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

描述(申请人提供)：鼻咽癌(NPC)具有极其不同的地理和种族分布。环境因素，如不理想的食物保存和暴露于EBV似乎与鼻咽癌的病因有关。遗传易感性也可能与鼻咽癌有关，但与鼻咽癌易感性相关的基因的身份仍然难以捉摸。与世隔绝的人群，特别是那些疾病患病率异常高的人群，为研究人类疾病的遗传原因提供了难得的机会。马来西亚沙捞越的比达尤族人有异常高的鼻咽癌患病率。我们已经确定了一个非常大的比达育多重谱系，其中26例鼻咽癌病例可以追溯到一个创始村庄。我们集中了对鼻咽癌病例的广泛招募，允许从11例鼻咽癌病例中采集血液样本，并可以为另外7例鼻咽癌病例推断基因信息。这项应用旨在利用高密度基因分型和直接整个外显子组DNA测序相结合的方式对该家系进行全面的遗传分析。在这个特别大的系谱中确定的感兴趣的基因将得到验证，并在更多的种群中复制。 公共卫生相关性：遗传易感性，以及环境因素，如不理想的食物保存和暴露于EBV，可能在鼻咽癌(NPC)的病因学中发挥作用。然而，与鼻咽癌易感性有关的基因，特别是具有重要遗传风险的基因，仍然难以确定。这项应用旨在对一个大型多基因马来西亚家系进行深入的遗传分析，以确定与鼻咽癌易感性有关的新基因，以及出现的感兴趣的基因，以便在更多的人群中验证和复制。

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.