Identification of Single Nucleotide Polymorphisms in Can

Can单核苷酸多态性的鉴定

• 批准号: 7038612
• 负责人: MICHAEL DEAN
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/7038612
• 关键词: African American; Asian Americans; breast neoplasms; cancer risk; caucasian American; clinical research; estrogen receptors; gene expression; gene mutation; genetic mapping; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human genetic material tag; human immunodeficiency virus 1; human population genetics; human subject; neoplasm /cancer genetics; oncogenes; progesterone receptors; virus diseases

Understanding the role of individual genetic background in his/her susceptibility to cancer, disease progression, and response to therapy is an important component of cancer research. Single nucleotide polymorphisms (SNPs) represent an abundant and useful source of genetic markers to understand complex diseases. We have characterized variants in the estrogen receptor gene (ESR1) and genotyped these variants in a cohort of breast cancer patients. The results show that a haplotype generated by several polymorphisms in this gene is associated with a reduced risk of breast cancer. In addition, we are characterizing variants in the ESR2 and progesterone receptor genes. While variants in these genes were not found to be associated with breast cancer, they may be relevant to other hormone responsive cancers. The tripartite motif-containing 5 (TRIM5) gene represents a newly described protein involved in the protection of cells from viral infection. We have sequenced the TRIM5 gene in a large collection of normal individuals as well as patients at risk for HIV-1 infection. We find a large number of non-synonymous variants in the gene, suggesting that these variants have been selected for and confer some protection to disease. In addition, the gene is conserved only in primates and is not found in the genome of the mouse, rat or dog. Evidence also shows that there is considerable variation in the gene in other primate species.

了解单个遗传背景在其对癌症，疾病进展和对治疗反应的敏感性中的作用是癌症研究的重要组成部分。单核苷酸多态性（SNP）代表了了解复杂疾病的丰富而有用的遗传标记来源。我们已经表征了雌激素受体基因（ESR1）中的变体，并在乳腺癌患者队列中对这些变体进行了基因分型。结果表明，该基因中几种多态性产生的单倍型与乳腺癌风险降低有关。此外，我们正在表征ESR2和孕酮受体基因中的变体。尽管这些基因中的变体没有发现与乳腺癌有关，但它们可能与其他激素反应性癌症有关。含三方基序5（TRIM5）基因代表了一种新描述的蛋白质，涉及细胞免受病毒感染的保护。我们已经在大量正常个体以及有HIV-1感染风险的患者中对TRIM5基因进行了测序。我们发现该基因中有大量的非同义变体，这表明这些变体已被选择并赋予疾病一些保护。另外，该基因仅在灵长类动物中保守，并且在小鼠，大鼠或狗的基因组中未发现。证据还表明，其他灵长类动物中该基因的差异很大。