title: Genome-wide analysis of copy number variation in type 1 diabetes.
abstract: Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Britney L
authors.initials: BL
authors.lastname: Grayson
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Smith
authors.forename: James W
authors.initials: JW
authors.lastname: Thomas
authors.forename: Lily
authors.initials: L
authors.lastname: Wang
authors.forename: Phil
authors.initials: P
authors.lastname: Dexheimer
authors.forename: Joy
authors.initials: J
authors.lastname: Jeffrey
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Priyaanka
authors.initials: P
authors.lastname: Nanduri
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Aune
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014430:Twins, Monozygotic / Q000235:genetics