{"database": "metadata", "table": "run_metadata", "rows": [[50705, "SRR8244075", "SRX5062204", "SRS4078143", "SRP170713", "PRJNA506958", "Mutations in NCAPG2 cause a severe neurodevelopmental syndrome that expands the phenotypic spectrum of condensinopathies", "GSE122932", "Transcriptome Analysis", "The use of whole exome/genome sequencing has been a catalyst for a genotype first approach to diagnostics. Under this paradigm  we have implemented systematic sequencing of neonates and young children with a suspected genetic disorder. Here we report two families with recessive mutations in NCAPG2 and overlapping clinical phenotypes that include severe neurodevelopmental defects; failure to thrive; ocular abnormalities; and defects in urogenital and limb morphogenesis. NCAPG2 encodes a member of the condensin II complex  necessary for the condensation of chromosomes prior to cell division. Consistent with a causal role for NCAPG2  we found abnormal chromosome condensation  augmented anaphase chromatin bridge formation and micronuclei in daughter cells of proband skin fibroblasts. To test the functional relevance of the discovered variants  we generated an ncapg2 zebrafish model. Morphants displayed clinically relevant phenotypes  such as microcephaly and renal anomalies with concomitant increases in apoptosis and altered mitotic progression. These could be rescued by wild type but not mutant human NCAPG2 mRNA and were recapitulated in CRISPR/Cas9 F0 mutants. Finally  we noted that the individual with a complex urogenital defect also harbored a heterozygous deletion of NPHP1  a common contributor to nephronophthisis. To test whether sensitization at the NPHP1 locus might contribute to a more severe renal phenotype  we co suppressed nphp1 and ncapg2  which resulted in significantly more dysplastic renal tubules. Together  our data suggest that impaired function of NCAPG2 results in a severe condensinopathy and highlight the potential utility of examining candidate pathogenic lesions beyond the primary disease locus. Overall design: To investigate the global impact of NCAPG2 loss in an in vivo developmental context  we performed transcriptome profiling of zebrafish embryo heads isolated at 2 dpf injected with gRNA1 alone or gRNA1+Cas9; 5 biological replicates", null, "pubmed:30609410", null, "phenol red rep2", "GSM3488830", null, "source name:embryo head|tissue:embryo head|time point:2 dpf red", "phenol red rep2", "Data were demultiplexed and Fastq files generated using Bcl2Fastq Illumina. RNAseq data were processed with the TrimGalore toolkit which employs Cutadapt to trim low quality bases and sequencing adapters from 3\u2019 ends of the reads. Only reads > 20nt post trimming were kept. Reads were mapped to the Zv10r87 version of the zebrafish genome and transcriptome using the STAR RNA seq alignment tool. Gene counts were compiled using the HTSeq tool. Only genes that had >10 reads were used in subsequent analysis. Normalization and differential expression were carried out with the DESeq2 Bioconductor38 package with the R statistical programming environment. Genome build: Zv10r87 Supplementary files format and content: Excel file include RPKM values for each Sample", "embryo head", null, "We extracted total RNA from embryo heads with Trizol ThermoFisher  according to manufacturer's instructions. N=20 embryos/pool RNAseq libraries were prepared using the Stranded mRNA Seq Kit KAPA following the manufacturer\u2019s protocol. In brief  mRNA transcripts were captured using magnetic oligo dT beads  fragmented with heat and magnesium  and reverse transcribed with random primers. Illumina sequencing adapters were ligated to dscDNA fragments and amplified to produce RNA seq libraries. Libraries were dual indexed; fragment length distribution and QC was assessed on a 2100 Bioanalyzer using the High Sensitivity DNA Kit Agilent Technologies. All libraries were pooled in equimolar ratio 5 libraries/lane and sequenced on an Illumina HiSeq 4000 flow cell to yield 66 million 50 bp single end sequences per sample.", "Embryos were obtained from natural matings of adult wild type zebrafish that were maintained on a 14h/10h light/dark cycle. Embryos were reared in embryo media 0.3 g/L NaCl  75 mg/L CaSO4  37.5 mg/L NaHC03  0.003% methylene blue at 28\u00b0C until 2 dpf.", "tissue:embryo head|time point:2 dpf red", "GSM3488830", "GSM3488830: phenol red rep2; Danio rerio; RNA Seq", "GSM3488830", null, "1", "We extracted total RNA from embryo heads with Trizol ThermoFisher  according to manufacturer's instructions. N=20 embryos/pool RNAseq libraries were prepared using the Stranded mRNA Seq Kit KAPA following the manufacturer's protocol. In brief  mRNA transcripts were captured using magnetic oligo dT beads  fragmented with heat and magnesium  and reverse transcribed with random primers. Illumina sequencing adapters were ligated to dscDNA fragments and amplified to produce RNA seq libraries. Libraries were dual indexed; fragment length distribution and QC was assessed on a 2100 Bioanalyzer using the High Sensitivity DNA Kit Agilent Technologies. All libraries were pooled in equimolar ratio 5 libraries/lane and sequenced on an Illumina HiSeq 4000 flow cell to yield 66 million 50 bp single end sequences per sample.", "GEO Accession:GSM3488830", "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "SINGLE", "ILLUMINA", "Illumina HiSeq 4000", null, "SRP170713", null, null, "4948-S2_S2_L003_R1_001.fastq.gz", "fastq", 890160681.0, 17454131.0, "GSM3488830 r3", "0:51 1:0", "A:219700893;C:215424116;G:204218333;T:250727670;N:89669", 51, 0, null, null, 219700893, 215424116, 204218333, 250727670, 89669, "SRX5062204", "SRS4078143", "SRA814826", "GEO", "Center for Human Disease Modeling, Duke University Medical Center", 1, 0.92091, null, 0.13895, null, 0.65977, null, 0.47244, null, 51, null, "B", null, "usable mapping rate", "illumina", "hiseq_era", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "United States", "2018-11-26", "Hatching", "Embryo", "Head", "Nervous System"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["50705"], "units": {}, "query_ms": 10.594079998554662}