Joint whole exome sequencing and linkage analysis in a multigenerational family segregating Type 1 Diabetes

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.

Grantor dc:publisher

Università degli Studi di Cagliari

Year dc:date

2015

Author dc:creator

• MEREU, ELISABETTA

• Sardegna
• Sardinia
• Type 1 Diabetes
• analisi di linkage
• diabete tipo 1
• exome sequencing
• linkage
• sequenziamento dell'esoma
• Settore MED/03 - Genetica Medica

Statement dc:rights

• info:eu-repo/semantics/openAccess
• license:Non specificato

Language dc:language

eng

Handle dc:identifier

http://hdl.handle.net/11584/266614

OAI identifier oai:identifier

oai:iris.unica.it:11584/266614