Finding Genes for Cancer Susceptibility and Growth Regul

奥斯特兰德医生？的研究兴趣是在遗传图谱和基因组学领域。我们主要关注两个领域。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患乳腺癌和前列腺癌的风险。基于家庭和人口的研究正在进行中。其次，我们对犬系统的发展感兴趣，以了解自然遗传变异以及识别疾病基因。 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，前列腺癌是非常异质性的，多个位点可能是重要的。通过疾病的临床特征和家族史对我们现在完整的基因分型数据集进行分层，提示了前列腺癌基因可能存在的多个感兴趣区域。关于乳腺癌，我们在几个病例对照组中重点分析了乳腺癌妇女的BRCA 1和BRCA 2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。我们最近的工作集中在近3000名女性的大型数据集上，其中约1/3是非洲裔美国人，提供了关于遗传易感性和乳腺癌信息的最大数据集之一。此外，我们正在采取进化的方法来理解癌症易感基因，并从一些有袋动物中克隆了BRCA 1和BRCA 2的部分基因。这使我们能够假设一组可能与疾病相关的误解变化。 关于犬系统，我们和我们的合作者已经开发了人类、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各种疾病的重要基因，特别是癌症。其他研究的重点是通过与狗主人、育种者和养犬俱乐部密切合作，收集DNA样本和记录生长测量结果，寻找在生长调节和发育中重要的基因。最后，我们感兴趣的组织犬的家谱和实用的连锁不平衡映射犬的基因的兴趣。为此，去年开始的研究继续进行，我们试图了解狗品种之间的关系，并最终与狼的祖先。

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.