FAMILIAL COLORECTAL NEOPLASIA LINKED TO CHROMOSOME 9Q222-312

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 结直肠癌是美国成年人癌症死亡的第二大原因。家族性腺瘤性息肉病和遗传性非息肉病性结直肠癌这两种常染色体显性遗传形式的疾病可能占所有病例的5%。然而，在大约20%的额外结肠癌病例中，受影响的个体报告了一级亲属的结肠癌家族史。在对53名亲属（其中2名或2名以上的兄弟姐妹在65岁时患有结肠癌）进行基因组扫描后，我们使用密集分布的微卫星标记对9号和6号染色体进行了精细定位。 我们进一步证实了这些信号在额外的70 kinetron的信号强度增加了一个数量级的染色体9。 SNP分型在这一地区完成，并确定了单倍型分离的情况下，而不是控制，确定优先。 我们编制了一个复制样本，以确认这种关联，并收集了额外的家庭成员，以确认这种单倍型。 一篇论文正在准备中，（1）在一个大型数据集中证实了相同的连锁，将连锁区域从13-5 cm缩小到7.7 cm，（2）通过对3,000多个SNP进行基于家族的关联分析，可以进一步分离这种效应，这些SNP在感兴趣的区域非常密集，（3）鉴定了与早发性家族性结肠肿瘤风险相关的单倍型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in about 20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative. Following a genome scan in 53 kindreds in which 2 or more sibling were affected by age 65 with colon cancer, we performed finemapping on chromosomes 9 and 6 using densely spaced microsatellite markers. We further confirmed these signals in an additional 70 kindreds for which signal strength on chromosome 9 was increased by an order of magnitude. SNP typing in this region was completed and identification of a haplotype segregating preferentially in cases, and not controls, identified. We compiled a replication sample to confirm this association and collected additional family members so as to confirm this haplotype. A paper is in preparation that (1) confirmed the same linkage in a large dataset, narrowing the linkage region from 13-5 to 7.7 cm, (2) could further isolate this effect by a family-based assocation analysis of over 3,000 SNPs very densely spaced over the region of interest, and (3) identified a haplotype associated with risk of early onset familial colon neoplasia.