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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:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. This study represents one child-parent trio (case 3) test for (de novo) copy number variants in the child.
2015-01-31 | E-GEOD-65453 | biostudies-arrayexpress