Project description:The 16p11.2 is the most common copy number variant (CNV) associated with Autism Spectrum Disorder (ASD). We used patient-derived cerebral organoids to investigate neurodevelopmental pathways dysregulated by dosage changes of 16p11.2 CNV. To investigate molecular dysregulation in DEL and DUP organoids, we carried out RNA sequencing and Tandem Mass Tag mass spectrometry (TMT-MS) on 1-month and 3-month organoids from the same samples. In proteomic analyses, we quantified a total of 6126 proteins in 1-month and 5481 proteins in 3-month organoids, with 13 and 11 proteins from within 16p11.2 CNV, respectively. Transcriptomic and proteomic profiling of organoids identifies the key drivers of functional effect by 16p11.2 CNV during neocortical development.
Project description:The absence of meiosis and sex are expected to lead to mutation accumulation in asexual (apomictic) plants. We have performed a double-validated analysis of copy number variation (CNV) on 10 biological replicates each of diploid sexual and diploid apomictic Boechera using a high-density (>700K) custom microarray, in order to compare mutation accumulation in the form of CNV between the transcribing regions of their genomes. The Boechera genome demonstrated higher levels of depleted compared to enriched CNV, irrespective of reproductive mode. Genome-wide patterns of CNV revealed four divergent lineages, three of which were characterized by both sexual and apomictic genotypes. Hence genome-wide CNV is reflective of at least 3 independent origins (i.e. expression) of apomixis from different sexual genetic backgrounds. CNV distributions for different families of transposable elements (TEs) were lineage specific, and a trend for enrichment in LINE/L1 and LTR/Copia elements in lineage 3 apomicts is consistent with sex and meiosis being mechanisms for purging genomic parasites. We hypothesize that significant overrepresentation of specific gene ontology classes (e.g. pollen-pistil interaction) in apomicts implies that gene enrichment could be an adaptive mechanism for genome stability in diploid apomicts by providing a polyploid-like system for buffering the effects of deleterious mutations.
Project description:Copy number variations (CNVs) at 7q11.23 cause Williams-Beuren (WBS) and 7q microduplication syndromes (7Dup), two neurodevelopmental disorders with shared and opposite cognitive-behavioral phenotypes. Using patient-derived and isogenic neurons, we integrated transcriptomics, translatomics and proteomics to elucidate the molecular underpinnings of this dosage effect. We found that 7q11.23 CNVs cause opposite alterations in neuronal differentiation and neuronal excitability. Here, the 7q11.23 CNV altered proteome in iPSC differentiating neurons was measured by a fast SWATH-MS method.
Project description:Copy number variations (CNVs) are abundant, possibly variable among populations, and can confer various phenotypic variations such as risk to complex disease. We determined a genome-wide high resolution SNP/CNV haplotype structure of Asians, by analyzing a collection of complete hydatidiform moles (CHMs) of Japanese, using high-density DNA arrays. CHMs are tissues carrying duplicated haploid genomes that originated from single sperm, and have advantages as materials over conventional diploid cells in detecting CNVs by hybridization, because greater S/N ratios are expected, and overlapping CNV segments are independently detected without being bothered by possible heterozygous situations. Overall occupancy of CNV segments per haploid found here was at a level similar to previous reports. Approximately a half of our polymorphic CNV regions have not been described in the previous report for Asians, but the frequencies of most of these new CNV regions were low. The limited number of examined samples is likely to be the reason that they have escaped detection in the previous report. Many common CNV regions are resolvable to clusters of CNV segmets (that is, CNV events) on the basis of mutual overlap of the segments. The similarity of haplotype backgrounds surrounding different CNV events within the same CNV regions suggests that ancestral recurrences of CNV events were predominantly haplotype preferential.
Project description:Copy number variations (CNVs) are abundant, possibly variable among populations, and can confer various phenotypic variations such as risk to complex disease. We determined a genome-wide high resolution SNP/CNV haplotype structure of Asians, by analyzing a collection of complete hydatidiform moles (CHMs) of Japanese, using high-density DNA arrays. CHMs are tissues carrying duplicated haploid genomes that originated from single sperm, and have advantages as materials over conventional diploid cells in detecting CNVs by hybridization, because greater S/N ratios are expected, and overlapping CNV segments are independently detected without being bothered by possible heterozygous situations. Overall occupancy of CNV segments per haploid found here was at a level similar to previous reports. Approximately a half of our polymorphic CNV regions have not been described in the previous report for Asians, but the frequencies of most of these new CNV regions were low. The limited number of examined samples is likely to be the reason that they have escaped detection in the previous report. Many common CNV regions are resolvable to clusters of CNV segmets (that is, CNV events) on the basis of mutual overlap of the segments. The similarity of haplotype backgrounds surrounding different CNV events within the same CNV regions suggests that ancestral recurrences of CNV events were predominantly haplotype preferential.
Project description:The genomic DNA sample of hPGES were compared to UCSC Human genome19 by CNV data. The data confirmed that the human parthenogenetic haploid ESCs sustained normal genome integrity