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. Affymetrix SNP arrays were processed according to the manufacturer's directions on DNA extracted from 13 arrested cleavage stage embryos and biopsied into individual blastomere cells. Individual blastomeres were randomized and blinded for SNP microarray analysis (n = 85). Afflymetrix SNP array analysis was successfully completed on 82 blastomeres.
2010-06-09 | E-GEOD-20975 | biostudies-arrayexpress
Project description:Preimplantation genetic diagnosis (PGD) of aneuploidy by fluorescence in situ hybridisation (FISH) has not delivered the expected clinical benefit. Many previous re-analysis studies of embryos deemed aneuploid by FISH on day 3 have found a high degree of chromosomal normalcy at the blastocyst stage. While most have interpreted this as “self correction,” there remains a lack of evidence for such a phenomenon. A more comprehensive technique for 24 chromosome aneuploidy screening was utilised here to re-evaluate blastocysts previously diagnosed as abnormal by FISH and investigate possible self correction mechanisms, including extrusion or duplication of aneuploid chromosomes resulting in uniparental isodisomy (UPID), and preferential segregation of aneuploidy to the trophectoderm (TE). Embryos that developed to a morphologically normal blastocyst after an aneuploidy diagnosis by cleavage stage FISH were biopsed into 4 sections, 3 TE and 1 inner cell mass (ICM), and randomised for evaluation by single nucleotide polymorphism (SNP) microarray based 24 chromosome aneuploidy screening (MA-PGD). Fifty-eight percent of blastocysts were euploid for all 24 chromosomes despite an aneuploid FISH result on day 3. Only 18% were consistent with the original FISH diagnosis, while the remaining 24% identified abnormalities that were different from the original FISH diagnosis. Abnormalities did not preferentially segregate to the TE and aneuploid chromosome extrusion or duplication resulting in UPID did not occur. Cleavage stage FISH is poorly predictive of aneuploidy in an embryo that develops into a morphologically normal blastocyst. Clinicians should consider re-evaluating embryos diagnosed as aneuploid by FISH that form morphologically normal blastocysts using a validated comprehensive 24 chromosome aneuploidy screening method.
2010-05-19 | GSE18932 | GEO
Project description:Preimplantation genetic diagnosis (PGD) of aneuploidy by fluorescence in situ hybridisation (FISH) has not delivered the expected clinical benefit. Many previous re-analysis studies of embryos deemed aneuploid by FISH on day 3 have found a high degree of chromosomal normalcy at the blastocyst stage. While most have interpreted this as âself correction,â there remains a lack of evidence for such a phenomenon. A more comprehensive technique for 24 chromosome aneuploidy screening was utilised here to re-evaluate blastocysts previously diagnosed as abnormal by FISH and investigate possible self correction mechanisms, including extrusion or duplication of aneuploid chromosomes resulting in uniparental isodisomy (UPID), and preferential segregation of aneuploidy to the trophectoderm (TE). Embryos that developed to a morphologically normal blastocyst after an aneuploidy diagnosis by cleavage stage FISH were biopsed into 4 sections, 3 TE and 1 inner cell mass (ICM), and randomised for evaluation by single nucleotide polymorphism (SNP) microarray based 24 chromosome aneuploidy screening (MA-PGD). Fifty-eight percent of blastocysts were euploid for all 24 chromosomes despite an aneuploid FISH result on day 3. Only 18% were consistent with the original FISH diagnosis, while the remaining 24% identified abnormalities that were different from the original FISH diagnosis. Abnormalities did not preferentially segregate to the TE and aneuploid chromosome extrusion or duplication resulting in UPID did not occur. Cleavage stage FISH is poorly predictive of aneuploidy in an embryo that develops into a morphologically normal blastocyst. Clinicians should consider re-evaluating embryos diagnosed as aneuploid by FISH that form morphologically normal blastocysts using a validated comprehensive 24 chromosome aneuploidy screening method. Affymetrix SNP arrays were processed according to the manufacturer's directions on DNA extracted from 50 cryopreserved blastocysts that were biopsied into 3 sections of trophectoderm and 1 inner cell mass section. Affymetrix SNP array analysis was successfully completed on 145 trophectoderm samples and 47 ICM samples from embryos, 8 lymphocyte samples from cell lines and 6 mixed male and female samples.
2010-05-19 | E-GEOD-18932 | biostudies-arrayexpress
Project description:SNP microarray based 24 chromosome aneuploidy screening demonstrates that cleavage stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts
| PRJNA121043 | ENA
Project description:Aneuploidy has been well documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening (PGS) in a 24-hour protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy, and distinguishes certain meiotic from mitotic errors. In this study our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from seventeen couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e., one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of fifty-one (96.1%) inner cell mass (ICM) samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that trophectoderm karyotype is an excellent predictor of inner cell mass karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations.
2010-09-28 | GSE22864 | GEO
Project description:A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: an integrated genomics approach reveals a wide dosage effect on gene and microRNA expression Multiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM. Keywords: Integrated genomics approach based on SNP microarray and FISH procedures to detect allelic imbalances in multiple myeloma.
2009-05-16 | GSE16121 | GEO
Project description:This was a retrospective comparison study of SNP-based preimplantation genetic screening (SNP-PGS) and FISH-based preimplantation genetic diagnosis (FISH-PGD) for 575 couples in total with chromosome translocations, including 169 couples treated by SNP-PGS between October 2011 and August 2012, and 406 couples treated by FISH- PGD between January 2005 and October 2011. In total, 773 blastocysts obtained from 169 couples were biopsied and frozen, embryo transfer was carried out on the balanced embryos. The PGS results and pregnancy outcomes were compared with those of FISH-PGD for 406 translocation carriers with 3,968 embryos biopsied on day 3. Of the 773 biopsied blastocysts, reliable SNP-PGS results were obtained for 717 (92.76%). For Robertsonian translocation carriers, the rate of normal/balanced embryos, embryos with translocation-related abnormalities, and embryos with abnormalities unrelated to a translocation were 57.80%, 23.39% and 18.81%, respectively. In reciprocal translocation carriers, the rate of normal/balanced embryos, embryos with translocation-related abnormalities and embryos with abnormalities unrelated to translocation were 35.47%, 52.10% and 12.42%, respectively. There was no significant differences in patient age, basal endocrine level and the average number of retrieved oocytes and good quality day 3 embryos before biopsy in the SNP-PGS group compared with the FISH-PGD group. The number of embryos biopsied in the FISH-PGD group was higher than in the SNP-PGS group. However, the pregnancy rate with successful delivery per oocyte retrieval and the implantation rate were both lower in the FISH-PGD group than in the SNP-PGS group. The spontaneous abortion rate was higher in the FISH-PGD group than in the SNP-PGS group.
2013-03-11 | GSE44994 | GEO
Project description:With the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by CMA.This retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n=55) and complex group (n=76) according to structural anomalies.Among the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis.SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group. The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant.Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities.Fetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE.
2023-10-22 | GSE230532 | GEO
Project description:Multiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM. Keywords: Integrated genomics approach based on SNP microarray and FISH procedures to detect allelic imbalances in multiple myeloma.
2009-04-14 | GSE13591 | GEO