INFERENCE AND ROBUST METHODS FOR LINKAGE MAPPING

描述(改编自《调查者摘要》)：近年来， 遗传学在方法学和计算方面都取得了很大的进步 连锁作图。然而，几个重要的组织已经收到了 注意不够。这项计划的长期目标是 开发新的统计和计算方法，以发现和 定位影响复杂性状的基因并改进设计 基因连锁研究。所有的方法都直接适用于实验 涉及近亲配对的十字架和人类研究，以及 直接的生物医学重要性。此外，从以下方面收集的见解 这些研究可能会扩大到更多的遗传流行病学 设计包括多个家系的参数分析。 具体目标是：i.制定通用和灵活的方法 构建遗传连锁中基因定位的置信度区间 学习。这里提出的一种方法出奇地简单和直接 ，并且可以由研究人员使用现有的 多点测绘软件。二、统一几个连锁作图 方法，以更好地理解 各种遗传流行病学设计。此外，统一 似乎能够简单而有力地调查效率和 各种联动设计的精度。三、发展极具一般性 QTL连锁分析的经验非参数方法 IBD状态的表型分布函数，以及TO 开发自适应伪似然方法，用于有效推断 基因定位。 这些目标将通过分析和计算来实现 方法，以及为此目的开发的任何计算机算法将是 分发给公众使用。此外，提出的许多方法都可以 其他调查人员使用现有软件即可轻松实现。这个 我们将检验所提出方法的稳健性和广泛适用性。 采用仿真和现有连杆机构分析相结合的方法 数据集。

DESCRIPTION (Adapted from the Investigator's Abstract): In recent years, great methodological and computational advances have been made in genetic linkage mapping. However, several important tissues have received insufficient attention. The long-term objectives of this project are to develop new statistical and computational methods for discovering and localizing genes influencing complex traits and to improve the design of genetic linkage studies. All of the methods apply directly to experimental crosses and human studies involving relative pairs, and so are of immediate biomedical importance. In addition, the insight gathered from these investigations may enable extensions to more genetic epidemiological designs including the parametric analysis of multiplex pedigrees. The specific aims are: I. to develop general and flexible methods for constructing confidence intervals for gene locations in genetic linkage studies. A method proposed here is surprisingly simple and straightforward , and can be implemented immediately by researchers using existing software for multipoint mapping. II. to unify several linkage mapping approaches, to obtain an improved understanding of the connections among various genetic epidemiological designs. In addition, the unification appears to enable simple and powerful investigation of efficiency and precision of various linkage designs. III. to develop extremely general non-parametric approaches to linkage analysis of QTLS using empirical distribution functions of phenotypes conditioned of IBD status, and to develop adaptive pseudo-likelihood methods for efficient inference for the gene location. These aims will be achieved using both analytic and computational approaches, and any computer algorithms developed for this purpose will be distributed for public use. In addition, many of the methods proposed can be easily implemented by other investigators using existing software. The robustness and wide applicability of the methods proposed will be examined using a combination of simulation and analysis of existing linkage datasets.