STATISTICAL METHODS FOR NONDISJUNCTION DATA

染色体失衡是智力低下的主要已知原因， 人类的自然流产和先天性心脏缺陷。 此外，超过50%的人类妊娠损失可归因于 导致胎儿染色体失衡，导致染色体异常 生殖失败的主要原因。产妇的年龄很好 被认为是染色体异常的主要风险因素。 重组的改变也被发现与 与人类的不分离。然而，使用的标准统计方法 在人类中，不分离的研究是有偏见的。此外，标准 方法在提取遗传信息方面效率低下。 非析取数据，其特征是有限数量的 可获得的材料，不析取误差起源的未知阶段， 一无所知的婚恋，以及父母的失踪。 基于我们之前对交叉过程的研究，有序的四分体， 和半四分体，我们将开发高效的多位点统计 用于人类非分离数据的方法包括：(1)关节标记 信息；(2)交叉干扰；(3)信息中的不确定性 不分离误差的起源阶段；(4)亲代年龄效应；(5) 无类型且无信息的标记；(6)只有一个可用标记的家庭 亲本；(7)基因分型错误。这些统计方法将 最大限度地利用人类非析取数据中的信息来 确定导致染色体异常的基本机制。 使用本项目中开发的统计方法，我们将 与人类不分离研究领域的领先研究人员合作 分析、解释和报告X染色体的科学发现， 13、15、16、18、21和22。将我们的方法提供给 科学界、高效且文档齐全的计算机软件 将在万维网上开发、测试和分发。这个 最终目标是理解重组及其变化 在不分离过程中，并提供监控所需的知识 并防止染色体异常。

Chromosome imbalance is the leading known cause of mental retardation, spontaneous abortion, and congenital heart defects in human. Furthermore, over 50 percent of all human pregnancy loss is attributable to chromosome imbalance in the fetus, making chromosome abnormalities the leading cause of reproductive failure. Maternal age is well recognized as a major risk factor for chromosome abnormalities. Alterations of recombinations are also found to be strongly associated with human nondisjunctions. However, standard statistical methods used in human nondisjunction studies are biased. In addition, the standard methods are inefficient in extracting genetic information from nondisjunction data, which are characterized by a limited amount of available materials, unknown stage of origin of nondisjunction error, uninformative matings, and missing parents. Built on our previous studies on the crossover process, ordered tetrads, and half-tetrads, we will develop efficient multilocus statistical methods for human nondisjunction data to include: (1) joint marker information; (2) crossover interference; (3) the uncertainty in the stage of origin of nondisjunction error; (4) parental age effects; (5) untyped and uninformative markers; (6) families with only one available parent; and (7) genotyping errors. These statistical methods will maximally utilize the information in human nondisjunction data to identify basic mechanisms responsible for chromosome abnormalities. Using the statistical methods developed in this project, we will collaborate with leading researchers in human nondisjunction studies to analyze, interpret, and report scientific findings for chromosomes X, 13, 15, 16, 18, 21 and 22. To make our methods available to the scientific community, efficient and well-documented computer software will be developed, tested, and distributed on the World Wide Web. The ultimate goals are to understand recombination and its alterations during nondisjunction, and to provide the knowledge needed to monitor and prevent chromosome abnormalities.