DESCRIPTION (provided by applicant): Nasopharyngeal carcinoma (NPC) has an extremely heterogeneous geographical and ethnic distribution. Environmental factors such as suboptimal food preservation and exposure to EBV appear involved in the etiology of NPC. Genetic susceptibility is also likely to be involved but the identity of the genes involved in susceptibiliy to NPC remains elusive. Isolated populations, particularly those with unusually high diseases prevalence, offer rare opportunities to investigate the genetic cause of human disease. The Bidayuh ethnic subgroup of Sarawak Malaysia has unusually high prevalence of NPC. We have identified one exceptionally large Bidayuh multiplex pedigree in which 26 NPC cases can be traced back to a single founding village. We have focused extensive recruitment of the NPC cases allowing the collection of blood samples from 11 of the NPC cases, and can to infer genetic information for an additional 7 NPC cases. This application aims to perform comprehensive genetic analysis of this pedigree using a combination of high density genotyping and direct whole exome DNA sequencing. The genes of interest identified in this exceptionally large pedigree will be validated and replicated in additional populations.
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