software for Integrated Linkage and Association Analysis

综合连锁和关联分析软件

• 批准号: 7022977
• 负责人: Elizabeth R Hauser
• 金额: $ 33.84万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7022977
• 关键词: alleles; chronic disease /disorder; computer program /software; computer simulation; computer system design /evaluation; family genetics; functional /structural genomics; gene expression; gene frequency; genetic markers; genotype; human data; linkage mapping; mathematical model; method development; phenotype; proteomics; statistics /biometry

DESCRIPTION (provided by applicant): The goal of this proposal is to continue the development of new methods of linkage and association analysis, and to combine the new methods with existing linkage and association methods for nuclear families into a single software package. Over the course of the past three years we have developed and released 5 software programs for the genetic analysis of complex traits including software for affected sib-pair linkage mapping, software for association analysis in general pedigrees, software for ordered subset linkage mapping and a general simulation package to explore the properties of these and other software packages. We propose to continue the development of these methods and accompanying software in the following ways: 1) Continue development of empirical p-value methods and accompanying software. The simulation package we developed and distributed is available for simulation of general pedigrees, which can include an observed marker map and observed allele frequencies. Our goal is to expand this package to simulate from the observed pedigree structures, including indicators of the observed phenotypes and genotypes. 2) Develop and distribute software for family-based association in the presence of linkage. In the course of our simulation studies comparing available software packages for family-based association, we observed grossly inflated type I errors in regions of linkage for one of the tests. We propose a new test that adjusts for the presence of linkage in families and gives the proper type 1 error rates. 3) Continue development of the ordered subset analysis (OSA) methods and software to incorporate more than one trait through recursive partitioning methods that use OSA to partition the linkage evidence and to apply this method to family-based association analysis. 4) Develop methods that will incorporate a variety of statistical tests, expression and proteomics results as well as incorporate genetic features emerging from the Human Genome Project such as identified genes, Haplotype Blocks, hot spots of recombination and at-risk sequences. Our research into methods development, assessment and comparison has been aided by the application of these new methods to a variety of ongoing applied linkage and association projects. Our collaborators have tested new software and have discussed the practical consequences of choices made during methods development and software programming. We will continue to utilize this resource to develop realistic and practical guidelines for application of these methods.

描述（由申请人提供）：本提案的目标是继续开发新的连锁关联分析方法，并将新方法与现有的核心家庭连锁关联方法结合到一个单一的软件包中。在过去的三年中，我们已经开发并发布了5个复杂性状遗传分析软件程序，包括受影响兄弟姐妹连锁图谱软件，一般谱系关联分析软件，有序子集连锁图谱软件和一个通用模拟包，用于探索这些软件包和其他软件包的特性。我们建议从以下几个方面继续开发这些方法和配套软件：1)继续开发经验p值方法和配套软件。我们开发和分发的模拟包可用于一般谱系的模拟，其中可以包括观察到的标记图谱和观察到的等位基因频率。我们的目标是扩展这个包来模拟观察到的谱系结构，包括观察到的表型和基因型的指标。2)在有联系的情况下开发和分发以家庭为基础的协会软件。在我们的模拟研究过程中，比较了基于家庭的关联的可用软件包，我们在其中一个测试的链接区域中观察到严重膨胀的I型错误。我们提出了一个新的测试，调整存在的连锁在家庭和给出适当的1型错误率。3)继续开发有序子集分析（OSA）方法和软件，通过使用OSA对关联证据进行划分的递归划分方法纳入多个特征，并将该方法应用于基于家族的关联分析。4)开发方法，包括各种统计测试，表达和蛋白质组学结果，以及从人类基因组计划中出现的遗传特征，如已识别的基因，单倍型块，重组热点和风险序列。我们对方法开发、评估和比较的研究得到了这些新方法在各种正在进行的应用链接和关联项目中的应用的帮助。我们的合作者已经测试了新软件，并讨论了在方法开发和软件编程期间所做选择的实际后果。我们将继续利用这一资源，为这些方法的应用制定切合实际的指导方针。