Joint whole exome sequencing and linkage analysis in a multigenerational family segregating Type 1 Diabetes
type: CreativeWork
description: Backround: Type 1 diabetes (T1D) is a complex autoimmune disease with a strong familial segregation. On the other hand, the recent and rapid increase in incidence is a proof of the importance of environmental factor in the etiology of disease. Linkage and Genome-wide association studies had revealed almost 60 loci associated with the risk of T1D, explaining about 80% of the total heritability, mostly due to HLA locus. However, many familial T1D cases remains unexplained. Objective: To identify rare variants contributing to T1D susceptibility, we studied a Sardinian family with 9 individuals affected across 3 generations. Methods: We performed exome sequencing in 3 affected members and a healthy individual. In addition, all samples were extensively genotyped using Illumina OmniExpress beadchips for about 750K SNPs. A combined linkage analysis was carried out. Results: This combined approach identified three variants predicted to be damaging that are very rare in the general population (frequency <1%) and that are likely causing the disease.
abstract: Backround: Type 1 diabetes (T1D) is a complex autoimmune disease with a strong familial segregation. On the other hand, the recent and rapid increase in incidence is a proof of the importance of environmental factor in the etiology of disease. Linkage and Genome-wide association studies had revealed almost 60 loci associated with the risk of T1D, explaining about 80% of the total heritability, mostly due to HLA locus. However, many familial T1D cases remains unexplained. Objective: To identify rare variants contributing to T1D susceptibility, we studied a Sardinian family with 9 individuals affected across 3 generations. Methods: We performed exome sequencing in 3 affected members and a healthy individual. In addition, all samples were extensively genotyped using Illumina OmniExpress beadchips for about 750K SNPs. A combined linkage analysis was carried out. Results: This combined approach identified three variants predicted to be damaging that are very rare in the general population (frequency <1%) and that are likely causing the disease.
author: MEREU, ELISABETTA
language: eng
keywords: Sardegna, Sardinia, Type 1 Diabetes, analisi di linkage, diabete tipo 1, exome sequencing, linkage, sequenziamento dell'esoma, Settore MED/03 - Genetica Medica
date published: 2015-05-04
date modified: 2026-07-24T01:30:05Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11584/266614