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学映射和基因组学领域。我们有两个主要感兴趣的领域。首先，我们正在绘制和克隆基因，这些基因在突变时会增加人类乳腺癌和前列腺癌的风险。基于家庭和基于人群的研究都在进行中。其次，我们对犬类系统的发展感兴趣，以了解自然遗传变异以及鉴定疾病基因。 对人类癌症感兴趣的学员有机会同时研究乳腺癌和前列腺癌。最近，我们完成了255个前列腺癌家族的基因组广泛扫描。到目前为止，我们数据的分析表明，前列腺癌是非常异质的，并且多个基因座可能很重要。通过疾病和家族史的临床特征对我们现在完整的基因分型数据集进行了分层，这表明有多个感兴趣的区域可能存在前列腺癌基因。关于乳腺癌，我们专注于在几种病例对照环境中乳腺癌女性中BRCA1和BRCA2突变的分析。我们的工作导致了基因基因和基因环境相互作用的研究，这些相互作用为未来的研究提供了新的假设。我们最近的工作集中在近3000名妇女的大量数据集上，其中约1/3是非裔美国人，在这一研究不佳的患者组中，提供了有关遗传易感性和乳腺癌的最大数据集之一。此外，我们正在采用一种进化方法来理解癌症的基因，并从许多有袋动物中克隆了BRCA1和BRCA2的部分。这使我们能够假设一组可能相关的疾病的错义变化。 关于犬类系统，我们和我们的合作者在人类，狗和小鼠之间开发了密集的比较图，并参加了狗基因组的测序。现在，我们正在使用这些资源来映射在各种疾病中很重要的基因，最著名的是癌症。其他研究的重点是通过与狗的主人，繁殖者和养犬俱乐部紧密合作，收集DNA样本并记录增长测量值，以寻找在生长调节和发展中重要的基因。最后，我们对犬类家族树的组织感兴趣，以及对映射感兴趣的犬基因的连锁不平衡的实用性。为此，当我们寻求了解狗的关系彼此并最终与狼祖先的关系时，去年开始的研究继续进行。