{"id":{"repo_id":"cagliari","oai_identifier":"oai:iris.unica.it:11584/266614"},"canonical_url":"https://search.dev.ndltd.org/etd/cagliari/oai:iris.unica.it:11584/266614","repository":{"repo_id":"cagliari","name":"Università di Cagliari","base_url":"https://iris.unica.it/oai/request"},"display":{"title":"Joint whole exome sequencing and linkage analysis in a multigenerational family segregating Type 1 Diabetes","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.","abstract_html":"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 &lt;1%) and that are likely causing the disease.","abstract_has_math":false,"creators":["MEREU, ELISABETTA"],"institution":"Università degli Studi di Cagliari","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-05-04","date_published":"2015-05-04","updated_at":"2026-07-24T01:30:05Z","subjects":["Sardegna","Sardinia","Type 1 Diabetes","analisi di linkage","diabete tipo 1","exome sequencing","linkage","sequenziamento dell'esoma","Settore MED/03 - Genetica Medica"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess","license:Non specificato"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11584/266614","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["MEREU, ELISABETTA"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-05-04"]},{"key":"dc:publisher","label":"Institution","values":["Università degli Studi di Cagliari"]},{"key":"dc:relation","label":"Dc Relation","values":["numberofpages:61"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Sardegna","Sardinia","Type 1 Diabetes","analisi di linkage","diabete tipo 1","exome sequencing","linkage","sequenziamento dell'esoma","Settore MED/03 - Genetica Medica"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess","license:Non specificato"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/11584/266614"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:title","label":"Title","values":["Joint whole exome sequencing and linkage analysis in a multigenerational family segregating Type 1 Diabetes"]}]}],"canonical_facts":{"dc:creator":["MEREU, ELISABETTA"],"dc:date":["2015-05-04"],"dc: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."],"dc:identifier":["http://hdl.handle.net/11584/266614"],"dc:language":["eng"],"dc:publisher":["Università degli Studi di Cagliari"],"dc:relation":["numberofpages:61"],"dc:rights":["info:eu-repo/semantics/openAccess","license:Non specificato"],"dc:subject":["Sardegna","Sardinia","Type 1 Diabetes","analisi di linkage","diabete tipo 1","exome sequencing","linkage","sequenziamento dell'esoma","Settore MED/03 - Genetica Medica"],"dc:title":["Joint whole exome sequencing and linkage analysis in a multigenerational family segregating Type 1 Diabetes"],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-24T01:30:05Z"}