Finding Genes for Cancer Susceptibility and Growth Regul

寻找癌症易感性和生长调节基因

• 批准号: 7148001
• 负责人: elaine ostrander
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7148001
• 关键词: Marsupialia; brca gene; breast neoplasms; cancer risk; cell growth regulation; developmental genetics; dogs; family genetics; functional /structural genomics; gene environment interaction; gene interaction; gene mutation; genetic mapping; genetic models; genetic polymorphism; genetic regulation; genetic susceptibility; genotype; growth factor; human subject; molecular biology information system; molecular cloning; neoplasm /cancer genetics; nucleic acid sequence; population genetics; prostate neoplasms

Dr. Ostrander?s research interests are in the area of genetic mapping and genomics. We have two main areas of interest. First, we are mapping and cloning genes that, when mutated, increase the risk of breast and prostate cancer in humans. Both family based and population based studies are underway. Second, we are interested in the development of the canine system for both understanding natural genetic variation as well as identifying disease genes. Trainees interested in human cancer have the opportunity to work on both breast and prostate cancer. Recently, we completed a genome wide scan of 255 prostate cancer families. Analyses of our data thus far has shown that prostate cancer is extremely heterogeneous, and that multiple loci are likely to be important. Stratification of our now complete genotyping dataset by clinical features of disease and family history are suggest multiple regions of interest where prostate cancer genes are likely to lie. With regard to breast cancer we have focused on analysis of BRCA1 and BRCA2 mutations in women with breast cancer in several case-control settings. Our work has led to studies of gene-gene and gene-environment interactions that provide new hypotheses for future studies. Our most recent work has focused on a large data set of nearly 3000 women, of whom about 1/3 are African American, providing one of the largest data sets of information about inherited susceptibility and breast cancer in this poorly studied group of patients. In addition, we are taking an evolutionary approach to understanding cancer susceptibly genes and have cloned portions of BRCA1 and BRCA2 from a number of marsupials. This has allowed us to hypothesize a set of missense changes that are likely disease associated. With regard to the canine system we and our collaborators have developed a dense comparative map between humans, dogs and mice and participated in the sequencing of the dog genome. We are now using those resources to map genes important in a variety of diseases, most notably cancer. Additional studies focus on finding genes important in growth regulation and development by working closely with dog owners, breeders and kennel clubs and collecting both DNA samples and recording growth measurements. Finally, we are interested in the organization of the canine family tree and the utility of linkage disequilibrium for mapping canine genes of interest. Towards that end, studies begun last year continue as we seek to understand the relationship of dog breeds one to another and ultimately to wolf ancestors.

Ostrander 博士的研究兴趣是遗传图谱和基因组学领域。我们有两个主要兴趣领域。首先，我们正在绘制和克隆基因，这些基因突变后会增加人类患乳腺癌和前列腺癌的风险。基于家庭和基于人群的研究正在进行中。其次，我们对犬科动物系统的发展感兴趣，以了解自然遗传变异和识别疾病基因。 对人类癌症感兴趣的学员有机会从事乳腺癌和前列腺癌的研究。最近，我们完成了 255 个前列腺癌家族的全基因组扫描。迄今为止我们的数据分析表明，前列腺癌具有极大的异质性，并且多个位点可能很重要。我们现在完整的基因分型数据集按疾病的临床特征和家族史进行分层，表明前列腺癌基因可能位于多个感兴趣的区域。关于乳腺癌，我们重点分析了几个病例对照环境中乳腺癌女性的 BRCA1 和 BRCA2 突变。我们的工作导致了基因-基因和基因-环境相互作用的研究，为未来的研究提供了新的假设。我们最近的工作重点关注近 3000 名女性的大型数据集，其中约 1/3 是非裔美国人，为这一研究不足的患者群体提供了有关遗传易感性和乳腺癌信息的最大数据集之一。此外，我们正在采用进化方法来了解癌症易感基因，并从许多有袋动物中克隆了部分 BRCA1 和 BRCA2。这使我们能够假设一系列可能与疾病相关的错义变化。 关于犬类系统，我们和我们的合作者开发了人类、狗和小鼠之间的密集比较图谱，并参与了狗基因组的测序。我们现在正在利用这些资源来绘制在各种疾病（尤其是癌症）中重要的基因图谱。其他研究的重点是通过与狗主人、饲养员和养犬俱乐部密切合作，收集 DNA 样本并记录生长测量结果，寻找对生长调节和发育重要的基因。最后，我们对犬类家谱的组织以及连锁不平衡在绘制感兴趣的犬类基因图谱中的效用感兴趣。为此，去年开始的研究仍在继续，我们试图了解狗品种之间的关系，并最终了解狗品种与狼祖先的关系。