Comment[ArrayExpressAccession]	E-GEOD-49045
MAGE-TAB Version	1.1										
Public Release Date	2013-07-19
Investigation Title	Genome-wide SNP analysis of the Systemic Capillary Leak Syndrome (Clarkson disease)										
Comment[Submitted Name]	Genome-wide SNP analysis of the Systemic Capillary Leak Syndrome (Clarkson disease)
Experiment Description	The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare, orphan disease that resembles systemic anaphylaxis. The disorder is characterized by repeated, transient, and seemingly unprovoked episodes of hypotensive shock and peripheral edema due to transient endothelial hyperpermeability. SCLS is often accompanied by a monoclonal gammopathy of unknown significance (MGUS). Using Affymetrix Single Nucleotide Polymorphism (SNP) microarrays, we performed the first genome-wide SNP analysis of SCLS in a cohort of 12 disease subjects and 18 controls. Exome capture sequencing was performed on genomic DNA from nine of these patients as validation for the SNP-chip discoveries and de novo data generation. We identified candidate susceptibility loci for SCLS, which included a region flanking CAV3 (3p25.3) as well as SNP clusters in PON1 (7q21.3), PSORS1C1 (6p21.3), and CHCHD3 (7q33). Among the most highly ranked discoveries were gene-associated SNPs in the uncharacterized LOC100130480 gene (rs6417039, rs2004296). Top case-associated SNPs were observed in BTRC (rs1235580, 3rs4436485), ARHGEF18 (rs11668246), CDH13 (rs4782779), and EDG2 (rs12552348), which encode proteins with known or suspected roles in B cell function and/or vascular integrity. SNPs that were significantly associated with SCLS by microarray analysis were also detected and validated by exome deep sequencing. Functional annotation of highly ranked SNPs revealed enrichment of cell projections, cell junctions and adhesion, and molecules containing pleckstrin homology, Ras/Rho regulatory, and immunoglobulin Ig-like C2/fibronectin type III domains, all of which involve mechanistic functions that correlate with the SCLS phenotype. These results highlight SNPs with potential relevance to SCLS. Our study cohort included 12 patients with SCLS. The control group included 17 age, sex and ethnicity-matched healthy donors (including two relatives of SCLS patients), and a reference sample  supplied by the SNP-chip manufacturer (Affymetrix), for which age information was not available. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from purified B lymphocytes.										
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl									
Person Last Name	Nagarajan	Xie	Nagarajan	Sturdevant	Iwaki	Chan	Wisch	Young	Nelson	Porcella	Druey
Person First Name	Vijayaraj	Zhihui	Vijayaraj	Daniel	Shoko	Eunice	Laura	Michael	Celeste	Stephen	Kirk
Person Mid Initials				E						F	M
Person Email	geo@ncbi.nlm.nih.gov										
Person Affiliation	NIAID/NIH										
Person Address	OCICB, NIAID/NIH, 31 Center Drive, Bethesda, Maryland, USA										
Person Roles	submitter										
Protocol Name	P-GSE49045-1	P-GSE49045-5	P-GSE49045-6	P-GSE49045-2	P-GSE49045-3	P-GSE49045-4	P-GSE49045-7				
Protocol Description	Quality analysis was performed by importing the CEL files into Genotyping Console (GTC 4.0) according to the “Quality Control Assessment 123 in Genotyping Console” primary data description: #SNP List=KMD_2_33S_99 primary data description: #GenomeWideSNP_6.na31.annot.db primary data description: #%genome-version-ucsc=hg19 primary data description: #%genome-version-ncbi=GRCh37 ID_REF =  VALUE = Genotype Call (SNP call): AA, AB, BB, NC, and NoCall Forward_Strand_Base_Calls = 	As per manufacturer (Affymetrix)	As per manufacturer (Affymetrix)	none	B cells were isolated from peripheral blood during flow sorting using anti-CD19 antibody (BD Biosciences)	DNA targets from patients and healthy controls were prepared and hybridized to Affymetrix Genome-Wide Human SNP array 6.0 chips following the manufacturer’s recommendations.	As per manufacturer (Affymetrix)				
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	growth protocol	nucleic acid extraction protocol	array scanning protocol				
Experimental Factor Name	DIAGNOSIS	SEX									
Experimental Factor Type	diagnosis	sex									
Comment[SecondaryAccession]	GSE49045										
Comment[GEOReleaseDate]	2013-07-19										
Comment[ArrayExpressSubmissionDate]	2013-07-19										
Comment[GEOLastUpdateDate]	2013-07-21										
Comment[AEExperimentType]	genotyping by array										
SDRF File	E-GEOD-49045.sdrf.txt