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| Status |
Public on May 01, 2012 |
| Title |
Genome-wide survey of large rare copy number variations in Alzheimer’s disease among Caribbean Hispanics |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Recently genome-wide association studies have identified significant association between Alzheimer’s disease and variations in CLU, PICALM, BIN1, CR1, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7. However, the pathogenic variants in these loci have not yet been found. We conducted a genome-wide scan for large copy number variations (CNVs) in a dataset of Caribbean Hispanic origin (554 controls and 559 cases with late-onset Alzheimer’s disease) that was previously investigated in a SNP-based genome-wide association study using Illumina HumanHap 650Y platform. We ran four CNV calling algorithms and analyzed rare large CNVs (>100 Kb) to obtain high-confidence calls that were detected by at least two algorithms. In total, 734 such CNVs were observed in our dataset. Global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications, total or average CNV size; and number of genes affected by CNVs. However, we observed a nominal association between Alzheimer’s disease and a ~470 Kb duplication on chromosome15q11.2 (P=0.037). This duplication, encompassing up to five genes (TUBGCP5, CYFIP1, NIPA2, NIPA1 and WHAMML1) was present in 10 cases (2.6%) and 3 controls (0.8%). The dosage increase of CYFIP1 and NIPA1 genes was further confirmed by quantitative PCR. The current study did not detect CNVs (including common CNVs) that affect novel Alzheimer’s disease loci reported by large genome-wide association studies. However, since the array technology used in our study has limitations in detecting small CNVs, future studies must carefully assess novel AD associated genes for the presence of disease related CNVs.
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| Overall design |
Case-control analysis, screening of large copy number variation in 559 Alzheimer cases and 554 control subjects of Caribbean Hispanic ancestry
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| Contributor(s) |
Ghani M, Pinto D, Lee JH, Grinberg Y, Sato C, Moreno D, Scherer SW, Mayeux R, St George-Hyslop P, Rogaeva E |
| Citation(s) |
22384383 |
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| Submission date |
Nov 07, 2011 |
| Last update date |
May 03, 2012 |
| Contact name |
Ekaterina Rogaeva |
| E-mail(s) |
ekaterina.rogaeva@utoronto.ca
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| Phone |
(416) 946-7927
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| Fax |
(416)-978-1878
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| Organization name |
Tanz Centre for Neurodegenerative Diseases
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| Street address |
6 Queen’s Park Crescent West
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| City |
Toronto |
| ZIP/Postal code |
M5S 3H2 |
| Country |
Canada |
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| Platforms (1) |
| GPL14932 |
Illumina HumanHap650Yv2 Genotyping BeadChip (HumanHap650Y_v2-0_GenotypingBC_11237679_A) |
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| Samples (1215)
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| Relations |
| BioProject |
PRJNA148797 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33528_RAW.tar |
13.7 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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