Genomics

Dataset Information

36

Genomic copy-number analysis in Alveolar capillary dysplasia (ACD) patient samples


ABSTRACT: Non-coding copy number changes in 16q24.1 upstream of FOXF1 were identified in two patients with ACD. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. Overall design: CNVs were identified by array CGH using 4.2M whole genome tiling arrays from Nimblegen in 3 ACD patients

INSTRUMENT(S): NimbleGen Human CGH 4.2M Whole-Genome Tiling Array v1.0 array [100710_HG19_WG_CGH_v1.0_UX1]

SUBMITTER: Pawel Stankiewicz  

PROVIDER: GSE39257 | GEO | 2012-07-11

SECONDARY ACCESSION(S): PRJNA170424

REPOSITORIES: GEO

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