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Series GSE60607 Query DataSets for GSE60607
Status Public on Oct 24, 2014
Title Affymetrix SNP 6.0 data for individuals with Trisomy 21 or Down syndrome
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Individuals with Down syndrome (DS) are at an increased risk for developing congenital heart defects especially atrioventricular septal defects (AVSD). Our goal was to identify the contribution of copy number variants (CNV) to DS-associated AVSD. We used the Affymetrix SNP 6.0 genotyping platform to comprehensively characterize CNVs in 452 ethnically matched individuals with DS, comprising of 210 cases (DS + complete AVSD) and 242 controls with a structurally normal heart (DS + NH). Results from burden and region-wise analyses using PLINK revealed that despite the 2000 fold elevated risk, common CNVs of large effect (OR > 2.0) do not account for the increased risk observed in DS-associated AVSD. In contrast, cases do harbor a significantly elevated burden of large rare variants (> 100kb, < 1% frequency) (p < 0.01) and case deletions intersect genes more often than those observed in controls (p < 0.007). Gene enrichment analysis showed a trend for enrichment among deletions impacting the ciliome pathway in cases compared to controls. Our findings suggest that the etiology of AVSD is highly complex and does not arise from the action of a few common variants of large effect. Instead, our data support a multifactorial model, wherein large rare deletions play a significant role in elevating the risk of AVSD in a trisomic background.
 
Overall design Copy Number Variation Analysis of individuals with DS using Affymetrix SNP 6.0 genotyping platform. A composite reference was generated using the same dataset to derive the log2 ratios using Affymetrix Power Tols (APT). Submitting here the preliminary data from 437 subjects, 15 were excluded due to privacy concerns.
 
Contributor(s) Zwick ME
Citation(s) 25341113, 26194203, 33093519
Submission date Aug 21, 2014
Last update date Oct 27, 2020
Contact name Michael Edward Zwick
E-mail(s) mzwick@emory.edu
Phone 404-727-9924
Organization name Emory University School of Medicine
Department Human Genetics
Lab Zwick
Street address 615 Michael Street, Suite 301
City Atlanta
State/province GA
ZIP/Postal code 30322
Country USA
 
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (437)
GSM1483196 Lymphoblastoid cell line Down Syndrome sample1
GSM1483197 Lymphoblastoid cell line Down Syndrome sample2
GSM1483198 Lymphoblastoid cell line Down Syndrome sample3
Relations
BioProject PRJNA259223

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60607_RAW.tar 25.4 Gb (http)(custom) TAR (of CEL, TXT)
Processed data provided as supplementary file

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