LINKAGE ANALYSIS METHODS FOR HUMAN GENE MAPPING

长期目标是提供新的统计分析方法， 基因作图中的连锁数据，从而提高可靠性和精确性 评估第一类误差， 连锁和异质性的测试。此外，从长远来看， 为软件提供可靠和普遍可用的支持， 连锁分析 具体目标是：（1）开发和实施高效的蒙特卡罗 方法在人类家庭谱系作为一个先决条件， 分析方法;（2）开发用于估计 与观察到的最大值相关的p值（经验显著性水平） 两点或多点lod得分在非常家庭分析的一个 研究人员;（3）开发方法，以寻找置信区间为 参数，如地图距离，并优化选择策略， （4）研究基因定位的影响因素， 不相等标记杂合性的作图;（5）找到合适的p值 在异质性的各种测试中，特别是在多点情况下; 以及（6）维护和更新计算机程序（LIPED，LINKAGE，HOMOG， 等等）。对于微型计算机和工作站，将程序副本发送到 研究人员要求他们，并保持程序用户最新的 每两年分发三至四次《联系通讯》， 年

The long-term goal is to provide new methods for statistical analysis of linkage data in gene mapping, thereby increasing reliability and precision of resulting estimates and enhancing the assessment of type I errors in tests for linkage and for heterogeneity. Also, on a long-term basis, the providing of reliable and generally available support for software in linkage analysis. Specific aims are: (1) To develop and implement efficient Monte Carlo methods in human family pedigrees as a prerequisite for computer-based analysis methods; (2) to develop a Monte Carlo method for estimating the p-value (empirical significance level) associated with an observed maximum two-point or multi-point lod score in the very families analyzed by a researcher; (3) to develop methods for finding confidence intervals for parameters such as map distances and to optimize strategies for selecting marker loci for mapping a new locus; (4) to study the effects on gene mapping of unequal marker heterozygosity; (5) to find appropriate p-values in various tests for heterogeneity, particularly in multi-point situations; and (6) to maintain and update computer programs (LIPED, LINKAGE, HOMOG, etc.) for microcomputers and workstations, send copies of programs to researchers requesting them, and keep program users abreast of new developments by circulating a Linkage Newsletter three to four times per year.