CLINICAL GENETICIST'S WORKSTATION

我们建议设计、实施和测试一个基于计算机的工作站， 协助临床遗传学家与患者进行咨询 关于遗传疾病的。 拟议的工具将有助于 咨询师收集有关咨询师及其家庭的相关数据， 根据公认的概率论原则来解释这些数据， 分析，并使用相关信息的数据库， 遗传学文献，集中咨询工作，以帮助 病人作出困难和价值的决定，以帮助生产 准确和翔实的报告和记录，并帮助组织和 将咨询过程中收集到的丰富的家谱数据进行汇总 为以后的研究提供投入。 已经开发并开始测试一个原型程序， 通过图形界面捕获家族谱系， 基因型概率为单基因座孟德尔疾病，我们建议 将其扩展到处理广泛的遗传问题， 临床实践 所需的一些扩展包括能够 在一个位点处理两个以上的等位基因， 而不是表型和家族结构的概率计算， 允许多位点连锁分析，特别是利用 越来越多的RFLP数据的可用性，允许使用不同的先验 基因频率的不同个体基于他们的种族 背景，并纳入年龄依赖性的认知模型。 我们也 计划允许该计划帮助辅导员确定 不同的遗传模式在一个特定的谱系。 另外我们 计划扩展程序的输入和输出能力， 制作适当的屏幕和打印报告，并接受 以灵活的方式提供信息，以鼓励收集已经- 现有的基因数据。 我们将测试该程序的可用性在遗传学系， 哈佛社区健康计划，后来评估其效用， 帮助遗传咨询师进行咨询。 我们还将开发 一个有限版本的程序，只包含一个遗传模型， 家族性乳腺癌，并进行这种版本的早期测试， Memorial Sloan Kettering癌症中心

We propose to design, implement and test a computer-based workstation to assist clinical geneticists in their tasks of consulting with patients concerning genetically-based diseases. The proposed tool will help the counselor to collect relevant data about the consultant and his family, to interpret those data according to accepted principles of probabilistic analysis, and, using a data base of relevant information from the genetics literature, to focus counseling effort toward helping the patient make difficult and value-laden decisions, to help produce accurate and informative reports and records, and to help organize and aggregate the wealth of pedigree data collected during counseling sessions for input into later research studies. Having already developed and begun to test a prototype program that captures family pedigrees via a graphical interface and calculates genotype probabilities for single-locus Mendelian disorders, we propose to extend it to deal with the wide range of genetic issues that arise in clinical practice. Some of the required extensions include being able to handle more than two alleles at a site, incorporate evidence other than phenotype and family structure into the probabilistic calculations, allow the analysis of multi-locus linkage, especially to exploit the growing availability of RFLP data, to allow the use of different a priori gene frequencies for different individuals based on their ethnic background, and to incorporate age-dependent penetrance models. We also plan to allow the program to help the counselor determine the likelihood of various inheritance patterns in a specific pedigree. In addition, we plan to extend the input and output capabilities of the program to produce appropriate on-screen and printed reports, and to accept information in flexible ways to encourage the capture of already- available genetic data. We will test the usability of the program at the Genetics Department of the Harvard Community Health Plan, and later assess its utility for helping genetic counselors perform consultations. We will also develop a limited version of the program that contains only a genetic model for familial breast cancer and perform early tests of this version in collaboration with Memorial Sloan Kettering Cancer Center.