BioProject

Genomic copy number analysis in patients with ACD/MPV. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. More...

Genomic copy number analysis in patients with ACD/MPV. 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.potentially cause many disorders of human development. CNVs were identified by array CGH with custom-designed 16q24.1 region specific (1Mb flanking FOXF1) 44K oligonucleotide microarrays (Agilent technologies) in 3 patients with ACD. This Series contains data for only two patients Overall design: custom targeted oligoarray, normal reference vs patient sample Less...