ENHANCED LINKAGE MAPS FROM FAMILY-BASED GENETICS STUDIES

基于家族的遗传学研究增强连锁图谱

• 批准号: 7956116
• 负责人: TARA C. MATISE
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956116
• 关键词: Asthma; Biomedical Research; Cardiovascular Diseases; Chromosome Mapping; Collection; Communities; Complex; Computer Retrieval of Information on Scientific Projects Database; Confidence Intervals; Data; Data Collection; Diabetes Mellitus; Disease; Ethnic group; Family; Foundations; Funding; Future; Genes; Genetic; Genetic Recombination; Genotype; Grant; High Performance Computing; Hypertension; Individual; Inherited; Institution; Linkage Disequilibrium; Lod Score; Malignant Neoplasms; Maps; Meiosis; Methods; Modeling; National Heart, Lung, and Blood Institute; Obesity; Research; Research Personnel; Resources; Services; Source; United States National Institutes of Health; base; follow-up; genetic linkage analysis; genetic pedigree; genome-wide linkage; hypercholesterolemia; improved; sex

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Meiotic linkage maps are the foundation of both linkage and linkage disequilibrium studies for mapping disease genes. Despite the importance of precise maps, existing genome-wide linkage maps were built using only a small collection of pedigrees, and so have wide confidence intervals surrounding estimates of map distance. Incorrect marker order and map distances can have a profound effect on linkage analyses. Using a sex-averaged map instead of a sex-specific map biases the lod scores upward, markedly increasing the false positive rate. Since it is very costly to follow-up many false-positive results, there is a clear need for more precise and accurate sex-specific genetic maps. Accurate estimates of meiotic map distance cannot be obtained by any means other than by linkage analysis using genotype data. We propose to build improved highly-precise sex-specific linkage maps utilizing thousands of individuals who have previously been genotyped. After filtering out obvious relationship and genotype errors, we will incorporate methods that properly model for genotyping errors. In addition to creating precise maps for the scientific community, we also propose to use these genotype data to study how recombination may vary between ethnic groups. The genotypes generated by the NHLBI Mammalian Genotyping Service are precisely the type of data required to produce more accurate maps. These data collections contain over 3,400 pedigrees with more than a 100-fold increase in information compared to that contained in the 8 CEPH families that have been used to construct current genome-wide linkage maps. Our new maps will be made publicly available by the MAP-O-MAT linkage mapping server. In the future, we anticipate broadening our study to incorporate genotype data from additional genotyping centers such as the Center for Inherited Disease Research (CIDR). The inaccuracies present in current maps can contribute to misleading results, and may be one of the reasons that disappointingly few genes have been definitively identified that contribute to such complex diseases as asthma, cardiovascular disease, hypertension, hypercholesterolemia, diabetes, obesity, and cancer. The more precise maps that we propose to construct will improve the power and value of many ongoing and new disease studies.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 减数分裂连接图是映射疾病基因的连锁和连锁不平衡研究的基础。尽管非常重要的是精确的地图，但现有的全基因组链接图还是仅使用一小部分血统建造，因此围绕地图距离的估计值具有较宽的置信区间。不正确的标记顺序和地图距离可能会对连锁分析产生深远的影响。使用性别平均地图而不是性别特异性地图会偏向LOD的得分，从而显着提高了假阳性率。由于跟进许多假阳性结果是非常昂贵的，因此显然需要更精确和准确的性别特异性遗传图。除了使用基因型数据的链接分析以外，无法通过任何其他方式获得对减数分裂图距离的准确估计。我们建议利用数千个以前被基因型的人来建立改进的高度专业性别的连锁图。在滤除了明显的关系和基因型误差之后，我们将合并正确模拟基因分型误差的方法。除了为科学界创建精确的地图外，我们还建议使用这些基因型数据来研究种族之间的重组如何变化。 NHLBI哺乳动物基因分型服务产生的基因型恰恰是产生更准确地图所需的数据类型。与8个用于构建当前全基因组链接图的CEPH家族相比，这些数据收集包含超过3,400个血统，信息增加了100倍以上。我们的新地图将由Map-O-Mat链接映射服务器公开提供。将来，我们预计我们的研究将扩大研究，以结合其他基因分型中心的基因型数据，例如遗传性疾病研究中心（CIDR）。当前地图中存在的不准确性可能导致误导性结果，这可能是令人失望的基因确定鉴定出令人失望的基因的原因之一，这些基因有助于哮喘，心血管疾病，高血压，高血压，高胆固醇血症，糖尿病，糖尿病，肥胖和癌症等复杂疾病。我们建议构建的更精确的地图将改善许多正在进行的和新疾病研究的能力和价值。