PROSTATE, BREAST AND KIDNEY CANCER SUSCEPTIBILITY GENES IN AFRICAN AMERICANS

一种新的遗传方法--混合连锁不平衡作图法 （MALD）已经提出并实施，它提供了一个群体， 基于患者群的疾病基因鉴定方法。的 方法使用具有显著等位基因频率的遗传标记 种族群体和有近代史的人口之间的差异 用于鉴定患者中涉及的新疾病基因 同伙这种方法特别适用于以下疾病： 收集大家庭进行连锁分析是困难的，或者 疾病发作涉及暴露于常见的环境或传染病， 剂我们一直在收集患有肾病的非裔美国人， 乳腺癌和前列腺癌。前列腺癌项目目前 正在进行中，我们希望开始分析其他疾病， 有足够数量的患者和对照可用。 我们已经开始对352名非裔美国人的微卫星进行基因分型 使用MALD图谱中的标记物的前列腺癌患者和对照 正在开发中（见项目Z 01 BC 10270- 01 LGD）。的区域 在染色体1 q24 -25，8 p，10和17上，由其他人鉴定为缺失， 目前正在仔细进行杂合性研究和遗传连锁分析， 在前列腺癌的MALD分析中仔细检查。剩下的标记 以10厘摩的分辨率扫描基因组所需的技术 根据非洲裔美国人和 白种人，以及我们有效进行多重分析的能力 在自动测序仪上该项目的成果正在 持续收集和分析。MALD阳性信号 连锁将通过筛选额外的标记从 用于确认信号的区域。传统疾病基因 实验室以前采用的鉴定方法， 用于鉴定前列腺疾病病因学相关基因 癌

A novel genetic method "Mapping by Admixture Linkage Disequilibrium" (MALD) has been proposed and implemented which provides a population and patient cohort-based approach for disease gene identification. The method uses genetic markers with significant allele frequency differences between racial groups and a population with a recent history of admixture to identify novel disease genes involved in patient cohorts. This methodology is particularly appropriate for diseases where collecting large families for linkage analysis is difficult or where disease onset involves exposure to a common environmental or infectious agent. We have been collecting African American patients with kidney, breast, and prostate cancer. The prostate cancer project is currently ongoing and we hope to begin analysis of the other diseases as sufficient numbers of patients and controls become available. We have begun genotyping microsatellites from 352 African American prostate cancer patients and controls using markers from the MALD map which is in development (see Project Z01 BC 10270- 01 LGD). The regions on chromosomes 1q24-25, 8p, 10, and 17 identified by others in loss of heterozygosity studies and genetic linkage analyses are being carefully scrutinized in MALD analysis of prostate cancer. The remaining markers necessary to scan the genome at a 10- centiMorgan resolution are being chosen on the basis of maximal differences between African Americans and Caucasians, and our ability to efficiently perform multiplex analysis on an automated sequencer. The results of this project are being collected and analyzed on an ongoing basis. Positive signals for MALD linkage will be followed up by screening additional markers from the region for confirmation of the signal. Traditional disease gene identification methods which the laboratory has applied before will then be used to identify the genes involved in the etiology of prostate cancer.