Jan_Friedman_20150805 - samples
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ABSTRACT:
PROVIDER: EGAD00001001467 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:We designed a microarray to test at exonic resolution for genomic imbalance for genes representative of all known chromosomal microdeletion/microduplication syndromes, all known causative genes for ID, all known genes encoding glutamate receptors and their known encoding proteins and all known genes encoding proteins with epigenetic regulatory function. We found 36 de novo copy number variants affecting 35 children in this study. 167 trios, each comprising an affected child and both its normal parents were analyzed by conducting two comparative hybridizations; child vs. mother and child vs. father, and only selecting a CNV if it appeared in both hybridizations, i.e., was de novo. De novo CNVs were independantly validated using quantitative PCR.
2012-07-23 | E-GEOD-39533 | biostudies-arrayexpress
Project description:Clinical laboratories are adopting array comparative genomic hybridization (AGH) as a standard clinical test. A number of whole genome AGH systems are available, but little is known about the comparative performance in a clinical context. We prospectively studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500K GeneChip SNP arrays, Agilent Human Genome 244K oligonucleotide arrays and NimbleGen 385K Whole-Genome oligonucleotide arrays. We determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP array. The Affymetrix 500K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosome CNVs in 30 trios. 147 of these CNVs were de novo, but only 33 (22%) of the de novo CNVs were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 pathogenic and 4 possibly pathogenic CNVs for MR. All 11 of these CNVs were detected by both the Agilent and NimbleGen arrays, 9 by the Affymetrix 500K and Illumina beadchips, and 5 by the SMRT BAC array. Two of the 4 pathogenic or possibly pathogenic CNVs present in the trios tested with the Affymetrix 6.0 array were identified. Our findings demonstrate that different results are obtained with different AGH platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls supports the need for validating clinically important findings with a different methodology. 15 trios were analysed consisting of child (proband) and both normal parents. We performed separate hybridizations for the mother, father, and child and then performed pair-wise comparisons of the normalized hybridization intensities for the child to the mother and of the child to the father in silico.
2011-02-17 | E-GEOD-27145 | biostudies-arrayexpress
Project description:The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically-detectable chromosomal abnormalities are the most frequent recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy number variants. We studied 100 children with idiopathic mental retardation and their parents using the Affymetrix GeneChip® Mapping 100K Assay and found de novo duplications as small as 1.1 Mb in three cases, de novo deletions as small as 178 kb in eight cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy number variants as conventional cytogenetic analysis in people with mental retardation. Experiment Overall Design: Using the Affymetrix GeneChip® Mapping 100K Assay we studied 100 trios that each included one child with idiopathic mental retardation (MR) and both of his/her unaffected biological parents. We also tested 10 unaffected siblings of the MR children from 10 of the above families. In addition, we analyzed 7 trios (child and both unaffected biological parents) as positive controls with previously identified chromosomal aberrations. Experiment Overall Design: Within each sample ID the four digit number refers to a family. Following this four digit family number, 'c' indicates child with MR, 'm' means unaffected mother, 'f' means unaffected father and 's' means unaffected sibling.
2008-06-21 | E-GEOD-7226 | biostudies-arrayexpress
Project description:Clinical laboratories are adopting array comparative genomic hybridization (AGH) as a standard clinical test. A number of whole genome AGH systems are available, but little is known about the comparative performance in a clinical context. We prospectively studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500K GeneChip SNP arrays, Agilent Human Genome 244K oligonucleotide arrays and NimbleGen 385K Whole-Genome oligonucleotide arrays. We determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP array. The Affymetrix 500K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosome CNVs in 30 trios. 147 of these CNVs were de novo, but only 33 (22%) of the de novo CNVs were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 pathogenic and 4 possibly pathogenic CNVs for MR. All 11 of these CNVs were detected by both the Agilent and NimbleGen arrays, 9 by the Affymetrix 500K and Illumina beadchips, and 5 by the SMRT BAC array. Two of the 4 pathogenic or possibly pathogenic CNVs present in the trios tested with the Affymetrix 6.0 array were identified. Our findings demonstrate that different results are obtained with different AGH platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls supports the need for validating clinically important findings with a different methodology. 45 trios were analysed consisting of child (proband) and both normal parents.
