Unknown,Transcriptomics,Genomics,Proteomics

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CNV and LOH analysis of patient sample PN11-0204

ABSTRACT: We saw a patient who presented with respiratory distress from birth due to interstitial lung disease. Before the age of three months a diagnosis of nephrotic syndrome was made. Lung biopsy revealed pulmonary interstitial glycogenosis. Despite extensive investigations, no known genetic or infectious cause was found for the congenital nephrotic syndrome. The patient died at the age of 8 months due to respiratory failure. A 20 Mb homozygous region was identified on chromosome 17 in the patientM-bM-^@M-^Ys DNA, revealing a novel homozygous missense variant in ITGA3 gene. Genomic DNA was obtained from peripheral blood samples of the patient with interstitial lung fibrosis and nephrotic syndrome. Copy number variation (CNV) screening by means of microarray analyses was carried out on the Affymetrix GeneChip 250k (NspI) SNP array platform (Affymetrix, Inc., Santa Clara, CA, USA), which contains 25-mer oligonucleotides representing a total of 262,264 SNPs. Hybridizations were performed according to the manufacturerM-bM-^@M-^Ys protocols. Copy numbers and M-bM-^@M-^\long contiguous stretches of homozygosityM-bM-^@M-^] (LCSH/LOH) were determined using the 2.0 version of the CNAG (Copy Number Analyzer for Affymetrix GeneChip mapping) software package (Nannya Y, Sanada M, et al (2005) "A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays." Cancer Res; 65: 6071M-bM-^@M-^S6079.). The average resolution of this array platform, described by McMullan et al is 150M-bM-^@M-^S200 kb (Mc McMullan DJ, Bonin M et al. (2009), M-bM-^@M-^\Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: a multicenter studyM-bM-^@M-^] Hum Mutat. Jul;30(7):1082-92).

ORGANISM(S): Homo sapiens

SUBMITTER: Rolph Pfundt

PROVIDER: E-GEOD-40405 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Immunoglobulin A Nephropathy (IgAN) is a complex multifactorial disease whose genetic bases remain unknown. Distinct linkage and genome-wide association studies in both familial and sporadic IgAN suggest that there is a strong genetic component in IgAN. In this context, an intriguing role could be ascribed to copy number variants (CNVs) that have been recognized as an important source of genetic variation in humans. Here, we performed a whole-genome screening of CNVs in IgAN patients, their healthy relatives and healthy subjects (HS). A total of 217 individuals consisting of 51 IgAN cases and 166 healthy relatives were included in the initial screening. The high-throughput analysis of structural genetic variations, to find concordant aberrations across classes of samples, identified 178 IgAN-specific aberrations, specifically 114 loss and 64 gain. Several CNVs overlapped with regions evidenced by previous genome-wide genetic studies. Moreover, we found that IgAN patients characterized by deteriorated renal function carried low copy numbers of a CNV in chromosome 3 (chr3_loss:52031010-52260722). This CNV contained the TLR9 gene whose expression significantly correlated with the loss aberration in patients with progressive renal damage. Conversely, IgAN patients with normal renal function had no chr3_loss:52031010-52260722 and the TLR9 mRNA was expressed at the same level as in HS, still maintaining a strong correlation with the CNV. In conclusion, here we performed the first genome-wide CNV study in IgAN identifying some structural variants specific to IgAN patients and providing a collection of new candidate genes and loci that could help to dissect the complex genomic setting of the disease. Moreover, we identified a specific CNV, spanning the TLR9 gene, which could explain the disease severity in IgAN patients. To perform a genome-wide CNV study in IgAN identifying some structural variants specific to IgAN patients and providing a collection of new candidate genes and loci that could help to dissect the complex genomic setting of the disease.

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CNV and LOH analysis of patient sample PN11-0204

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