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，以 协助临床遗传学家完成咨询患者的任务 关于基于基因的疾病。拟议的工具将有助于 咨询师收集关于咨询者及其家人的相关数据， 根据公认的概率原理来解释这些数据 分析，并使用数据库中的相关信息 遗传学文献，将咨询努力集中在帮助 患者做出困难和有价值的决定，以帮助产生 准确和翔实的报告和记录，并帮助组织和 汇总咨询期间收集的家谱数据的丰富信息 为以后的研究研究提供投入的会议。 已经开发并开始测试原型程序，该程序 通过图形界面捕获家庭谱系并计算 我们提出了单基因座孟德尔疾病的基因型概率 将其扩展到处理出现在 临床实践。一些必需的扩展包括能够 要在一个站点处理两个以上的等位基因，请结合其他证据 将表型和家庭结构纳入概率计算， 允许进行多位点连锁分析，特别是利用 RFLP数据的可用性不断提高，以允许使用不同的先验 基于种族的不同个体的基因频率 背景，并纳入年龄相关的外显模型。我们也 计划允许该计划帮助顾问确定可能性 在特定的谱系中有不同的遗传模式。此外，我们 计划将程序的输入和输出能力扩展到 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，以鼓励捕获已经- 现有的遗传数据。 我们将在遗传部测试该程序的可用性 哈佛社区健康计划，以及后来评估其对 帮助遗传咨询师进行咨询。我们还将发展 该程序的一个有限版本，其中只包含一个遗传模型 家族性乳腺癌并对该版本进行早期测试 与纪念斯隆·凯特琳癌症中心合作。

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.