EXPERIMENT_TITLE: GSM8248707: IPSCs, control, Hi-C; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Genomic DNA of cells was crosslinked in situ using serum-free DMEM with 2% formaldehyde and then were flash-frozen in liquid nitrogen before digested. The crosslinked cells were lysed and digested with MboI restriction enzyme. After biotinylated and ligated, the fragments were purified and assessed for quality. The qualified samples were reverse crosslinked and then submitted for library constructions. Standard library constructions were performed, including sonication fragment, end repair, A-tailing, biotin enrichment, adapter ligation, and amplification.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression. Overall design: High-throughput chromosome conformation capture (Hi-C) for three dimensional genome structure in the induced pluripotent stem cells (iPSCs) from one patient and one normal control.
SAMPLE_TITLE: IPSCs, control, Hi-C
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Peripheral blood"}, {"TAG": "tissue", "VALUE": "Peripheral blood"}, {"TAG": "cell line", "VALUE": "IPSCs"}, {"TAG": "cell type", "VALUE": "IPSCs"}, {"TAG": "genotype", "VALUE": "normal"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: IPSCs, control, Hi-C
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