2026-09-23T18:06:50Zhttps://iris.unica.it/oai/request

oai:iris.unica.it:11584/2666142022-10-15T19:58:05Zcom_11584_207615com_11584_111066col_11584_265854

Joint whole exome sequencing and linkage analysis in a multigenerational family segregating Type 1 Diabetes MEREU, ELISABETTA Sardegna Sardinia Type 1 Diabetes analisi di linkage diabete tipo 1 exome sequencing linkage sequenziamento dell'esoma Settore MED/03 - Genetica Medica 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. 2015-05-04 info:eu-repo/semantics/doctoralThesis http://hdl.handle.net/11584/266614 eng numberofpages:61 info:eu-repo/semantics/openAccess Università degli Studi di Cagliari license:Non specificato