2011-02-17 | E-GEOD-27216 | biostudies-arrayexpress
Project description:Clinical laboratories are adopting array comparative genomic hybridization (AGH) as a standard clinical test. A number of whole genome AGH systems are available, but little is known about the comparative performance in a clinical context. We prospectively studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500K GeneChip SNP arrays, Agilent Human Genome 244K oligonucleotide arrays and NimbleGen 385K Whole-Genome oligonucleotide arrays. We determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP array. The Affymetrix 500K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosome CNVs in 30 trios. 147 of these CNVs were de novo, but only 33 (22%) of the de novo CNVs were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 pathogenic and 4 possibly pathogenic CNVs for MR. All 11 of these CNVs were detected by both the Agilent and NimbleGen arrays, 9 by the Affymetrix 500K and Illumina beadchips, and 5 by the SMRT BAC array. Two of the 4 pathogenic or possibly pathogenic CNVs present in the trios tested with the Affymetrix 6.0 array were identified. Our findings demonstrate that different results are obtained with different AGH platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls supports the need for validating clinically important findings with a different methodology. 30 trios were analysed consisting of child (proband) and both normal parents.
2011-02-17 | E-GEOD-27251 | biostudies-arrayexpress
Project description:Clinical laboratories are adopting array comparative genomic hybridization (AGH) as a standard clinical test. A number of whole genome AGH systems are available, but little is known about the comparative performance in a clinical context. We prospectively studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500K GeneChip SNP arrays, Agilent Human Genome 244K oligonucleotide arrays and NimbleGen 385K Whole-Genome oligonucleotide arrays. We determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP array. The Affymetrix 500K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosome CNVs in 30 trios. 147 of these CNVs were de novo, but only 33 (22%) of the de novo CNVs were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 pathogenic and 4 possibly pathogenic CNVs for MR. All 11 of these CNVs were detected by both the Agilent and NimbleGen arrays, 9 by the Affymetrix 500K and Illumina beadchips, and 5 by the SMRT BAC array. Two of the 4 pathogenic or possibly pathogenic CNVs present in the trios tested with the Affymetrix 6.0 array were identified. Our findings demonstrate that different results are obtained with different AGH platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls supports the need for validating clinically important findings with a different methodology. 30 trios were analysed consisting of child (proband) and both normal parents.
2011-02-17 | E-GEOD-27229 | biostudies-arrayexpress
Project description:This is array CGH data of recurrent 17q21.31 deletions used to delineate breakpoints within segmental duplications in a study by Itsara et al. Somatic cell hybrids were generated from three parent-child trios probands with 17q21.31 deletions and three 17q21.31 probands for which no parental DNA was available that isolated individual chromosome 17 homologues. In parents, this isolated the H2 from the H1 haplotypes in distinct cell lines, and in probands, isolated the deletion-bearing chromosomes from the unaffected chromosome 17. In parent-child trios, the deletion-bearing chromosomes were hybridized against the progenitor parental chromosome. In probands with no parental DNA, the deletion-bearing chromosomes were hybridized against an H2 chromosome.
2012-06-02 | GSE34867 | GEO
Project description:Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a functional association study (pathway-based analysis) has been conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung's disease that have been further validated in a larger population of 146 trios. The study revealed a strong association of 10 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes to the disease. A total of 10 new loci among the preselected candidates were found to be significantly associated to HSCR. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases. DNA derived from peripheral blood was hybridized to Affymetrix GeneChip® 500K mapping arrays. In total, 53 trios were analyzed consisting of affected child and their unaffected parents.
2012-03-18 | E-GEOD-33732 | biostudies-arrayexpress
Project description:This is array CGH data of recurrent 17q21.31 deletions used to delineate breakpoints within segmental duplications in a study by Itsara et al. Somatic cell hybrids were generated from three parent-child trios probands with 17q21.31 deletions and three 17q21.31 probands for which no parental DNA was available that isolated individual chromosome 17 homologues. In parents, this isolated the H2 from the H1 haplotypes in distinct cell lines, and in probands, isolated the deletion-bearing chromosomes from the unaffected chromosome 17. In parent-child trios, the deletion-bearing chromosomes were hybridized against the progenitor parental chromosome. In probands with no parental DNA, the deletion-bearing chromosomes were hybridized against an H2 chromosome. 6 experimental hybes of deletion-bearing proband vs H2 chromosome reference. 3 control hybes of H1 vs H2 haplotype, H2 vs H2 haplotype (different individuals), and H1 vs deletion-bearing H2 haplotype.
2012-06-01 | E-GEOD-34867 | biostudies-arrayexpress
Project description:This is the validation data for candidate de novo CNV calls made in the asthma trios by Itsara et al., Genome Research 2010. In this study, de novo CNV calls in the asthma data set were initially made with Illumina 550K SNP arrays. Validation was performed with custom Nimblegen array CGH for which DNA was available. de novo CNVs would be expected to validate in the child of each trio tested, and not be detected in either parent.
2010-09-01 | GSE23572 | GEO