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| Status |
Public on Jul 11, 2012 |
| Title |
Genomic copy-number analysis in Alveolar capillary dysplasia (ACD) patient samples |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
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.
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| Overall design |
CNVs were identified by array CGH using 4.2M whole genome tiling arrays from Nimblegen in 3 ACD patients
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| Contributor(s) |
Kolodziejska KE, Szafranski P |
| Citation missing |
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| Submission date |
Jul 11, 2012 |
| Last update date |
Jul 11, 2012 |
| Contact name |
Pawel Stankiewicz |
| E-mail(s) |
pawels@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Molecular Human Genetics
|
| Street address |
One Baylor Plaza
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL15746 |
NimbleGen Human CGH 4.2M Whole-Genome Tiling Array v1.0 array [100710_HG19_WG_CGH_v1.0_UX1] |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE39258 |
Small non-coding differentially-methylated copy-number variants, involving lncRNAs, cause a lethal lung developmental disorder |
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| Relations |
| BioProject |
PRJNA170424 |
