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Published on: April 19, 2013
Genome-wide analysis of copy number variation in type 1 diabetes
Britney L Grayson1, Mary Ellen Smith, James W Thomas
1Department of Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
Plos One
|November 19, 2010
Summary
Copy number variations (CNVs) may play a role in Type 1 diabetes (T1D) susceptibility. This study identified specific CNVs associated with T1D in families and discordant twins, suggesting their involvement in islet autoimmunity development.
Area of Science:
- Genetics
- Immunology
- Endocrinology
Background:
- Type 1 diabetes (T1D) shows familial clustering, indicating a genetic basis.
- Genome-wide association studies (GWAS) using single nucleotide polymorphisms (SNPs) have not fully explained T1D familiality.
- Copy number variations (CNVs), large genomic deletions or amplifications, represent another form of genetic variation.
Purpose of the Study:
- To investigate the role of CNVs in T1D susceptibility.
- To identify CNVs associated with T1D in unrelated adults and discordant monozygotic twins.
- To explore the potential contribution of CNVs to islet autoimmunity in T1D.
Main Methods:
- Genome-wide CNV analysis was performed on 20 unrelated T1D adults and 20 controls using Affymetrix SNP Array 6.0 and Birdsuite software.
- CNV analysis was also conducted on 10 monozygotic twin pairs discordant for T1D.
- Identification of CNVs enriched or depleted in T1D cases compared to controls and within twin pairs.
Main Results:
- Thirty-nine CNVs were found to be significantly enriched or depleted in T1D patients versus controls.
- Eleven of these CNVs were also differentially present in the discordant twin cohort.
- A deletion on chromosome 6p21, near an HLA-DQ allele, was among the identified CNVs.
- CNVs were identified that were both increased and decreased in individuals with T1D or at high risk.
Conclusions:
- CNVs may contribute to the genetic predisposition and familial aggregation of T1D.
- Specific CNVs, including one near the HLA-DQ locus, are associated with T1D and islet autoimmunity.
- These findings highlight CNVs as potential genetic factors influencing T1D development and risk.
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Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
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