STATISTICAL METHODS FOR NONDISJUNCTION DATA

染色体不平衡是智力迟钝的主要已知原因， 自然流产和人类先天性心脏缺陷。 此外，超过50%的人类妊娠失败归因于 导致胎儿染色体不平衡， 是导致繁殖失败的主要原因 产妇年龄好 被认为是染色体异常的主要危险因素。 重组的改变也被发现是强烈相关的 人类的不分离性然而，使用的标准统计方法 不分离研究是有偏差的。 此外，标准 方法在提取遗传信息方面效率低下， 不分离数据，其特征在于有限的数量， 可用的材料，不分离误差起源的未知阶段， 没有信息的交配和父母失踪 基于我们之前对交叉过程的研究，有序四分体， 和半四分体，我们将开发有效的多位点统计 人类不分离数据的方法包括：（1）联合标记 （2）交叉干扰;（3）信息的不确定性 不分离错误的起源阶段;（4）父母年龄效应;（5） 未分型和无信息标记;（6）只有一个可用标记的家系 （7）基因分型错误。 这些统计方法将 最大限度地利用人类不分离数据中的信息， 确定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。 为了使我们的方法能够被 科学界，高效和有据可查的计算机软件 将在万维网上开发、测试和分发。 的 最终的目标是了解重组和它的改变 在不分离期间，并提供监测所需的知识 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.