GENE MAPPING TECHNOLOGY AND BIOINFORMATICS

利用DNA标记检测颅面和口腔疾病的基因定位研究利用了各种各样的统计技术。我们正在开发一种方案，以便更好地集成这些软件工具。由于这些程序中的许多是在其他地方使用各种计算机语言和输入格式编写的，因此将它们与我们的内部数据库集成将简化分析过程。随着遗传流行病学领域的快速发展，我们不断更新我们的统计分析工具套件，定期提供改进的方法和计算机程序。与NIAAA和昆士兰医学研究所的同事合作，为我们提供了未发表的基因分析软件程序。此外，我们正在继续努力提高大规模基因定位研究的速度、准确性和效率。在过去的一年里，我们已经评估了几种用于筛选整个人类基因组的替代分子标记集，包括一套新的基于二核苷酸和四核苷酸重复序列的微卫星标记。我们与NHGRI的合作使我们获得了他们在开发另一种标记集方面的丰富经验，包括被称为尾尾标记的方法，该方法已被证明可以大大减少与该标记基因分型方法相关的人工制品。额外的努力集中在将我们的新仪器纳入这些分析，包括DNA测序仪和机器人实验室工作站。为了有效地跟踪进行大规模遗传流行病学研究所必需的大量信息，我们正在不断开发我们的综合数据管理系统。该系统用于管理临床、系谱和基因型数据，用于基因定位研究和其他研究设计，涉及高级研究员正在调查的口腔和牙齿疾病的研究。我们的目标是建立一个完全集成的系统，可以管理临床信息、家族史和标记等位基因分型。此外，该系统应提供交互式程序，包括：(1)广泛的错误检查；(2)生成适合输入各种联动分析程序的格式化文件；(3)提供引物清单，用于跟踪DNA样本和其他生物标本及实验室试剂。

Gene mapping studies using DNA markers to detect craniofacial and oral diseases utilize a wide variety of statistical techniques. We are developing a scheme to better integrate these software tools. Since many of these programs were written elsewhere using a variety of computer languages and input formats, integrating them with our internal database will streamline the analysis process. We are constantly updating our suite of statistical analysis tools as the field of genetic epidemiology is under very rapid development, with improved methods and computer programs regularly being made available. Collaborations with colleagues at the NIAAA and Queensland Institute of Medical Research have provided us with access to unpublished software programs for genetic analyses. In addition, we are continuing our efforts to improve the speed, accuracy and efficiency of genotyping for large-scale gene mapping studies. During the past year we have evaluated several alternative molecular marker sets for screening the entire human genome, including a newly available set of microsatellite markers based primarily on dinucleotide versus tetranucleotide repeats. Our collaboration with the NHGRI has provided us with access to their extensive experience in developing another marker set, including the method known as pig-tailing, which has been shown to substantially reduce artifacts associated with this method of marker genotyping. Additional efforts have been focused on incorporating our new instruments into these analyses including DNA sequencers and a robotic laboratory workstation.In order to efficiently keep track of the very large amounts of information essential for conducting large-scale genetic epidemiological studies, we are continuously undertaking ongoing development of our comprehensive data management system. This system is used for the management of clinical, pedigree and genotype data for gene mapping studies and other study designs involving research aimed at the oral and dental disorders under investigation by the Senior Investigator. Our goal is to have a fully integrated system that can manage clinical information, family histories, and marker-allele typing. In addition, this system should provide interactive procedures including: (1) extensive error checking; (2) generation of formatted files suitable for input to various linkage analysis programs; and (3) provide primer inventories and for tracking DNA samples and other biological specimens and laboratory reagents.