Genetic analysis of a large multiplex Nasopharyngeal Carcinoma (NPC)family from S

描述（由申请人提供）：鼻咽癌（NPC）具有极其异质性的地理和种族分布。环境因素，如不理想的食物保存和暴露于EBV似乎涉及鼻咽癌的病因。遗传易感性也可能参与，但参与鼻咽癌易感性的基因的身份仍然难以捉摸。孤立的人口，特别是那些疾病发病率异常高的人口，为调查人类疾病的遗传原因提供了难得的机会。马来西亚砂拉越的比达耶族亚群有异常高的NPC患病率。我们已经确定了一个特别大的比达耶多元谱系，其中26个NPC病例可以追溯到一个单一的创始村庄。我们集中广泛地收集了11例鼻咽癌病例的血液样本，并可以推断另外7例鼻咽癌病例的遗传信息。该应用程序旨在使用高密度基因分型和直接全外显子组DNA测序的组合对该谱系进行全面的遗传分析。在这个特别大的谱系中发现的感兴趣的基因将在其他人群中得到验证和复制。

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. PUBLIC HEALTH RELEVANCE: Genetic susceptibility, along with environmental factors such as suboptimal food preservation and exposure to EBV, are likely to play a role in the etiology of nasopharyngeal carcinoma (NPC). However, the identity of the genes involved in NPC susceptibility, particularly genes that confer an important genetic risk, remain elusive. This application aims to perform in depth genetic analysis of a large multiplex Malaysian pedigree to identify new genes involved in the susceptibility to NPC, with the genes of interest that arise to be validated and replicated in additional populations.